Professional Documents
Culture Documents
Chronic kidney disease affects approximately 19 million adult Americans, and its incidence is increasing rapidly. Diabetes
and hypertension are the underlying causes in most cases of chronic kidney disease. Evidence suggests that progression to
kidney failure can be delayed or prevented by controlling blood sugar levels and blood pressure and by treating protein-
uria. Unfortunately, chronic kidney disease often is overlooked in its earliest, most treatable stages. Guidelines from the
National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) recommend estimating glomerular
filtration rate and screening for albuminuria in patients with risk factors for chronic kidney disease, including diabetes,
hypertension, systemic illnesses, age greater than 60 years, and family history of chronic kidney disease. The glomerular
filtration rate, calculated by using a prediction equation, detects chronic kidney disease more accurately than does the
serum creatinine level alone; the glomerular filtration rate also is used for disease staging. In most clinical situations,
analysis of random urine samples to determine the albumin-creatinine or protein-creatinine ratio has replaced analysis
of timed urine collections. When chronic kidney disease is detected, an attempt should be made to identify and treat
the specific underlying condition(s). The KDOQI guidelines define major treatment goals for all patients with chronic
kidney disease. These goals include slowing disease progression, detecting and treating complications, and managing
cardiovascular risk factors. Primary care physicians have an important role in detecting chronic kidney disease early, in
instituting measures to slow disease progression, and in providing timely referral to a nephrologist. (Am Fam Physician
2005;72:1723-32, 1733-4. Copyright © 2005 American Academy of Family Physicians.)
A
S
Patient information: pproximately 19 million Amer- treatment goals for each stage. This article
A handout on chronic icans older than 20 years have focuses on the detection of chronic kidney
kidney disease, written by
the authors of this article, chronic kidney disease, and an disease and the initial evaluation of affected
is provided on page 1733. additional 435,000 have end-stage patients.
renal disease (Table 11). The incidence of
end-stage renal disease, with its annual mor- Detection of Chronic Kidney Disease
tality rate of 24 percent, has doubled every WHICH PATIENTS TO SCREEN
decade since 1980.2 Chronic kidney disease The KDOQI guidelines1,6 recommend assess-
is 100 times more prevalent than end-stage ing all patients for kidney-disease risk factors.
renal disease, and its incidence is increasing Further screening is performed in patients
at an even faster rate. with identified risk factors. Although screen-
Early treatment of chronic kidney disease ing methods for chronic kidney disease have
and its complications may delay or prevent not been evaluated in randomized controlled
the development of end-stage renal disease. trials,7 the high prevalence of the disease in
Consequently, detection of chronic kidney at-risk populations, the ease of screening,
disease should be a priority for family physi- and the availability of effective treatments
cians. However, data from national screen- during early asymptomatic stages of the dis-
ing programs suggest that chronic kidney ease provide sufficient rationale for screen-
disease often is not detected, even when ing.8 Nonetheless, screening rates for patients
patients have access to primary care.3,4 with known risk factors for chronic kidney
The Kidney Disease Outcomes Quality disease are as low as 20 percent.3,4
Initiative (KDOQI) from the National Kid- High-risk groups that should be screened
ney Foundation (NKF) has developed guide- for chronic kidney disease include patients
lines for the detection and evaluation of who have a family history of the disease
chronic kidney disease.5,6 These guidelines and patients who have diabetes, hyperten-
define the disease and its stages and outline sion, recurrent urinary tract infections,
November 1, 2005 U Volume 72, Number 9 www.aafp.org/afp American Family Physician 1723
Chronic Kidney Disease
SORT: KEY RECOMMENDATIONS FOR PRACTICE
Evidence
Clinical recommendation rating References
All adults with risk factors for chronic kidney disease should be screened with a serum creatinine C 1, 5, 6
determination for GFR estimation and analysis of a random urine sample for proteinuria.
Instead of a timed urine collection, a random urine sample for the microalbumin-creatinine C 1, 24, 25
or protein-creatinine ratio should be used to quantify proteinuria.
Interventions proved to slow the progression of chronic kidney disease include blood pressure A 1, 24, 33,
control, glycemic control, and reduction of proteinuria with an angiotensin-converting enzyme 34, 37
inhibitor or angiotensin-II receptor blocker.
