Angiotensin II type 1 (AT1) receptor antagonists in the treatment of hypertension after renal transplantation

Abstract

Hypertension is highly prevalent after renal transplantation and has been associated with lower graft survival. Optimum management of post-transplant hypertension remains to be defined. Losartan, a potent, orally active and selective non-peptide blocker of the angiotensin subtype 1 receptor, could represent a useful drug for treating post-transplant hypertension. Recently, a prospective study of 12 weeks treatment with losartan has showed a satisfactory control of arterial hypertension associated with a decrease in proteinuria in this high-risk group of renal transplant patients. A retrospective study was performed to review the role of losartan as a renoprotective agent (evaluating blood pressure and proteinuria) in renal transplant recipients in a long-term follow-up. A total of 150 transplant recipients were included in the study. None of the patients had a serum creatinine >3 mg/dl, or suspected renal artery stenosis, or other severe concomitant diseases. The indication for losartan therapy was hypertension, proteinuria and/or post-transplant erythrocytosis. The values of blood pressure, results of fasting haematology, blood chemistry and total proteinuria in 24-h urine samples were recorded at the time of initiation of losartan therapy, 6 and 3 months before the start, and at 3, 6, 12, 18 and 24 months thereafter. A tendency analysis by linear regression comparing two slopes before and after treatment was realized. A decrease in mean blood pressure and proteinuria, from 106.7+/-0.9 to 98.2+/-2.1 mmHg and from 1253.9+/-188 to 91.2+/-33.7 mg/24 h, P<0.05, respectively, was observed after introduction of losartan. A progressive increase in creatinine clearance was observed after the third month of losartan treatment. No significant changes were seen in haematocrit or serum potassium levels. We can conclude that a progressive decrease in mean arterial pressure associated with a decrease in proteinuria was observed during long-term follow-up. Based on the capacity of losartan to improve renal function, this drug could be decisive for the treatment and prevention of chronic allograft nephropathy.

Immunologic risk factors and glomerular C4d deposits in chronic transplant glomerulopathy

“…These results support recent evidence that renoprotection could be achieved when long-lasting angiotensin-converting enzyme (ACE) inhibition results in persistent reduction in proteinuria [29,30]. ACE inhibitors and angiotensin II antagonists are well tolerated in transplant recipients with chronic allograft nephropathy and are associated with stabilization of renal function [31,32].…”

Renal Sodium Transporters Are Increased in Urinary Exosomes of Cyclosporine-Treated Kidney Transplant Patients

“…In addition, these kidney recipients are also treated with antihypertensive drugs and calcium antagonists to control hypertension that can ameliorate CsA renal vasoconstriction effects [31,32]. On the other hand, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are effective in reducing BP in renal transplant patients [33,34]. …”

Circulating Angiotensin-Converting Enzyme 2 Activity in Kidney Transplantation: A Longitudinal Pilot Study

“…In addition, renin-angiotensin system (RAS) blockade has been shown to reduce proteinuria in KT patients [6,7]. Whereas ACE mediates the cleavage of Ang I into Ang II, ACE2 mediates the cleavage of Ang II into Ang(1–7) and Ang I into Ang(1–9).…”