Urine microscopy can identify cholemic nephropathy as a distinct form of kidney dysfunction in patients with acute on chronic liver failure

Cholemic nephropathy(CN) is an unrecognized cause of kidney dysfunction in patients with acute on chronic liver failure (ACLF). We aimed to evaluate whether urine microscopy(UM) could identify CN in ACLF patients and differentiate from hepatorenal syndrome (HRS) and acute tubular necrosis (ATN). Forty-five patients with ACLF with AKI stratified based on UM as HRS(bland sediment; n = 15), CN(bilirubin crystals; n = 15) and ATN (coarse granular casts; n = 15) were compared to no AKI (n = 15). ACLF patients with mean age of 44 ± 10 years, 93% males were enrolled. Patients with HRS and CN showed significantly elevated biomarkers of renal repair (EGF, Osteopontin, calbindin) and lower levels of renal injury (renin, lipocalin-2, cystatin c, alpha-1 macroglobulin, albumin, TIMP-1, IP-10 and KIM-1) compared to ATN. CN patients had significantly elevated bile acids, proinflammatory cytokines (20 out of 29) compared to other groups. Metabolomic analysis of plasma and renal tubule epithelial cells (RTEC)identified 190 (151 up- and 39 downregulated) and 196 (61 up and 135-down) differentially expressed metabolites in biopsy-proven CN compared to ATN(FC > 1.5, P < 0.05). Preservation of mitochondrial function was seen in the RTEC of CN compared to ATN. The top 5 biomarkers which predicted CN included GST-alpha, IL-15, bile acids, IL-3, and osteopontin. Clinical models including GST-alpha, IL-15, bilirubin (> 22 mg/dl) or AARC score identified CN with more than 95% accuracy. Taken together, our study shows higher bile acids, preserved renal repair and lesser tubular injury despite intense systemic inflammation with preserved metabolic adaptation of the host differentiated CN from ATN.