A low-density lipoprotein goal of less than 100 mg per dL (2.60 mmol per L) is recommended C 37
for patients with chronic kidney disease, because these patients are statistically at highest risk
for cardiovascular disease.
A blood pressure goal of 130/80 mm Hg is recommended in patients with normal urinary B 1, 30
albumin concentrations, and a blood pressure goal of 125/75 mm Hg is recommended in
patients with proteinuria equal to or greater than 1 g per 24 hours.
1724 American Family Physician www.aafp.org/afp Volume 72, Number 9 U November 1, 2005
Chronic Kidney Disease
TABLE 2
Stages of Chronic Kidney Disease
Based on Estimated GFR
November 1, 2005 U Volume 72, Number 9 www.aafp.org/afp American Family Physician 1725
Chronic Kidney Disease
TABLE 4
Preferred Methods for Assessing Kidney Function
1726 American Family Physician www.aafp.org/afp Volume 72, Number 9 U November 1, 2005
Evaluation for Proteinuria and Microalbuminuria
Urine dipstick*
Diagnostic evaluation
and treatment Diagnostic evaluation
and treatment
Repeat yearly.
*—If available, an albumin-specific dipstick may be used in place of a standard urine dipstick as the initial step
in screening.
Figure 1. Algorithm for proteinuria and microalbuminuria screening in the patient with risk fac-
tors for chronic kidney disease.
Adapted with permission from National Kidney Foundation. K/DOQI, clinical practice guidelines for chronic kidney disease:
evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 suppl 1):S1-266. Accessed online February 21, 2005,
at: http://www.kidney.org/professionals/kdoqi/guidelines_ckd/Gif_File/kck_f57.gif.
chronic kidney disease, including those who ders (e.g., cystic kidney diseases); and known
are taking an ACE inhibitor or ARB, for per- medical problems. Underlying diseases may
sistence of microalbuminuria or for progres- be identified by the physical examination,
sion to overt proteinuria. The medication with special attention given to the skin,
dosage should be adjusted as tolerated, with joints, and cardiovascular system. Table 528
the goal of eliminating albuminuria. summarizes the common presentations and
appropriate serologic evaluations for the most
Evaluation of Patients with common causes of chronic kidney disease.
Chronic Kidney Disease Several tests may help determine the
Once chronic kidney disease has been iden- underlying cause of chronic kidney disease.
tified, goals include determining the stage Tests for complements 3 and 4 are used to
of the disease, establishing the cause of the screen for collagen vascular disease, hepati-
disease, and evaluating comorbid conditions. tis C–related disease, and infection-related
All patients with chronic kidney disease immune complex disease. The antineutro-
should undergo urinalysis and renal imaging phil cytoplasmic antibody assay identifies
as part of the diagnostic evaluation. Patients vasculitis, whereas serum protein electro-
with long-standing diabetes, hypertension, phoresis and urine protein electrophoresis
and a clinical course consistent with chronic detect multiple myeloma.
