title: Renin-Angiotensin System Blockage and Avoiding High Doses of Calcineurin Inhibitors Prevent Interstitial Fibrosis and Tubular Atrophy in Kidney Transplant Recipients.
abstract: OBJECTIVE
  Chronic allograft dysfunction is a complex and multifactorial process characterized by progressive interstitial fibrosis and tubular atrophy. The finding of interstitial fibrosis and tubular atrophy is prevalent among kidney transplant patients receiving a calcineurin inhibitor-based immunosuppressive regimen and may be considered as a surrogate of allograft survival. Both immune (acute rejection episodes, sensitization, and HLA incompatibility) and nonimmune (donor age, delayed graft function, calcineurin inhibitor toxicity, infections, and hypertension) mechanisms play a role in chronic allograft dysfunction, and different causes all lead to similar histologic and clinical final pathways, with the end result of graft loss. In our study, we aimed to compare the outcomes of kidney transplant recipients with or without interstitial fibrosis and tubular atrophy in protocol biopsies to determine the conditions that may affect allograft survival.
  
  
  METHODS
  We divided 192 kidney transplant recipients into 2 groups (96 patients with interstitial fibrosis and tubular atrophy; 96 patients without interstitial fibrosis and tubular atrophy) according to protocol biopsy at 6 months. Patient groups were compared according to their risk factors for chronic allograft dysfunction (cold ischemia time, delayed graft function, donor age, infections, mean blood calcineurin levels, and hypertension).
  
  
  RESULTS
  Cold ischemia time, delayed graft function, high 24-hour proteinuria levels, and higher mean blood calcineurin levels were found to be major risk factors for poor graft function in kidney transplant recipients with interstitial fibrosis and tubular atrophy. Renin-angiotensin system blockage with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was found to be preventive for interstitial fibrosis and tubular atrophy after kidney transplant.
  
  
  CONCLUSIONS
  Preventing prolongation of cold ischemia time, lowering blood cholesterol levels, angiotensin-converting enzyme inhibitors and angiotensin receptor blocker treatment even without existing proteinuria and avoiding higher doses of calcineurin inhibitors should be major approaches in kidney transplant recipients.
authors.affiliation: Department of Nephrology, Baskent University Faculty of Medicine, Ankara, Turkey.
authors.forename: Burak
authors.initials: B
authors.lastname: Sayin
authors.forename: Burak
authors.initials: B
authors.lastname: Canver
authors.forename: Bahar
authors.initials: B
authors.lastname: Gurlek Demirci
authors.forename: Turan
authors.initials: T
authors.lastname: Colak
authors.forename: Binnaz Handan
authors.initials: BH
authors.lastname: Ozdemir
authors.forename: Mehmet
authors.initials: M
authors.lastname: Haberal
mesh_terms: D000328:Adult; D064591:Allografts; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001284:Atrophy; D001706:Biopsy; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D050377:Cold Ischemia / Q000009:adverse effects; D051799:Delayed Graft Function / Q000209:etiology; D005260:Female; D005355:Fibrosis; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007674:Kidney Diseases / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D011507:Proteinuria / Q000209:etiology; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents