You are on page 1of 10

Detection and Evaluation

of Chronic Kidney Disease

Harbor-University of California, Los Angeles Medical Center, Torrance, California

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.)


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 American Family Physician 1723
Chronic Kidney Disease

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.

GFR = glomerular filtration rate.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-
oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 1639 or

urinary obstruction, or a systemic illness that glomerulonephritis (less than 10 percent),

affects the kidneys.1 A recent analysis9 sug- and cystic kidney (2 to 3 percent). Unknown
gested that screening all patients older than causes account for the remaining patients
60 years is cost-effective even when other risk with end-stage renal disease.2
factors for chronic kidney disease are absent;
screening low-risk patients younger than
60 years does not appear to be cost-effective. Screening patients at risk for chronic kid-
Diabetes is the most common cause of ney disease relies on the detection of func-
kidney disease. From 40 to 60 percent of tional abnormalities using readily available,
patients who progress to end-stage renal dis- inexpensive laboratory tests. The measured
ease have diabetes. Other underlying condi- serum creatinine level is used to calculate an
tions in patients with end-stage renal disease estimated glomerular filtration rate (GFR).
include hypertension (15 to 30 percent), Screening for proteinuria often alerts the
physician to the presence of chronic kidney
disease before changes in the GFR become
TABLE 1 apparent.
Definitions from the National Kidney Foundation’s Current KDOQI guidelines1,5,6 recommend
Kidney Disease Outcomes Quality Initiative screening for kidney disease with a serum
creatinine measurement for use in GFR
Chronic kidney disease
estimation and analysis of a random urine
Kidney damage for three or more months based on findings of abnormal
sample for albuminuria. Significant kidney
structure (imaging studies) or abnormal function (blood tests, urinalysis)
or disease can present with decreased GFR or
GFR below 60 mL per minute per 1.73 m2 for three or more months proteinuria, or both. An analysis7 of data
with or without evidence of kidney damage from the third National Health and Nutrition
End-stage renal disease (kidney failure) Examination Survey (NHANES III) showed
GFR below 15 mL per minute per 1.73 m2 that 20 percent of persons with diabetes, and
or 43 percent of persons with hypertension and
Need for kidney replacement therapy (dialysis or transplant) a GFR below 30 mL per minute per 1.73 m2,
had no proteinuria. Therefore, an estimate of
GFR = glomerular filtration rate.
the GFR and a screening method for protein-
Adapted with permission from National Kidney Foundation. K/DOQI, clinical practice
uria are required.1
guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J
Kidney Dis 2002;39(2 suppl 1):S1-266. Accessed online February 15, 2005, at: http:// Selected patients with risk factors for kid- ney disease should be screened with renal
ultrasonography. Indications for this study

1724 American Family Physician Volume 72, Number 9 U November 1, 2005
Chronic Kidney Disease
Stages of Chronic Kidney Disease
Based on Estimated GFR

