Specific Management of Anemia and Hypertension in Renal Transplant Recipients: Influence of Renin-Angiotensin System Blockade

Abstract

Background: Renin-angiotensin system (RAS) inhibition has proven to be helpful in reducing cardiovascular and kidney disease progression in the general population; whether kidney transplant patients would derive similar benefits is unknown. RAS inhibition also reduces posttransplantation erythrocytosis in kidney transplant recipients, but its effect on hemoglobin (Hb) levels in patients without posttransplantation erythrocytosis is unclear. Methods: The Specific Management of Anemia and Hypertension in Renal Transplant (SMAhRT) recipients study was designed to examine the cardiovascular benefits of RAS blockade with telmisartan 80 mg versus placebo, and Hb management with darbepoetin α in a randomized, double-blind, single-center controlled trial in 2,000 patients over 3 years. The primary efficacy variable was a composite of all-cause mortality, myocardial infarction or stroke. Results: The SMAhRT study was stopped prematurely due to a lower than expected event rate. At that point, 136 patients were enrolled and were followed for a mean duration of 15 months. The use of RAS blockade was not associated with an increased risk of adverse events such as worsening anemia or hyperkalemia. Likewise, the correction of Hb with darbepoetin was not associated with any increase in thrombotic events. Conclusions: This study provides insight into the safety of RAS inhibition and Hb correction with an erythrocyte-stimulating agent in kidney transplant recipients.

Assessment and Management of Hypertension in Transplant Patients

“…78 However, the trials included small sample sizes and limited follow-up periods. [79][80][81][82][83][84][85][86] A study by Suwelack et al of 96 nondiabetic hypertensive patients randomized to receive either quinapril or atenolol within 3 months of transplant offers the longest reported follow-up, showing similar effects on BP and graft function between groups at 5 years and a significant increase in proteinuria in atenololtreated patients compared with those receiving quinapril.…”

Effect of renin‐angiotensin system inhibitors on survival in kidney transplant recipients: A systematic review and meta‐analysis

“…Of these, we excluded 12 for the following reasons: 6 provided insufficient data; 4 study pairs investigated the same population, so we excluded the 4 with the shortest follow‐up, smallest population, or least complete outcome; 1 study was only reporting a protocol and 1 study used ACEI/ARBs in both the experimental and control arms. Therefore, 24 studies involving a total of 54,096 patients were included [26–49], of which 9 were RCTs (n = 1569) and 15 were cohort studies (n = 52,527).…”

“…Three trials had a Jadad score of 5 [33,47,49], two trials had a score of 4 [45,48] and four had a score of 3 [27,38,40,46], yielding a mean score of 3.9. Seven trials introduced allocation concealment, one doing so through the pharmacy department [27], four using computer‐generated random lists in permuted blocks of 4 or 6 stratified by centre and GFR [33,45,47,48], and two by using sequentially numbered, opaque, sealed envelopes [37,49]. Two trials did not provide details of allocation concealment [40,46].…”

“…Two trials did not provide details of allocation concealment [40,46]. Eight RCTs [27,33,38,45–49] reported completeness of follow‐up and performed intention‐to‐treat analyses, except for the trial by Philipp [39], which was stopped prematurely because only 25% met the expected outcome in an interim analysis [51]. The methodological qualities of the 18 included cohort studies ranged from 4 to 9 stars (mean = 6.1).…”

“…Five studies reported change in haemoglobin [28,33,38,47,49] and there was no significant descend (WMD = −8.79 g/24 h, 95%CI −14.33 to −3.25, P = 0.002) (see Supplementary Fig. S9 online).…”