NephrologyTimesPractical News, Trends, and Analysis

Predialysis Systolic Blood Pressure and Risk of All-Cause Mortality Postdialysis

The incidence of end-stage renal disease (ESRD) among individu-als with chronic kidney disease

(CKD) is high, despite advances in the understanding of CKD progression. Patients with CKD not dependent on dialysis who transition to ESRD have the highest mortality within the first few months following the transition to dialysis therapy. Those patients also have exceptionally high healthcare costs and burden. Identifying modifiable risk factors and interventions during the period prior to the transition to dialysis could lessen the adverse outcomes in this vulnerable population.

In the general population, a common risk factor for cardiovascular disease and death is hypertension; however, low blood pressure has been associated with mortality in patients on dialysis therapy. Some studies have suggested a J-shaped association between systolic blood pressure and mortality in patients with non–dialysis-dependent CKD. Cur-rent clinical guidelines suggest a target blood pressure <140/90 or <130/80 mm Hg for patients with CKD, depend-ing on age, severity of albuminuria, and comorbid conditions. However, there are few data on the association between blood pressure and mortality in patients with advanced non–dialysis-dependent CKD, including those transitioning to maintenance dialysis therapy.

Biomarkers of Kidney Injury and Repair Measured in Marathon Runners

In 2014, a record number of individuals in the United States competed in a marathon; the increase in marathon participation to 550,600 has subsequently increased the need to more closely examine the relationship between marathon

running and kidney injury. Because runners are generally seen as healthy athletes with trained physiology to tolerate high states of energy expenditure, the relationship

Hemoglobin A1c Level Control and Risk of ESRD and Mortality in Patients with CKD

Patients with both diabetes and chronic kidney disease (CKD) are at in-creased risk for death, compared with those with diabetes or CKD alone. Diabetic kidney disease is increasing in prevalence; diabetic nephropathy

is the leading cause of end-stage renal disease (ESRD). The ideal level of glycat-ed hemoglobin (hemoglobin A1c [HbA1c]) has not been positively established; results of some clinical trials in the general population have shown an associa-tion between intensive glycemic control and adverse outcomes in patients with diabetes. The American Diabetes Association recommends targeting an HbA1c level <7% for most nonpregnant adults and <8% for those at risk for hypoglycemia,

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October 2017 VOLUME 9, NUMBER 7

Appropriateness of Antibiotics Prescribed to Hemodialysis PatientsThe oral antibiotics most commonly prescribed inappropriately were amoxicillin/clavulanic acid and cephalexin. 7

Peritoneal Dialysis Compared with Hemodialysis in Infants Younger than One YearThere are cases where peritoneal dialysis is contraindicated and hemodialysis is the only alternative prior to kidney transplantation. 9

Focus on TransplanTaTion

Differentiating between Allograft Active Rejection and Allograft InjuryResults of the DART study. 12

PLUS....

From The Field

Cheap Billing Can Be CostlyThe costs of preventative services outweigh the costs of penalties and poor quality scores. 18

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Increases Healthy Red Blood Cells Hemoglobin enables red blood cells to carry oxygen to all parts of the body, providing energy.

Gives Iron When and Where Patients Need itTriferic® enters the blood via dialysate and donates its iron immediately to transferrin, making red blood cells and maintaining hemoglobin.

Proven Safety ProfileNo iron trapped in the liver and no increase in ferritin, inflammation, toxicity or infections. No anaphylaxis. Decrease in blood transfusions.1

IMPORTANT SAFETY INFORMATIONWarnings and PrecautionsSerious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been lifethreatening and fatal, have been reported in patients receiving parenteral iron products. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after hemodialysis until clinically stable. Personnel and therapies should be immediately available for the treatment of serious hypersensitivity reactions. Hypersensitivity reactions have been reported in 1 (0.3%) of 292 patients receiving Triferic® in two randomized clinical trials. Iron status should be determined on pre-dialysis blood samples. Post dialysis serum iron parameters may overestimate serum iron and transferrin saturation.

Adverse ReactionsThe most common adverse reactions (>3% and at least 1% greater than placebo) in controlled clinical studies include: headache, peripheral edema, asthenia, AV fistula thrombosis, urinary tract infection, AV fistula site hemorrhage, pyrexia, fatigue, procedural hypotension, muscle spasms, pain in extremity, back pain, and dyspnea.

For full Safety and Prescribing Information please visit www.triferic.com.

1 In Clinical Trials vs. Placebo. Triferic® [Package Insert]. Rockwell Medical, Wixom, MI, September 2015.

The Triferic® logo and blood drop character are Registered Trademarks of Rockwell Medical, Inc.

The Only Iron Replacement Therapy That Maintains HemoglobinTriferic® is an innovative iron therapy that effectively treats the iron loss and anemia that hemodialysis patients suffer from.

To schedule a web-enabled presentation on the benefits that Triferic® can provide to your patients email us at trifericpres@rockwellmed.com or call 800.449.3353 Triferic®

www.triferic.comRockwell Medical

The Only FDA Approved Drug Indicated to Replace Iron and Maintain Hemoglobin in Adult CKD-HD Patients

From the early days of hemodialysis, many, including the late Dr. Bernard Scribner at the University of Seattle, worked tire-lessly to promote home hemodialysis. In the early 1970s, the

use of home hemodialysis peaked, with nearly 40% of all patients in the United States receiving home hemodialysis (HHD). Since then, and for a variety of reasons, in-center hemodialysis has become dominant. In part, this has been because the population on dialysis is older and less stable from a cardiovascular perspective, but also because of changes in the way Medicare funds dialysis.

Frequent daily dialysis or nocturnal dialysis appears to have several benefits, including cardiovascular, mortality, and quality of life. However, the benefit depends on ensuring that the total duration of dialysis is not curtailed1,2. Management of volume and electrolytes also seems to be better with HHD. However, frequent dialysis attenuates residual kidney function3, which impacts volume control and, potentially, mortality4.

While HHD is attractive to some patients, there is substantial impact on a patient’s ability to work, unless HHD is performed at night. Further, until recently HHD required a caregiver be present. Currently, only approximately 10% of patients in the United States receive HHD.

The recently announced decision by the FDA to approve the NxStage Medical System One™5 allows patients, on their own, to perform HHD6. This represents major progress, and it is likely to result in more patients opting for HHD. The recent acquisition of NxStage by Fresenius7 might also represent a powerful signal, in that the dialysis industry sees tremendous financial benefit of shifting the patient mix back towards HHD; in addition, Fresenius championed in-center dialy-sis dating back to the origins of commercially available dialysis in the United States and now has more than 300,000 patients on hemodialy-sis globally.

The question is whether Fresenius’s $2 billion bet will pay off. Rice Powell, chairman and CEO of Fresenius Medical Care, said, “The

acquisition supports our 2020 strategic initiative of driving growth in the core business with innovation, better clinical outcomes through Care Coordination, and improving the patient experience…combining our two companies would strengthen and diversify our business in the United States and help meet the evolving needs of our patients.7”

What is Fresenius looking for in its purchase of NxStage? Two

things: first, the financing of dialysis is now bundled. The onus is on providers to find savings, since many aspects of dialysis care, including injectable drugs such as erythropoietin, are covered in the bundle. Thus, shifting patients to a less expensive therapy could be financially beneficial. Second, HHD’s major survival benefits over more conventional forms of dialysis will ultimately lead to greater demand for HHD, and Fresenius will be able to serve this demand through NxStage.

Still, for some, the dream of a patient independently undergoing dialy-sis using a portable wearable device remains. Perhaps Fresenius is mak-ing an additional bet: NxStage is sufficiently innovative that even further portability in dialysis care beyond just “doing it at home” will emerge. Either way, acquiring NxStage seems to represent a masterful big step.

REFERENCES1. Naso A, Scaparrotta G, Naso E, Calò LA. Intensive Home Hemodialysis:

An Eye at the Past Looking for the Hemodialysis of the Future. Artif Organs. 2015 Sep;39(9):736-40. doi:10.1111/aor.12458. Epub 2015 Apr 29.

2. Chertow GM, Levin NW, Beck GJ, et al. FHN Trial Group In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363(24):2287–2300. doi:10.1056/NEJMoa1001593. 

3. Daugirdas JT, Greene T, Rocco et al FHN Trial Group Effect of frequent hemodialysis on residual kidney function. Kidney Int. 2013;83(5):949–958. doi:10.1038/ki.2012.457.

4. Wang AY, Lai KN The importance of residual renal function in dialysis patients. Kidney Int. 2006;69(10):1726.

5. https://seekingalpha.com/article/4096008-fresenius-aims-take-home-dialysis-nxstage

6. https://www.medpagetoday.com/nephrology/esrd/67620 Accessed September 14, 2017

7. http://www.nasdaq.com/press-release/fresenius-medical-care-to-acquire-nxstage-medical-inc-to-strengthen-its-vertically-integrat-ed-20170807-00024

From the Chair

Home Dialysis Takes a Big Step

3Nephrology Times | October 2017

Ajay K. Singh, MBBS, FRCP, MBABrigham and Women’s Hospital and Harvard Medical SchoolBOSTON, MASSACHUSETTS

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NxStage System One™

Increases Healthy Red Blood Cells Hemoglobin enables red blood cells to carry oxygen to all parts of the body, providing energy.

Gives Iron When and Where Patients Need itTriferic® enters the blood via dialysate and donates its iron immediately to transferrin, making red blood cells and maintaining hemoglobin.

Proven Safety ProfileNo iron trapped in the liver and no increase in ferritin, inflammation, toxicity or infections. No anaphylaxis. Decrease in blood transfusions.1

IMPORTANT SAFETY INFORMATIONWarnings and PrecautionsSerious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been lifethreatening and fatal, have been reported in patients receiving parenteral iron products. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after hemodialysis until clinically stable. Personnel and therapies should be immediately available for the treatment of serious hypersensitivity reactions. Hypersensitivity reactions have been reported in 1 (0.3%) of 292 patients receiving Triferic® in two randomized clinical trials. Iron status should be determined on pre-dialysis blood samples. Post dialysis serum iron parameters may overestimate serum iron and transferrin saturation.

Adverse ReactionsThe most common adverse reactions (>3% and at least 1% greater than placebo) in controlled clinical studies include: headache, peripheral edema, asthenia, AV fistula thrombosis, urinary tract infection, AV fistula site hemorrhage, pyrexia, fatigue, procedural hypotension, muscle spasms, pain in extremity, back pain, and dyspnea.

For full Safety and Prescribing Information please visit www.triferic.com.

1 In Clinical Trials vs. Placebo. Triferic® [Package Insert]. Rockwell Medical, Wixom, MI, September 2015.

The Triferic® logo and blood drop character are Registered Trademarks of Rockwell Medical, Inc.

The Only Iron Replacement Therapy That Maintains HemoglobinTriferic® is an innovative iron therapy that effectively treats the iron loss and anemia that hemodialysis patients suffer from.

To schedule a web-enabled presentation on the benefits that Triferic® can provide to your patients email us at trifericpres@rockwellmed.com or call 800.449.3353 Triferic®

www.triferic.comRockwell Medical

The Only FDA Approved Drug Indicated to Replace Iron and Maintain Hemoglobin in Adult CKD-HD Patients

EDITORIAL BOARD CHAIR

Ajay K. Singh, MBBS, MBASenior NephrologistBrigham and Women’s Hospital Associate Professor of Medicine Harvard Medical SchoolBOSTON, MASSACHUSETTS

BOARD

Mohamed G. Atta, MD, MPHAssociate Professor of MedicineJohns Hopkins School of MedicineDivision of NephrologyBALTIMORE, MARYLAND

Vinod K. Bansal MD, FACP, FASNProfessor of MedicineDivision of Nephrology and HypertensionLoyola University Medical CenterMAYWOOD, ILLINOIS

Timothy E. Bunchman, MDProfessor & Director Pediatric NephrologyChildren’s Hospital of RichmondVCU School of MedicineRICHMOND, VIRGINIA

Suphamai Bunnapradist, MD, MSProfessor of MedicineDavid Geffen School of Medicine at UCLAResearch DirectorKidney Transplant Program, UCLALOS ANGELES, CALIFORNIA

Fernando C. Fervenza, MD, PhDProfessor of MedicineDivision of Nephrology & HypertensionMayo ClinicROCHESTER, MINNESOTA

Kenneth A. Liss, DOHypertension and Nephrology AssociatesEATONTOWN, NEW JERSEY

Sayeed K Malek, MD, FACSClinical Director of Transplant SurgeryBrigham and Women’s HospitalInstructor in SurgeryHarvard Medical SchoolBOSTON, MASSACHUSETTS

Alan Salama, MBBS, PhDReader in NephrologyUniversity College LondonLONDON, UNITED KINGDOM

Lynda A. Szczech, MD, MSCEAssociate Professor of MedicineDivision of NephrologyDuke University Medical CenterDURHAM, NORTH CAROLINA

News

There are few data on the relationship between strenuous activity and kidney function; research-ers conducted a prospective observational study of participants in the 2015 Hartford Marathon.

