Chronic Kidney Disease

2/2/2014 Chronic kidney disease

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Chronic kidney disease

Deborah Cohen, MD, Martin Goldberg, MD, FACP, Ankush Gulati, MD, and Fred F Ferri, MD, FACPRevised: 05 May 2010Copyright Elsevier BV. All rights reserved.

Summary

Description

Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) work group has defined chronic kidney disease(CKD) as the presence of markers of kidney damage (abnormalities in blood, urine, or imaging tests ) for

≥3 months or a glomerular filtration rate (GFR) <60 mL/minute/1.73 m2for ≥3 months, with or without othersigns of kidney damage

CKD must be distinguished from acute kidney injury and from end-stage renal disease (ESRD) as definedby GFR <15 mL/minute with the uremic syndrome

Immediate action

Urgent referral to a nephrologist for dialysis is indicated when chronic renal insufficiency progresses to ESRD, asmanifested by a creatinine clearance <15 mL/minute and the presence of one or more of the following uremicmanifestations:

Incessant vomiting

Encephalopathy

Overload of fluid in the lungs that cannot be removed by diuretics

Metabolic acidosis

Electrolyte abnormalities (especially hyperkalemia)

Uremic pericarditis

Uremic neuropathy

Severe malnutrition

Loss of energy, appetite, or weight, and anemia unresponsive to epoetin alfa and iron therapy

Background

Cardinal features

Progressive deterioration in renal function of >3 months' duration

Includes chronic renal insufficiency but not ESRD

Accumulation of nitrogenous waste products in the blood ( eg , urea, creatinine)

Electrolyte disturbances

Metabolic acidosis

Volume overload

Anemia

Most patients will progress to ESRD

http://www.kidney.org/Professionals/kdoqi/


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Typically, the above features do not become clinically evident until GFR drops to <15 mL/minute

CKD is divided into different stages of disease according to the GFR and presence of albuminuria:

Stage 1 disease is defined by a normal GFR (>90 mL/minute/1.73 m2) and persistent albuminuria

Stage 2 disease is a GFR between 60 to 89 mL/minute/1.73 m2and persistent albuminuria

Stage 3 disease is a GFR between 30 and 59 mL/minute/1.73 m2

Stage 4 disease is a GFR between 15 and 29 mL/minute/1.73 m2

Stage 5 disease is a GFR of <15 mL/minute/1.73 m2or ESRD

Causes

Common causes

Diabetes mellitus (most common cause in U.S. and in other developed countries)

Hypertension (severe)

Chronic glomerulonephritis, either idiopathic or secondary to systemic diseases such as lupus nephritis,focal segmental glomerulosclerosis, membranous nephropathy

Polycystic kidney disease (most common cause in European countries, although diabetes mellitus type 2is catching up fast)

Obstructive nephropathy ( eg , due to benign prostatic hypertrophy , nephrolithiasis )

Rare causes

Tubular interstitial nephritis

Drug toxicity

Bilateral renal artery stenosis causes CKD (ischemic nephropathy) and hypertension, but not all patientswith renal artery stenosis have ESRD

Viruses: hepatitis B , hepatitis C , HIV , by causing glomerular diseases

Autoimmune diseases, particularly systemic lupus erythematosus associated nephritis

Epidemiology

Incidence and prevalence

The prevalence of CKD is 1700 per 1,000,000 population

There are 26 million adults with CKD in the U.S. and 500,000 with ESRD on dialysis

The incidence continues to increase in the U.S.

DemographicsAge

May occur at any age, although the various underlying causes are themselves more common in specific agegroups.

Race

In the U.S., blacks are more commonly affected by chronic renal insufficiency than are whites, although itis unclear whether this difference results from genetic or socioeconomic causes


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Focal segmental glomerulosclerosis (FSGS) is more common in individuals of African descent.Hypertension and diabetes mellitus type 2 are also overrepresented in black patients

Genetics

Various inherited diseases result in chronic renal insufficiency (eg, polycystic kidney disease , Alport'sdisease )

Renal failure associated with type 1 diabetes mellitus has a strong genetic component

Socioeconomic status

In the U.S., patients who are impoverished with less access to health care facilities and inadequate financialsupport are more likely to progress to ESRD than patients with better financial support and insurance.

Codes

ICD-9 code

585 Chronic kidney disease

585.1 Stage 1 CKD

585.2 Stage 2 CKD

585.3 Stage 3 CKD

585.4 Stage 4 CKD

585.5 Stage 5 CKD

585.6 End-stage renal disease

Diagnosis

Clinical presentation

Symptoms

Symptoms usually do not begin until the GFR is <15 mL/minute and, when present, suggest ESRD:

Fatigue

Nausea

Anorexia

Pruritus

Insomnia

Breathlessness

Taste disturbances

Chest pain due to pericarditis

Altered mental status

Signs

Most signs of chronic renal insufficiency except hypertension do not appear until the GFR is <15 mL/minute and,when present, suggest ESRD:

Skin pallor


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Skin excoriation

Muscle wasting

Asterixis (a late manifestation)

Hypertension

Edema

Tachypnea and pulmonary rales, secondary to volume overload

Pericardial rub due to pericarditis

Hyperpnea or tachypnea secondary to severe metabolic acidosis

Chest pain secondary to uremic pericarditis

Uremic neuropathy

Skin discoloring described typically as sallow

Uremic fetor (smell like urine)

Uremic ash (skin deposit of fine whitish powdery substance)

Hypothermia

Localized or generalized peripheral neuropathy

Coma (uremic coma in ESRD)

Uremic seizures (generalized or myoclonic)

Differential diagnosis

Acute kidney injury

Workup

Diagnostic decision

Presence of small, shrunken kidneys on renal ultrasound

Evidence of impaired renal function for >3 months

Presence of known underlying kidney disease, eg , diabetes, glomerulonephritis, polycystic kidneydisease

Guidelines

The National Kidney Foundation has produced the following guidelines:

National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation,classification, and stratification . Kidney Disease Outcomes Quality Initiative. Am J Kidney Dis.2002;39:S1-266

National Kidney Foundation. Testing for chronic kidney disease: a position statement from the NationalKidney Foundation . Am J Kidney Dis. 2007;50:169-80

The Department of Veterans Affairs and the Department of Defense have produced the following guideline:

VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease in Primary Care .Washington, DC: Department of Veterans Affairs and Department of Defense, 2007

The American College of Radiology has produced the following diagnostic guideline:

http://www.kidney.org/

http://www.kidney.org/professionals/kdoqi/pdf/ckd_evaluation_classification_stratification.pdf

http://www.kidney.org/news/newsroom/pdf/Testing%20for%20CKD.pdf

http://www.va.gov/

http://www.defense.gov/

http://www.healthquality.va.gov/ckd/ckd_v478.pdf

http://www.acr.org/


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Bush WH Jr, Choyke PL, Bluth RI, et al, Expert Panel on Urologic Imaging. Renal failure . Reston, VA:American College of Radiology (ACR), 2008

The Infectious Diseases Society of America has produced the following guideline:

Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease inHIV-infected patients : recommendations of the HIV Medicine Association of the Infectious DiseasesSociety of America. Clin Infect Dis. 2005;40:1559-85

The Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group has produced the followingguideline:

KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidneydisease-mineral and bone disorder (CKD-MBD) . Kidney Int Suppl. 2009;76:S1-S130

The American Academy of Family Physicians has produced the following guidance articles:

Snyder S, Pendergraph B. Detection and evaluation of chronic kidney disease . Am Fam Physician.2005;72:1723-32

Johnson CA, Levey AS, Coresh J, et al. Clinical practice guidelines for chronic kidney disease in adults:part I . Definition, disease stages, evaluation, treatment, and risk factors. Am Fam Physician. 2004;70:869-76

Johnson CA, Levey AS, Coresh J, et al. Clinical practice guidelines for chronic kidney disease in adults:part II . Glomerular filtration rate, proteinuria, and other markers. Am Fam Physician. 2004;70:1091-7

Snively CS, Gutierrez C. Chronic kidney disease: prevention and treatment of common complications . AmFam Physician. 2004;70:1921-8

Don't miss!

