Clinical journal of the American Society of Nephrology : CJASN
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Clin J Am Soc Nephrol · Jul 2008
Randomized Controlled Trial Multicenter StudyPharmacokinetic and pharmacodynamic profiles of extended dosing of epoetin alfa in anemic patients who have chronic kidney disease and are not on dialysis.
Emerging evidence suggests that epoetin alfa can be administered at extended intervals of up to 4 wk. This open-label, randomized study was performed to characterize the pharmacokinetic and pharmacodynamic profiles of four dosing regimens of epoetin alfa administered subcutaneously in anemic patients who had chronic kidney disease and were not on dialysis. ⋯ Extended dosing interval regimens of epoetin alfa yielded modest pharmacokinetic differences but a similar pharmacodynamic response, suggesting that less frequent, higher dosages of epoetin alfa may be as effective as the current three-times-weekly regimen in anemic patients who have chronic kidney disease and are not on dialysis.
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Clin J Am Soc Nephrol · Jul 2008
Lessons for successful study enrollment from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study.
Design elements of clinical trials can introduce recruitment bias and reduce study efficiency. Trials involving the critically ill may be particularly prone to design-related inefficiencies. ⋯ The Acute Renal Failure Trial Network Study's enrollment efficiency compared favorably with previous intensive care unit intervention trials and supports the representativeness of its enrolled population. Impediments to informed consent highlight the need for nontraditional acquisition methods. Restrictive enrollment windows may hamper recruitment but can be effectively modified. The low rate of physician refusal acknowledges clinical equipoise in the study design. Underlying comorbidities are important design considerations for future trials that involve the critically ill with acute kidney injury.
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Clin J Am Soc Nephrol · Jul 2008
ReviewApproaches to testing new treatments in autosomal dominant polycystic kidney disease: insights from the CRISP and HALT-PKD studies.
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease characterized by a prolonged subclinical course of gradual renal cyst expansion, resulting in massively enlarged kidneys and renal failure by the fifth to sixth decade. Renal cyst expansion results in intrarenal ischemia and activation of the renin-angiotensin-aldosterone system (RAAS) and relates to the development and maintenance of hypertension in ADPKD. Hypertension relates to disease progression in ADPKD with regard to renal volume, proteinuria, cardiovascular complications, and progression to end-stage renal disease. ⋯ PKD1 status, male gender, hypertension, reduced renal blood flow, and proteinuria are associated with increased renal volume and change in renal volume over time. HALT-Polycystic Kidney Disease (HALT-PKD) is designed to test whether blockade of RAAS and/or rigorous blood pressure control play a role in slowing renal progression during early (using magnetic resonance imaging methods developed in CRISP) and during late (using measures, including composite of time to doubling of serum creatinine, onset of end-stage renal disease, or death) phases in ADPKD. Findings from CRISP and the rationale for interventions in ADPKD are described, and the design of the HALT-PKD clinical trial is outlined.
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Calciphylaxis, or calcific uremic arteriolopathy, is a well-described entity in end-stage kidney disease and renal transplant patients; however, little systematic information is available on calciphylaxis from nonuremic causes. This systematic review was designed to characterize etiologies, clinical features, laboratory abnormalities, and prognosis of nonuremic calciphylaxis. ⋯ Calciphylaxis should be considered while evaluating skin lesions in patients with predisposing conditions even in the absence of end-stage kidney disease and renal transplantation. Nonuremic calciphylaxis is reported most often in white women. Mineral abnormalities that are invoked as potential causes in calcific uremic arteriolopathy are often absent, suggesting that heterogeneous mechanisms may contribute to its pathogenesis. Nonuremic calciphylaxis is associated with high mortality, and there is no known effective treatment.
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Clin J Am Soc Nephrol · Jul 2008
Ascertainment and epidemiology of acute kidney injury varies with definition interpretation.
Differences in defining acute kidney injury (AKI) may impact incidence ascertainment. We assessed the effects of different AKI definition interpretation methods on epidemiology ascertainment. ⋯ AKI definition variation causes interstudy heterogeneity. AKI definition should be standardized so that results can be compared across studies.