Creatinine with Estimated GFR (MDRD), Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
In muscle metabolism, creatinine is synthesized endogenously from creatine and creatine phosphate. Creatinine is removed from plasma by glomerular filtration into the urine without being reabsorbed by the tubules to any significant extent. Renal tubular secretion also contributes a small quantity of creatinine to the urine. As a result, creatinine clearance often overestimates the true glomerular filtration rate (GFR) by 10% to >20%.
Determinations of creatinine and renal clearance of creatinine are of value in the assessment of kidney function. Serum or blood creatinine levels in renal disease generally do not increase until renal function is substantially impaired.
Estimated GFR (eGFR):
Use of an estimating or prediction equation to estimate GFR from serum creatinine should be employed for people with chronic kidney disease (CKD) and those with risk factors for CKD (diabetes, hypertension, cardiovascular disease, and family history of kidney disease).
Studies have shown that GFR can be reliably estimated from serum creatinine in adults by utilizing the Modification of Diet in Renal Disease (MDRD) Study equation, which includes the patient's age, sex, and race.(1,2) In Caucasian and African American populations between the ages of 18 and 70 with impaired kidney function (eGFR <60 mL/min/1.73 m), the MDRD equation has been validated at length and is considered the best available means to estimate GFR from creatinine.(3) Estimation of GFR using the MDRD equation has demonstrated good correlation with measured iothalamate clearance in patients with all common causes of kidney disease, including kidney transplant recipients.(4) However, MDRD eGFR significantly underestimates true GFR in patients with normal renal function (EGFR >60 mL/min/1.73 m). Some advantages of the estimated GFR calculation are listed in the following paragraphs:
-GFR and creatinine clearance are poorly inferred from serum creatinine alone. GFR and creatinine clearance are inversely and nonlinearly related to serum creatinine. The effects of age, sex, and, to a lesser extent, race, on creatinine production further cloud interpretation.
-Creatinine is commonly measured in routine clinical practice. Microalbuminuria may be a more sensitive marker of early renal disease, especially among patients with diabetic nephropathy. However, there is poor adherence to guidelines that suggest annual urinary albumin testing of patients with known diabetes. Therefore, if a depressed eGFR is calculated from a serum creatinine measurement, it may help providers recognize early CKD and pursue appropriate follow-up testing and therapeutic intervention.
-Monitoring of kidney function (by GFR or creatinine clearance) is essential once albuminuria is discovered. Estimated GFR is a more practical means to closely follow changes in GFR over time, when compared to direct measurement using methods such as iothalamate clearance.
-The MDRD equation is the most thoroughly validated of the estimating equations. It has been extensively validated in patients with CKD and is currently being evaluated for other populations such as people with normal GFR, people with diabetes, and Hispanics. New equations, or modifications of the MDRD equation, may be necessary in these groups.
-The MDRD equation is superior to other methods of estimating GFR. The MDRD equation correlates better with measured GFR than other equations, including the Cockcroft-Gault equation. The MDRD equation is also superior to a 24-hour creatinine clearance measurement. Measured iothalamate clearance remains the gold standard for measuring GFR.
-Nephrology specialists already routinely use estimating equations. It has long been appreciated among nephrologists that serum creatinine alone is an insensitive index of GFR. Therefore, renal specialists have employed estimating equations to convert serum creatinine to an approximate GFR. Reporting eGFR values with serum creatinine results allows primary care providers and specialists in other fields to better interpret their results.
-The MDRD equation does not require weight or height variables. From a serum creatinine measurement, it generates a GFR result normalized to a standard body surface area (1.73 m) using sex, age, and race. Unlike the Cockcroft-Gault equation, height and weight, which are often not available in the laboratory information system, are not required. The MDRD equation does require race (African American or non-African American), which also may not be readily available. For this reason, eGFR values for both African Americans and non-African Americans are reported. The difference between the 2 estimates is typically about 20%. The patient or provider can decide which result is appropriate for a given patient.
-Diagnosing and monitoring treatment of acute and chronic renal diseases
-Adjusting dosage of renally excreted medications
-Monitoring renal transplant recipients
Estimated Glomerular Filtration Rate (eGFR):
Serum creatinine measurement is used in estimating GFR for people with chronic kidney disease (CKD) and those with risk factors for CKD (diabetes, hypertension, cardiovascular disease, and family history of kidney disease).
Because serum creatinine is inversely correlated with glomerular filtration rate (GFR), when renal function is near normal, absolute changes in serum creatinine reflect larger changes than do similar absolute changes when renal function is poor. For example, an increase in serum creatinine from 1 mg/dL to 2 mg/dL may indicate a decrease in GFR of 50 mL/min (from 100 mL/min to 50 mL/min), whereas an increase in serum creatinine level from 4 mg/dL to 5 mg/dL may indicate a decrease of only 5 mL/min (from 25 mL/min to 20 mL/min).
Because of the imprecision of serum creatinine as an assessment of GFR, there may be clinical situations where a more accurate GFR assessment must be performed, iothalamate or inulin clearance are superior to serum creatinine.