Signs of pericarditis, including pericardial rub, pericardial tamponade

Manifestations of hyperkalemia (life threatening)

Questions to askPresenting condition

Have you ever been told you have blood or protein in your urine?May indicate a longer history ofkidney disease than is perceived by the patient

Have you ever been told your kidney tests are abnormal?May indicate a longer history of kidneydisease than is perceived by the patient

What medications or over-the-counter drugs do you take and for how long?This may provide cluesto possible analgesic nephropathy from combinations of drugs such as NSAIDs, aspirin, andacetaminophen

Do you have difficulty initiating your urinary stream, increased frequency of urination, increasedurination at night after retiring?Possible obstructive symptoms of prostatism in male patients; recurrentor chronic urinary tract infection in female patients

Contributory or predisposing factors

Do you have any history of kidney problems?Especially inherited conditions

Are you diabetic?Risk of renal disease is greater in diabetic patients

Do you have high blood pressure?Risk of renal disease is greater in patients with hypertension

Do you have hepatitis B , hepatitis C , or HIV ?All of these can predispose to chronic renal insufficiency

http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/pdf/ExpertPanelonUrologicImaging/RenalFailureDoc15.aspx

http://www.idsociety.org/

http://www.journals.uchicago.edu/doi/pdf/10.1086/430257?cookieSet=1

http://www.kdigo.org/

http://www.kdigo.org/guidelines/mbd/index.html

http://www.aafp.org/

http://www.aafp.org/afp/2005/1101/p1723.html





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Do you have lupus?This is another disease that can predispose to chronic renal insufficiency

Family history

Do any diseases run in your family?Inherited renal diseases ( eg , polycystic kidney disease , Alport'ssyndrome ) can lead to renal failure.

Examination

Check blood pressure:Hypertension is frequently associated with CKD

Auscultate heart and lungs:Listen for signs of pulmonary edema, pleuritis, and pericarditis (pleural orpericardial rub), which occur in ESRD

Skin:Look for excoriations caused by the patient scratching (may indicate uremic pruritus); indicatesESRD

Abdomen:Kidneys may be palpable if enlarged ( eg , in polycystic kidney disease or ureteric obstruction).Presence of a palpable bladder may indicate bladder outflow obstruction

Vascular:Check for bruits of carotid arteries and renal arteries, and examine for diminished peripheralpulses (femoral, dorsalis pedis, posterior tibial). The presence of generalized atheromatous diseaseincreases the likelihood of renal artery stenosis

Asterixis:Check for flapping tremors of the flexor muscles of the forearm on dorsiflexion of the wrist joint

Examine retinafor diabetic retinopathy

Test for diminished vibration sensation,particularly in lower extremities to detect neuropathy

Summary of tests

Urinalysis (dipstick) should be performed in all patients and will provide rapid confirmation of a variety ofabnormalities, including hematuria (if microscopic) and proteinuria

Urine microscopy : Microscopic examination of urine sediment will confirm the presence or absence of redor white blood cells and casts

Creatinine clearance : must be an accurate, 24-hour collection of urine, performed by a specialist; from thisand concomitant serum creatinine, the GFR can be estimated

Complete blood count including iron indices should be performed in all patients as anemia may be present

Blood urea nitrogen and serum creatinine : Serial estimation of serum creatinine and blood urea nitrogen(BUN) is mandatory for diagnosis and monitoring of this condition

Serum bicarbonate (or total CO2), to diagnose and monitor severity of metabolic acidosis

Calcium , phosphorous , and intact parathyroid hormone (PTH) levels : Low calcium, high phosphorous andhigh PTH are commonly seen in the advanced stages of CKD as manifestations of renal osteodystrophy

Serum potassium should be measured, and serial measurements may be required, as patients are at riskfor hyperkalemia when they reach ESRD

24-hour urine protein or spot urine protein/creatinine ratio to quantify the magnitude of proteinuria

Chest radiography should be performed if there is dyspnea or if pulmonary edema is suspected

A renal ultrasound scan is the imaging investigation of choice, as it can measure the size of each kidneyand determine the presence or absence of hydronephrosis


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Renal biopsy is occasionally performed, but it is generally not recommended in patients with a solitarykidney, bilateral small kidneys, or advanced renal disease as they are unlikely to respond to any form ofspecific medical therapy. If indicated, it would be performed by an experienced nephrologist or an invasiveradiologist. If this is not feasible, an open renal biopsy might, on rare occasions, be performed by aurologist

Microalbuminuria screening in diabetic patients: elevated in early diabetic nephropathy

25-hydroxy vitamin D test to assess for nutritional vitamin D deficiency

Order of tests

Urinalysis (dipstick)

Urine microscopy

Creatinine clearance

Complete blood count

Blood urea nitrogen and serum creatinine

Serum potassium

Chest radiography

Renal ultrasound scan

Renal biopsy

Microalbuminuria screening

Serum bicarbonate

Calcium , phosphorous , and intact PTH levels

24-hour urine protein

Spot urine specimen for protein and creatinine

25-hydroxy vitamin D

TestsBody fluidsUrinalysis (dipstick)Urine microscopyComplete blood countBlood urea nitrogen and serum creatinineSerum potassiumSerum bicarbonateSerum calciumSerum phosphorusIntact PTH levels24-hour urine proteinSpot urine specimen for protein and creatinine25-hydroxy vitamin DTests of functionCreatinine clearanceMicroalbuminuria screeningProceduresRenal biopsyImagingChest radiography


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Renal ultrasound scan

Clinical pearls

Renal ultrasonography is most helpful in the differential diagnosis of CKD. Bilateral small kidneys definitelyindicate chronic, long-standing renal disease, but normal-sized or large kidneys are also compatible withsome important chronic renal diseases, including diabetic nephropathy, myeloma kidney, amyloidosis, andHIV nephropathy

In the assessment of patients with CKD, prior to end-stage, it is useful to identify the category of renaldisease, ie , glomerular vs tubulointerstitial. It is important, therefore, to have available a reliable urinalysiswith microscopy in these patients. In chronic glomerulopathies, the urine usually contains significantnumbers of red blood cells and a variety of casts, and usually moderate to heavy proteinuria (>2.0 g/24hours). Chronic tubulointerstitial disease (which includes toxic nephropathy and obstructive nephropathy) ischaracterized by minimal to moderate proteinuria (<2.0 g/24 hours) and minimal hematuria

