Arterial hypertension in renal transplant recipients warrants antihypertensive treatment. The preferable choice of antihypertensives that should be used in patients after kidney transplantation remains a matter of debate; however, calcium channel blockers (CCB) and angiotensin-converting enzyme inhibitors (ACEI) are currently the most commonly used antihypertensives. This educational review summarizes the current evidence about the effects of these two classes of medications in transplant recipients. Several studies have demonstrated that both classes of drugs can reduce blood pressure (BP) to similar extents. Meta-analyses of adult randomized controlled trials have shown that graft survival is improved in patients treated with ACEIs and CCBs, and that CCBs increase, yet ACEIs decrease, graft function. Proteinuria is usually decreased by ACEIs but remains unchanged with CCBs. In children, no randomized controlled study has ever been performed to compare BP or graft survival between CCBs and ACEIs. Post-transplant proteinuria could be reduced in children along with BP by ACEIs. The results of the most current meta-analyses recommend that due to their positive effects on graft function and survival, along with their lack of negative effects on serum potassium, CCBs could be the preferred first-line antihypertensive agent in renal transplant recipients. However, antihypertensive therapy should be individually tailored based on other factors, such as time after transplantation, presence of proteinuria/albuminuria, or hyperkalemia. Furthermore, due to the difficulty in controlling hypertension, combination therapy containing both CCBs and ACEIs could be a reasonable first-step therapy in treating children with severe post-transplantation hypertension.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Weir MR, Burgess ED, Cooper JE, Fenves AZ, Goldsmith D, McKay D, Mehrotra A, Mitsnefes MM, Sica DA, Taler SJ (2015) Assessment and management of hypertension in transplant patients. J Am Soc Nephrol 26:1248–1260
Baluarte HJ, Gruskin AB, Ingelfinger JR, Stablein D, Tejani A (1994) Analysis of hypertension in children post renal transplantation - a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Nephrol 8:570–573
Sorof JM, Sullivan EK, Tejani A, Portman RJ (1999) Antihypertensive medication and renal allograft failure: a North American Pediatric Renal Transplant Cooperative Study report. J Am Soc Nephrol 10:1324–1330
Kramer AM, van Stralen KJ, Jager KJ, Schaefer F, Verrina E, Seeman T, Lewis MA, Boehm M, Simonetti GD, Novljan G, Groothoff JW (2011) Demographics of blood pressure and hypertension in children on renal replacement therapy in Europe. Kidney Int 80:1092–1098
Opelz G, Wujciak T, Ritz E, Collaborative Transplant Study (1998) Association of chronic kidney graft failure with recipient blood pressure. Kidney Int 53:217–222
Mange KC, Gizman B, Joffe M, Feldman HI (2000) Arterial hypertension and renal allograft survival. JAMA 283:633–638
Mitsnefes MM, Omoloja A, McEnery PT (2001) Short-term pediatric renal transplant survival: blood pressure and allograft function. Pediatr Transpl 5:160–165
Mitsnefes MM, Khoury PR, McEnery PT (2003) Early posttransplantation hypertension and poor long-term renal allograft survival in pediatric patients. J Pediatr 143:98–103
Hamdani G, Nehus EJ, Hanevold CD, VanSickle JS, Hooper DK, Blowey D, Warady BA, Mitsnefes MM (2017) Ambulatory blood pressure control in children and young adults after kidney transplantation. Am J Hypertens 30:1039–1046
Seeman T (2009) Hypertension after renal transplantation. Pediatr Nephrol 24:959–972
Ferraris JR, Ghezzi L, Waisman G, Krmar RT (2007) ABPM vs. office blood pressure to define blood pressure control in treated hypertensive paediatric renal transplant recipients. Pediatr Transplantation 11:24–30
Sorof JM, Poffenbarger T, Portman R (2000) Abnormal 24-hour blood pressure patterns in children after renal transplantation. Am J Kidney Dis 35:681–686
