Gut–kidney axis in chronic kidney disease: Pathophysiological mechanisms and microbiome-targeted therapeutic strategies

Abstract

Chronic kidney disease (CKD) is increasingly linked to alterations in the gut microbiome; however, current evidence remains fragmented regarding the causal contribution of dysbiosis, the mechanisms connecting intestinal disturbances with renal injury, and the clinical effectiveness and safety of microbiome-targeted interventions. This review aims to synthesize current knowledge on the gut–kidney axis in CKD and to identify emerging therapeutic and research directions. The review discusses the physiological functions of the gut microbiota in maintaining metabolic homeostasis, intestinal barrier integrity, immune regulation, and short-chain fatty acid production. It further examines CKD-associated dysbiosis, including the depletion of beneficial saccharolytic bacteria, expansion of urease- and toxin-producing microorganisms, accumulation of indoxyl sulfate and p-cresyl sulfate, impaired intestinal barrier function, endotoxemia, systemic inflammation, oxidative stress, renal fibrosis, and progressive kidney dysfunction. Variations in gut–kidney interactions across diabetic kidney disease, hypertension, aging, pediatric populations, and kidney transplantation are also considered. Therapeutic approaches discussed include probiotics, prebiotics, synbiotics, postbiotics, dietary modification, fecal microbiota transplantation, intestinal adsorbents, selective antibiotics, bacteriophages, engineered bacteria, and other emerging precision strategies. Particular attention is given to differences in the maturity of clinical evidence, potential safety concerns, and barriers to implementation. The review highlights the need for standardized microbiome assessment, prospective clinical studies, and integration of metagenomics, metabolomics, proteomics, and artificial intelligence to support patient-specific interventions. The gut–kidney axis represents a promising therapeutic target, but its translation into routine CKD management requires stronger clinical validation.