Effect of Angiotensin II Receptor Blocker on Plasma Levels of TGF-β1 and Interstitial Fibrosis in Hypertensive Kidney Transplant Patients

Abstract

Background/Aim: Transforming growth factor-β1 (TGF-β1) is involved in the pathogenesis of chronic allograft nephropathy after kidney transplantation. The aim of the study was to evaluate the effect of the angiotensin receptor blocker losartan on TGF-β1 plasma levels and proteinuria in hypertensive transplant recipients. Methods: A total of 162 transplant recipients were included in the study. The patients were randomized into 3 groups: group 1 received losartan; group II received an angiotensin-converting enzyme inhibitor (captopril), and group III received a calcium channel blocker (amlodipine). All the parameters were recorded at the time of therapy initiation and at 1, 4 and 12 weeks and 12 months thereafter. Graft biopsy before the start and at the end of the study was done to evaluate histopathological progression. Results: Blood pressure was controlled in the 3 groups; however, the need for other antihypertensive agents was significant in groups I and II. Treatment with losartan significantly decreased the plasma level of TGF-β1, 24-hour urinary protein and serum uric acid (p < 0.05). No significant changes were seen in the hemoglobin or serum potassium levels. The rate of histopathological progression was significantly lower in the losartan group. No patient was discharged from the study due to side effects. Conclusions: After transplantation all drugs were able to control blood pressure with good safety and tolerability. The study demonstrates that ARB significantly decreases the plasma levels of TGF-β1, proteinuria and uric acid. These results could play an important and decisive role in the treatment and prevention of chronic allograft nephropathy.

Intestinal Fibrosis and Liver Fibrosis: Consequences of Chronic Inflammation or Independent Pathophysiology?

“…Consistent with such clinical evidence for the reversibility of liver fibrosis, we have previously reported that bone marrow-derived cells migrating into fibrotic liver contribute to the regression of experimental liver fibrosis by expressing MMP-13 and MMP-9 [97]. The concept of reversibility of intestinal fibrosis is in concordance with various observations from other organs such as the skin, kidney, lung, or heart [98,99,100,101,102,103]. …”

Effector Mechanisms of Rejection

“…(Coupes et al 1994;Lu et al 2002;el-Agroudy et al 2003;Baczkowska Summers et al 2005;Roos-van Groningen et al 2006). Extracellular matrix accumulation is a lesion of fibrosis.…”

Does Blockade of the Renin-Angiotensin-Aldosterone System Slow Progression of All Forms of Kidney Disease?

“…RAAS blockade decreases the synthesis and secretion of renal TGF-β1 in patients with chronic allograft injury and can decrease the rate of histopathologic progression in chronic allograft nephropathy [38,39]. In a recent double-blind, placebo-controlled and crossover study, losartan exerted a beneficial effect against tubular injury and graft fibrosis and thus may have a role in preventing chronic allograft injury [40].…”