A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects.

AIM: Dolutegravir (DTG; S/GSK1349572) is under clinical development as a once daily, unboosted integrase inhibitor for the treatment of HIV infection. The effect of DTG on glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and creatinine clearance (CLcr ) was evaluated in 34 healthy volunteers. METHODS: Subjects received DTG 50 mg (once daily or twice daily) or placebo for 14 days. GFR was measured by iohexol plasma clearance, ERPF was assessed by para-aminohippurate plasma clearance and CLcr was measured by 24 h urine collection. RESULTS: All treatments were generally well tolerated. A modest decrease (10-14%) in CLcr was observed, consistent with clinical study observations. DTG 50 mg once daily and twice daily had no significant effect on GFR or ERPF compared with placebo over 14 days in healthy subjects. CONCLUSIONS: These findings support in vitro data that DTG increases serum creatinine by the benign inhibition of the organic cation transporter 2, which is responsible for tubular secretion of creatinine.

Comparison of the safety, tolerability, and pharmacokinetic profile of a single oral dose of pitavastatin 4 mg in adult subjects with severe renal impairment not on hemodialysis versus healthy adult subjects.

Pitavastatin is a novel statin recently approved in the United States as an adjunctive therapy with diet to reduce elevated total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and triglycerides and to increase high-density lipoprotein cholesterol. This open-label study enrolled 16 subjects as follows: group A: 8 adult subjects with severe renal impairment who were not on hemodialysis (estimated glomerular filtration rate of 15-29 mL/min/1.73 m2) and group B: 8 healthy adult subjects (estimated glomerular filtration rate ≥80 mL/min/1.73 m2). On day 1, the subjects received a single oral dose of pitavastatin 4 mg and remained in the clinic on days 1-3 for safety and pharmacokinetic assessments. Comparing group A with group B, the geometric mean ratio of AUC(0-inf) for pitavastatin was 1.36 (90% confidence interval, 0.88-2.11). For Cmax, the corresponding ratio was 1.18 (90% confidence interval, 0.68-2.02). There were no severe treatment-emergent adverse events (AEs), serious AEs, deaths, or treatment-emergent AEs leading to study drug discontinuation. A single dose of pitavastatin 4 mg was safe and well tolerated by the subjects in this study with severe renal impairment, who were not on hemodialysis.

Donor exchange programs in kidney transplantation: rationale and operational details from the north central donor exchange cooperative.

The increasing need for kidney transplants has led to innovations such as donor exchange programs. These programs offer transplant recipients with incompatible donors an opportunity to receive a compatible kidney. They also provide an alternative to costly desensitization protocols that have unproven long-term outcomes. Donor exchange programs have multiple options, including simple 2-pair exchanges, more complicated domino exchanges, or chain donations. The United States currently is limited by regional programs that provide for kidney donor exchanges. However, with the increasing public interest in and need for kidney transplants, general nephrologists will be approached with questions about these donor exchange programs. The goal of this review is to discuss donor exchange programs, including their role in expanding the donor pool, various types of exchanges, regional centers that provide these programs, and the process involved in patient enrollment. General knowledge of donor exchange programs will help providers in discussing options with patients approaching end-stage kidney disease and transplant.

Impact of congestive heart failure, chronic kidney disease, and anemia on survival in the Medicare population.

BACKGROUND: Congestive heart failure (CHF) is a common clinical problem in the elderly, yet few studies have focused on this population. In addition, information on mortality rates conferred by chronic kidney disease (CKD) and anemia in elderly patients with CHF is lacking. METHODS AND RESULTS: A cohort of 1,136,201 patients in the 5% Medicare database, excluding those with end-stage renal disease (ESRD), was identified for a 2-year period (1996-1997). Subgroups with CHF, CKD, and anemia were identified. The effect of each disease as an independent predictor of mortality was examined in a comorbidity-adjusted Cox model, with patients followed for 2 years and censored for death or ESRD. In the study population, 61% were women; 89% were white and 7% were black. Mean +/- SD age was 76.5 +/- 6.9 years. The annual mortality rate for patients with no CHF, CKD, or anemia was 4%. Anemia was associated with an annual mortality of 8%, which was the same as CKD (8%). The annual mortality for CHF was 13%. The highest annual mortality was found in patients with all 3 comorbid conditions; mortality in these patients was 23%. CONCLUSIONS: Elderly CHF patients are at high risk of death; this risk is magnified in the presence of CKD and anemia.