POMA District VIII 31 D8 18-S… · •Briefly review anemia and ... A., Yevzlin, A., Wu, S.,Beathard, G. McGraw Hill Companies, Inc. Chapter ... Increase form 8.5 to 11% from 2010

“End Stage Renal Disease Updates”Joseph C. Sysak, DO

POMA District VIII 31st Annual Educational Winter SeminarJanuary 25‐28, 2018 1

Joshua C. Sysak, DO

•Brief history of dialysis•Review the incidence, prevalence, and costs of ESRD•Renal replacement options in ESRD•Dialysis Access issues•Briefly review anemia and bone disease•Cardiovascular disease in ESRD•Kidney transplant•Future treatment options

1854 - Concept of dialysis began when the term diffusion was described by Thomas Graham, MD in Glasgow, Scotland Diffusion – solute transport across a semi-permeable membrane

1924 – George Haas performed the first hemodialysis in humans Lasted for 15 minutes

Dialyzers were made from vegetable and animal membranes

Blood was obtained from the radial artery and returned to the antecubital vein



March 17, 1943 – Willem Kolff performed the first effective dialysis on a 29 year old housemaid with uremia, CHF, and malignant HTN Rotating drum artificial kidney by wrapping 20 m of cellophane tubing around a horizontal drum

The Revolution in the treatment of kidney failure. Individual website. Lilly Crum.

Blood was obtained through a glass cannula that was placed in the radial artery through a small incision

1946-1960 – Dr. Nils Alwall from Lund, Sweden enclosed the Kolff drum artificial kidney in a stainless steel cannister Allowed for positive pressure to the blood larger quantity of fluid by ultrafiltration

1500 dialysis treatments

Access limited dialysis from being a long term life sustaining therapy



1950’s-1960s – Dr. Belding Scribner modified the glass arterial-venous shunt by making them from Teflon Two Teflon tubes were used to cannulate the radial artery and an adjacent cephalic vein at

the wrist

March 9, 1960 – Clyde Shields a 39 year old machinist with a 7 year history of CKD and proteinuria was the first patient who was dialyzed successfully on a chronic basis Initially one treatment per week that lasted 24 hours

Survived for 11 years, died in 1971 from massive MI

Interventional Nephrology. Asif, A., Agarwal, A., Yevzlin, A., Wu, S.,Beathard, G. McGraw Hill Companies, Inc. Chapter 1. Pg 3-7.

Columns Archives. The University of Washington Alumni Magazine. Internet site.

Renal Support Network. Web ID 223

1962 – Dr. Scribner and Dr. James Havilland established the Seattle Artificial Kidney Center This was the first outpatient dialysis center in the world 6 dialysis machines

Created an ethical question on who should be dialyzed

This was known as the “Seattle Experience” and led to the creation of one of the first bioethical committees



2015

124,114 patients Male – 72,142 Female – 51,972

Race White - 83,265 Black/African American – 32,481 Asian – 1,127

Etiology Diabetes – 56,269 HTN – 34,762 GN – 9,209 Cystic – 2,835

2016

124,701 patients Male – 72,192 Female – 52,509

Etiology Diabetes – 58,191 HTN – 34,828 GN – 9,120 Cystic – 3,519

2017 Annual Data ReportVolume 2, Chapter 1

14

Data Source: Reference Table D1. Abbreviation: ESRD, end‐stage renal disease.


15

Data Source: Reference Table A.2(2) and special analyses, USRDS ESRD Database. Standardized for sex and race. The standard population was the U.S. population in 2011. Abbreviation: ESRD, end‐stage renal disease.




16

Data Source: Reference Table A.2(2) and special analyses, USRDS ESRD Database. Standardized for age and sex. The standard population was the U.S. population in 2011. Abbreviations; AI/AN: Americans Indian/Alaska Native; NA/PI: Native Hawaiian/Pacific Islander; ESRD, end‐stage renal disease.