Of the 22 marathon runners in the study, 82% developed an increase in creati-nine level equivalent to acute kidney injury (AKI) stages 1 and 2, defined by AKI Network criteria.

Levels of serum creatinine, urine albumin, and injury and repair biomarkers peaked on the day of the marathon, with significant elevation compared with the day prior to and the day following the marathon.

TAKEAWAY POINTS

between marathon running and kidney function has not been well studied.

Marathon runners can maximize their oxygen uptake nearly 50% more than healthy nonrunners of the same age; as oxygen uptake increases, cardiac output increases 3- to 5-fold above resting levels. However, according to Sherry G. Mansour, DO, and colleagues, the increased blood flow to skeletal muscles and skin is ac-companied by a decrease of up to 25% in renal blood flow during strenuous activity compared with resting levels. Because in normal circumstances kidneys receive 20% of cardiac output, it is possible that this re-duction in blood supply to the kidneys may lead to ischemic tubular damage.

Increases in core body temperature may also contribute to tubular damage in marathon runners, resulting in heat stress leading to kidney injury. Further, previous studies have demonstrated that kidney injury may occur during running even with adequate hydration.

The researchers conducted a prospective observational study designed to assess the kidney function of runners participating in

the 2015 Hartford (Connecticut) Marathon. The study utilized conventional and renal biomarkers of injury and repair to highlight the association between rigorous activity and kidney function. Study results were reported in the American Journal of Kidney Diseases [2017;70(2):252-261].

The primary outcome of interest was acute kidney injury (AKI) defined by AKI Network (AKIN) criteria: stage 1 was defined as a 1.5- to 2-fold or 0.3 mg/dL increase in serum creatinine level within 48 hours of day 0 and stage 2 was defined as >2- to 3-fold increase in creatinine level. Microscopy score was defined by the number of granular casts and renal tubular epithelial cells.

Samples were collected 24 hours before the marathon (day 0), immediately follow-ing the marathon (day 1), and 24 hours after the marathon (day 2). Measurements of serum creatinine, creatinine kinase, and urine albumin were conducted, as was urine microscopy. The six biomarkers mea-sured were: (1) interleukin 6 (IL-6); (2) IL-8; (3) IL-18; (4) kidney injury molecule 1 (KIM-1); (5) neutrophil gelatinase-as-sociated lipocalin (NGAL); and (6) tumor necrosis factor a (TNF-a). Two repair

markers were also examined: (1) human cartilage glycoprotein 39 (YKL-40) and (2) monocyte chemoattractant protein 1 (MCP-1).

Marathon participants were offered an online survey; 132 responded. Of those, 68 met inclusion criteria and 22 agreed to

participate in the study. The cohort includ-ed nine men (41%) and 13 women (59%). Mean age was 44.2 years, mean body mass index was 22.4 kg/m2. Median running experience was 12 years and participants had completed a median of five marathons prior to the Hartford race. The cohort was healthy; two individuals had comorbid conditions (one had hypertension and one had type 2 diabetes). Average training for the marathon was 31.8 miles per week. Six participants had consumed nonste-roidal anti-inflammatory drugs within 2 weeks of the race, but not within 48 hours of race day; 11 participants were taking herbal supplements. All study participants completed the 26.2 miles; average finishing time was 4.02 hours.

In all runners, serum creatinine peaked on day 1. Median creatinine values on days 0, 1, and 2 were 0.81, 1.28, and 0.90 mg/dL, respectively. At least stage 1 AKI was seen in 82% of the runners; one runner developed AKI stage 2. Urine albumin also peaked on day 1. However, serum creati-nine kinase level continued to increase 24 hours after the marathon. Day 2 values were significantly higher than days 0 and 1. Across all three time points, fractional

excretion of sodium was <1%; there was a significant decrease from day 0 to days 1 and 2.

With the exception of YKL-40 and IL-8, there were no significant correlations between levels of creatine kinase and both conventional and novel biomarkers across the time points; YKL-40 positively cor-related with creatine kinase level on day 1 (r=0.51; P<.02) and IL-8 negatively cor-related with creatine kinase level on day 1 (r=–0.51; P<.003).

On day 0, urine microscopy yielded minimal findings; significant increases in scores among the runners were seen on days 1 and 2 (positive scores were seen in 9%, 65%, and 59% on days 0, 1, and 2, respectively). Sixteen runners (73%) were seen as having positive microscopy scores in day 1 or day 2.

Compared with days 0 and 2, there was significant elevation in levels of urine biomarkers. The highest-fold increases on day 1 compared with day 0 values were in IL-6, KIM-1, and IL-8. On day 1, levels of YKL-40 and MCP-1 peaked. MCP-I levels had a 7.5-fold increase on day 1 following completion of the marathon compared with day 0 levels.

The small sample size, making the find-ings subject to possible confounding, was cited as a limitation to the study by the researchers.

In summary, the researchers said, “in this study, we have shown that marathon runners develop an increase in creatinine level that is equivalent to AKI stages 1 and 2 based on AKIN criteria, with urine sedi-ments that are diagnostic of acute tubular injury. This is accompanied by an increase in levels of injury and repair biomarkers, further indicating structural damage in the kidney. The results of our study are mainly hypothesis generating and should be fur-ther validated in larger cohorts.”

4 Nephrology Times | October 2017

Kidney Injury in Marathonerscontinued from page 1 Based on findings of urine microscopy, serum

creatinine changes and novel biomarkers, marathon

running causes acute kidney injury. However, this

kidney injury is completely reversible within 48-72

hours after the race. However, it is unclear if

repeated short-term injuries to the kidney

due to marathon running may lead to long

term fibrosis in participants with preexisting

kidney disease or risk factors such as

diabetes, hypertension, or NSAID use.

Chirag R. Parikh, MD, PhD, FACPProfessor of Medicine

Director, Program of Applied Translational ResearchYale University and Veterans Affairs Medical Center

In all runners, serum creatinine peaked on day

1. Median creatinine values on days 0, 1, and 2

were 0.81, 1.28, and 0.90 mg/dL, respectively.

News

5Nephrology Times | October 2017

extensive comorbid conditions, and long-standing diabetes.

There are few data available assessing the associations between HbA1c levels and clinical outcomes in individuals with CKD; findings from previous studies have been inconsistent. Sankar D. Navaneethan, MD, MS, MPH, and colleagues conducted an observational cohort study designed to examine the associations of HbA1c levels with ESRD and death in a population with diabetes and non–dialysis-dependent CKD who were receiving care in a large health-care system in the United States. Study re-sults were reported in the American Journal of Kidney Diseases [2017;70(2):191-296].

The outcomes of interest were all-cause and cause-specific mortality, ascertained from the Ohio Department of Health mor-tality files, and ESRD, ascertained from the US Renal Data System. The study included 6165 patients with diabetes and CKD stages 1 to 5, identified via a pre-existing electronic medical record developed by the Cleveland Clinic.

Inclusion criteria were residents of Ohio with at least one outpatient encounter with a healthcare provider at the Cleveland Clinic and (1) either two estimated glomerular filtration rate (eGFR) values <60 mL/min/1.73 m2 more than 90 days apart or In-ternational Classification of Diseases, Ninth Revision codes for various kidney diseases, (2) diabetes treated with oral hypoglycemic agents and/or insulin, and (3) HbA1c mea-sured in the year prior to the second eGFR <60 mL/min/1.73 m2 or a CKD diagnosis. Exclusion criteria were age <18 years and a previous diagnosis of ESRD. Patients meet-ing inclusion and exclusion criteria from January 1, 2005, to September 15, 2009, were included in the current analysis.

The final cohort included 6165 patients; mean age was 70.1 years, 46.7% were men, and 20.7% were black. Mean body mass index was 32.3 kg/m2; the prevalence of hy-pertension was 96.3%, malignancy, 17.0%, and coronary artery disease, 96.3%. Mean eGFR was 50.5 mL/min/1.73 m2; 58.8% of patients were in CKD stage 3a, 24.5% were in CKD stage 3b, and 7.4% were in CKD stage 4.

Median follow-up was 2.3 years. Dur-ing that time, 957 patients died, including 887 pre-ESRD deaths, and 205 patients reached ESRD. In unadjusted competing-

risk analyses, there were differences in the incidence of ESRD across different HbA1c levels (P<.001) and differences in all-cause mortality (P<.05). In multivariable Cox proportional hazards regression, there was an independent association between HbA1c level and pre-ESRD mortality. Compared with HbA1c levels of 6% to 6.9%, there was an association between HbA1c level <6%

and a higher risk for death (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.01-1.50); results were similar with HbA1c level ≥9% (HR, 1.34; 95% CI, 1.06-1.69). In adjusted competing-risk model of ESRD, there was no significant difference between baseline HbA1c levels <6% and ≥9% and baseline HbA1c levels of 6% to 9%. In analy-ses for cause-specific mortality, diabetes accounted for >12% of deaths overall and >19% of deaths among participants with HbA1c levels >9%.

The researchers cited some limitations to the study, including the observational design of the study that made establishment of a causal relationship between HbA1c levels and outcomes impossible; deriving the study population from a single, large in-tegrated health system, possibly limiting the generalizability of the findings; the lack of information on the duration of diabetes and other complications related to diabetes and on newer noninsulin injectable antidiabetic drugs; and the limited number of patients with CKD stage 5.

“In summary, we report increased risk for all-cause mortality among patients with dia-betes and CKD who had HbA1c levels <6% and among those who had HbA1c levels ≥9%. By contrast, HbA1c level was not asso-ciated with ESRD in this study population. The proportion of deaths due to diabetes in-creased as HbA1c levels increased. Clinical trials comparing different diabetes control targets and specific medication strategies in patients with established CKD are war-ranted,” the researchers said.

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In analyses for cause-specific

mortality, diabetes accounted for

>12% of deaths overall and >19%

of deaths among participants with

HbA1c levels >9%.

HbA1c Level Control and Risk of ESRDcontinued from page 1

Nephrology Times on

the iPad.www.nephtimes.com

Researchers conducted an ob-servational cohort study to examine the associations be-tween hemoglobin A1c (HbA1c) levels and end-stage renal disease (ESRD) and mortality in a population of pa-tients with diabetes and chronic kidney disease (CKD).

The study included 6165 patients treated at the Cleveland Clinic (Ohio) for diabetes and CKD; of those, 957 died during a median follow-up of 2.3 years and 205 reached ESRD.

HbA1c levels of <6% and ≥9% were as-sociated with higher risk for all-cause mortality compared with HbA1c levels of 6% to 9%.

TAKEAWAY POINTS

News

Researchers conducted an observational study among a cohort of US veterans with chronic kidney disease during the transition period to end-stage renal disease to examine the association between blood pressure prior to initiation of dialysis therapy and mortal-ity following dialysis initiation.

There was a reverse J-shaped asso-ciation between systolic blood pressure and post-dialysis mortality; the mortality risk was significantly higher with systolic blood pressure <140 mm Hg.

The mortality risks associated with lower systolic blood pressure were greatest in the first 3 months following initiation of dialysis therapy.

TAKEAWAY POINTS

Keiichi Sumida, MD, and colleagues conducted an observational study designed to examine the associations of systolic and diastolic blood pressure in the period of transition to dialysis therapy with postdialysis all-cause mortality in a large, nationally repre-sentative cohort of US veterans transitioning to dialysis therapy. The researchers reported results of the study in the American Journal of Kidney Diseases [2017;70(2):207-217].