Morgan H, Khan I, Hashmi A, Hebert D, McCrindle BW, Balfe JW (2001) Ambulatory blood pressure monitoring after renal transplantation in children. Pediatr Nephrol 16:843–847
Serdaroglu E, Mir S, Berdelli A (2005) Hypertension and ACE gene insertion/deletion polymorphism in pediatric renal transplant patients. Pediatr Transplant 9:612–617
Seeman T, Šimková E, Kreisinger J, Vondrák K, Dušek J, Gilík J, Feber J, Dvořák P, Janda J (2006) Control of hypertension in children after renal transplantation. Pediatr Transplant 10:316–322
McGlothan KR, Wyatt RJ, Ault BH, Hastings MC, Rogers T, DiSessa T, Jones DP (2006) Predominance of nocturnal hypertension in pediatric renal allograft recipients. Pediatr Transplant 10:558–564
Cameron C, Vavilis G, Kowalski J, Tydén G, Berg UB, Krmar RT (2014) An observational cohort study of the effect of hypertension on the loss of renal function in pediatric kidney recipients. Am J Hypertens 27:579–585
Hamdani G, Nehus EJ, Hanevold CD, Sebestyen Van Sickle J, Woroniecki R, Wenderfer SE, Hooper DK, Blowey D, Wilson A, Warady BA, Mitsnefes MM (2017) Ambulatory blood pressure, left ventricular hypertrophy, and allograft function in children and young adults after kidney transplantation. Transplantation 101:150–156
Seeman T, Vondrák K, Dušek J (2019) Effects of the strict control of blood pressure in pediatric renal transplant recipients—ESCORT trial. Pediatr Transplant Febr 23:e13329
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group (2009) KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant Suppl 3:S1–S155
Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group (2012) KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl 2:337–414
Ruzicka M, Quinn RR, McFarlane P, Hemmelgarn B, Ramesh Prasad GV, Feber J, Nesrallah G, MacKinnon M, Tangri N, McCormick B, Tobe S, Blydt-Hansen TD, Hiremath S (2014) Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for the management of blood pressure in CKD. Am J Kidney Dis 63:869–887
Knoll GA, Fergusson D, Chassé M, Hebert P, Wells G, Tibbles LA, Treleaven D, Holland D, White C, Muirhead N, Cantarovich M, Paquet M, Kiberd B, Gourishankar S, Shapiro J, Prasad R, Cole E, Pilmore H, Cronin V, Hogan D, Ramsay T, Gill J (2016) Ramipril versus placebo in kidney transplant patients with proteinuria: a multicentre, double-blind, randomised controlled trial. Lancet Diabetes Endocrinol 4:318–326
Cross NB, Webster AC, Masson P, O'connell PJ, Craig JC (2009) Antihypertensives for kidney transplant recipients: systematic review and meta-analysis of randomized controlled trials. Transplantation 88:7–18
Pisano A, Bolignano D, Mallamaci F, D'Arrigo G, Halimi JM, Persu A, Wuerzner G, Sarafidis P, Watschinger B, Burnier M, Zoccali C (2019) Comparative effectiveness of different antihypertensive agents in kidney transplantation: a systematic review and meta-analysis. Nephrol Dial Transplant. https://doi.org/10.1093/ndt/gfz092
Midtvedt K, Ihlen H, Hartmann A, Bryde P, Bjerkely BL, Foss A, Fauchald P, Holdaas H (2001) Reduction of left ventricular mass by lisinopril and nifedipin in hypertensive renal transplant recipients: a prospective randomized double-blind study. Transplantation 72:107–111
Seeman T, Dusek J, Vondrák K, Janda J (2010) Ramipril in the treatment of proteinuria in children after renal transplantation. Pediatr Transplant 14:283–287
Silverstein DM, Palmer J, Baluarte HJ, Brass C, Conley SB, Polinsky MS (1999) Use of calcium-channel blockers in pediatric renal transplant recipients. Pediatr Transplant 3:288–292
Rogan JW, Lyszkiewicz DA, Blowey D, Khattak S, Arbus GS, Koren G (2000) A randomized prospective crossover trial of amlodipin in pediatric hypertension. Pediatr Nephrol 14:1083–1087
Arbeiter K, Pichler A, Stemberger R, Mueller T, Ruffingshofer D, Vargha R, Balzar E, Aufricht C (2004) ACE inhibition in the treatment of children after renal transplantation. Pediatr Nephrol 19:222–226
