Effect of Treatment on the Evolution of Renal Abnormalities in Lupus Nephritis

Abstract

We retrospectively studied the evolution of histopathologic features in successive renal biopsies in patients with lupus nephritis, to evaluate the effects of various treatment regimens. Repeat renal biopsies had been performed in 62 patients after more than 18 months of observation (median interval, 44 months) in randomized therapeutic trials comparing prednisone with cytotoxic drugs. Renal histopathologic features were graded individually, and a composite score reflecting the number and severity of irreversible lesions was defined as a chronicity index. The chronicity index for patients treated with conventional high-dose prednisone increased linearly with the interval between biopsies, whereas the index in the group receiving cytotoxic-drug treatments did not increase over time. After statistical adjustment for important prognostic factors (age and initial chronicity index) identified by multiple linear regression, the difference in the slopes between the group receiving prednisone and the group receiving cytotoxic drugs was significant (P less than 0.0001). We conclude that cytotoxic-drug treatment reduces the likelihood of progressive renal scarring in lupus nephritis.

Dexamethasone Induces Connective Tissue Growth Factor Expression in Renal Tubular Epithelial Cells in a Mouse Strain-Specific Manner

“…If phosphorylated STAT3 is truly involved in this signaling process, then a tyrosine kinase most likely plays a direct role because it phosphorylates STAT3. 34 The observation has often been made that sclerotic and fibrotic reactions occur at the same time that inflammatory and immune reactions subside in the diseased kidney after glucocorticoid treatment 35 ; our above findings may provide a possible explanation for this. Such processes are likely mediated by high concentrations of glucocorticoids because patients with sustained exposure to low levels of glucocorticoids, such as those with Cushing's syndrome and asthmatics treated with glucocorticoids, have not been reported to develop renal fibrosis.…”

The American college of rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials

“…The committee noted that different definitions have been used to quantify activity (14,24,25,91,(107)(108)(109)(110)(111), chronicity (8,12,14,24,25,48,91,110), and "inactive lesions" (107,108). There are no published data or criteria by which to establish a clinically significant threshold of either activity or chronicity.…”

Risk factors for ovarian failure in patients with systemic lupus erythematosus

“…In the study performed by Wang et al (6), 92 patients treated with oral cyclophosphamide presented with a permanent amenorrhea rate of 27%, and patient age at the initiation of treatment and cumulative dose of cyclophosphamide were associated with ovarian insufficiency. Other studies which employed dosages of 1-4 mg kg -1 day -1 of oral cyclophosphamide for 4 to 4.3 years have reported higher rates of amenorrhea in approximately 53-71% of the patients (13,(30)(31)(32). In a more recent retrospective cohort study by Mok et al (8), of the 70 women treated with cyclophosphamide, 18 (26%) developed ovarian insufficiency, with a higher rate in patients who had received the oral immunosuppressor (oral cyclophosphamide: 30%; venous cyclophosphamide: 13%).…”