Cystatin C-estimated Glomerular Filtration Rate in Pediatric Autologous Hematopoietic Stem Cell Transplantation

Abstract

Formal evaluation of kidney function is essential to determine chemotherapy dosing based on established treatment protocols in children undergoing autologous stem cell transplantation. Cystatin C has been widely studied as a marker of the glomerular filtration rate (GFR), although data regarding its use in stem cell transplantation are limited. We evaluated the performance of cystatin C-based equations and determined their sensitivity to detect a nuclear GFR of \100 mL/min/1.73 m 2 in children undergoing autologous transplantation. We performed a retrospective cohort analysis in 16 children undergoing 26 transplantations using a modified Bland-Altman analysis to account for repeated measures. Cystatin C-based equations published by Hoek, Le Bricon, Rule, Filler, Zappitelli, Larsson, and Schwartz (the New Chronic Kidney Disease in Children formula, New CKiD formula) were evaluated and compared to the creatinine-based modified Schwartz equation. We found that cystatin C-based equations demonstrated improved sensitivity to detect a nuclear GFR of \100 mL/min/1.73 m 2 compared to the creatinine-based modified Schwartz equation, which significantly overestimated GFR. Most cystatin C-based equations, however, tended to underestimate the nuclear GFR. The New CKiD formula, combining cystatin C and creatinine, offered a sensitivity of 100% and a specificity of 95% for detecting a nuclear GFR \100 mL/min/1.73 m 2. Institutions using cystatin C-based GFR estimation should be aware of the specific prediction formula and GFR measurement techniques available at their center, as each method's performance can vary considerably. As more research becomes available, this easily measured marker should become a valuable component of GFR estimation, providing cost savings (a nuclear GFR is 5.5 times more costly than a cystatin C) and reducing radiation exposure.

Estimated versus Measured Glomerular Filtration Rate in Children before Hematopoietic Cell Transplantation

“…Of these 100 subjects, 95 had a nuclear GFR performed for clinical indications prior to transplant. Two autologous recipients have been reported in our prior study [6]. Clinical data were recorded from the medical record and included age, gender, primary diagnosis, race, height, weight, exposure to prior chemotherapy, number of prior HCT (if any), corticosteroid therapy prior to transplant, and creatinine and blood urea nitrogen values.…”

“…For subjects with a >3 day lag between the measured and the creatinine and/or cystatin C-estimated GFRs, we only included subjects who were not admitted to the hospital and had not received nephrotoxic antibiotics between testing. In addition, for analyses incorporating cystatin C, we excluded subjects with cystatin C testing performed after the start of conditioning and also those with unstable kidney function (defined as an intra-subject creatinine standard deviation of ≥0.1, as reported previously [6]) between cystatin C and nuclear GFR testing. The research was approved by the Institutional Review Board at CCHMC.…”

“…The procedure was performed and clearance was calculated as previously described [6, 14]. In brief, after a single injection of DTPA, plasma samples were obtained at approximately 120, 150, 180, and 210 minutes.…”

“…We reported that cystatin C was more accurate than creatinine in estimating GFR in 16 children receiving autologous HCT [6]. Unlike serum creatinine, cystatin C may be independent of muscle mass, but possibly affected by other non-renal factors such as corticosteroid treatment or body weight [5, 7].…”

Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults

“…In contrast, kidney dysfunction assessed by serum creatinine was a very late marker, highlighting its limitations, as it remains an insensitive marker to detect impaired renal function in HSCT recipients, who potentially have low muscle mass and thus low creatinine generation rates. 17,25,26,28,29 These observations suggest that a diagnosis of TMA should be considered in HSCT recipients with an acute elevation in LDH, proteinuria, and hypertension out of proportion to what would be expected from calcineurin inhibitor and steroid therapy. Importantly, these markers were apparent up to 2 weeks before schistocytes were detected.…”