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Treatment-Resistant Hypertension in the Transplant Recipient

      Summary

      Treatment-resistant hypertension (TRH) is defined as follows: (1) the failure to achieve optimal blood pressure control to levels less than 140/90 mm Hg despite the concomitant use of 3 or more different classes of antihypertensive agents, one of which is a diuretic, or (2) the simultaneous use of 4 or more different classes of antihypertensive agents in a patient irrespective of blood pressure control and the exclusion of pseudoresistance. Patients with TRH constitute only a subset of patients with poorly controlled hypertension, which also includes other subsets of patients who are treated inadequately or who are noncompliant with prescribed pharmacologic and nonpharmacologic therapy. TRH does occur in kidney-transplant recipients. This may be related to a variety of factors including reduced renal function, renal artery stenosis, concurrent use of medications that increase blood pressure, lack of use or insufficient use of diuretics, noncompliance related to complex medication regimens, or activated neurohormonal pathways, especially aldosterone or the sympathetic nervous system. After kidney transplantation, normalization of blood pressure occurs only in a minority of patients, and it is estimated that 67% to 90% of kidney transplant patients have arterial hypertension and the improvement in glomerular filtration rate and fluid management offered by the kidney transplant may be offset by a wide array of factors. Epidemiologic studies that describe the prevalence of TRH in kidney transplant recipients are lacking.

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      References

        • Tanner R.M.
        • Calhoun D.A.
        • Bell E.K.
        • et al.
        Prevalence of apparent treatment-resistant hypertension among individuals with CKD.
        Clin J Am Soc Nephrol. 2013; 8: 1583-1590
        • Textor S.C.
        • Canzanello V.J.
        • Taler S.J.
        • et al.
        Cyclosporine-induced hypertension after transplantation.
        Mayo Clin Proc. 1994; 69: 1182-1193
        • Agena F.
        • Prado E.S.
        • Souza P.S.
        • et al.
        Home blood pressure (BP) monitoring in kidney transplant recipients is more adequate to monitor BP than office BP.
        Nephrol Dial Transplant. 2011; 26: 3745-3749
        • Calhoun D.A.
        • Jones D.
        • Textor S.
        • et al.
        Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research.
        Circulation. 2008; 117: e510-e526
        • Prasad G.V.R.
        • Nash M.M.
        • Zaltzman J.S.
        A prospective study of the physician effect on blood pressure in renal-transplant recipients.
        Nephrol Dial Transplant. 2003; 18: 996-1000
        • Stenehjem A.E.
        • Gudmundsdottir H.
        • Os I.
        Office blood pressure measurements overestimate blood pressure control in renal transplant patients.
        Blood Press Monit. 2006; 11: 125-133
        • Wen K.C.
        • Gourishankar S.
        Evaluating the utility of ambulatory blood pressure monitoring in kidney transplant recipients.
        Clin Transplant. 2012; 26: E465-E470
        • Wadei H.M.
        • Amer H.
        • Taler S.J.
        • et al.
        Diurnal blood pressure changes one year after kidney transplantation: relationship to allograft function, histology, and resistive index.
        J Am Soc Nephrol. 2007; 18: 1607-1615
        • Fresnedo G.
        • Franco G.
        • Cabello D.
        • et al.
        Ambulatory blood pressure monitoring in kidney transplant patients: RETENAL study.
        Transplant Proc. 2012; 44: 2601-2602
        • Beltran S.
        • Crespo J.
        • Kanter J.
        • et al.
        Ambulatory blood pressure monitoring in renal transplant patients: should it be routinely performed?.
        Transplant Proc. 2010; 42: 2868-2870
        • Haydar A.A.
        • Covic A.
        • Jayawardene S.
        • et al.
        Insights from ambulatory blood pressure monitoring: diagnosis of hypertension and diurnal blood pressure in renal transplant recipients.
        Transplantation. 2004; 77: 849-853
        • Paoletti E.
        • Gherzi M.
        • Amidone M.
        • Massarino F.
