Peripheral Artery Disease: Its Adverse Consequences With and Without CKD.

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.

Safety of Intravenous Iron in Dialysis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: The safety of intravenous iron dosing in dialysis is uncertain. Higher-dose intravenous iron may be associated with a higher risk of infections, cardiovascular events, hospitalizations, and mortality. This systematic review aimed to determine the safety of higher-dose versus lower-dose intravenous iron, oral iron, or no iron supplementation in adult patients treated with dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We searched Medline, EMBASE, Cochrane library, and CINAHL from inception to January 6, 2017 for randomized, controlled trials and observational studies comparing higher-dose intravenous iron with lower-dose intravenous iron, oral iron, or no iron in patients treated with dialysis that had all-cause mortality, infection, cardiovascular events, or hospitalizations as outcomes. RESULTS: Of the 2231 eligible studies, seven randomized, controlled trials and 15 observational studies met inclusion criteria. The randomized, controlled trials showed no association between higher-dose intravenous iron (>400 mg/mo for most studies) and mortality (six studies; n=970; pooled relative risk, 0.93; 95% confidence interval, 0.47 to 1.84; follow-up ranging from 35 days to 26 months) or infection (four studies; n=743; relative risk, 1.02; 95% confidence interval, 0.74 to 1.41). The observational studies showed no association between higher-dose intravenous iron (>200 mg/mo for most studies) and mortality (eight studies; n=241,408; hazard ratio, 1.09; 95% confidence interval, 0.98 to 1.21; follow-up ranging from 3 to 24 months), infection (eight studies; n=135,532; pooled hazard ratio, 1.13; 95% confidence interval, 0.99 to 1.28), cardiovascular events (seven studies; n=135,675; hazard ratio, 1.18; 95% confidence interval, 0.90 to 1.56), or hospitalizations (five studies; n=134,324; hazard ratio, 1.08; 95% confidence interval, 0.97 to 1.19). CONCLUSIONS: Higher-dose intravenous iron does not seem to be associated with higher risk of mortality, infection, cardiovascular events, or hospitalizations in adult patients on dialysis. Strength of this finding is limited by small numbers of participants and events in the randomized, controlled trials and statistical heterogeneity in observational studies.