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.

The pharmacokinetics of meropenem were studied in nine anuric critically ill patients treated by continuous venovenous hemodiafiltration. Peak levels after infusion of 1,000 mg over 30 min amounted to 103.2 ± 45.9 μg/ml, and trough levels at 12 h were 9.6 ± 3.8 μg/ml. A dosage of 1,000 mg of meropenem twice a day provides plasma drug levels covering intermediately susceptible microorganisms. Further reductions of the dosage might be appropriate for highly susceptible bacteria or when renal replacement therapies with lower clearances are applied.

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This report is about a 23-year-old man who required hemodialysis in connection with an acute renal failure resulting from uric acid nephropathy without hyperuricemia. After recovering renal function he showed extreme hypouricemia (0.1-0.3 mg/dl) and elevated uric acid clearance (100-300 ml/min). The fractional excretion of uric acid (Cua/Ccr) could be suppressed by oral pyrazinamide and enhanced by probenecid. As no other renal tubular or metabolic abnormalities were detected, it is suggested that a markedly increased renal tubular urate secretion was responsible for the hypouricemia and also for the rare side-effect of an uric acid nephropathy in this patient.

Loop diuretics increase the fractional excretion of volume, sodium, potassium, chloride and calcium in all stages of renal failure, and their potency is directly correlated with these excretory activities. Tubular secretion of loop diuretics in renal failure is impaired both by reduced renal blood flow and by reduced activity of the tubular carrier system. For these reasons, high concentrations of diuretics in the peritubular capillaries are necessary to guarantee delivery of sufficient drug to their site of action in the ascending limb of the loop of Henle. Piretanide and furosemide have a constant extrarenal elimination and thus accumulate in renal failure. Decreased renal excretion of bumetanide is compensated by hepatic elimination and hence bumetanide does not accumulate. Elimination of torasemide is also independent of its renal excretion. Thus in renal failure, torasemide is the only loop diuretic in which the plasma concentration is strictly dose dependent. Loop diuretics follow a number of different metabolic pathways, but this may not be clinically relevant.