        • Cannella G.
        Association of arterial hypertension with renal target organ damage in kidney transplant recipients: the predictive role of ambulatory blood pressure monitoring.
        Transplantation. 2009; 87: 1864-1869
        • Toprak A.
        • Koc M.
        • Tezcan H.
        • Ozener I.C.
        • Oktay A.
        • Akoglu E.
        Night-time blood pressure load is associated with higher left ventricular mass index in renal transplant recipients.
        J Hum Hypertens. 2003; 17: 239-244
        • Ibernon M.
        • Moreso F.
        • Sarrias X.
        • et al.
        Reverse dipper pattern of blood pressure at 3 months is associated with inflammation and outcome after renal transplantation.
        Nephrol Dial Transplant. 2012; 27: 2089-2095
        • Wadei H.M.
        • Amer H.
        • Griffin M.D.
        • Taler S.J.
        • Stegall M.D.
        • Textor S.C.
        Abnormal circadian blood pressure pattern 1-year after kidney transplantation is associated with subsequent lower glomerular filtration rate in recipients without rejection.
        J Am Soc Hypertens. 2011; 5: 39-47
        • Grote L.
        • Hedner J.
        • Peter J.H.
        Sleep-related breathing disorder is an independent risk factor for uncontrolled hypertension.
        J Hypertens. 2000; 18: 679-685
        • Lavie P.
        • Hoffstein V.
        Sleep apnea syndrome: a possible contributing factor to resistant.
        Sleep. 2001; 24: 721-725
        • Logan A.G.
        • Perlikowski S.M.
        • Mente A.
        • et al.
        High prevalence of unrecognized sleep apnoea in drug-resistant hypertension.
        J Hypertens. 2001; 19: 2271-2277
        • Calhoun D.A.
        • Nishizaka M.K.
        • Zaman M.A.
        • Thakkar R.B.
        • Weissmann P.
        Hyperaldosteronism among black and white subjects with resistant hypertension.
        Hypertension. 2002; 40: 892-896
        • Eide I.K.
        • Torjesen P.A.
        • Drolsum A.
        • Babovic A.
        • Lilledahl N.P.
        Low-renin status in therapy-resistant hypertension: a clue to efficient treatment.
        J Hypertens. 2004; 22: 2217-2226
        • Alawwa I.A.
        • Wahbeh A.
        Benign pheochromocytoma presented 6 years after kidney transplantation.
        Iran J Kidney Dis. 2013; 7: 323-325
        • Manger W.M.
        • Gifford R.W.
        Pheochromocytoma.
        J Clin Hypertens (Greenwich). 2002; 4: 62-72
        • Arnaldi G.
        • Mancini T.
        • Polenta B.
        • Boscaro M.
        Cardiovascular risk in Cushing’s syndrome.
        Pituitary. 2004; 7: 253-256
        • Bakris G.L.
        A practical approach to achieving recommended blood pressure goals in diabetic patients.
        Arch Intern Med. 2001; 161: 2661-2667
        • Molnar M.Z.
        • Lazar A.S.
        • Lindner A.
        • et al.
        Sleep apnea is associated with cardiovascular risk factors among kidney transplant patients.
        Clin J Am Soc Nephrol. 2010; 5: 125-132
        • Campistol J.M.
        • Romero R.
        • Paul J.
        • Gutierrez-Dalmau A.
        Epidemiology of arterial hypertension in renal transplant patients: changes over the last decade.
        Nephrol Dial Transplant. 2004; 19: iii62-iii66
        • Genovese G.
        • Friedman D.J.
        • Ross M.D.
        • et al.
        Association of trypanolytic ApoL1 variants with kidney disease in African Americans.
        Science. 2010; 329: 841-845
        • Bahous S.A.
        • Stephan A.
        • Blacher J.
        • Safar M.E.
        Aortic stiffness, living donors, and renal transplantation.
        Hypertension. 2006; 47: 216-221
        • Delahousse M.
        • Chaignon M.
        • Mesnard L.