GFR (mL per minute 14.2 percent of persons with hypertension

Stage per 1.73 m2) but no diabetes, have a GFR below 60 mL
1 r90 per minute per 1.73 m2. The prevalence of
2 60 to 89 GFRs below 60 mL per minute per 1.73 m2
3 30 to 59 increases steadily with age; 22.5 percent of
4 15 to 29 nondiabetic, nonhypertensive octogenarians
5 < 15 or dialysis have a GFR below this level.
Clinically useful GFR estimates are calcu-
GFR = glomerular filtration rate. lated from the measured serum creatinine
Information from reference 1. level12,13 after adjustments for age, sex, and
race. A GFR of 100 mL per minute per
1.73 m2 is considered normal for women,
include suspected urinary tract obstruction, and 120 mL per minute per 1.73 m2 is a
recurrent urinary tract infections, vesico- normal GFR for men.1 The two most com-
ureteral reflux, and a family history of poly- monly used formulas for GFR estimation
cystic kidney disease.1 are shown in Table 3.12-18 These methods
have been studied in a variety of popula-
ESTIMATING THE GFR tions.12,14-18 Validation studies12 performed
The GFR is an indication of functioning kid- in middle-aged patients with chronic kidney
ney mass; it has implications for treatment disease showed that the Modification of
goals and for the dosing of renally excreted Diet in Renal Disease (MDRD) study equa-
medications.10 The KDOQI guidelines define tion was more accurate than the Cockcroft-
stages of chronic kidney disease based on an Gault equation, which calculates creatinine
estimated GFR that is calculated from the clearance. In a recent study,18 however, the
serum creatinine level (Table 21). MDRD study equation was found to system-
The standard for GFR measurement is the atically underestimate the GFR in patients
clearance rate of inulin, a substance that passes without chronic kidney disease.
through the kidney unchanged. Creatinine In most situations and as long as kidney
clearance, as measured by a 24-hour urine col- function is stable, a calculated GFR can
lection, usually overestimates the GFR because replace measurement of a 24-hour urine
of the active secretion of creatinine by the kid- collection for creatinine clearance. A user-
ney and can vary with muscle mass.11
Significant kidney dysfunction may be
present despite a normal serum creatinine TABLE 3
level. An estimation of the GFR based on Formulas for Estimating GFR in Adults*
the serum creatinine level correlates bet-
ter with direct measures of the GFR and Abbreviated MDRD study equation12†
detects more cases of chronic kidney disease GFR (mL per minute per 1.73 m2) = 186  (SCr) 1.154  (age) 0.203
than does the serum creatinine level alone.  (0.742, if female)  (1.210, if black)
Furthermore, patients with the same serum Cockcroft-Gault equation13
creatinine level may have different estimated (140 – age)  weight
CCr (mL per minute) =  (0.85, if female)
GFRs. For example, a 45-year-old black man 72  SCr
whose serum creatinine level is 1 mg per dL
(88 μmol per L) has normal kidney function GFR = glomerular filtration rate; MDRD = Modification of Diet in Renal Disease;
SCr = serum creatinine concentration; CCr = creatinine clearance.
with an estimated GFR of 130 mL per min-
ute per 1.73 m2, whereas a 65-year-old white *—For each equation, SCr is in milligrams per deciliter, age is in years, and weight is
in kilograms.
woman with the same serum creatinine level †—In validation studies,14-17 the MDRD study equation performed as well as versions
has an estimated GFR of 59 mL per minute with more variables; however, a recent study18 found that the equation underesti-
per 1.73 m2, or stage 3 kidney disease. mated the GFR in patients who did not have chronic kidney disease.
Based on an analysis7 of NHANES III data, Information from references 12 through 18.
20 percent of persons with diabetes, and

November 1, 2005 U Volume 72, Number 9 American Family Physician 1725
Chronic Kidney Disease
Preferred Methods for Assessing Kidney Function

Method Situations for use

tions, immunoglobulins also may be excreted
MDRD study equation Patients with diabetic kidney disease†
for estimating GFR* in urine. The protein-creatinine ratio in an
Patients with chronic kidney disease in
middle-age (average age: 51 years)†
early-morning random urine sample corre-
Black patients with hypertensive chronic
lates well with 24-hour urine protein excre-
kidney disease† tion and is much easier to obtain.1
Patients with a kidney transplant† An analysis7 of NHANES III data showed
Cockcroft-Gault equation Older patients (performs better than the that 8.3 percent of 14,622 adults had micro-
for estimating creatinine MDRD study equation) albuminuria (i.e., excretion of 30 to 300 mg
clearance* of albumin per 24 hours ) and 1 percent had
24-hour urine collection Pregnant women macroalbuminuria (i.e., excretion of more
for creatinine clearance Patients with extremes of age and weight than 300 mg of albumin per 24 hours).
Patients with malnutrition Albuminuria was detected in one of every
Patients with skeletal muscle diseases three persons with diabetes, one of every
Patients with paraplegia or quadriplegia seven persons with hypertension but no
Patients with a vegetarian diet and rapidly diabetes, and one of every six persons older
changing kidney function than 60 years.
MDRD = Modification of Diet in Renal Disease; GFR = glomerular filtration rate.
Microalbuminuria often heralds the onset
*—Requires stable kidney function.
of diabetic nephropathy. In a recent study21
†—Validated for use in these patients. of patients with type 1 diabetes, spontaneous
Based on information from references 3 and 12 through 17.
regression of microalbuminuria occurred in
some patients, suggesting that microalbu-
minuria may represent an initial reversible
friendly GFR calculator is available online phase of kidney damage rather than the
at beginning of an inexorable progression to
kdoqi/gfr_page.cfm. Determination of cre- end-stage renal disease.22
atinine clearance using a 24-hour urine The KDOQI guidelines1 and the Ameri-
collection is still required to assess kidney can Diabetes Association (ADA) guidelines23
function in patients with the conditions recommend screening for microalbumin-
listed in Table 4.3,12-17 uria in all patients at risk for kidney dis-
ease. Screening can be performed using a
DETECTING AND QUANTITATING PROTEINURIA microalbumin-sensitive dipstick or analysis
Proteinuria is associated with more rapid of a random morning urine sample to deter-
progression of chronic kidney disease and a mine the microalbumin-creatinine ratio.
greater likelihood of developing end-stage Microalbumin dipsticks have a sensitivity of
renal disease. Consequently, detection and 51 to 100 percent and a specificity of 27 to
quantitation of proteinuria are essential to 97 percent. 24 The ADA 25 recommends
the diagnosis and treatment of chronic kid- repeated sampling, but the NKF1 and others
ney disease. question the necessity for this. An algorithm
Reducing proteinuria with an angiotensin- for detecting proteinuria and microalbu-
converting enzyme (ACE) inhibitor or an minuria is provided in Figure 1.1
angiotensin-II receptor blocker (ARB) slows The value of screening for microalbumin-
the progression of chronic kidney disease in uria has been questioned in patients who
patients with or without diabe- already are receiving ACE-inhibitor therapy26
tes.19,20 Quantitative measures on the basis that the results are unlikely to
Proteinuria is associated of proteinuria also are used to change management. One study27 in patients
with more rapid progres- monitor response to therapy. with type 2 diabetes showed that increasing
sion of chronic kidney Albumin, the predominant the dose of an ARB to decrease or eliminate
disease and a greater protein excreted by the kidney microalbuminuria provides additional bene-
likelihood of developing in most types of renal disease, fit in slowing progression to overt nephropa-
end-stage renal disease. is detected readily by urine dip- thy. Therefore, current research suggests that
stick testing. In some condi- it may be beneficial to monitor patients with

