Diffuse Proliferative Glomerulonephritis Treatment & Management

  • Author: Moro O Salifu, MD, MPH, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Jan 12, 2012
 

Medical Care

Early, aggressive therapy is indicated because of the high risk of ESRD. Initiate the following as induction therapy: pulse methylprednisolone of 1 g daily for 3 days, followed by 1 mg/kg for 4-6 weeks and then tapered to 5-10 mg/d for maintenance therapy by 6 months. Alternatively, prednisolone 1 mg/kg (not to exceed 80 mg/d) can be started and tapered as above. Additional induction and maintenance therapy may be indicated, depending on the type of DPGN. Evidence suggests that mycophenolate mofetil (MMF) treatment benefits problematic patients who are refractory to conventional therapies for glomerulopathies.[5]

  • Diffuse proliferative glomerulonephritis due to lupus
    • Pulse methylprednisolone, in combination with mycophenolate mofetil or cyclophosphamide, is indicated for DPGN due to lupus nephritis.[6, 7] Studies show that mycophenolate mofetil is equal to or better than cyclophosphamide in inducing remission of lupus nephritis.[8] MMF treatment appears to aid problematic patients who are refractory to conventional therapies for glomerulopathies, with fewer adverse effects.[5, 9] As a result, mycophenolate mofetil should be the drug of choice for use with steroids.
      • In one study, 42 patients were randomized to receive prednisolone and mycophenolate for 12 months (21 patients, group 1) or prednisolone plus cyclophosphamide for 6 months followed by prednisolone and azathioprine for 6 months (21 patients, group 2).[10] Of the 21 patients treated with mycophenolate mofetil and prednisolone (group 1), 81% had a complete remission and 14% had a partial remission, as compared with 76% and 14%, respectively, of the 21 patients treated with cyclophosphamide and prednisolone followed by azathioprine and prednisolone (group 2). Mycophenolate therapy was associated with fewer side effects than cyclophosphamide.
      • In another study, oral mycophenolate mofetil (initial dose, 1000 mg/d, increased to 3000 mg/d) was compared with monthly intravenous cyclophosphamide (0.5 g/m2 of body surface area, increased to 1 g/m2 of body surface area) as induction therapy for active lupus nephritis over a 6-month period.[11] The study protocol specified adjunctive care and the use and tapering of corticosteroids.
      • Complete remission was observed in 22.5% of patients who received mycophenolate mofetil, as compared with 5.8% of patients treated with cyclophosphamide (p=0.005). There was no difference in the rate of partial remissions (29% vs 24%, respectively). There were fewer severe infections and hospitalizations, but patients receiving mycophenolate experienced more diarrhea. The investigators concluded that mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile.
    • Plasmapheresis, total lymphoid irradiation, and cyclosporine produce variable results but may be considered in severe, refractory cases. Azathioprine is often used as an alternative to cyclophosphamide, particularly in patients concerned about infertility.[12]
    • In a study of 40 patients with class V+IV lupus nephritis, investigators found that multitarget therapy using a combination of MMF, tacrolimus, and steroids achieved a higher rate of complete remission than did intravenous cyclophosphamide therapy.[13] After 9 months, 65% of patients receiving multitarget therapy had experienced complete remission of the nephritis, compared with 15% of patients who received cyclophosphamide treatment. In addition, most adverse events occurred less frequently in the multitarget treatment patients than they did in the cyclophosphamide group.
  • Diffuse proliferative glomerulonephritis due to immunoglobulin A nephropathy
    • Treatment is controversial, due in part to the indolent course of the disease. Patients with proteinuria less than 3 g/d, minimal glomerular changes only, and preserved renal function (creatinine clearance >70 mL/min) may benefit from treatment with prednisone. Those with aggressive disease as manifested by hypertension, progressive azotemia, and nephrotic syndrome may also be offered a trial of prednisone. Gross hematuria alone does not merit steroid use.
    • In patients with progressive disease, fish oil should be considered. Most, but not all, studies thus far show benefit, albeit at high doses.
    • A tonsillectomy may reduce proteinuria and hematuria in those patients with recurrent tonsillitis.
    • Corticosteroids in combination with cyclophosphamide may be tried in those who manifest crescentic DPGN on renal biopsy, although no controlled trials exist. In one study, the use of mycophenolate mofetil did not retard disease progression.
    • No specific therapy is currently offered for milder forms of IgA nephropathy, although the use of ACE inhibitors and/or angiotensin receptor blockers is generally recommended.[14]
  • Anti-GBM antibody–induced diffuse proliferative glomerulonephritis/crescentic glomerulonephritis
    • Initiate treatment early.
    • Induction with steroids, as noted above, plus cyclophosphamide 0.5-1 mg/m2 of body surface area intravenously for 3 months should be initiated, followed by maintenance therapy with azathioprine 1-1.5 mg/kg/d and tapering doses of steroids.
    • Immunosuppression should be discontinued by 12 months, as there has been no benefit of additional therapy beyond this period. Studies show that plasmapheresis is effective in anti-GBM disease. It is most effective if the patient is not yet on dialysis. It should be provided over a course of 2 weeks.
  • Pauci-immune diffuse proliferative glomerulonephritis/crescentic glomerulonephritis
    • Induction with steroids, as noted above, plus cyclophosphamide 0.5-1 mg/m2 of body surface area intravenously for 3 months should be initiated, followed by maintenance therapy with azathioprine 1-1.5 mg/kg/d and tapering doses of steroids.
    • Immunosuppression should be discontinued by 24 months, as there has been no benefit of additional therapy beyond this period. Studies show that plasmapheresis is effective in DPGN due to pauci-immune glomerulonephritis even if the patient is on dialysis or has a serum creatinine level of greater than 5.6 mg/dL. It should be provided over a course of 2 weeks. Patients who cannot tolerate or are not responsive to cyclosporine may benefit from mycophenolate mofetil, although large trials are lacking.
  • Diffuse proliferative glomerulonephritis due to infectious complications
    • The prognosis is good when crescent formation is absent.
    • Patients who are acutely uremic or show progression to end-stage renal failure need dialytic therapy or kidney transplantation.
  • Recurrences: Clinicians generally manage a recurrence in the native kidney or after transplantation similarly, adding appropriate supportive therapy for chronic renal failure.
Next

