Urinary neprilysin - Another marker to predict postoperative acute kidney injury.

Abstract

Dear Editor, Perioperative acute kidney injury (AKI) is a serious complication which is multifactorial, which leads to increased hospital and intensive care unit stay, possibility of chronic kidney disease and hemodialysis, increased cost of treatment, significant morbidity, and mortality. Neprilysin or neutral endopeptidase (NEP) is a single-pass membrane glycoprotein with zinc-dependent endopeptidase activity and a short cytosolic tail. NEP is found predominantly within the kidneys, gastrointestinal tract, liver, male genital organs, lungs, adipose tissue, brain, and heart. The renal brush border of proximal tubule on the luminal side is rich in membrane-bound NEP. NEP is involved in the degradation of both atrial and B-type natriuretic peptides, adrenomedullin, endothelin-1 and angiotensin II, and also nonvasoactive peptides, such as glucagon, glucagon-like peptide, enkephalins, and somatostatin. Circulating NEP estimation in serum has been used as a biomarker in acute and chronic heart failure patients for predicting cardiovascular death and time-to-first admission for an acute event.[1] The prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin-converting enzyme (ACE) inhibitor (ACEi) to determine impact on global mortality and morbidity in heart failure (PARADIGM-HF) study reported significant clinical benefits with the combination of an angiotensin receptor blocker valsartan with a neprilysin inhibitor sacubitril over ACEi in heart failure with reduced ejection fraction.[2] However, trends of serum NEP could never correlate NT-pro-BNP and even clinically. In AKI, NEP is flushed out from the kidneys due to shedding of the tubular brush border and thus is available for estimation in the urine as a marker. Bernardi et al.[3] conducted a prospective, observational cohort study involving 96 patients undergoing elective cardiac surgeries with cardiopulmonary bypass. They estimated urinary neprilysin levels in the immediate postoperative period and on day 1. The authors concluded that estimation of urinary neprilysin levels after cardiac surgeries has comparable discriminatory power to presently studied AKI biomarkers and has potential as a biomarker for the early detection of AKI after cardiac surgery. Pajenda et al.[4] analyzed urinary neprilysin levels of 90 critically ill patients admitted to intensive or intermediate care unit over 2–5 days. On analysis, they found that NEP levels who suffered AKI according to the KDIGO (Kidney Disease Improving Global Outcomes) criteria were significantly elevated in comparison to healthy controls. In a comparative study performed by Gutta et al.[5] between 20 nondiabetics and 40 diabetic patients, authors compared urinary ACE2, NEP, disintegrin and metalloproteinase 17 (ADAM17) between two groups. The authors concluded that urinary ACE2 and NEP can be used as early biomarkers to predict the incidence or progression of chronic kidney disease at early stages among individuals with type 2 diabetes. The normal values of urinary neprilysin derived from recent studies are in the range of 0.5–1 ng/mL. To conclude, urinary NEP needs to be validated with adequately powered randomized controlled studies in various postoperative scenarios like thoraco-abdominal aneurysm repair, major laparotomies including cytoreductive surgeries and heated intraperitoneal chemotherapy. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.