        • et al.
        Aortic stiffness of kidney transplant recipients correlates with donor age.
        J Am Soc Nephrol. 2008; 19: 798-805
        • Lilien M.R.
        • Stroes E.S.
        • Op׳t Roodt J.
        • de Jongh S.
        • Schröder C.H.
        • Koomans H.A.
        Vascular function in children after renal transplantation.
        Am J Kidney Dis. 2003; 41: 684-691
        • Litwin M.
        • Wühl E.
        • Jourdan C.
        • et al.
        Evolution of large-vessel arteriopathy in paediatric patients with chronic kidney disease.
        Nephrol Dial Transplant. 2008; 23: 2552-2557
        • Ducloux D.
        • Motte G.
        • Kribs M.
        • et al.
        Hypertension in renal transplantation: donor and recipient risk factors.
        Clin Nephrol. 2002; 57: 409-413
        • Joannidés R.
        • Monteil C.
        • de Ligny B.H.
        • et al.
        Immunosuppressant regimen based on sirolimus decreases aortic stiffness in renal transplant recipients in comparison to cyclosporine.
        Am J Transplant. 2011; 11: 2414-2422
        • Seckinger J.
        • Sommerer C.
        • Hinkel U.P.
        • Hoffmann O.
        • Zeier M.
        • Schwenger V.
        Switch of immunosuppression from cyclosporine A to everolimus: impact on pulse wave velocity in stable de-novo renal allograft recipients.
        J Hypertens. 2008; 26: 2213-2219
        • Guidi E.
        • Menghetti D.
        • Milani S.
        • Montagnino G.
        • Palazzi P.
        • Bianchi G.
        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: 1131-1138
        • Bianchi G.
        • Fox U.
        • Di Francesco G.F.
        • Giovanetti A.M.
        • Pagetti D.
        Blood pressure changes produced by kidney cross-transplantation between spontaneously hypertensive rats and normotensive rats.
        Clin Sci Mol Med. 1974; 47: 435-448
        • Patschan O.
        • Kuttler B.
        • Heemann U.
        • Uber A.
        • Rettig R.
        Kidneys from normotensive donors lower blood pressure in young transplanted spontaneously hypertensive rats.
        Am J Physiol. 1997; 273: R175-R180
        • Sinclair A.M.
        • Isles C.G.
        • Brown I.
        • Cameron H.
        • Murray G.D.
        • Robertson J.W.
        Secondary hypertension in a blood pressure clinic.
        Arch Intern Med. 1987; 147: 1289-1293
        • Kone B.C.
        • Whelton A.
        • Santos G.
        • Saral R.
        • Watson A.J.
        Hypertension and renal dysfunction in bone marrow transplant recipients.
        QJM. 1988; 69: 985-995
        • Textor S.C.
        • Schwartz L.
        • Wilson D.J.
        • et al.
        Systemic and renal effects of nifedipine in cyclosporine-associated hypertension.
        Hypertension. 1994; 23: I220-I224
        • Thompson M.E.
        • Shapiro A.P.
        • Johnsen A.M.
        • et al.
        The contrasting effects of cyclosporin-A and azathioprine on arterial blood pressure and renal function following cardiac transplantation.
        Int J Cardiol. 1986; 11: 219-229
        • Iijima K.
        • Hamahira K.
        • Kobayashi A.
        • Nakamura H.
        • Yoshikawa N.
        Immunohistochemical analysis of renin activity in chronic cyclosporine nephropathy in childhood nephrotic syndrome.
        J Am Soc Nephrol. 2000; 11: 2265-2271
        • Kurtz A.
        • Della Bruna R.
        • Kühn K.
        Cyclosporine A enhances renin secretion and production in isolated juxtaglomerular cells.
        Kidney Int. 1988; 33: 947-953
        • Lassila M.
        Interaction of cyclosporine A and the renin-angiotensin system; new perspectives.
        Curr Drug Metab. 2002; 3: 61-71
        • Mason J.
        • Müller-Schweinitzer E.