2015

706,352

2016

727,276


18

Data Source: Reference Table D.1. Abbreviation: ESRD, end‐stage renal disease.




19

Total HemodialysisPeritoneal

dialysisTransplant

N % N % N %

Age

0‐21 9,738 1,775 18.2 1,008 10.4 6,955 71.4

22‐44 102,744 51,188 49.8 9,072 8.8 42,484 41.3

45‐64 308,616 184,098 59.7 21,791 7.1 102,727 33.3

65‐74 166,679 112,875 67.7 10,899 6.5 42,905 25.7

75+ 113,575 94,401 83.1 6,435 5.7 12,739 11.2

Sex

Male 405,248 254,066 62.7 27,262 6.7 123,920 30.6

Female 296,046 190,240 64.3 21,941 7.4 83,865 28.3

Race

White 430,569 251,259 58.4 32,543 7.6 146,767 34.1

Black/African American 215,299 160,990 74.8 12,304 5.7 42,005 19.5

American Indian or Alaska Native 7,497 5,228 69.7 421 5.6 1,848 24.6

Asian 32,968 18,927 57.4 3,104 9.4 10,937 33.2

Native Hawaiian or Pacific Islander 8,453 6,208 73.4 640 7.6 1,605 19.0

Other or Multiracial 3,333 1,176 35.3 142 4.3 2,015 60.5

Unknown 3,233 549 17.0 51 1.6 2,633 81.4

Ethnicity

Hispanic 122,272 82,510 67.5 7,733 6.3 32,029 26.2

Non‐Hispanic 561,794 359,578 64.0 41,248 7.3 160,968 28.7

Unknown 17,286 2,249 13.0 224 1.3 14,813 85.7

Primary Cause of ESRD

Diabetes 267,956 203,295 75.9 18,294 6.8 46,367 17.3

Hypertension 178,875 130,537 73.0 13,459 7.5 34,879 19.5

Glomerulonephritis 112,235 44,897 40.0 8,785 7.8 58,553 52.2

Cystic Kidney 33,194 10,357 31.2 2,268 6.8 20,569 62.0

Other/Unknown 109,092 55,251 50.6 6,399 5.9 47,442 43.5

Total 701,352 444,337 63.4 49,205 7.0 207,810 29.6

Data Source: Special analyses, USRDS ESRD Database. The numbers in this table exclude “Other PD” and “Uncertain Dialysis.” Abbreviation: ESRD, end‐stage renal disease; HD, hemodialysis; PD, peritoneal dialysis.

Congress expanded the Medicare program in 1973 to include any patient that needed coverage for dialysis This initially covered 10,000 patients

This now encompasses approximately 500,000 patients

ESRD patients consume a large amount of resources Total cost of ESRD program in the US was approximately $34 billion in 2016

Current costs per person per year were $88,000 based on 2016 estimates Ranges from $29,000 for transplant patients to $88,000 for hemodialysis patients and $72,000 for PD

patients

In 2011 Medicare began to bundle payments in an attempt to control costs

In 2012 Medicare approved other drugs to stimulate blood cell production

Now incentivizing dialysis centers to encourage home dialysis Waived the 90 day waiting period for reimbursement for home dialysis patients (this is still

required for in center patients)

Increased home dialysis training rates

Increased some of supply reimbursements for home dialysis patients

In 2015-2016 Medicare has put 2% of dialysis payments at risk based on providers meeting certain quality measures



United States Renal Data Systems Report (USRDS) in 2013 60 month survival measured from Day 1 of therapy for all patients in a Cohort starting in

2006 was 0.36

Improvement when compared to a Cohort starting from 1998 when the 60 month survival was 0.3

Survival rates are substantially higher in Europe and Japan Increased risk factors seem to also exist in the US – older age, higher prevalence of

diabetes, more comorbid conditions

One of the highest survival rates is in Tassin, France Greatest difference is dialysis times – 24 hours per week in Tassin

In center hemodialysis

Home dialysis Peritoneal dialysis

Home hemodialysis

3x per week

Typically 4 hours per treatment

Frequency and length of treatment are dependent on clearance

Clearance is determined by Kt/V and the urea reduction ratio (URR) Numerous factors are involved in clearance Size and weight of the patient, volume of distribution, access, blood flow, dialysate flow, and size of

the dialyzer



Treatment done every day

Can be done at night when patient sleeps – Continuous cycler peritoneal dialysis (CCPD)

Four to six exchanges can be done each day – Continuous ambulatory peritoneal dialysis (CAPD)

Nephcure. Kidney International.