Consultations

  • Involve a nephrologist in the initial management and as part of the multidisciplinary team.
  • Involve a surgeon when progression to dialysis is inevitable for the creation of an arteriovenous fistula or a graft for dialysis or for insertion of a peritoneal dialysis catheter in the abdomen and for evaluation for kidney transplantation.
  • Consult an otolaryngologist (ENT) and a pulmonologist for diagnosis and management of sinopulmonary disease in cases of Wegener granulomatosis and Goodpasture syndrome, respectively.
Previous
Next

Diet

  • Salt restriction (ie, < 2 g/d) is recommended in all patients with hypertension and nephrosis.
  • Protein restriction (ie, 40-60 g/d or 0.6-0.8 mg/kg/d) may slow progressive renal disease, but evidence in support of this view is still being debated.
  • In those with diuretic-resistant edema, fluid restriction may be required.
Previous
Next

Activity

No restriction in activity is required, and patients should be encouraged to maintain physical activity as tolerated.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Moro O Salifu, MD, MPH, FACP  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, FACP 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, and National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Barbara G Delano, MD, MPH  Director of Home Hemodialysis and Peritoneal Dialysis, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Brooklyn

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

Disclosure: Nothing to disclose.

Specialty Editor Board

James H Sondheimer, MD, FACP  Associate Professor of Medicine, Wayne State University School of Medicine; Medical Director of Hemodialysis, Harper University Hospital at Detroit Medical Center; Medical Director, DaVita Greenview Dialysis (Southfield)

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

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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.

