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.

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End-stage kidneys are known to undergo cystic transformation in patients treated with long-term hemodialysis. Little has been published, however, on the occurrence of acquired renal cystic disease (ACD) in renal transplant recipients. The available clinical and histopathological data were gathered on 22 renal transplant recipients who had undergone either necropsy or nephrectomy. None of our patients exhibited cystic changes in their donor kidneys. However, 11 patients (50%) had ACD of the native kidneys while the remaining patients lacked ACD. The duration of dialysis prior to transplantation was significantly longer and the life of the functional transplant kidney was significantly shorter in the ACD group as compared to the noncystic group. The combined duration of ESRD (dialysis + transplantation), however, was comparable in the two groups. It thus appears that the presence of a functioning renal allograft somehow retards the evolution of cystic changes in the diseased native kidneys. 1 of the patients in the ACD group exhibited superimposed multifocal clear cell carcinoma of the affected kidney, while none of the patients in the noncystic group exhibited renal neoplasm.

SUMMARY Carnosinase, the dipeptidase which hydrolyses carnosine and other histidine-containing dipeptides, was assayed in mucosal tissues of the human and of the rat gut. Kinetic properties of the intestinal enzyme were found to be similar to carnosinase of other animal tissues. Little or no activity was detected in human gastric or colonic mucosa, and the levels were lower in duodenal than jejunal mucosa. The distribution of carnosinase is similar to that of the disaccharidases. Mean carnosinase activity was 8'8 units/g weight in 15 patients with histologically normal mucosa compared with 5-7 units in five with villous atrophy. The enzyme levels increased with histological improvement of the mucosa in patients with coeliac disease on a gluten-free diet. Tolerance curves for carnosine and its constitutent amino acids showed malabsorption of the dipeptide in a patient with carnosinase deficiency. It is concluded that the intestinal mucosa has much less hydrolase activity for carnosine than for glycylglycine and other dipeptidases, and the relatively slow hydrolysis appears to be the rate-limiting step in the total absorptive process.

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