Chronic Kidney Disease: Detection and Evaluation

MARGARET BAUMGARTEN; TODD GEHR

MARGARET BAUMGARTEN, MD, AND TODD GEHR, MD

A more recent article on chronic kidney disease is available.

Am Fam Physician. 2011;84(10):1138-1148

Author disclosure: No relevant financial affiliations to disclose.

Chronic kidney disease affects an estimated 27 million adults in the United States, and is associated with significantly increased risk of cardiovascular disease and stroke. Patients should be assessed annually to determine whether they are at increased risk of developing chronic kidney disease based on clinical and sociodemographic factors. Diabetes mellitus, hypertension, and older age are the primary risk factors that warrant screening. Other risk factors include cardiovascular disease, family history of chronic kidney disease, and ethnic and racial minority status. Serum creatinine levels can be used to estimate the glomerular filtration rate, and spot urine testing can detect proteinuria. After the diagnosis of chronic kidney disease is made, staging based on estimated glomerular filtration rate determines prognosis, evaluation, and management. Further evaluation should focus on the specific type of kidney disease and on identifying complications related to the disease stage. Patients should be assessed for risk factors leading to the further loss of kidney function and cardiovascular disease. Patients with estimated glomerular filtration rates less than 30 mL per minute per 1.73 m², significant proteinuria, or rapid loss of kidney function should be referred to a nephrologist for further evaluation and management.

Chronic kidney disease (CKD) affects an estimated 27 million adults in the United States and is associated with increased mortality, morbidity, and health care costs.^1,2 CKD is also associated with significantly increased risks of cardiovascular disease³ and stroke.⁴ The incidence and prevalence of CKD among U.S. adults have increased dramatically since 1991.⁵ More than 500,000 Americans were treated for end-stage renal disease in 2007.⁶ The increases are partly explained by the increasing prevalence of diabetes mellitus and hypertension, the leading risk factors for CKD. Awareness of CKD among patients has modestly increased in recent years, but remains low. According to the 2003–2004 National Health and Nutrition Examination Survey, less than 5 percent of patients with stage 1 or 2 CKD and less than 10 percent with stage 3 reported having been diagnosed with CKD; only 45 percent of patients with stage 4 were aware of their condition.⁷ Although clinical laboratories report estimated glomerular filtration rate (GFR) directly to physicians, CKD recognition remains low.⁸ In 2002, the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative published practice guidelines to help primary care physicians identify patients with early CKD and improve health outcomes.⁹

Clinical recommendation	Evidence rating	References
Physicians should screen at-risk populations for CKD using serum creatinine levels and random urine testing for albuminuria.	C	⁹, ¹¹, ¹², ¹⁵
Adults with cardiovascular disease should be screened for CKD.	C	¹³
The Chronic Kidney Disease Epidemiology Collaboration formula is more accurate than the Modification of Diet in Renal Disease equation or the Cockcroft-Gault equation, and should be used to estimate GFR.	C	¹⁹, ²¹
Acetaminophen is the analgesic of choice for short-term treatment of mild to moderate pain in patients with stage 3 to 5 CKD.	C	³³
Nephrology consultation is indicated when the estimated GFR is less than 30 mL per minute per 1.73 m².	C	⁹

CKD is defined by the presence of structural or functional abnormalities of the kidney with or without an accompanying reduction in GFR. Persons with CKD may have one or more of the following: pathologic abnormalities, markers of kidney damage (i.e., imaging abnormalities and abnormalities in serum or urine, including proteinuria and abnormal urinary sediment), or GFR less than 60 mL per minute per 1.73 m² for at least three months. If the duration of the abnormality is unknown, the possibility of acute kidney injury should be considered and appropriate evaluation performed for reversible causes. Most persons who have received kidney transplants are considered to have CKD.

