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Donna Myers, M.D.
02-03-2011
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Serum creatinine: useful and convenient measure to monitor renal status. Serum creatinine in the normal range may not reflect normal glomerular filtration rate (GFR). Age, gender and muscle mass need to be considered.
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GFR: simplest measure of renal function; 24 hour urine collection not required. Elevated GFR indicates hyperfiltration, an early predictor of subsequent diabetic renal disease. GFR then declines as renal disease progresses. The four variable MDRD equation calculates GFR based on serum creatinine, age, race and gender. The six variable expanded MDRD equation also includes blood urea nitrogen (BUN) and serum albumin. The Cockcroft-Gault equation calculates GFR based on serum creatinine, weight, gender and age. It is of limited value in patients with obesity in whom weight may not reflect muscle mass.
- The reciprocal serum creatinine curve useful but cumbersome, plotting change in creatinine over time. Sudden acceleration of the slope of deterioration suggests a potentially reversible component such as volume depletion resulting in acute on chronic kidney injury. Similarly, a successful intervention such as blood pressure or glycemic control may flatten the curve over time.
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BUN: varies inversely with GFR, but can be affected by factors other than GFR (see "Limitations").
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Microalbuminuria: earliest evidence of diabetic nephropathy, especially in type I diabetes, and should be monitored routinely in diabetes
- The spot urine albumin/creatinine ratio to assess microalbuminuria preferred for monitoring the impact of therapeutic interventions such as renin-angiotensin blockade on proteinuria. Twenty-four hour urine protein collections rarely required.
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Microscopic urinalysis: a bland sediment may be seen with either pre-renal or post-renal failure. Glomerulonephritis: documented proteinuria and hematuria with dysmorphic rbc's, rbc casts, granular casts and lipiduria. Nephrosis: proteinuria and lipiduria with a bland sediment. Infection: dipstick positive leukocyte esterase and nitrites and confirmed by the microscopic finding of pyuria, hematuria and bacteriuria with or without wbc casts and a positive urine culture. Acute interstital nephritis: wbcs and wbc casts without infection; finding eosinophiluria confirms suspicion of an allergic reaction. Acute tubular necrosis: muddy brown granular casts.
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Radiographic examinations: include renal and bladder ultrasound to detect anatomic changes; functional nuclear medicine scans for split function, GFR and obstruction; and CT angiography, renal MRA or Doppler flow studies for renal artery stenosis. (see Limitations)
- Serum creatinine and BUN: serum creatinine measured by the alkaline picrate method, a colorimetric assay. Values more reproducible at the lower end of the scale.
- GFR (ml/min/1.73m2): most laboratories will report an estimated GFR on the basis of the measured serum creatinine, gender, race and age.
- Urine albumin and creatinine (to assess microalbuminuria): see Module on Albuminuria.
- Preventive annual screening for microalbuminuria starting at diagnosis in type 1 diabetes and beginning five years after diagnosis in type 2 diabetes (ADA Standards of Medical Care)
- Measure serum creatinine at least annually in all adults with diabetes, regardless of the degree of urine albumin excretion, to stage CKD using GFR (ADA Standards of Medical Care)
- Signs or symptoms of renal failure including: frothy urine, edema, uncontrolled hypertension, congestive heart failure, uremia
- Presence of electrolyte abnormalities often associated with chronic renal insufficiency (e.g. hyperkalemia, hyponatremia, hypocalcemia, hyperphosphatemia, metabolic acidosis) or anemia
- Medications with potential nephrotoxic effects (i.e. metformin) or predominantly renal clearance (i.e. insulin, sulfonylureas)
- Elevated creatinine: pre-renal, renal or post-renal failure; drug reaction (see below).
- Elevated BUN: pre-renal, renal or post-renal failure; non-renal factors (see below).
- Reduced GFR: pre-renal, renal or post-renal failure; 24 hr urine collection error.
- Elevated urinary albumin: micro- or macroalbuminuria from intrinsic glomerular disease; renal vein thrombosis; congestive heart failure; febrile states; benign postural proteinuria.
- A doubling of the serum creatinine results in halving of the GFR. A serum creatinine of 0.6 mg/dL at baseline and 1.2 mg/dL at follow-up may reflect advanced kidney disease although the creatinine level remains in the "normal" laboratory range.
- The curve of creatinine and GFR is non-linear. At the lower end a small rise in creatinine reflects a large change in GFR; at the upper end a small change in creatinine is of less significance. Plotting the reciprocal creatinine obviates these difficulties. An awareness of the fact that every doubling of creatinine indicates a 50% reduction in GFR is helpful; a rise in serum creatinine from 0.6 to 1.2 mg/dL is similar in magnitude to a rise from 4.0 to 8.0 mg/dL change.
- Chronic kidney disease is classified by GFR and urinary albumin: Stage 1: proteinuria, GFR > 90ml/min; Stage 2: proteinuria, GFR = 60-89ml/min; Stage 3: GFR = 30-59ml/min; Stage 4: GFR = 15-29ml/min; Stage 5: GFR < 15ml/min.
- The reciprocal creatinine over time plot may predict when the patient reaches stage 5 CKD but the actual initiation of maintenance dialysis depends on the patient's comorbidities and symptoms.