1726 American Family Physician Volume 72, Number 9 U November 1, 2005
Evaluation for Proteinuria and Microalbuminuria

Patient with risk factors for chronic kidney disease

Urine dipstick*

Positive: r1+ protein Negative or trace

Analysis of random urine sample Microalbumin-specific dipstick test

for protein-creatinine ratio or analysis of random urine sample
for microalbumin-creatinine ratio

r200 mg of protein < 200 mg of protein Negative or < 30 mg Positive or r30 mg

per g of creatinine per g of creatinine of microalbumin of microalbumin
per g of creatinine per g of creatinine

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,

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 American Family Physician 1727
Chronic Kidney Disease
Diagnostic Evaluation in Chronic Kidney Disease

Disorder Clinical clues Urine sediment Protein-creatinine ratio Additional tests

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
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,
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,
Urinary tract Urinary symptoms Benign, or RBCs None KUB radiography,
obstruction intravenous pyelography,
spiral CT scanning, renal
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
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:
Chronic Kidney Disease
Imaging Options in Chronic Kidney Disease

Imaging study What the study helps identify

irreversible disease. Asymmetry in kidney
Plain-film radiography of Ureter or bladder stones
size suggests renovascular disease. kidneys, ureters, and bladder
Imaging studies that may be useful in iden- Renal ultrasonography Kidney size, obstructive kidney disease,
tifying the cause of chronic kidney disease are polycystic kidney disease
listed in Table 6.1,28 Renal biopsy is indicated Renal Doppler Renovascular disease, renal vein
when the cause cannot be determined by the ultrasonography thrombosis
history and laboratory evaluation, when the Radioisotope renal scanning Individual kidney function, renovascular
patient’s signs and symptoms suggest paren- disease, obstructive uropathy
chymal disease, and when the differential Computed tomography Kidney mass or complex cyst
diagnosis includes diseases that require dif- Magnetic resonance Renovascular disease
ferent treatments or that have different prog-
Renal angiography Renovascular disease, renal artery
noses.11 Biopsy more commonly is required
in patients with chronic kidney disease that polyarteritis nodosa
is not related to diabetes, and biopsy often Retrograde ureterography Upper urinary tract obstruction
is indicated in adult patients with nephrotic
syndrome or suspected glomerulonephritis. NOTE: Intravenous pyelography generally is not performed in patients with chronic

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 American Family Physician 1729
Estimating the Time to Kidney Failure

GFR (mL per minute per 1.73 m2)

Slower disease progression:
60 decrease of 2 mL per minute
50 per 1.73 m2 per year

Rapid disease progression:
20 decrease of 10 mL per minute
10 per 1.73 m2 per year

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.

