Hypertension after renal transplantation
- John Vella, MD, FACP, FRCP, FASN
John Vella, MD, FACP, FRCP, FASN
- Associate Professor of Medicine
- Tufts University School of Medicine
- Daniel C Brennan, MD, FACP
Daniel C Brennan, MD, FACP
- Editor-in-Chief — Nephrology
- Section Editor — Renal Transplantation
- Professor of Medicine
- Medical Director and Co-Director of the Comprehensive Transplant Center, Department of Internal Medicine, Division of Nephrology
- Johns Hopkins Medical School
- Section Editors
- Barbara Murphy, MB, BAO, BCh, FRCPI
Barbara Murphy, MB, BAO, BCh, FRCPI
- Section Editor — Renal Transplantation
- Professor of Medicine
- Mount Sinai School of Medicine
- George L Bakris, MD
George L Bakris, MD
- Editor-in-Chief — Nephrology
- Section Editor — Hypertension
- Professor of Medicine
- The University of Chicago
Hypertension is prevalent in most patients with ESRD/advanced CKD. The blood pressure frequently often rises early after kidney transplantation after saline loading interacts with initial high-dose immunosuppression. Long-term blood pressure is often easier to control after transplantation, as long as the individual achieves a good GFR. However, poorly controlled blood pressure is common among kidney transplant recipients [1-4]. In a single-center study, for example, only 5 percent of kidney transplant patients were normotensive, as defined by blood pressures less than 130/80 mmHg, as measured by ambulatory blood pressure monitoring .
Elevated blood pressure and pulse pressure can result in decreased allograft survival and left ventricular hypertrophy, with the latter being an independent risk factor for heart failure and death in the general population and renal transplant recipients [5-9]. (See "Clinical implications and treatment of left ventricular hypertrophy in hypertension".)
RISK FACTORS AND PATHOGENESIS
The following risk factors have been associated with a higher incidence of posttransplant hypertension [6,10-14]:
●Delayed and/or chronic allograft dysfunction
●Deceased-donor allografts, especially from a donor with a family history of hypertension
- Kasiske BL, Anjum S, Shah R, et al. Hypertension after kidney transplantation. Am J Kidney Dis 2004; 43:1071.
- Paoletti E, Gherzi M, Amidone M, et al. Association of arterial hypertension with renal target organ damage in kidney transplant recipients: the predictive role of ambulatory blood pressure monitoring. Transplantation 2009; 87:1864.
- Mangray M, Vella JP. Hypertension after kidney transplant. Am J Kidney Dis 2011; 57:331.
- Rossi AP, Vella JP. Hypertension, living kidney donors, and transplantation: where are we today? Adv Chronic Kidney Dis 2015; 22:154.
- Rigatto C, Foley R, Jeffery J, et al. Electrocardiographic left ventricular hypertrophy in renal transplant recipients: prognostic value and impact of blood pressure and anemia. J Am Soc Nephrol 2003; 14:462.
- Hernández D. Left ventricular hypertrophy after renal transplantation: new approach to a deadly disorder. Nephrol Dial Transplant 2004; 19:1682.
- Mange KC, Feldman HI, Joffe MM, et al. Blood pressure and the survival of renal allografts from living donors. J Am Soc Nephrol 2004; 15:187.
- de Vries AP, Bakker SJ, van Son WJ, et al. Metabolic syndrome is associated with impaired long-term renal allograft function; not all component criteria contribute equally. Am J Transplant 2004; 4:1675.
- Fernández-Fresnedo G, Escallada R, Martin de Francisco AL, et al. Association between pulse pressure and cardiovascular disease in renal transplant patients. Am J Transplant 2005; 5:394.
- Sayegh, MH, Lazarus, JM. Renal parenchymal disease and hypertension. In: Current Management of Hypertension and Vascular Disease, Cooke, JP, Frohlich, ED (Eds), Decker, Philadelphia 1992. p.76.
- First MR, Neylan JF, Rocher LL, Tejani A. Hypertension after renal transplantation. J Am Soc Nephrol 1994; 4:S30.
- Textor SC, Canzanello VJ, Taler SJ, et al. Cyclosporine-induced hypertension after transplantation. Mayo Clin Proc 1994; 69:1182.