Detection of CKD

INDICATIONS FOR SCREENING

Annual CKD screening is recommended by the American Diabetes Association,¹⁰ by the National Kidney Foundation for patients at risk,^9,11 by the Joint National Committee on Hypertension¹² for patients with diabetes and hypertension, and by the American Heart Association for patients with cardiovascular disease.¹³ The U.S. Preventive Services Task Force has not examined the evidence or made recommendations for screening. Cardiovascular disease, a family history of CKD, and ethnic or racial minority status do not significantly increase the risk of CKD in adults older than 60 who have diabetes and hypertension.¹⁴ Risk factors are listed in Table 1.⁹

SCREENING TESTS

CKD is typically detected by measuring serum creatinine levels to calculate the GFR and by measuring the urinary albumin/creatinine ratio to detect proteinuria.¹⁵ Although the most common causes of CKD are diabetes and hypertension (Table 2^9,16 ), the disease can be caused by many other conditions. Urinalysis can detect signs of glomerulonephritis, tubulointerstitial disease, vasculitis, hereditary nephritis, and lupus nephritis; however, it is not routinely recommended in otherwise healthy patients.

Disease type		Etiology and examples	Prevalence among patients with end-stage renal disease in 2010 (%)
Diabetic kidney disease		Type 2 diabetes mellitus	32.5
Diabetic kidney disease		Type 1 diabetes mellitus	5.7
Nondiabetic kidney disease
	Vascular diseases	Hypertension, ischemic renal disease	24.8
	Glomerular diseases	Primary: lupus nephritis, vasculitis, membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, immunoglobulin A nephropathy	18
	Glomerular diseases	Secondary: infections (e.g., hepatitis B and C, human immunodeficiency virus–associated bacterial endocarditis), amyloidosis, heroin use, malignancy (e.g., leukemia, Hodgkin lymphoma, carcinoma)	18
	Cystic diseases	Polycystic kidney disease	7
	Tubulointerstitial disease	Urinary tract infections, nephrolithiasis, obstruction, sarcoidosis, multiple myeloma, drug toxicity (e.g., proton pump inhibitors, lithium, nonsteroidal anti-inflammatory drugs)	3.8

ESTIMATING GFR

The GFR is the best measure of kidney function. Normal GFR varies by age, sex, and body size. GFR is approximately 120 to 130 mL per minute per 1.73 m² in young adults, and decreases by an average of 1 mL per minute per 1.73 m² per year after 30 years of age.⁹ A GFR less than 60 mL per minute per 1.73 m² represents a loss of at least one-half of normal kidney function; below this level, there is an increased prevalence of CKD complications.

Creatinine clearance is used to estimate the GFR. Because creatinine is filtered and secreted by the proximal tubules, the creatinine clearance exceeds the GFR. Generation of creatinine is determined by muscle mass and diet, whereas tubular secretion could be decreased by the use of medications such as trimethoprim and cimetidine (Tagamet).

The serum creatinine level is an insensitive marker of GFR early in the course of CKD. A 33 percent decrease in GFR may raise the creatinine level from 0.8 to only 1.2 mg per dL (70.72 to 106.08 μmol per L). If the prior creatinine level is not known, this decrease in GFR may go unrecognized. When estimated GFR is suspected to be inaccurate—for example, in patients with severe malnutrition or paraplegia—a 24-hour urine collection should be performed to evaluate creatinine clearance.

Three equations are typically used to estimate GFR: the Cockcroft-Gault equation,¹⁷ the Modification of Diet in Renal Disease (MDRD) equation,¹⁸ and the more accurate Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)¹⁹ formula (Table 3).^17–19 The Cockcroft-Gault equation systematically overestimates GFR. The MDRD is reasonably accurate in patients with CKD, but it underestimates GFR when it is greater than 60 mL per minute per 1.73 m², and it may misidentify persons with normal kidney function as having CKD. The MDRD can also be affected by fluctuations in creatinine production and fluid balance; it gives falsely elevated estimated GFRs in malnourished and overhydrated patients and falsely decreased GFRs due to increased serum creatinine levels in patients taking trimethoprim and cimetidine.²⁰ The CKD-EPI formula provides better GFR estimation in patients with reduced and normal kidney function.¹⁹ In a recent study, the CKD-EPI was found to be the most accurate formula in estimating GFR.²¹