Suszynski TM, Rizzari MD, Gillingham KJ, Rheault MN, Kraszkiewicz W, Matas AJ, Chavers BM (2013) Antihypertensive pharmacotherapy and long-term outcomes in pediatric kidney transplantation. Clin Transpl 27:472–480
Heinze G, Mitterbauer C, Regele H, Kramar R, Winkelmayer WC, Curhan GC, Oberbauer R (2006) Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation. J Am Soc Nephrol 17:889–899
Opelz G, Zeier M, Laux G, Morath C, Dohler B (2006) No improvement of patient or graft survival in transplant recipients treated with angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers: a Collaborative Transplant Study report. J Am Soc Nephrol 17:3257–3262
Steuber TD, Lee J, Holloway A, Andrus MR (2019) Nondihydropyridine calcium channel blockers for the treatment of proteinuria: a review of the literature. Ann Pharmacother 53:1050–1059
Derwa A, Peeters P, Vanholder R (2004) Calcium channel blockers in the prevention of end stage renal disease: a review. Acta Clin Belg 59:44–56
Sica DA (2000) Class effects of angiotensin-converting enzyme inhibitors. Am J Manag Care 6(3 Suppl):S85–S108
Xu R, Sun S, Huo Y, Yun L, Huang S, Li G, Yan S (2015) Effects of ACEIs versus ARBs on proteinuria or albuminuria in primary hypertension: a meta-analysis of randomized trials. Medicine (Baltimore) 94(39):e1560
Lurbe E, Agabiti-Rosei E, Cruickshank JK, Dominiczak A, Erdine S, Hirth A, Invitti C, Litwin M, Mancia G, Pall D, Rascher W, Redon J, Schaefer F, Seeman T, Sinha M, Stabouli S, Webb NJ, Wühl E, Zanchetti A (2016) 2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents. J Hypertens 34:1887–1920
Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, de Ferranti SD, Dionne JM, Falkner B, Flinn SK, Gidding SS, Goodwin C, Leu MG, Powers ME, Rea C, Samuels J, Simasek M, Thaker VV, Urbina EM, Subcommittee on screening and management of high blood pressure in children (2017) Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 140. https://doi.org/10.1542/peds.2017-1904
Ruggenenti P, Perna A, Mosconi L, Gaspari F, Benigni A, Amuchastegui CS, Bruzzi I, Remuzzi G (1993) Calcium channel blockers protect transplant patients from cyclosporine-induced daily renal hypoperfusion. Kidney Int 43:706–711
Curtis JJ (1997) Treatment of hypertension in renal allograft patients: does drug selection make a difference. Kidney Int 52(Suppl 63):S75–S77
Trachtman H, Frymoyer A, Lewandowski A, Greenbaum LA, Feig DI, Gipson DS, Warady BA, Goebel JW, Schwartz GJ, Lewis K, Anand R, Patel UD, Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee (2015) Pharmacokinetics, pharmacodynamics, and safety of lisinopril in pediatric kidney transplant patients: implications for starting dose selection. Clin Pharmacol Ther 98:25–33
Stigant CE, Cohen J, Vivera M, Zaltzman JS (2000) ACE inhibitors and angiotensin II antagonists in renal transplantation: an analysis of safety and efficacy. Am J Kidney Dis 35:58–63
Seeman T, Simková E, Kreisinger J, Vondrák K, Dusek J, Gilík J, Dvorák P, Janda J (2007) Improved control of hypertension in children after renal transplantation: results of a two-yr interventional trial. Pediatr Transplant 11:491–497
Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I, Authors/Task Force Members (2018) 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens 36:1953–2041
This study is supported by the National Sustainability Program I (NPU I) Nr. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic. We wish to thank Brandy Brookings for her assistance with editing.
Conflict of interest
The authors declare that they have no conflict of interest.
1. d; 2. d; 3. a; 4. e; 5. a
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Seeman, T., Feber, J. Should ACE inhibitors or calcium channel blockers be used for post-transplant hypertension?. Pediatr Nephrol 36, 539–549 (2021). https://doi.org/10.1007/s00467-020-04485-8
- Renal transplantation
- Calcium channel blockers
- Angiotensin-converting enzyme inhibitors
- Graft function