kidney disease secondary to these conditions Renal ultrasonography helps establish the
may not require further evaluation.1 diagnosis and prognosis by documenting
The evaluation of all patients is guided by the size of the kidneys. Normal size indi-
the symptoms (e.g., rash, arthritis, or urinary cates kidney disease that may be amenable
symptoms); family history of kidney disor- to medical treatment. Small kidneys suggest
November 1, 2005 U Volume 72, Number 9 www.aafp.org/afp American Family Physician 1727
Chronic Kidney Disease
TABLE 5
Diagnostic Evaluation in Chronic Kidney Disease
Diabetes mellitus Diabetes for > 15 years, RBCs in < 25 > 30 to > 3,500 mg Fasting blood sugar, A1C
retinopathy percent of of protein per g of
affected creatinine
patients
Essential Left ventricular Benign > 30 to 3,000 mg No additional tests
hypertension hypertrophy, of protein per gram of
retinopathy creatinine
Glomerulonephritis History and physical Dysmorphic > 30 to > 3,500 mg C3 and C4 for all patients
examination: RBCs or RBC of protein per g Tests for infections: anti-ASO,
infections; rash, casts of creatinine ASK, HIV, HBsAg, HCV, RPR,
arthritis; patient blood cultures
older than 40 years Tests if there is rash or arthritis:
ANA, ANCA, cryoglobulin,
anti-GBM
Tests if patient is older than
40 years: SPEP, UPEP
Interstitial nephritis Medications, fever, WBCs, WBC 30 to 3,000 mg ACE level; SS-A, SS-B
rash, eosinophilia casts, of protein per g
eosinophils of creatinine
Low flow states Volume depletion, Hyaline casts, < 200 mg of protein FENa: < 1 percent; eosinophilia
hypotension, eosinophils per g of creatinine
congestive heart
failure, cirrhosis,
atherosclerosis
Urinary tract Urinary symptoms Benign, or RBCs None KUB radiography,
obstruction intravenous pyelography,
spiral CT scanning, renal
ultrasonography
Chronic urinary Urinary symptoms WBCs, RBCs < 2,000 mg of protein Pelvic examination,
tract infection per g of creatinine urine culture, voiding
cystourethrography, renal
ultrasonography, CT scanning
Neoplasm, Patient older than RBCs, RBC casts, False-negative result or SPEP, UPEP, calcium level, ESR
paraproteinemia 40 years, constitutional granular casts > 30 to > 3,500 mg
symptoms, anemia of protein per g of
creatinine
Cystic kidney Palpable kidneys with RBCs 30 to 3,000 mg of Renal ultrasonography or CT
disease or without family protein per g of scanning if there is a complex
history of cystic kidney creatinine kidney cyst or mass
disease, flank pain
Renovascular Late-onset or refractory Benign < 200 mg of protein Renal Doppler ultrasonography,
disease hypertension, sudden per g of creatinine radioisotope renal scanning,
onset of hypertension MRA, renal angiography
in young woman,
smoking history,
abdominal bruit
Vasculitis Constitutional RBCs; granular > 30 to > 3,500 mg C3, C4, ANA, ANCA; HBsAg,
symptoms, peripheral casts of protein per g of HCV, cryoglobulins, ESR, RF,
neuropathy, rash, creatinine SS-A, SS-B, HIV
respiratory symptoms
RBC = red blood cell; A1C = glycosylated hemoglobin; C3 = complement 3; C4 = complement 4; anti-ASO = steptolysin O latex antibody;
ASK = antistreptokinase; HIV = human immunodeficiency virus; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; RPR = rapid plasma
reagin; ANA = antinuclear antibodies; ANCA = antineutrophil cytoplasmic antibody; anti-GBM = anti-glomerular basement membrane antibody;
SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis; WBC = white blood cell; ACE = angiotensin-converting enzyme;
SS-A = anti-Ro antibody; SS-B = anti-La antibody; FENa = fractional excretion of sodium; KUB = kidney, ureters, and bladder; CT = computed tomog-
raphy; ESR = erythrocyte sedimentation rate; MRA = magnetic resonance angiography; RF = rheumatoid factor.
Adapted from Chronic kidney disease and pre-ESRD. Management in the primary care setting. Accessed February 24, 2005, at: http://www.oqp.med.
va.gov/cpg/ESRD/ESRD_cpg/app/bot_app_1.htm.
Chronic Kidney Disease
TABLE 6
Imaging Options in Chronic Kidney Disease
Based on an international survey29 of nephrol- kidney disease because it may precipitate acute renal failure.
ogists, rates of biopsy vary widely in practice. Information from references 1 and 28.
