Renin-Angiotensin System Blockade and Long-term Clinical Outcomes in Kidney Transplant Recipients: A Meta-analysis of Randomized Controlled Trials

Hiremath, Swapnil; Fergusson, Dean; Fergusson, Nicholas A; Bennett, Alexandria; Knoll, Greg

doi:10.1053/j.ajkd.2016.08.018

Cited by 69 publications

(48 citation statements)

References 30 publications

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“…57 Several primary and secondary prevention measures in the general population have led to a temporal decline in cardiovascular disease and mortality. [10][11][12]59 We also note that congestive heart failure, and not ischemic heart disease, is the most common cause of CVEs after kidney transplantation, with a crude incidence of 21.23 events per 1000 person-years. [10][11][12]59 We also note that congestive heart failure, and not ischemic heart disease, is the most common cause of CVEs after kidney transplantation, with a crude incidence of 21.23 events per 1000 person-years.…”

Section: Discussionmentioning

confidence: 74%

“…57,58 This is unlikely to occur in the KT recipient population, as mean recipient age at transplantation is rising, there is a high prevalence of cardiovascular disease with age in this population, and conventional therapeutic strategies are often ineffective. [10][11][12]59 We also note that congestive heart failure, and not ischemic heart disease, is the most common cause of CVEs after kidney transplantation, with a crude incidence of 21.23 events per 1000 person-years. A previous study has reported a higher incidence of de novo heart failure but a similar incidence of de novo ischemic heart disease among KT recipients when compared to the population-based cohorts from Framingham and Minnesota.…”

Section: Discussionmentioning

confidence: 74%

“…[10][11][12] Hence, there is a need to better understand the risk factors associated with CVEs in this specific population and to develop therapeutics tailored to prevent and treat these events. [10][11][12] Hence, there is a need to better understand the risk factors associated with CVEs in this specific population and to develop therapeutics tailored to prevent and treat these events.…”

mentioning

confidence: 99%

“…cardioprotective therapies might be ineffective in KT recipients. [10][11][12] Hence, there is a need to better understand the risk factors associated with CVEs in this specific population and to develop therapeutics tailored to prevent and treat these events.…”

mentioning

confidence: 99%

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Induction immunosuppression agents as risk factors for incident cardiovascular events and mortality after kidney transplantation

Sandal

Bae

McAdams‐DeMarco

et al. 2019

American Journal of Transplantation

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Low T cell counts and acute rejection are associated with increased cardiovascular events (CVEs); T cell–depleting agents decrease both. Thus, we aimed to characterize the risk of CVEs by using an induction agent used in kidney transplant recipients. We conducted a secondary data analysis of patients who received a kidney transplant and used Medicare as their primary insurance from 1999 to 2010. Outcomes of interest were incident CVE, all‐cause mortality, CVE‐related mortality, and a composite outcome of mortality and CVE. Of 47 258 recipients, 29.3% received IL‐2 receptor antagonist (IL‐2RA), 33.3% received anti‐thymocyte globulin (ATG), 7.3% received alemtuzumab, and 30.0% received no induction. Compared with IL‐2RA, there was no difference in the risk of CVE in the ATG (adjusted hazard ratio [aHR] 0.98, 95% confidence interval [CI] 0.92‐1.05) and alemtuzumab group (aHR 1.01, 95% CI 0.89‐1.16), but slightly higher in the no induction group (aHR 1.06, 95% CI 1.00‐1.14). Acute rejection did not modify this association in the latter group but did increase CVE by 46% in the alemtuzumab group. There was no difference in the hazard of all‐cause or CVE‐related mortality. Only in the ATG group, a 7% lower hazard of the composite outcome of mortality and CVE was noted. Induction agents are not associated with incident CVE, although prospective trials are needed to determine a personalized approach to prevention.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 74%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Induction immunosuppression agents as risk factors for incident cardiovascular events and mortality after kidney transplantation

Sandal

Bae

McAdams‐DeMarco

et al. 2019

American Journal of Transplantation

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“…Transplant specific diagnoses, specifically antibody‐mediated rejection (AMR), transplant glomerulopathy (TG) and interstitial fibrosis and tubular atrophy (IFTA), have been more commonly found on biopsy studies in transplant recipients with proteinuria than native kidney diseases . Strategies to inhibit AMR and non‐immunological interventions used to slow the progression of IFTA, such as renin‐angiotensin‐aldosterone system (RAAS) blockade, have had little success in clinical trials in kidney transplant recipients . Therefore, new approaches to stop progressive graft dysfunction are needed.…”

Section: Introductionmentioning

confidence: 99%

Paricalcitol versus placebo for reduction of proteinuria in kidney transplant recipients: a double-blind, randomized controlled trial

et al. 2018

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Proteinuria after kidney transplantation is accompanied by an increased risk of graft failure. In this single-center, placebo-controlled, double-blind trial we studied whether vitamin D receptor activator paricalcitol might reduce proteinuria. Patients with urinary protein-to-creatinine ratio (UPCR) ≥20 mg/mmol despite optimization of the renin angiotensin aldosterone system (RAAS) blockade were randomly assigned to receive 24 weeks' treatment with 2 μg/day paricalcitol or placebo. Primary endpoint was change in UPCR, and main secondary endpoints were change in urinary albumin-to-creatinine ratio (UACR) and 24-h proteinuria. Analysis was by intention to treat. One hundred and sixty-eight patients undergo randomization, and 83 were allocated to paricalcitol, and 85 to placebo. Compared with baseline, UPCR declined in the paricalcitol group (-39%, 95% CI -45 to -31) but not in the placebo group (21%, 95% CI 9 to 35), with a between group difference of -49% (95% CI -57 to -41; P < 0.001). UACR and 24-h proteinuria decreased only on paricalcitol therapy and significantly differed between groups at end-of-treatment (P < 0.001). Paricalcitol was well tolerated but incidence of mild hypercalcemia was higher than in placebo. In conclusion, addition of 2 μg/day paricalcitol lowers residual proteinuria in kidney transplant recipients. Long-term studies are needed to determine if the reduction in proteinuria improves transplant outcomes (ClinicalTrials.gov, number NCT01436747).

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Antihypertensive treatment for kidney transplant recipients

Natale,

Mooi,

Green

et al. 2024

Cochrane Database of Systematic Reviews

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Renin-Angiotensin System Blockade and Long-term Clinical Outcomes in Kidney Transplant Recipients: A Meta-analysis of Randomized Controlled Trials

Cited by 69 publications

References 30 publications

Induction immunosuppression agents as risk factors for incident cardiovascular events and mortality after kidney transplantation

Induction immunosuppression agents as risk factors for incident cardiovascular events and mortality after kidney transplantation

Paricalcitol versus placebo for reduction of proteinuria in kidney transplant recipients: a double-blind, randomized controlled trial

Antihypertensive treatment for kidney transplant recipients

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