Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients.Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Results Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. ConclusionsIn the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.
Cardiac hemodynamics were assessed by right and left heart catheterizations in nine patients on hemodialysis. Results showed increased stroke work index and left ventricular work indices. Left ventricular end-diastolic pressure was elevated in all patients (markedly so in five) and did not fall with occlusion of arteriovenous communications. Cardiac output was significantly elevated, but fell to normal postocclusion. Myocardial oxygen consumption, indirectly assessed by tension time and pressure rate indices, appeared increased. Six patients died: four from complications attributed to myocardial failure without infarction, one from transplant-related complications, and one from bacterial meningitis. Five had increased cardiac weights at autopsy, but none showed infarction. This study suggests that increased cardiac work is present in chronic renal failure. Myocardial mass increases result in increased myocardial oxygen demand; however, the increased oxygen requirements may not be met because of reduced erythrocyte mass. Persistance of pressure-volume overload and severe anemia are conducive to myocardial failure.
The objective of this study was to analyze risk factors affecting mortality rates (MR) in hemodialysis patients undergoing shortened dialysis time who were regularly kinetically modeled. Over a 14-month period, 180 in-center hemodialysis patients, 54% male, 46% female, 57% Black, 39% Caucasian, and 4% Hispanic, treated with rapid high efficiency dialysis (RHED = 2-3 h, 3 times/ week) and conventional dialysis (3-4 h, 3 times/week) were studied. Median patient age was 56.7 years (16-84 years) and dialysis care ranged from 6 months to 18 years (mean ± SD = 4.0 ± 4.2 years). The patients underwent monthly urea kinetic modeling. The dialysis prescription was based upon normalizing Kt/V between 0.8 and 1.2 and the protein catabolic rate (PCRn) between 0.9 and 1.1. Thirty-three percent of the patients received recombinant human erythropoietin (r-HuEPO). The effects of various covariates, including primary diagnosis, post/predialysis BUN ratios, creatinine, albumin, calcium, phosphate, cholesterol, hemoglobin, r-HuEPO, Kt/V, and PCRn were analyzed using analysis of variance, χ2 and linear discriminant function (DF) statistical methods. Several significant factors emerged as influencing outcome. The DF analysis produced a highly statistically significant (p < 0.0001) model to predict mortality based upon certain laboratory and dialysis parameters. Further, the linear DF correctly predicted mortality rate in 86% of cases. The results of the analysis revealed an overall mortality rate of 15.6%; hospitalization rates (HR) were 1.4 ± 1.8 times/year. Length of dialysis time, i.e., dialysis times between 2 and 4 h, when adjusted for Kt/V has no correlation with MR or HR. Variables associated with survival were higher post/predialysis BUN ratios, normal Kt/V (0.8-1.2), normal albumin levels ( > 3.5 g/dl), higher postdialysis BUN, creatinine, and cholesterol levels, and use of r-HuEPO. The use of r-HuEPO when analyzed by DF significantly improved MR, 8.3% as opposed to 19.2%. It is concluded that urea kinetic modeling permits shortening dialysis times without affecting mortality or hospitalization rates, and that low postdialysis BUN, post/predialysis BUN ratios, creatinine, and albumin values are correlated with a lower chance of survival.
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