The most important predictor of the rate of progression of CKD to end-stage is the magnitude of proteinuria.In fact, estimation of the protein and creatinine in an early morning spot urine specimen, and calculatingthe albumin:creatinine ratio, appears to be as useful a predictor as a 24-hour urine protein measurement

The reciprocal of the creatinine plotted over a period of time, usually at few-monthly intervals, is the bestindicator of the rate of progression to ESRD

Urine dipstick does not detect microalbuminuria, the first abnormality in diabetes mellitus type 1. A samplemust be sent to the laboratory with specific instructions

The dipstick does not detect proteins other than albumin. If other proteins are important to detect ( eg ,Bence-Jones), use of sulfosalicylic acid is required

Consider consult

All patients with CKD should be referred to a nephrologist who will help to plan the management of anycomplications and, if required, prepare for initiation of dialytic therapy and/or transplantation if/when ESRDdevelops

All patients with serum creatinine persistently above normal levels ( ie , higher than the normal range forthe laboratory on two or more successive laboratory determinations) should be referred to a nephrologist asearly as possible. This facilitates the development of a plan for further diagnostic procedures whenindicated ( eg , renal biopsy to determine etiologic diagnosis and pathologic extent of the disease) andrecommendations for indicated specific and/or supportive therapy ( eg , angiotensin-converting enzymeinhibitors in diabetic nephropathy or immunosuppressive therapy in vasculitis, lupus)

Patients are shown to have improved outcomes with earlier referral to a nephrologist

Treatment

Goals

Provide support for patient and caretakers

Regularly monitor patient's condition so that any deterioration can be quickly recognized and advice sought

Educate patient about CKD and the options of various dialysis modalities and kidney transplant

Immediate action

Patients with ESRD with overt signs and symptoms of renal failure urgently requiring dialysis require emergencyconsultation with a nephrologist, who can administer therapies and monitor progress.

Therapeutic options

Summary of therapies


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The goal of management of CKD is to prevent progression of renal dysfunction and to delay need for dialysis orrenal transplantation . Depending on the stage of CKD, several clinical parameters should be addressed at eachvisit in an effort to delay decline in renal function:

Blood pressure: Should be controlled to a goal of 130/80 mm Hg or less in all patients with CKD ordiabetes. If patient has proteinuria of > 1 g/24 hours, blood pressure should be even lower with a goal <125/75 mm Hg. Most patients will require at least 3 to 4 drugs to control blood pressure, and usually one ofthese drugs should be an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin-II receptorblocker (ARB)

Urinary protein: Reduction in proteinuria to <500 mg/day to prevent further decline in renal function isusually accomplished by using either an ACE inhibitor or an ARB alone, but frequently patients will requiredual renin-angiotensin-aldosterone system (RAAS) blockade with a combination of an ACE inhibitor and/oran ARB and/or a mineralocorticoid blocker to reduce proteinuria further. It may occasionally be necessaryto use triple RAAS blockade with an ACE inhibitor, ARB, and mineralocorticoid blocker ( spironolactone oreplerenone ). It is important to monitor for hyperkalemia in these patients

Hyperlipidemia: Patients with CKD are considered at high risk for coronary artery disease, and patientsshould be treated aggressively, aiming to reduce LDL to <100 mg/dL in subjects with CKD and to a lowergoal of <70 mg/dL if patients also have preexisting coronary artery disease. Most patients requiretreatment with a statin . Fibrates should be used cautiously in patients with CKD as they can occasionallycause acute kidney injury, which is usually reversible

Volume status: Volume status should be optimized, and patients should be instructed to follow a lowsodium diet. Most patients require some diuretic therapy as renal function declines. Higher doses offurosemide are often required

Secondary hyperparathyroidism: PTH levels should be obtained at least once a year when patients reachstage 3 CKD. PTH levels in CKD are abnormally elevated before changes in calcium and phosphorus areseen in the blood work. Elevated PTH levels are usually treated with activated oral Vitamin D. There are 3forms of 1-alpha-hydroxy Vitamin D (activated Vitamin D), but calcitriol is usually used as first-line therapyfor CKD with careful monitoring for hypercalcemia every 3 to 4 months. Newer activated Vitamin D analogsdeliver Vitamin D in a more physiologic manner and cause less hypercalcemia. These two analogs,paricalcitol and doxercalciferol , are more costly

Hyperphosphatemia: Hyperphosphatemia occurs later, usually in stage 4/5 CKD. Phosphate binders areused to bind dietary phosphorus in the gastrointestinal tract. Calcium-containing binders include calciumcarbonate and calcium acetate . Calcium carbonate is inexpensive and is an adequate binder ofphosphorus but delivers a high calcium load and is best avoided if possible. Calcium acetate is anexcellent phosphate binder but it also contains calcium. It causes less calcium loading than calciumcarbonate and is usually the first-line phosphate binder in patients who are initially relatively hypocalcemic.Non–calcium–based binders are advantageous as they do not contribute to the total body calcium load.Sevelamer is a resin with no systemic absorption but is a less potent binder, requiring patients to take alarge number of tablets to achieve adequate phosphate binding. It also is expensive and rarely leads totoxic megacolon but is the preferred binder of choice in most dialysis patients. Lanthanum carbonate , aheavy metal, is an excellent binder but is also costly and is absorbed into bone, the significance of whichis as yet unknown. It has a chalky taste and needs to be chewed. Aluminum hydroxide is never used inpatients with CKD because of the potential for systemic absorption but is on rare occasions used to bindphosphorus in patients with acute kidney injury

Nutritional Vitamin D: It is now recommended that 24-hydroxy vitamin D levels be check in patients withstage 3 CKD and that repletion for six months be initiated if needed


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Anemia: Anemia is caused by erythropoietin deficiency and usually develops in late stage 3 CKD.Hemoglobin levels should be monitored every 4 to 6 months. Most patients with anemia and CKD are alsoiron deficient. If so, iron repletion can be accomplished orally or by intravenous infusion. Oral iron ( ironsalts ) is frequently used but has poor absorption and poor patient compliance mainly because ofgastrointestinal side effects. Of the intravenous iron preparations, iron dextran is less frequently usedbecause of the risk for anaphylaxis. Sodium ferric gluconate complex and iron sucrose are both available iniron preparations and have significantly fewer risks for anaphylaxis. A new parenteral iron preparation,ferumoxytol , has recently been approved by the FDA in the U.S.. Once patients are repleted with iron, ifthey are still anemic, they may be started on erythropoietin-stimulating agents . Patients can be treatedwith recombinant erythropoietin, epoetin alfa or darbepoetin alfa . The main difference between these drugsis that darbepoetin has a longer half-life and thus can be dosed much less frequently. Patients usuallyreceive an erythropoietin-stimulating agent every 1 to 4 weeks depending on the degree of anemia and theagent used. There is controversy about treating patients with CKD and anemia with these agents, andrecent studies using recombinant erythropoietin and darbepoetin show no advantage in treating anemiawith regard to cardiovascular outcomes. The recent TREAT study actually showed an increased risk ofstroke in patients with a higher hemoglobin target, and current guidelines recommend treating anemia lessaggressively to a target hemoglobin of 10 to 11 mg/dL. These recommendations differ for patients who areon dialysis

Acidosis: In stage 4/5 CKD, patients develop a chronic metabolic acidosis. The rationale for repletingbicarbonate is to decrease progression of CKD, prevent bone buffering, and improve nutritional status. Arecent study has shown repletion of bicarbonate slows progression of CKD. If the bicarbonate level is below20 mmol/L, it can be repleted with sodium bicarbonate or sodium citrate

Vascular access for dialysis: Planning for permanent vascular dialysis access should be initiated when thepatient has a GFR of approximately 20 mL/minute or stage 4 CKD. The decision about access alsodepends on the choice of ultimate dialysis modality and transplantation options. Ideally, all patients shouldhave an arteriovenous fistula (AVF) placed approximately 4 to 6 months prior to requiring initiation ofdialysis. The non-dominant hand should be preserved for vascular access, and intravenous lines should notbe placed in that arm

Transplantation : Referral to a transplant center for evaluation should be made when patients reach a GFRof <20 mL/minute. If living donors are available, referral can be considered sooner. Average waiting time ona transplantation list in the U.S. in approximately 5 years

Hepatitis B status: Patients should be immunized against hepatitis B if not immune when they reach stage4 CKD before starting dialysis

Dietary protein: Dietary modification is often necessary to provide adequate calories while minimizingaccumulation of uremic toxins. Recommendations vary depending on individual circumstances. The optimallevel of protein intake has not been determined, but it may be reasonable to restrict intake to 0.8 to 1 g/kgbody weight of high biologic value protein. This should be accompanied by sodium and phosphaterestriction. Dietary advice would normally be given by a specialist nephrologist or a dietitian with an interestin renal disease

Medications and contrast agents: Doses of nephrotoxic or potentially nephrotoxic medications need to bereduced or the medication(s) discontinued. Patients should avoid NSAIDS, iodinated intravenous contrast,and gadolinium

Patients with CKD are at increased risk for cardiovascular morbidity and mortality, and all traditionalcardiovascular risk factors should be addressed to decrease cardiovascular risk. Patients with stage 3CKD have higher risk of dying from coronary artery disease than ever reaching dialysis. Loweringhomocysteine levels in dialysis patients ( eg , with high doses of folic acid or B vitamins), as in the generalpopulation, has not been shown to prevent coronary artery disease

Guidelines




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National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation,classification, and stratification . Kidney Disease Outcomes Quality Initiative. Am J Kidney Dis.2002;39:S1-S266

National Kidney Foundation. K/DOQI clinical practice guidelines on hypertension and antihypertensiveagents in chronic kidney disease . Am J Kidney Dis. 2004;43:S1-S29

National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease inchronic kidney disease . Am J Kidney Dis. 2003;42:S1-S201

National Kidney Foundation.. KDOQI clinical practice guidelines and clinical practice recommendations foranemia in chronic kidney disease . Am J Kidney Dis. 2006;47:S1-S145

National Kidney Foundation. K/DOQI clinical practice guidelines for managing dyslipidemias in chronickidney disease . Am J Kidney Dis. 2003;41:S1-S91










Order of therapies

Angiotensin-converting enzyme (ACE) inhibitors

Angiotensin-II receptor blockers

Diuretics ( furosemide )

Phosphate binders ( calcium carbonate , calcium acetate , lanthanum carbonate , sevelamer )

Vitamin D analogs ( calcitriol , paricalcitol , doxercalciferol )

Sodium bicarbonate

Iron ( iron salts , parenteral iron )

Erythropoietin-stimulating agents

Statins

Dialysis

Renal transplantation

http://www.kidney.org/professionals/kdoqi/guidelines_ckd/toc.htm

http://www.kidney.org/professionals/kdoqi/guidelines_bp/index.htm

http://www.kidney.org/professionals/kdoqi/guidelines_bone/index.htm

http://www.kidney.org/professionals/kdoqi/guidelines_anemia/index.htm

http://www.kidney.org/professionals/kdoqi/guidelines_lipids/index.htm

http://www.va.gov/











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Efficacy of therapies

Efficacy of treatment of chronic renal insufficiency varies by underlying etiology, patient compliance, andcomorbidities.

Medications and other therapiesMedicationsAngiotensin-converting enzyme (ACE) inhibitorsAngiotensin-II receptor blockers (ARBs)FurosemideCalcium carbonateCalcium acetateLanthanum carbonateSevelamerCalcitriolParicalcitolDoxercalciferolSodium bicarbonateIron saltsParenteral ironErythropoietin-stimulating agentsStatinsSurgical therapyRenal transplantationOther therapiesDialysis

Clinical pearls

Control of the level of serum phosphate is very important in the treatment and prevention of renalosteodystrophy. This is accomplished by strict dietary phosphate restriction and the use of phosphate-binding medications in the intestinal tract. Because of the risk of aluminum intoxication, aluminum-containing binders are no longer used in patients with CKD; however, calcium and non-calcium phosphatebinders are used

ACE inhibitors and ARBs are now established as playing an important role in retarding the rate ofprogression to end-stage disease in patients with diabetes mellitus type 1 (ACE inhibitors) and type 2(ARBs). These drugs may be used together to reduce proteinuria further. Spironolactone has also shown tohave an additive effect on reducing proteinuria when used together with an ACE inhibitor or ARB. Patientsmust be monitored for hyperkalemia. There is also increasing evidence that these drugs may be effective inproteinuric renal disease of diverse etiologies, independent of their antihypertensive action. There are somerisks in their use, however. If the patient has renal vascular disease with bilateral renal artery stenosis,he/she is vulnerable to developing acute kidney injury following the initiation of ACE inhibitor therapy. Also,while on ACE inhibitors and/or ARBs, patients are intolerant to even moderate increases in dietarypotassium intake

Remarkable progress has been made in the management of diabetic nephropathy, the major cause of CKDin the U.S.. The following measures are most important in retarding progression to end-stage: early referralto a nephrologist once the urinary dipstick is positive for protein or microalbuminuria is detected; initiationof therapy with ACE inhibitors and/or ARBs once the diagnosis is made; rigorous control of blood pressure;if feasible, tight control of glycemia

Never

Never commence treatment for hyperkalemia without knowing a recent serum potassium result andpreferably not without discussing it with a renal physician

Never change the drug regimens of patients who have had renal transplants without discussing with a renalphysician first


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Management in special circumstances

Coexisting disease

Coexisting disease that has caused or contributed to the poor renal function ( eg , diabetes, hypertension ,bladder outflow obstruction, hyperlipidemia) should be treated vigorously with the aim of slowing the declinein renal function

Some coexisting diseases add to the complexity of managing patients who reach ESRD and requiredialysis (notably congestive heart failure , chronic obstructive pulmonary disease )

Anemia has emerged as one of the most important factors in the CKD state. It predicts development of leftventricular hypertrophy and adverse outcomes if not aggressively treated

There is an increased prevalence of coronary artery disease in CKD, and CKD is an independent risk factorfor coronary artery disease. Patients with CKD should be considered at high risk for coronary arterydisease and should have lower lipid level goals (LDL <100 mg/dL)

Coexisting medication

Drugs that are renally excreted may need to have their doses reduced in patients with renal insufficiency orESRD:

Patients with a GFR >50 mL/minute can, in general, have the same dosing as patients with normal renalfunction

Patients with a GFR of 10 to 50 mL/minute need reduced doses

Patients with a GFR <10 mL/minute need substantially reduced doses

Nephrotoxic drugs may need to be stopped altogether

The situation may change if a patient with ESRD starts dialysis, since some drugs will be removed by thedialysis

Special patient groups

Patients with renal allograft: Any change in a patient's renal function should be discussed with the patient'snephrologist before treatment is changed.

