Research presented at the American Society of Nephrology meeting

The annual meeting of the American Society of Nephrology (Kidney Week) was held this year from Nov. 2 to 5 in Philadelphia and attracted participants from around the world, including nephrology specialists, researchers, scientists, and other health care professionals. The conference featured presentations focusing on the latest advances in the management of patients with kidney diseases and related disorders.

In one study, Amit Garg, M.D., of McMaster University in Hamilton, Ontario, Canada, and colleagues found that the rate of completed steps toward receiving a kidney transplant does not significantly differ between a multicomponent intervention versus usual care.

A pragmatic cluster-randomized trial was conducted to determine if chronic kidney disease (CKD) program-wide use of a multicomponent intervention was superior to usual care in helping eligible patients complete four key steps toward receiving a kidney transplant. This 4.2-year trial included 20,375 patients with advanced CKD cared for by more than 3,600 health care staff in Ontario's 26 CKD programs. The trial was negatively impacted by the COVID-19 pandemic due to staffing challenges and shifting priorities.

"Despite evidence of intervention uptake, the rate of completed steps toward receiving a kidney transplant did not significantly differ between the multicomponent intervention versus usual care groups," Garg said. "Acknowledging the pandemic complicated intervention delivery, the team failed to show this intervention increased access to kidney transplantation and living kidney donation."

In another study, Michelle Rheault, M.D., of the University of Minnesota Medical School in Minneapolis, and colleagues found a clinically meaningful reduction in proteinuria in patients with focal segmental glomerulosclerosis (FSGS) treated with sparsentan.

As part of the DUPLEX phase 3 study, the authors randomly assigned 371 patients (children and adults) with FSGS to receive sparsentan, a novel endothelin and angiotensin receptor antagonist, or irbesartan, an active control, for two years.

The researchers found that patients treated with sparsentan were 55 percent more likely to achieve partial remission at 36 weeks compared with patients taking irbesartan. Treatment with sparsentan lead to a significant and durable reduction in proteinuria, with sparsentan-treated patients achieving a 50 percent reduction from baseline compared with a 32 percent reduction with irbesartan.

There were also more patients who achieved complete remission on sparsentan (18.5 percent compared with 7.5 percent with irbesartan). Partial and complete remission have been associated with better long-term kidney function. Sparsentan was well tolerated, with a safety profile similar to that of irbesartan.

"Patients with FSGS who do not respond to standard immunosuppressive therapy have few options for treatment," Rheault said. "Sparsentan provides a nonimmunosuppressive option for treatment for these patients that can reduce proteinuria and induce partial and complete remission."

In a phase 2 study, Katherine R. Tuttle, M.D., of the University of Washington School of Medicine in Seattle, and colleagues found that the renal benefit of aldosterone synthase inhibition, in the form of BI 690517, along with the sodium-glucose cotransporter-2 inhibitor empagliflozin may be additive by acting through different protective mechanisms.

The authors randomly assigned adults with CKD on a renin-angiotensin system inhibitor to an eight-week run-in to background empagliflozin 10 mg or placebo and then randomly assigned a second time to BI 690517 (3, 10, or 20 mg) or placebo. The researchers found that BI 690517 demonstrated dose-dependent reductions in albuminuria by up to 40 percent versus placebo in patients with CKD.

Albuminuria reduction greater than 30 percent, indicating treatment response, occurred in 70 percent of patients who were also randomly assigned to receive empagliflozin along with BI 690517. In contrast, the response rate with BI 690517 alone was 50 percent.

"Aldosterone synthase inhibition is a promising new therapy for CKD, with or without type 2 diabetes, that will be tested in a large, international phase 3 clinical trial called EASi-KIDNEY conducted by Oxford Population Health and Boehringer Ingelheim," Tuttle said. "In 2024, the new trial will begin recruitment aiming to test definitively the efficacy and safety of 690517 versus placebo, given on top of standard of care, including empagliflozin 10 mg once daily. EASi-KIDNEY will recruit and follow about 11,000 participants with CKD."

In the phase 3 PROTECT trial, Brad Rovin, M.D., of The Ohio State University Wexner Medical Center in Columbus, and colleagues found that compared with irbesartan, sparsentan significantly reduces proteinuria, leading to better preservation of kidney function in immunoglobulin A (IgA) nephropathy patients at risk for progression.

The authors compared the efficacy of sparsentan to irbesartan for the treatment of IgA nephropathy. They found that patients receiving sparsentan had a significantly greater decline in proteinuria than those receiving irbesartan. This led to accelerated approval of sparsentan for treatment of IgA nephropathy patients at high risk for CKD progression.

To verify that this significant decline in proteinuria translated to better preservation of kidney function, the trial was continued through week 110 to assess changes in glomerular filtration rate over time. The decline in proteinuria between sparsentan and irbesartan was maintained for the entire duration of the trial.

"The totality of the evidence suggests that the dual endothelin/angiotensin receptor blocker sparsentan, by significantly reducing proteinuria, leads to better preservation of kidney function in IgA nephropathy patients at risk of progression than treatment with an angiotensin receptor blocker alone," Rovin said.

"Sparsentan can be used as a foundational drug for initiating treatment in IgA nephropathy that is likely to allow more rapid and superior control of proteinuria than traditionally used renin-angiotensin-aldosterone system antagonists."

ASN: Multicomponent intervention does not increase steps toward kidney transplant

A multicomponent intervention does not increase the rate of completed steps toward receiving a kidney transplant, according to a study published online Nov. 3 in JAMA Internal Medicine to coincide with Kidney Week, the annual meeting of the American Society of Nephrology, held from Nov. 2 to 5 in Philadelphia.

ASN: eGFR No different with sparsentan, irbesartan in focal segmental glomerulosclerosis

No significant differences are seen in the estimated glomerular filtration rate with sparsentan versus irbesartan among patients with focal segmental glomerulosclerosis, according to a study published online Nov. 3 in the New England Journal of Medicine to coincide with Kidney Week, the annual meeting of the American Society of Nephrology, held from Nov. 2 to 5 in Philadelphia.

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