Equation	Variables	Available at
Chronic Kidney Disease Epidemiology Collaboration	Age, sex, race, serum creatinine level	National Kidney Foundation
			Web site: http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm
		Nephron Information Center
			Web site: http://www.nephron.com/MDRD_GFR.cgi
Cockcroft-Gault	Age, weight, sex, serum creatinine level	Nephron Information Center
Cockcroft-Gault	Age, weight, sex, serum creatinine level		Web site: http://nephron.com/cgi-bin/CGSI.cgi
Modification of Diet in Renal Disease	Age; sex; race; and serum urea, nitrogen, albumin, and creatinine levels	National Kidney Disease Education Program
			Web site: http://www.nkdep.nih.gov/professionals/gfr_calculators/idms_con.htm
		Nephron Information Center
			Web site: http://nephron.com/cgi-bin/MDRDSIdefault.cgi

Markers of Kidney Damage

PROTEINURIA

Proteinuria refers to increased excretion of any urinary protein, including albumin and other serum proteins (tubular proteins). A normal urinary protein/creatinine ratio is less than 200 mg per g; proteinuria is a predictor of total mortality and CKD progression, and can help determine the type of CKD. A normal urinary albumin/creatinine ratio is less than 30 mg per g. Patients with albumin/creatinine ratios of 30 to 300 mg per g are classified as having microalbuminuria, and those with ratios greater than 300 mg per g are classified as having macroalbuminuria.^10,11

Urine dipstick testing is insensitive for the measurement of small amounts of albumin and is not recommended for CKD screening in patients at risk. This test is positive when a large amount (greater than 500 to 1,000 mg per day) of protein is excreted. Patients with positive urine dipstick results should repeat the test in the absence of urinary tract infection, ketosis, and hypovolemia. If the second result is positive, the urinary protein/creatinine ratio should be obtained within three months. Persistent proteinuria can be diagnosed by two positive protein/creatinine ratios one to two weeks apart.⁹ Diabetes, the leading cause of nephrotic syndrome in the United States, is diagnosed when the protein/creatinine ratio is greater than 3,000 mg (3.0 g) per g.

ALBUMINURIA

Albumin is a sensitive marker of CKD caused by diabetes, hypertension, and glomerular diseases. Microalbuminuria was the most common abnormality associated with the diagnosis of stages 1 and 2 CKD in the National Health and Nutrition Examination Survey.⁵ Microalbuminuria is an inherent part of the diabetes disease process but also can be present with nonrenal conditions (e.g., obesity, inflammation, cancer).²² Microalbuminuria may indicate increased vascular permeability rather than kidney injury.²³

Patients with diabetes and microalbuminuria who progress to macroalbuminuria are more likely to progress to end-stage renal disease. Diabetic kidney disease can be diagnosed based on the urinary albumin/creatinine ratio, duration of diabetes, and presence of diabetic retinopathy (Table 4).¹¹ When albuminuria reaches the range of macroalbuminuria, albumin becomes the dominant urinary protein, and the advantage of measuring albuminuria over proteinuria is generally lost.⁹ Two out of three abnormal readings are required to confirm persistent albuminuria (Figure 1).^9,15,24

OTHER MARKERS

Other markers of kidney damage include hematuria, cellular casts, serum markers, and imaging abnormalities. Clinical judgment based on the assessment of CKD risk factors should be used to determine if measurement of other markers of kidney damage is indicated.

CKD Staging

Staging is an important step for determining the prognosis, evaluation, and management of CKD. Staging is based on the level of estimated GFR, irrespective of diagnosis (Table 5).⁹ Markers of kidney damage are required for stages 1 and 2. Using the current classification system, nearly 50 percent of U.S. adults older than 70 years have stage 3 CKD, and most have no evidence of albuminuria.⁵ Older patients with stage 3 CKD without proteinuria and stable creatinine levels on repeat testing at three to six months are unlikely to progress to end-stage renal disease and do not have increased mortality risk. Physicians may choose to defer further evaluation in such patients, avoid the use of nephrotoxic medications (Table 6²⁵ ), and adjust the dosages of those that are excreted by the kidneys²⁰ (Table 7^9,26 ).

