Nephrology Month in Review: April 2024

Coming off of a strong first quarter of 2024, April was a fitting continuation to what shows promise to be a historic year in nephrology. As more agents continue to progress through the pipeline, this month saw notable clinical trial data in IgA nephropathy (IgAN) as well as other key strategies to improve kidney disease care, including a new digital algorithm for predicting kidney failure and death risk in chronic kidney disease (CKD), a landmark international consensus statement calling for action on kidney disease from the World Health Organization (WHO), and new research about risk stratification, all of which we spotlight in our April 2024 month in review.

Clinical Trial Data

Updated Clinical Data for Povetacicept in IgA Nephropathy Support Advancement to Phase 3 Trial

On April 10, 2024, Alpine Immune Sciences announced updated clinical data for povetacicept in IgAN from the phase 1b/2a RUBY-3 study, noting it would be presented as a late-breaking poster at the World Congress of Nephrology meeting a few days later. As detailed in the press release, results showed povetacicept was well tolerated and associated with urine protein to creatinine ratio (UPCR) reductions of > 60% at 36 weeks, additionally linked to remission, resolution of hematuria, and stable renal function as measured through estimated glomerular filtration rate (eGFR).

“I think fundamentally, what we'd like to do is to switch off the production of that pathogenic Gd-IgA1,” Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester, explained in an interview with HCPLive. Specifically, he described the targeting of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) signaling that stops the production of Gd-IgA1, as seen with povetacicept.

Calliditas Announces Open Label Extension Results for Budesonide (Nefecon) in IgA Nephropathy

In another clinical trial update later in the month, Calliditas Therapeutics announced positive topline results from the global open-label extension of the phase 3 NefIgArd study of budesonide (Nefecon) in adult patients with primary IgAN on optimized renin-angiotensin system inhibitor (RASi) therapy. Results showed a treatment response consistent with the NefIgArd study across UPCR and eGFR endpoints, regardless of whether participants had previously been treated with budesonide or placebo.

“It is exciting to see these results on both proteinuria reduction and eGFR stabilization at 9 months across all patients irrespective of previous treatment regimen in the Phase 3 trial,” Renée Aguiar-Lucander, CEO of Calliditas Therapeutics, said in a press release. “These topline results support the study thesis that the response to retreatment with Nefecon was unaffected by previous treatment cycles.”

Strides to Improve Nephrology Care

Electronic Health Record-Based Population Health Management Strategy May Improve CKD Care

Findings from this pragmatic, cluster-randomized clinical trial highlight the potential of a multifaceted electronic health record and population health management strategy for addressing barriers to the implementation of evidence-based CKD care. Although the intervention did not reduce patients’ risk of CKD progression compared with usual care, it did increase exposure to angiotensin-converting enzyme inhibitors (ACEi)/angiotensin 2 receptor blockers (ARB).

“Despite the null result, we found that the Kidney-CHAMP framework is scalable, provides equitable access and overcomes barriers on the provider, patient and health system levels,” Manisha Jhamb, MD, MPH, associate chief of the renal-electrolyte division in the University of Pittsburgh School of Medicine, explained in a press release.

Digital Algorithm Outperforms Current Prediction Model for Kidney Failure, Death Risk in CKD

KDpredict, a predictive algorithm and digital dashboard for assessing patients’ risk of kidney failure and all-cause death, consistently outperformed the kidney failure risk equation in external testing, suggesting it may be a promising alternative to the current benchmark risk prediction model for CKD. Designed to simultaneously predict kidney failure and death over 1-5 year time horizons, KDpredict was created to address shortcomings of the current kidney failure risk equation and support holistic decision-making for patients with moderate to severe CKD.

International Consensus Statement Calls for Prioritization of Kidney Disease by the WHO

A landmark international consensus statement led by the American Society of Nephrology, European Renal Association, and International Society of Nephrology is sounding the alarm on the growing global burden of kidney disease and the need for its prioritization by the WHO. Specifically, it calls for kidney disease to be labeled as a major non-communicable disease driver of premature mortality and outlines several policy, advocacy, and implementation needs to alleviate its growing impact.

"This consensus statement marks a significant first step in recognizing the impact kidney diseases have on more than 850,000,000 people globally and the need to eliminate disparities in kidney health and achieve equity in kidney care for people from all walks of life. I believe that the WHO and governments worldwide will rise to meet this call to action," said Deidra Crews, MD, president of the American Society of Nephrology.

Assessing Risk in Kidney Disease

Even Normal-Range Albuminuria May Increase Risk of CKD Progression, Kidney Failure

Although moderate to severe albuminuria is widely recognized as a major risk factor for adverse kidney and cardiovascular outcomes, findings from this study shine light on the prognostic value of albuminuria within the normoalbuminuric range for predicting the risk of CKD progression and eventual kidney failure. Indeed, results showed increasing albuminuria was linked to excess risk of CKD progression and kidney failure, even in patients with normoalbuminuria (urine albumin–creatinine ratio <30 mg/g).

Glomerulonephritis Patients Face High Risk of Recurrence After Kidney Transplant

Data from this single-center study suggests patients with glomerulonephritis may face a high risk of recurrent disease within 1 year of kidney transplantation. After a mean follow-up period of 3 years, investigators observed 5 cases of glomerulonephritis in 23 (21%) biopsies from a cohort of 125 patients who received kidney transplantation and post-operation care. Among them, 4 cases were recurrence of primary disease in the transplanted kidney (17.4%).