Nephrology Month in Review: January 2024

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Our January 2024 month-in-review spotlights some of our top coverage in nephrology, ranging from FDA news to clinical trial data and research about approaches to improving renal health.

Given the rising prevalence of kidney disease in the US, renal health was a major topic of discussion in 2023 that shows promise to continue into 2024. Coming off of the landmark approval of oral budesonide (Tarpeyo) as the first IgA nephropathy treatment in the final days of 2023, the first month of 2024 had high expectations to meet and certainly did not disappoint.

Characterized by data for another potential agent in the pipeline for IgA nephropathy as well as the addition of a Boxed Warning to a RANK ligand inhibitor for severe hypocalcemia in patients with advanced chronic kidney disease (CKD) and research about the impact of diabetes remission on CKD and cardiovascular disease risk, January was replete with news and groundbreaking research in nephrology.

FDA News

FDA Adds Boxed Warning to Denosumab (Prolia) for Severe Hypocalcemia

The US Food and Drug Administration (FDA) announced the addition of a Boxed Warning to denosumab (Prolia) for increased risk of severe hypocalcemia in patients with advanced CKD. The decision was based on an evaluation of studies and multiple cases reported to the FDA’s Adverse Event Report System database.

“Based on a completed U.S. Food and Drug Administration (FDA) review of available information, we have concluded that the osteoporosis medicine Prolia (denosumab) increases the risk of severe hypocalcemia, very low blood calcium levels, in patients with advanced chronic kidney disease (CKD), particularly patients on dialysis,” read the FDA Drug Safety Communication.

Data on Treatments in Kidney Disease

OPTIMISE-CKD: Dapagliflozin is Effective for Patients with CKD, Low Albuminuria

Results from OPTIMISE-CKD, billed as the first study to assess the real-world effectiveness of dapagliflozin 10 mg in patients with CKD and UACR < 200 mg/g, showed the sodium-glucose cotransporter 2 inhibitor may be an effective treatment option for this understudied patient population. Following dapagliflozin initiation, the difference in median estimated glomerular filtration rate (eGFR) slope between initiators and matched non-initiators was 1.07 mL/min/1.73 m2/year (95% CI, 0.40 to 1.74) in all patients with UACR < 200 mg/g. Of note, the benefit of dapagliflozin 10 mg initiation was observed across the entire eGFR slope distribution among patients with UACR < 200 mg/g.

72-Week Phase 2B ORIGIN Data Highlight Potential Benefit of Atacicept in IgA Nephropathy

Results from the open-label portion of Vera Therapeutics’ phase 2b ORIGIN trial showed the use of atacicept in patients with IgA nephropathy was associated with eGFR stabilization as well as improvements hematuria, Gd-IgA1, and UPCR over 72 weeks. Those treated with atacicept for 72 weeks (n = 106) in the global, multicenter, randomized, double-blind, placebo-controlled trial demonstrated a 62% reduction in Gd-IgA1, a reduction in the percentage of participants with hematuria to 19%, and a 48% reduction in UPCR in the per-protocol analysis. Coming on the heels of oral budesonide (Tarpeyo)’s approval as the first treatment for IgA nephropathy, ORIGIN shows promise that atacicept may not be far behind.

Improving Patient Outcomes

Achieving Diabetes Remission, For No Matter How Long, Can Lower Kidney, Cardiovascular Risk

Findings from the Look AHEAD study highlight the impact of diabetes remission from weight loss on rates of chronic kidney disease (CKD) and cardiovascular disease among people with type 2 diabetes. A multicenter, randomized clinical trial conducted in 16 sites across the US, Look AHEAD was launched by the National Institutes of Health in June 2021 and followed 5000 patients with type 2 diabetes for more than a decade, ultimately finding remission was associated with > 30% reductions in rates of both CKD and cardiovascular disease relative to not achieving remission.

“As the first intervention study to associate remission with reduction of diabetes-related complications, this is encouraging news for those who can achieve remission from type 2 diabetes,” said Edward Gregg, PhD, head of the School of Population Health, RCSI University of Medicine and Health Sciences. “While our study is also a reminder that maintenance of weight loss and remission is difficult, our findings suggests any success with remission is associated with later health benefits.”

Alkaline Water Has Minimal Alkali Content, Negligible Effect on Urinary pH

Anion chromatography and direct chemical measurements of 5 popular alkaline water brands revealed a negligible alkali content and presumed minimal impact on urinary pH and urinary citrate levels. An analysis of Essentia, Smart Water Alkaline, Great Value Hydrate Alkaline Water, Body Armor SportWater, and Perfect Hydration suggested none had any added benefit over tap water for providing alkali content and alkalinizing urine pH in patients with uric acid and cystine urolithiasis.

Study Details Consequences of Delayed CRRT Initiation in Children, Young Adults

Delayed initiation of continuous renal replacement therapy (CRRT) in children and young adults with acute kidney injury or volume overload may increase the risk of adverse events, including death, dialysis dependence, and persistent kidney dysfunction. The secondary analysis of data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease registry showed each 1-day delay in initiation was associated with 3% greater odds of major adverse kidney events at 90 days.