Nephrology Month in Review: August 2024

Ending the summer months with as much vigor as they began, August was a fitting conclusion to what was a busy season in the field of nephrology. Our August 2024 month in review spotlights our top coverage of some of the renal news and research that helped define August, including FDA news and pipeline developments, a cross-specialty feature project, and recent news and research about renal risk stratification and improving outcomes.

Renal Pipeline Developments

Iptacopan Receives Accelerated Approval for Reducing Proteinuria in IgA Nephropathy

On August 7, 2024, the US Food and Drug Administration granted accelerated approval to iptacopan (Fabhalta) for the reduction of proteinuria in adults with primary IgA nephropathy (IgAN), making it the first complement inhibitor to be approved for such an indication. The decision was based on interim data from the phase 3 APPLAUSE-IgAN trial, which concluded use of iptacopan was associated with a 38% reduction in proteinuria at 9 months relative to placebo therapy.

"The heterogeneous and progressive nature of IgA nephropathy has made it challenging to effectively treat this disease. Thankfully, the treatment landscape is rapidly evolving," said Dana Rizk, MD, investigator and APPLAUSE-IgAN steering committee member for APPLAUSE-IgAN and professor at the University of Alabama at Birmingham division of nephrology. "Mounting clinical evidence underscores the pivotal role of complement activation in IgA nephropathy. I am thrilled that this advancement is now available to help enable a targeted treatment approach for IgAN patients."

VALIANT: Pegcetacoplan Significantly Reduces Proteinuria in C3 Glomerulopathy, IC-MPGN

The next day, on August 8, 2024, Apellis Pharmaceuticals and Sobi announced positive topline results from the phase 3 VALIANT study investigating systemic pegcetacoplan in patients with C3 glomerulopathy or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). Results showed the study met the primary endpoint, demonstrating a statistically significant and clinically meaningful 68% (P <.0001) proteinuria reduction in patients with C3 glomerulopathy and IC-MPGN treated with pegcetacoplan compared to placebo, both in addition to background therapy, at week 26.

Based on these findings, Apellis plans to submit a supplemental New Drug Application to the US Food and Drug Administration in early 2025, and Sobi plans to submit a marketing application with the European Medicines Agency in 2025.

Cross-Specialty Care

Lifesaving But Not Perfect: Addressing Sleep Health in Patients on Dialysis

Often, care for patients receiving dialysis focuses primarily on their renal health and fails to address other symptoms stemming from treatment. In this feature, the editorial teams of HCPLive Nephrology and HCPLive Sleep Health spoke with a trio of sleep and renal experts as well as a former dialysis patient to discuss the need for interdisciplinary care that addresses kidney, psychiatric, and sleep health.

Improving Kidney Outcomes

Low-Dose Spironolactone Safe, Effective for Proteinuria Reduction in IgA Nephropathy

New research points to the safety and efficacy of mineralocorticoid receptor antagonists for reducing urine protein excretion in patients with IgAN, confirming the beneficial effects of spironolactone for proteinuria reduction within 2 months of treatment and complementing the effects of renin-angiotensin-aldosterone system (RAAS) blockers and glucocorticoids. Of note, results showed response varied among patients, with those showing endocapillary proliferation in renal biopsies having poor spironolactone responsiveness.

Reduced-Dose Methylprednisolone Improves Kidney Outcomes, Delays Renal Failure in High-Risk IgAN

A prespecified secondary analysis of the reduced-dose cohort of the therapeutic effects of steroids in IgAN global (TESTING) trial found a reduced-dose oral methylprednisolone regimen tapered over 6 to 9 months improves kidney outcomes in patients with high-risk IgAN. Specifically, results showed a 0.4 mg/kg/d methylprednisolone regimen is associated with a 76% reduced risk of the primary composite kidney outcome compared to supportive care alone, additionally highlighting a delay in the progression to kidney failure for patients already established on maximal supportive care.

Higher Thiazide Doses Reduce Urine Calcium, Prevent Kidney Stone Recurrence

Findings from a recent study are providing clinicians with an overview of the benefit of thiazides for preventing kidney stone recurrence, suggesting greater thiazide doses are linked to increased reductions in urine calcium and fewer symptomatic kidney stone events. Results offer a potential explanation for findings from the multicenter Hydrochlorothiazide for Kidney Stone Recurrence Prevention (NOSTONE) trial, which reported hydrochlorothiazide once daily at a dose of 12.5 mg, 25 mg, or 50 mg did not reduce the recurrence of kidney stone events compared to placebo in a cohort of 416 patients with a history of kidney stone episodes at 12 centers in Switzerland.

“What this means for patients is that thiazides remain an important option in the toolkit for preventing kidney stone recurrence,” Ryan Hsi, MD, an associate professor in the department of urology at Vanderbilt University Medical Center, said in a press release. “It may be beneficial to monitor calcium excretion while on thiazide therapy to adjust dose and diet to attain an adequate reduction in urine calcium.”

Renal Risk Stratification

Nutritional Scores May Aid ESRD Risk Stratification in IgA Nephropathy

Recent research suggests nutritional indexes may be useful tools for determining IgAN severity and identifying individuals at risk of progressing to end-stage renal disease (ESRD). Study findings point to a notable correlation between controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI) with the severity of crescents in patients with IgAN. However, although PNI and GNRI were significantly reduced in patients with IgAN who developed ESRD, only GNRI emerged as a predictor of ESRD in multivariable analysis.

New Prediction Tool Projects Pediatric IgA Nephropathy Progression Post-Biopsy

A new IgAN prediction tool for pediatric patients allows clinicians to determine their risk of disease progression 1 to 2 years post-biopsy, a resource previously only available for adult patients. The updated pediatric model was developed based on existing, externally validated adult post-biopsy prediction tool models to facilitate the identification of children at risk of a 30% decline in estimated glomerular filtration rate or end-stage kidney disease up to 2 years after biopsy.

Atopic Dermatitis Linked to Increased Risk of IgA Nephropathy

Findings from a recent study suggest atopic dermatitis may increase the risk of IgAN through a decrease in GALNT12 and C1GALT1C1 expression and an increase in aberrant IgA1 production. Although the bidirectional 2-sample Mendelian randomization study explored the causality between atopic dermatitis, acne, and psoriasis with IgAN, it found only atopic dermatitis was causally associated with IgAN, providing new insights into the pathogenesis of IgAN and potential strategies for its prevention and treatment.