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Background: Diffuse Proliferative Glomerulonephritis (DPGN) is the most ominous form of lupus nephritis. Treatment according to the "NIH Protocol" is considered by many physicians to be the treatment of choice for this form of disease, but this is not accepted exclusively. OUR AIM: To evaluate the outcome of SLE patients with biopsy proven DPGN diagnosed and treated in our department, between the years 1976-1996, and to compare the results achieved by using the "NIH Protocol" as opposed to other forms of treatment., Patients and Methods: The archive of the Department of Pathology was screened for patients with SLE and DPGN. The specimens were re-examined to confirm the diagnosis and calculate the activity and chronicity scores. The pertinent data was extracted from the patients medical records., Results: Twenty-six patients fulfilled the inclusion criteria, 22 females and 4 males. We followed-up on these patients for an average period of 89 +/- 74 months (range 9-255). More than 80% of the patients achieved remission, about a third experienced at least one relapse. Only one patient died during the follow-up period and 4 others developed end stage renal failure necessitating chronic renal replacement therapy. Sixteen patients were treated according to the NIH protocol, the other 10 were treated with high dose Prednisone, either alone or in combination with oral immunosuppressive drugs. At time of diagnosis there was no statistically significant difference between the two groups regarding the age and gender distribution, blood levels of creatinine and C3 and the level of proteinuria. We were unable to demonstrate any statistically significant difference between the two groups in any of the evaluated parameters, regarding neither patient and kidney survival nor the type and rate of complications., Conclusion: Following treatment, patient and kidney survival is good. The NIH protocol is the treatment of choice, but the use of high dose steroids for six months with or without oral immunosuppressive drugs may yield comparable results in selected cases.