The primary outcome of interest was all-cause mortality postdialysis, assessed over different follow-up periods: <3, 3 to <6, 6 to <12, and ≥12 months following initiation of dialysis therapy. Cox regression analyses adjusted for demographics, comorbid condi-tions, medications, cardiovascular medica-tion adherence, body mass index, estimated glomerular filtration rate, and type of vascular access were conducted.

The data analyzed were from the TC-CKD (Transition of Care in CKD) study. TC-CKD was a retrospective cohort study that included veterans in the United States with CKD who transitioned to chronic kidney failure requir-ing renal replacement therapy; data from October 1, 2007, through September 30, 2011, were analyzed. The primary exposure of interest were systolic blood pressure and diastolic blood pressure averaged over the 1-year period prior to initiation of dialysis.

The cohort included 17,729 patients. Of those, 98% were men (n=17,388), mean age at baseline was 73.7 years, 31.4% were Afri-can American (n=5559), and 73% (n=12,941) had diabetes. Median estimated glomerular filtration rate (eGFR) prior to dialysis initia-tion was 11.0 mL/min/1.73 m2. There were a median of 10 outpatient blood pressure measurements per patient: mean systolic blood pressure was 141.2 mm Hg and mean diastolic blood pressure was 73.7 mm Hg.

Those with higher systolic blood pressure were younger, more likely to be African American, and had a higher prevalence

of diabetes and lower prevalence of other comorbid conditions compared with pa-tients with lower systolic blood pressure. Participants in the higher systolic blood pressure group were also more likely to be

prescribed antihypertensive medications, less likely to be adherent to cardiovascular medications, and had lower levels of serum albumin, blood hemoglobin, and eGFR.

Median follow-up was 2.0 years. During that time, following initiation of dialysis ther-apy (total time at risk, 37.969 patient-years), there were 9064 all-cause deaths (crude in-cidence rate, 238.7; 95% confidence interval [CI], 233.9-243.7) per 1000 patient-years. Among the 9064 deaths, 1515 occurred in the first 3 months following initiation of dialysis therapy, 1097 in 3 to <6 months, 1529 in 6 to <15 months, and 4923 in ≥12 months after dialysis therapy initiation.

Following adjustment for possible con-founders, there was an inverse association between category of systolic blood pressure and all-cause mortality: adjusted hazard ratios (HRs) of systolic blood pressure <120, 120 to <130, and 130 to <140 (compared with 140 to <150) mm Hg were 2.40 (95% CI, 1.96-2.93), 1.99 (95% CI, 1.66-2.40), and 1.35 (95% CI, 1.13-1.62), respectively. There was a nonsignificant lower risk for mortality associated with systolic blood pres-sure categories of ≥150 mm Hg. The highest risk of death was observed in patients with systolic blood pressure <120 mm Hg.

There was no consistent association seen between predialysis diastolic blood pressure and risk of mortality following initiation of

dialysis therapy.Limitations to the study cited by the

authors included the observational design, which precluded the establishment of cause-effect relationships and created the inability

to conclude that the mortality risk associ-ated with various systolic blood pressures equals the risk associated with the same systolic blood pressures when they occur as a result of antihypertensive interventions in clinical practice. Further, because most of the participants were male US veterans, the results may not be generalizable to women or patients from other geographic areas.

The researchers said, “In this large national cohort of US veterans transition-ing to dialysis therapy, we found a reverse J-shaped association of predialysis systolic blood pressure with all-cause mortality following dialysis therapy initiation, with significantly higher death risk seen with systolic blood pressures <140 mm Hg, but found no consistent association with predi-alysis diastolic blood pressure. Our findings suggest that pretransition low systolic blood pressure could be a useful predictor of early post-transition mortality, and also that physi-cians should be cautious when substantially lowering systolic blood pressure below the currently established targets in this unique patient population. Future clinical trials are needed to clarify the ideal predialysis systolic blood pressure and determine whether active interventions targeting predialysis systolic blood pressure could be applied to improve the high early mortality seen among incident dialysis patients.”

6 Nephrology Times | October 2017

Predialysis Systolic Blood Pressurecontinued from page 1

The primary exposure of interest were

systolic blood pressure and diastolic blood

pressure averaged over the 1-year period

prior to initiation of dialysis.

Kidney Injuries at a Level 1 Trauma Center

Orlando—Elmhurst Hospital Cen-ter at the Icahn School of Medicine in Queens, New York, is a level 1 trauma center. Approximately 3% of all trauma admissions at the center are renal trau-ma cases; among patients who sustain abdominal trauma, as many as 10% of trauma admissions involve renal trauma.

Researchers at the center, led by Jayaramakrishna Depa, MD, con-ducted a retrospective review to examine the epidemiology of renal trauma over the past decade; they also sought to identify any changes in acute kidney function associ-ated with renal trauma. Results of

the analysis were reported during a poster session at the NKF 2017 Spring Clinical Meetings in a poster titled Review of Kidney Injuries and Subsequent Function at a Level 1 Trauma Center over a 13-Year Span.

The review included the electronic health records for all trauma patients with kidney injury treated at Elmhurst Hospital Center from January 2004 through October 2016. Collected data included age, sex, mechanisms of injury, length of stay, and mortality.

Computed tomography scans of kidney injury were also examined to grade injury severity. Grade 1 was de-

fined as contusion or non-enlarging injury; grade 2 as superficial laceration <1 cm in depth not involving the col-lecting system; grade 3 as laceration >1 cm without extension into the renal pelvis; grade 4 as laceration extending to the renal pelvis or a vascular injury; and grade 5 as a shattered kidney.

The study included 71 patients: 61 adults and 10 pediatric patients. Over-all, mean age was 31.8 years, and 87% were male (n=62). The most com-mon kidney injury was blunt trauma (76%, n=54). Twenty-five (64.1%) were non-serious grade (grade 1-3) and 14 (35.9%) were serious grade (grade

4-5). Among patients with penetrating trauma (n=17), nine had non-serious grade injury (grade 1-3) and five had serious grade injury (grade 4-5).

Length of stay for blunt trauma was significantly longer than for penetrat-ing injury (21.04 days vs 7.14 days) (P=.009). There was no change in creatinine levels between admission and discharge in either group.

Source: Depa C, Rajnish I, Ahlborn D, Adjei-Bosompem T, Kalosza B, Coritsidis GN. Review of kidney injuries and subsequent function at a level 1 trauma center over a 13-year span. Poster presented at the National Kidney Foundation 2017 Spring Clinical Meetings, April 21, 2017, Orlando, Florida.

National Kidney Foundation

News

7Nephrology Times | October 2017

Worldwide, mortality and hospi-talization in patients receiving maintenance hemodialysis are due,

in part, to infection. Individuals in this patient population are also at risk of infections caused by multi-drug resistant organisms. Inappropri-ate use of antibiotics is a driver for the accel-eration of antimicrobial resistance, giving rise to global efforts to optimize antimicrobial use.

Patients in Australia receive maintenance hemodialysis in community satellite dialysis units, outpatient or inpatient hospital dialysis units, or at home. Patients with minor infec-tions are likely to receive care from their primary healthcare provider; those with more serious infections are likely to be admitted to the hospital for treatment.

According to Katrina Hui and David C. M. Kong, PhD, et al. at the Center for Medi-cine Use and Safety, Monash University, Mel-bourne, Australia, there are few data avail-able on the types and appropriateness of oral and intravenous (IV) antibiotics prescribed to patients on maintenance hemodialysis. The researchers conducted a prospective, observational study across four community hemodialysis units, two community satellite units, and two hospital inpatient hemodialy-sis units in Melbourne. Results of the study were reported online in BMC Nephrology [2017. doi:10.1186/s12882-017-0575-9].

A total of 239 patients were approached to participate in the study. Of those, 63 were unable to provide consent due to medi-cal reasons or language barriers and were excluded. Of the remaining 176 patients, 114 agreed to participate. Of those, 81 were being treated at the community hemodialy-sis units and 33 were being treated at the hospital inpatient hemodialysis units.

During the study period (July 2014 to January 2015), 19 participants at the com-munity hemodialysis centers were admitted to a participating hospital inpatient hemodi-alysis unit and four hospital inpatient hemo-dialysis unit participants were transferred into a participating community hemodialysis center. Eight participants were considered withdrawals from the study due to death (two community unit and two hospital unit) or kidney transplantation (one community

unit and two hospital unit). Overall, there were 340 patient-months of follow-up: 308 for the community unit participants and 32 for the in-patient hospital unit participants.

Median participant age was 64 years, 59.7% (n=68/114) were male, and the majority were white. The most common reason for end-stage renal disease requiring renal replacement therapy was diabetes. There were statistically significant differences for ethnicity, type of vascular access, duration of hemodialysis therapy at study enrollment, and respiratory disease between the community unit and hospital unit participants. There were no dif-ferences between those who were prescribed no antibiotics, those who were prescribed ap-propriate antibiotic regimens, and those with at least one inappropriate antibiotic regimen.

During the study period, there were 114 documented indications for antibiotic therapy. There were 76 suspected and documented in-fections that were community acquired (22.4 episodes of infection/100 patient-months) and 17 that were hospital acquired (5.0 episodes of infection/100 patient-months). The most com-mon infections were respiratory tract infection (RTI) (27/114), skin and soft tissue infec-tion (SSTI) (19/114), blood stream infection (BSI) (14/114), urinary tract infection (UTI) (11/114), and vascular access infection (VAI) (7/114). Five of the BSI episodes involved par-ticipants with catheters as vascular access.

Of the 190 requested microbiologic cultures, blood (97/190), wound (28/190), and urine (24/190) were the most common. Three were requested from the community unit setting; the remainder from the hospital unit setting.

Sixty-three of the 114 participants (55.3%) received antibiotics: 35 of 81 community unit participants (43.2%) and 28 of 33 hospital unit participants (84.8%). A total of 235 antibiotic regimens were prescribed (110 oral and 125 IV). The overall rate of prescribed antibiotic regimens was 69.1 per 100 patient-months (32.4/100 patient-months oral and 36.8/100 patient-months IV). In the community unit setting, the rate was 15.5 regimens per 100 patient-months; in the hospital unit setting, the rate was 584.4 regimens per 100 patient-months.

The most common oral antibiotics pre-

scribed were amoxicillin/clavulanic acid for RTI and SSTIs, and cephalexin for SSTO and UTIs. The most commonly prescribed IV anti-biotics were vancomycin, piperacillin/tazobac-tam, cephazolin, and ceftriaxone. Vancomycin and cephazolin were most commonly pre-scribed for BSI, SSTI, and VAIs; piperacillin/tazobactam for SSTIs; and ceftriaxone for RTIs.

The prescribed antibiotic regimens were compared to the recommendations from the Australian National Therapeutic Guidelines: Antibiotic Version 14 and 15. Of the 235 anti-biotic regimens prescribed, 224 (95.3%) could be assessed for appropriateness of prescribing. Of the 224, 169 (75.4%) were appropriate and 55 (24.6%) were inappropriate. The rate of inappropriately prescribed regimens was 16.2 regimens per 100 patient months.

In the community unit setting, 15 of 43 regimens (34.9%) were classified as inap-propriate; in the hospital unit setting, 40 of 181 regimens (22.1%) were classified as inappropriate. Incorrect dosing was the most common reason for inappropriate classifica-tion; the dose was either too high or the dosing interval was too short.

The oral antibiotics most commonly prescribed inappropriately were amoxicil-lin/clavulanic acid and cephalexin. The IV antibiotics more commonly inappropriately prescribed were cephazolin and meropenem, often due to dosing interval being too short.

The small sample size and short follow-up period were cited as limitations to the study.

“The current study has provided impor-tant insight into the types and appropriate-ness of antibiotics prescribed to patients receiving hemodialysis in an environment where data are scant. Indeed, for the first time, the appropriateness of orally admin-istered antibiotics prescribed to this cohort was investigated. Our data indicate that there is a high burden of antibiotic exposure and considerable inappropriate prescribing of antibiotics in those receiving hemodialy-sis. Our study suggests that antimicrobial stewardship or continuing education related interventions are needed to optimize the use of antibiotics in patients receiving organisms and importantly, to optimize patient safety and outcomes,” the researchers said.

