Impact of deteriorated calcium-phosphate homeostasis on amputation-free survival after endovascular revascularization in patients with critical limb ischemia on hemodialysis

Abstract

Patients on hemodialysis (HD) have abnormalities of calcium-phosphate (CaP) homeostasis and high CaP product contributes to atherosclerosis pathogenesis and adverse events. Patients on HD with critical limb ischemia (CLI) are at risk for major amputation and death because of advanced systemic atherosclerotic disease. The aim of this study was to evaluate the relationship between CaP product and amputation-free survival (AFS) in CLI after endovascular treatment (EVT). We retrospectively analyzed 221 CLI patients on HD. In Kaplan-Meier analysis, AFS was significantly lower in patients with CaP product ⩾ 55 mg(2)/dL(2) compared to those with CaP product<55 mg(2)/dL(2) (54.3% vs 78.5%, p = 0.002). However, neither serum phosphate nor calcium levels were individually associated with AFS. In multivariate analysis, CaP product ⩾ 55 mg(2)/dL(2) was an independent predictor for AFS in CLI patients on HD (hazard ratio, 3.03; 95% confidence interval, 1.78-5.15; p-value < 0.001). We concluded abnormal CaP homeostasis was associated with lower AFS after EVT in CLI patients on HD, and can serve for their risk stratification.

Calcium‐phosphate product and its impact on mortality in hospitalized patients

“…[33][34][35][36][37] In addition, elevated CaP levels have also been associated with insulin resistance, diabetes 38,39 and cardiovascular events. 6,10,[12][13][14][15][16][17][18][19][20][21] This is consistent with our finding of high admission serum CaP levels among patients with an admission diagnosis of cardiovascular disease. Among patients with trauma, Kovar et al recently conducted a cohort study of 577 patients with fractures of the proximal femur to assess the impact of CaP levels on patient outcomes.…”

“…High CaP levels may place patients at higher risk of acute kidney injury (AKI) via hypercalcaemia related AKI and acute phosphate nephropathy, both associated with significant morbidity, mortality and healthcare expenditure . In addition, elevated CaP levels have also been associated with insulin resistance, diabetes and cardiovascular events . This is consistent with our finding of high admission serum CaP levels among patients with an admission diagnosis of cardiovascular disease.…”

“…Although the role of CaP as an independent risk factor for mortality and morbidity is controversial, 26 a number of epidemiologic data have demonstrated correlations between CaP and both cardiovascular outcomes and mortality. 6,10,[12][13][14][15][16][17][18][19][20][21]27 Among ESRD patients on dialysis, 6 elevated CaP levels are associated with significantly increased cardiovascular complications and mortality risk. 28 CaP derangements are also considered as a marker of renal osteodystrophy in CKD and ESRD patients.…”

“…Thus, our study population might not be generalizable to other patient populations. Third, while there have been concerns regarding systemic ectopic calcification among patients with elevated CaP levels, 13,[18][19][20][21] exceeding the solubility product of the plasma concentrations of Ca 2+ and HPO 4 has never been clearly demonstrated to produce ectopic CaP deposition in vivo. 26,42,43 Hence, the association between high hospital mortality and elevated CaP could be due to other underlying mechanisms as discussed above, such as an increased AKI risk.…”

“…Disturbances of calcium‐phosphate (CaP) metabolism has been shown to be positively associated with worse outcomes not only in patients with chronic kidney disease (CKD) and end‐stage renal disease (ESRD), but also in those with diabetes, stroke and cardiovascular diseases . Elevated CaP concentrations have further been associated with higher risks of atherosclerosis, cardiovascular events and systemic ectopic calcification . However, little is known about the impact of admission CaP on risk of in‐hospital mortality in the general hospitalized population.…”