Patient satisfaction/lifestyle priorities

Children and adults of working age are likely to request treatment that will allow them to have as normal lifeas possible and interfere as little as possible with schooling, ability to work, etc

Elderly patients may frequently prefer simpler, less invasive treatments

Patient and caregiver issues

Forensic and legal issues

Emergency treatment can be life-saving; occasionally this may need to be carried out without the patient'sconsent.

Impact on career, dependants, family, friends

CKD is a long-term illness. As it progresses to ESRD, it may have a severe impact on a patient's ability to attendschool, to work, or to undertake sporting or social activities. Treatment regimens may also be very disruptive.

Health-seeking behavior

Has there been a delay in seeking medical attention?


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The symptoms of CKD are often nonspecific ( eg , fatigue, general malaise, anorexia), and renalinsufficiency is often long-standing by the time it comes to medical attention

Many patients are told that they have hypertension, diabetes, or a rise in serum creatinine levels. Failure toobtain adequate medical care at an early stage often means that they present with severe renalinsufficiency or with ESRD. Adequate medical care early in the illness could often slow or prevent thedecline in renal function

Follow-up

Plan for review

All patients require regular (often life-long) review with serum potassium, blood urea nitrogen, and creatinineestimation. Factors affecting frequency of review include the severity of the condition and the age of the patient.

Information for patient or caregiver

The chronic nature of the condition and the need for life-long therapy will need to be discussed with the patient.

Ask for advice

Question 1

How does one advise a patient approaching ESRD on the best mode of renal replacement therapy, dialysis vstransplantation?

Answer 1

First, make it absolutely clear that, regardless of the ultimate mode of therapy, most patients start out on a formof dialysis. This is due to the limitation on the availability of cadaver donor kidneys. Even if the patient andphysician agree that transplantation is desirable, the average wait for a cadaver kidney in most parts of the U.S. is4 to 5 years. If a living related donor is available and is found to be a suitable donor immunologically andmedically, then the wait is much shorter and often transplantation can be performed before the patient requiresinitiation of dialysis. Regarding dialysis, the patient's wishes and the home environment are the major factors indeciding between peritoneal dialysis at home and hemodialysis in a center. Home hemodialysis is being activelyencouraged and is becoming more popular.

Question 2

How does a physician manage congestive heart failure effectively in patients with advanced renal disease?

Answer 2

The best two-word answer to this question is 'with difficulty.' If the creatinine clearance is <15 mL/minute, the bestdecision is to initiate dialysis and rectify the fluid overload, since the native kidneys no longer have the capacity tohandle the sodium and fluid excesses even with potent diuretic therapy. On the other hand, at earlier phases ofCKD (GFR >30 mL/minute), many compliant patients can be treated effectively with a combination of measuresincluding rigorous dietary sodium restriction, careful control of hypertension, and the use of loop-acting diureticssuch as furosemide. Thiazide diuretics as first-line drugs are essentially ineffective in advanced renal failure, butoccasionally they are effective in combination with loop-acting drugs.

Question 3

Patients with CKD often feel weak and tired with poor energy levels but they may not be ready for dialysis basedon their creatinine clearance. Why is this so?

Answer 3


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One of the most common and often ignored complications of CKD is the development of anemia due to epoetinalfa deficiency (mainly), which causes these symptoms. It is also associated with left ventricular hypertrophy andincreased mortality. The treatment of this anemia requires weekly to biweekly doses of epoetin alfa injectionsalong with iron supplementation. An alternative is darbepoetin, which is usually dosed every 4 weeks. A referral toa nephrologist is best sought for this complex management. Patients feel remarkably better after treatment withthese injections and correction of the anemia.

Consider consult

Diabetic patients may be referred even before a rise in serum creatinine level is evident on the basis ofmicroalbuminuria results

Degree of urgency of referral depends on the severity of the renal damage and rapidity of the deterioration ofrenal function, and whether the patient is approaching ESRD soon as manifested by serum creatinine level>6.0 mg/dL; 24-hour creatinine clearance <15 mL/minute; uremic symptoms of nausea, vomiting, severeanorexia, bleeding, encephalopathy; intractable congestive heart failure; metabolic acidosis; andhyperkalemia

Summary of evidence

Evidence

ACE inhibitors and ARBs

ACE inhibitors reduce the decline in renal function even if blood pressure is not raised:

In patients with chronic nephropathies and proteinuria of 3g or more per day, the ACE inhibitor ramiprilreduces the rate of decline of GFR and halves the combined risk of doubling of serum creatinineconcentration or ESRD, compared with placebo plus conventional antihypertensive drugs at the same levelof blood pressure control [1] Level A

In patients with chronic nephropathy and at high risk of rapid progression to ESRD, ramipril reverses thetendency of GFR to decline with time. Moreover, a treatment period of 36 months or longer eliminates theneed for dialysis. Even patients previously treated with antihypertensive drugs, other than ACE inhibitors,benefit from shifting to ramipril [2] Level A

Treatment of CKD patients with ACE inhibitors delays disease progression compared with placebo, acrossa spectrum of disease causes and renal dysfunction [3] Level A

ARBs, including losartan and irbesartan, can slow the rate of progression of type 2 diabetic nephropathy:

Losartan, compared with placebo, reduces the incidence of a doubling of the serum creatinineconcentration and ESRD, but has no effect on the rate of death. The benefit exceeds that attributable tochanges in blood pressure [7] Level A

The risk of a doubling of the serum creatinine concentration is a third lower in irbesartan-treated patients,compared with placebo. Treatment with irbesartan is also associated with a 23% reduction in relative riskof ESRD compared both to placebo and to amlodipine. These differences are independent of any changesin blood pressure [8] Level A

Combination of ACE inhibitor and ARB further reduces proteinuria:

The National Kidney Foundation suggests that ACE inhibitors and ARBs may be used in combination toreduce proteinuria in patients with CKD; however, larger outcomes trials are needed [4] Level C

Adding aldosterone blockers to ACE inhibitors or ARBs further reduces proteinuria:


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Data suggest that adding mineralocorticoid receptor blockers (MRBs) to ACE inhibitor and/or ARB therapyyields significant decreases in proteinuria without adverse effects of hyperkalemia and impaired renalfunction; however, routine use of MRBs as additive therapy in patients with CKD cannot be recommendedas routine yet [5] Level A

A systematic review and meta-analysis of 10 studies involving 845 patients with CKD evaluated the effect ofadding an aldosterone antagonist to ongoing treatment with an ACE inhibitor or an ARB versus addingplacebo. Although addition of an aldosterone antagonist reduced proteinuria and systolic and diastolicblood pressure, it did not lead to improvement in GFR [6] Level A

