Inflammatory bowel disease and renal disorders: from clinical associations to shared mechanisms and management strategies

A growing body of evidence indicates a strong relationship between inflammatory bowel disease (IBD) and a range of renal conditions, including chronic kidney disease, glomerulonephritis, tubulointerstitial disorders, nephrolithiasis, and secondary (AA) amyloidosis, which are rare yet severe systemic complications. In this review, we integrated clinical and epidemiological data to clarify the pathophysiological mechanisms underlying the gut–kidney axis.

Existing evidence was critically appraised with the observation that, although associative data are plentiful, causal pathways in humans remain incompletely understood. We describe how dysbiosis of the gut microbiota, breakdown of the intestinal barrier, and altered microbial metabolites (e.g., trimethylamine N-oxide [TMAO] and short-chain fatty acids [SCFAs]) drive systemic inflammation and contribute to renal injury.

Newer findings point to intestinal lymphatic dysfunction as a crucial intermediary. Injury to the proteinuric kidney triggers lymphangiogenesis within the gut and reshapes the composition of the lymph, thereby facilitating the systemic delivery of pro-inflammatory mediators, including IsoLG-modified apolipoprotein AI and Th17 cells, that worsen renal damage, thus establishing a self-reinforcing pathological loop.