- Pérez Fontán M, Rodríguez-Carmona A, García Falcón T, et al. Early immunologic and nonimmunologic predictors of arterial hypertension after renal transplantation. Am J Kidney Dis 1999; 33:21.
- Audard V, Matignon M, Hemery F, et al. Risk factors and long-term outcome of transplant renal artery stenosis in adult recipients after treatment by percutaneous transluminal angioplasty. Am J Transplant 2006; 6:95.
- Cowley AW Jr, Roman RJ. The role of the kidney in hypertension. JAMA 1996; 275:1581.
- Curtis JJ, Luke RG, Dustan HP, et al. Remission of essential hypertension after renal transplantation. N Engl J Med 1983; 309:1009.
- 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 1996; 7:1131.
- Guidi E, Cozzi MG, Minetti E, Bianchi G. Donor and recipient family histories of hypertension influence renal impairment and blood pressure during acute rejections. J Am Soc Nephrol 1998; 9:2102.
- Scherrer U, Vissing SF, Morgan BJ, et al. Cyclosporine-induced sympathetic activation and hypertension after heart transplantation. N Engl J Med 1990; 323:693.
- Passauer J, Lässig G, Büssemaker E, et al. Reduced endothelin-1- and nitric oxide-mediated arteriolar tone in hypertensive renal transplant recipients. Kidney Int 2004; 65:1782.
- Hricik DE, Lautman J, Bartucci MR, et al. Variable effects of steroid withdrawal on blood pressure reduction in cyclosporine-treated renal transplant recipients. Transplantation 1992; 53:1232.
- Woodle ES, First MR, Pirsch J, et al. A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Ann Surg 2008; 248:564.
- Linas SL, Miller PD, McDonald KM, et al. Role of the renin-angiotensin system in post-transplantation hypertension in patients with multiple kidneys. N Engl J Med 1978; 298:1440.
- Bruno S, Remuzzi G, Ruggenenti P. Transplant renal artery stenosis. J Am Soc Nephrol 2004; 15:134.
- Shiba N, Chan MC, Kwok BW, et al. Analysis of survivors more than 10 years after heart transplantation in the cyclosporine era: Stanford experience. J Heart Lung Transplant 2004; 23:155.
- Margreiter R, European Tacrolimus vs Ciclosporin Microemulsion Renal Transplantation Study Group. Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study. Lancet 2002; 359:741.
- Gonwa T, Mendez R, Yang HC, et al. Randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 6 months. Transplantation 2003; 75:1213.
- Takeda Y, Miyamori I, Wu P, et al. Effects of an endothelin receptor antagonist in rats with cyclosporine-induced hypertension. Hypertension 1995; 26:932.
- Watschinger B, Sayegh MH. Endothelin in organ transplantation. Am J Kidney Dis 1996; 27:151.
- Perico N, Ruggenenti P, Gaspari F, et al. Daily renal hypoperfusion induced by cyclosporine in patients with renal transplantation. Transplantation 1992; 54:56.
- Esteva-Font C, Ars E, Guillen-Gomez E, et al. Ciclosporin-induced hypertension is associated with increased sodium transporter of the loop of Henle (NKCC2). Nephrol Dial Transplant 2007; 22:2810.
- Pouria S, State OI, Wong W, Hendry BM. CMV infection is associated with transplant renal artery stenosis. QJM 1998; 91:185.
- Humar A, Matas AJ. Surgical complications after kidney transplantation. Semin Dial 2005; 18:505.
- Hricik DE, Browning PJ, Kopelman R, et al. Captopril-induced functional renal insufficiency in patients with bilateral renal-artery stenoses or renal-artery stenosis in a solitary kidney. N Engl J Med 1983; 308:373.
- Voiculescu A, Schmitz M, Hollenbeck M, et al. Management of arterial stenosis affecting kidney graft perfusion: a single-centre study in 53 patients. Am J Transplant 2005; 5:1731.
- Sankari BR, Geisinger M, Zelch M, et al. Post-transplant renal artery stenosis: impact of therapy on long-term kidney function and blood pressure control. J Urol 1996; 155:1860.
- Loubeyre P, Abidi H, Cahen R, Tran Minh VA. Transplanted renal artery: detection of stenosis with color Doppler US. Radiology 1997; 203:661.
