Liver-kidney crosstalk in primary biliary cholangitis: insights into the mechanisms of renal involvement.

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease primarily affecting the intrahepatic small bile ducts. Although PBC is mainly a hepatobiliary disease, renal abnormalities have been reported in a subset of patients and should be regarded as uncommon but clinically relevant extrahepatic manifestations. Reported glomerular lesions in patients with PBC include membranous nephropathy, immunoglobulin A nephropathy, crescentic glomerulonephritis, and minimal change disease, although most evidence is derived from case reports and small series. Tubulointerstitial involvement has also been described, most commonly as distal renal tubular acidosis in reported cases and less commonly as Fanconi syndrome; these conditions may reflect immune-mediated tubular dysfunction in selected patients. In addition, metabolic disturbances secondary to cholestasis and tubular injury may increase the risk of nephrolithiasis and nephrocalcinosis, whereas advanced cirrhosis can precipitate hepatorenal syndrome. Limited reports further suggest that cholestatic nephropathy and drug-related nephrotoxicity may contribute to renal impairment in selected patients. From a mechanistic perspective, immune complex deposition, T-cell-mediated inflammation, mitochondrial dysfunction, cholestatic/metabolic disturbances, and gut microbiota dysbiosis have been proposed as potential contributors, but direct causal evidence remains limited. Given the heterogeneity and potential clinical significance of renal manifestations in PBC, early detection, thorough nephrological assessment, and individualized therapeutic strategies are essential.