The management of chronic kidney dis-
ease depends on the specific treatment of
the underlying cause, the stage of the kid- ARB.19,20,31,32 Other interventions that may be
ney disease, and the presence or absence of beneficial include lipid-lowering measures,
proteinuria. Treatment goals for all patients partial correction of anemia,1 and limiting
include slowing disease progression, detect- dietary protein intake to 0.60 to 0.75 g per kg
ing and managing complications, and pre- of body weight per day in patients with a GFR
venting cardiovascular disease. below 25 mL per minute per 1.73 m2.33
The rate of progression for chronic kidney Complications of chronic kidney disease
disease depends on the underlying cause. In affect every organ system. Patients with a
general, tubulointerstitial diseases progress GFR below 60 mL per minute per 1.73 m2
more slowly than do glomerular diseases, should undergo periodic monitoring for the
diabetic and hypertensive nephropathy, and complications listed in Table 7.1,28
polycystic kidney disease.11 Rates of progres- Clinical evaluation may detect gastroin-
sion also vary widely among patients with the testinal, neurologic, dermatologic, and mus-
same type of kidney disease. culoskeletal complications in the advanced
In rapidly progressing kidney disease, the stages of chronic kidney disease. Gastro-
GFR may decrease by as much as 10 to 20 mL intestinal symptoms may herald the onset
per minute per 1.73 m2 per year. In more of uremia, indicating the need for kidney
slowly progressing disease, the GFR may replacement therapy.
decrease by as little as 2 mL per minute per Laboratory tests detect complications
1.73 m2 per year. Plotting the GFR against such as electrolyte abnormalities, disordered
time is helpful in estimating the rate of dis- calcium or phosphorus metabolism, and
ease progression and the time to kidney fail- anemia. Patients with nephrotic-range pro-
ure, and it helps predict the need for kidney teinuria are at risk for hypoalbuminemia
replacement therapy (Figure 21). and immune dysfunction because of the loss
Three interventions have been proved of immunoglobulins. Periodic monitoring of
to slow the progression of kidney disease: the total serum protein level and the albumin
blood pressure control,30 glycemic control level is indicated in these patients. Nutri-
in patients with diabetes,1 and reduction tional status should be evaluated because
of proteinuria with an ACE inhibitor or malnutrition adversely affects prognosis.
November 1, 2005 U Volume 72, Number 9 www.aafp.org/afp American Family Physician 1729
Estimating the Time to Kidney Failure
90
40
30
Rapid disease progression:
20 decrease of 10 mL per minute
10 per 1.73 m2 per year
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Age (years)
Figure 2. Estimating the progression of chronic kidney disease. A plot of the glomerular filtration
rate (GFR) over time can be used to predict the time to end-stage renal disease.
Information from reference 1.
1730 American Family Physician www.aafp.org/afp Volume 72, Number 9 U November 1, 2005
Chronic Kidney Disease
TABLE 7
Screening for Complications in Chronic Kidney Disease
(Stages 3 and 4*)
1. National Kidney Foundation. K/DOQI, clinical practice GFR = glomerular filtration rate.
guidelines for chronic kidney disease: evaluation, clas-
Information from references 6, 11, 28, 38, and 40.
sification, and stratification. Am J Kidney Dis 2002;39
(2 suppl 1):S1-266. Accessed online February 15, 2005, at:
http://www.kidney.org/professionals/kdoqi/guidelines
_ckd/toc.htm. population screening: results from the NHANES III.
2. United States renal data survey. Annual data report, Kidney Int 2002;61:2165-75.
2003. Accessed online February 15, 2005, at: http:// 8. Barratt A, Irwig L, Glasziou P, Cumming RG, Raffle A,
www.usrds.org/adr_2003.htm. Hicks N, et al. Users’ guides to the medical literature:
3. National Kidney Foundation. KEEP: Kidney Early Evalu- XVII. How to use guidelines and recommendations
ation Program. Annual data report. Program intro- about screening. Evidence-Based Medicine Working
duction. Am J Kidney Dis 2003;42(5 suppl 4):S5-15. Group. JAMA 1999;281:2029-34.
Accessed online February 15, 2005, at: http://www. 9. Boulware LE, Jaar BG, Tarver-Carr ME, Brancati FL,
kidney.org/keep/pdf/ajkd_KEEP_nov_2003.pdf. Powe NR. Screening for proteinuria in US adults: a cost-
4. McClellan WM, Ramirez SP, Jurkovitz C. Screening for effectiveness analysis. JAMA 2003;290:3101-14.
chronic kidney disease: unresolved issues. J Am Soc 10. National Kidney Foundation. Kidney learning system.