- Baxter GM, Ireland H, Moss JG, et al. Colour Doppler ultrasound in renal transplant artery stenosis: which Doppler index? Clin Radiol 1995; 50:618.
- O'neill WC, Baumgarten DA. Ultrasonography in renal transplantation. Am J Kidney Dis 2002; 39:663.
- Johnson DB, Lerner CA, Prince MR, et al. Gadolinium-enhanced magnetic resonance angiography of renal transplants. Magn Reson Imaging 1997; 15:13.
- Rubin GD. Spiral (helical) CT of the renal vasculature. Semin Ultrasound CT MR 1996; 17:374.
- Erley CM, Duda SH, Wakat JP, et al. Noninvasive procedures for diagnosis of renovascular hypertension in renal transplant recipients--a prospective analysis. Transplantation 1992; 54:863.
- Shamlou KK, Drane WE, Hawkins IF, Fennell RS 3rd. Captopril renography and the hypertensive renal transplantation patient: a predictive test of therapeutic outcome. Radiology 1994; 190:153.
- Reisfeld D, Matas AJ, Tellis VA, et al. Late follow-up of percutaneous transluminal angioplasty for treatment of transplant renal artery stenosis. Transplant Proc 1989; 21:1955.
- Fervenza FC, Lafayette RA, Alfrey EJ, Petersen J. Renal artery stenosis in kidney transplants. Am J Kidney Dis 1998; 31:142.
- Ruggenenti P, Mosconi L, Bruno S, et al. Post-transplant renal artery stenosis: the hemodynamic response to revascularization. Kidney Int 2001; 60:309.
- Henning BF, Kuchlbauer S, Böger CA, et al. Percutaneous transluminal angioplasty as first-line treatment of transplant renal artery stenosis. Clin Nephrol 2009; 71:543.
- Sierre SD, Raynaud AC, Carreres T, et al. Treatment of recurrent transplant renal artery stenosis with metallic stents. J Vasc Interv Radiol 1998; 9:639.
- Leertouwer TC, Gussenhoven EJ, van Overhagen H, et al. Stent placement for treatment of renal artery stenosis guided by intravascular ultrasound. J Vasc Interv Radiol 1998; 9:945.
- Rosenthal, JT. Chapter 7. In: Handbook of kidney transplantation, 2nd ed, Danovitch, GM (Eds), Little, Brown, and Company, Boston 1996. p.130.
- Gill JS. Cardiovascular disease in transplant recipients: current and future treatment strategies. Clin J Am Soc Nephrol 2008; 3 Suppl 2:S29.
- Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004; 43:S1.
- Wheeler DC, Becker GJ. Summary of KDIGO guideline. What do we really know about management of blood pressure in patients with chronic kidney disease? Kidney Int 2013; 83:377.
- Ruzicka M, Quinn RR, McFarlane P, et al. Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for the management of blood pressure in CKD. Am J Kidney Dis 2014; 63:869.
- EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.5.2. Cardiovascular risks. Arterial hypertension. Nephrol Dial Transplant 2002; 17 Suppl 4:25.
- Sanders CE Jr, Curtis JJ. Role of hypertension in chronic renal allograft dysfunction. Kidney Int Suppl 1995; 52:S43.
- Cheigh JS, Haschemeyer RH, Wang JC, et al. Hypertension in kidney transplant recipients. Effect on long-term renal allograft survival. Am J Hypertens 1989; 2:341.
- Paul LC, Benediktsson H. Post-transplant hypertension and chronic renal allograft failure. Kidney Int Suppl 1995; 52:S34.
- Opelz G, Döhler B, Collaborative Transplant Study. Improved long-term outcomes after renal transplantation associated with blood pressure control. Am J Transplant 2005; 5:2725.
- Mourer JS, de Koning EJ, van Zwet EW, et al. Impact of late calcineurin inhibitor withdrawal on ambulatory blood pressure and carotid intima media thickness in renal transplant recipients. Transplantation 2013; 96:49.
- Mourad G, Ribstein J, Mimran A. Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants. Kidney Int 1993; 43:419.
- Ponticelli C, Montagnino G, Aroldi A, et al. Hypertension after renal transplantation. Am J Kidney Dis 1993; 21:73.
- Ladefoged SD, Pedersen E, Hammer M, et al. Influence of diltiazem on renal function and rejection in renal allograft recipients receiving triple-drug immunosuppression: a randomized, double-blind, placebo-controlled study. Nephrol Dial Transplant 1994; 9:543.
- Ladefoged SD, Andersen CB. Calcium channel blockers in kidney transplantation. Clin Transplant 1994; 8:128.
- Midtvedt K, Hartmann A, Foss A, et al. Sustained improvement of renal graft function for two years in hypertensive renal transplant recipients treated with nifedipine as compared to lisinopril. Transplantation 2001; 72:1787.
- Kuypers DR, Neumayer HH, Fritsche L, et al. Calcium channel blockade and preservation of renal graft function in cyclosporine-treated recipients: a prospective randomized placebo-controlled 2-year study. Transplantation 2004; 78:1204.
- Kovarik JM, Beyer D, Bizot MN, et al. Pharmacokinetic interaction between verapamil and everolimus in healthy subjects. Br J Clin Pharmacol 2005; 60:434.
- Cross NB, Webster AC, Masson P, et al. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev 2009; :CD003598.
- Lafayette RA, Mayer G, Meyer TW. The effects of blood pressure reduction on cyclosporine nephrotoxicity in the rat. J Am Soc Nephrol 1993; 3:1892.
- Pichler RH, Franceschini N, Young BA, et al. Pathogenesis of cyclosporine nephropathy: roles of angiotensin II and osteopontin. J Am Soc Nephrol 1995; 6:1186.
- Curtis JJ, Laskow DA, Jones PA, et al. Captopril-induced fall in glomerular filtration rate in cyclosporine-treated hypertensive patients. J Am Soc Nephrol 1993; 3:1570.
- Vlahakos DV, Canzanello VJ, Madaio MP, Madias NE. Enalapril-associated anemia in renal transplant recipients treated for hypertension. Am J Kidney Dis 1991; 17:199.
- Gaston RS, Julian BA, Curtis JJ. Posttransplant erythrocytosis: an enigma revisited. Am J Kidney Dis 1994; 24:1.
- Stigant CE, Cohen J, Vivera M, Zaltzman JS. ACE inhibitors and angiotensin II antagonists in renal transplantation: an analysis of safety and efficacy. Am J Kidney Dis 2000; 35:58.
- Holgado R, Anaya F, Del Castillo D. Angiotensin II type 1 (AT1) receptor antagonists in the treatment of hypertension after renal transplantation. Nephrol Dial Transplant 2001; 16 Suppl 1:117.
- Formica RN Jr, Friedman AL, Lorber MI, et al. A randomized trial comparing losartan with amlodipine as initial therapy for hypertension in the early post-transplant period. Nephrol Dial Transplant 2006; 21:1389.
- Paoletti E, Cassottana P, Amidone M, et al. ACE inhibitors and persistent left ventricular hypertrophy after renal transplantation: a randomized clinical trial. Am J Kidney Dis 2007; 50:133.
- Hiremath S, Fergusson D, Doucette S, et al. Renin angiotensin system blockade in kidney transplantation: a systematic review of the evidence. Am J Transplant 2007; 7:2350.
- Ibrahim HN, Jackson S, Connaire J, et al. Angiotensin II blockade in kidney transplant recipients. J Am Soc Nephrol 2013; 24:320.
- Curtis JJ, Luke RG, Diethelm AG, et al. Benefits of removal of native kidneys in hypertension after renal transplantation. Lancet 1985; 2:739.
- Fricke L, Doehn C, Steinhoff J, et al. Treatment of posttransplant hypertension by laparoscopic bilateral nephrectomy? Transplantation 1998; 65:1182.
- RISK FACTORS AND PATHOGENESIS
- Role of glucocorticoids
- Role of calcineurin inhibitors
- RENAL ARTERY STENOSIS
- - Arteriography
- - Ultrasonography
- - Magnetic resonance imaging
- - Spiral computed tomography angiography
- - Radioisotope renography
- - Angioplasty
- - Surgery
- DEFINITIONS AND GOALS OF THERAPY
- Patient is taking a calcineurin inhibitor
- - Calcium channel blockers
- - Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and other agents
- Patient is not taking a calcineurin inhibitor
- Resistant hypertension
- SUMMARY AND RECOMMENDATIONS