Beyond solute clearance: the kidney–gut–immune–nutrition axis in hemodialysis and peritoneal dialysis and a proposed framework for integrated risk stratification
- 1Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
- 2Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
Abstract
Kidney disease affects approximately ~850 million people globally, with millions dependent on dialysis as life-sustaining renal replacement therapy. While dialysis corrects solute accumulation and fluid overload, it incompletely replicates normal renal physiology and introduces its own biological stressors, perpetuating a cycle of systemic dysfunction that extends well beyond the kidney. Central to this dysfunction is the kidney–gut–immune–nutrition (KGIN) axis: a bidirectional network linking renal clearance, intestinal microbial homeostasis, immune regulation, and nutritional metabolism. In end-stage renal disease, each component of this axis is simultaneously disrupted and becomes a driver of further deterioration. Uremic toxin accumulation remodels the gut microbiome toward a dysbiotic state, characterized by depletion of short-chain fatty acid-producing organisms and expansion of pathobionts. The resulting compromise of intestinal barrier integrity permits systemic translocation of lipopolysaccharide and other microbial products, sustaining chronic low-grade inflammation and a paradoxical state of immune dysfunction marked by heightened inflammatory signaling alongside impaired pathogen defense. These perturbations converge on nutritional status, driving protein-energy wasting through catabolic cytokine signaling, anorexia, and suppression of anabolic pathways, with sarcopenia reported in several dialysis cohorts to progress at two to three fold faster than age related muscle loss. Hemodialysis and peritoneal dialysis produce distinct patterns of axis disruption: hemodialysis is characterized by intermittent toxin peaks, bioincompatible membrane-driven complement activation, and more severe dysbiosis, whereas peritoneal dialysis introduces continuous peritoneal glucose exposure and a unique local immune microenvironment, with generally slower decline in residual kidney function. These modality-specific differences translate into divergent cardiovascular, infectious, and nutritional risk profiles that are incompletely explained by traditional clinical variables. Emerging multi-omics approaches, including metagenomics, metabolomics, and high-throughput immune profiling, are beginning to characterize axis disruption with unprecedented resolution, enabling in-depth characterization of host-microbiome-immune identification of patient subgroups with distinct mechanistic signatures that cannot be captured by single domain analysis alone. To bridge this analytical capability with clinical practice, we propose the Microbiome–Immune–Nutrition (MIN) Index, a conceptual, hypothesis generating composite biomarker framework designed to synthesize data across all three axis domains and stratify patients by the severity of disruption to guide targeted, personalized interventions, which remain to be demonstrated through prospective validation studies. Therapeutic strategies targeting the axis, including dietary fiber and plant-based approaches, synbiotics, fecal microbiota transplantation, advanced dialysis modalities, and omega-3 and polyphenol supplementation, show mechanistic promise but require larger, better-designed trials with hard clinical endpoints before routine clinical adoption. Standardization of microbiome research methodology, investment in longitudinal multi-omics cohorts, and development of international collaborative consortia are research priorities that will be essential to translate mechanistic insights into improvements in survival and quality of life for patients on maintenance dialysis.
