High-impact clinical trials generate promisin

Results from numerous high-impact Phase 3 clinical trials that could impact kidney care will be presented in person at ASN Kidney Week 2024, October 23-27.

• Hyponatremia, or a chronically low blood salt level, is the most common electrolyte disturbance in hospitalized patients and is associated with higher risks of death and readmission. In a recent study, 2,173 hospitalized patients with hyponatremia from 9 centers in Europe were assigned either to undergo guideline-directed correction of blood salt levels or to receive routine care for hyponatremia. The primary outcome was the combined risk of death or hospital readmission within 30 days of study entry. During the study, 60.4% of patients in the target group achieved normal blood salt levels, compared with 46.2% of patients in the control group. Within 30 days, 8.6% and 13.0% of patients in the intervention group died or were readmitted to the hospital, respectively, compared with 8.5% and 14.0% of patients in control group, resulting in a combined event rate of 21.0% in the intervention. group and 22.2% in the control group. “Better correction of hyponatremia did not lead to an improvement in mortality and hospitalization rates,” said corresponding author Julie Refardt, MD, PhD, of Erasmus MC in the Netherlands. “Therefore, in hospitalized patients, hyponatremia appears to be a marker of worse outcome rather than a cause of it.”

Impact of targeted correction of hyponatremia on 30-day mortality and readmission rate

• The randomized VALIANT trial investigated the efficacy and safety of pegcetacoplan, a complement inhibitor, in adolescents and adults with native (pre-transplant) or post-transplant recurrent complement 3 glomerulopathy or primary immune complex-mediated membranoproliferative glomerulonephritis. In the study, 63 patients received pegcetacoplan and 61 received placebo for 6 months. Pegcetacoplan reduced proteinuria (increased protein in the urine, which is a sign of kidney dysfunction) by 68.3% compared to placebo. “The results were consistent among patients with different characteristics,” said corresponding author Carla M. Nester, MD, of the University of Iowa. “Furthermore, pegcetacoplan has demonstrated favorable safety in native and post-transplant populations.”

VALIANT: A Randomized, Multicenter, Double-Blind, Placebo-Controlled (PBO), Phase 3 Study of Pegcetacoplan in Patients With Recurrent Native or Post-Transplant Glomerulopathy (C3G) or Primary Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)

• Compared with placebo, semaglutide (a glucagon-like peptide 1 receptor agonist) significantly reduced the risks of major kidney outcomes, cardiovascular events, and all-cause death in adults with type 2 diabetes and chronic kidney disease (CKD ) in the FLOW study. In a recent analysis of data on 3,533 participants, investigators assessed whether kidney outcomes differed based on people’s kidney function at the start of the study. “We found that the benefit on kidney outcomes was consistent regardless of the severity of CKD at study entry,” said corresponding author Katherine R. Tuttle, MD, of the University of Washington, Seattle. “Ongoing studies are investigating the mechanisms of kidney protection by semaglutide and whether semaglutide is also safe and effective for CKD in people with type 1 diabetes or those without diabetes.”

Semaglutide reduced the risks of major kidney outcomes regardless of CKD severity in the FLOW study

• Chronic pain is common among people receiving maintenance hemodialysis for renal failure, but treatment options are limited due to the unacceptable toxicity of many pain medications. “The HOPE Consortium Trial to Reduce Pain and Opioid Use in Hemodialysis,” funded by NIH Helping to End Addiction Long Term^® Initiative (NIH HEAL Initiative^®) and administered by the National Institute of Diabetes and Digestive and Kidney Diseases, was a multicenter, randomized clinical trial of Pain Coping Skills Training, a non-pharmacological cognitive-behavioral therapy intervention designed to increase self-efficacy in pain management. The study, which enrolled 643 participants at 16 centers and 103 outpatient dialysis units, showed that the intervention had benefits on the primary outcome of pain interference (a measure of the effects of pain on activities, mood and relationships) and on several outcomes secondary. including depression, anxiety and quality of life. “Future work will focus on how best to implement this intervention on a large scale in the dialysis setting,” said corresponding author Laura M. Dember, MD, of the University of Pennsylvania Perelman School of Medicine.

Pain coping skills training for patients receiving hemodialysis: the HOPE consortium randomized clinical trial

• Arteriovenous fistulas (AVFs) are a preferred method for initial vascular access in patients requiring hemodialysis, but failure of AVF maturation may occur in some patients. In a study of 242 hemodialysis patients undergoing surgical vascular access, half of the patients were randomized to the Humacyte Acellular Tissue Engineered Vessel (ATEV), a bioengineered human tissue that can be used to repair and replace blood vessels and for access to hemodialysis. The ATEV group had higher success rates in maintaining 6-month functional patency (81% vs. 68%) and 12-month secondary patency (68% vs. 62%) compared with traditional AVF, particularly in patients with female, diabetic and obese. “These findings suggest that VTE could be a reliable option for vascular access for these subgroups at high risk of AVF failure without compromising safety,” said corresponding author Mohamad A. Hussain, MD, PhD, of Brigham Hospital and Women. “Next steps include the sponsor discussing the potential path to approval with the US Food and Drug Administration and an ongoing trial, CLN-PRO-V012, in which the use of ATEV versus AVF is being studied in dialysis patients, a large unmet need. population.”

Prospective randomized trial of acellular tissue engineering vessel of Humacyte vs. autologous arteriovenousFistula for hemodialysis access

• Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, improves kidney health in patients with CKD, but there is uncertainty about the magnitude of its effects when started after CKD has progressed to later stages. In the Dapagliflozin and Renal Surrogate Outcomes in Advanced Chronic Kidney Disease (DAPA advKD) study, 180 patients with stages 4 and 5 CKD were randomized 2:1 to dapagliflozin plus integrated CKD care or integrated CKD care. Over a median period of 1.62 years, the estimated mean glomerular filtration rate slopes were -2.24 and -3.67 mL/min/1.73 m² in the dapagliflozin and control groups, respectively, indicating a slower decline in renal function in the dapagliflozin group. The dapagliflozin group also had lower rates of kidney and cardiovascular outcomes, such as acute kidney injury and heart failure. “Our study focused on patients with advanced chronic kidney disease to test whether dapagliflozin can still benefit those with severely reduced kidney function. We found that this drug helped slow the decline in kidney function and reduced the need for dialysis or other advanced treatments,” said corresponding author Yi-Wen Chiu, MD, of Kaohsiung Medical University Hospital in Taiwan. “Our next steps are to continue to study long-term safety and efficacy in this group.”

Efficacy and safety of dapagliflozin in patients with CKD Stages 4-5

Join ASN and approximately 12,000 other kidney professionals from around the world at Kidney Week 2024 in San Diego, CA. The world’s leading nephrology meeting, Kidney Week offers attendees exciting and challenging opportunities to share knowledge, learn about the latest scientific and medical advances, and listen to engaging and challenging discussions with leading experts in the field. Early bird programs begin on October 23, followed by the Annual Meeting on October 24-27. Follow the conversation at #KidneyWk.

About ASN

Since 1966, ASN has been leading the fight to prevent, treat and cure kidney disease worldwide by educating healthcare professionals and scientists, promoting research and innovation, communicating new knowledge and supporting the highest quality patient care. ASN has almost 21,000 members corresponding to 140 countries. For more information, visit www.asn-online.org and follow us further Facebook, X, LinkedInand Instagram.

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