Benefits, Risks of Immunosuppressive Treatment for High-Risk IgA Nephropathy

Savaş Ozturk

Credit: Istanbul University

Findings from a recent study are providing clinicians with an overview of the benefit of immunosuppressive treatment with corticosteroids for inducing remission in patients with high-risk IgA nephropathy (IgAN).¹

Results showed systemic corticosteroid treatment provided the greatest benefit, whereas remission rates were lower when corticosteroids were combined with other immunosuppressive treatments in a cohort of Turkish patients with estimated glomerular filtration rate (eGFR) > 30 mL/min and proteinuria > 0.75 g/d under optimal supportive care.¹

In the absence of a complete cure, treatment for IgAN seeks to prevent the need for dialysis or a kidney transplant. The variable clinical course of IgAN means some patients may require more intensive treatment than others. For those at a greater risk of disease progression, immunosuppressants are a mainstay of treatment but are often associated with serious side effects, raising questions as to their viability as a treatment alone or in combination with other medications.²

“Although there are more studies comparing supportive care and immunosuppressive treatment, knowledge about efficacy of other immunosuppressive regimens is limited and controversial,” Savaş Ozturk, professor in the division of medical sciences at Istanbul University, and colleagues wrote.¹

To investigate the results of initial immunosuppressive treatment and outcome determinants among high-risk IgAN patients, investigators examined data for patients with biopsy-proven IgAN from the primary glomerulonephritis registry of the Turkish Society of Nephrology Glomerular Diseases Study Group (TSN-GOLD). Patient data were obtained from 26 centers in Turkey that followed treatment protocols consistent with the KDIGO guidelines and the TSN Consent Report on Diagnosis and Treatment of Primary Glomerular Diseases.¹

Patients with liver disease, inflammatory bowel disease, rheumatologic disease, and patients who were not administered immunosuppressive treatment were excluded. Investigators additionally excluded patients with inaccurate biopsy diagnoses, IgA vasculitis, and those who were missing laboratory or treatment response data. After excluding patients who did not meet the criteria for high-risk IgAN, defined as those with an eGFR > 30 mL/min and proteinuria > 0.75 g/d under optimal supportive care, 408 high-risk primary IgAN patients who received immunosuppressive treatment were evaluated.¹

Among the cohort, 65.4% of patients were male, the mean age was 38.4 ± 12.5 years, and the majority (70.6%) received isolated corticosteroid treatment as opposed to combined immunosuppressive treatment (29.4%). Systemic corticosteroid protocols were oral administration with a dose of 0.5–1 mg/kg/d prednisolone (maximum 60 mg/d) tapering within 4-8 months according to the response at least for 3–6 months, Pozzi protocol (intravenous methylprednisolone for 3 consecutive days in the first, third, and fifth months and 0.5 mg/kg/d oral prednisone every other day for 6 months). Combined therapy included a combination of corticosteroids with another immunosuppressive agent, including azathioprine, cyclophosphamide, calcineurin inhibitors, and mycophenolate mofetil.¹

Treatment responses were defined as complete remission (proteinuria <0.5 g/d with stable or improved serum creatinine level), partial remission (proteinuria 0.5–3.5 g/d, >%50 decrease, and <3.5 g/d with stable or improved serum creatinine level) and unresponsive.¹

Investigators noted remission was achieved in 74.7% of the patients in a median duration of 4 (1–69) months, with partial remission in 65.5% and complete remission in 34.5%. They pointed out remission was achieved at significantly greater rates in the corticosteroid group (78% vs 66.7%; P = .016).¹

Steroid-associated adverse events (n = 74) were significantly more frequent in the corticosteroid group (93.4% vs 56.7%; P <.001), as were mild infection (n = 1; 3.3% vs 0%), severe infection (n = 6; 13.3% vs 3.3%), and other treatment-associated adverse events (n = 10; 26.7% vs 3.3%) (all P <.001).¹

Further analysis revealed the remission rate was significantly greater among patients with segmental sclerosis compared to those without (60.4% vs 49%; P = .047). In multivariate analysis, MEST-C S1 (Hazard ratio [HR], 1.43; 95% CI, 1.08-1.89; P = .013), MEST-C T1 (HR, 0.68; 95% CI, 0.51-0.91; P = .008) and combined immunosuppressive treatment (HR, 0.66; 95% CI, 0.49-0.91; P = .009) were significantly associated with remission.¹

Investigators outlined several potential limitations to these findings, including the retrospective study design, the heterogeneity of the data, the inability to account for histopathologic findings regarding segmental sclerosis rate and sclerosis type, and incomplete data on follow-up laboratory parameters.¹

“In conclusion, systemic corticosteroid treatment in IgAN patients with high risk of progression may lead to significant remission rates in the Turkish cohort,” investigators wrote.¹ “In contrast, conventional immunosuppressive drugs do not provide a clear benefit. However, it is important to exercise caution due to the potential for serious side effects associated with immunosuppressive treatment.”

References:

1. ^{Oruc A, Sumnu A, Turkmen A, et al. Immunosuppressive treatment results in patients with primary IgA nephropathy in Turkiye; the data from TSN-GOLD working group. Ren Fail. 2024;46(1):2341787. doi:10.1080/0886022X.2024.2341787}
2. ^{Mayo Clinic. IgA nephropathy (Berger disease). Diagnosis & Treatment. June 9, 2023. Accessed May 15, 2024. https://www.mayoclinic.org/diseases-conditions/iga-nephropathy/diagnosis-treatment/drc-20352274}