Hypertension 3 Yrs

Effect of Hypertension on Transplant Kidney Function: Three Year of Follow-up G.A. Raiss Jalali, A. Fazelzadeh, and A.R. Mehdizadeh ABSTRACT Background. Hypertension significantly increases the risk for chronic graft loss and accelerates the deterioration of transplanted kidney function. Aggressive control of blood pressure (BP) is recommended in the posttransplant period when maintenance levels of immunosuppressive drugs are achieved. The aim of this study was to investigate whether the improved control improved the graft survival. Methods. We compared transplant kidney function in two groups of hypertensive patients matched for age, gender, donor–recipient relation, primary disease, early posttransplant course, and immunosuppressant and hypertensive therapy during 3 years follow-up. The patients were divided into satisfactory and unsatisfactory controlled blood pressure. Group 1 consisted of 98 patients with satisfactory BP control (arterial pressure ⬍160/90 mmHg) and group 2, 98 patients with unsatisfactory BP control. Results. The mean through levels of cyclosporine in whole blood were similar in both groups and did not exceed 185 ng/mL. A slow but significant increase in mean creatinine levels was observed among group 2 during 3 years follow-up, whereas, among group 1, graft function remained stable. Cardiovascular events were observed only in group 2: stroke in one patient and death because of heart failure in one patient. Factors which correlated with development of post transplant hypertension were age, gender, duration of disease before transplant, and underlying disease. Conclusion. Lowering BP, even several years posttransplantation, was associated with improved graft and patient survival in renal transplant recipients.

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ONIMMUNOLOGIC factors have been increasingly identified as potentially important mediators of reduced long-term renal allograft function, known as chronic allograft nephropathy.1 One such factor is hypertension. Hypertension in patients with kidney disease is thought to be one of the most important risk factors for the progression of renal failure. Higher blood pressures (BP) have been observed among patients whose allografts failed most rapidly.2 Based on the European Collaborative Transplant Study (CTS), Opelz et al3 a close relationship between arterial hypertension (AHT) and graft survival. Hypertension accelerates the deterioration of transplanted kidney function Aggressive BP control is recommended in the posttransplant period when maintenance levels of the immunosuppressive drugs are achieved.4 The aim of this study was to analyze the effect of high BP on transplanted kidney function. © 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 39, 941–942 (2007)

MATERIALS AND METHODS We compared transplanted kidney function in two groups of hypertensive patients transplanted in 2003. Patients were matched for age, gender, donor–recipient relation, primary disease, early posttransplant course, and immunosuppression and antihypertensive medications over 3 years, follow-up. We divided the patients into two groups. Group 1 were patients who had satisfactory BP control and group 2, unsatisfactory control. Then we analyzed the effect of high BP on 3-year patient and graft survivals by reviewing follow-up records. From the Shiraz Organ Transplant Ward, Nemazee Hospital (G.A.R.J); The School of Medicine, Fasa University of Medical Sciences (A.F.); and the School of Medicine, Mashad University of Medical Sciences (A.R.M.), Shiraz, Iran. Address reprint requests to Ghanbar Ali Raiss Jalali 9137673119, PO Box 91375-1471, Mashad-Iran. E-mail: fazelzadeh23@ yahoo.com 0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.03.057 941

942 For statistical analysis the results were expressed as mean values ⫾ SD. For comparisons of mean values, we used the ␹2 test. To study the impact of unsatisfactory BP control we evaluated creatinine clearance and graft survival, building a second Cox model whereby graft loss was defined as death or a definitive return to dialysis.

RESULTS

There were no differences in gender, etiology of renal failure, or HLA mismatches. The mean trough levels of cyclosporine in whole blood were similar in both groups, and did not exceed 185 ng/mL. Group 1 consisted of 98 patients with satisfactory BP control (arterial pressure ⬍ 160/90 mmHg) and group 2, 98 patients with unsatisfactory BP control. A slow but significant increase of the mean creatinine levels was observed in group 2 during 3 years of follow-up. We observed a negative correlation between creatinine clearance and 3-year blood pressure (P ⬍ .01), whereas in group 1, graft function remained stable. The mean 3-year creatinine clearance was 54 ⫾ 18 mL/min (range, 15–108) in group 2 and 69 ⫾ 24 mL/min (range, 25–149) for group 1. A multivariate Cox analysis showed that 3-year BP (P ⬍ .0029; RR ⫽ 1.76) and early creatinine clearance (P ⬍ .000; RR ⫽ 3.27) had a significant influence on graft survival. Cardiovascular events were observed only in group 2: stroke in one patient and death because of heart failure in one patient. DISCUSSION

