Peripheral Artery Disease: Its Adverse Consequences With and Without CKD

Abstract

Rationale & objectives: Chronic kidney disease (CKD) is a potent risk factor for macrovascular disease and death. Peripheral artery disease (PAD) is more common in patients with CKD and is associated with lower-limb complications and mortality. We sought to compare the prevalence of PAD in and outside the setting of kidney disease and examine how PAD affects the risk for adverse health outcomes, specifically lower-limb complications, cardiovascular events, and survival.

Study design: Retrospective cohort study.

Setting & participants: 453,573 adult residents of Manitoba with at least 1 serum creatinine measurement between 2007 and 2014.

Exposure: PAD defined by hospital discharge diagnosis codes and medical claims.

Outcomes: All-cause mortality, cardiovascular events, and lower-limb complications, including foot ulcers and nontraumatic amputations.

Analytical approach: Survival analysis using Cox proportional hazards models.

Results: The prevalence of PAD in our study population was 4.5%, and patients with PAD were older, were more likely to be male, and had a higher burden of comorbid conditions, including diabetes and CKD. PAD was associated with higher risks for all-cause mortality, cardiovascular events, and lower-limb complications in patients with estimated glomerular filtration rate (eGFR) ≥ 60mL/min/1.73m², those with CKD GFR categories 3 to 5 (G3-G5), and those treated by dialysis (CKD G5D). Although HRs for PAD were lower in the CKD population, event rates were higher as compared with those with eGFR≥60mL/min/1.73m². In particular, compared with patients with eGFR≥60mL/min/1.73m² and without PAD, patients with CKD G5D had 10- and 12-fold higher risks for lower-limb complications, respectively (adjusted HRs of 10.36 [95% CI, 8.83-12.16] and 12.02 [95% CI, 9.58-15.08] for those without and with PAD, respectively), and an event rate of 75/1,000 patient-years.

Limitations: Potential undercounting of PAD and complications using administrative codes and the limited ability to examine quality-of-care indicators for PAD.

Conclusions: PAD is more common in patients with CKD G3-G5 and G5D compared with those with eGFR≥60mL/min/1.73m² and frequently leads to lower-limb complications. Medical interventions and care pathways specifically designed to slow or prevent the development of lower-limb complications in this population are urgently needed.

Keywords: Epidemiology; arteriolosclerosis; cardiovascular disease (CVD); chronic kidney disease (CKD); complications; dialysis; estimated glomerular filtration rate (eGFR); foot ulcer; lower-limb amputation; lower-limb complication; mortality; mortality/survival; nephrology and kidney; peripheral artery disease (PAD); renal function; serum creatinine (Scr).