        • Dupont M.
        • et al.
        Cyclosporine and the renin-angiotensin system.
        Kidney Int Suppl. 1991; 32: S28-S32
        • Tufro-McReddie A.
        • Gomez R.A.
        • Norling L.L.
        • Omar A.A.
        • Moore L.C.
        • Kaskel F.J.
        Effect of CsA on the expression of renin and angiotensin type 1 receptor genes in the rat kidney.
        Kidney Int. 1993; 43: 615-622
        • Canzanello V.J.
        • Textor S.C.
        • Taler S.J.
        • et al.
        Renal sodium handling with cyclosporin A and FK506 after orthotopic liver transplantation.
        J Am Soc Nephrol. 1995; 5: 1910-1917
        • Textor S.C.
        • Burnett J.C.
        • Romero J.C.
        • et al.
        Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation.
        Kidney Int. 1995; 47: 1426-1433
        • Ciresi D.L.
        • Lloyd M.A.
        • Sandberg S.M.
        • Heublein D.M.
        • Edwards B.S.
        The sodium retaining effects of cyclosporine.
        Kidney Int. 1992; 41: 1599-1605
        • Sturrock N.D.
        • Lang C.C.
        • MacFarlane L.J.
        • et al.
        Serial changes in blood pressure, renal function, endothelin and lipoprotein (a) during the first 9 days of cyclosporin therapy in males.
        J Hypertens. 1995; 13: 667-673
        • Hoorn E.J.
        • Walsh S.B.
        • McCormick J.A.
        • et al.
        The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension.
        Nat Med. 2011; 17: 1304-1309
        • Melnikov S.
        • Mayan H.
        • Uchida S.
        • Holtzman E.J.
        • Farfel Z.
        Cyclosporine metabolic side effects: association with the WNK4 system.
        Eur J Clin Invest. 2011; 41: 1113-1120
        • Kihm L.P.
        • Blume C.
        • Seckinger J.
        • et al.
        Acute effects of calcineurin inhibitors on kidney allograft microperfusion visualized by contrast-enhanced sonography.
        Transplantation. 2012; 93: 1125-1129
        • Strozecki P.
        • Adamowick A.
        • Wlodarczyk Z.
        • Manitius J.
        The influence of calcineurin inhibitors on pulse wave velocity in renal transplant recipients.
        Ren Fail. 2007; 29: 679-684
        • Textor S.C.
        • Wiesner R.
        • Wilson D.J.
        • et al.
        Systemic and renal hemodynamic differences between FK506 and cyclosporine in liver transplant recipients.
        Transplantation. 1993; 55: 1332-1339
        • Copley J.B.
        • Staffeld C.
        • Lindberg J.
        • et al.
        Cyclosporine to tacrolimus: effect on hypertension and lipid profiles in renal allografts.
        Transplant Proc. 1998; 30: 1254-1256
        • Ligtenberg G.
        • Hené R.J.
        • Blankestijn P.J.
        • Koomans H.A.
        Cardiovascular risk factors in renal transplant patients: cyclosporin A versus tacrolimus.
        J Am Soc Nephrol. 2001; 12: 368-373
        • Margreiter R.
        • European Tacrolimus vs Ciclosporin Microemulsion Renal Transplantation Study Group
        Efficacy and safety of tacrolimus compared with cyclosporin microemulsion in renal transplantation: a randomised multicentre study.
        Lancet. 2002; 359: 741-746
        • Vincenti F.
        • Jensik S.C.
        • Filo R.S.
        • Miller J.
        • Pirsch J.
        A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years.
        Transplantation. 2002; 73: 775-782
        • Taler S.J.
        • Textor S.C.
        • Canzanello V.J.
        • et al.
        Role of steroid dose in hypertension early after liver transplantation with tacrolimus (FK506) and cyclosporine.
        Transplantation. 1996; 62: 1588-1592
        • Goodwin J.E.
        • Zhang J.
        • Geller D.S.
