Long-term low-dose cyclosporine therapy for severe psoriasis: effects on renal function and structure.

BACKGROUND: The effectiveness of cyclosporine in the treatment of severe psoriasis is well known. OBJECTIVE: We evaluated the efficacy and toxicity of systemic cyclosporine in patients with severe psoriasis, observing short-term (12 weeks) and long-term (3 to 5 years) effects. METHODS: To further elucidate efficacy and safety, 42 patients with severe psoriasis were treated initially with cyclosporine 5 to 6 mg/kg per day for 12 weeks. A subset of 14 patients continued maintenance treatment for 3.5 years to study the long-term effects of cyclosporine on renal function and structure. Renal biopsies were performed after 2.5 years and 3.5 years of treatment. Renal histologic findings were correlated with renal function. RESULTS: By weeks 8 and 12, 64% (n = 27) and 86% (n = 36) of patients, respectively, were rated clear or almost clear of the psoriasis. However, a subpopulation of 15 patients did not respond to 5 mg/kg daily but improved when the dose was increased to 6 mg/kg daily. Clearance or near clearance was achieved in 67% of this subpopulation after 4 weeks. For the 29 patients whose glomerular filtration rate (GFR) was measured, mean GFR fell by 7% from baseline to week 4 (p < 0.05). This change was reversible when dosage was reduced by 1 mg/kg per day in each of these patients. Patients older than 45 years of age experienced significant elevation of mean diastolic blood pressure and had reduced GFR and increased serum creatinine. After 2.5 years, of the 14 patients who continued maintenance treatment, two had biopsy specimens that showed moderate interstitial fibrosis and tubular atrophy. The remainder showed only minimal to mild structural damage. After 3.5 years of cyclosporine treatment, repeat renal biopsy specimens revealed slight increases in structural changes in nine subjects. These changes correlated with increasing age and drug-induced hypertension. CONCLUSION: We conclude that 5 mg/kg of cyclosporine daily is usually an effective initial dose for psoriasis. Patients who do not respond will often benefit from elevation of the dose to 6 mg/kg daily. Older patients experience cyclosporine-induced hypertension and changes in renal function and structure more frequently than do younger patients.

Response of lupus nephritis to plasmapheresis without demonstration of circulating immune complexes.

A case of post-partum SLE in a 25-year-old Mexican-American woman is presented. The disease was associated with systemic vasculitis and diffuse proliferative glomerulonephritis. Abundant evidence for the deposition of complement activating immune complexes was found in skin and kidney biopsies, but no circulating immune complexes could be measured. Therapeutic modalities including corticosteroids administered both orally and intravenously, azathioprine, antihypertensives, and hemodialysis failed to effectuate lasting benefit. Large volume plasmapheresis led to immediate improvement and a dramatic return of renal function. A mechanism of action for the resulting effect is considered.

Kappa light chain nephropathy without evidence of myeloma cells. Response to chemotherapy with cessation of maintenance hemodialysis.

A rarely diagnosed nodular glomerulopathy is presented arising secondary to kappa light chain deposition and clinically characterized by hypertension, congestive heart failure, massive proteinuria and slowly progressive azotemia. Kappa light chains were detected in the urine, the glomerular nodules, and the basement membranes of both glomeruli and tubules. A malignant proliferation of plasma cells could not be detected. Two morphologic features were unusual: the presence of microaneurysms, and the deposition of immunoglobulin and complement in a similar pattern to the kappa light chains. Noteworthy clinical aspects included the elusiveness of the proper diagnosis, the massive proteinuria in the absence of amyloid deposits, and the remarkable improvement in renal function following intermittent chemotherapy.

Contraindications for mannitol in aphakic glaucoma.

When prescribing mannitol to decrease intraocular pressure, the physician must be alert to potential complications. A 72-year-old woman suffered obtundation, intractable pulmonary edema, acidemia, and irreversible renal insufficiency despite vigorous hemodialysis. When renal function is compromised, careful monitoring of electrolyte levels, daily urine output, and renal function is necessary with mannitol therapy.