POTENTIAL THERAPEUTIC OPTIONS TARGETING THE GUT DYSBIOSIS IN CHRONIC KIDNEY DISEASE

Abstract

The gut microbiota plays an important physiological role in controlling not only the function of the gastrointestinal tract, but also in maintaining systemic homeostasis. Quantitative and /or qualitative disturbances of the gut microbiota (dysbiosis) are an important element in the complex pathogenesis of many diseases, including chronic kidney disease (CKD). In the disease, the mutual interactions between disturbed gut microbiota and the progression of CKD (pathophysiological “kidney-gut axis”) have been demonstrated. The kidney failure causes water and nitrogen waste retention which leads to disturbances of motility, secretion and absorption in the gastrointestinal tract. These abnormalities contribute to the development of gut dysbiosis, accompanied by overproduction of toxic bacterial metabolites, with their translocation to the peripheral blood and development of endotoxemia. As a consequence, chronic kidney “low-grade” inflammation and oxidative stress develop, with further deterioration of kidney function in the mechanism of the “vicious cycle” of the kidney-gut axis. Considering the key role of gut dysbiosis and the kidney-gut axis, the attempts to restore the gut eubiosis seem to have an important role in the treatment of CKD and may be even regarded as a form of causal therapeutic intervention. The paper briefly discusses the basics of the pathophysiological kidney-gut axis in CKD and potential methods of modulating the abnormal gut microbiota in this disease, including the use of probiotic or prebiotic preparations, agents that absorb bacterial-derived toxins in the intestinal lumen, fecal microbiota transplantation and drugs used so far for other indications (acarbose, meclofenamate, lubiprostone).