        A critical role for vascular smooth muscle in acute glucocorticoid-induced hypertension.
        J Am Soc Nephrol. 2008; 19: 1291-1299
        • 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: 95-99
        • Bruno S.
        • Remuzzi G.
        • Ruggenenti P.
        Transplant renal artery stenosis.
        J Am Soc Nephrol. 2004; 15: 134-141
        • Ghazanfar A.
        • Tavakoli A.
        • Augustine T.
        • Pararajasingam R.
        • Riad H.
        • Chalmers N.
        Management of transplant renal artery stenosis and its impact on long-term allograft survival: a single-centre experience.
        Nephrol Dial Transplant. 2011; 26: 336-343
        • Halimi J.M.
        • Al-Najjar A.
        • Buchler M.
        • et al.
        Transplant renal artery stenosis: potential role of ischemia/reperfusion injury and long-term outcome following angioplasty.
        J Urol. 1999; 161: 28-32
        • 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: 1731-1738
        • Wong W.
        • Fynn S.P.
        • Higgins R.M.
        • et al.
        Transplant renal artery stenosis in 77 patients--does it have an immunological cause?.
        Transplantation. 1996; 61: 215-219
        • Grünfeld J.P.
        • Kleinknecht D.
        • Moreau J.F.
        • et al.
        Permanent hypertension after renal homotransplantation in man.
        Clin Sci Mol Med. 1975; 48: 391-403
        • Hagen G.
        • Wadström J.
        • Magnusson M.
        • Magnusson A.
        Outcome after percutaneous transluminal angioplasty of arterial stenosis in renal transplant patients.
        Acta Radiol. 2009; 50: 270-275
        • Henning B.F.
        • Kuchlbauer S.
        • Böger C.A.
        • et al.
        Percutaneous transluminal angioplasty as first-line treatment of transplant renal artery stenosis.
        Clin Nephrol. 2009; 71: 543-549
        • Zhang Z.
        • Liang H.
        • Feng G.
        • Zheng C.
        • Wu H.
        • Zhou G.F.
        • et al.
        Interventional treatment of transplanted renal artery stenosis.
        J Interv Radiol. 2008; 17: 623-626
        • Hurst F.P.
        • Abbott K.C.
        • Neff R.T.
        • et al.
        Incidence, predictors and outcomes of transplant renal artery stenosis after kidney transplantation: analysis of USRDS.
        Am J Nephrol. 2009; 30: 459-467
        • Curtis J.J.
        • Luke R.G.
        • Diethelm A.G.
        • Whelchel J.D.
        • Jones P.
        Benefits of removal of native kidneys in hypertension after renal transplantation.
        Lancet. 1985; 2: 739-742
        • Hausberg M.
        • Kosch M.
        • Harmelink P.
        • et al.
        Sympathetic nerve activity in end-stage renal disease.
        Circulation. 2002; 106: 1974-1979
        • Huysmans F.T.
        • Hoitsma A.J.
        • Koene R.A.
        Factors determining the prevalence of hypertension after renal transplantation.
        Nephrol Dial Transplant. 1987; 2: 34-38
        • Fricke L.
        • Doehn C.
        • Steinhoff J.
        • Sack K.
        • Jocham D.
        • Fornara P.
        Treatment of posttransplant hypertension by laparoscopic bilateral nephrectomy?.
        Transplantation. 1998; 65: 1182-1187
        • Fornara P.
        • Doehn C.
        • Fricke L.
        • Durek C.
        • Thyssen G.
        • Jocham D.
        Laparoscopic bilateral nephrectomy: results in 11 renal transplant patients.
        J Urol. 1997; 157: 445-449
        • Zazgornik J.
        • Biesenbach G.
        • Janko O.
        • et al.
        Bilateral nephrectomy: the best, but often overlooked, treatment for refractory hypertension in hemodialysis patients.
        Am J Hypertens. 1998; 11: 1364-1370
        • Macsim L.S.
        • Strócecki P.
        • Miskowiec-Wisniewska I.
