WASHINGTON, D.C.—Class IV patients with diffuse lupus glomerulonephritis with crescents may require more aggressive therapy directed at non-immune complex mediated necrotizing glomerulonephritis compared to patients without crescents, according to a new study.
Crescents are epithelial cellular proliferations outside the capillary loops in the glomerulus. “Patients without crescents may just have simply an intense inflammatory reaction and may respond to steroids and cyclophosphamide, and they tend to do quite well over the long term,” said lead investigator Robert S. Katz, MD, associate professor of medicine at Rush Medical College in Chicago. “However, those with crescents may be somewhat refractory to treatment and may need more intense or longer treatment with alkylating drugs and steroids.”
He and his colleagues reviewed 39 renal biopsies from patients with diffuse lupus glomerulonephritis for histologic features of vasculitis. The patients were enrolled into a therapeutic trial of plasmapheresis and followed for more than 10 years. All biopsies showed diffuse, global endocapillary proliferation involving all or nearly all glomeruli, and wire-loops, hyaline thrombi, and massive subendothelial and mesangial electron-dense deposits. These features were common findings among all the study patients.
After taking into account fibrinoid necrosis (which was found in 15 of the 39 biopsies), karyorrhexis (found in 28 biopsies), and “breaks” in the glomerular basement membrane (found in 13 biopsies), the researchers concluded that crescents were a surrogate for glomerular necrosis.
Overall, 22 patients (57%) had crescents and 17 (43%) did not. The groups did not differ significantly in age or gender. The disease activity index was higher in biopsies with crescents than without (14.7 vs. 10.1). The chronicity index, mean number of sclerotic glomeruli, and the number of biopsies with sclerotic glomeruli did not differ.
At baseline, patients with crescents had a higher serum creatinine level than those without (1.9 vs. 1.3 mg/dL), but the researchers observed no difference in protein excretion, age, sex, race, BP, and treatment (including randomization to receive plasmapheresis). After baseline, renal status at four weeks and throughout the course of the study was not significantly different between patients with and without crescents.
Nine patients with crescents (41%) had remissions compared with 13 patients without crescents (76%). Twelve patients (54.5%) with crescents had adverse outcomes—defined as end-stage renal disease, non-renal death, or deteriorating renal function—compared with three patients without crescents (17.6%).
Adverse outcomes were reflected in decreased patient survival without ESRD after 10 years (59% for patients with crescents vs. 82% for patients without crescents) and 15 years (40% vs. 82%, respectively).
“We have identified in biopsies that the presence of crescents correlates with more of a necrotizing process that can seriously damage the glomerulus,” said Dr. Katz, who reported study findings here at the American College of Rheumatology annual meeting. “So, in this way the biopsy may actually give us more information about which patients will actually respond to treatment.”
Glomerulonephritis progressed de-spite standard immunosuppressive therapy with high dose prednisone and two months of oral Cytoxan with or without plasmapheresis in the patients with crescents. The researchers theorize that a pathogenic mechanism is involved that is separate from the glomerular deposition of DNA and anti-DNA immune complexes.