Clinical Usefulness of Cystatin C for the Estimation of Glomerular Filtration Rate in Type 1 Diabetes

Abstract

1OBJECTIVE -Assessment and follow-up of early renal dysfunction is important in diabetic nephropathy. Plasma creatinine is insensitive for a glomerular filtration rate (GFR) Ͼ50 ml/min and creatinine clearance is unwieldy and subject to collection inaccuracies. We aimed to assess the reproducibility, reliability, and accuracy of plasma cystatin C as a measure of GFR ranging from normal to moderate impairment due to type 1 diabetes in the presence of a normal plasma creatinine concentration. RESEARCH DESIGN AND METHODS-A sensitive immunoturbidimetric cystatin C assay was examined in 29 subjects with type 1 diabetes and 11 nondiabetic subjects. Duplicate measurements of the following were collected from each subject, 2 weeks apart: cystatin C, enzymatic plasma creatinine, 24-h creatinine clearance, GFR estimated from plasma creatinine by the Cockcroft-Gault equation, and iohexol clearance as a gold standard.RESULTS -Iohexol clearance ranged from 35 to 132 ml ⅐ min -1 ⅐ 1.73 m -2 . Plasma cystatin C compared well with the other clinically used tests. The reliability of cystatin C, as assessed by the discriminant ratio, was superior to creatinine clearance (3.4 vs. 1.5, P Ͻ 0.001) and the correlation of cystatin C with iohexol clearance (Rs -0.80) was similar to that of creatinine clearance (Rs -0.74) and superior to that of plasma creatinine and the Cockcroft-Gault estimate (Rs Ϫ0.54 and 0.66, respectively). Duplicate estimations were used to provide an unbiased equation to convert plasma cystatin C to GFR.CONCLUSIONS -Based on this study, cystatin C is a more reliable measure of GFR than creatinine clearance, is more highly correlated with iohexol clearance than plasma creatinine, and is worthy of further investigation as a clinical measure of GFR in type 1 diabetes. Diabetes Care 25:2004 -2009, 2002R enal failure develops in Յ30% of people with type 1 diabetes; however, our ability to assess renal function is poor in early diabetic nephropathy, when active management is important. Serum creatinine level, the most commonly used surrogate measure of glomerular filtration rate (GFR), does not increase until renal function decreases to ϳ50% of its normal value; its excretion rate varies with age, sex, physical exercise, and lean body mass (1,2). The population variance of serum creatinine level is large, making it a poor measure for comparison with a reference range. Creatinine clearance, measured from a 24-h urine collection and a concurrent plasma creatinine concentration, is unwieldy and often inaccurate but is widely used in clinical practice (3). 'Gold standard' tests such as clearance methods using radioisotopes (such as 51 Cr-labeled EDTA, 99m Tcl a b e l e d D T P A , a n d 1 2 5 I -l a b e l e d iothalamate) or iohexol (4,5) are too cumbersome to use in the clinic setting (3). A more precise and accurate marker of GFR as an assessment of renal function would be clinically useful.Cystatin C has been proposed as a good marker of GFR (6,7), particularly in patients with moderate to severe renal impairment. It i...

Measured GFR as a Confirmatory Test for Estimated GFR

“…38 Studies comparing urinary and plasma clearance of either iothalamate or iohexol show high agreement, although some studies showed that plasma clearance slightly overestimates urinary clearance at lower levels of GFR (Table 5). 17,34 In studies of repeated measurements of plasma clearance of iothalamate or iohexol, the coefficient of variation ranged from 5.6 to 11.5%, 37,39,42,43 similar to the variation observed with urinary clearance reported above. More studies are necessary to determine the precision of these methods.…”

Monitoring renal function: measured and estimated glomerular filtration rates - a review

“…The error induced by this phenomenon is particularly relevant at low levels of GFR. No difference was found between the plasma clearance of 51 Cr-EDTA and of 99m Tc-DTPA (4,5).…”

“…Several compounds labeled with radioisotopes have been used for the assessment of GFR. Among these are 125 I-iothalamate, 99m Tc-diethylenethiaminepenta-acetic acid ( 99m Tc-DTPA) and 51 Cr-ethylenediaminetetra-acetic acid ( 51 Cr-EDTA). All these compounds have a low molecular weight and their plasma protein binding and extrarenal elimination are negligible.…”

“…These data suggest that extrarenal elimination of 99m Tc-DTPA occurs, thus limiting its use as a marker of glomerular filtration. 51 Cr-EDTA is a chelate of 51 Cr and EDTA. Plasma clearance of 51 Cr-EDTA measured after intravenous bolus injection of the compound exceeds its urinary clearance by an average of 6 mL/min.…”

“…51 Cr-EDTA is a chelate of 51 Cr and EDTA. Plasma clearance of 51 Cr-EDTA measured after intravenous bolus injection of the compound exceeds its urinary clearance by an average of 6 mL/min. This may be the result of extrarenal elimination of the substance.…”