Calcium and non–calcium-containing phosphate binders

Calcium and non–calcium-containg phosphate binders are useful when dietary restriction does not not accomplishtarget serum phosphate levels in patients with CKD:

In hemodialysis patients, calcium acetate controls serum phosphorus and calcium phosphate levels moreeffectively than the 'non-calcium' phosphate binder, sevelamer hydrochloride [10] Level B

A systematic review and meta-analysis of randomized controlled trials assessing the benefits and harms ofphosphate binders in CKD showed there were insufficient data to establish the comparative superiority ofnon-calcium-binding agents over calcium-containing phosphate binders for all-cause mortality andcardiovascular end points [9] Level A

Vitamin D analogs

Vitamin D analogs reduce serum PTH:

In patients with pre-dialysis CKD, calcitriol reduces both serum PTH and bone resorption indices,compared with placebo - suggesting a mechanism of action that suppresses parathyroid hyperfunction,which in turn leads to preservation and/or restoration of bone metabolism. Calcitriol can, therefore, be auseful adjunct in the treatment of renal bone disease [11] Level B

A small trial involving patients in the pre-dialysis phase of CKD showed an increase in bone mineral densityduring calcitriol treatment over one year, compared with placebo. This effect may also be (partly) due tosuppression of secondary hyperparathyroidism [12] Level B

A systematic review of 60 trials of vitamin D compounds in patients with CKD requiring dialysis showedthat these compounds lowered serum PTH levels better than placebo but also increased phosphorouslevels and tended to increase calcium levels. Newer agents such as paricalcitol, maxacalcitol anddoxercalciferol increased risk for hypercalcemia. All of the studies, however, were not powered adequatelyto assess the effect of these vitamin D compounds on clinical outcomes such as bone pain, risk forparathyroidectomy, or risk for death as has been suggested by observational data [13] Level A

Sodium bicarbonate

Supplementation with sodium bicarbonate to treat chronic metabolic acidosis may slow progression to ESRD:

A small RCT in 134 adults with CKD with creatinine clearance between 15 and 30 mL/minute and serumbicarbonate levels between 16 and 20 mmol/L showed that supplementary bicarbonate was associatedwith slower progression to ESRD and better nutritional parameters. [14] Level B

Erythropoietin-stimulating agents

Erythropoietin-stimulating agents for treatment of chronic anemia, but there is controversy regarding theappropriate target hemoglobin level:

A three-year RCT including 603 patients with stage 3 or 4 CKD with a serum hemoglobin level between 11and 12.5 g/dL, evaluated the effect of beginning treatment with subcutaneous erythropoietin at the start ofthe trial versus initiating it when the hemoglobin fell to 10.5 g/dL. Early correction of the anemia to normaldid not affect the risk of a first cardiovascular event [15] Level A


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An open label trial including 1432 patients with CKD randomized patients to epoetin alfa to achieve ahemoglobin level of 13.5 g/dL versus a target hemoglobin level of 11.3 g/dL. After 16 months, use of the13.5-g/dL target was associated with a higher incidence of the composite outcome of death, myocardialinfarction, hospitalization for heart failure, and stroke [16] Level A

An RCT including 4038 patients with diabetes mellitus, CKD, and anemia compared the use of darbepoetinalfa to correct the anemia to a target level of 13 g/dL or 9 g/dL. At the end of the study, the use of the drugdid not reduce the risk for either of two composite outcomes, death or a cardiovascular event, or death or arenal event, and was associated with an increased risk for stroke [17] Level A

Statins

Studies have shown no benefit to treating lipids aggressively with statins in dialysis patients, and lower LDL levelsoften reflect malnutrition in these patients:

A systematic review of 14 RCTs comparing statins with placebo in 2086 patients receiving hemodialysisand/or continuous ambulatory peritoneal dialysis found that after 12 weeks of treatment, statins decreasedcholesterol levels in dialysis patients similar to the general population. In patients on hemodialysis andtaking statins, nonfatal cardiovascular events were reduced, but cardiovascular and overall mortality werenot decreased [18] Level A

A similar systematic review of 16 studies on the use of statins in kidney transplant recipientsdemonstrated lipid lowering but no effect on mortality [19] Level A

A systematic review of 26 studies including more than 25,000 patients showed that HMG CoA reductaseinhibitors given to patients with CKD not requiring dialysis decreased 24-hour urinary protein excretion anddid not improve kidney function as measured by creatinine clearance. Total and LDL cholesterol werereduced as was all-cause mortality [20] Level A

A multicenter RCT involving 2776 adults on maintenance hemodialysis and randomized to rosuvastatin orplacebo showed that LDL cholesterol levels were reduced but there was no effect on cardiovascular deaths,nonfatal myocardial infarction, or nonfatal stroke after a median follow-up period of 3.8 years [21] Level A

An RCT (the 4D study) showed that atorvastatin had no statistically significant effect on the composite ofcardiovascular death, nonfatal myocardial infarction, and stroke in patients with type 2 diabetes undergoinghemodialysis [22] Level A

Dialysis

A systematic review identified only one, small, trial comparing the relative effectiveness of continuousambulatory peritoneal dialysis (CAPD) with hemodialysis for people with kidney failure. It found nostatistical difference between them in death or quality-adjusted life years score (QALYs) at 2 years. Thesize of the trial, however, meant there were insufficient data to allow definitive conclusions to be drawn [23]Level B

Six large-scale, registry studies and three prospective cohort studies conducted in the U.S., Canada,Denmark, and the Netherlands were reviewed to compare mortality among ESRD patients receivinghemodialysis verus peritoneal dialysis. Peritoneal dialysis was generally found to be associated with equalor better survival among non-diabetic patients and younger diabetic patients. However, in the U.S.,hemodialysis was associated with better survival for diabetic patients aged 45 and older. Peritoneal dialysiswas generally associated with equivalent or better survival during the first year or two of dialysis. Overallpatient survival was similar for peritoneal dialysis and hemodialysis, but important differences exist withinselect subgroups of patients, particularly those subgroups defined by age and the presence or absence ofdiabetes [24] Level B

A systematic review of 12 randomized controlled trials (RCTs), or quasi-RCTs, sought to determine ifmodifications of the transfer set (Y-set or double bag systems) used in CAPD exchanges are associatedwith a reduction in peritonitis in patients with ESRD undergoing peritoneal dialysis. It found thatsignificantly fewer patients suffered peritonitis with Y-set and double bag systems compared with standardexchange systems [25] Level A


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References

[ [10] , [25] , [1] , [2] , [3] , [7] , [8] , [11] , [12] , [4] [5] [6] [9] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23][24]

Outcomes

Prognosis

Depends on individual variables, comorbidities, and patient compliance with therapy.

Progression of diseaseTherapeutic failure

Patients with chronic renal insufficiency who do not respond to simple measures (diet, diuretics,antihypertensive agents) are likely to progress to ESRD

Selected patients on long-term dialysis may be considered for renal transplantation

All patients should be referred to a nephrologist

Terminal illness

Some patients with CKD fail to respond to treatment; some repeatedly reject donor kidneys; and for some,a suitable donor never becomes available. In such cases further treatment choices are usually very limited

If a patient's quality of life is poor with no likelihood of improvement, it may not be appropriate to continuewith treatment or to initiate any new therapies

This should be discussed, as appropriate, with the patient, other physicians caring for the patient, and thepatient's family or caregivers

Clinical complications

Fertility is substantially reduced in female patients with ESRD, and erectile dysfunction is common in malepatients.

