Several high-impact phase 3 clinical trials presented at ASN Kidney Week 2024 reveal promising advancements in kidney-related medical care. The studies address a range of conditions, from hyponatremia to chronic kidney disease, and explore novel therapeutic interventions.
Targeted Hyponatremia Correction Fails to Improve Outcomes
A randomized trial involving 2,173 hospitalized patients with hyponatremia across nine European centers assessed whether targeted correction of blood salt levels, according to guidelines, improved outcomes compared to routine care. While the targeted group achieved normal blood salt levels more frequently (60.4% vs. 46.2%), there was no significant difference in the combined risk of death or rehospitalization within 30 days. The event rate was 21.0% in the intervention group and 22.2% in the control group. According to Dr. Julie Refardt, "Better correction of hyponatremia did not lead to an improvement in mortality and hospitalization rates. Therefore, in hospitalized patients, hyponatremia seems to be rather a marker of worse outcome instead of its cause."
Pegcetacoplan Reduces Proteinuria in Glomerulopathy Patients
The VALIANT trial investigated the efficacy and safety of pegcetacoplan, a complement inhibitor, in adolescents and adults with native or post-transplant recurrent complement 3 glomerulopathy or primary immune complex–mediated membranoproliferative glomerulonephritis. Sixty-three patients received pegcetacoplan, and 61 received a placebo for six months. Pegcetacoplan reduced proteinuria by 68.3% compared with the placebo. Dr. Carla M. Nester noted, "The results were consistent across patients with different characteristics. In addition, pegcetacoplan demonstrated favorable safety across native and post-transplant populations."
Semaglutide Benefits Kidney Outcomes Irrespective of CKD Severity
An analysis of the FLOW trial data, which included 3,533 participants, examined whether kidney outcomes with semaglutide differed based on the severity of chronic kidney disease (CKD) at the trial's start. Semaglutide, a glucagon-like peptide 1 receptor agonist, significantly reduced the risks of major kidney outcomes, cardiovascular events, and death from any cause in adults with type 2 diabetes and CKD. "We found that the benefit on kidney outcomes was consistent regardless of CKD severity at study entry," said Dr. Katherine R. Tuttle. Ongoing studies are investigating the mechanisms of kidney protection by semaglutide and whether it is safe and efficacious for CKD in persons with type 1 diabetes or those without diabetes.
Pain Coping Skills Training Improves Outcomes in Hemodialysis Patients
The "HOPE Consortium Trial to Reduce Pain and Opioid Use in Hemodialysis" evaluated Pain Coping Skills Training, a non-pharmacologic cognitive behavioral therapy intervention, in 643 participants across 16 centers. The intervention improved pain interference, depression, anxiety, and quality of life. Dr. Laura M. Dember stated, "Future work will focus on how to best broadly implement this intervention in the dialysis setting."
Acellular Tissue Engineered Vessel Shows Promise for Hemodialysis Access
In a trial of 242 patients undergoing surgical vascular access creation for hemodialysis, half were randomized to receive Humacyte's acellular tissue-engineered vessel (ATEV). The ATEV group had higher success rates in maintaining 6-month functional patency (81% versus 68%) and 12-month secondary patency (68% versus 62%) compared with traditional arteriovenous fistulas (AVFs), especially in female, diabetic, and obese patients. According to Dr. Mohamad A. Hussain, "These findings suggest that ATEV could be a reliable option for vascular access for these subgroups with a high risk of AVF failure, without compromising safety." The sponsor is discussing the potential pathway to pursuing approval with the US Food and Drug Administration.
Dapagliflozin Slows Kidney Function Decline in Advanced CKD
The DAPA advKD trial randomized 180 patients with stages 4 and 5 CKD to dapagliflozin plus integrated CKD care or integrated CKD care alone. Over a median of 1.62 years, the dapagliflozin group experienced a slower reduction in kidney function, with average estimated glomerular filtration rate slopes of -2.24 versus -3.67 mL/min/1.73 m2 in the control group. The dapagliflozin group also had lower rates of kidney and cardiovascular outcomes. Dr. Yi-Wen Chiu stated, "We found that this medication helped slow the decline in kidney function and reduced the need for dialysis or other advanced treatments. Our next steps are to continue studying its long-term safety and effectiveness in this group."
