Abstract

Chronic kidney disease (CKD) is an increasing global health burden. Current treatments for CKD include therapeutics to target factors that contribute to CKD progression, including renin–angiotensin–aldosterone system inhibitors, and drugs to control blood pressure and proteinuria control. Recently, associations between chronic disease processes and the human microbiota and its metabolites have been demonstrated. Dysbiosis—a change in the microbial diversity—has been observed in patients with CKD. The relationship between CKD and dysbiosis is bidirectional; gut-derived metabolites and toxins affect the progression of CKD, and the uremic milieu affects the microbiota. The accumulation of microbial metabolites and toxins is linked to the loss of kidney functions and increased mortality risk, yet renoprotective metabolites such as short-chain fatty acids and bile acids help restore kidney functions and increase the survival rate in CKD patients. Specific dietary interventions to alter the gut microbiome could improve clinical outcomes in patients with CKD. Low-protein and high-fiber diets increase the abundance of bacteria that produce short-chain fatty acids and anti-inflammatory bacteria. Fluctuations in the urinary microbiome are linked to increased susceptibility to infection and antibiotic resistance. In this review, we describe the potential role of the gut, urinary and blood microbiome in CKD pathophysiology and assess the feasibility of modulating the gut microbiota as a therapeutic tool for treating CKD.

Highlights

  • Chronic kidney disease (CKD) is a growing healthcare burden affecting about 13.4% of the population worldwide [1]

  • It is well-established that an increase in levels of harmful metabolites including trimethylamine N-oxide (TAMO), indoxyl sulfate, and p-cresyl sulfate are associated with renal fibrosis, endothelial dysfunction, a decline in the estimated glomerular filtration rate, cardiovascular complications, and increased mortality and morbidity in CKD [27,28,29,30]

  • We summarized and reviewed the literature examining the dual role of the gut microbiome and its metabolic products in the pathophysiology and progression of CKD

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Summary

INTRODUCTION

Chronic kidney disease (CKD) is a growing healthcare burden affecting about 13.4% of the population worldwide [1]. The human microbiome is the collection of all microbial DNA in the human body, which is distributed in various body parts as; skin, gastrointestinal, urinary tract, respiratory tract, and oral cavity [16] These microbes play crucial roles in the digestion and metabolic processes, stimulation and regulation of the immune response, production of vitamins, and protection against pathogens [17, 18]. It is well-established that an increase in levels of harmful metabolites including trimethylamine N-oxide (TAMO), indoxyl sulfate, and p-cresyl sulfate are associated with renal fibrosis, endothelial dysfunction, a decline in the estimated glomerular filtration rate (eGFR), cardiovascular complications, and increased mortality and morbidity in CKD [27,28,29,30]. While the gut is the main repertoire of microbes and the most studied site to date, urine and blood harbor different types of microbes and microbial signatures in both healthy and disease

52 ESRD patients and 44 healthy controls
77 CKD patients undergoing hemodialysis and 30 healthy
IS and PCS were high in the CKD group compared with controls
The advanced stage of CKD showed
The CKD rats group showed
28 CKD dogs and 28 healthy dogs
Resveratrol treatment showed a
The low soluble fiber plus betaine food significantly reduced genus
60 CKD patients
16 S rRNA gene Sequencing and GC-MS
CONCLUSION
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