Results of high-impact clinical trials could improve kidney-related medical care

American Society of Nephrology (ASN)Nov 21 2016

The results of numerous high-impact clinical trials that could affect kidney-related medical care will be presented at ASN Kidney Week 2016, November 15-20 at McCormick Place in Chicago, IL.

•In the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial, 9340 patients with type 2 diabetes and high cardiovascular risk were randomized liraglutide (a long-acting glucagon-like peptide-1 analog) or placebo. Over a median follow-up of 3.84 years, a composite outcome of kidney dysfunction or death due to kidney disease occurred in fewer participants treated with liraglutide (268 of 4668) than with placebo (337 of 4672), translating to a 21% reduced risk. "Liraglutide in addition to standard of care therapy reduced the progression of diabetic nephropathy," the study's investigators concluded.
Liraglutide and Renal Outcomes in Type 2 Diabetes: Results of the LEADER Trial

•In a trial that involved 406 adult live donor/recipient kidney transplant pairs, remote ischemic preconditioning (RIPC), a safe and virtually cost-free intervention, resulted in sustained improvement in kidney function after transplantation, reaching 13% by 5 years. "Given the resultant clinical, economic, and quality of life implications, we recommend that RIPC is adopted into routine care for these patients," stated the trial's investigators. The intervention involves reducing blood flow in both the donor and recipient as a preconditioning step before surgery, which can involve more significant and prolonged blood flow reductions. A blood pressure cuff placed on the upper arm that is inflated for short periods of time activates a reflex that makes internal organs more resistant to the harmful effects of low blood flow that occurs during transplantation.
Remote ischaemic preconditioning (RIPC) leads to sustained improvement in allograft function following live donor (LD) kidney transplantation: 5 year follow up in the REnal Protection Against Ischaemia Reperfusion in transplantation (REPAIR) study

•A study that randomized 615 kidney transplant recipients to receive either basiliximab induction with low dose tacrolimus, mycophenolate mofetil, and steroid maintenance therapy (arm A), or rapid corticosteroid withdrawal on day 8 (arm B), or rapid corticosteroid withdrawal on day 8 following rabbit antithymocyte globulin (ATG) instead of basiliximab (arm C), rejections at 12 months were similar in all groups (11.2%, 10.6%, and 9.9%, respectively). As a secondary endpoint, rapid steroid withdrawal reduced posttransplantation diabetes in arm B to 23.9% and in arm C to 22.7% compared with standard arm A with 39.2%. "Rabbit ATG failed to show superiority over basiliximab induction for the prevention of biopsy proven acute rejections after rapid steroid withdrawal within one year after renal transplantation. Nevertheless, rapid steroid withdrawal after induction therapy for patients with a low immunologic risk profile can be achieved without any loss of efficacy and is highly advantageous in regard to posttransplantation diabetes mellitus incidence," the researchers wrote. Rabbit ATG, an infusion of rabbit-derived antibodies against human T cells, is used in the prevention and treatment of acute rejection in organ transplantation. Basiliximab is a monoclonal antibody that is an interleukin-2 receptor antagonist.
Rabbit-ATG or Basiliximab Induction for Rapid Steroid Withdrawal after Renal Transplantation: an Open-label, Multicentre, Randomized Controlled Trial

•In a trial of 99 individuals on hemodialysis, lower sodium levels in patients' dialysate solutions did not effectively reduce their left ventricular mass, an indicator of heart health. Enlarged left ventricles, or left ventricular hypertrophy, contributes to premature cardiovascular mortality in dialysis patients. Other studies have shown benefits (such as reduced blood pressure) to lowering dialysate sodium concentrations.
The Sodium Lowering In Dialysate (SoLID) Trial: a Randomised Controlled Trial of Low Versus Standard Dialysate Sodium Concentration (DNa) During Hemodialysis (HD) for Regression of Left Ventricular (LV) Mass

•In a trial of 265 patients with lupus nephritis, 32.6% of patients receiving low dose voclosporin and 27.3% of patients receiving high dose voclosporin achieved complete remission at 24 weeks, compared with 19.3% of patients receiving placebo. Also, partial remissions were more common in patients receiving either low or high dose voclosporin than in those receiving placebo. Side effects were higher in the patients treated with voclosporin, consistent with increased immunosuppression. "These favorable data will help plan subsequent studies of voclosporin in lupus nephritis," the study's investigators wrote. Voclosporin is a novel calcineurin inhibitor, a type of immunosuppressant.
AURA-LV: Successful treatment of active lupus nephritis with Voclosporin

•In the phase 2 DUET trial that included 96 patients with focal segmental glomerulosclerosis (FSGS), which is characterized by scarring of the kidneys, sparsentan, a dual angiotensin II (Ang II) and endothelin type A receptor antagonist, reduced urinary protein excretion to a greater extent than blockade of Ang II alone. "In accord with prior studies in essential hypertension, sparsentan appears to be safe and well tolerated in patients with FSGS," noted the study's investigators.
Efficacy and Safety of Sparsentan, a Dual Angiotensin II (Ang II) and Endothelin (ET) Type A Receptor Antagonist, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Phase 2 Trial (DUET)