Urinary neprilysin for early detection of acute kidney injury after cardiac surgery

Abstract

BACKGROUND Acute kidney injury (AKI) predicts adverse outcomes after cardiac surgery. The accuracy of using changes in serum creatinine for diagnosis and grading of AKI is limited in the peri-operative cardiac surgical setting and AKI may be underdiagnosed due to haemodilution from cardiopulmonary bypass priming and the need for intra-operative and postoperative volume resuscitation. OBJECTIVES To determine whether the urinary biomarker neprilysin can be used as a marker for the early detection of AKI after cardiac surgery. DESIGN Prospective, observational cohort study. SETTING Austrian tertiary referral centre. PATIENTS 96 Patients undergoing elective cardiac surgery with cardiopulmonary bypass. MAIN OUTCOME MEASURES Differences and discriminatory power of neprilysin levels early after cardiac surgery and on postoperative day 1 between patients with or without AKI, as defined by the Kidney Disease Improving Global Outcomes Group. RESULTS AKI was found in 27% (n=26). The median neprilysin levels on postoperative day 1 were significantly higher in the AKI than in the non-AKI group, 4.0 [interquartile range (IQR): 2 to 6.25] vs. 2.0 ng ml−1 [IQR: 1.0 to 4.5], P = 0.0246, respectively. In addition, the median neprilysin levels at the end of surgery were significantly different between both groups, 5.0 [IQR: 2.0 to 9.0] vs. 2.0 ng ml−1 [IQR: 1.0 to 4.0], P = 0.0055, respectively. The discriminatory power of neprilysin for detecting early AKI corresponded to an area under the curve of 0.77 (95% confidence interval, 0.65 to 0.90). CONCLUSION Urinary neprilysin has potential as a biomarker for the early detection of AKI after cardiac surgery and has comparable discriminatory power to recently studied AKI biomarkers. TRIAL REGISTRATION The trial was registered at ClinicalTrials.gov (NCT03854825, https://clinicaltrials.gov/ct2/show/NCT03854825).

Tubular epithelial progenitors are excreted in urine during recovery from severe acute kidney injury and are able to expand and differentiate in vitro

“…1G ) experienced a steady increase in urine output accompanied by decreasing urinary excretion of the cell injury marker neprilysin. The decrease in sCr showed a delay of about 5 days compared with urinary neprilysin as marker of tubular cell damage ( Bernardi et al, 2021 ; Knafl et al, 2017 ; Pajenda, Mechtler & Wagner, 2017 ). Peak urinary neprilysin levels were significantly higher in infection-associated AKI ( Fig.…”

“…Moreover, the renal cell injury marker neprilysin in urine ( Bernardi et al, 2021 ; Pajenda, Mechtler & Wagner, 2017 ) decreased rapidly after elimination of nephrotoxic substances or restoration of oxygenation. The course of urinary neprilysin showed that excretion of hyperplastic epithelial cells began with a short delay of approximately 2 days when urinary neprilysin had flattened.…”

Association of intra-operative muscular tissue oxygen saturation with postoperative acute kidney injury in older patients undergoing major abdominal surgery: A prospective cohort study

“…In view of adverse prognosis caused by AKI, prompt identi cation of renal function deterioration is urgently required. Urinary biomarkers were shown to be sensitive indices for AKI prediction, [22,23] but they cannot be measured continuously and involve time-consuming assessments. NIRS enables real-time monitoring and may earlier detect AKI.…”

Diagnosis, pathophysiology and preventive strategies for cardiac surgery-associated acute kidney injury: a narrative review

“…During kidney injury, neprilysin is shed from the tubular brush edge of the kidney and is excreted, which can be detected in urine. The discriminatory power of neprilysin for detecting POD 1 AKI corresponded to an AUC of 0.77 (95% CI 0.65–0.90) [ 24 ].…”