Hypertension is one of the most common complications after renal transplantation. In the precyclosporine (CsA), era, posttransplant hypertension affected 40% to 50% of renal allograft recipients. However, the incidence of posttransplant hypertension has approximated 70% in the contemporary era of immunosuppression.5 Posttransplant hypertension is a major risk factor for cardiovascular disease and chronic renal allograft dysfunction. A significant number of transplant recipients suffer from posttransplant hypertension in part because of corticosteroids and calcineurin inhibitor therapy.6 Posttransplant hypertension is a significant risk factor for long-term graft loss and mortality.7 The nature of the effect of hypertension on graft function has not been clearly described, so the impact of tight control of BP after transplantation is not entirely clear. The presence of hypertension findings in allograft biopsies and their association with renal function parameters suggests a significant role for a tissue-level renin–angiotensin system in regulating allograft function. The systemic renin–angiotensin system is suppressed early after renal transplantation.8

RAISS JALALI, FAZELZADEH, MEHDIZADEH ET AL

However, animal studies have emphasized that the tissuelevel renin–angiotensin system is activated after renal transplantation.9 This local renin–angiotensin activation is linked to chronic CsA-induced hypertension, changes in angiotensin type 1 receptor mRNA expression10 as well as the allograft histopathology of chronic injury, interstitial fibrosis and tubular atrophy.11,12 Our study also, emphasized the role of hypertension on allograft function and the usefulness of tight BP control to improve graft and patient survival. Obviously, our study need to be interpreted with caution. A small number of stable patients were included in this analysis and not all patients had blood pressure control evaluation in their follow ups, a result of sequential studies and limited sample. In conclusion, lowering BP, even several years posttransplantation, is associated with improved graft and patient survival in renal transplant recipients. REFERENCES 1. Curtis J: Hypertension following kidney transplantation. Am J Kidney Dis 23:471, 1994 2. Guidi E, Cozzi MG, Minetti E, et al: Donor and recipient family histories of HTN influence renal impairment and blood pressure during acute rejections. J Am Soc Nephrol 9:2102, 1998 3. Opelz G, Wujciak T, Ritz E, for the Collaborative Transplant Study. Association of chronic kidney graft failure with recipient blood pressure. Kidney Int 53:217, 1998 4. Cheigh J, Haschmeyer R, Wang J, et al: Hypertension in kidney transplant recipients. Effect on long-term renal allograft survival. Am J Hyperten 2:341, 1989 5. Brazy P, Pirsch J, Belzer F: Factors affecting renal allograft function in long-term recipients. Am J Kidney Dis 19:558, 1992 6. Guidi E, Menghetti D, Milani S, et al: Hypertension may be transplanted with the kidney in humans: a long-term historical prospective follow-up of recipients grafted with kidneys coming from donors with or without hypertension in their families. J Am Soc Nephrol 7:1131, 1996 7. El Amm JM, Harririan A: The effects of blood pressure and lipid control on kidney allograft outcome. Am J Cardiovasc Drugs 6:1, 2006 8. Hestin D, Mertes P, Hubert J, et al: Relationship between blood pressure and renin, angiotensin II, and atrial natriuretic factor after renal transplantation. Clin Nephrol 48:98, 1997 9. Rettig R, Buch M, Gerstberger R, et al: Effects of kidney transplantation on renin-angiotensin systems of the recipients. Kidney Int 44:1536, 1994 10. Regitz Zagrosek V, Auch-Schwelk W, Hess B: Tissue and subtype specific modulation of angiotensin II receptors by chronic treatment with cyclosporine A, angiotensin-converting enzyme inhibitors and AT1 antagonists. J Cardiovasc Pharmacol 26:66, 1995 11. Kagami S, Border WA, Miller DE, et al: Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression rat glomerular mesangial cells. J Clin Invest 91:2268, 1994 12. Paul LC, Benediktsson H: Post-transplant hypertension and chronic renal allograft failure. Kidney Int 48(Suppl 52):S34, 1995