Diminishing Kidney Reserve and the "Pseudo"normal Creatinine.

Abstract

TO THE EDITOR: We read, with great interest, the study by Cullaro et al., which showed that “apparently normal” baseline serum creatinine levels are associated with increased risk of persistent kidney injury and mortality in patients with liver cirrhosis.(1) We commend the investigators for undertaking such a rigorous analysis and would like to share our opinion on the utility of renal functional reserve (RFR) in this clinical setting. RFR, originally described more than 30 years ago,(2) remains an underexplored concept. It is defined as the difference between “stress” glomerular filtration rate (GFR) and baseline GFR, where stress GFR is the supranormal GFR that can be clinically elicited by administering a protein load and represents the reserve capacity of the kidney to increase GFR in response to certain stimuli.(3) Even with up to 50% of the functional nephron mass damaged during an episode of acute kidney injury (AKI), hyperfiltration in the remaining nephrons would compensate for the lost function, keeping the serum creatinine value near baseline or “normal” (Fig. 1). During subsequent episodes of AKI, the serum creatinine settles at a higher baseline because of complete or partial loss of RFR during previous episodes. Therefore, RFR is likely to be a sensitive index for early detection of renal disease and also an appropriate marker to follow up patients with renal dysfunction, compared to serum creatinine.(4) In our opinion, measuring RFR at baseline and after AKI in certain high‐risk subgroups (e.g., patients with cirrhosis) could be a valuable tool for prognostication and development of appropriate risk‐reduction protocols. Future studies should focus on developing simplified protocols for RFR testing to make its use more practical.Figure 1: Illustration depicting the (A) baseline GFR (120 mL/min) and stress GFR (180 mL/min). Renal functional reserve is the difference between stress and baseline GFRs, that is, 60 mL/min in this example. (B,C) GFR returning back to baseline after recovery from an AKI at the expense of partially or completely lost renal functional reserve because of hyperfiltration in the remaining nephrons.Potential Conflict of Interest Nothing to report.