Consider consult

Patients with CKD should have a plan for long-term follow-up that includes the following specialists:

A nephrologist to develop plans for future renal replacement therapy ( eg , dialysis, transplantation) and topresent patient with the latest knowledge on ameliorating the progression to end-stage disease

Transplant surgeon and transplant coordinators for placement on the list

Social workers/case managers/dialysis professionals, as this is a lifestyle-changing treatment modality

Prevention

Primary prevention

Pre-existing renal diseaseshould be carefully monitored. It may not be possible to prevent renal failurefrom occurring but if recognized early, its long-term effects may be lessened. Early referral to anephrologist is strongly advised

Diabetes mellitusand all aspects of this disease should be treated promptly and patients should bemonitored to reduce the risk of complications such as renal failure

Hypertensionshould be treated aggressively to prevent permanent renal damage

Modifiable risk factors


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Tobacco

Patients with progressive renal disease should be advised to stop smoking.

Medication history

Care should be taken when prescribing potentially nephrotoxic drugs to at-risk patients. Reduce the dose or usealternative medication if possible.

Other

Those with a family history of hereditary renal disease should be monitored regularly, so that any deterioration inrenal function can be recognized early and the potential for permanent renal damage may be reduced. (It may notbe possible to prevent renal failure from occurring.)

Secondary prevention

Once permanent renal damage has occurred, a return to completely normal renal function is unlikely tooccur

Thus, recurrence as such does not occur; however, all patients should be followed so that any deteriorationin their condition can be recognized early

Early referral to a nephrologist is strongly recommended

Screening

Screening for microalbuminuria is appropriate for patients with diabetes mellitus.

Resources

References

Evidence references[1] Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). A long-term, randomised clinical trial to evaluatethe effects of ramipril on the evolution of renal function in chronic nephropathies. J Nephrol 1991;3:193-202[2] Ruggenenti P, Perna A, Gherardi G, et al. Renal function and requirement for dialysis in chronic nephropathypatients on long-term ramipril: REIN follow-up trial. Lancet 1998;352:1252-6CrossRef[3] Kshirsagar AV, Joy MS, Hogan SL, et al. Effect of ACE inhibitors in diabetic and nondiabetic chronic renaldisease: a systematic overview of randomized placebo-controlled trials. Am J Kidney Dis 2000;35:695-707[4] Kidney Disease Outcomes Quality Initiative (K/QODI): K/DOQI clinical practice guidelines on hypertension andantihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43:S1-S290[5] Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosteroneblockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis.2008;51:199-211[6] Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GF: Aldosterone antagonists for preventing theprogression of chronic kidney disease. Cochrane Database Syst Rev 2009:CD007004CrossRef[7] Brenner BM, Cooper ME, deZeeuw D, et al. The RENAAL Study investigators. Effects of losartan on renal andcardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861-9CrossRef[8] Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of angiotensin-receptor antagonist irbesartanin patients with nephropathy due to type 2 diabetes. The Collaborative Study Group. N Engl J Med 2001;345:851-60CrossRef[9] Navaneethan SD, Palmer SC, Craig JC, et al. Benefits and harms of phosphate binders in CKD: a systematicreview of randomized controlled trials. Am J Kidney Dis. 2009;54:619-637CrossRef[10] Qunibi WY, Hootkins RE, McDowell LL, et al. Treatment of hyperphosphatemia in hemodialysis patients: The

http://dx.doi.org/10.1016/S0140-6736(98)04433-X

http://dx.doi.org/10.1002/14651858.CD007004.pub2

http://dx.doi.org/10.1056/NEJMoa011161


http://dx.doi.org/10.1053/j.ajkd.2009.06.004


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Calcium Acetate Renagel Evaluation (CARE Study). Kidney Int 2004;65:1914-26

CrossRef[11] Nordal KP, Dahl E. Low dose calcitriol versus placebo in patients with predialysis chronic renal failure. J ClinEndocrinol Metab 1988;67:929-36[12] Przedlacki J, Manelius J, Huttunen K. Bone mineral density evaluated by dual-energy X-ray absorptiometryafter one-year treatment with calcitriol started in the predialysis phase of chronic renal failure. Nephron1995;69:433-7[13] Palmer SC, McGregor DO, Craig JC, et al. Vitamin D compounds for people with chronic kidney diseaserequiring dialysis. Cochrane Database Syst Rev. 2009;CD005633CrossRef[14] de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM: Bicarbonate supplementation slows progressionof CKD and improves nutritional status. J Am Soc Nephrol. 2009;20:2075-2084CrossRef[15] Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidneydisease and anemia. N Engl J Med. 2006;355:2071-2084CrossRef[16] Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. NEngl J Med 2006; 355:2085-98.CrossRef[17] Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidneydisease. N Engl J Med. 2009;361:2019-2032CrossRef[18] Navaneethan SD, Nigwekar SU, Perkovic V, et al. HMG CoA reductase inhibitors (statins) for dialysispatients. Cochrane Database Syst Rev. 2009;(3):CD004289CrossRef[19] Navaneethan SD, Perkovic V, Johnson DW, et al. HMG CoA reductase inhibitors (statins) for kidneytransplant recipients. Cochrane Database Syst Rev. 2009;(2):CD005019CrossRef[20] Navaneethan SD, Pansini F, Perkovic V, et al. HMG CoA reductase inhibitors (statins) for people with chronickidney disease not requiring dialysis. Cochrane Database Syst Rev. 2009;(2):CD007784[21] Fellstrom BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and cardiovascular events in patientsundergoing hemodialysis. N Engl J Med. 2009;360:1395-1407CrossRef[22] Krane V, Winkler K, Drechsler C, Lilienthal J, Marz W, Wanner C, German Diabetes and Dialysis StudyInvestigators. Effect of atorvastatin on inflammation and outcome in patients with type 2 diabetes mellitus onhemodialysis. Kidney Int. 2008;74:1461-1467CrossRef[23] Vale L, Cody J, Wallace S, et al. Continuous ambulatory peritoneal dialysis (CAPD) versus hospital or homehaemodialysis for end-stage renal disease in adults. Cochrane Database of Systematic Reviews 2004, Issue 4| Cochrane Review[24] Vonesh EF, Snyder JJ, Foley RN, Collins AJ. Mortality studies comparing peritoneal dialysis andhemodialysis: what do they tell us? Kidney Int Suppl. 2006;(103):S3-S11CrossRef[25] Daly C, Campbell M, Cody J, et al. Double bag or Y-set versus standard transfer systems for continuousambulatory peritoneal dialysis in end-stage renal disease. Cochrane Database of Systematic Reviews 2000, Issue3| Cochrane ReviewGuidelines


National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation,classification, and stratification . Kidney Disease Outcomes Quality Initiative. Am J Kidney Dis.2002;39:S1-S266

