title: Cyclosporine associated lesions in native kidneys of diabetic pancreas transplant recipients.
abstract: Five years of normoglycemia following pancreas transplantation (PT) does not ameliorate glomerular lesions in patients with their own kidneys and with long-term insulin-dependent diabetes (IDDM) (Lancet 342:1193, 1993). All these patients received cyclosporine (CsA) as part of their immunosuppression. Here we examined the relationship of CsA dose and blood levels to the presence and severity of CsA-associated renal lesions and changes in renal function in these PT patients. Renal biopsies were taken before (0) and two and five years after PT from 13 non-uremic IDDM patients and were compared with baseline and five year biopsies from 10 IDDM controls (C). CsA dose was reduced from 10 +/- 3 mg/kg/day in the first month to 5 +/- 2 in the fifth year post-PT. Creatinine clearance (CCr) decreased by 34% at one year post-PT and was stable thereafter, and did not change in C. The decline in CCr from 0 to one year was related to CsA blood levels and dose (P < 0.005) at one year. Cortical interstitial volume fraction [Vv(Int/Cortex)], the index of tubular atrophy, and % sclerotic glomeruli increased significantly from 0 to five years post-PT (P < 0.005, 0.01 and 0.001, respectively), but did not change in C. There was no significant change from 0 to two years post-PT in these lesions, while there was a clear progression from two to five years. Mean CsA dose and blood levels in the first year post-PT correlated with the increase (delta) in Vv(Int/Cortex) at five years (P < 0.05 for both).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Internal Medicine, University of Padova Medical School, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Fioretto
authors.forename: M W
authors.initials: MW
authors.lastname: Steffes
authors.forename: M J
authors.initials: MJ
authors.lastname: Mihatsch
authors.forename: E H
authors.initials: EH
authors.lastname: Strøm
authors.forename: D E
authors.initials: DE
authors.lastname: Sutherland
authors.forename: M
authors.initials: M
authors.lastname: Mauer
mesh_terms: D000293:Adolescent; D000328:Adult; D001160:Arterioles / Q000473:pathology; D001284:Atrophy; D001706:Biopsy; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*; D005260:Female; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D016035:Pancreas Transplantation; D012079:Renal Circulation
chemical_list: D016572:Cyclosporine