Why do patient’s choose PD Freedom during the day

Time

Some control over their treatment

Preserves their GFR for a longer period of time

Factors influencing PD Pre dialysis education

2011 reimbursement change Bundled payments

Increase form 8.5 to 11% from 2010 to 2014 in the 10 largest dialysis providers



Comorbidity of PD patients is less in most studies CHOICE study looking at ESRD cohort 270 PD patients, 759 HD patients

Comorbidities were significantly less in PD patients

What does the PD patient look like in my clinical practice Less comorbidities

Younger

More active

Much more likely to be working full or part time

Higher education level

In 2009 – 94% in center HD and 6% PD

Generally thought that the survival is equal

Extremely difficult to do a randomized control trial Attempted in the Netherlands

738 patients were eligible to participate, only 38 agreed to be randomized

Several studies have found short term survival benefits with PD but very comparable survival after one to two years Intention to treat analysis of 35, 265 Canadian patients (1991-2004) Better survival with PD for the first 18 months

Better survival with HD after 36 months

Subgroup analysis of patient who started dialysis between 2001 and 2004 had better survival for 2 years and then comparable survival after 2 years

USRDS data suggests a survival benefit associated with peritoneal dialysis during the first three years on dialysis but which is lost over time Propensity matched cohort study compared survival between PD and HD between 2001 and

2013 in a healthcare organization in the US Cumulative risk of death remained lower for almost 3 years in the treated and two years in the

intention to treat analysis

Kumar VA, Sidell MA, Jones JP, Vonesh EF. Survival of propensity matched incident peritoneal and hemodialysis patients in a United States health system. Kidney Int 2014; 86: 1016

The survival is equal at five years – 34%



The survival benefit depends on multiple variables Age – the lowest RR in patients 18-44 Patients older than 65 with diabetes on HD had a lower mortality risk

Diabetes

CHF

Similar trends in other countries

Nocturnal dialysis Better BP control, regression of LV hypertrophy, improved sleep patterns

Better clearance, less hemodynamic changes

Prospective randomized studies show significant improvement in cardiovascular endpoints

HD at home, 5-6 times per week for 1.5 to 2 hours per treatment Limited data suggest relatively better survival among patients on short daily hemodialysis

compared to patients with in center HD

Patient’s are referred for Arterio-venous access creation when the GFR is 20 ml/min or less

Types of access AV fistula Takes at least 8 weeks for an AV fistula to develop

AV graft Takes 4 weeks for an AV graft to mature

Dialysis catheter Can be used immediately



©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Open Journal of Fluid Dynamics. Vol.2 No.4A(2012), Article ID:26364,7 pages DOI:10.4236/ojfd.2012.24A040



Impact of dialysis access on survival. (Astor, et al. JASN 60; 1449‐1455; 2005).

Table 3. Relative Per Person Per Year Total Medicare Costs According to the Type of VA: A CPM Cohort Study

Fistula Graft Catheter1999 43,704 51,288 61,3412003 52,751 61,929 69,893

Eggers P, et al. JASN 16; 259A: 2005.

Several obstacles to having an AV access placed Patient resistance

Small veins

Patients suddenly starting dialysis as a result of AKI

Advanced age of patients

No needle sticks are required when a dialysis catheter is used

Patients do not have to wait for bleeding to stop



Lower survival and more hospitalizations for patients with catheters

Catheters cause increased release of inflammatory mediators, interleukins, and cytokines

Higher cost

Require frequent exchanges because of dysfunction Usually because of development of a fibrin sheath

Central stenosis Subclavian dialysis catheters should not be placed unless there is no other option

Vachharajani, T. Atlas of Dialysis Vascular Access. Wake Forest University. November 21, 2010.