Stage	Description	Estimated GFR (mL per minute per 1.73 m² )	Action plan
1	Kidney damage* with normal or increased GFR	≥ 90	Diagnose and treat CKD, treat comorbid conditions, slow progression of CKD, reduce cardiovascular risk
2	Kidney damage* with mildly decreased GFR	60 to 89	Estimate progression
3	Moderately decreased GFR	30 to 59	Evaluate and treat complications
4	Severely decreased GFR	15 to 29	Prepare for kidney transplant
5	Kidney failure	< 15 (or dialysis)	Kidney transplant if uremia present

Drug	Mechanism of kidney injury
Acyclovir (Zovirax)	Acute interstitial nephritis, crystal nephropathy
Aminoglycosides	Tubular cell toxicity
Amphotericin B	Tubular cell toxicity
Chinese herbal preparations containing aristolochic acid	Chronic interstitial nephritis
Contrast media	Renal ischemia
Lithium	Chronic interstitial nephritis
Nonsteroidal anti-inflammatory drugs	Acute and chronic interstitial nephritis, impaired glomerular hemodynamics
Phenytoin (Dilantin)	Acute interstitial nephritis
Sulfonamides	Acute interstitial nephritis, crystal nephropathy
Vancomycin	Acute interstitial nephritis
Zoledronic acid (Zometa)	Tubular cell toxicity

Medication	Dosage adjustment based on GFR (mL per minute per 1.73 m² )*
Medication	> 50	10 to 50	< 10
Acyclovir (Zovirax; oral)	100%	100%	200 mg every 12 hours
Allopurinol (Zyloprim)	75%	50%	25%
Amoxicillin	Every 8 hours	Every 8 to 12 hours	Every 24 hours
Amoxicillin/clavulanate (Augmentin)	Every 12 hours	Estimated GFR 10 to 30 mL per minute per 1.73 m²: every 12 hours	Every 24 hours
Amoxicillin/clavulanate (Augmentin)	Every 12 hours	Estimated GFR < 30 mL per minute per 1.73 m²: do not use 875-mg/125-mg tablets	Every 24 hours
Atenolol (Tenormin)	100%	50%	25%
Cefazolin	Every 8 hours	Every 12 hours	50% every 24 to 48 hours
Cephalexin (Keflex)	Every 8 hours	Every 8 to 12 hours	Every 12 to 24 hours
Ciprofloxacin (Cipro)	100%	50 to 75%	50%
Clarithromycin (Biaxin)	100%	50 to 100%	50%
Famotidine (Pepcid)	50%	25%	10%
Fluconazole (Diflucan)	100%	50%	50%
Gabapentin (Neurontin)	Estimated GFR 30 to 60 mL per minute per 1.73 m²: 200 to 700 mg twice daily
	Estimated GFR 16 to 29 mL per minute per 1.73 m²: 200 to 700 mg daily
	Estimated GFR ≤ 15 mL per minute per 1.73 m²: 100 to 300 mg daily
Glyburide	100%	Avoid	Avoid
Levofloxacin (Levaquin)	100%	Estimated GFR 20 to 49 mL per minute per 1.73 m²: 500- to 750-mg initial dose, then 250 to 750 mg every 24 to 48 hours	—
Levofloxacin (Levaquin)	100%	Estimated GFR 10 to 19 mL per minute per 1.73 m²: 500-mg initial dose, then 250 to 500 mg every 48 hours	—
Metformin (Glucophage)	Avoid if serum creatinine level is greater than 1.5 mg per dL (132.60 μmol per L) in men or greater than 1.4 mg per dL (123.76 μmol per L) in women, and in patients older than 80 years
Metoclopramide (Reglan)	100%	75%	50%
Ranitidine (Zantac)	75%	50%	25%
Rosuvastatin (Crestor)	—	GFR < 30 mL per minute per 1.73 m²: 5 mg per day initially; 10 mg per day maximum
Simvastatin (Zocor)	—	GFR < 30 mL per minute per 1.73 m²: 5 mg per day initially
Thiazide diuretics†	100%	100%	Avoid
Valacyclovir (Valtrex)	100%	Every 12 to 24 hours	500 mg every 24 hours

CKD staging does not include risk-modifying parameters such as degree of albuminuria, age, sex, and cardiovascular risk factors. Revised guidelines, currently under development, will address those issues.

