B BOSE 1,2, R HONG 3, G STRIPPOLI 4,5,6, D JOHNSON 2,7,8, W YANG 9, S BADVE 2,3,10, S PALMER 11
1Department of Nephrology, Nepean Hospital, Kingswood, Australia, 2Australasian Kidney Trials Network, The University of Queensland, , Australia, 3Department of Nephrology, St George Hospital, Sydney, Australia, 4University of Bari, Department of Emergency and Organ Transplantation, Bari, Italy, 5The University of Sydney, Sydney School of Public School, Sydney, Australia, 6The Children’s Hospital at Westmead, Cochrane Kidney and Transplant, Centre for Kidney Research, Westmead, Australia, 7Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia, 8Translational Research Institute, Brisbane, Australia, 9Department of Nephrology, Peking University Third Hospital, Beijing, China, 10The George Institute of Global Health, UNSW Medicine, Sydney, Australia, 11Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
Aim: To evaluate the comparative efficacy and safety of immunosuppression strategies compared to alkylating agent strategies in adults with idiopathic membranous nephropathy.
Background: Immunosuppressive agents are proven to prevent progression of kidney disease in adults with idiopathic membranous nephropathy, but the comparative efficacy and safety of different immunosuppressive agents is not clear.
Methods: Randomized control trials evaluating treatment for idiopathic membranous nephropathy were searched in MEDLINE, Embase and CENTRAL till September 2020. Outcomes such as complete remission, partial remission, kidney failure, estimated glomerular filtration rate, doubling of serum creatinine, proteinuria, serious adverse events, discontinuation of treatment, serious infection, onset of diabetes mellitus and bone marrow suppression were compared using network meta-analysis.
Results: Fifty-eight studies including 3067 participants proved eligible. Alkylating agents were probably more effective at inducing complete remission than non-immunosuppressive strategies (OR 4.64, CI 2.13–10.1) or steroids (OR 4.36, CI 1.43-13.3) and had uncertain effects when compared to rituximab, mycophenolate mofetil, calcineurin inhibitor and calcineurin inhibitor plus rituximab. Compared to other immunosuppression strategies, there was limited evidence that alkylating agents had different effects on partial remission, kidney failure, doubling of serum creatinine, glomerular filtration rate, proteinuria, discontinuation of treatment, serious infection, and onset of diabetes mellitus. Alkylating agents probably incurred more serious adverse events than a calcineurin inhibitor plus rituximab (OR 2.89, CI 1.09–7.66). Alkylating agents may have incurred more bone marrow suppression than calcineurin inhibitors (OR 15.1, CI 4.59–49.8), mycophenolate mofetil (OR 13.4, CI 2.29–78.8) and non-immunosuppressive strategies (OR 23.5, CI 7.09–77.9).
Conclusion: There is limited evidence to establish the comparative effectiveness and safety of other immunosuppression strategies compared to alkylating agents in adults with idiopathic membranous nephropathy.
Dr Bhadran Bose is a Renal Staff Specialist at Nepean and Blue Mountains hospital and is also clinical lecturer with University of Sydney. He has special interests in glomerular diseases. He completed his Nephrology training at the Princess Alexandra Hospital, Brisbane. Dr Bose then did a year of post FRACP fellowship at the University of Toronto, Canada on glomerular disorders and pregnancies in patients with renal disorders.
He has published original research and narrative review in international nephrology journals, has co-authored chapters in text books. He is actively involved in research and teaching.