Agarwal, A. AJPKD. Vol 61, Issue 6. June 2013. Pg 1001‐1015



Large initiative by insurance carriers/Medicare Reimbursement incentives based on dialysis clinic catheter rates

Increased education efforts in patients with stage 3 and 4 CKD

Attempting to get patient families involved in the education process Presence of family seems to increase the chance that a patient will get an AV access

Attempting to get vein mapping soon after a patient is deemed ESRD

Designating an access nurse in each dialysis unit

PICC line approval by nephrology service

Protecting an arm for future access creation

Subjectively more fatigue

More blood transfusions

Higher incidence of hepatitis

Goal Hemoglobin is between 9 and 11 g/dl

Treatment with iron and erythropoietin is recommended to achieve this goal

Erythropoietin agents Procrit, Epogen, Aranesp, Mircera (newest agent)

Medications in this class now have a black box warning

These medications are usually adjusted based on a protocol depending on a patient’s hemoglobin level

Most common side effects include hypertension, headaches, nasopharyngitis, diarrhea



Administered at 1 to 4 week intervals

Most physicians do not acknowledge that the short or long acting agents are superior in treatment of anemia

FDA approved in the US in 2007

Not indicated for treatment of anemia secondary to chemotherapy

Contraindications Uncontrolled hypertension

Pure Red cell aplasia that begins after treatment with mircera

Allergic reactions

Phosphorous Goal is to keep the level less than 5.5 mmol/L

Elevated levels will lead to calcium/phosphorous deposition in the coronary blood vessels, vasculature throughout the body, and eventually in the soft tissues

Phosphorous is present in most foods Foods with large amounts of phosphorous are dairy, dark sodas, and nuts

Treated with a low phosphorous diet and phosphorous binders PO4 binders

Phoslo (Calcium acetate)

Renvela or renagel (Sevelamer)

Fosrenol (Lanthanum Carbonate)

Auryxia (Ferric citrate)



Auryxia (ferric citrate)

Ferric citrate binds phosphorus and precipitates to become ferric phosphate which is insoluble and is eliminated in the stool

210 mg of iron

Similar phosphorus lowering effects to calcium acetate and sevelamer

Improved iron saturation and increased ferritin levels

GI side effects are the most common side effects

Keep out of the reach of children

Doxycycline and ciprofloxacin should be taken 1 to 2 hours after auryxia as the bioavailability of these antibiotics can be affected

Secondary Hyperparathyroidism Goal PTH is between 150-300 mmol/L

Elevated PTH can lead to bone disease, increased risk for cardiovascular disease, and calciphylaxis

Treated with activated vitamin D analogues (1,25 vitamin D3 and PTH blockers) 1, 25 vitamin D analogues

Calcitriol, Hectorol, zemplar

PTH blockers

Sensipar

Main side effects are hypocalcemia and GI side effects

•Leading cause of mortality in ESRD•Cardiovascular disease accounts for 50% of all deaths•Largest specific cause of death is attributed to arrhythmic mechanisms/sudden cardiac arrest – 60%•Coronary heart disease – 20% of deaths

•Incidence of coronary disease is increased among dialysis patients versus those without kidney disease

Collins AJ, Foley RN, Herzog C, et al. Excerpts from the US Renal Data System 2009 Annual Data Report. Am J Kidney Dis 2010; 55: S1



•40% of incident dialysis patients have ischemic heart disease•Cheung AK, Sarnak MJ, Yan G, et al. Cardiac Diseases in maintenance hemodialysispatients: results of the HEMO Study. Kidney Int 2004; 65:2380

