Systematic Review and Meta-Analysis of the Effect of Chronic Kidney Disease on Amputation and Mortality in Patients With Peripheral Artery Disease

Background The influence of presence/absence chronic kidney disease (CKD) on the clinical course and outcomes of patients with peripheral artery disease (PAD) has not been extensively investigated. We aimed to measure the relative rates of amputation and mortality in individuals with different stages of CKD compared to those without CKD, and to assess whether revascularization treatments might reduce these risks for PAD patients. Methods We conducted a thorough search of the literature across multiple databases, including MEDLINE, EMBASE, the Cochrane Library, and Web of Science. The risk of bias assessment was assessed using the Newcastle-Ottawa Quality Assessment scale. All studies that reported relevant results in PAD patients were included. The statistical analysis involved the calculation of pooled prevalence estimates using a random-effects model, along with the performance of subgroup analyses and meta-regression to evaluate heterogeneity. Results We included fourteen observational studies encompassing a total of 554,270 patients with PAD that met the predefined inclusion criteria. Eleven studies reported on amputation rates in patients with and without CKD. Our analysis showed that CKD patients faced nearly double the risk of amputation compared to those without CKD (1.94; 1.90 to 1.97; P < 0.001; I 2 = 96.8%, P < 0.001). Additionally, a significant rise in mortality risk among CKD patients was observed across 14 studies, in comparison to patients without CKD (OR 2.04; 95% CI 1.99 to 2.08; P < 0.001; I 2 = 78.6%, P < 0.001). Moreover, we observed a graded increase in both amputation and mortality rates with the progression of CKD severity. In terms of therapeutic interventions, the potential of revascularization procedures to lower mortality and amputation rates appeared to be attenuated in the presence of CKD in PAD patients. Meta-regression analysis revealed that only a baseline diabetic population exceeding 50% exhibited a borderline association with amputation rate (β 0.422; 95% CI [-0.189; 1.035]) after adjusting for other covariates, including sample size, percentage of patients with critical limb ischemia, and follow-up time. Conclusion The significant association noted between CKD and risk of amputation and mortality with PAD, with this risk intensifying as renal insufficiency progresses. Furthermore, the effectiveness of revascularization procedures in reducing amputation and mortality rates is diminished in patients with PAD who also have CKD.