Psoriasis, a chronic immune-mediated inflammatory disease affecting 125 million globally, is characterized by scaly erythematous rash and epithelial hyperplasia. It significantly impacts quality of life and is increasingly linked to various comorbidities, including cardiovascular disease, cancer, infections, and mental health issues. A growing body of evidence suggests a correlation between psoriasis and renal injury, with increased prevalence of microalbuminuria and renal failure reported in psoriasis patients. Chronic kidney disease (CKD), a syndrome defined by persistent kidney structure and function alterations, affects ~11% of the population, significantly reducing health-related quality of life. While some studies have shown a link between psoriasis and CKD/ESRD, the relationship remains unclear, hampered by potential bias in cross-sectional and case-control studies. This meta-analysis aimed to clarify this association by analyzing cohort studies, hypothesizing that psoriasis patients are at increased risk of renal injury, ultimately improving clinicians' understanding and patient care.

Existing research on the association between psoriasis and CKD/ESRD yielded inconsistent results. Some cohort studies reported an increased prevalence of CKD and ESRD in psoriasis patients, with the severity of psoriasis potentially influencing the risk. For example, one study found a higher risk of CKD and ESRD in patients with severe psoriasis compared to those with mild psoriasis or no psoriasis. However, the relationship between psoriasis severity and renal outcomes lacked consistent reporting across studies. The existing literature highlighted the need for a robust meta-analysis to evaluate the strength and consistency of this association, accounting for potential confounding factors.

A systematic review of PubMed, Web of Science, Embase, and Cochrane Library databases (up to March 2023) was performed using keywords related to psoriasis, CKD, and ESRD. Two investigators independently screened studies for eligibility, with disagreements resolved by a third reviewer. Inclusion criteria required cohort studies (prospective or retrospective) comparing psoriasis patients to controls, reporting relative risk (RR), hazard ratio (HR), or standardized incidence rate (SIR) with 95% confidence intervals (CI) or sufficient raw data. Studies with baseline CKD/ESRD were excluded. Data extraction included first author, publication year, region, study population, number of cases and controls, and HRs/CIs for CKD and ESRD. Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analysis was performed using Review Manager 5.4 software, employing a DerSimonian-Laird random-effects model to account for heterogeneity. Heterogeneity was assessed using the I² statistic. Subgroup analysis stratified the results based on psoriasis severity (mild vs. severe).

The initial search yielded 968 studies. After removing duplicates and screening titles/abstracts, 7 full-text articles were included in the meta-analysis, representing 738,104 psoriasis patients and 3,443,438 controls. The mean age of psoriasis patients was 44.9 years compared to 44.1 years for controls; 50.8% of psoriasis patients were male versus 49.2% in the control group. All included studies used population databases and diagnostic codes for identifying psoriasis, CKD, and ESRD, adjusting for age and sex. Six studies reported on CKD risk; pooled analysis showed a significantly increased risk of CKD in psoriasis patients (HR=1.65, 95% CI 1.29–2.12, I²=96%). Subgroup analysis showed a significantly higher risk of CKD among patients with severe psoriasis (HR=1.91, 95% CI 1.78–2.05, I²=0%), but not in those with mild psoriasis (HR=1.14, 95% CI 0.87–1.48, I²=95%). Five studies reported on ESRD; pooled analysis indicated a significantly increased risk (HR=1.37, 95% CI 1.14–1.64, I²=60%). Subgroup analysis revealed a significantly increased risk of ESRD for patients with severe psoriasis (HR=2.72, 95% CI 1.70–4.34, I²=21%), but not for those with mild psoriasis (HR=1.07, 95% CI 0.86–1.33, I²=31%). Quality assessment using the Cochrane Handbook revealed that the included studies had some limitations in terms of randomization, allocation concealment, and blinding.

This meta-analysis demonstrates a significantly increased risk of incident CKD and ESRD in psoriasis patients, particularly those with severe psoriasis. This association likely stems from the systemic inflammatory nature of psoriasis. Overactivation of Th1 and Th17 lymphocytes and inflammatory mediators like TNF-α and IL-23, implicated in psoriasis pathogenesis, may also contribute to renal injury. Studies evaluating the impact of biologics, which target these inflammatory factors, suggest that reducing the inflammatory response improves associated kidney damage. Although drugs used to treat psoriasis (methotrexate and cyclosporine) may induce nephrotoxicity, the impact on ESRD risk remains uncertain. Comorbidities like hypertension and diabetes may also contribute to increased CKD/ESRD risk in psoriasis patients. The findings support the consideration of psoriasis as a systemic inflammatory disorder with potentially severe renal implications.

This meta-analysis highlights the increased risk of CKD/ESRD in psoriasis patients, especially those with severe disease. Routine screening for renal insufficiency in patients with moderate to severe psoriasis is warranted for early detection and intervention. Future research should focus on clarifying the specific mechanisms linking psoriasis and renal disease and evaluating the long-term renal safety of psoriasis treatments, particularly biologics.

Limitations of this meta-analysis include the limited number of studies addressing psoriasis severity and renal outcomes, reliance on diagnostic codes from electronic health records (potentially leading to misclassification), and high heterogeneity among studies. The lack of detailed information on randomization and blinding methods in the included studies also restricts the generalizability of the findings.