Finerenone Improves Urinary-Creatinine Ratio
For patients with diabetic nephropathy who receive an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB), the addition of the medication finerenone resulted in improvement in albuminuria compared with placebo in a recent study.
George L. Bakris, MD, and colleagues designed the study to evaluate the safety and efficacy of varying oral doses of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, given for 90 days compared with placebo.
The randomized, double-blind, placebo-controlled, parallel-group study was conducted at 143 sites in 23 countries. The recruitment period was June 2013 through February 2014; the study was completed in August 2014. The researchers screened a total of 1501 patients; of those, 823 were randomized and 821 received the study drug.
Patients were randomized to either once-daily finerenone (1.25 mg/d, n=96; 2.5 mg/d, n=92; 5 mg/d, n=100; 7.5 mg/d, n=97; 10 mg/d, n=98; 15 mg/d, n=125; and 25 mg/d, n=119) or matching placebo (n=94) for 90 days. The primary outcome of interest was the ratio of the urinary albumin-creatinine ratio (UACR) at day 90 compared with baseline. Safety end points included changes from baseline in serum potassium and estimated glomerular filtration rate (eGFR).
Mean age of participants was 64.2 years and 78% were male. Finerenone showed a dose-dependent reduction in UACR: in the finerenone 7.5-, 10-. 15-, and 20-mg/d groups, there was a reduction in the placebo-corrected mean ratio of the UCAR at day 90 relative to baseline (0.79, P=.004; 0.76, P=.001; 0.67, P=.001; and 0.62, P=<.001, respectively).
There were no differences in the incidence of prespecified secondary outcome of eGFR decrease of ≥30% or in incidences of adverse events or serious adverse events between the finerenone and placebo groups.
“Among patients with diabetic nephropathy, most receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, the addition of finerenone compared with placebo resulted in improvement in the urinary albumin-creatinine ratio. Further trials are needed to compare finerenone with other active medications,” the researchers said.
Efficacy and Safety of the NxStage System One™ Examined
American Journal of Kidney Diseases. 2015;65(5):A1-A2.
At the NKF 2015 Spring Clinical Meetings, Brigitte Schiller, MD and Brent W. Miller, MD, presented results of an open-label, prospective, two-treatment period crossover, non-inferiority study designed to assess the safety and efficacy of low dialysate volume nocturnal hemodialysis (NHD) therapy in the home setting using the NxStage System One™. Study results were presented during a late breaking abstracts session.
The study included patients who were undergoing home short daily hemodialysis (SDHD). Participants were enrolled and followed for 8 weeks on their prescribed SHDH, and trained and transitioned to NHD over the following 4 weeks. They were followed for another 8 weeks at home. Of the 58 patients enrolled, 39 completed the study protocol.
Intent-to-treat patients who performed at least one NHD treatment had a post-treatment weight of 94 kg and were prescribed 26 L of dialysate at blood flow rate of 271 mL/min for 407 minutes of therapy, 6800 units of heparin, and 1.8 L of fluid removed per treatment.
Comparing treatment parameters for NHD and SDHD, therapy duration (407 vs 168 minutes), blood flow rate (271 vs 466 mL/min), and total heparin delivered (6800 vs 4000 units/treatment) were substantially different. NHD was associated with a significant increase in standard Kt/V (stdKt/V) (2.48 on NHD vs 2.24 on SHDH. P=.006) and improved serum phosphorus (4.6 vs 5.4 mg/dL, P<.001).
The rate of adverse events (6.9 event/100 treatments on NHD vs 8.2 events/100 treatments during the transition period vs 8.3 events/100 treatments on SHDH) was comparable in all study phases.
“Safety and efficacy of NHD therapy at home using the NxStage System One are comparable to SDHD. NHD therapy using the same dialysate volume as SDHD resulted in increased stdKt/V and improved phosphorus control,” the researchers said.
Associations Between Hyperuricemia and CKD
Nephrourol Mon. 2015 May 23;7(3):e27233. doi:10.5812.numonthly.
Uric acid is the poorly soluble circulating end product of the purine nucleotide metabolism. Hyperuricemia, frequently seen in patients with chronic kidney disease (CKD), is associated with a decline in glomerular filtration rate (GFR). Researchers in China, led by Om Shankar Prasad Sah, MD, recently published a review outlining the associations between hyperuricemia and CKD in the journal Nephro-Urology Monthly.
The authors defined hyperuricemia as a serum uric acid level >7.0 mg/dL in males and >6.0 mg/dL in females. They defined CKD as kidney damage or a GFR <60 mL/min/1.73 m2 for ≥3 months, regardless of the cause. Hyperuricemia in patients with CKD may occur due to decreased excretion, increased production, or a combination of both mechanisms.
The authors said that the causes for hyperuricemia in overproducers may be either exogenous or endogenous. CKD is a global health problem because of its high prevalence and the associated increase in the risk of end-stage renal disease, cardiovascular disease, and premature death. Risk factors for CKD include obesity and the metabolic syndrome, which are both strongly associated with hyperuricemia, due in part to insulin resistance and the effects of insulin to reduced the urinary urate excretion.
Patients with recurring bouts of gout or hyperuricemia should have blood tests and joint fluid tests to determine whether medications taken are effective. Interventional studies are useful in further defining the role of hyperuricemia in CKD.
“Although many evidence-based studies have suggested that uric acid itself may harm patients with CKD by increasing inflammation and CKD progression, the issue is still a matter of controversy. Special attention should be paid to specific contraindications to certain drugs and the possibility of infectious arthritis,” the authors said.
Pharmacological Management of Hyperuricemia and Gout after Kidney Transplant
Progress in Transplantation. 2015;25(3):263-270.
In an article in the journal Progress in Transplantation, Peter M. Sullivan, PharmD, and colleagues, describe the pharmacological management of hyperuricemia and gout in solid-organ transplant patients.
Hyperuricemia is a common comorbid condition in as many as 28% of patients who have undergone kidney transplantation. Patients with hyperuricemia are at increased risk for active gout flare-ups due to transplant-specific factors that include impaired renal function, chronic contributing pharmacotherapy (calcineurin inhibitors and diuretics, for example), and associated comorbid conditions.
Post-transplant treatment may be complicated by drug-drug interactions, ongoing renal impairment, and the toxic effects of drugs with the use of first-line recommended agents. Dose modifications of historic agents and newer pharmacotherapeutic options are among the therapeutic options available for kidney transplant recipients.
The Kidney Disease Improving Global Outcomes guidelines of 2009 address the management of hyperuricemia and gout, but new data and treatment options have emerged since then. In this article, the authors reviewed current strategies for the management of hyperuricemia and acute and chronic gout, including the use of novel agents such as urate oxidases, interleukin 1 inhibitors, and human urate transporter 1 inhibitors as well as alternative immunosuppressive therapy strategies.