Evaluation of CKD

A thorough initial investigation includes determining the etiology and type of CKD and evaluating for comorbidities. The patient and family histories, physical examination, and blood pressure and weight measurements are the most valuable parts of the CKD evaluation (Table 8).^9,27,28 Laboratory tests should include measurement of serum electrolytes and glucose, and a fasting lipid panel. Urinalysis should be performed to evaluate urinary sediment and the urinary albumin/creatinine or protein/creatinine ratio⁹ (Table 9^9,11,29 ). Additional testing may be required to identify rare causes of CKD. Renal ultrasonography is recommended to evaluate kidney size and assess for possible structural abnormalities.⁹

Examination component	Diagnostic clues	Findings suggestive of CKD risks and etiology
Review of systems	Recent infections	Poststreptococcal glomerulonephritis
	Risk factors for sexually transmitted disease	HIV infection, hepatitis B or C
	Skin rash or arthritis	Autoimmune disease (e.g., systemic lupus erythematosus, cryoglobulinemia)
	Symptoms during urination	Urinary tract infection, obstruction, or stone
Medical history	Diabetes mellitus (5 to 10 years' duration)	Microalbuminuria with evidence of retinopathy and elevated BP
	Diabetes (10 to 15 years' duration)	Albuminuria, retinopathy, hypertension
	Hypertension	Severe BP elevation, often with target organ damage
Family history of kidney disease	Males and females are affected equally in every generation	Autosomal dominant polycystic kidney disease
	Males in every generation are affected	Sex-linked recessive disease (e.g., Alport syndrome)
	Less frequent than every generation	Autosomal recessive polycystic kidney disease
Physical examination	Abdominal findings	Bruit (renal artery stenosis, fibromuscular dysplasia), flank pain, distended bladder
	Cardiovascular findings	Heart failure, ventricular hypertrophy
	Carotid bruit	Carotid artery disease
	Decreased peripheral pulses	Peripheral vascular disease
	General findings	Cushingoid appearance, edema
	Increased BP and weight	Hypertension, obesity
	Musculoskeletal findings	Arthritis, synovitis
	Ophthalmoscopic findings	Hypertensive or diabetic retinal disease
	Skin changes	Rash and skin changes in autoimmune disease or neurofibromatosis
Laboratory tests	Abnormal serum and urine protein electrophoresis	Multiple myeloma, amyloidosis, light-chain deposition disease
	Decreased serum complement levels C3 and C4	Poststreptococcal glomerulonephritis, membranoproliferative glomerulonephritis, lupus nephritis, cryoglobulinemia
	Eosinophiluria	Atheroembolic disease, tubulointerstitial disease
	Positive antiglomerular basement membrane antibody test	Goodpasture syndrome, antiglomerular basement membrane–associated rapidly progressive glomerulonephritis
	Positive antineutrophil cytoplasmic antibody test	Wegener granulomatosis, microscopic polyangiitis, pauci-immune rapidly progressive glomerulonephritis
	Positive antinuclear antibody test	Lupus nephritis
	Positive cryoglobulin test	Cryoglobulinemia
	Positive hepatitis B serology	Membranous nephropathy, membranoproliferative nephritis
	Positive hepatitis C serology	Mixed cryoglobulinemia, membranoproliferative glomerulonephritis, membranous nephropathy
	Positive HIV serology	Focal and segmental glomerulosclerosis
Ultrasonography	Doppler ultrasonography	May be useful in investigation of venous thrombosis, less so in arterial stenosis
	General findings	May show nephrocalcinosis, discrete stones, hydronephrosis, cysts,* or masses
	Increased echogenicity	May indicate cystic disease or medical renal disease
	Large kidneys	Generally indicate tumors, infiltrating diseases, or diseases causing nephrotic syndrome
	Size disparities and scarring	Suggest vascular, urologic, or tubulointerstitial diseases due to stones or infection
	Small hyperechoic kidneys	Generally indicate CKD

Associated kidney disease	Predominant abnormality on urinalysis
Associated kidney disease	ACR or PCR (mg per g creatinine)	RBCs	RBC casts*	WBCs	WBC casts	Tubular cells	Granular casts
Cystic kidney disease	PCR 200 to 1,000	+
Diabetic kidney disease, earlier stages	ACR 30 to 300
Diabetic kidney disease, later stages	ACR > 300 or PCR > 500 to 1,000
Hereditary nephritis or disease of small vessels (microangiopathy)	PCR < 1,000	+				+	+
Hypertensive disease	PCR 200 to 1,000
Noninflammatory glomerular disease (minimal change disease, focal segmental glomerulosclerosis, associated with neoplasm)	PCR > 1,000
Proliferative glomerulonephritis (systemic lupus erythematosus, vasculitis, infections) or hereditary nephritis	PCR > 500	+	+	±	±
Tubulointerstitial nephritis	PCR 200 to 1,000	±		+	+

Cardiovascular disease risk assessment—especially smoking status and lipid levels—is important because death is more likely than progression to dialysis in any stage of CKD.⁹ Electrocardiography is recommended to identify left ventricular hypertrophy.