National Kidney Foundation. K/DOQI clinical practice guidelines on hypertension and antihypertensiveagents in chronic kidney disease . Am J Kidney Dis. 2004;43:S1-S29

http://dx.doi.org/10.1111/j.1523-1755.2004.00590.x


http://dx.doi.org/10.1681/ASN.2008111205







http://dx.doi.org/10.1038/ki.2008.484

http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD003963/frame.html

http://dx.doi.org/10.1038/sj.ki.5001910

http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD003078/frame.html


http://www.kidney.org/professionals/kdoqi/guidelines_ckd/toc.htm

http://www.kidney.org/professionals/kdoqi/guidelines_bp/index.htm


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National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease inchronic kidney disease . Am J Kidney Dis. 2003;42:S1-S201

National Kidney Foundation.. KDOQI clinical practice guidelines and clinical practice recommendations foranemia in chronic kidney disease . Am J Kidney Dis. 2006;47:S1-S145

National Kidney Foundation. K/DOQI clinical practice guidelines for managing dyslipidemias in chronickidney disease . Am J Kidney Dis. 2003;41:S1-S91

National Kidney Foundation. K/DOQI clinical practice guidelines and clinical practice recommendation foranemia in chronic kidney disease: 2007 update of hemoglobin target . Am J Kidney Dis. 2007;50:471-530



The American College of Radiology has produced the following diagnostic guideline:

Bush WH Jr, Choyke PL, Bluth RI, et al, Expert Panel on Urologic Imaging. Renal failure . Reston, VA:American College of Radiology (ACR), 2008



The Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group has produced the followingguideline:

KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidneydisease-mineral and bone disorder (CKD-MBD) . Kidney Int Suppl. 2009;76:S1-S130






Further reading

McClellan WM. Epidemiology and risk factors for chronic kidney disease. Med Clin North Am.2005;89:419-45

Levin A, Stevens LA. Executing change in the management of chronic kidney disease: perspectives onguidelines and practice. Med Clin North Am. 2005;89:701-9

Stevens LA, Levey AS. Measurement of kidney function. Med Clin North Am. 2005;89:457-73

Zandi-Nejad K, Brenner BM. Strategies to retard the progression of chronic kidney disease. Med Clin NorthAm. 2005;89:489-509

http://www.kidney.org/professionals/kdoqi/guidelines_bone/index.htm

http://www.kidney.org/professionals/kdoqi/guidelines_anemia/index.htm

http://www.kidney.org/professionals/kdoqi/guidelines_lipids/index.htm

http://www.kidney.org/professionals/KDOQI/guidelines_anemiaUP/index.htm

http://www.va.gov/



http://www.acr.org/

http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/pdf/ExpertPanelonUrologicImaging/RenalFailureDoc15.aspx



http://www.kdigo.org/

http://www.kdigo.org/guidelines/mbd/index.html







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Andersen MJ, Agarwal R. Etiology and management of hypertension in chronic kidney disease. Med ClinNorth Am. 2005;89:525-47

Pendse S, Singh AK. Complications of chronic kidney disease: anemia, mineral metabolism, andcardiovascular disease. Med Clin North Am. 2005;89:549-61

Goodman WG. Calcium and phosphorus metabolism in patients who have chronic kidney disease. MedClin North Am. 2005;89:631-47

Gabardi S, Abramson S. Drug dosing in chronic kidney disease. Med Clin North Am. 2005;89:649-87

Codreanu I, Perico N, Remuzzi G. Dual blockade of the renin-angiotensin system: the ultimate treatmentfor renal protection? J Am Soc Nephrol. 2005;16:S34-S38

Tonelli M, Bohm C, Pandeya S, et al. Cardiac risk factors and the use of cardioprotective medications inpatients with chronic renal insufficiency. Am J Kidney Dis. 2001;37:484-9

Wilcox CS. New Insights into Ddiuretic Uuse in Ppatients with Cchronic Rrenal Ddisease. J Am SocNephrol. 2002;13:798-805

Qamar M, Bender F, Rault R, Piraino B. The United States' perspectives on home dialysis. Adv ChronicKidney Dis. 2009;16:189-97

Juergensen E, Wuerth D, Finkelstein SH, et al. Hemodialysis and peritoneal dialysis: patients'assessment of their satisfaction with therapy and the impact of the therapy on their lives. Clin J Am SocNephrol. 2006;1:1191-6. Epub 2006 Aug 30

Abdel-Kader K, Myaskovsky L, Karpov I, et al. Individual quality of life in chronic kidney disease: influenceof age and dialysis modality. Clin J Am Soc Nephrol. 2009;4:711-8. Epub 2009 Apr 1

Saxena R, West C. Peritoneal dialysis: a primary care perspective. J Am Board Fam Med. 2006;19:380-9

Salusky IB. A new era in phosphate binder therapy: what are the options? Kidney Int Suppl. 2006;(105):S10-5

Sprangers B, Evenepoel P, Vanrenterghem Y. Late referral of patients with chronic kidney disease: no timeto waste. Mayo Clin Proc. 2006;81:1487-94

Molitch ME. Management of dyslipidemias in patients with diabetes and chronic kidney disease. Clin J AmSoc Nephrol. 2006;1:1090-9. Epub 2006 Jul 26

Campbell KH, Dale W, Stankus N, Sachs GA. Older adults and chronic kidney disease decision makingby primary care physicians: a scholarly review and research agenda. J Gen Intern Med. 2008;23:329-36

House AA, Silva Oliveira S, Ronco C. Anti-inflammatory drugs and the kidney. Int J Artif Organs.2007;30:1042-6

Perazella MA. Advanced kidney disease, gadolinium and nephrogenic systemic fibrosis: the perfect storm.Curr Opin Nephrol Hypertens. 2009;18:519-25

Rozen-Zvi B, Gafter-Gvili A, Paul M, et al. Intravenous versus oral iron supplementation for the treatment ofanemia in CKD: systematic review and meta-analysis. Am J Kidney Dis. 2008;52:897-906. Epub 2008 Oct8

Rothberg MB, Kehoe ED, Courtemanche AL, et al. Recognition and management of chronic kidneydisease in an elderly ambulatory population. J Gen Intern Med. 2008;23:1125-30. Epub 2008 Apr 29

Muntner P, Jones TM, Hyre AD, et al. Association of serum intact parathyroid hormone with lowerestimated glomerular filtration rate. Clin J Am Soc Nephrol. 2009;4:186-94

Mange KC, Joffe MM, Feldman HI. Effect of the use or nonuse of long-term dialysis on the subsequentsurvival of renal transplants from living donors. N Engl J Med. 2001;344:726-31


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Jamison RL, Hartigan P, Kaufman JS, et al. Effect of homocysteine lowering on mortality and vasculardisease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial.JAMA. 2007;298:1163-70

Associations

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Tel: (800) 891-5390

Fax: (703) 738-4929

http://kidney.niddk.nih.gov/

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Tel: (800) 622-9010 or (212) 889-2210

Fax: (212) 689-9261


Patient and caregiver information

Contributors

Deborah Cohen, MD

Martin Goldberg, MD, FACP

Ankush Gulati, MD

Fred F Ferri, MD, FACP

http://kidney.niddk.nih.gov/


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Chronic Kidney Disease