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Natriuretic peptides in acute kidney injury – A sojourn on parallel tracks?

Published:December 04, 2019DOI:https://doi.org/10.1016/j.ejim.2019.11.025

      Highlights

      • NP cause diuresis and natriuresis, enhances GFR and are anti-inflammatory.
      • Despite mixed results in several trials, NP decrease postoperative AKI.
      • AKI is a complex interplay between renal injury, renal hemodynamics and inflammation.
      • Natriuretic peptides modulate only some of these pathways.
      • Endpoints of dialysis/death in trials were overambitious nullifying the true effects of NP.

      Abstract

      Objective

      The focus of this review was to elicit the mechanistic logic of the experimental and clinical study designs of natriuretic peptides (NP) in acute kidney injury (AKI) and to understand their respective outcomes.

      Methods

      Online search of PubMed and manual review of articles. Randomized trials, observational and physiologic studies of NPs and AKI were extracted. Rationale, design and study outcomes were analyzed.

      Results

      In experimental models of AKI, infusion of NP prevented post-ischemic fall in renal blood flow (RBF) or improvement in RBF, GFR, diuresis and natriuresis and demonstrated anti-inflammatory properties. NPs were most effective in the early stages of AKI, also in established phase of AKI but their effectiveness were limited to the time of infusion. Hypotension was a major side-effect. Based on these observations, preliminary clinical studies were performed which demonstrated improved urine output, RBF and GFR and reduced need for dialysis. However, randomized, controlled trials failed to demonstrate improvement in dialysis-free survival in different cohorts and study designs. Although NPs reduced the incidence of AKI in the postoperative period in cardiac surgery, it was not associated with improved long-term survival. In contrast to randomized trials, meta-analysis reported favorable results.

      Conclusions

      Reasons for the divergence of experimental and clinical outcomes of NPs in AKI are discussed in this review article.

      Keywords

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