        • Kardymowicz A.
        • Manitius J.
        Bilateral nephrectomy as a rescue therapy for hemodialyzed patient with malignant hypertension - case report.
        Case Rep Nephrol Urol. 2012; 2: 11-14
        • Bales G.T.
        • Fellner S.K.
        • Chodak G.W.
        • Rukstalis D.B.
        Laparoscopic bilateral nephrectomy for renin-mediated hypertension.
        Urology. 1994; 43: 874-877
        • Sanjeevan K.V.
        • Bhat H.S.
        • Sudhindran S.
        Laparoscopic simultaneous bilateral pretransplant nephrectomy for uncontrolled hypertension.
        Transplant Proc. 2004; 36: 2011-2012
        • Shoma A.M.
        • Eraky I.
        • El-Kappany H.A.
        Pretransplant native nephrectomy in patients with end-stage renal failure: assessment of the role of laparoscopy.
        Urology. 2003; 61: 915-920
        • Midtvedt K.
        • Hartmann A.
        • Bentdal O.
        • Brekke I.B.
        • Fauchald P.
        Bilateral nephrectomy simultaneously with renal allografting does not alleviate hypertension 3 months following living-donor transplantation.
        Nephrol Dial Transplant. 1996; 11: 2045-2049
        • Symplicity H.T.N.
        • Esler M.D.
        • Krum H.
        • et al.
        Renal sympathetic denervation in patients with treatment-resistant hypertension (the Symplicity HTN-2 trial): a randomised controlled trial.
        Lancet. 2010; 376: 1903-1909
        • Chobanian A.V.
        • Bakris G.L.
        • Black H.R.
        • et al.
        The Seventh Report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report.
        JAMA. 2003; 289: 2560-2572
        • Marin J.M.
        • Agusti A.
        • Villar I.
        • et al.
        Association between treated and untreated obstructive sleep apnea and risk of hypertension.
        JAMA. 2012; 307: 2169-2176
        • Meier-Kriesche H.U.
        • Li S.
        • Gruessner R.W.G.
        • et al.
        Immunosuppression: evolution in practice and trends, 1994-2004.
        Am J Transplant. 2006; 6: 1111-1131
        • Knight S.R.
        • Morris P.J.
        Steroid avoidance or withdrawal after renal transplantation increases the risk of acute rejection but decreases cardiovascular risk.
        A meta-analysis. Transplantation. 2010; 89: 1-14
        • Ahsan N.
        • Hricik D.
        • Matas A.
        • et al.
        Prednisone withdrawal in kidney transplant recipients on cyclosporine and mycophenolate mofetil--a prospective randomized study. Steroid Withdrawal Study Group.
        Transplantation. 1999; 68: 1865-1874
        • Höcker B.
        • Weber L.T.
        • Feneberg R.
        • et al.
        Prospective, randomized trial on late steroid withdrawal in pediatric renal transplant recipients under cyclosporine microemulsion and mycophenolate mofetil.
        Transplantation. 2009; 87: 934-941
        • Hricik D.E.
        • Lautman J.
        • Bartucci M.R.
        • Moir E.J.
        • Mayes J.T.
        • Schulak J.A.
        Variable effects of steroid withdrawal on blood pressure reduction in cyclosporine-treated renal transplant recipients.
        Transplantation. 1992; 53: 1232-1235
        • Sarwal M.M.
        • Vidhun J.R.
        • Alexander S.R.
        • Satterwhite T.
        • Millan M.
        • Salvatierra O.
        Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation.
        Transplantation. 2003; 76: 1331-1339
        • Vanrenterghem Y.
        • Lebranchu Y.
        • Hené R.
        • Oppenheimer F.
        • Ekberg H.
        Double-blind comparison of two corticosteroid regimens plus mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection.
        Transplantation. 2000; 70: 1352-1359
        • Sivaraman P.
        • Nussbaumer G.
        • Landsberg D.
        Lack of long-term benefits of steroid withdrawal in renal transplant recipients.