•Annual rate of myocardial infarction and/or angina is approximately 10% per year•Collins AJ, Foley RN, Herzog C, et al. Excerpts from the US Renal Data System 2009 Annual Data Report. Am J Kidney Dis 2010; 55:S1

•Choices for Healthy Outcomes in Caring for ESRD (CHOICE)•Large percentage of incident dialysis patients have traditional CV risk factors

•DM (54%), low HDL (30%), HTN (96%), LVH (22%), low physical activity (80%)

•Many dialysis patients have multiple risk factors

CKD alone Some consider CKD a CAD equivalent

Uremia and renal replacement therapy Enhanced oxidant stress, production of complement fragments and cytokines, increased

adhesion molecules in endothelial cells, and other pro-inflammatory factors which provide the proper milieu for accelerated atherosclerosis

Disorders of mineral metabolism Vascular calcification in dialysis patients from increased calcium intake, increased Ca-PO4

product, and abnormal bone metabolism

Calcium deposit in the media or intima layers or the media layer alone is associated with stiffening of the vasculature May not cause luminal narrowing but it decreases diastolic filling and increases afterload to the heart



Published May 16, 2013 at 594 × 396 in Hyperparathyroidism in Chronic Kidney Disease

IBMS BoneKEY Published Online Feb 2008

Traditional treatment of stable anginal or CAD ASA, Beta-blocker, ACE inhibitor/ARB, Nitroglycerin

Unstable CAD treatment Heparin, glycoprotein 2b/3a inhibitors, fibrinolytics Lovenox and integrelin (eptifibatide) are contra-indicated

Increased risk of bleeding in ESRD patients

Increased complications in ESRD vs non HD patients Observational studies

Hemodialysis patients were excluded from virtually all well designed studies of CABG vs PCI in coronary heart disease No randomized trials comparing CABG to PCI

Retrospective studies Drug eluding stents are more effective than bare metal stents

Lower mortality in the first 3 months after PCI compared to CABG but higher mortality and risk for the need for re-vascularization after 3 months



CABG favored over PCI unless there are higher peri-operative risks

Cardiac events and mortality are higher following PCI when compared to CABG The evidence is weak and is retrospective

Systemic Review and Meta analysis The American Journal of Cardiology. Volume 117. Issue 10, May 15, 2016. Pg 1596-1603.

Effectiveness of Percutaneous Coronary Intervention vs CABG in patients with ESRD. Ashok Krishnaswami, MD. Mas Anne, C.H Goh, MD, Alan S. Go, MD, Robert L. Lundstrom, MD, Jonathan Zaroff, MD, James J. Jang, MD, Elaine Allen, PHD. Small decrease in the relative risk of long term mortality in CABG compared with PCI

3 to 4 times increased mortality risk compared to patients with an eGFR of >60 ml/min

Use ASA and Plavix after PCI but there is definitely an increased risk of bleeding



Statins in ESRD Not recommended in mild or moderate LDL elevation (Grade 1B evidence) Continue statins if patient is already on one (Grade 2C evidence) Several large well designed trials showed no cardiovascular benefits in the primary analysis SHARP showed a benefit of statin and ezetimibe in the entire study cohort Included non HD CKD patients and HD patients Effect was not significant in dialysis sub-group

4D 1255 HD patients with DM and increased LDL were followed for 4 years Atorvastatin vs placebo No difference in incidence of the primary endpoint which was composite CV death, non fatal MI, or CVA Post Hoc analysis revealed that patients with an LDL >145 and on a statin did have a decrease in the primary

endpoint AURORA 2776 dialysis patients, rosuvastatin vs placebo Median follow up 2.8 years No difference in the primary outcome which was composite CV death, non fatal MI, or CVA

Hypertriglyceridemia Common in HD patients because of retention of atherogenic particles (ie lipoproteins)

2013 KDIGO guidelines If triglycerides are >500 treat with therapeutic life style changes

>1000 consider treatment with fibric acid derivative

Aspirin Limited data regarding the efficacy of aspirin in dialysis patients

A couple of observational studies have suggested that aspirin is associated with increased cardiovascular mortality and cardiovascular events