Nephrol 2003;14(7 suppl 2):S81-7. CKD clinical action plan. Accessed online March 9, 2005,
5. Patel SS, Kimmel PL, Singh A. New clinical practice at: http://www.kidney.org/kls/professionals/cap.cfm.
guidelines for chronic kidney disease: a framework for 11. Greenberg A, Cheung, AK, National Kidney Founda-
K/DOQI. Semin Nephrol 2002;22:449-58. tion. Primer on kidney diseases. 3d ed. San Diego:
6. Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes Academic Press, 2001.
MW. National Kidney Foundation practice guidelines 12. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth
for chronic kidney disease: evaluation, classification, D. A more accurate method to estimate glomerular
and stratification. Ann Intern Med 2003;139:137-47. filtration rate from serum creatinine: a new prediction
7. Garg AX, Kiberd BA, Clark WF, Haynes RB, Clase CM. equation. Modification of Diet in Renal Disease Study
Albuminuria and renal insufficiency prevalence guides Group. Ann Intern Med 1999;130:461-70.
November 1, 2005 U Volume 72, Number 9 www.aafp.org/afp American Family Physician 1731
Chronic Kidney Disease
13. Cockcroft DW, Gault MH. Prediction of creatinine clear- 28. Chronic kidney disease and pre-ESRD. Management in
ance from serum creatinine. Nephron 1976;16:31-41. the primary care setting. Accessed February 24, 2005,
14. Lewis J, Agodoa L, Cheek D, Greene T, Middleton J, at: http://www.oqp.med.va.gov/cpg/ESRD/ESRD_cpg/
O’Connor D, et al. Comparison of cross-sectional mea- frameset.htm.
surements in African Americans with hypertensive neph- 29. Fuiano G, Mancuso D, Comi N, Mazza G, Fabiano G.
rosclerosis and of primary formulas to estimate glomeru- Renal biopsy: clinical indications. In: 2nd International
lar filtration rate. Am J Kidney Dis 2001;38:744-53. Congress of Nephrology in Internet. 2001. Accessed
15. Vervoort G, Willems HL, Wetzels JF. Assessment of online March 25, 2005, at: http://www.uninet.edu/
glomerular filtration rate in healthy subjects and nor- cin2001/html/conf/fuiano.html.
moalbuminuric diabetic patients: validity of a new 30. Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA,
(MDRD) prediction equation. Nephrol Dial Transplant Hunsicker, LG, et al. Blood pressure control, proteinuria,
2002;17:1909-13. and the progression of renal disease. The Modifica-
16. Beddhu S, Samore MH, Robert MS, Stoddard GJ, Pap- tion of Diet in Renal Disease Study. Ann Intern Med
pas LM, Cheung AK. Creatinine production, nutrition, 1995;123:754-62.
and glomerular filtration rate estimation. J Am Soc 31. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch
Nephrol 2003;14:1000-5. WE, Parving HH, et al. Effects of losartan on renal and
17. Lamb EJ, Webb MC, Simpson DE, Coakley AJ, Newman cardiovascular outcomes in patients with type 2 diabe-
DJ, O’Riordan SE. Estimation of glomerular filtration tes and nephropathy. N Engl J Med 2001;345:861-9.
rate in older patients with chronic renal insufficiency: 32. Jafar TH, Schmid CH, Landa M, Giatras I, Toto R,
is the modification of diet in renal disease formula an Remuzzi G, et al. Angiotensin-converting enzyme
improvement? J Am Geriatr Soc 2003;51:1012-7. inhibitors and progression of nondiabetic renal disease:
18. Rule AD, Larson TS, Bergstrahl EJ, Slezak JM, Jacobsen SJ, a meta-analysis of patient level data [published correc-
Cosio FG. Using serum creatinine to estimate glomerular tion appears in Ann Intern Med 2002;137:299]. Ann
filtration rate: accuracy in good health and in chronic Intern Med 2001;135:73-87.
kidney disease. Ann Intern Med 2004;141:929-37. 33. Kopple JD, Levey AS, Greene T, Chumlea WC, Gassman
19. Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, JJ, Hollinger DL, et al. Effect of dietary protein restric-
de Jong PE, et al. Progression of chronic kidney disease: tion on nutritional status in the Modification of Diet in
the role of blood pressure control, proteinuria, and Renal Disease Study. Kidney Int 1997;52:778-91.