Rebecca J Schmidt, DO, FACP, FASN  Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association

Disclosure: Renal Ventures Ownership interest Other

Chief Editor

Vecihi Batuman, MD, FACP, FASN  Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

References

  1. Xie Q, Liu Y, Liu G, Yang N, Yin G. Diffuse proliferative glomerulonephritis associated with dermatomyositis with nephrotic syndrome. Rheumatol Int. Apr 2010;30(6):821-5. [Medline].

  2. 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. Apr 25 2009;[Medline].

  3. 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. [Medline].

  4. Haas M, Rahman MH, Cohn RA, et al. IgA nephropathy in children and adults: comparison of histologic features and clinical outcomes. Nephrol Dial Transplant. Aug 2008;23(8):2537-45. [Medline].

  5. Sahin GM, Sahin S, Kantarci G, Ergin H. Mycophenolate mofetil treatment for therapy-resistant glomerulopathies. Nephrology (Carlton). 2007;Jun;12(3):285-8. [Medline].

  6. Opastirakul S, Chartapisak W. Pulse cyclophosphamide induction treatment in Thai children with diffuse proliferative lupus nephritis. Nephrology (Carlton). Dec 19 2011;[Medline].

  7. 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. Jul-Sep 2010;62(3):215-20. [Medline].

  8. Ong LM, Hooi LS, Lim TO, et al. Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Nephrology (Carlton). Oct 2005;10(5):504-10. [Medline].

  9. Jayne D. Current management of lupus nephritis: popular misconceptions. Lupus. 2007;16(3):217-20. [Medline].

  10. 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. Oct 19 2000;343(16):1156-62. [Medline].

  11. Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. Nov 24 2005;353(21):2219-28. [Medline]. [Full Text].

  12. Kamijo Y, Hashimoto K, Takahashi K, Ehara T, Shigematsu H, Higuchi M. Treatment with cyclosporine A improves SLE disease activity of Japanese patients with diffuse proliferative lupus nephritis. Clin Nephrol. Aug 2011;76(2):136-43. [Medline].

  13. [Best Evidence] Bao H, Liu ZH, Xie HL, et al. Successful treatment of class V+IV lupus nephritis with multitarget therapy. J Am Soc Nephrol. Oct 2008;19(10):2001-10. [Medline].

  14. Glassock RJ. IgA nephropathy: challenges and opportunities. Cleve Clin J Med. 2008;Aug;75(8):569-76. [Medline]. [Full Text].

  15. 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). May 2008;47(5):702-7. [Medline].

  16. Aasarod K, Iversen BM, Hammerstrom J. Wegener's granulomatosis: clinical course in 108 patients with renal involvement. Nephrol Dial Transplant. May 2000;15(5):611-8. [Medline].

  17. Andrews M, Edmunds M, Campbell A. Systemic vasculitis in the 1980s--is there an increasing incidence of Wegener's granulomatosis and microscopic polyarteritis?. J R Coll Physicians Lond. Oct 1990;24(4):284-8. [Medline].

  18. Austin HA, Balow JE. Natural history and treatment of lupus nephritis. Semin Nephrol. Jan 1999;19(1):2-11. [Medline].

  19. Bosch X, Mirapeix E, Font J. [Neutrophil anticytoplasmic antibodies: their diagnostic utility in vasculitis and glomerulonephritis]. Med Clin (Barc). Mar 26 1994;102(11):412-7. [Medline].

  20. Chan TM, Tse KC, Tang CS, et al. Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis. J Am Soc Nephrol. Apr 2005;16(4):1076-84. [Medline].

  21. Clark WF, Moist LM. Management of chronic renal insufficiency in lupus nephritis: role of proteinuria, hypertension and dyslipidemia in the progression of renal disease. Lupus. 1998;7(9):649-53. [Medline].

  22. Coppo R, Gianoglio B, Porcellini MG. Frequency of renal diseases and clinical indications for renal biopsy in children (report of the Italian National Registry of Renal Biopsies in Children). Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology and Group of Renal. Nephrol Dial Transplant. Feb 1998;13(2):293-7. [Medline].

  23. D'Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis. Aug 2000;36(2):227-37. [Medline].

  24. Flanc RS, Roberts MA, Strippoli GF. Treatment of diffuse proliferative lupus nephritis: a meta-analysis of randomized controlled trials. Am J Kidney Dis. Feb 2004;43(2):197-208. [Medline].