Patients with an estimated GFR of less than 60 mL per minute per 1.73 m² require further evaluation to assess for complications. Evaluation for anemia is recommended in women with hemoglobin levels less than 12 g per dL (120 g per L) and in men with levels less than 13.5 g per dL (135 g per L), in addition to nutritional assessment and evaluation for bone disease (Table 10).^9,30,31

Clinical finding	CKD stage	Parameters to assess	Frequency of evaluation
Anemia	All	Complete blood count with differential; reticulocyte count; iron, ferritin, and transferrin levels	Once per year (more frequently if abnormal)
Malnutrition	3 to 5	Weight, serum albumin level, dietary history	Every 6 to 12 months in stage 3; every 1 to 3 months in stages 4 and 5
Metabolic bone disease	3 to 5	Alkaline phosphatase level	Once in stage 3; every 12 months in stages 4 and 5
		Calcium and phosphorus levels	Every 6 to 12 months in stage 3; every 3 to 6 months in stage 4; every 1 to 3 months in stage 5
		Consider duel energy x-ray absorptiometry	No routine testing
		25-hydroxyvitamin D level	Once, then as indicated
		Parathyroid hormone level	Once, then as indicated in stage 3; every 6 to 12 months in stage 4; every 3 to 6 months in stage 5
Neuropathy	3 to 5	Paresthesias, mental status, sleep disturbances (e.g., restless legs syndrome); consider sleep study and nerve conduction study	As indicated
Reduced level of functioning and well-being	3 to 5	Health literacy assessment, social support, standardized self-administered instruments (e.g., Dartmouth-Northern New England Primary Care Cooperative Information Project charts, Duke Health Profile, 36-item Medical Outcomes Study [SF-36], Kidney Disease Quality of Life scale)	Once, then as indicated

Short-term risks of GFR reduction (e.g., volume depletion, urinary tract obstruction, use of nephrotoxic agents) require immediate recognition to prevent irreversible deterioration of renal function. High cumulative exposure to nonsteroidal anti-inflammatory drugs is associated with rapid progression of CKD.³² Acetaminophen is the analgesic of choice for short-term treatment of mild to moderate pain in patients with stage 3 to 5 CKD.³³ Nonsteroidal anti-inflammatory drugs may be used in patients with stage 3 CKD for short-term therapy with regular renal function monitoring.³³

Indications for Nephrology Referral

Nephrology consultation is indicated when the estimated GFR is less than 30 mL per minute per 1.73 m², or earlier if necessary (Table 11).^9,15 Partnership between primary care physicians and nephrologists is key to successful CKD management. The National Kidney Foundation's suggested multidisciplinary clinical action plan for CKD is available at http://www.kidney.org/professionals/KDOQI/cap.cfm.

U.S. Department of Health and Human Services. Annual report targets chronic kidney disease in the United States [news release]. http://www.nih.gov/news/health/oct2008/niddk-08.htm. Accessed April 21, 2011.

Collins AJ, Li S, Gilbertson DT, Liu J, Chen SC, Herzog CA. Chronic kidney disease and cardiovascular disease in the Medicare population. Kidney Int Suppl. 2003;87:S24-31.

Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med. 2004;164(6):659-663.

Abramson JL, Jurkovitz CT, Vaccarino V, Weintraub WS, McClellan W. Chronic kidney disease, anemia, and incident stroke in a middle-aged, community-based population: the ARIC Study. Kidney Int. 2003;64(2):610-615.

Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298(17):2038-2047.

U.S. Renal Data System. USRDS 2009 annual data report. Chapter 2: incidence & prevalence. http://www.usrds.org/2009/slides/flash/vol2_02_incid_prev_09.swf. Accessed October 6, 2010.

