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

Naim Issa, Fernando Ortiz, Scott A Reule, Aleksandra Kukla, Bertram L Kasiske, Michael Mauer, Scott Jackson, Arthur J Matas, Hassan N Ibrahim, Behzad Najafian, Naim Issa, Fernando Ortiz, Scott A Reule, Aleksandra Kukla, Bertram L Kasiske, Michael Mauer, Scott Jackson, Arthur J Matas, Hassan N Ibrahim, Behzad Najafian

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.

Trial registration: ClinicalTrials.gov NCT01467895.

Conflict of interest statement

DISCLOSURE

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Plasma Renin Activity and Plasma Aldosterone over time: A. overall and B. by treatment group). Error bars are ± 1 SE.
Figure 1
Figure 1
Plasma Renin Activity and Plasma Aldosterone over time: A. overall and B. by treatment group). Error bars are ± 1 SE.
Figure 2
Figure 2
Plasma Renin Activity vs. Plasma Aldosterone at A. baseline and B. visit number 5 (four years post-transplant). Shaded area indicates patients with normal values for both parameters.
Figure 2
Figure 2
Plasma Renin Activity vs. Plasma Aldosterone at A. baseline and B. visit number 5 (four years post-transplant). Shaded area indicates patients with normal values for both parameters.
Figure 3
Figure 3
Plasma Renin Activity and Plasma Aldosterone levels vs. Iothalamate GFR values A., B. baseline and C., D. visit number 5.
Figure 3
Figure 3
Plasma Renin Activity and Plasma Aldosterone levels vs. Iothalamate GFR values A., B. baseline and C., D. visit number 5.
Figure 3
Figure 3
Plasma Renin Activity and Plasma Aldosterone levels vs. Iothalamate GFR values A., B. baseline and C., D. visit number 5.
Figure 3
Figure 3
Plasma Renin Activity and Plasma Aldosterone levels vs. Iothalamate GFR values A., B. baseline and C., D. visit number 5.

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