title: Specificity of histological markers of long-term CNI nephrotoxicity in kidney-transplant recipients under low-dose cyclosporine therapy.
abstract: The specificity of chronic histological lesions induced by calcineurin inhibitors (CNI) is often questioned, but few studies have directly compared long-term lesions in renal-transplant patients who received this treatment and those who did not. We therefore conducted a retrospective study of 141 kidney-transplant recipients treated with (n = 48) or without (n = 93) cyclosporine (CsA) to compare the histological lesions observed at 3-month, 24-month and 10-year protocol biopsies. All of the chronic elementary lesions (glomerulosclerosis, interstitial fibrosis, tubular atrophy, arteriolar hyalinosis, fibrointimal thickening) progressed in frequency and severity in both groups, although significantly more in the CsA group. Ten-year biopsy results showed that 92% of patients in the CsA-treated group and 65% in the control group had arteriolar hyalinosis lesions. When we focused on muscular arteriolar hyaline deposits more specific to CsA arteriolopathy, we observed these lesions in 68% of CsA patients and 28% of patients who had never received CsA. CsA was not the sole factor involved in the development of arteriolar hyalinosis and was independently associated with an increased risk of graft loss. In summary, we observed that histological lesions commonly attributed to CsA nephrotoxicity were not sufficiently specific to definitively diagnose CNI nephrotoxicity.
authors: Service de Transplantation Rénale Adulte, Hopital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France. renaud.snanoudj@nck.aphp.fr
authors: R
authors: R
authors: Snanoudj
authors: V
authors: V
authors: Royal
authors: C
authors: C
authors: Elie
authors: M
authors: M
authors: Rabant
authors: C
authors: C
authors: Girardin
authors: E
authors: E
authors: Morelon
authors: H
authors: H
authors: Kreis
authors: J-C
authors: JC
authors: Fournet
authors: L-H
authors: LH
authors: Noël
authors: C
authors: C
authors: Legendre
mesh_terms: D000328:Adult; D001160:Arterioles / Q000187:drug effects / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis*; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000175:diagnosis* / Q000401:mortality; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine