Creatinine–Based and Cystatin C–Based GFR Estimating Equations and Their Non-GFR Determinants in Kidney Transplant Recipients

Abstract

Background and objectives eGFR equations have been evaluated in kidney transplant recipients with variable performance. We assessed the performance of the Modification of Diet in Renal Disease equation and the Chronic Kidney Disease Epidemiology Collaboration equations on the basis of creatinine, cystatin C, and both (eGFR creatinine-cystatin C) compared with measured GFR by iothalamate clearance and evaluated their non-GFR determinants and associations across 15 cardiovascular risk factors.Design, setting, participants, & measurements A cross-sectional cohort of 1139 kidney transplant recipients .1 year after transplant was analyzed. eGFR bias, precision, and accuracy (percentage of estimates within 30% of measured GFR) were assessed. Interaction of each cardiovascular risk factor with eGFR relative to measured GFR was determined.Results Median measured GFR was 55.0 ml/min per 1.73 m 2 . eGFR creatinine overestimated measured GFR by 3.1% (percentage of estimates within 30% of measured GFR of 80.4%), and eGFR Modification of Diet in Renal Disease underestimated measured GFR by 2.2% (percentage of estimates within 30% of measured GFR of 80.4%). eGFR cystatin C underestimated measured GFR by 213.7% (percentage of estimates within 30% of measured GFR of 77.1%), and eGFR creatinine-cystatin C underestimated measured GFR by 28.1% (percentage of estimates within 30% of measured GFR of 86.5%). Lower measured GFR associated with older age, women, obesity, longer time after transplant, lower HDL, lower hemoglobin, lower albumin, higher triglycerides, higher proteinuria, and an elevated cardiac troponin T level but did not associate with diabetes, smoking, cardiovascular events, pretransplant dialysis, or hemoglobin A1c. These risk factor associations differed for five risk factors with eGFR creatinine, six risk factors for eGFR Modification of Diet in Renal Disease, ten risk factors for eGFR cystatin C, and four risk factors for eGFR creatinine-cystatin C.Conclusions Thus, eGFR creatinine and eGFR creatinine-cystatin C are preferred over eGFR cystatin C in kidney transplant recipients because they are less biased, more accurate, and more consistently reflect the same risk factor associations seen with measured GFR.

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly: AGES-Kidney and MESA-Kidney

“…All three LMW serum proteins have multiple biological functions and prior studies have suggested associations with CVD and CVD risk factors, including obesity, smoking, diabetes, inflammation, dyslipidemia and proteinuria independent of mGFR, although the mechanisms for these associations are not understood. 1, 10, 20–22 Cystatin C is a 120 amino acid protein cysteine protease inhibitor, which is generated in all nucleated cells, modulates the immune system, has antibacterial and antiviral activities, and modifies the response to brain injury. 23 B2M is a 100 amino acid protein component of class I major histocompatibility molecules, which is found on the surface of nucleated cells, and is used clinically as a marker for tumor burden in some lymphoproliferative and plasma cell disorders.…”

Belatacept Compared With Tacrolimus for Kidney Transplantation

“…Likewise we explored the serum creatinine data reported in the follow-up file; 74% of tacrolimus patients and 71% of belatacept patients had serum creatinine reported at 1 year posttransplant. 1 year posttransplant estimated glomerular filtration rate (eGFR; calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (23)) was slightly lower among tacrolimus patients compared to belatacept patients (tacrolimus median eGFR 58.5 mL/min/1.73m 2 , IQR 45.9-72.9 versus belatacept median eGFR 62.3 mL/min/1.73m2, IQR 49.1-76.2, ranksum p-value <0.001).…”

Chronic kidney disease and the risk of incident hearing loss

“…Estimation of GFR from CysC alone has been demonstrated to be no more accurate than SCr‐based estimates. In a study of renal transplant patients, the eGFR CysC equation was inferior to the performance of eGFR Cr when compared to the gold standard of measured GFR, with more bias and less accuracy . Stevens et al found that after adjusting for measured GFR, CysC was 4.3% lower for every 20 years of age and 9.2% lower for female sex .…”

“…Several studies have demonstrated that CysC levels are affected by factors other than GFR, suggesting that unmeasured non‐GFR determinants may be similar in magnitude for both CysC and SCr . For instance, CysC is associated with older age, hemoglobin A1c, smoking, past cardiovascular events, uric acid levels, and hypertriglyceridemia . Inflammation is also thought to modulate CysC levels .…”