Appropriateness of Antibiotics Prescribed to Hemodialysis Patients

In a prospective observational study, researchers sought to describe patterns of use and the appropriateness of oral and intravenous (IV) antibiotics pre-scribed to patients receiving mainte-nance hemodialysis.

Patients were re-cruited from com-munity hemodialysis units as well as from in-patient hospital hemodialysis units. In the commu-nity unit setting, antibiotics were prescribed inap-propriately in 15 of 43 patients (34.9%); in the hospital unit setting, antibiotics were prescribed inappropriately in 40 of 181 patients (22.1%).

Thirty of 102 (29.4%) of oral antibiot-ics and 25 of 122 (20.5%) IV antibiotics were prescribed inappropriately. In-correct dosing was the primary reason for classification as inappropriate.

TAKEAWAY POINTS

News

Survival and quality of life for patients on dialysis are associated with residual kid-ney function. The preferred modality for

preservation of residual kidney function is peri-toneal dialysis, according to Hao Yan, MD, and colleagues in the department of nephrology, Renji Hospital, School of Medicine, Shanghai Jiaotong University and Shanghai Center for Peritoneal Dialysis Research, Shanghai, China. The preservation of residual kidney function is a key factor accounting for improved survival outcomes of patients on peritoneal dialysis compared with those on hemodialysis during the first 1 to 2 years of renal replacement therapy, the researchers said.

Incident dialysis patients treated with continuous ambulatory (CA) peritoneal dialysis are commonly prescribed either three or four exchanges per day. Previous studies have reported similar survival rates among patients undergoing three- or four-exchange CA perito-neal dialysis. However, larger peritoneal dialy-sis fluid volume per day has been shown to be a strong, independent predictor of a steeper slope of residual decline in kidney function. It is unclear whether effects on deterioration of residual kidney function of 3- and 4-exchange CA peritoneal dialysis vary.

The researchers conducted a single-center, prospective, randomized, controlled, open-label study designed to compare the effect of 3-ex-change CA peritoneal dialysis with 4-exchange CA peritoneal dialysis on residual kidney function. They reported results of the study in the American Journal of Kidney Diseases [2017;69(4):506-513].

During the study period (June 1, 2004, through December 31, 2008), 285 patients ini-tiated therapy with CA peritoneal dialysis. Of those, the study recruited 139 patients: 70 in the 3-exchange group and 69 in the 4-exchange group. The two groups were similar in demo-graphic characteristics, cause of end-stage renal disease, and comorbid conditions. No patients were lost to follow-up during the study.

By the end of 2 years, there were six deaths in the 3-exchange group (cerebral hemorrhage,

n=3; acute myocardial infarction, n=1; sudden death n=1; and gastrointestinal hemorrhage, n=1). In the 4-exchange group, there were three deaths during that same time period (ce-rebral hemorrhage, n=1; and acute myocardial infarction, n=2). One patient in the 3-exchange group and two in the 4-exchange group expe-rienced technique failure and were switched to maintenance hemodialysis therapy due to refractory peritonitis. There was no significant difference in patient survival or technique survival between the two groups.

Twelve patients in the 3-exchange group changed their regimens to four exchanges daily during the study period. Of those 12, three switched prior to the development of anuria. Three patients in the 4-exchange group changed to three exchanges per day based on their own will, one increased to five exchanges per day, and one underwent daytime perito-neal dialysis due to intolerance to overnight dwell. All 12 changed regimens prior to the onset of anuria.

Estimated glomerular filtration rates (eGFRs) were measured at baseline, and 1, 6, 12, 18, and 24 months following initiation of peritone-al dialysis. There were no significant differences between the two groups at each time point. In addition, there were no statistically significant differences between the groups in urine volume at each time point, and there was no significant difference between the groups in urine volume decline rate for the entire study period.

During the study period, 15 patients in the 3-exchange group and 16 in the 4-exchange group developed anuria. Anuria-free survival was similar between the two groups.

Peritonitis occurred in a slightly smaller proportion of patients in the 3-exchange group compared with the 4-exchange group, but the difference was not statistically significant. Results of Kaplan-Meier analysis demonstrated that peritonitis-free survival time was slightly longer in the 3-exchange group than in the 4-exchange group. There were nine patients having 15 episodes in the 3-exchange group and 18 having 23 episodes in the 4-exchange

group. Rates of peritonitis were 0.13 episodes per year in the 3-exchange group and 0.20 episodes per year in the 4-exchange group.

During most of the study, peritoneal ultrafil-tration was significantly less in the 3-exchange group than in the 4-exchange group; daily fluid removal (the sum of daily urine volume and net ultrafiltration) in the 3-exchange group was comparable to that in patients in the 4-ex-change group. During the entire study period, blood pressure, body weight, and levels of hemoglobin and serum albumin were similar between the two groups.

As predicted, Kt/V (dialyzer clearance of urea-dialysis time/volume of distribution of urea) was significantly lower in the 3-exchange group. The ratio of dialysate creatinine to plasma creatinine was comparable in patients in both groups.

Researcher-cited study limitations included the single-center design and all participants be-ing of small stature and all from China, limiting the generalizability of the findings to patients at other centers and in other populations. The study may have been underpowered to distin-guish differences in residual kidney function and patient and technique survival due to the last of formal sample-size calculation. Finally, some factors that influence residual kidney function (eg, proteinuria) were not assessed, creating the possibility that the researchers may not have been able to detect possible differences in volume status between the two groups.

“In summary, this single-center, prospec-tive, randomized, controlled study showed that CA peritoneal dialysis regimens of three and four exchanges had similar effects on residual GFR, urine volume, and time to anuria within a 2-year period in incident patients. The 3-exchange regimen provided nominally less susceptibility to peritonitis and similar patient survival and technique survival compared with the 4-exchange regimen. Incremental perito-neal dialysis therapy starts appear safe when patients are monitored. Clearly, further study with a large sample size is needed to confirm our results,” the researchers said.

8 Nephrology Times | October 2017

Three versus Four Daily Exchanges in Continuous Ambulatory Peritoneal Dialysis and Residual Kidney Function

The effects on residual kidney function and clinical outcomes of three versus four exchanges per day in patients treated with continuous ambulatory (CA) peritoneal dialysis are unknown.

Researchers in China recently conducted a small sample-size study designed to compare the effect on residual kidney function of 3-exchange CA peritoneal dialysis with that of 4-ex-change per day CA peritoneal dialysis.

In this study popula-tion, CA peritoneal dialysis regimens with three and four exchanges per day had similar effects on residual glomerular filtration rate, urine volume, and time to anuria.

TAKEAWAY POINTS

News

9Nephrology Times | October 2017

Pediatric nephrologists face significant challenges in managing infants re-quiring maintenance dialysis. Factors

such as difficulties feeding and maintain-ing fluid balance, growth failure, increased risk of infection, and possible comorbid conditions contribute to the management hurdles in children younger than 1 year. Due in part to these challenges, infants with kidney failure on maintenance dialysis have higher mortality rates than older children on dialysis.

During the past few decades, the num-ber of infants treated with renal replace-ment therapy has increased; according to the 2011 North American Pediatric Renal Trials and Collaborative Studies report, 13.2% of patients on maintenance dialysis were younger than 2 years at initiation of dialysis therapy.

The preferred treatment modality in infants is maintenance peritoneal dialysis, with potentially better preservation of residual kidney function, fewer dietary re-strictions, avoidance of central vascular ac-cess placement, and the option to perform dialysis at home. Hemodialysis in infants is technically difficult and requires skilled nursing staff. However, there are cases where peritoneal dialysis is contraindicated and hemodialysis is the only alternative treatment prior to kidney transplantation.

There are few data reporting on com-parisons of long-term outcomes of the two modalities in infants. Enrico Vidal, MD, PhD, and colleagues conducted a cohort study designed to compare clinical characteristics and outcomes of peritoneal dialysis and hemodialysis patients in a large cohort of patients initiating dialysis therapy prior to age 1 year. Results were reported in the American Journal of Kidney Diseases [2017;69(5):617-625].

Utilizing the European Society for Pediatric Nephrology(EPN)/European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry, the researchers identified 1063 infants initiating dialysis therapy at 12 months or younger from January 1, 1991, to December 21, 2013, who met inclusion

criteria. Of the 1063 infants, 919 started on peritoneal dialysis and 144 started on he-modialysis therapy. At day 30, 14 patients had switched from peritoneal dialysis to hemodialysis and 12 had switched from hemodialysis to peritoneal dialysis. Four-teen patients died prior to day 30 (12 in the peritoneal dialysis group and two in the hemodialysis group).

Sixty-one percent of the infants (n=649) were started on dialysis therapy at age 0 to 6 months, and 39% (n=414) at age 7 to 12 months. Median age at initiation of dialy-sis therapy was 4.5 months and median body weight was 5.7 kg. The proportion of hypoalbuminemic infants was higher in the peritoneal dialysis group; the likely explana-tion for this is the increased protein losses via the peritoneal membrane that is charac-terized by a hyperpermeable state in infants in this age group. Infants on hemodialysis presented with significantly lower hemo-globin levels, possibly related to substantial blood loss with the extracorporeal systems, or, more likely, due to fluid overload at the time of blood sampling (performed immedi-ately prior to a dialysis session).

The 5-year crude mortality rate overall

in the total cohort was 52.3 deaths per 1000 patient-years. The overall cumulative incidence of death at 1, 2, and 5 years was 10.0% (95% confidence interval [CI], 8.10%-11.7%), 13.1% (95% CI, 11.0%-15.2%), and 16.1% (95% CI, 13.8%-18.5%), respectively. Causes of death were infections (25.1%), cardiovascular disease (13.6%), withdraw-ing renal replacement therapy (6.8%), respiratory failure due to fluid overload (3.1%), cerebrovascular accident (5.8%), malignancy (2.1%), miscellaneous (23.6%), and unknown/unavailable causes (19.9%).

A significant risk factor for death was

Peritoneal Dialysis Compared with Hemodialysis in Infants Younger than One Year

The preferred treatment modality

is maintenance peritoneal dialysis

with potentially better preservation

of residual kidney function, fewer

dietary restrictions, and the option

to perform dialysis at home.

continued on page 10

News

Patients with chronic kidney disease face increased risk of diabetes, car-diovascular morbidity, and mortal-

ity; nondiabetic CKD accounts for most of the incidence worldwide. Hypertension is strongly associated with the development of progression of nondiabetic CKD, and control of blood pressure can decrease the risk of decline in renal function and car-diovascular mortality. However, according to Wan-Chuan Tsai, MD, and colleagues in Taiwan, the optimal blood pressure target for the prevention of kidney disease progression is unclear.

Current guidelines suggest a target blood pressure of less than 140/90 mm Hg for patients with nondiabetic CKD; some suggest a reduction of that target to less than 130/80 mm Hg for patients with proteinuria. Results from the SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated that intensive blood pres-sure did not result in reduction of the risk of dialysis or decline in renal function in patients with nondiabetic CKD, but rather increased the risk of acute kidney injury. Dr. Tsai et al. recently conducted a system-ic review and meta-analysis of results from randomized controlled trials to examine the effects of intensive treatment to lower blood pressure on major renal outcomes and mortality in patients with non-diabetic CKD. Results of the review were reported online in JAMA Internal Medicine [doi:10.1001/jamainternmed.2017.0197].

The researchers conducted literature searches of PubMed, MEDLINE, Embase, and the Cochrane Library from the earliest available date of indexing through March 24, 2016. They also hand searched the reference lists of identified publications

for additional studies. The review included randomized controlled trials that com-pared different blood pressure targets in primarily nondiabetic CKD patients >18 years of age.

To be eligible for the review, the studies had to report at least one of the outcomes of interest: changes in glomerular filtration rate (GFR), doubling of serum creatinine level, 50% reduction in GFR, progression to end-stage renal disease (ESRD), or all-cause mortality. ESRD was defined as the need for dialysis therapy or kidney trans-plantation. Eligible studies were required to be published as full-length articles in peer-reviewed journals.