- Spot urine albumin:creatinine ratio of 30 - 300 mg/gram creatinine indicates microalbuminuria; >300mg/gram creatinine indicates macroalbuminuria
- The alkaline picrate assay for serum creatinine may be affected by creatinine chromogens such as acetoacetate in diabetic ketoacidosis, spuriously elevating the serum creatinine by up to 2.0 mg/dL.
- The serum creatinine may fluctuate as a function of pre-renal factors such as volume status, cardiac performance and serum oncotic pressure. Increasing muscle mass from exercise or decreasing muscle mass from wasting or amputation may affect the serum creatinine irrespective of a change in GFR.
- Enhanced creatinine production may occur with a large meat meal or with enhanced muscle breakdown (rhabdomyolysis) with release of creatine.
- Wasting disorders with severe malnutrition (cirrhosis, cancer, bulimia, low protein intake) may present with low serum creatinine (poor muscle mass) and low BUN even in the setting of acute kidney injury such as the hepatorenal syndrome.
- Drugs that block proximal tubular secretion of creatinine, resulting in a spurious elevation of the serum creatinine without a fall in GFR, include trimethoprim and cimetidine.
- The blood urea nitrogen may be elevated during dehydration (pre-renal azotemia), with increased protein in the diet (certain fad diets) or gut (g.i.bleeding), during increased catabolism from sepsis or steroids. Pre-renal azotemia is characterized by a BUN:creatinine ratio > 20:1.
- Urine microalbumin should be verified on two separate collections and is affected by: exercise, hypermetabolic states including fever and congestive heart failure.
- The MDRD formula for GFR was developed in a population of chronic kidney disease patients and is not useful when the GFR is > 60 ml/min (uniformly reported as "> 60 ml/min" rather than a specific number).
- CT contrast should be avoided once the serum creatinine is elevated above 1.8 mg/dL, especially in patients with diabetes and proteinuria or heart disease. If contrast needed, consider using N-acetylcysteine beforehand. Gadolinium to enhance MRI examination of renal arteries is contraindicated with GFR < 60 ml/min because of the associated risk of nephrogenic systemic fibrosis. Doppler evaluation of renal blood flow is limited by body habitus (obesity) and technician expertise.
- Earliest clinical evidence of diabetic nephropathy is microalbuminuria (30-300 mg/day), typically 10 years after disease. Without tight glycemic control and renin angiotensin system blockade by ACE-I and ARB therapy, can evolve into macroalbuminuria (> 300 mg/day) within several years, followed by a fall in GFR, hypertension and progressive renal failure within 3-5 years. (See module on Albuminuria)
- Only 25% of diabetic patients develop classic diabetic nephropathy (diabetic glomerulosclerosis or "Kimmelstiel Wilson Disease"). After 20 years, unlikely to occur . Long-term survivors of diabetes may go on to develop arteriosclerotic renal disease (nephrosclerosis), typically non-proteinuric and often very slowly progressive.
- Renovascular disease (RAS) commonly present with diabetic nephropathy, and should be suspected in persons with history of peripheral vascular disease with or without vascular bruits, asymmetric kidneys, a sudden rise in the serum creatinine after initiating ACE-I or ARB therapy, or flash pulmonary edema (bilateral RAS).
- Day-to-day minor fluctuations in serum creatinine reflect volume changes and hydration status.
- Physicians should avoid over-zealous use of diuretics, particularly in conjunction with RAAS blockade.
- The fractional excretion of sodium (FENa) or urea (FEurea) may be helpful in distinguishing acute kidney injury from volume depletion, but not important in the evaluation of stable renal function.
- Dipstick evaluation of the urine does not provide information on renal function but provides indirect evidence of infection (positive leukocyte esterase and nitrites), nephritis and nephrosis.
- Serum electrolytes directly associated with renal function include hyponatremia, hyperkalemia and metabolic acidosis and may reflect CKD. Hyperkalemia in a diabetic patient with early CKD raises suspicion of hyporenin-hypoaldosteronism (type IV RTA).
- At each clinical visit the patient should be assessed for orthostatic hypotension.
- Renal consult should be considered for CKD Stage 3.
- Levey AS, Schoolwerth AC, Burrows NR, et al.;
Comprehensive public health strategies for preventing the development, progression, and complications of CKD: report of an expert panel convened by the Centers for Disease Control and Prevention.;
Am J Kidney Dis;
2009; Vol.
53; pp.
522-35;
ISSN:
1523-6838;
PUBMED: 19231739
Rating:
Basis for recommendation
Comments:Physician awareness of the patient's GFR is recommended for timely referral and appropriate management of CKD.
- High WA, Ayers RA, Chandler J, et al.;
Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis.;
J Am Acad Dermatol;
2007; Vol.
56; pp.
21-6;
ISSN:
1097-6787;
PUBMED: 17097388
Rating:
Basis for recommendation
Comments:The toxicity of gadolinium in patients with kidney disease was suspected when gadolinium was detected in tissue of a number of patients with Nephrogenic Systemic Fibrosis (NSF). This association has been confirmed and new guidelines established for the use of this agent.
- Schwab SJ, Christensen RL, Dougherty K, et al.;
Quantitation of proteinuria by the use of protein-to-creatinine ratios in single urine samples.;
Arch Intern Med;
1987; Vol.
147; pp.
943-4;
ISSN:
0003-9926;
PUBMED: 3555378
Rating:
Basis for recommendation
Comments:This article describes the utility of single voided urine samples to measure protein-to-creatinine ratios, an observation that obviated the need, in most instances, of a 24 hr urine collection.
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