Increased risk of bleeding with any dose of aspirin

KDOQI guidelines do suggest aspirin 81 mg in dialysis patients (Grade 2C evidence) Dialysis patients who want to limit their risk of bleeding should not take aspirin

the cardiovascular benefit of aspirin is unproven



Hyperhomocysteinemia Lowering levels does not improve cardiovascular outcomes in dialysis patients

HOST – double blind, randomized control trial comparing folic acid, pyridoxine, and vitamin B12 to placebo 2056 patients with advanced CKD; included patients on dialysis

3.2 year follow up

Fish oil Limited data

One randomized, placebo controlled trial that showed no benefit in dialysis patients

At this point, there is no evidence to support using fish oil for cardiovascular protection in dialysis patients

Treatment of choice for ESRD

Patients are referred for transplant when their GFR is 20 ml/min or less

Multiple tests are usually required to be approved for renal transplantation Typically takes a minimum of 3 months to get on the transplant list

The waiting list for cadaveric transplants continues to lengthen

By BruceBlaus - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=44925836



Two types of Kidney transplants Cadaveric renal transplant – average graft survival approximately 12 years

Living donor renal transplant – average graft survival approximately 15 years Living related and living unrelated

Immunosuppression regimens have improved from years ago Patients are usually on 2 medications Calcineurin inhibitor - Prograf/FK-506 or Cyclosporine/Neoral/Gengraf

Inosine monophosphate dehydrogenase inhibitor (IMPDH) - Cellcept/Myfortic

UNOS 2016 96, 120 patients on the waiting list

19,060 Kidney transplants Deceased donor – 12,250

Living donor – 5,628



There are other immunosuppression agents that are being evaluated but none are used on a regular basis Sirolimus and Everolimus

Mainly will be used when patients have developed rejection on calcineurin inhibitor or if severe side effects develop while on calcineurin inhibitors

Almost all centers use steroid with-drawl protocols Meaning they get steroids at the time of transplant (induction) but they are quickly weaned off

If you see a patient on steroids, they either had a transplant many years ago or they had rejection and were therefore placed back on steroids

Generally patients subjectively feel better after having a renal transplant, have much more free time, have improved survival

Risks of renal transplant Cardiovascular disease, peri-operative mortality, infection, malignancy

Type of Donor 1 Year 3 Years 5 Years 10 Years 15 Years

Living Donor Graft survival 95% 88% 80% 57%

Patient survival 98% 95% 90% 64%

Deceased Donor

Graft survival 90% 79% 67% 41%

Patient survival 95% 88% 81% 61%

Source: SRTR -- Scientific Registry of Transplant Recipients

Graft and Patient Survival in Renal Transplant



Weighs 10 pounds

9 volt batteries used to power the device

Connects to the patient via catheter

Being tested on 7 patients in Seattle, Washington

Blood Purification Technologies Inc. of Beverley Hills, California

Bioartificial kidney

Two waste removing modules Hemofilter module processes incoming blood to create an ultrafiltrate that contains dissolved

toxins

Bioreactor of kidney cells that processes the ultrafiltrate and sends the sugars and salts back into the blood, water is reabsorbed back into the body Cells will be isolated from the patient’s immune system by the scaffold on which they are grown

Grown on a porous scaffold which allows water, salts, glucose, amino acids, and other molecules to pass freely through it



No immunosuppression will be needed

No anticoagulation will be needed

Supposed to be permanent

Could be available for implantation in humans by 2020

Could be associated with over 50% cost savings

https://pharm.ucsf.edu/kidney. University of California, San Francisco. School of Pharmacy and Medicine. Department of Bioengineering and Therapeutic Sciences.

Documents

POMA District VIII 31 D8 18-S… · •Briefly review anemia and ... A., Yevzlin, A., Wu, S.,Beathard, G. McGraw Hill Companies, Inc. Chapter ... Increase form 8.5 to 11% from 2010