There were 1158 articles retrieved initial-ly. Of those, 328 were excluded because of duplicate publication and 816 were exclud-ed on the basis of titles and abstracts. Of the remaining 14 articles that underwent full-text evaluation, 10 met the inclusion criteria and were included in the review.

The 10 eligible articles reported on nine randomized controlled trials, enrolling a total of 8127 participants. Median length of in-trial follow-up was 3.3 years, mean age of participants was 55 years, and 58% were men. Six of the studies included mostly white participants, two had mostly black participants, and one included mostly Asians. Most of the studies exclud-ed all patients with diabetes; two excluded patients with poorly controlled diabetes and a small percentage of each study popu-lation had diabetes. The studies had simi-lar baseline blood pressure between the intensive and standard treatment groups.

During the in-trial follow-up period, 194 patients had doubling of serum creati-nine level or decline in GFR by 50%, 314

10 Nephrology Times | October 2017

Review and Meta-Analysis to Assess Renal Outcomes with Intensive Blood Pressure Control

younger age at initiation of dialysis therapy; there was a 5% lower risk per month of later initiation (hazard ratio [HR], 0.95; 95% CI, 0.90-0.97; P<.001). Patients with non-congenital anomalies of kidney and urinary tract diseases had a significantly higher risk for death (HR, 1.49; 95% CI, 1.08-2.04; P=.03). There was no significant morality risk difference by sex (female vs male: HR, 1.28; 95% CI, 0.95-1.71) or between infants initiating dialysis therapy before and after 2000 (2000 or later vs pre-2000: HR, 0.93; 95% CI, 0.67-1.29).

A comparison of mortality risk based on dialysis modality found crude 5-year mor-tality rates of 51.0 deaths per 1000 patient-years for peritoneal dialysis and 62.2 deaths per 1000 person-years for hemodialysis. In the intention-to-treat analysis, while censoring for transplantation, there was no significant difference between the treat-ment groups in crude (HR, 1.08; 95% CI, 0.69-1.68) and adjusted (aHR, 1.06; 95% CI, 0.67-1.67). There were no significant differences in HRs for hemodialysis versus peritoneal dialysis between infants initiat-ing dialysis therapy before and from 2000 onwards (P for interaction=.06).

In the group whose initial dialysis modality was peritoneal dialysis, 135 of 143 deaths occurred while still on peritoneal dialysis and eight infants died while switched to hemodialysis therapy. In the initial hemodialysis group, 19 of 23 deaths occurred while still on hemodialy-sis and four occurred while switched to peritoneal therapy.

The mortality risk and likelihood of transplantation were equal in peritoneal dialysis patients and hemodialysis patients. The risk for changing dialysis modality was higher in hemodialysis patients (adjusted HR, 1.64; 95% CI, 1.17-2.31).

Limitations to the study cited by the authors included the inability to control for unmeasured confounders not included in the Registry database and missing data such as comorbid conditions. The study has low statistical power due to the relatively small number of participants.

In conclusion, the researchers said, “Thus study provides evidence that may help physicians in the decision-making process when facing the management of chronic kidney failure in infants. According to our results, patient survival and access to kidney transplantation appeared similar for infants initiating dialysis therapy on peritoneal dialysis or hemodialysis, suggest-ing that hemodialysis may represent a safe and effective alternative dialysis modality in infants with chronic kidney failure. The choice of dialysis modality in this age group should take into account specific benefits and drawbacks of either technique, this individualizing the choice that best fits the needs of the patient and family.”

Management of infants with chronic kidney failure carries significant chal-lenges for pediatric nephrologists; the preferred modality for renal replace-ment therapy in children younger than 1 year is perito-neal dialysis.

Researchers in Europe conducted a study to compare long-term out-comes of peritoneal dialysis with hemo-dialysis in a large cohort of patients who initiated dialysis therapy before 1 year of age.

Patient survival and access to kidney transplantation were similar for infants initiating dialysis therapy on peritoneal dialysis or hemodialysis; he-modialysis may be a safe and effective alternative dialysis modality in this patient population.

TAKEAWAY POINTS

continued from page 9

News

11Nephrology Times | October 2017

There are few data on the optimal blood pressure target in patients with chronic kidney disease without diabetes; researchers in Taiwan conducted a systematic review and meta-analysis to compare intensive blood pressure control with standard control on major renal outcomes.

There was no significant difference on the annual rate of change in glomerular filtration rate (GFR) with intensive versus standard blood pressure control, or on doubling of serum creatinine level or 50% reduction in GFR.

In nonblack participants and in patients with higher levels or proteinuria, there was a trend of lower risk of kidney disease progression to end-stage renal disease with intensive blood pressure control.

TAKEAWAY POINTS

Is it time for a new school of thought?In CKD, progressive loss of renal function along with chronic inflammation leads to1:• High concentrations and reduced clearance of hepcidin

– Impaired intestinal iron absorption– Restricted release of iron from storage

Iron-defi ciency anemia in CKD is diff erent.

Can different thinking help us address these challenges for iron-deficiency anemia in CKD?

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Reference: 1. Ganz T, Nemeth E. Iron balance and the role of hepcidin in chronic kidney disease. Semin Nephrol. 2016;36(2):87-93.

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progressed to ESRD, 306 reached the composite renal outcomes, and 111 died. Compared with standard strategy to lower blood pressure, participants in groups treated with intensive blood pressure strat-egies did not exhibit a significant differ-ence in the annual rate of change in GFR (mean difference, 0.07; 95% confidence interval [CI], –0.16 to 0.29 mL/min/1.73 m2 per year), doubling of serum creatinine or 50% reduction in GFR (risk ratio [RR], 0.99; 95% CI, 0.76-1.29), ESRD (RR, 0.96; 95% CI, 0.78-1.18), compos-ite renal outcome (RR, 0.99; 95% CI, 0.81-1.21) or all-cause mortality (RR, 0.95; 95% CI, 0.66-1.37).

Results were similar following omis-sion of studies with imputed missing data for the annual rate of change in GFR (mean difference, 0.09; 95% CI, –0.38 to 0.55 mL/min/1.73 m2 per year). In sensitivity analyses that omit-ted results of the two trials that in-cluded small percentage of patients with diabetes, results were also similar.

Univariable meta-regression analyses found that the annual rate of decline in GFR with intensive blood pressure control tended to be faster among blacks compared with nonblacks (b value, –0.44; 95% CI, –0.96 to 0.07 mL/min/1.73 m2 per year; P=.09). In subgroup analyses, there was a trend of faster decline in GFR for intensive blood pressure control in studies that included mostly black participants (mean differ-ence, –0.26; 95% CI, –0.70 to 0.18 mL/min/1.73 m2 per year) and a slower decline in GFR in studies with nonblack participants (mean difference, 0.18; 95% CI, –0.08 to 0.45; P for interaction=.09).

The only outcomes that could be as-sessed by different levels of proteinuria were annual rate of change in GFR and progression to ESRD. There were no significant differences in the effects of intensive blood pressure control among patients with different levels of protein-uria. There was, however, a trend for intensive blood pressure control to slow the rate of decline of GFR level among patients with proteinuria higher than 1 g/d (mean difference, 0.75; 95% CI, –0.40-1.89 mL/min/1.73 m2 per year), and a trend for lower risk of ESRD among patients with proteinuria level higher than 0.5 g/d (RR, 0.92; 95% CI, 0.70-1.21).

The researchers cited some limitations to the review, including between-study variability due to varying patient char-acteristics and trial designs, most of the included studies had follow-up time less than 4 years, and the review was limited to published studies.

“Targeting blood pressure below the current standard did not provide

additional benefit for renal outcomes compared with standard treatment during a follow-up of 3.3 years in patients with CKD without diabetes. However, non-black patients or those with higher levels of proteinuria might benefit from the intensive blood pressure lowering and the risk of adverse events are mostly similar among different blood pressure targets,” the researchers said.

News | Focus on Transplantation

Long-term survival of a renal transplant depends on accurate and timely detec-tion of allograft rejection and effective

treatment. The standard for diagnosis of rejec-tion is histology obtained via needle biopsy; however, the technique is rarely utilized for surveillance due to high cost, complicated logistics, and potential complications, as well as patient discomfort and inconvenience.

A possible noninvasive marker for diag-nosis of graft rejection is donor-derived cell-free DNA (dd-cfDNA) detected in the blood of transplant recipients. Data from several single-center studies indicate that dd-cfDNA levels in blood, measured as a fraction of the total cell-free DNA (cfDNA), can discriminate rejection from non-rejection in heart, lung, liver, and kidney allografts.

To date, there are few data on dd-cfDNA in renal transplants. In renal transplanta-tion, there are no existing biomarkers that adequately measure the status of active injury to the allograft. Roy D. Bloom, MD, and colleagues reported on the Circulat-ing Donor-Derived Cell-Free DNA in Blood for Diagnosing Acute Rejection in Kidney Transplant Recipients (DART) study in the Journal of the American Society of Nephrol-ogy [2017;28:2221-2232]. The DART study is a multicenter study of kidney transplant recipients using an analytically validated dd-cfDNA test that used targeted amplification and sequencing of single-nucleotide poly-morphisms to quantify donor and recipient DNA contributions, with no need for prior genotyping of donor or recipient DNA.

The study enrolled 384 renal transplant recipients from April 2015 until May 2016; participants were recruited from 14 clinical sites. Of the 384 patients, 245 were en-rolled within 1 to 3 months of their kidney transplant and 139 at the time of a clinically

indicated renal biopsy. A subset of 107 clini-cally indicated biopsies that had matched plasma dd-cfDNA results provided the core dataset used for the analyses of dd-cfDNA to discriminate rejection from no rejection sta-tus. The biopsy-based pathologists’ reports were used as the diagnostic standard.

The characteristics of the DART study population were representative of the popula-

tion in the United States renal transplanta-tion registry. Patients in the active rejection group were more likely to be black and have received a transplant from a deceased donor compared with the no rejection group and with the overall DART population. Those in the active rejection group were significantly younger than those in the no rejection group.

At the time of the data lock, 219 patients had at least one renal biopsy; 242 biopsies had sufficient specimens and associated pa-thologists’ reported results. Of those 242, 204 were performed for clinical suspicion of rejec-tion, 34 for surveillance, and four for follow-up of treated rejection. Of the 34 surveillance biopsies, only one revealed rejection; the scenario of no clinical indication for biopsy was not included in the subsequent calcula-tions for the performance characteristics for dd-cfDNA to discriminate active rejection.

Three subclasses of rejection were com-bined in the primary analyses: (1) T-cell-mediated rejection (TCMR); (2) acute/active antibody-mediated rejection (ABMR); and (3) chronic, active ABMR. A review of 59 pathologists’ biopsy reports confirmed diag-nosis of active rejection: 58 cases of active rejection in 204 biopsies performed for clin-ical suspicion (most commonly an elevation in serum creatinine), and one case of active rejection in 34 surveillance biopsies.

The researchers included all dd-cfDNA results that were collected at the same

time that a clinically indicated biopsy was performed to define the area under the curve-received operating characteristic (AUC-ROC) performance of dd-cfDNA. There were 27 biopsy specimens from 27 patients with active rejection and 80 speci-mens from 75 patients without active rejec-tion. Samples with >1% dd-cfDNA occurred significantly more often (P<.01) in these types of rejection and subelements: acute/active ABMR; chronic, active ABMR; any or moderate microvascular inflammation; lin-ear C4d staining in peritubular capillaries; and presence of donor-specific antibody.

There were significant differences between groups in the fraction of dd-cfDNA in blood plasma. In the active rejection group, the median level of dd-cfDNA was significantly higher than in the comparator group of biopsy specimens without active rejection (1.6% vs 0.3%; P<.001). There was variation in median levels of dd-cfDNA by type of active rejection: 2.9% (ABMR); 1.2% (TCMR only, types IB and IIA); and 0.2% (TCMR only type IA).

Positive predictive value for active rejec-tion at a cutoff of 1.0% dd-cfDNA was 61%; negative predictive value was 84%. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% confidence interval, 0.75-0.97). Positive predictive value for ABMR at a cutoff of 1.0% dd-cfDNA was 44%; negative predictive value was 96%.

