title: The renin-aldosterone axis in kidney transplant recipients and its association with allograft function and structure.
abstract: The level of the renin-angiotensin-aldosterone system (RAAS) activity in kidney transplant recipients has not been extensively studied or serially profiled. To describe this axis and to determine its association with glomerular filtration rate (GFR) change, interstitial expansion, and end-stage renal disease (ESRD), we measured plasma renin activity (PRA) and plasma aldosterone levels annually for 5 years in 153 kidney transplant recipients randomly assigned to losartan or placebo. PRA and plasma aldosterone levels were in the normal range at all times and did not vary by immunosuppression regimen. Those on losartan exhibited higher PRA but similar plasma aldosterone levels. Neither baseline nor serial PRA or plasma aldosterone levels were associated with GFR decline, proteinuria, or interstitial expansion. Losartan use (hazard ratio (HR) 0.48 (95% confidence interval (CI) 0.21-1.0), insignificant) and Caucasian donor (HR 0.18 (95% CI 0.07-0.4) significant) were associated with less doubling of serum creatinine, death, or ESRD. Hypertension, <3 human leukocyte antigen matches, the combination of tacrolimus-rapamycin, and acute rejection were associated with more events. Neither PRA nor plasma aldosterone levels were independently associated with this outcome. Higher serial plasma aldosterone levels were associated, however, with a significantly higher risk of ESRD (HR 1.01 (95% CI 1.00-1.02)). Thus, systemic RAAS is not overly activated in kidney transplant recipients, but this may not reflect the intrarenal system. Importantly, plasma aldosterone levels may be associated with more ESRD.
authors: Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Naim
authors: N
authors: Issa
authors: Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Fernando
authors: F
authors: Ortiz
authors: Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Scott A
authors: SA
authors: Reule
authors: Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Aleksandra
authors: A
authors: Kukla
authors: Nephrology Division, Hennepin County Medical Center, Minneapolis, Minnesota, USA.
authors: Bertram L
authors: BL
authors: Kasiske
authors: Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Michael
authors: M
authors: Mauer
authors: Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Scott
authors: S
authors: Jackson
authors: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Arthur J
authors: AJ
authors: Matas
authors: Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, Minnesota, USA.
authors: Hassan N
authors: HN
authors: Ibrahim
authors: Department of Pathology, University of Washington, Seattle, Washington, USA
authors: Behzad
authors: B
authors: Najafian
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D000450:Aldosterone / Q000097:blood; D064591:Allografts; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D000450:Aldosterone; D003404:Creatinine; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D019808:Losartan
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