Effect of angiotensin II receptor blocker on plasma levels of TGF-beta 1 and interstitial fibrosis in hypertensive kidney transplant patients.
OBJECTIVE
Transforming growth factor-beta1 (TGF-beta 1) 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-beta 1 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-beta1, 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-beta1, proteinuria and uric acid. These results could play an important and decisive role in the treatment and prevention of chronic allograft nephropathy.
el-Agroudy
Amgad E
AE
Urology and Nephrology Center, Mansoura University, Mansoura, Egypt. amgadelbaz@ahram0505.net
Hassan
Nabil A
NA
Foda
Mohamed A
MA
Ismail
Amani M
AM
el-Sawy
Essam A
EA
Mousa
Omar
O
Ghoneim
Mohamed A
MA
D000328:Adult; D017311:Amlodipine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis / Q000473:pathology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D007674:Kidney Diseases / Q000473:pathology*; D016030:Kidney Transplantation; D019520:Living Donors; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology; D016212:Transforming Growth Factor beta / Q000097:blood*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D016212:Transforming Growth Factor beta; D017311:Amlodipine; D002216:Captopril; D019808:Losartan