  25. Frisch G, Lin J, Rosenstock J. Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. Nephrol Dial Transplant. Oct 2005;20(10):2139-45.

  26. Garrett PJ, Dewhurst AG, Morgan LS. Renal disease associated with circulating antineutrophil cytoplasm activity. Q J Med. Oct 1992;85(306):731-49. [Medline].

  27. Golbus J, McCune WJ. Lupus nephritis. Classification, prognosis, immunopathogenesis, and treatment. Rheum Dis Clin North Am. Feb 1994;20(1):213-42. [Medline].

  28. Grotz W, Wanner C, Keller E. Crescentic glomerulonephritis in Wegener's granulomatosis: morphology, therapy, outcome. Clin Nephrol. Jun 1991;35(6):243-51. [Medline].

  29. Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis. Jun 1997;29(6):829-42. [Medline].

  30. Huong DL, Papo T, Beaufils H. Renal involvement in systemic lupus erythematosus. A study of 180 patients from a single center. Medicine (Baltimore). May 1999;78(3):148-66. [Medline].

  31. Ioannidis JP, Boki KA, Katsorida ME. Remission, relapse, and re-remission of proliferative lupus nephritis treated with cyclophosphamide. Kidney Int. Jan 2000;57(1):258-64. [Medline].

  32. Jindal KK. Management of idiopathic crescentic and diffuse proliferative glomerulonephritis: evidence-based recommendations. Kidney Int Suppl. Jun 1999;70:S33-40. [Medline].

  33. Kasinath BS, Neilson EG, Hebert L. Short-term prognosis of severe proliferative lupus nephritis. Am J Kidney Dis. Oct 1986;8(4):239-43. [Medline].

  34. Lim CS, Chin HJ, Jung YC. Prognostic factors of diffuse proliferative lupus nephritis. Clin Nephrol. Sep 1999;52(3):139-47. [Medline].

  35. Little MA, Pusey CD. Rapidly progressive glomerulonephritis: current and evolving treatment strategies. J Nephrol. Nov-Dec 2004;17 Suppl 8:S10-9.

  36. McCarty DJ, Manzi S, Medsger TA Jr. Incidence of systemic lupus erythematosus. Race and gender differences. Arthritis Rheum. Sep 1995;38(9):1260-70. [Medline].

  37. Mekhail TM, Hoffman GS. Longterm outcome of Wegener's granulomatosis in patients with renal disease requiring dialysis. J Rheumatol. May 2000;27(5):1237-40. [Medline].

  38. Nolin L, Courteau M. Management of IgA nephropathy: evidence-based recommendations. Kidney Int Suppl. Jun 1999;70:S56-62. [Medline].

  39. Polenakovic M, Grcevska L. Survival rate of patients with glomerulonephritis. Acta Med Croatica. 1992;46(1):15-20. [Medline].

  40. Research Group on Progressive Chronic Renal Disease. Nationwide and long-term survey of primary glomerulonephritis in Japan as observed in 1,850 biopsied cases. Research Group on Progressive Chronic Renal Disease. Nephron. 1999;82(3):205-13. [Medline].

  41. Shoji T, Nakanishi I, Suzuki A. Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy. Am J Kidney Dis. Feb 2000;35(2):194-201. [Medline].

  42. Tomino Y. IgA nephropathy. From molecules to men. Contrib Nephrol. 1999;126:III-IX, 1-115. [Medline].

  43. Wyatt RJ, Julian BA, Baehler RW. Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994. Central Kentucky Region of the Southeastern United States IgA Nephropathy DATABANK Project. J Am Soc Nephrol. May 1998;9(5):853-8. [Medline].

  44. Yahya TM, Pingle A, Boobes Y. Analysis of 490 kidney biopsies: data from the United Arab Emirates Renal Diseases Registry. J Nephrol. May-Jun 1998;11(3):148-50. [Medline].

 
Previous
Next
 
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.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.