Limitations to the study cited by the researchers included the inability to estimate the performance of dd-cfDNA to discriminate active rejection or ABMR in patients who may have had subclinical rejection because there were only 34 surveillance biopsies and only one finding of active rejection. Further, the number of active rejections was limited. Finally, biopsy-matched blood samples were not collected for all biopsy specimens.

In summary, the researchers said, “This report sets the initial foundation for the perfor-mance characteristics of dd-cfDNA to detect active rejection and injury of the renal allograft beyond serum creatinine and without the need for a biopsy. The next steps of development include studies to validate these findings and to demonstrate the clinical utility of this new type of immune monitoring of the graft.”

12 Nephrology Times | October 2017

Differentiating between Allograft Active Rejection and Allograft Injury

Researchers reported on the DART (Circulating Donor-Derived Cell-Free DNA in Blood for Diagnos-ing Acute Rejection in Kidney Transplant Recipients) study of the use of donor-derived cell-free DNA (dd-cfDNA) to differentiate active rejection of allograft from allograft injury.

The positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively.

Using dd-cfDNA to assess allograft re-jection and injury is feasible; levels <1% reflect the absence of active rejection and levels >1% indi-cate a probability of active rejection.

TAKEAWAY POINTS

The area under the curve for discriminating

ABMR from samples without ABMR was 0.87

(95% confidence interval, 0.75-0.97).

Focus on Transplantation | News

Patients who undergo kidney trans-plantation for long-term curative treatment of end-stage renal disease

are required to maintain lifelong immuno-suppressive treatment to ensure adequate graft function. The immunosuppression therapy is associated with an increase in the risk of certain kinds of cancers, particularly cancer of the skin, leading to increased morbidity and mortality in transplant recipients.

The risk of skin cancer, such as mela-noma, is increased according to the type, intensity, and duration of immunosuppres-sive therapy following transplantation. Two mechanisms are associated with the in-creased risk of melanoma: (1) immunosup-pressive agents are inherently carcinogenic, and (2) the body’s self-defense against malignant changes is inhibited with chronic immunosuppression. Compared with the general population, the risk of melanoma in solid-organ transplant recipients is in-creased 3- to 5-fold.

In the past decade, there have been changes in immunosuppression regimens and novel immunosuppressive agents have been developed. Mona Ascha, MD, and colleagues in Cleveland, Ohio, conducted a retrospective cohort study designed to provide an up-to-date review of the inci-dence of melanoma in kidney transplant recipients. The researchers utilized a cohort from the United States Renal Data System (USRDS) from the years 2004 through 2012 to assess the risk factors associated with the development of melanoma in that patient population. They reported study results in JAMA Dermatology [doi:10.1001/jamadermatol.2017.2291].

The USRDS combines data from the United Network for Organ Sharing with Medicare and Medicaid payment data. The researchers identified 105,174 people who were first-time kidney transplantation re-cipients between 2004 and 2012 and had a record of a Medicare claim. Of those, 0.46%

(n=488) had an International Classification of Diseases, Ninth Revision, Clinical Modifica-tion code for melanoma.

Compared with those who did not develop melanoma, those who did receive a melano-ma diagnosis were older (49.7 vs 60.4 years; P<.001), and more likely to be male (60.7% vs 71.5%, P<.001). When stratified accord-ing to four or more human leukocyte antigen (HLA) mismatches compared with fewer than four HLA mismatches, the proportion of those with four or more HLA mismatches was greater among patients without mela-noma than among those with a diagnosis of melanoma (62.9% vs 55.1%; P<.001). Mean donor age was greater for those with mela-noma than for those in the nonmelanoma group (42.6 vs 39.2 years; P<.001)

Nearly all of the patients with melanoma were white (96.1%); proportions of Native Americans, Asians, blacks, and Hispanics were 0.6%, 1.0%, 2.3%, and 5.5%, respec-tively. In the nonmelanoma group, 66.5% were white, with the other racial groups being 1.0%, 5.0%, 27.5%, and 14.2%, respectively.

There was a significant difference in the proportion of white kidney donors in the melanoma group compared with the non-melanoma group (92.4% vs 82.9%, P<.001). The proportion of living donors was also higher in the group that developed mela-noma compared with the nonmelanoma group (44.7% vs 33.7%, P<.001). Finally, those in the melanoma group were signifi-cantly more likely to be taking cyclosporine (4.9% vs 3.2%; P=.04) or sirolimus (22.3% vs 13.2%; P<.001) compared with those in the nonmelanoma group.

The overall crude prevalence of mela-noma in the USRDS cohort was 0.47%; the prevalence in the USRDS and the Surveil-lance, Epidemiology, and End Results (SEER) database were standardized to the 2000 US standard population. The over-all relative rate of melanoma for USRDS patients compared with SEER patients is

4.9, indicating that USRDS patients were 4.0 times more likely to develop melanoma compared with SEER counterparts. When adjusted for age, the prevalence of mela-noma in the kidney transplant population is 208 per 100,000 patients, while the crude prevalence is 462 per 100,000 patients.

In a multivariable Cox proportional hazards model of disease-free survival, age, race, sex, donor type, cyclosporine therapy, and sirolimus therapy had statisti-cally different hazard ratios. There was an association between 1.06 times the hazard with each extra year of age (95% confidence interval [CI], 1.05-1.06; P<.001). In race/ethnicity models, Asian, African American, and Hispanic transplant recipients had decreased hazard ratios of 0.16 (95% CI, 0.06-0.38; P<.001), 0.06 (95% CI, 0.03-0.11; P<.001), and 0.30 (95% CI, 0.20-0.45, P<.001), respectively, compared with white recipients.

Transplant recipients with living donors had 1.35 times the hazard of those with de-ceased donors (95% CI, 1.11-1.64; P=.002), and long-term immunosuppression with cyclosporine and sirolimus had hazard ratios of 1.93 (95% CI, 1.24-2.99; P=.004) and 1.54 (95% CI, 1.22-1.94; P<.001), respectively.

The study did have some limitations, according to the researchers, including defining participants with melanoma from diagnosis codes, which may have led to under reporting the incidence of melano-ma; using SEER as a reference group; and the inability to assess certain melanoma risk factors that were not captured in the USRDS database.

In conclusion, the researchers said, “Re-nal transplant recipients are at greater risk of developing melanoma than the general population. We provide detained informa-tion and identified several important trends and risk factors in this vulnerable patient group that we believe can guide clinicians in providing adequate care.”

13Nephrology Times | October 2017

Risk of Melanoma in Kidney Transplant Recipients Associated with Older Age, Sex, and Donor Type

Researchers con-ducted a retrospec-tive cohort study to assess the risk of renal transplant recipients for de-veloping melanoma and to identify the factors associated with that risk.

Using data from the United States Renal Data System for the years 2004 through 2012, the research-ers identified 105,174 first-time kidney transplanta-tion recipients who had a Medicare claim; of those, 0.46% (n=488) had a ICD-9-CM diagnosis code for melanoma.

The risk factors for development of melanoma identi-fied in the study included older age among recipients and donors, white race, living donors, and long-term ther-apy with sirolimus and cyclosporine.

TAKEAWAY POINTS

News Briefs

LUTONIX® 035 DCB Granted FDA ApprovalIn late August, the US FDA granted pre-market approval to the LUTONIX® 035 drug coated balloon (DCB) PTA catheter. The LUTONIX 035 is now available in the United States.

In a press release from C.R. Bard, Inc., the manufacturer of the catheter, Timothy M. Ring, chairman and chief executive officer, said, “This approval offers a new treatment option for patients suffering from end-stage renal disease. In line with our continued commitment to deliver products that improve patient care, we are proud to extend the benefits of the LUTONIX 035 DCB catheter to help preserve treatment options for US patients.”

The LUTONIX 035 is the first and only drug-coated balloon that is approved by the FDA as safe and effective in patients who are facing kidney failure and who have ste-notic lesions in arteriovenous (AV) dialysis fistulae. This approval adds to the previous FDA indication of the LUTONIX 035 DCB catheter for the treatment of superficial femoral artery and popliteal artery disease.

Scott O. Treotola, MD, the Stanley Baum

professor of radiology, associate chair, and chief, international radiology at the Perel-man School of Medicine at the University of Pennsylvania, Philadelphia, and the principal investigator of the LUTONIX AV clinical trial, said, “For patients undergoing hemodi-alysis for kidney failure, who already spend a significant portion of their time undergoing dialysis and other treatments, repeated rein-terventions to maintain AV access can be an added burden, with many patients returning as frequently as every other month. The LU-TONIX 035 DCB catheter provides another option for physicians. It’s intended to offer patients with end-stage renal disease fewer interruptions in treatment and less time undergoing access maintenance, potentially leading to improved patient satisfaction and quality of life.”

No Link Between Marijuana Use and Kidney Function in Young Healthy AdultsA recent study found little evidence that

kidney function in young healthy adults is affected by marijuana use. Researchers at the Univer-sity of California, San Francisco, and the San Francisco Veterans Affairs Medical Center recently conducted the first study de-signed to examine potential links between marijuana use and kidney function in a population of young healthy adults. Data from the Coronary Artery Risk Development in Young Adults study were used for the current study. That data includes repeated assessments of marijuana use and kidney outcomes.

In an article in Medical News Today, Julie Ishida, MD, MAS, said, “Results from our observa-tional study in young adults with normal kidney function may not translate into a clinically meaning-ful difference and may be insuf-ficient to inform decision-making concerning marijuana use; however, it is possible that the association between marijuana use and kidney function could be different in other populations such as older adults or patients with kidney disease, so additional research is needed.”

Results of the study are report-ed in the Clinical Journal of the American Society of Nephrology.

NxStage System One™ Used in Nine of Top Ten Nephrology Hospitals in USIn a press release from NxStage Medical, Inc., the company announced that the NxStage System One™ is now used in nine of the top ten nephrology hospitals in the United States and in 15 of the top 20. The System One simplifies care in acute care settings and allows staff to deliver the prescribed renal replacement therapy via a variety of modalities to critically ill patients. The ranking was reported in US News & World Report.

According to the press release, System One offers multiple features designed to simplify therapies in hospitals. The features include the NxView interface with graphic touch system display that pro-vides treatment information and charting assistance, a drop-in cartridge that allows multiple therapies, no waste bags, and no special electrical or plumbing needs. In addition, the range of flow rates in System One allows hospital staff to customize therapy based on the patient’s condition.

NxStage Medical and Dialyze Direct Partner in OhioIn a recent press release from NxStage Medical, Inc., the company announced that its NxStage Kidney Care subsidiary is forming a partnership with Dialyze Direct to provide on-site dialysis to skilled nursing facility patients in Ohio. NxStage Medical is a medical technology company that focuses on advancements in renal care; Dialyze Direct is a leader in geriatric dialysis that provides staff-assisted home hemodialysis to patients in skilled nursing facilities.

Dialyze Direct will combine its model of care specifically designed for the geriat-ric patient population in skilled nursing facilities in Ohio to provide on-site dialy-sis utilizing the NxStage System One™. On-site dialysis lessens the burdens of organizational and operational challenges and reduces or eliminates the stress that transporting patients for dialysis creates. Results of studies have demonstrated re-ductions in hospitalizations and mortality in patients receiving on-site, more frequent hemodialysis at skilled nursing facilities.

Henry Kauftheil, chairman of Dialyze Direct, said in the press release, “Our mis-sion is to deliver innovative and compas-sionate dialysis care to geriatric patients in skilled nursing facilities and we real-

Nephrology Times | October 201714

At Sceptre Management, we’re renal billing specialists. But what we really specialize in is improving your cash flow, reducing your receivables, eliminating frustration, and keeping you in compliance.

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News Briefs

ized we needed an alternative strategy to meet the growing demand for our services in certain states such as Ohio where we do not yet have an operating presence. NxStage is an ideal partner to help us expand our footprint and bring our much-needed services to skilled nursing facility patients.”