angiotensin-converting enzyme inhibition: a patient- 34. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY.
level meta-analysis. Ann Intern Med 2003;139:244-52. Chronic kidney disease and the risks of death, car-
20. Heart Outcomes Prevention Evaluation Study Investiga- diovascular events, and hospitalization. N Engl J Med
tors. Effects of ramipril on cardiovascular and microvas- 2004;351:1296-305.
cular outcomes in people with diabetes mellitus: results 35. Sarnak MJ, Green T, Wang X, Beck G, Kusek JW, Collins
of the HOPE study and the MICRO-HOPE substudy. AJ, et al. The effect of a lower target blood pressure on
Lancet 2000;355:253-9. the progression of kidney disease: long-term follow-up
21. Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, War- of the Modification of Diet in Renal Disease Study. Ann
ram JH, Krolewski AS. Regression of microalbuminuria Intern Med 2005;142:342-51.
in type 1 diabetes. N Engl J Med 2003;348:2285-93. 36. National Kidney Foundation. K/DOQI clinical practice
22. Winocour PH, Marshall SM. Microalbuminuria: bio- guidelines for managing dyslipidemias in chronic kidney
chemistry, epidemiology, and clinical practice. New disease, part 3, guideline 4. Accessed online February
York: Cambridge University Press, 1998. 16, 2005, at: http://www.kidney.org/professionals/
kdoqi/guidelines_lipids/iii.htm.
23. Molitch ME, DeFronzo RA, Franz MJ, Keane WF,
Mogensen CE, Parving HH, et al. American Diabetes 37. Liu Y, Coresh J, Eustace JA, Longenecker JC, Jaar B, Fink
Association. Nephropathy in diabetes. Diabetes Care ME, et al. Association between cholesterol level and
2004;29(suppl 1):S79-83. mortality in dialysis patients: role of inflammation and
malnutrition. JAMA 2004;291:451-9.
24. National electronic Library for Health. Clinical guidelines
for type 2 diabetes: renal disease-prevention and early 38. National Kidney Foundation. K/DOQI clinical practice
management, part 6: screening tests for renal disease guidelines for anemia of chronic kidney disease: update
in type 2 diabetes. Accessed online February 16, 2005, 2000 [published correction appears in Am J Kidney Dis
at: http://www.nelh.nhs.uk/guidelinesdb/html/fulltext- 2001;38:442]. Am J Kidney Dis 2001;37(1 suppl 1):
guidelines/rcgprenal-6.html. S182-238.
25. Scheid DC, McCarthy LH, Lawler FH, Hamm RM, 39. United States Department of Health and Human Ser-
Reilly KE. Screening for microalbuminuria to prevent vices, National Institutes of Health, National Institute of
nephropathy in patients with diabetes: a systematic Diabetes and Digestive and Kidney Diseases. Chronic
review of the evidence. J Fam Pract 2001;50:661-8. kidney disease in the United States. Accessed online
February 16, 2005, at: http://www.nkdep.nih.gov/edu-
26. Hale WA, Nashelsky J, Wilson SA. Clinical inquiries.
cresources/nkdep_cdk_presentation.pdf.
Does screening for microalbuminuria in diabetes pre-
vent complications? J Fam Pract 2003;52:229-31. 40. Kinchen KS, Sadler J, Fink N, Brookmeyer R, Klag M,
Levey AS, et al. The timing of specialist evaluation in
27. Parving HH, Lehnert H, Brochner-Mortensen J, Gomis
chronic kidney disease and mortality. Ann Intern Med
R, Andersen S, Arner P. Irbesartan in Patients with Type
2002;137:479-86.
2 Diabetes and Microalbuminuria Study Group. The
effect of irbesartan on the development of diabetic 41. Levinsky NG. Specialist evaluation in chronic kidney
nephropathy in patients with type 2 diabetes. N Engl J disease: too little, too late. Ann Intern Med 2002;137:
Med 2001;345:870-8. 542-3.
1732 American Family Physician www.aafp.org/afp Volume 72, Number 9 U November 1, 2005