Corticosteroid Therapy Reduces Proteinuria But Does Not Delay ESKD in Patients with IgAN

In the absence of effective treatment options for immunoglobulin A nephropathy (IgAN), corticosteroids serve as the cornerstone of disease management – however, a retrospective cohort study found that although corticosteroid therapy reduced proteinuria, it did not affect progression to end-stage kidney disease (ESKD).¹

All study participants reached ESKD after a median of 5 years, regardless of whether they received supportive therapy alone or in combination with corticosteroid therapy. The time from diagnosis until ESKD was similar between the groups, although corticosteroid treatment was associated with adverse effects.¹

Though multiple agents have been progressing through clinical programs for the treatment of IgAN, only budesonide (Tarpeyo) has earned full US Food and Drug Administration approval thus far.² The Kidney Disease Improving Global Outcomes guideline from 2012 recommended long-term angiotensin-converting enzyme inhibitor or angiotensin II receptor inhibitor treatment for patients with IgAN and proteinuria > 1 g/d, a threshold that was eventually lowered to 0.5 g/d in the 2021 guideline. However, the safety and efficacy of corticosteroids in this patient population have been widely debated.³

“The efficacy of corticosteroids for treating patients with IgAN remains controversial. While some studies have suggested that corticosteroids are associated with improved clinical outcomes, other studies have questioned the benefits of immunosuppression,” Thomas Knoop, MD, PhD, head of the department of nephrology at the University of Bergen/Haukeland University Hospital in Norway, and colleagues wrote.¹

Thus, investigators sought to describe the use of corticosteroid therapy combined with supportive therapy in a cohort of Norwegian patients with IgAN who had progressed to ESKD. They leveraged data from the Norwegian Renal Registry for patients diagnosed with primary IgAN from May 1988 - 2012, retrospectively examining a total of 143 patients who were divided into 2 groups based on whether they received supportive therapy alone (n = 103) or in combination with corticosteroids (n = 40).¹

Kidney function, time to ESKD, and adverse effects were compared between the groups. The observation period lasted from the diagnostic kidney biopsy until the initiation of kidney replacement therapy.¹

Among the cohort, 79% of patients were male. The median age at diagnosis was 41 years, median proteinuria was 3.0 g/24 h, and median eGFR was 42 mL/min/1.73 m2. Investigators observed crescents (in > 50% of the glomeruli) in 38% and tubular atrophy or segmental sclerosis in 36% of the biopsies.¹

Most (94%) patients were treated with renin-angiotensin-system (RAS) blockade, and all patients reached ESKD after a median of 5 years (Interquartile range [IQR], 2-9 years). Investigators noted the time from diagnosis until ESKD was similar in the 2 study groups (P = .98).¹

Of note, the urine albumin-to-creatinine ratio (UACR) and proteinuria were higher in the corticosteroid group before (P = .0015) and after (P <.001) the use of RAS inhibitors. During 6 months of corticosteroid therapy, the median eGFR declined from 21 (IQR, 13-46) mL/min/1.73 m2 to 20 (IQR, 12-40) mL/min/1.73 m2, and median proteinuria decreased from 5.5 g/24 h to 3.0 g/24 h. Investigators observed a similar reduction in proteinuria of a median -1.5 g/24 h in both groups during treatment.¹

Most (88%) patients treated with corticosteroids reported adverse events. Of these, 65% were labeled as mild and 23% were severe, including sepsis, femoral head avascular necrosis, and paranoid psychosis.¹

Upon analysis, age (β = -0.079; P = .008) and proteinuria at diagnosis (β = -0.50; P = .01) exhibited statistically significant associations with a delay in the progression to ESKD.¹

“The therapy might have significantly reduced proteinuria; however, it did not delay progression to ESKD,” investigators concluded.¹

References:

1. ^{Rivedal M, Haaskjold YL, Eikrem Ø. Use of corticosteroids in Norwegian patients with immunoglobulin a nephropathy progressing to end-stage kidney disease: a retrospective cohort study. BMC Nephrol. 2024;25(1):42. doi:10.1186/s12882-024-03481-6}
2. ^{Brooks, A. FDA Awards Full Approval to Budesonide (Tarpeyo) in Treatment of IgA Nephropathy. HCPLive. December 20, 2023. Accessed March 4, 2024. https://www.hcplive.com/view/fda-awards-full-approval-to-budesonide-tarpeyo-in-treatment-of-iga-nephropathy}
3. ^{Beck LH, Ayoub I, Caster D, et al. KDOQI US Commentary on the 2021 KDIGO Clinical Practice Guideline for the Management of Glomerular Diseases. American Journal of Kidney Diseases. https://doi.org/10.1053/j.ajkd.2023.02.003}