Determining Glomerular Filtration Rate in Homozygous Sickle Cell Disease: Utility of Serum Creatinine Based Estimating Equations

Abstract

BackgroundVarious estimating equations have been developed to estimate glomerular filtration rate (GFR) for use in clinical practice. However, the unique renal physiological and pathological processes that occur in sickle cell disease (SCD) may invalidate these estimates in this patient population. This study aims to compare GFR estimated using common existing GFR predictive equations to actual measured GFR in persons with homozygous SCD. If the existing equations perform poorly, we propose to develop a new estimating equation for use in persons with SCD.Methods98 patients with the homozygous SS disease (55 females: 43 males; mean age 34±2.3 years) had serum measurements of creatinine, as well as had GFR measured using 99mTc-DTPA nuclear renal scan. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and the serum creatinine based CKD-EPI equations. The Bland-Altman limit of agreement method was used to determine agreement between measured and estimated GFR values. A SCD-specific estimating equation for GFR (JSCCS-GFR equation) was generated by means of multiple regression via backward elimination.ResultsThe mean measured GFR±SD was 94.9±27.4 mls/min/1.73 m2 BSA, with a range of 6.4–159.0 mls/min/1.73 m2. The MDRD and CG equations both overestimated GFR, with the agreement worsening with higher GFR values. The serum creatinine based CKD-EPI equation performed relatively well, but with a systematic bias of about 45 mls/min. The new equation developed resulted in a better fit to our sickle cell disease data than the MDRD equation.ConclusionCurrent estimating equations, other than the CKD-EPI equation, do not perform very accurately in persons with homozygous SS disease. A fairly accurate estimating equation, suitable for persons with GFR >60 mls/min/1.73 m2 has been developed from our dataset and validated within a simulated dataset.

Cystatin C: A useful marker of glomerulopathy in sickle cell disease?

“…We have shown in the past that the serum creatinine based CKD-EPI equation performed better than the other commonly used equations to estimate GFR in clinical practice [19] yet from this study, the Cys-C based CKD-EPI equation is seen to have a better estimate than the latter. Whereas, the combined (serum creatinine + Cys-C based) equations are thought to be the best overall estimator [34] of GFR in persons with CKD, we have found the best to be the Cys-C based equation.…”

“…Various estimating equations, most notably the Modification of Diet in Renal Disease (MDRD) equation and more recently the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, have been recommended for use in adults [15][16][17]. In persons with SCD however, both these equations have been found to be inaccurate, possibly due to various pathophysiological mechanisms unique to SCD [18,19].…”

The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease to sickle trait

“…Creatinine levels in individuals with SCD have been noted to be lower than controls, suggesting that estimates of creatinine clearance may underestimate renal dysfunction in SCD. In fact, creatinine-based estimation equations for GFR all appear to overestimate kidney function when compared to radionucleotide measures of GFR [32]. Because of this phenomenon, cystatin C has been suggested as a more accurate marker of CKD in both children and adults with SCD with GFR greater than 30 mL/min/1.73 m 2 [27,33].…”

Increased vancomycin dosing requirements in sickle cell disease due to hyperfiltration-dependent and independent pathways

“…11 In the pathway analysis, we found evidence that SCD contributed to lower vancomycin trough levels via both hyperfiltration-dependent and -independent mechanisms. The fitness of the pathway model was best when a hyperfiltration threshold was used instead of CrCl as a linear variable, consistent with hyperfiltration as one mechanism for increased drug clearance.…”