RISK OF CARDIOVASCULAR DISEASE with excretion of more than 1 g of protein

Cardiovascular disease is the most com- per 24 hours. A long-term follow-up study35
mon cause of death in patients with chronic of patients with nondiabetic kidney disease
kidney disease. The risk of cardiovascular and an average GFR of 32 mL per minute per
disease and associated mortality increases 1.73 m2 found that the patients randomized
in proportion to the decrease in the GFR.34 to a low blood pressure target were one third
Patients with albuminuria and normal GFR less likely to develop kidney failure than were
also are at increased risk. Evaluation for tra- the patients randomized to a usual blood
ditional cardiovascular risk factors, including pressure goal.
smoking, high lipid levels, hypertension, and The KDOQI guidelines on managing
sedentary lifestyle, is essential. The KDOQI dyslipidemias36 in chronic kidney disease
guidelines1 recommend a blood pressure goal recommend a low-density lipoprotein cho-
of 130/80 mm Hg in patients with normal lesterol goal of less than 100 mg per dL
urinary albumin concentrations, and a blood (2.60 mmol per L) for patients with chronic
pressure goal of 125/75 mm Hg in patients kidney disease, because they are statistically
at highest risk for cardiovascular disease. In
these patients, the 10-year risk for mortal-
The Authors ity from cardiovascular disease exceeds 20
SUSAN SNYDER, M.D., is associate clinical professor of family medicine in the percent.36
Department of Family Medicine at the David Geffen School of Medicine at the Paradoxically, dialysis patients with the
University of California, Los Angeles (UCLA). She also is vice chair for academic lowest cholesterol levels are the most likely to
affairs for the Department of Family Medicine and director of the primary care die of cardiovascular disease. This is because
faculty development fellowship at Harbor-UCLA Medical Center, Torrance, Calif.
Dr. Snyder received her medical degree from the University of Vermont College
low levels of cholesterol are associated with
of Medicine, Burlington, and completed a family medicine residency at San nontraditional cardiac risk factors of malnu-
Francisco General Hospital. trition and are markers of chronic inflam-
mation.37 Lipid disorders should be treated
BERNADETTE PENDERGRAPH, M.D., is a faculty member in the family medicine
aggressively in patients with chronic kidney
residency program at Harbor-UCLA Medical Center and serves as assistant direc-
tor of the primary care sports medicine fellowship. Dr. Pendergraph earned her disease and end-stage renal disease.36
medical degree at the David Geffen School of Medicine at UCLA. She completed Additional cardiac risk factors specific
a surgical internship, family medicine residency, faculty development fellowship, to chronic kidney disease include volume
and sports medicine fellowship at Harbor-UCLA Medical Center. overload, hyperparathyroidism, and uremia.
Address correspondence to Susan Snyder, M.D., Harbor-UCLA Medical Center,
Anemia caused by decreased erythropoietin
1403 W. Lomita Blvd., Suite 102, Harbor City, CA 90710 (e-mail: ssnyder@ production also may contribute to cardiovas- Reprints are not available from the authors. cular mortality. Treatment with exogenous

1730 American Family Physician Volume 72, Number 9 U November 1, 2005
Chronic Kidney Disease
Screening for Complications in Chronic Kidney Disease
(Stages 3 and 4*)

erythropoietin has been shown to improve Test Complications detected

the prognosis.38 Hemoglobin concentration Anemia
WHEN TO REFER Red blood cell indexes, For ruling out other causes of anemia
reticulocyte count, iron before erythropoietin therapy is
Nephrology referral generally is recom- studies, fecal occult blood test started
mended for patients with a serum creatinine Serum electrolyte levels Hyperkalemia, hyponatremia, acidosis
level of 1.5 to 2.0 mg per dL (133 to 177 μmol Calcium, phosphorus, and Hypocalcemia, hyperphosphatemia,
per L). According to one estimate, that would parathyroid hormone levels secondary hyperparathyroidism
mean seven new patients per day for every Serum albumin and total Hypoalbuminemia, decreased levels
nephrologist in the United States.39 Some protein levels of immunoglobulins in patients
with nephritic levels of proteinuria
indications for nephrology referral are listed or signs of malnutrition
in Table 8.6,11,28,38,40
The value of timely referral has been dem- *—Patients with a glomerular filtration rate below 60 mL per minute per 1.73 m2.
onstrated,40 but the contribution of primary Information from references 1 and 28.
care to outcomes in patients with chronic
kidney disease has not been studied.41 Given
the magnitude of the rapid increase in the
number of cases of chronic kidney disease, TABLE 8
primary care evaluation and timely referral Indications for Nephrology Referral
are recommended. The KDOQI endorses in Chronic Kidney Disease
a model of collaboration between primary
care physicians and subspecialists.6 The Underlying cause unclear after basic work-up
National Kidney Disease Education Program Renal biopsy indicated
provides tools to promote this collaboration; Management of underlying cause beyond the scope of primary care
they may be accessed online at http://www. Stage 3 chronic kidney disease (GFR < 60 mL per minute per 1.73 m2): consider comanagement
Stage 4 chronic kidney disease (GFR < 30 mL per minute per 1.73 m2):
Author disclosure: Nothing to disclose. nephrologist involvement essential
Rapid progression of chronic kidney disease
REFERENCES Superimposed acute kidney failure

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:
_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, 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, 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:
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 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:
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:
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:
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: 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:
26. Hale WA, Nashelsky J, Wilson SA. Clinical inquiries.
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
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 Volume 72, Number 9 U November 1, 2005