Plantinga LC, Boulware LE, Coresh J, et al. Patient awareness of chronic kidney disease: trends and predictors. Arch Intern Med. 2008;168(20):2268-2275.

McClellan WM, Ramirez SP, Jurkovitz C. Screening for chronic kidney disease: unresolved issues. J Am Soc Nephrol. 2003;14(7 suppl 2):S81-S87.

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-S266.

American Diabetes Association. Standard of medical care in diabetes—2011. Diabetes Care. 2011;34(suppl 1):S11-S61.

KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Am J Kidney Dis. 2007;49(2 suppl 2):S12-S154.

Chobanian AV, Bakris GL, Black HR, et al.; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report [published correction appears in JAMA. 2003;290(2):197]. JAMA. 2003;289(19):2560-2572.

Brosius FC, Hostetter TH, Kelepouris E, et al.; American Heart Association Kidney and Cardiovascular Disease Council. Council on High Blood Pressure Research; Council on Cardiovascular Disease in the Young; Council on Epidemiology and Prevention; Quality of Care and Outcomes Research Interdisciplinary Working Group. Detection of chronic kidney disease in patients with or at increased risk of cardiovascular disease. Circulation. 2006;114(10):1083-1087.

Vassalotti JA, Fox CH, Becker BN. Risk factors and screening for chronic kidney disease. Adv Chronic Kidney Dis. 2010;17(3):237-245.

Vassalotti JA, Stevens LA, Levey AS. Testing for chronic kidney disease: a position statement from the National Kidney Foundation. Am J Kidney Dis. 2007;50(2):169-180.

U.S. Renal Data System. ESRD reference tables. http://www.usrds.org/2010/pdf/v2_aa_ref_tables.pdf. Accessed April 21, 2011.

Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.

Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D Modification of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130(6):461-470.

Levey AS, Stevens LA, Schmid CH, et al.; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-612.

National Kidney Foundation. Frequently asked questions about GFR estimates. http://www.kidney.org/professionals/kls/pdf/kba_faqs_aboutgfr.pdf. Accessed September 29, 2010.

Michels WM, Grootendorst DC, Verduijn M, Elliott EG, Dekker FW, Krediet RT. Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol. 2010;5(6):1003-1009.

Jones CA, Francis ME, Eberhardt MS, et al. Microalbuminuria in the US population: third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2002;39(3):445-459.

Viazzi F, Leoncini G, Ratto E, et al. Microalbuminuria, blood pressure load, and systemic vascular permeability in primary hypertension. Am J Hypertens. 2006;19(11):1183-1189.

Molitch ME, DeFronzo RA, Franz MJ, et al.; American Diabetes Association. Nephropathy in diabetes. Diabetes Care. 2004;27(suppl 1):S79-S83.

Naughton CA. Drug-induced nephrotoxicity. Am Fam Physician. 2008;78(6):743-750.

Munar MY, Singh H. Drug dosing adjustments in patients with chronic kidney disease. Am Fam Physician. 2007;75(10):1487-1496.

U.S. Department of Veterans Affairs; U.S. Department of Defense. VA/DoD clinical practice guideline for management of chronic kidney disease in primary care. http://www.healthquality.va.gov/ckd/ckd_v478.pdf. Accessed October 2, 2010.

Levey A. Chronic kidney disease: progression. http://ocw.tufts.edu/data/33/497964.pdf. October 2, 2010.

Levey AS, Perrone RD, Madaio MP. Laboratory assessment of renal disease: clearance, urinalysis and renal biopsy. In: Brenner BM, Rector FR. The Kidney. Philadelphia, Pa.: W.B. Saunders; 1991:919–968.

KDOQI clinical practice guideline and clinical practice recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis. 2007;50(3):471-530.

National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease [published correction appears in Am J Kidney Dis. 2006;48(3):518]. Am J Kidney Dis. 2006;47(5 suppl 3):S11-S145.

Gooch K, Culleton BF, Manns BJ, et al. NSAID use and progression of chronic kidney disease. Am J Med. 2007;120(3):280.e1-280.e7.

De Broe ME, Elseviers MM. Over-the-counter analgesic use. J Am Soc Nephrol. 2009;20(10):2098-2103.