Jeff Burbank, chief executive officer and founder of NxStage Medical, added, “We believe the skilled nursing facility market represents an opportunity to improve out-comes and quality of life for skilled nurs-ing patients, as well as to improve overall costs of care, by reducing transportation costs and rehospitalization rates. We look forward to working with Dialyze Direct to address unmet needs in skilled nursing facility end-stage renal disease.”

FDA Approval for Vabomere Granted in AugustThe US FDA approved Vabomere for adults with complicated urinary tract infections, including pyelonephritis, a type of kidney infection caused by specific bacteria. Va-bomere contains meropenem, an antibac-terial, and vaborbactam, which inhibits certain types of resistance mechanisms used by bacteria.

In a press release from the FDA, Edward Cox, MD, director of the Office of Antimi-crobial Products in the agency’s Center for Drug Evaluation and Research, said, “The FDA is committed to making new safe and effective antibacterial drugs available. This approval provides an additional treat-ment option for patients with complicated urinary tract infection, a type of serious bacterial infection.”

In a clinical trial that included 545 adults with complicated urinary tract infection, including patients with pyelo-nephritis, approximately 98% of patients treated with Vabomere were cured or had improvements in symptoms and a negative urine culture test, compared with 94% of the group treated with another antibacte-rial drug (piperacillin/tazobactam). At 7 days following completion of treatment, 77% of those in the Vabomere group had resolved symptoms and a negative urine culture compared with 73% in the control group.

The Vabomere approval was granted to Rempex Pharmaceuticals.

15Nephrology Times | October 2017

Major Meetings 2017–2018American Society of Nephrology Kidney Week 2017October 31-November 5, 2017

New Orleans, Louisiana

www.asn-online.org/education/kidneyweek/2017/ meeting-overview.aspx

Annual Dialysis ConferenceMarch 3-6, 2018

Orlando, Florida

http://annualdialysisconference.org

National Kidney Foundation Spring Clinical Meetings 2018April 10-14, 2018

Austin, Texas

www.kidney.org/professionals/news/meetings

American Transplant Congress 2018June 2-6, 2018

Seattle, Washington

www.atcmeeting.org

American Society of Nephrology Kidney Week 2018October 23-28, 2018

San Diego, California

American Nephrology Nurses Association 2018 National SymposiumApril 15-18, 2018

Las Vegas, Nevada

http://bit.ly/2m3ilvX

Abstract Roundup

16 Nephrology Times | October 2017

ACUTE KIDNEY INJURY

30-Day Outcomes Poor Following Discharge from the ED with AKIClinical Journal of the American Nephrology Society. 2017, doi: 10.2215/CJN.10431016Rey R. Acedillo, MD, and colleagues con-ducted a population-based retrospective co-hort study designed to examine the charac-teristics and outcomes of patients discharged home from an emergency department (ED) with acute kidney injury (AKI). The cohort included 6346 patients ≥40 years of age in Ontario, Canada, who were discharged from the ED with AKI defined using serum creati-nine values from 2003 to 2012.

The outcomes of interest were all-cause mortality, receipt of acute dialysis, and hospi-talization within 30 days following discharge from the ED. The researchers matched 4379 discharged patients to 4379 patients who were hospitalized from the ED with similar stage of AKI. They also matched 6188 dis-charged patients to 6188 patients who were discharged home from the ED with no AKI.

Of the 63465 patients discharged with AKI, 95% (n=6012) had stage 1 AKI, 5% (n=290) had stage 2, and 0.7% (n=44) had stage 3. Within 30 days of discharge from the ED, 2% with stage 1 AKI (n=127), 5% with stage 2 AKI (n=15), and 16% of those with stage 3 AKI (n=7), died; 0.3% (n=22) received acute dialysis; and 16% (n=1032) were hospitalized.

There was an association with lower morality among those who were discharged from the ED versus those who were hos-pitalized (3% vs 12%; relative risk [RR], 0.3; 95% confidence interval [CI], 0.2-0.3). There was an association with higher mortality among those discharged from the ED with a diagnosis of AKI versus those discharged without a diagnosis of AKI (2% vs 1%; RR, 1.5; 95% CI, 1.2-2.0).

In conclusion, the researchers said, “Pa-tients discharged home from the emergency department with AKI are at risk of poor 30-day outcomes. A better understanding of care in this at-risk population is warranted, as are testing strategies to improve care.”

Nephrologists’ Role in Follow-Up Care for Patients with AKIAdvances in Chronic Kidney Disease. doi:org/10.1053/j.ackd.2017.05.008Acute kidney injury (AKI) is associated with long-term health outcomes. When AKI is severe or persistent, it is associated with all-cause mortality, chronic kidney disease, end-stage renal disease, cardiovascular events, and reductions in quality of life.

Data from a previous study found that pa-tients with AKI that requires dialysis therapy benefit from nephrologist care. However, other studies have demonstrated that the majority of patients with AKI do not seek

care from a nephrologist, raising questions about the elements of care that may improve outcomes in survivors of AKI and which sur-vivors would benefit from nephrologist care.

Samuel A. Silver, MD, and colleagues reviewed the evidence supporting patient follow-up after AKI. The researchers also described the current state of follow-up care and examined strategies to improve long-term outcomes among AKI patients.

Possible opportunities to improve care, according to Dr. Silver et al., include ap-propriate risk stratification, closer monitor-ing of kidney function, management of complications related to chronic kidney disease, blood pressure control, reconcilia-tion of medication, and patient education. Nephrologists are in the best position to “lead and advocate for outpatient pathways for survivors of AKI,” the researchers said.

CHRONIC KIDNEY DISEASE

Treating Patients with Kidney Disease and HCV InfectionWorld Journal of Hepatology. 2019;9(19):833-839Among patients with chronic kidney dis-ease and end-stage renal disease, the preva-lence of hepatitis C virus (HCV) infection is greater than that in the general population. Direct-acting antiviral agents have been shown to achieve higher sustained virologic response rates than protocols based on interferon therapy.

According to Marco Ladino, MD, and colleagues, when treating patients with reduced kidney function, glomerular filtra-tion rate <30 mL/min/1.73 m2 may make therapy with some direct-acting antivirals unadvisable. However, there are now direct-acting antivirals approved by the US FDA for treatment of patients with kidney disease and reduced renal function. Those agents have been shown to be effective with sustained viral response rates compa-rable to the general population with good safety profiles.

“A disease that was only recently con-sidered to be very challenging to treat in

patients with kidney dysfunction is now curable with these medications,” the re-searchers said.

Current Best Practice for High-Quality CRRT DeliveryAdvances in Chronic Kidney Diseases. doi:10.1053/j.ackd.2017.05.003The use of continuous renal replacement therapy (CRRT) is expanding worldwide; however, despite improvements in technol-ogy, CRRT remains a complex intervention, according to Michael J. Connor, Jr, MD, and Nithin Karakala, MD.

CRRT requires the close cooperation of a multidisciplinary team, including critical care clinicians, nephrologists, nurses, phar-macists, and nutritionists. A growing evi-dence base supports evolving best practice and consensus to define high-quality CRRT.

Drs. Connor and Karakala reviewed the current best practice on several aspects of CRRT delivery, including optimal CRRT dose, anticoagulation, dialysis vascular ac-cess, fluid management, and drug dosing.

Treating CKD Patients with SOF-Based HCV TherapyClinical and Molecular Hepatology. doi:org.10.3350/chm.2016.0087It is essential to treat chronic hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD). The availabil-ity of direct-acting antiviral (DAA) therapy has improved overall HCV cure rates, but there are few data on DDA therapy use in patients with CKD.

Hyun Phil Shin, MD, and colleagues recently conducted a retrospective analysis of all patients treated with a regimen based on sofosbuvir (SOF) from December 2013 through September 2015 at Virginia Mason Medical Center. Data on HCV G1 patients with stage 3 CKD was collected.

During the study period, 28 patients with HCV G1 and stage 3 CKD were treated with a SOF-based regimen. Of those, 21 had stage 3A CKD, defined as estimated glomerular filtration rate (eGFR) 45 to 60 mL/min/1.73 m2, and seven had stage 3B CKD, defined as eGFR 30 to 45 mL/min/1.73 m2. After 12 weeks of SOF-based therapy, the overall sustained virologic re-sponse (SVR12) rate was 85.7% (n=24/28 patients). Among patients with 3A CKD, the SVR12 rate was 81.0% (n=17/21) and among stage 3B CKD patients, the SVR12 rate was 100% (n=7/7). More than 30% reduction in eGFR was seen in 5 of the 28 patients.

In conclusion, the researchers said, “SOF-based regimens resulted in high SVR12 rates in patients with moderately impaired renal function. During therapy, HCV patients with CKD should be carefully monitored for worsening renal function.” Im

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Abstract Roundup

17Nephrology Times | October 2017

Education Intervention Improves Nutritional Status in Spanish StudyJournal of Renal Nutrition. doi:org/10.1053/j.jrn.2017.02.004In patients with chronic kidney disease, protein-energy wasting (PEW) is associated with increased morbidity and mortality as well as a rapid deterioration of kidney func-tion. According to Almudena Pérez-Torres, MS, and colleagues, there are few data avail-able on the effect of nutrition intervention in that patient population.

The Spanish researchers conducted a 6-month, longitudinal, prospective, and interventional study designed to evaluate the efficacy and safety of a nutrition educa-tion program (NEP) in patients with non–dialysis-dependent CKD (NDD-CKD), based on the diagnostic criteria for PEW proposed by the International Society of Renal Nutri-tion and Metabolism. The study period was March 2008 to September 2011.

Of the 160 NDD-CKD patients who started the NEP, 128 completed it. The NEP included design of an individualized diet plan based on the patient’s nutritional status at baseline, as well as four sessions devoted to nutrition education. The pri-mary outcome measures were changes in nutritional status (PEW) and parameters of biochemical, anthropometric, and body composition.

Following 6 months of intervention, there were decreases in levels of potassium and inflammation and improvement in lipid profile. In men, there were decreased levels of albumin and prealbumin, and in women, there were decreased levels of proteinuria. Overall, the prevalence of PEW decreased (27/3% to 10.9%); in men, the decrease was from 29.5% to 6.5% and in women, the decrease was from 25.4% to 14.9%.

“The NEP in NDD-CKD generally im-proved nutritional status as measured by PEW parameters, but individual poorer results indicated the need to pay special attention to female sex and low body mass index at the start of the program,” the researchers said.

Feedback on Salt Intake Improves Reduction Efforts in CKD Patients Journal of Renal Nutrition. doi:org/10.1053/j.jrn.2017.04.005Reduction in dietary salt intake in patients with chronic kidney disease (CKD) can help reduce hypertension, cardiovascular events, CKD progression, and mortality. However, according to Kiyotaka Uchiyama, MD, and colleagues, it is difficult to recommend salt reduction for patients whose actual sodium intake is unknown. The research-ers conducted a prospective cohort study to measure dietary sodium intake in 127 adult outpatients with CKD.

The primary outcome of interest was esti-

mated salt excretion; a secondary outcome was the urinary protein to creatinine ratio (UPCR). Patients’ spot urine-estimated salt intake was measured each time they visited the outpatient clinic. Patients were urged to achieve their salt restriction goal based on the collected data.

During a follow-up of 12 months, the medi-an number of patient visits was seven. There was significant reduction in the estimated salt intake from 7.98 g/day to 6.77 g/day. There was also reduction in median UPCR from 0.20 to 0.10. In multiple regression analysis, there was a positive association between a reduction in UPCR and baseline UPCR and a reduction in systolic blood pressure. There was a positive correlation with a reduction in the estimated salt intake.

In conclusion, the researchers said, “Providing spot urine-estimated salt intake feedback effectively motivated CKD patients to reduce their salt intake. Spot urine-guided salt reduction may slow CKD progression through decreased urinary protein excretion.”

TRANSPLANTATION

Outcomes and Characteristics of Deceased-Donor Kidney OffersClinical Journal of the American Society of Nephrology. 2017;12(8):1311-1320Researchers led by Anne M. Huml, MD, conducted a cohort study aimed at deter-mining outcomes of offers of deceased donor kidneys and the association of the outcomes with characteristics of waitlisted patients and organ donors. Data from the United Network of Organ Sharing database were used to examine all seven million deceases-donor adult kidney offers in the United States from 2007 to 2012 that led to eventual transplantation.

