Kidney-gut-skin axis in CKD-associated pruritus: mechanisms and therapeutic implications
This narrative review synthesizes mechanistic evidence on gut microbiota and the kidney-gut-skin axis in CKD-associated pruritus without providing quantifiable therapeutic efficacy data.
| Outcome | Grade | Direction | Effect | Studies |
|---|---|---|---|---|
| Prevalence of moderate-to-severe pruritus in CKD | C | — Insufficient | 24% (estudo transversal citado, sem IC 95%) | 1 |
| All-cause mortality associated with severe CKD-aP | C | ▼ Unfavorable | +17–22% (literatura citada, sem IC 95%) | — |
| Fatigue risk in CKD-aP patients | C | ▼ Unfavorable | RR 2–5.8 (literatura citada, sem IC 95%) | — |
| Cutaneous κ-opioid receptor expression in CKD-aP vs. non-pruritic | C | ▼ Unfavorable | Reduzida em HD com prurido vs. sem prurido (sem tamanho de efeito quantificado) | 1 |
| Serum IL-31 levels in CKD-aP | C | ▼ Unfavorable | Elevada vs. controles sem prurido (sem OR/RR/IC 95%) | 3 |
| Efficacy of microbiota interventions (FMT, probiotics, AST-120) in CKD-aP | D | — Insufficient | Sem dados quantificáveis de ensaios clínicos em CKD-aP | — |
| Quality of life and sleep disturbance in CKD-aP | C | ▼ Unfavorable | 60% com insônia em CKD-aP moderado-grave (literatura citada, sem IC 95%) | — |
Context
CKD-aP affects 18–80% of end-stage kidney disease patients and increases all-cause mortality by 17–22%. Pathophysiological mechanisms remain incompletely understood, limiting treatment. The kidney-gut-skin axis hypothesis represents a conceptual reorientation warranting investigation of microbiota-centered therapeutic targets.
What the study showed
The study presents no original trial data or meta-analysis; it synthesizes existing literature. CKD-aP patients show elevated IL-31, IL-2, and IL-6 versus non-pruritic controls and reduced cutaneous κ-opioid receptor expression. A cited multinational cross-sectional study reported 24% prevalence of moderate-to-severe pruritus in CKD stages 3–5. Fatigue risk is 2–5.8× higher in pruritic patients; all-cause mortality elevated 17–22%. No 95% CI or effect size for microbiota interventions on pruritus outcomes is reported.
How it was done
Structured narrative review. Databases: PubMed, Web of Science, Embase, Scopus, CNKI, and Wanfang, from inception to May 2, 2026. No PRISMA-based risk-of-bias assessment; no quantitative meta-analysis. Eligible studies included clinical, observational, interventional, review, meta-analytic, and mechanistic reports.
Effect magnitude
No primary effect size calculated by the authors. Data cited from secondary literature: all-cause mortality elevated 17–22% and fatigue risk 2–5.8× higher in severe CKD-aP — no 95% CI reported in this review.
Limitations
Narrative review without PRISMA protocol or risk-of-bias assessment (RoB 2, ROBINS-I, AMSTAR-2 not applied). Study selection susceptible to author confirmation bias. Mechanistic evidence predominantly from animal models and in vitro studies; generalization to human CKD-aP undemonstrated. Source population heterogeneity precludes causal conclusions. No RCT on microbiota interventions for CKD-aP is systematically evaluated.
In clinical practice
This review does NOT support practice change at evidence level A or B for any microbiota intervention in CKD-aP. Clinicians should maintain established treatments (phosphate control, skin hydration, difelikefalin where available). The kidney-gut-skin axis framework may guide hypotheses for future trials but does not alter current clinical protocols.
What is still missing
Randomized controlled trials with a validated pruritus primary endpoint (WI-NRS or VAS), evaluating specific microbiota interventions (FMT, probiotics, AST-120) in confirmed CKD-aP patients, with adequate follow-up and confounder control.