Estimating Glomerular Filtration Rate in Kidney Transplantation

Abstract

Accurate measurement of GFR is critical for the evaluation of new therapies and the care of renal transplant recipients. Although not accurate in renal transplantation, GFR is often estimated using creatinine-based equations. Cystatin C is a marker of GFR that seems to be more accurate than creatinine. Equations to predict GFR based on the serum cystatin C concentration have been developed, but their accuracy in transplantation is unknown. GFR was estimated using four equations (Filler, Le Bricon, Larsson, and Hoek) that are based on serum cystatin C and seven equations that are based on serum creatinine in 117 adult renal transplant recipients. GFR was measured using radiolabeled diethylenetriaminepentaacetic acid ( 99m Tc-DTPA), and the bias, precision, and accuracy of each equation were determined. The mean 99m Tc-DTPA GFR was 58 ؎ 23 ml/min per 1.73 m 2 . The cystatin C-based equations of Filler and Le Bricon had the lowest bias (؊1.7 and ؊3.8 ml/min per 1.73 m 2 ), greatest precision (11.4 and 11.8 ml/min per 1.73 m 2 ), and highest accuracy (87 and 89% within 30% of measured GFR, respectively). The cystatin C equations remained accurate even when the measured GFR was >60 ml/min per 1.73 m 2 . The creatinine-based equations were not as accurate, with only 53 to 80% of estimates within 30% of measured GFR. Cystatin C-based equations are more accurate at predicting GFR in renal transplant recipients than traditional creatininebased equations. Further prospective studies with repetitive measurement of cystatin C are needed to determine whether cystatin C-based estimates of GFR will be sufficiently accurate to monitor long-term allograft function.

Diagnostic Accuracy of Cystatin C–Based eGFR Equations at Different GFR Levels in Children

“…This observation becomes clinically relevant as it can provide insight into the clinical applicability of the equations at different GFR levels. It can also explain the variability in the performance of various equations in different studies (3,11,26).…”

Cystatin C Levels in Functionally Anephric Patients Undergoing Dialysis

“…Hoek et al (17) found similarly that cystatin C gave a good estimate of residual GFR in cohorts of both HD and PD patients. Filler and colleagues have shown in both children and adults with chronic kidney disease that an estimated GFR (eGFR) can be derived from the following formula: eGFR ϭ 10 exp (1.962 ϩ [1.23 ϫ log (1/cystatin C)] (6,18). Therefore, a knowledge of the Std Kt/V and the cystatin C level in a dialyzed patient with residual renal function might theoretically allow a knowledge of both dialytic and residual renal clearance: the Std Kt/V providing an "expected" cystatin C; a lower value indicating a finite eGFR.…”

Cystatin C: current position and future prospects

“…These equations also appear to offer limited precision (52,110,113,116,124,129,130). As we shall see below, they could be more useful in certain subpopulations in which creatinine-based equations are particularly inaccurate, as in paediatrics (116,117,124), transplantation (113,115,(131)(132)(133) or oncology (134). Validation studies on large independent populations, however, would appear to be needed.…”

“…Overall, equations using CysC appear to offer better predictive performance, although it remains to be shown that this improvement in prediction is clinically significant (52, 131, 133, 157, 158). They provide a more accurate estimate of GFR than the MDRD equation (133) and improve classification of renal transplant patients into the different stages of chronic renal disease (158). It should be noted, however, that in a recently published study, the superiority of GFR estimation based on CysC compared to serum creatinine was not confirmed in renal transplantation (130).…”