The study cohort included 178,625 patients who were waitlisted for a deceased-

donor kidney transplant and 31,230 deceased donors. Kidneys from deceased donors were offered to transplantation centers a median of seven times before being accepted for trans-plantation. Refusals were most commonly made due to donor-related factors (age or organ quality; 3.2 million offers; 45.0%) and transplant center bypass (minimal criteria not met; 3.2 million offers, 44.0%).

Following adjustment for characteristics of waitlisted patients, organ donors, and transplantation centers, male and Hispanic waitlisted donors were less likely to have an offer accepted than female and white patients, respectively. There was wide varia-tion across transplantation centers in the likelihood of offer acceptance.

In conclusion, the researchers said, “Transplant centers frequently refuse deceased-donor kidneys. Such refusals differ by patient and donor characteristics, may contribute to disparities in access to transplantation, and vary greatly across transplant centers.”

Induction Treatment of IL-2RAb in Pediatric Transplantation RecipientsTransplantation. 2017;101(9):2146-2151The benefits of induction of interleukin-2-receptor antibody (IL-2RAb) in reduc-ing the risk of acute rejection in adult recipients of kidney transplantation is well established; however, there are few data on a similar benefit in pediatric kidney transplantation recipients. In a recent study, Christine Marie Mincham, MBBS, and colleagues sought to assess the efficacy of IL-2RAb in reducing acute rejection in pe-diatric and adolescent recipients ≤21 years of age. Data from the Australia and New Zealand Dialysis and Transplant registry were used in the study.

Between 2001 and 2012, there were 658 eligible transplant recipients; follow-up con-tinued for a median of 5.5 years. There was an association between the use of IL-2RAb induction and adjusted odds rations of 0.61 (95% confidence interval [CI], 0.41-0.91; P=.007) for any rejection, and 0.57 (95% CI, 0.35-0.92; P=.020) for early rejection, defined as occurring in the first 6 months following transplant.

The associations were attenuated in a pro-pensity score analysis, but remained statisti-cally significant. Adjusted odds ratios were 0.65 (95% CI, 0.49-0.87) for any rejection and 0.64 (95% CI, 0.44-0.93) for early rejec-tion. There were no associations between induction, graft loss, and incident cancer.

“Induction treatment with IL-2RAb in pediatric and adolescent kidney transplant recipients is associated with at least a 40% reduction in the odds of acute rejection, independent of age, era, immunological status, and initial immunosuppression,” the researchers said. Im

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We can do your billing for much lower fees than you’re paying now!”

While this is a tantalizing phrase for physicians, management, ownership, and accountants, paying for “cheap” billing frequently

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Eighteen months later I met with the owners and their accountant to review and compare our performance against that of the other company. The accountant took the amounts collected by each billing company and subtracted the billing fees to obtain a net dollar result. While our fees were nearly twice those charged by the other billing company, the accountant found we had generated $400,000 more in net reimbursement. Thus, while saving money on billing costs had appeared attractive, owners discovered the other billing company was costing them much more money due to lower reimbursement. The end of the story is that the owners transferred the billing for all of their facilities to us.

What Services Are Included in Your Fee?The owner of another billing company shared with me that they lost a relatively small client to another billing service who offered dramatically lower fees. Six months later, the former client called and begged the billing service to take them back. It turned out that the customer had not understood the competitor’s fee schedule correctly. It turned out that the rock-bottom price included only the filing of claims. Everything else was the responsibility of the health care provider unless they wanted to pay additional fees, which brought the total rate to the same as the prior billing company.

Rates charged for billing services vary significantly and the services covered by the rate can be dramatically different between companies. Fees can also be charged by the number of claims filed or number of visits or treatments. These fees can sound much lower than those charged by billing companies that charge a percentage of what they collect. The billing company that charges based on the number of claims or visits has less incentive to col-lect than a company paid on collections.

Let’s Have Our EHR Company Do Our BillingElectronic health record (EHR) companies learned years ago that they can significantly increase their revenue and profits by adding billing modules and, in some cases, offer billing services. While terms such as “seamless integration” and “built-in data checks” sound great, EHR companies are first and foremost technology companies. Their focus is on technology and their solution to billing problems is more technology.

As the owner of a billing company, I have found that many of the billing modules created by EHR companies lack features that can hinder the revenue cycle process. While EHRs can speed up the data exchange process, other por-tions of the billing process, such as unpaid claim follow-up, can be slowed, even resulting in a reduction in amounts collected.

Another problem with integrated clinical and billing modules is that updates to one module can have unintended consequences in the other. Clini-

cians may enter data correctly in the clinical piece of the EHR, but sometimes the data can be missing or misreported in the billing

piece. Some of the errors may be caught in the billing mod-ule’s data check process, but sometimes incorrect or incom-plete data can sail past claim scrubbing software and appear on claims that are processed for payment. Unfortunately, the errors can go on undetected for months or longer before an audit or quality reporting issue arises and an investiga-tion catches the error. The incorrect data can result in erroneous quality reporting scores and/or cause payments to be reduced or recouped.

HOW TO PROTECT YOURSELFMy recommendations to protect yourself from ineffective billing services are: (1) Before going with a service, always speak to several of their current customers to find out how the service actually performs and what the costs re-ally are; and (2) Have a qualified outside entity audit your billing at least annually, regardless of whether or not you, your EHR company, or another company provides your billing services.

In the long run, the costs of preventive services far outweigh the costs of penalties, recoupments, and poor quality scores that may go undetected otherwise.

3 Waysto read Nephrology Times:

or Online at www.nephtimes.com

Inside, you will find:

✓ Important news, views, and events in the world of nephrology

✓ Interviews with key opinion leaders

✓ Insights into clinical data and how it impacts your practice

✓ Highlights and news from Kidney Week and more

NephrologyTimesPractical News, Trends, and Analysis

Predialysis Systolic Blood Pressure and Risk of All-Cause Mortality Postdialysis

The incidence of end-stage renal disease (ESRD) among individu-als with chronic kidney disease

(CKD) is high, despite advances in the understanding of CKD progression. Patients with CKD are not dependent on dialysis who transition to ESRD have the highest mortality within the first few months following the transition to dialysis therapy. Those patients also have exceptionally high healthcare costs and burden. Identifying modifiable risk factors and interventions during the period prior to the transition to dialysis could lessen the adverse outcomes in this vulnerable population.

In the general population, a common risk factor for cardiovascular disease and death is hypertension; however, low blood pressure has been associated with mortality in patients on dialysis therapy. Some studies have suggested a J-shaped association between systolic blood pressure and mortality in patients with non–dialysis-dependent CKD. Cur-rent clinical guidelines suggest a target blood pressure <140/90 or <130/80 mm Hg for patients with CKD, depend-ing on age, severity of albuminuria, and comorbid conditions. However, there are few data on the association between blood pressure and mortality in patients with advanced non–dialysis-dependent CKD, including those transitioning to maintenance dialysis therapy.

Biomarkers of Kidney Injury and Repair Measured in Marathon Runners

In 2014, a record number of individuals in the United States competed in a marathon; the increase in marathon participation to 550,600 has subsequently increased the need to more closely examine the relationship between marathon

running and kidney injury. Because runners are generally seen as healthy athletes with trained physiology to tolerate high states of energy expenditure, the relation-

Hemoglobin A1c Level Control and Risk of ESRD and Mortality in Patients with CKD

Patients with both diabetes and chronic kidney disease (CKD) are at in-creased risk for death, compared with those with diabetes or CKD alone. Diabetic kidney disease is increasing in prevalence; diabetic nephropathy is

the leading cause of end-stage renal disease (ESRD). The ideal level of glycated he-moglobin (hemoglobin A1c [HbA1c]) has not been positively established; results of some clinical trials in the general population have shown an association be-tween intensive glycemic control and adverse outcomes in patients with diabetes. The American Diabetes Association recommends targeting an HbA1c level <7% for most nonpregnant adults and <8% for those at risk for hypoglycemia, exten-

continued on page 6

continued on page 4

continued on page 5

October 2017 VOLUME 9, NUMBER 7

Appropriateness of Antibiotics Prescribed to Hemodialysis PatientsThe oral antibiotics most commonly prescribed inappropriately were amoxycillin/clavulanic acid and cephalexin. 7

Peritoneal Dialysis Compared with Hemodialysis in Infants Younger than One YearThere are cases where peritoneal dialysis is contraindicated and hemodialysis is the only alternative prior to kidney transplantation. 9

Focus on Transplantation: Differentiating between Allograft Active Rejection and Allograft InjuryResults of the DART study. 12

PLUS....

From the FieldCheap Billing Can Be Costly 18

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From the Field

Cheap Billing Can Be Costly

18 Nephrology Times | October 2017

Rick Collins

Rick Collins is the chief operating officer of Sceptre Management Solutions, Inc., a company specializing in billing for outpatient ESRD facilities, nephrology practices, and vascular access. Your questions are welcome and he can be reached at rcollins@sceptremanagement.com or 801.775.8010.

“

3 Waysto read Nephrology Times:

or Online at www.nephtimes.com

Inside, you will find:

✓ Important news, views, and events in the world of nephrology

✓ Interviews with key opinion leaders

✓ Insights into clinical data and how it impacts your practice

✓ Highlights and news from Kidney Week and more

NephrologyTimesPractical News, Trends, and Analysis

Predialysis Systolic Blood Pressure and Risk of All-Cause Mortality Postdialysis

The incidence of end-stage renal disease (ESRD) among individu-als with chronic kidney disease

(CKD) is high, despite advances in the understanding of CKD progression. Patients with CKD are not dependent on dialysis who transition to ESRD have the highest mortality within the first few months following the transition to dialysis therapy. Those patients also have exceptionally high healthcare costs and burden. Identifying modifiable risk factors and interventions during the period prior to the transition to dialysis could lessen the adverse outcomes in this vulnerable population.

In the general population, a common risk factor for cardiovascular disease and death is hypertension; however, low blood pressure has been associated with mortality in patients on dialysis therapy. Some studies have suggested a J-shaped association between systolic blood pressure and mortality in patients with non–dialysis-dependent CKD. Cur-rent clinical guidelines suggest a target blood pressure <140/90 or <130/80 mm Hg for patients with CKD, depend-ing on age, severity of albuminuria, and comorbid conditions. However, there are few data on the association between blood pressure and mortality in patients with advanced non–dialysis-dependent CKD, including those transitioning to maintenance dialysis therapy.

Biomarkers of Kidney Injury and Repair Measured in Marathon Runners

In 2014, a record number of individuals in the United States competed in a marathon; the increase in marathon participation to 550,600 has subsequently increased the need to more closely examine the relationship between marathon

running and kidney injury. Because runners are generally seen as healthy athletes with trained physiology to tolerate high states of energy expenditure, the relation-

Hemoglobin A1c Level Control and Risk of ESRD and Mortality in Patients with CKD

Patients with both diabetes and chronic kidney disease (CKD) are at in-creased risk for death, compared with those with diabetes or CKD alone. Diabetic kidney disease is increasing in prevalence; diabetic nephropathy is

the leading cause of end-stage renal disease (ESRD). The ideal level of glycated he-moglobin (hemoglobin A1c [HbA1c]) has not been positively established; results of some clinical trials in the general population have shown an association be-tween intensive glycemic control and adverse outcomes in patients with diabetes. The American Diabetes Association recommends targeting an HbA1c level <7% for most nonpregnant adults and <8% for those at risk for hypoglycemia, exten-

continued on page 6

continued on page 4

continued on page 5

October 2017 VOLUME 9, NUMBER 7

Appropriateness of Antibiotics Prescribed to Hemodialysis PatientsThe oral antibiotics most commonly prescribed inappropriately were amoxycillin/clavulanic acid and cephalexin. 7

Peritoneal Dialysis Compared with Hemodialysis in Infants Younger than One YearThere are cases where peritoneal dialysis is contraindicated and hemodialysis is the only alternative prior to kidney transplantation. 9

Focus on Transplantation: Differentiating between Allograft Active Rejection and Allograft InjuryResults of the DART study. 12

PLUS....

From the FieldCheap Billing Can Be Costly 18

PrintiPad

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