IgA nephropathy: a review of existing and emerging therapies

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. Recently, there have been multiple advances in the understanding of IgAN pathophysiology and therapeutic options. Despite the advent of new treatment options, individual risk stratification of the disease course and choosing the best treatment strategy for the patient remains challenging. A multitude of clinical trials is ongoing, opening multiple opportunities for enrollment. In this brief review we discuss the current approach to the management of IgAN and highlight the ongoing clinical trials.

[1]  Eddie B. S. Tan,et al.  Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial , 2023, The Lancet.

[2]  F. Hou,et al.  Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy: A Randomized Clinical Trial. , 2023, JAMA network open.

[3]  Shankun Zhao,et al.  Current knowledge of targeted-release budesonide in immunoglobulin A nephropathy: A comprehensive review , 2023, Frontiers in Immunology.

[4]  B. Rovin,et al.  Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy. , 2022, Kidney international.

[5]  David W. Johnson,et al.  Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. , 2022, JAMA.

[6]  L. Prikhodina,et al.  KDIGO 2021 Clinical Practice Guideline for the Management of GLOMERULAR Diseases , 2022, Nephrology and Dialysis.

[7]  B. Rovin,et al.  KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. , 2021, Kidney international.

[8]  V. Werth,et al.  Rituximab versus Mycophenolate Mofetil in Patients with Pemphigus Vulgaris. , 2021, The New England journal of medicine.

[9]  J. McMurray,et al.  A pre-specified analysis of the DAPA-CKD trial indicates effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. , 2021, Kidney international.

[10]  J. McMurray,et al.  Dapagliflozin in Patients with Chronic Kidney Disease. , 2020, The New England journal of medicine.

[11]  C. Fitzner,et al.  Single versus dual blockade of the renin-angiotensin system in patients with IgA nephropathy , 2020, Journal of Nephrology.

[12]  C. Wanner,et al.  After ten years of follow-up, no difference between supportive care plus immunosuppression and supportive care alone in IgA nephropathy. , 2020, Kidney international.

[13]  anonymous,et al.  Comprehensive review , 2019 .

[14]  Hong Zhang,et al.  Effects of Hydroxychloroquine on Proteinuria in IgA Nephropathy: A Randomized Controlled Trial. , 2019, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[15]  F. Schena,et al.  Epidemiology of IgA Nephropathy: A Global Perspective. , 2018, Seminars in nephrology.

[16]  T. Muthukumar,et al.  Bortezomib for Reduction of Proteinuria in IgA Nephropathy , 2018, Kidney international reports.

[17]  David W. Johnson,et al.  Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial , 2017, JAMA.

[18]  C. Zeng,et al.  Mycophenolate Mofetil Combined With Prednisone Versus Full-Dose Prednisone in IgA Nephropathy With Active Proliferative Lesions: A Randomized Controlled Trial. , 2017, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[19]  F. Locatelli,et al.  Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial , 2017, The Lancet.

[20]  G. Markowitz.  Glomerular disease: Updated Oxford Classification of IgA nephropathy: a new MEST-C score , 2017, Nature Reviews Nephrology.

[21]  B. Rovin,et al.  A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction. , 2017, Journal of the American Society of Nephrology : JASN.

[22]  C. Schmid,et al.  Early Change in Urine Protein as a Surrogate End Point in Studies of IgA Nephropathy: An Individual-Patient Meta-analysis. , 2016, American Journal of Kidney Diseases.

[23]  M. Harrison.  A Global Perspective , 2015, Bulletin of the history of medicine.

[24]  C. Fitzner,et al.  Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. , 2015, The New England journal of medicine.

[25]  Yusuke Suzuki,et al.  A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy , 2014, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[26]  A. Diehl,et al.  Individual-patient meta-analysis , 2012 .

[27]  C. Zeng,et al.  Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[28]  D. Isenberg,et al.  Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. , 2011, The New England journal of medicine.

[29]  L. Thibaudin,et al.  Predicting the risk for dialysis or death in IgA nephropathy. , 2011, Journal of the American Society of Nephrology : JASN.

[30]  A. McGrogan,et al.  The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[31]  B. Kollen,et al.  A Double-blind Randomized Controlled Trial , 2011 .

