Cyclosporine nephrotoxicity: how does it affect renal allograft function and transplant morphology?
Chronic CSA nephrotoxicity is the second most important diagnosis responsible for the late graft failure. CSA associated arteriolopathy (CAA) is a well-known lesion of chronic CSA nephrotoxicity. The clinicopathological characteristics and the significance of CSA nephrotoxicity have changed following reduction in CSA doses and implementation of monitoring of blood levels. Seventy-four CAA patients on CSA therapy were classified as functioning (n=30) or loss groups (n=44). There was no significant difference in severity of CAA. The concomitant lesion of chronic rejection, but not the severity of CAA, was the most important risk factor for graft loss. Among 54 recipients with focal segmental glomerulosclerosis lesions (FGS), 32 (59%) were diagnosed as CAA associated glomerulopathy (CAG). Eighteen of the 32 CAG patients lost their grafts upon follow-up. Decreasing the CSA dosage to maintain lower blood levels than the usually optimal concentrations, but not discontinuation of CSA, has been useful to retard the progression of graft dysfunction in half of 15 isolated pure CAG patients. Patients with increasing daily proteinuria exceeding 2 grams lost their graft function despite CSA reductions. CAA is not a specific lesion of chronic CSA nephrotoxicity; the FGS lesion is also a nonspecific lesion often seen in renal allografts. Isolated chronic CSA arteriolopathy of severe degree has a fairly good prognosis under controlled CSA therapy. The FGS lesion accompanying CAA is considered to be CSA-associated glomerulopathy. These data contribute to therapeutic plans for renal transplant patients during long-term CSA treatment.
Morozumi
K
K
Kidney Center, Nagoya Daini Red Cross Hospital, Nagoya, Japan. morozumi@nagoya2.jrc.or.jp
Takeda
A
A
Uchida
K
K
Mihatsch
M J
MJ
D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D002908:Chronic Disease; D016572:Cyclosporine / Q000633:toxicity*; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects / Q000473:pathology; D017211:Treatment Failure; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine