Medication Summary

Corticosteroids and cytotoxic therapy can induce remission. Corticosteroids are potent anti-inflammatory agents and immunosuppressants. These drugs suppress cellular and humoral response to tissue injury, thereby reducing inflammation. Oral prednisone generally is required for maintenance therapy. Cytotoxic drugs induce alkylation of DNA.

Class Summary

These agents have anti-inflammatory (glucocorticoid) and salt-retaining (mineralocorticoid) properties. Glucocorticoids have profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Prednisone (Deltasone, Orasone, Meticorten, Sterapred)

View full drug information

Most patients require long-term oral prednisone after inducing remission. Immunosuppressants for treatment of autoimmune disorders may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Methylprednisolone (Solu-Medrol)

View full drug information

For pulse therapy. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Class Summary

Inhibit cell growth and proliferation.

Cyclophosphamide (Cytoxan)

View full drug information

DOC in DPGN. Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Low dose is used when creatinine clearance is < 33 mL/min.

Maintain white blood cell count >2000/mL.

A dose of 50-100 mg/m² PO qd is associated with a higher incidence of hemorrhagic cystitis.

Mycophenolate (CellCept, Myfortic)

View full drug information

Inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production.

Two formulations are available and are not interchangeable. The original formulation, mycophenolate mofetil (MMF, Cellcept) is a prodrug that once hydrolyzed in vivo, releases the active moiety mycophenolic acid. A newer formulation, mycophenolic acid (MPA, Myfortic) is an enteric-coated product that delivers the active moiety.

Xie Q, Liu Y, Liu G, Yang N, Yin G. Diffuse proliferative glomerulonephritis associated with dermatomyositis with nephrotic syndrome. Rheumatol Int. 2010 Apr. 30(6):821-5. [QxMD MEDLINE Link].
[Guideline] Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016 Sep. 75 (9):1583-94. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis Chapter 13: Pauci-immune focal and segmental necrotizing glomerulonephritis. Kidney Int Suppl (2011). 2012 Jun. 2 (2):233-239. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis Chapter 9: Infection-related glomerulonephritis. Kidney Int Suppl (2011). 2012 Jun. 2 (2):200-208. [QxMD MEDLINE Link]. [Full Text].
Prendecki M, Clarke C, Cairns T, Cook T, Roufosse C, Thomas D, et al. Anti-glomerular basement membrane disease during the COVID-19 pandemic. Kidney Int. 2020 Sep. 98 (3):780-781. [QxMD MEDLINE Link].
[Guideline] Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis Chapter 12: Lupus nephritis. Kidney Int Suppl (2011). 2012 Jun. 2 (2):221-232. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis Chapter 14: Anti-glomerular basement membrane antibody glomerulonephritis. Kidney Int Suppl (2011). 2012 Jun. 2 (2):240-242. [QxMD MEDLINE Link]. [Full Text].
Almaani S, Meara A, Rovin BH. Update on Lupus Nephritis. Clin J Am Soc Nephrol. 2017 May 8. 12 (5):825-835. [QxMD MEDLINE Link]. [Full Text].
Vachvanichsanong P, Dissaneewate P, McNeil E. Diffuse proliferative glomerulonephritis does not determine the worst outcome in childhood onset lupus nephritis: a 23-year experience in a single centre. Nephrol Dial Transplant. 2009 Apr 25. [QxMD MEDLINE Link].
Pesce F, Stea ED, Rossini M, Fiorentino M, Piancone F, Infante B, et al. Glomerulonephritis in AKI: From Pathogenesis to Therapeutic Intervention. Front Med (Lausanne). 2020. 7:582272. [QxMD MEDLINE Link]. [Full Text].
van Daalen EE, Jennette JC, McAdoo SP, Pusey CD, Alba MA, Poulton CJ, et al. Predicting Outcome in Patients with Anti-GBM Glomerulonephritis. Clin J Am Soc Nephrol. 2018 Jan 6. 13 (1):63-72. [QxMD MEDLINE Link].
Hiramatsu N, Kuroiwa T, Ikeuchi H, et al. Revised classification of lupus nephritis is valuable in predicting renal outcome with an indication of the proportion of glomeruli affected by chronic lesions. Rheumatology (Oxford). 2008 May. 47(5):702-7. [QxMD MEDLINE Link].
Demircin G, Oner A, Erdogan O, et al. Long-term efficacy and safety of quadruple therapy in childhood diffuse proliferative lupus nephritis. Ren Fail. 2008. 30(6):603-9. [QxMD MEDLINE Link].
Haas M, Rahman MH, Cohn RA, et al. IgA nephropathy in children and adults: comparison of histologic features and clinical outcomes. Nephrol Dial Transplant. 2008 Aug. 23(8):2537-45. [QxMD MEDLINE Link].
Lazarus B, John GT, O'Callaghan C, Ranganathan D. Recent advances in anti-neutrophil cytoplasmic antibody-associated vasculitis. Indian J Nephrol. 2016 Mar-Apr. 26 (2):86-96. [QxMD MEDLINE Link]. [Full Text].
Nasr SH, Collins AB, Alexander MP, Schraith DF, Herrera Hernandez L, Fidler ME, et al. The clinicopathologic characteristics and outcome of atypical anti-glomerular basement membrane nephritis. Kidney Int. 2016 Apr. 89 (4):897-908. [QxMD MEDLINE Link].
Sahin GM, Sahin S, Kantarci G, Ergin H. Mycophenolate mofetil treatment for therapy-resistant glomerulopathies. Nephrology (Carlton). 2007. Jun;12(3):285-8. [QxMD MEDLINE Link].
Opastirakul S, Chartapisak W. Pulse cyclophosphamide induction treatment in Thai children with diffuse proliferative lupus nephritis. Nephrology (Carlton). 2011 Dec 19. [QxMD MEDLINE Link].
Tani C, Mosca M, d'Ascanio A, Neri R, Tavoni A, Carli L, et al. [Long term outcome of treatment of diffuse proliferative glomerulonephritis with pulse steroids and short course pulse cyclophosphamide]. Reumatismo. 2010 Jul-Sep. 62(3):215-20. [QxMD MEDLINE Link].
Chan TM, Li FK, Tang CS. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med. 2000 Oct 19. 343(16):1156-62. [QxMD MEDLINE Link].
Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005 Nov 24. 353(21):2219-28. [QxMD MEDLINE Link]. [Full Text].
Parikh SV, Rovin BH. Current and Emerging Therapies for Lupus Nephritis. J Am Soc Nephrol. 2016 Oct. 27 (10):2929-2939. [QxMD MEDLINE Link]. [Full Text].
Tektonidou MG, Dasgupta A, Ward MM. Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971-2015: A Systematic Review and Bayesian Meta-Analysis. Arthritis Rheumatol. 2016 Jun. 68 (6):1432-41. [QxMD MEDLINE Link]. [Full Text].
Bao H, Liu ZH, Xie HL, et al. Successful treatment of class V+IV lupus nephritis with multitarget therapy. J Am Soc Nephrol. 2008 Oct. 19(10):2001-10. [QxMD MEDLINE Link].
Imran TF, Yick F, Verma S, Estiverne C, Ogbonnaya-Odor C, Thiruvarudsothy S, et al. Lupus nephritis: an update. Clin Exp Nephrol. 2016 Feb. 20 (1):1-13. [QxMD MEDLINE Link].
Plantinga LC, Patzer RE, Drenkard C, Kramer MR, Klein M, Lim SS, et al. Association of time to kidney transplantation with graft failure among U.S. patients with end-stage renal disease due to lupus nephritis. Arthritis Care Res (Hoboken). 2014 Sep 23. [QxMD MEDLINE Link].
Glassock RJ. IgA nephropathy: challenges and opportunities. Cleve Clin J Med. 2008. Aug;75(8):569-76. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis Chapter 10: Immunoglobulin A nephropathy. Kidney Int Suppl (2011). 2012 Jun. 2 (2):209-217. [QxMD MEDLINE Link]. [Full Text].
Kusunoki Y, Namba-Hamano T, Kakimoto T, Yamamoto S, Ikeda N, Wakabayashi K, et al. A case of proliferative glomerulonephritis with immunoglobulin A1-lambda deposits successfully treated by chemotherapy. CEN Case Rep. 2020 Nov. 9 (4):326-332. [QxMD MEDLINE Link]. [Full Text].
Jindal KK. Management of idiopathic crescentic and diffuse proliferative glomerulonephritis: evidence-based recommendations. Kidney Int Suppl. 1999 Jun. 70:S33-40. [QxMD MEDLINE Link].
[Guideline] Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis Chapter 2: General principles in the management of glomerular disease. Kidney Int Suppl (2011). 2012 Jun. 2 (2):156-162. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Yuzawa Y, Yamamoto R, Takahashi K, Katafuchi R, Tomita M, Fujigaki Y, et al. Evidence-based clinical practice guidelines for IgA nephropathy 2014. Clin Exp Nephrol. 2016 Aug. 20 (4):511-535. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Light microscopy (trichrome stain) shows globally increased cellularity, numerous polymorphonuclear cells, cellular crescent (at left of photomicrograph) and fibrinoid necrosis (brick red staining at right of photomicrograph). These findings are characteristic of diffuse proliferative glomerulonephritis.
Diffuse proliferative glomerulonephritis (DPGN). Immunofluorescent microscopy shows (except for anti–glomerular basement membrane [GBM] disease) a granular deposition of immunoglobulins, complement, and fibrin along the GBM, tubular basement membranes, and peritubular capillaries (image 2a). Linear deposition occurs in the GBM in anti-GBM disease (image 2b).
Diffuse proliferative glomerulonephritis (DPGN). Using electron microscopy, electron-dense deposits are visible in the mesangial, subendothelial, intramembranous, and subepithelial locations.

of 3

Author

Moro O Salifu, MD, MPH, MBA, MACP Associate Professor, Department of Internal Medicine, Chief, Division of Nephrology, Director of Nephrology Fellowship Program and Transplant Nephrology, State University of New York Downstate Medical Center

Moro O Salifu, MD, MPH, MBA, MACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Artificial Internal Organs, American Society of Diagnostic and Interventional Nephrology, American Society of Nephrology, American Society of Transplantation, National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Barbara G Delano, MD, MPH, FACP Professor and Chair, Department of Community Health Sciences, School of Public Health, State University of New York Downstate

Barbara G Delano, MD, MPH, FACP is a member of the following medical societies: American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ajay K Singh, MB, MRCP, MBA Associate Professor of Medicine, Harvard Medical School; Director of Dialysis, Renal Division, Brigham and Women's Hospital; Director, Brigham/Falkner Dialysis Unit, Faulkner Hospital

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Interim Chair, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

James H Sondheimer, MD, FACP, FASN Professor of Medicine, Nephrology and Hypertension, Department of Medicine, Wayne State University School of Medicine; Medical Director, DaVita Kresge Dialysis (Detroit)

James H Sondheimer, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology

Disclosure: Nothing to disclose.

Sections Diffuse Proliferative Glomerulonephritis
Overview
Presentation
DDx
Workup
Treatment
Guidelines
Medication
Media Gallery
References

Diffuse Proliferative Glomerulonephritis Medication

Medication Summary

Corticosteroids

Class Summary

Prednisone (Deltasone, Orasone, Meticorten, Sterapred)