Association Between Psoriasis and Chronic Kidney Disease/End-Stage Renal Disease: A Meta-Analysis of Cohort Studies

Psoriasis is a common chronic immune-mediated disease affecting approximately 125 million people worldwide, characterized clinically by scaly erythematous plaques and histologically by epidermal hyperplasia and inflammatory cell infiltration. Beyond skin involvement, psoriasis is associated with systemic comorbidities including cardiovascular disease, cancers, infections, and mental health disorders. Evidence has suggested potential renal involvement, with increased prevalence of microalbuminuria and renal failure reported in psoriasis patients. Chronic kidney disease (CKD) is defined by persistent kidney structural or functional abnormalities (e.g., eGFR <60 mL/min/1.73 m2 or albuminuria) for more than 3 months; end-stage renal disease (ESRD) corresponds to GFR <15 mL/min/1.73 m2. Given reports of increased CKD/ESRD risk in psoriasis, but uncertainty about causality and potential biases from non-cohort designs, the authors conducted a meta-analysis of cohort studies to assess whether psoriasis is associated with incident CKD and ESRD, including evaluation by psoriasis severity.

Prior studies have examined links between psoriasis and renal outcomes. A large cohort (n=143,883) reported elevated risks of CKD (HR 1.05) and ESRD (HR 1.15), with stronger associations in severe psoriasis (CKD HR 1.93; ESRD HR 4.15) compared with mild disease (CKD HR 0.99; ESRD HR 0.98). Other work suggested correlations of psoriatic arthritis, longer disease duration, and higher PASI with increased albumin-to-creatinine ratios. However, findings across studies vary, and the strength and independence of the association remain uncertain. Mechanistically, psoriasis involves systemic immune activation (e.g., Th1/Th17, TNF-α, IL-23/IL-17) that may contribute to renal inflammation and endothelial dysfunction. Drug effects (e.g., methotrexate, cyclosporine) and shared comorbidities (obesity, hypertension, diabetes) may further mediate risk.

Search strategy: Systematic searches of PubMed, Web of Science, Embase, and Cochrane Library through March 2023 using MeSH and free-text terms for psoriasis, chronic kidney disease, and end-stage renal disease, adapted per database. References of included studies and relevant reviews were screened. Authors planned to contact corresponding authors for missing data. Inclusion criteria: Cohort study design (prospective or retrospective); included both psoriasis and non-psoriasis comparator groups with incident CKD and/or ESRD outcomes; reported RR/HR/SIR with 95% CI or provided data to calculate them; excluded studies with CKD/ESRD present at baseline. Data extraction: Two independent reviewers extracted study characteristics (first author, year, country/region, population, numbers of cases/controls) and outcome HRs (95% CI) for CKD and ESRD; discrepancies resolved with a third reviewer. Quality assessment: Risk of bias assessed per Cochrane Handbook domains (sequence generation, allocation concealment, blinding of participants/providers, blinding of outcome assessment, incomplete outcome data, selective reporting, other biases), rated as low/unclear/high risk. Statistical analysis: Log-HRs with SEs were meta-analyzed using DerSimonian–Laird random-effects models due to expected between-study differences. Heterogeneity assessed with I2 (0–25% insignificant, >25–50% low, >50–75% moderate, >75% high). P<0.05 considered significant. Subgroup analyses stratified by psoriasis severity (mild vs severe, typically defined by use of phototherapy/systemic therapy).

Study selection and characteristics: Of 968 records, 7 cohort studies (UK, Taiwan, Korea) met criteria, comprising 738,104 psoriasis cases and 3,443,438 comparators. Mean age was 44.9 years in psoriasis vs 44.1 in controls; males were 50.8% vs 49.2%. All studies used administrative databases and diagnostic codes; age and sex adjustment was performed in all. Risk of CKD: Six studies contributed to CKD analysis. Pooled HR 1.65 (95% CI 1.29–2.12), with high heterogeneity (I2=96%). Severity subgroup (3 studies): Severe psoriasis vs controls HR 1.91 (95% CI 1.78–2.05; I2=0%); mild psoriasis vs controls HR 1.14 (95% CI 0.87–1.48; I2=95%). Risk of ESRD: Five studies contributed to ESRD analysis. Pooled HR 1.37 (95% CI 1.14–1.64; I2=60%). Severity subgroup (3 studies): Severe psoriasis vs controls HR 2.72 (95% CI 1.70–4.34; I2=21%); mild psoriasis vs controls HR 1.07 (95% CI 0.86–1.33; I2=31%). Quality assessment: Many studies did not report details on randomization/allocation (not typically applicable to observational cohorts) or blinding; one study (Parisi et al.) was assessed high risk for not adjusting effect estimates for confounders. Reporting bias was generally low. Funnel plots were not used due to the small number of studies (n=7).

This meta-analysis indicates that psoriasis is associated with higher risks of incident CKD and ESRD compared with non-psoriatic populations. The association is stronger and statistically robust in severe psoriasis, while mild psoriasis shows no clear elevation in ESRD risk and an inconclusive association with CKD due to heterogeneity. Findings remained significant in studies adjusting for key metabolic and cardiovascular confounders, suggesting psoriasis may independently contribute to CKD/ESRD risk. Potential mechanisms include systemic inflammation central to psoriasis pathogenesis (Th1/Th17 activation, mediators such as TNF-α and IL-23/IL-17) that can promote renal inflammation, alter renal hemodynamics, and contribute to hypertension and albuminuria. Endothelial inflammation and dysfunction observed in psoriasis may increase vascular permeability and proteinuria, linking to CKD progression. Drug-related nephrotoxicity (e.g., methotrexate, cyclosporine) is biologically plausible, though current cohort evidence does not conclusively implicate these agents in increased ESRD risk, and biologic therapies may improve renal parameters in some contexts. Additionally, shared and interrelated comorbidities common in psoriasis (obesity, hypertension, diabetes, NAFLD, atherosclerosis) likely contribute to renal risk, especially in older patients with existing cardiovascular risk factors. Clinically, these findings underscore the need for heightened renal risk assessment and monitoring in psoriasis, particularly for moderate-to-severe disease.

Psoriasis is associated with a significantly increased risk of incident CKD and ESRD, with the greatest risk observed in severe disease. Clinicians should consider routine renal monitoring (e.g., urine microalbumin, serum creatinine, BUN) in patients with moderate-to-severe psoriasis to enable early detection and intervention. Further well-designed prospective studies and clinical trials are needed to clarify causality, refine risk stratification (including validated severity metrics such as PASI), and evaluate the renal safety and potential renoprotective effects of psoriasis therapies. Improved understanding of this association can inform prevention strategies and reduce CKD-related morbidity and mortality in psoriasis populations.

Key limitations include: (1) Only three studies stratified by psoriasis severity, and severity was defined by treatment pattern (phototherapy/systemic therapy) rather than validated clinical measures (e.g., PASI), limiting causal inference on severity gradients; (2) All analyses relied on administrative databases and diagnostic codes, which may introduce misclassification of exposure and outcomes; (3) High heterogeneity in CKD analyses (I2=96%), potentially reflecting differences in populations (race, age, sex), definitions, and adjustments across cohorts; (4) Limited number of studies (n=7) precluded robust assessment of publication bias; (5) Incomplete reporting of methodological details typical for observational studies (e.g., blinding, allocation concealment) complicates formal risk-of-bias assessments.