D J TUNNICLIFFE1,2, S REID1, J A SAMUEL3, D A MOLONY4, G FM STRIPPOLI1,2,5
1School of Public Health, The University Of Sydney, Sydney, Ausrtralia, 2Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Australia, 3Division of Pediatric Nephrology and Hypertension, McGovern Medical School UTHealth, , Houston, United States of America, 4Internal Medicine, McGovern Medical School UTHealth, Houston, United States of America, 5Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
Aim: To evaluate the benefits and harms of non-immunosuppressive therapy for the management of patients with immunoglobulin A (IgA) nephropathy.
Background: STOP-IgA illustrated the importance supportive therapy in the management of IgA nephropathy. However, the efficacy and safety of non-immunosuppressive therapies, such as, the class of antihypertensives, anti-malarial and tonsillectomy are unclear.
Methods: We updated a random-effects meta-analysis of non-immunosuppressive therapy in patients with IgA nephropathy. This review was first published in 2011. Certainty of the evidence was assessed using GRADE.
Results: Eighty trials (4559 participants) were identified, including 21 new trials published since 2011. There was little or no difference between the class of antihypertensive in clinical outcomes, but renin-angiotensin aldosterone system (RAAS) inhibition compared to non-RAAS inhibition may decrease proteinuria (g/24hr) (MD 0.48 lower, 95%CI 0.73, 0.23 lower). High-dose versus low-dose RAAS inhibition or dual versus single RAAS inhibition exhibited little or no differences in outcomes. One RCT found that hydroxychloroquine compared to placebo probably increased >50% reduction in proteinuria (RR 3.13, 95%CI 1.17, 8.36), but there were too few events to determine safety. In Japanese trials, tonsillectomy compared to standard of care may increase remission of proteinuria (RR 1.90, 95%CI 1.45, 2.47) and microscopic haematuria (RR 1.93, 95%CI 1.47, 2.53), but have little or no effect on macroscopic haematuria (RR 1.33, 95%CI 0.80, 2.23). The efficacy and safety of other non-immunosuppressive therapies are unclear.
Conclusions: Further trials are required to determine the effectiveness and safety of hydroxychloroquine, and classes of antihypertensives in IgA nephropathy. Tonsillectomy combined with standard of care may be beneficial in Japanese patients with IgA nephropathy. However, the generalisability of tonsillectomy to the wider IgA nephropathy population is unclear.
Dr David Tunnicliffe was awarded a PhD (medicine) at the Sydney School of Public Health, The University of Sydney in 2018. He is a Research Fellow at the School of Public Health, The University of Sydney based at the Centre for Kidney Research, The Children’s Hospital at Westmead.