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Diffuse Proliferative Glomerulonephritis Treatment & Management

  • Author: Moro O Salifu, MD, MPH, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
Updated: Apr 28, 2015

Medical Care

Early, aggressive therapy is indicated in diffuse proliferative glomerulonephritis (DPGN) because of the high risk of progression to end-stage renal disease (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 patients with DPGN that is refractory to conventional therapies for glomerulopathies.[5]

Diffuse proliferative glomerulonephritis due to lupus

Pulse methylprednisolone, in combination with MMF or cyclophosphamide, is indicated for DPGN due to lupus nephritis.[6, 7] Studies show that MMF is as good as or better than cyclophosphamide in inducing remission of lupus nephritis.[8] MMF treatment appears to aid patients with DPGN that is refractory to conventional therapies for glomerulopathies, with fewer adverse effects.[5, 9] Consequently MMF should be the drug of choice for use with steroids.

In one study, 42 patients were randomized to receive prednisolone and MMF 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 patients in group 1, 81% had a complete remission and 14% had a partial remission, as compared with 76% and 14%, respectively, of the patients in group 2. MMF therapy was associated with fewer side effects than cyclophosphamide.

In another study, oral MMF (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 MMF, 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 MMF 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.

Kidney transplantation in patients with ESRD secondary to lupus nephritis is typically delayed to allow for quiescence of lupus-related immune activity. However, a review of national ESRD surveillance data by Plantinga and colleagues determined that white LN-ESRD patients who were transplanted after 3 or more months on dialysis were at increased risk of graft failure. No such association was seen in black recipients.[45]

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. 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 angiotensin-converting enzyme (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 ESRD need dialysis or kidney transplantation. Clinicians generally manage a recurrence in the native kidney or after transplantation similarly, adding appropriate supportive therapy for chronic renal failure.



See the list below:

  • 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.


See the list below:

  • 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.


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

Contributor Information and Disclosures

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 Society of Transplantation, American Society of Diagnostic and Interventional Nephrology, American Medical Association, American Society for Artificial Internal Organs, American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.


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

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, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, 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, International Society of Nephrology

Disclosure: Nothing to disclose.

Additional Contributors

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

Disclosure: Receive dialysis unit medical director fee (as independ ent contractor) for: DaVita .

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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.
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