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.
To determine the impact of indomethacin on the course of uremic pericarditis we performed a prospective, double blind study in which 24 patients with endstage chronic renal failure and pericarditis randomly received indomethacin, 25 mg four times daily, (11 patients) or a placebo (13 patients) for a 3-week period. All patients received peritoneal or hemodialysis treatment concurrently with the study drug. In contrast to the placebo, indomethacin produced an immediate and sustained reduction of fever in all but one patient. On the other hand, indomethacin had no effect on the duration of chest pain (mean days +/- SE: placebo 1.4 +/- 0.6, indomethacin 5.5 +/- 3.3), duration of pericardial friction rub (placebo 10.3 +/- 1.7, indomethacin 16.0 +/- 3.8), or on the amount of pericardial effusion. Further, indomethacin did not diminish the need for invasive surgical procedures for relief of tamponade (three of 13 placebo patients, two of 11 indomethacin patients) or result in decreased mortality rate. Death (not due to pericarditis) occurred in two patients treated with indomethacin and one patient who received the placebo. In our patients pericarditis encompassed a wide spectrum ranging from a mild illness of several days duration to a painful and debilitating disease lasting weeks and requiring surgical intervention. Although the size of our population prohibits definitive conclusions, it would appear that, except for fever, the manifestations and natural history of this illness are unaffected by indomethacin.
Peripheral mononeuropathies may complicate distal arteriovenous fistulas for chronic renal dialysis. We observed three diabetic patients who developed pain, paresthesias, and weakness in the distribution of the median, ulnar, and radial nerves shortly after construction of proximal brachial artery-antecubital vein fistulas. EMG confirmed multiple distal nerve injuries. All three patients improved after shunt banding or ligation. Twenty additional patients with proximal shunts were examined for risk factors for brachial neuropathy. Although all patients had severe atherosclerosis and many had polyneuropathy, we identified no predictive risk factors other than diabetes.
A previously asymptomatic carrier of hepatitis B virus receiving chronic hemodialysis developed acute delta hepatitis. The patient regularly received dialysis treatments on the same machine as a parenteral drug abuser with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis whose serum was strongly positive for delta antibody. The drug abuser had a major bleeding episode that caused extensive environmental contamination 3 months before onset of illness in the index patient. No other patients receiving dialysis or staff members had evidence of delta infection. A surgeon previously infected with hepatitis B from the same parenteral drug abuser also had delta antibody. Testing for delta virus is indicated for both HBsAg-positive parenteral drug abusers and patients with hemophilia receiving chronic hemodialysis. All patients who are HBsAg- and delta-positive should receive dialysis separately from patients who are HBsAg-positive and delta-negative. Susceptible patients on dialysis and staff should receive hepatitis B vaccine to protect against both hepatitis B and delta virus infection.
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