The purpose of this study is to determine whether two distinct histopathological-immunopathological lesions, which have been reported in severe lupus nephritis, diffuse global glomerulonephritis (GN) (WHO IV) and a segmental and necrotising GN (WHO III) can be reported to coexist in a single patient. We examine the evidence of coexistence of these disparate lesions and the prognostic significance in a group of patients with severe lupus nephritis who have been subjected to a common therapeutic regimen by protocol. The simple, reproducible parameter indicating the presence of glomerular capillary necrosis was the presence of crescents. We, therefore, reviewed 39 renal biopsies with diffuse global lupus GN (WHO IV) (Churg, J, Sobin, LH. Lupus nephritis. Renal disease, classification and atlas of glomerular diseases. New York: Igaku-Shoin; 1982. p. 127-149). and used crescents as a surrogate for glomerular necrosis. Peripheral capillary immune deposits were less prominent in WHO IV with crescents compared with those without and resembled the reduced immune deposits seen in severe segmental GN (WHO III >or= 50%). Patients with WHO IV with crescents had decreased survival without end-stage renal disease (P = 0.02), fewer remissions (P = 0.04) and more adverse outcomes (12/22 vs 3/17) (P = 0.02) than those without crescents, and this was similar to patients with WHO III >or=50%. We conclude that, on the basis of immunological and morphological features, WHO IV with crescents appears to be the result of two distinct pathogenetic mechanisms. We propose that diffuse global lupus GN, associated with crescents, is best described as WHO class IV + WHO class III.

The level of renal function at biopsy is predictive of outcome in patients with severe lupus nephritis (SLN). While renal function has been based on serum creatinine (SCr) alone, measuring the estimated glomerular filtration rate (eGFR) utilizing the Modification of Diet in Renal Disease (MDRD) Study equation has been found to be more accurate. The MDRD eGFR (ml/min/1.73 m(2)) at biopsy was calculated in 86 patients with SLN and patients were categorized based on eGFR: ≥60 (33 pts), 59-30 (33 pts) and <30 (20 pts). An eGFR was <60 in 18% of patients with a normal SCr. After 120 ± 65 months of follow-up, attainment of a complete remission (76% versus 30% versus 10%, p < 0.0001) and patient survival without end-stage renal disease (ESRD; 10 year survival: 85% versus 45% versus 14%, p < 0.0001 overall) was highest in patients with an eGFR ≥60 and lowest in those with an eGFR <30. The long-term prognosis for patients with severe lupus nephritis and an eGFR ≥60 was extremely good. Since the prognosis for patients with an eGFR <60 was poor even in those patients with a normal SCr, renal function is more accurately determined by the MDRD eGFR.

A randomized, double-blind, placebo-controlled, multicenter trial was performed to assess the safety and efficacy of subcutaneous recombinant erythropoietin (EPO) in peritoneal dialysis patients. Seventy-eight patients were randomized to receive EPO and 74 received placebo during the first 12 wk. After this, placebo patients with hematocrit less than 32% entered the EPO maintenance phase along with the initial EPO patients. Hematocrit rose significantly in the EPO group from 23.8 to 32% after 6 wk, and this was sustained at 33.7% at 12 wk. In the placebo group, the prestudy hematocrit was 23.8% as well, and no significant change in hematocrit occurred over 12 wk. Concomitant with the rise in hematocrit, transfusion requirements fell only in the EPO group. Eighty-eight percent of patients receiving EPO had their anemia ameliorated by Week 12 of the study. There was a wide range of dosage requirements during the maintenance phase, ranging from 8,000 U thrice weekly to 4,000 U every other week. Adverse events after EPO were similar to those seen in hemodialysis patients given this agent, with hypertension developing or worsening in 55% of EPO patients during the initial 12 wk of therapy. Blood pressure was more likely to rise in patients with hypertension before receiving EPO. EPO is safe and effective in peritoneal dialysis patients, as it is in hemodialysis patients. Other than a rise in blood pressure, which is manageable with antihypertensives and ultrafiltration with dialysis, no serious side effects are seen. The optimal target hematocrit, effects of anemia improvement on quality of life, and end-organ (heart, brain) effects of anemia improvement in this patient population require further study.

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