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.

Background: It is critical to preserve residual renal function (RRF) in peritoneal dialysis (PD), as RRF is associated with lower morbidity and mortality. There is no uniform definition of RRF, and rapidly declining RRF has rarely been studied and predominately limited to single factor analysis and not corrected for lead-time bias. Methods: An observational study in 71 incident PD patients. RRF was defined as urine output (UO) ≥500 ml/day and renal glomerular filtration rate (rGFR) ≥2 ml/min/1.73 m², rapid declining RRF as UO <500 ml/day and rGFR <2 ml/min/1.73 m² occurring within 6 months which were separately evaluated. Independent risk factors associated with rapid RRF decline were identified while correcting for lead-time bias. Results: RRF declined rapidly by both definitions in 65% patients 2.5 years after PD start. Both definitions of RRF decline were consistent in 96%. Nephrotoxic drugs, renal transplant failure and absent angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) were independent risk factors associated with rapidly declining RRF defined both by definitions, intravascular radiocontrast additionally for UO decline. Conclusions: Most PD patients demonstrated rapid RRF decline, independent of its definition. Both definitions are highly consistent and interchangeable. Nephrotoxic drugs and radiocontrast were identified as risk factors of acute, absent ACEI or ARB, and renal transplant failure of chronic renal injury.