Several factors may influence serum creatinine independent of changes in GFR. For instance, creatinine generation is dependent upon muscle mass. Thus, young, muscular males may have significantly higher serum creatinine levels than elderly females, despite having similar GFRs. Also, because some renal clearance of creatinine is due to tubular secretion, drugs that inhibit this secretory component (eg, cimetidine and trimethoprim) may cause small increases in serum creatinine without an actual decrease in GFR.
Chronic kidney disease (CKD) is defined as the presence of: persistent and usually progressive reduction in GFR (GFR <60 mL/min/1.73 m) and/or albuminuria (>30 mg of urinary albumin per gram of urinary creatinine), regardless of GFR.
According to the National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) classification, among patients with CKD, irrespective of diagnosis, the stage of disease should be assigned based on the level of kidney function:
GFR mL/min/1.73 m(2)
Kidney damage with normal or increased GFR
Kidney damage with mild decrease in GFR
60 to 89
Moderate decrease in GFR
30 to 59
Severe decrease in GFR
15 to 29
<15 (or dialysis)
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The following interferences have been reported:
-Calcium dobesilate (Dexium) at levels of > or =5 mg/dL may cause falsely low results
-N-ethylglycine at therapeutic concentrations and DL-proline at concentrations > or =1 mmol/L may give falsely high results
-Dobutamine can lead to falsely low results
-Hemolyzed specimens from patients with hemoglobin F (Hbg F) values > or =600 mg/dL interfere with the test. For patients with normal Hgb, no interference is expected for Hgb levels <1,000 mg/dL
-Total bilirubin >25 mg/dL interferes with this assay
-Ascorbic acid >300 mg/L interferes with this assay
-In patients receiving catecholamines (dopamine, dobutamine, epinephrine, and norepinephrine) falsely low results might be observed(7)
-Calcium dobesilate (eg, Dexium), Levodopa and α-methyldopa cause artificially low creatinine results
The following do not interfere with this assay:
The National Kidney Disease Education Program (NKDEP) does not endorse the use of the MDRD equation for estimating glomerular filtration rate (GFR) in patients that meet any of the following criteria:
-Are not between the ages of 18 and 70
-Have serious comorbid conditions
-Have extremes of body size
-Have extremes of muscle mass
-Have extremes of nutritional status
-Are non-Caucasian or non-African American
-Have normal kidney function
Although use of the MDRD equation to estimate GFR with such patients is not endorsed by the NKDEP, validation studies are underway for use in additional ethnic groups, those older than 70 years, those with various comorbidities, and those with normal kidney function.
The MDRD equation was developed in a population of patients with known CKD, and is known to underestimate GFR in patients without CKD. Application of the equation to inappropriate patient groups may lead to errors in GFR estimation.(5) GFR estimating equations also have poorer agreement with measured GFR for ill hospitalized patients.(6) Whenever a very accurate assessment of GFR is needed, a direct measure of GFR should be considered. Appropriate methods include an iothalamate clearance (short renal clearance) or a carefully collected creatinine clearance.
The estimated GFR (eGFR) equation is not accurate for GFRs >60 mL/min/1.73 m(2); therefore, values above this are not reported as an exact value, but rather as ">60 mL/min/1.73 m(2)."
eGFR is not a precise measure of GFR and is less precise in the upper end of GFRs as compared to lower GFRs.
Our current laboratory information system cannot readily obtain ethnic patient data; therefore, the report includes an eGFR for both African Americans and non-African Americans.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
1-2 years: 0.1-0.4 mg/dL
3-4 years: 0.1-0.5 mg/dL
5-9 years: 0.2-0.6 mg/dL
10-11 years: 0.3-0.7 mg/dL
12-13 years: 0.4-0.8 mg/dL
14-15 years: 0.5-0.9 mg/dL
> or =16 years: 0.8-1.3 mg/dL
Reference values have not been established for patients that are <12 months of age.
1-3 years: 0.1-0.4 mg/dL
4-5 years: 0.2-0.5 mg/dL
6-8 years: 0.3-0.6 mg/dL
9-15 years: 0.4-0.7 mg/dL
> or =16 years: 0.6-1.1 mg/dL
Reference values have not been established for patients that are <12 months of age.
Note: eGFR results will not be calculated for patients <18 or >70 years old.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Levey AS, Coresh J, Balk E, et al: National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003;139:137-147
2. Manjunath G, Sarnak MJ, Levey AS: Prediction equations to estimate glomerular filtration rate: an update. Curr Opin Nephrol Hypertens 2001;10:785-792
3. National Kidney Disease Education Program: Suggestions for Laboratories. Revised February 2007. Available from http://http://nkdep.nih.gov/resources/laboratory_reporting.htm
4. Poggio ED, Wang X, Greene T, et al: Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol 2005:16:459-466
5. Myers GL, Miller WG, Coresh J, et al: Recommendations for improving serum creatinine measurement: a report from the laboratory working group of the National Kidney Disease Education Program. Clin Chem 2006;52:5-18
6. Poggio ED, Nef PC, Wang X, et al: Performance of the Cockcroft-Gault and modification of diet in renal disease equations in estimating GFR in ill hospitalized patients. Am J Kidney Dis 2005;46:242-252
7. Saenger AK, Lockwood C, Snozek CL, et al: Catecholamine interference in enzymatic creatinine assays. Clin Chem 2009;55(9):1732-1736