Abstract
Although it is known that glomerular filtration rate (GFR) declines in response to angiotensin converting enzyme (ACE) inhibition, recent observations using GFRCYSTATIN C have shown a paradoxical increase calling into question its validity. In this descriptive study, we aimed to reconcile this observation by simultaneously measuring GFRCYSTATIN C, GFRCREATININE, and gold standard GFRINULIN responses to ACE inhibition. Adolescents with type 1 diabetes and hyperfiltration (n = 9, GFRINULIN ≥ 135 mL/min/1.73 m2) or normofiltration (n = 11) were studied during clamped euglycemia at baseline and after 3-week enalapril therapy. In hyperfilterers, the anticipated GFRINULIN decline before and after enalapril was observed (174 ± 29 mL/min/1.73 m2 to 140 ± 26 mL/min/1.73 m2, P = .01). Although GFRCYSTATIN C equations tended to underestimate while GFRCREATININE equations tended to overestimate baseline GFRINULIN in hyperfilterers, both approaches generally reflected declining GFRINULIN responses to enalapril. Normofilterers demonstrated a trend toward rising GFRINULIN in response to enalapril (112 ± 16 mL/min/1.73 m2 to 119 ± 27 mL/min/1.73 m2, P = .35). Although all estimating equations tended to overestimate baseline GFRINULIN, they generally reflected the rising trend in GFRINULIN in response to enalapril in normofilterers. Although GFRINULIN declines in response to enalapril among hyperfilterers, we confirm the previous observation that it demonstrates a trend to rising among normofilterers. These group trends are both reflected by cystatin C- and creatinine-based estimates.
ACKNOWLEDGMENTS
We thank Tim Shin and Drew Hume, Research Assistants, for statistical assistance and manuscript preparation. We offer particular gratitude to the study participants for their time and commitment.
Declaration of interest: Dr. B.A. Perkins is supported as a Scholar of the Canadian Diabetes Association. Dr. D.Z.I. Cherney is a recipient of a Kidney Foundation of Canada Scholarship and a Canadian Diabetes Association-KRESCENT Program New Investigator Award. This work was supported by operating grants from the Juvenile Diabetes Foundation (to Dr. E.B. Sochett), Canadian Institutes of Health Research (to Dr. D.Z.I. Cherney), a University of Toronto Dean’s Fund Award (to Dr. D.Z.I. Cherney), and a donation from the Harvey and Annice Frisch Family Fund (to Dr. B.A. Perkins). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.