[32]  D. Lokanatha,et al.  Abstract P2-16-03: Sorafenib in Combination with Paclitaxel as a First-Line Therapy in Patients with Locally Recurrent or Metastatic Breast Cancer: Overall Survival Results from a Double-Blind, Randomized, Placebo-Controlled, Phase 2b Trial , 2010 .

[33]  P. Tan,et al.  Global Evolutionary Trend of the Prevalence of Primary Glomerulonephritis over the Past Three Decades , 2010, Nephron Clinical Practice.

[34]  S. Tang,et al.  Long-term study of mycophenolate mofetil treatment in IgA nephropathy. , 2010, Kidney international.

[35]  F. Schena,et al.  Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. , 2009, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[36]  K. Simpson,et al.  Centre variation in incidence, indication and diagnosis of adult native renal biopsy in Scotland. , 2009, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[37]  Ajay K. Singh,et al.  Combination therapy of prednisone and ACE inhibitor versus ACE-inhibitor therapy alone in patients with IgA nephropathy: a randomized controlled trial. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[38]  J. Scholey,et al.  Remission of proteinuria improves prognosis in IgA nephropathy. , 2007, Journal of the American Society of Nephrology : JASN.

[39]  R. Hogg,et al.  Mycophenolate mofetil in children with frequently relapsing nephrotic syndrome: a report from the Southwest Pediatric Nephrology Study Group. , 2006, Clinical journal of the American Society of Nephrology : CJASN.

[40]  M. Hosoya,et al.  Efficacy of tonsillectomy pulse therapy versus multiple-drug therapy for IgA nephropathy , 2006, Pediatric Nephrology.

[41]  B. Julian,et al.  Clinical trial to evaluate omega-3 fatty acids and alternate day prednisone in patients with IgA nephropathy: report from the Southwest Pediatric Nephrology Study Group. , 2006, Clinical journal of the American Society of Nephrology : CJASN.

[42]  K. Chow,et al.  Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[43]  V. D’Agati,et al.  Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. , 2005, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[44]  A. Sanabria,et al.  Randomized controlled trial. , 2005, World journal of surgery.

[45]  B. Maes,et al.  Mycophenolate mofetil in IgA nephropathy: results of a 3-year prospective placebo-controlled randomized study. , 2004, Kidney international.

[46]  Claudio Pozzi,et al.  Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. , 2004, Journal of the American Society of Nephrology : JASN.

[47]  E. Morales,et al.  Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. , 2003, Journal of the American Society of Nephrology : JASN.

[48]  M. Kubo,et al.  Controlled, prospective trial of steroid treatment in IgA nephropathy: a limitation of low-dose prednisolone therapy. , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[49]  Xiangmei Chen,et al.  [A randomized control trial of mycophenolate mofeil treatment in severe IgA nephropathy]. , 2002, Zhonghua yi xue za zhi.

[50]  S. Gabriel,et al.  Systematic Review of the Literature , 2021, Adherence to Antiretroviral Therapy among Perinatal Women in Guyana.

[51]  T. Larson,et al.  A randomized trial of high-dose compared with low-dose omega-3 fatty acids in severe IgA nephropathy. , 2001, Journal of the American Society of Nephrology : JASN.

[52]  M. Hori,et al.  Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy. , 2000, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[53]  T. Larson,et al.  The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Mayo Nephrology Collaborative Group. , 1999, Journal of the American Society of Nephrology : JASN.

[54]  E. Bergstralh,et al.  A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group. , 1994, The New England journal of medicine.

[55]  Y. Taguma,et al.  Early intensive therapy for clinical remission of active IgA nephropathy: a three-year follow-up study. , 1993, Nihon Jinzo Gakkai shi.

[56]  B. Julian,et al.  Alternate-Day Prednisone Therapy in IgA Nephropathy , 1993 .

[57]  F. Lai,et al.  Corticosteroid therapy in IgA nephropathy with nephrotic syndrome: a long-term controlled trial. , 1986, Clinical nephrology.

[58]  M. Sasa,et al.  A Three-year Follow-up Study , 1981 .

[59]  E. Glaser.  The randomized clinical trial. , 1972, The New England journal of medicine.

[60]  J. Berger,et al.  [Intercapillary deposits of IgA-IgG]. , 1968, Journal d'urologie et de nephrologie.