Renin–angiotensin system blockade and kidney transplantation: a longitudinal cohort study

Hernández, Domingo; Muriel, Alfonso; Abraira, Víctor; Pérez, Germán; Porrini, Esteban; Marrero, Domingo Hernández; Zamora, Javier; González-Posada, José Manuel; Delgado, Patricia; Rufino, Margarita; Torres, Armando

doi:10.1093/ndt/gfr276

Cited by 37 publications

(23 citation statements)

References 27 publications

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“…However, losartan was associated with a reduction in the the secondary outcome of doubling of interstitium from baseline to 5 year biopsies or all-cause ESRD, [odds ratio of 0.36 (95%CI 0.13–0.99), p= 0.05] (5). Hernandez et al recently published the results of a longitudinal cohort study of 414 patients who received ACE inhibitors or angiotensin-receptor blockers with a follow-up that ranged between 6 and 40 months and demonstrated that the use of these agents was associated with a reduction in the risk of mortality but they were not associated with a significant improvement of allograft survival (7). On the other hand, the evidence regarding the impact of the ACE gene polymorphisms on kidney transplant function has been mixed.…”

Section: Discussionmentioning

confidence: 99%

The renin–aldosterone axis in kidney transplant recipients and its association with allograft function and structure

Issa

Ortiz

Reule

et al. 2014

Kidney International

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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 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, [HR 0.48 (95% 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, less than 3 HLA-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.

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Section: Discussionmentioning

confidence: 99%

The renin–aldosterone axis in kidney transplant recipients and its association with allograft function and structure

Issa

Ortiz

Reule

et al. 2014

Kidney International

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show abstract

“…In another retrospective study from Austria, ACEi/ARB therapy was shown to improve long‐term patient survival, but not death‐censored graft survival ( P = 0.57) . A recent single center study also has noted that ACEi/ARB therapy was associated with lower risk of patient mortality, but not graft loss . These studies were about the usual practice of transplanting adult donor kidneys to adult recipients and about treating the late development of proteinuria and CAN.…”

Section: Discussionmentioning

confidence: 99%

“…They are believed to reduce glomerular capillary pressure by dilating the efferent arterioles of glomeruli and to alleviate or inhibit hemodynamic and molecular injuries from glomerular hyperfiltration . However, the renal protective effect of ACEi/ARB therapy in the kidney transplant population remains inconclusive . To our knowledge, there is no publication investigating ACEi/ARB therapy in adults transplanted with single pediatric donor kidneys.…”

Section: Introductionmentioning

confidence: 99%

Early inhibition of the renin-angiotensin system improves the long-term graft survival of single pediatric donor kidneys transplanted in adult recipients

et al. 2013

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SummaryTransplanting single pediatric donor kidneys into adult recipients has an increased risk of hyperfiltration injury and graft loss. It is unknown if reninangiotensin system (RAS) blockers are beneficial in this setting. We retrospectively analyzed 94 adults who received single kidneys from donors <10 years old during 1996-2009. The recipients were divided into group 1 with RAS blockers (n = 40) and group 2 without RAS blockers (n = 54) in the first year of transplant. There was no significant difference in any donor/recipient demographic between the two groups. Graft function, incidence of delayed graft function, acute rejection, and persistent proteinuria were not statistically different either. KaplanMeier estimated death-censored graft survivals were significantly better in group 1 than in group 2: 95 vs. 81.2%, 82.4 vs. 61.2%, 72.6 vs. 58.5%, and 68.5 vs. 47.2% at 1, 3, 5, and 7 years, respectively (log rank P = 0.043). Multivariable analysis found persistent proteinuria was a risk factor for graft loss (OR 2.70, 95% CI 1.33-5.49, P = 0.006), while RAS blockers reduced the risk of graft loss (OR 0.38, 95% CI 0.18-0.79, P = 0.009). Early RAS blockade therapy in the first year of transplant is associated with superior long-term graft survival among adults transplanted with single pediatric donor kidneys.

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“…Indeed, threatment with enalapril reduced the number of circulating monocytes in allograft recepients in the current study, and consequently fewer of these cells accumulated in the graft as assessed by imaging, histology and flow cytometry. Previous clinical reports described prolonged graft survival in patients taking an ACE inhibitor or angitensin-II receptor blocker in kidney transplants 26 and heart allografts 27 while others did not 28 . A prospective trial of ACE inhibitor administration in patients after heart transplantation could provide clarity in this regard.…”

Section: Discussionmentioning

confidence: 97%

Nanoparticle PET-CT Detects Rejection and Immunomodulation in Cardiac Allografts

Ueno

Dutta

Keliher

et al. 2013

Circ: Cardiovascular Imaging

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Background Macrophages (MΦ) predominate among the inflammatory cells in rejecting allografts. These innate immune cells, in addition to allospecific T cells, can damage cardiomyocytes directly. Methods and Results We explored if sensitive PET/CT imaging of MΦ-avid nanoparticles detects rejection of heart allografts in mice. In addition, we employed the imaging method to follow the immunomodulatory impact of angiotensin converting enzyme inhibititor therapy (ACEi) on myeloid cells in allografts. Dextran nanoparticles were derivatized with the PET isotope copper-64 and imaged seven days after transplantation. C57/BL6 recipients of BALB/c allografts displayed robust PET signal (standard uptake value allograft, 2.8±0.3; isograft control, 1.7±0.2; p<0.05). Autoradiography and scintillation counting confirmed the in vivo findings. We then imaged the effects of ACEi (5mg/kg Enalapril). ACEi significantly decreased nanoparticle signal (p<0.05). Histology and flow cytometry showed a reduced number of myeloid cells in the graft, blood and lymph nodes, as well as diminished antigen presentation (p<0.05 versus untreated allografts). ACEi also significantly prolonged allograft survival (12 versus 7 days, p<0.0001). Conclusions Nanoparticle MΦ PET-CT detects heart transplant rejection and predicts organ survival by reporting on myeloid cells.

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Renin–angiotensin system blockade and kidney transplantation: a longitudinal cohort study

Abstract: ACEI/ARB prescription may be suggested as beneficial among multiple medications for reducing mortality in kidney transplant recipients, but its use was not associated with longer graft survival.

Cited by 37 publications

References 27 publications

The renin–aldosterone axis in kidney transplant recipients and its association with allograft function and structure

The renin–aldosterone axis in kidney transplant recipients and its association with allograft function and structure

Early inhibition of the renin-angiotensin system improves the long-term graft survival of single pediatric donor kidneys transplanted in adult recipients

Nanoparticle PET-CT Detects Rejection and Immunomodulation in Cardiac Allografts

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