Non‐resolution of acute kidney injury in the first week portends the development of chronic kidney disease in critically ill patients with cirrhosis

Abstract

SummaryBackgroundRenal tubular epithelial cells (RTECs) cause maladaptive repair and perpetuate renal fibrosis.AimTo evaluate urinary neutrophil gelatinase‐associated lipocalin (NGAL) and RTEC as risk factors for non‐resolution of acute kidney injury (AKI–NR) at day seven and chronic kidney disease (CKD) in critically ill patients with cirrhosis.MethodsWe performed urinary NGAL and microscopy at enrolment and day 7 in all patients. We assessed 17 renal injury, endothelial injury and repair markers, genes for mitochondrial biogenesis by qRT–PCR in RTEC, and post‐mortem renal biopsies for understanding mechanisms of AKI non‐resolution (n = 30).ResultsWe enrolled 310 patients, aged 48.1 ± 11.6 years, 87% male, 90% alcoholic. Of these, 36% had RTEC at enrolment, and 53% had AKI–NR on day 7. On mean follow‐up of 136 days (range 43–365), 150 (48.3%) developed CKD. The presence of RTEC or granular casts, NGAL and AKI–NR were independent predictors of CKD development on competing risk analysis. Higher MCP‐1, renal endothelial injury, decrease in tubular repair markers and failure of mitochondrial biogenesis in RTEC were seen in patients with AKI–NR compared with AKI–R (p < 0.05). Renal biopsies showed infiltration with monocyte–macrophage, increased α‐SMA, and tubulointerstitial fibrosis.ConclusionAlmost two‐thirds of critically ill patients with cirrhosis have AKI, which resolves in only one‐half at day seven and predicts the development of CKD. Higher NGAL, RTEC, or granular casts were independent predictors of AKI–NR and CKD development. Enhanced tubular and endothelial injury, decreased repair, monocyte–macrophage infiltration and mitochondrial dysfunction in RTEC are associated with AKI non‐resolution and risk of renal fibrosis.