Related
- Optimal prediction of peritoneal dialysis to hemodialysis transition: a penalized fine-gray model
- Catheter-related deep vein thrombosis complicated by iatrogenic pulmonary embolism after thrombectomy leading to hemodialysis failure and successful rescue by automated peritoneal dialysis : A case report
- Latent profiles of nutrition literacy among patients receiving peritoneal dialysis and their associations with dietary adherence and nutritional and metabolic indicators: a multicenter cross-sectional study
- Blood pressure variability and serum sodium for long-term mortality risk stratification in maintenance hemodialysis patients: a real-world retrospective cohort study
- Integrated Multi-Omic Analysis of Paired Primary and Peritoneal Metastatic Tumors Reveals GPAA1 as a Therapeutic Target in Colorectal Cancer
BibTeX
@article{rawat2026beyond,
title = {{Beyond solute clearance: the kidney–gut–immune–nutrition axis in hemodialysis and peritoneal dialysis and a proposed framework for integrated risk stratification}},
author = {Atul Rawat and Narayan Prasad and Pratima Rawat and Sultan Ahmed and Brijendra Kumar and Ananya Singh and Tanya Nayak and Ravi S. Kushwaha},
journal = {Frontiers in Nutrition},
year = {2026},
month = oct,
doi = {10.3389/fnut.2026.1931760},
url = {https://doi.org/10.3389/fnut.2026.1931760},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Beyond solute clearance: the kidney–gut–immune–nutrition axis in hemodialysis and peritoneal dialysis and a proposed framework for integrated risk stratification
AU - Atul Rawat
AU - Narayan Prasad
AU - Pratima Rawat
AU - Sultan Ahmed
AU - Brijendra Kumar
AU - Ananya Singh
AU - Tanya Nayak
AU - Ravi S. Kushwaha
PY - 2026
DA - 2026/10/21
JO - Frontiers in Nutrition
DO - 10.3389/fnut.2026.1931760
UR - https://doi.org/10.3389/fnut.2026.1931760
AB - Kidney disease affects approximately ~850 million people globally, with millions dependent on dialysis as life-sustaining renal replacement therapy. While dialysis corrects solute accumulation and fluid overload, it incompletely replicates normal renal physiology and introduces its own biological stressors, perpetuating a cycle of systemic dysfunction that extends well beyond the kidney. Central to this dysfunction is the kidney–gut–immune–nutrition (KGIN) axis: a bidirectional network linking renal clearance, intestinal microbial homeostasis, immune regulation, and nutritional metabolism. In end-stage renal disease, each component of this axis is simultaneously disrupted and becomes a driver of further deterioration. Uremic toxin accumulation remodels the gut microbiome toward a dysbiotic state, characterized by depletion of short-chain fatty acid-producing organisms and expansion of pathobionts. The resulting compromise of intestinal barrier integrity permits systemic translocation of lipopolysaccharide and other microbial products, sustaining chronic low-grade inflammation and a paradoxical state of immune dysfunction marked by heightened inflammatory signaling alongside impaired pathogen defense. These perturbations converge on nutritional status, driving protein-energy wasting through catabolic cytokine signaling, anorexia, and suppression of anabolic pathways, with sarcopenia reported in several dialysis cohorts to progress at two to three fold faster than age related muscle loss. Hemodialysis and peritoneal dialysis produce distinct patterns of axis disruption: hemodialysis is characterized by intermittent toxin peaks, bioincompatible membrane-driven complement activation, and more severe dysbiosis, whereas peritoneal dialysis introduces continuous peritoneal glucose exposure and a unique local immune microenvironment, with generally slower decline in residual kidney function. These modality-specific differences translate into divergent cardiovascular, infectious, and nutritional risk profiles that are incompletely explained by traditional clinical variables. Emerging multi-omics approaches, including metagenomics, metabolomics, and high-throughput immune profiling, are beginning to characterize axis disruption with unprecedented resolution, enabling in-depth characterization of host-microbiome-immune identification of patient subgroups with distinct mechanistic signatures that cannot be captured by single domain analysis alone. To bridge this analytical capability with clinical practice, we propose the Microbiome–Immune–Nutrition (MIN) Index, a conceptual, hypothesis generating composite biomarker framework designed to synthesize data across all three axis domains and stratify patients by the severity of disruption to guide targeted, personalized interventions, which remain to be demonstrated through prospective validation studies. Therapeutic strategies targeting the axis, including dietary fiber and plant-based approaches, synbiotics, fecal microbiota transplantation, advanced dialysis modalities, and omega-3 and polyphenol supplementation, show mechanistic promise but require larger, better-designed trials with hard clinical endpoints before routine clinical adoption. Standardization of microbiome research methodology, investment in longitudinal multi-omics cohorts, and development of international collaborative consortia are research priorities that will be essential to translate mechanistic insights into improvements in survival and quality of life for patients on maintenance dialysis.
SN - 2296-861X
ER -