        Am J Kidney Diseases. 2001; 37: 1162-1169
        • Pelletier R.P.
        • Akin B.
        • Ferguson R.M.
        Prospective, randomized trial of steroid withdrawal in kidney recipients treated with mycophenolate mofetil and cyclosporine.
        Clin Transplant. 2006; 20: 10-18
        • Woodle E.S.
        • First M.R.
        • 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: 564-577
        • Johnson R.W.
        • Kreis H.
        • Oberbauer R.
        • Brattström C.
        • Claesson K.
        • Eris J.
        Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure.
        Transplantation. 2001; 72: 777-786
        • Hueso M.
        • Bover J.
        • Serón D.
        • et al.
        Low-dose cyclosporine and mycophenolate mofetil in renal allograft recipients with suboptimal renal function.
        Transplantation. 1998; 66: 1727-1731
        • Schnuelle P.
        • van der Heide J.H.
        • Tegzess A.
        • et al.
        Open randomized trial comparing early withdrawal of either cyclosporine or mycophenolate mofetil in stable renal transplant recipients initially treated with a triple drug regimen.
        J Am Soc Nephrol. 2002; 13: 536-543
        • Wong W.
        • Tolkoff-Rubin N.
        • Delmonico F.L.
        • et al.
        Analysis of the cardiovascular risk profile in stable kidney transplant recipients after 50% cyclosporine reduction.
        Clin Transplant. 2004; 18: 341-348
        • Vincenti F.
        • Larsen C.
        • Durrbach A.
        • et al.
        Costimulation blockade with belatacept in renal transplantation.
        N Engl J Med. 2005; 353: 770-781
        • Ekberg H.
        • Grinyó J.
        • Nashan B.
        • et al.
        Cyclosporine sparing with mycophenolate mofetil, daclizumab and corticosteroids in renal allograft recipients: the CAESAR study.
        Am J Transplant. 2007; 7: 560-570
        • Martinez-Castelao A.
        • Hueso M.
        • Sanz V.
        • et al.
        Double-blind, crossover, comparative study of doxazosin and enalapril in the treatment of hypertension in renal transplant patients under cyclosporine immunosuppression.
        Transplant Proc. 2002; 34: 403-406
        • Premasathian N.C.
        • Muehrer R.
        • Brazy P.C.
        • Pirsch J.D.
        • Becker B.N.
        Blood pressure control in kidney transplantation: therapeutic implications.
        J Hum Hypertens. 2004; 18: 871-877
        • Pilmore H.L.
        • Skeans M.A.
        • Snyder J.J.
        • Israni A.K.
        • Kasiske B.L.
        Cardiovascular disease medications after renal transplantation: results from the Patient Outcomes in Renal Transplantation study.
        Transplantation. 2011; 91: 542-551
        • Iñigo P.
        • Campistol J.M.
        • Lario S.
        • et al.
        Effects of losartan and amlodipine on intrarenal hemodynamics and TGF-beta(1) plasma levels in a crossover trial in renal transplant recipients.
        J Am Soc Nephrol. 2001; 12: 822-827
        • Madsen J.K.
        • Sørensen S.S.
        • Hansen H.E.
        • Pedersen E.B.
        The effect of felodipine on renal function and blood pressure in cyclosporin-treated renal transplant recipients during the first three months after transplantation.
        Nephrol Dial Transplant. 1998; 13: 2327-2334
        • Ruggenenti P.
        • Perico N.
        • Mosconi L.
        • et al.
        Calcium channel blockers protect transplant patients from cyclosporine-induced daily renal hypoperfusion.
        Kidney Int. 1993; 43: 706-711
        • Jones T.E.
        • Morris R.G.
        Pharmacokinetic interaction between tacrolimus and diltiazem: dose-response relationship in kidney and liver transplant recipients.
        Clin Pharmacokinet. 2002; 41: 381-388
        • Schrama Y.C.
        • Koomans H.A.
        Interactions of cyclosporin A and amlodipine: blood cyclosporin A levels, hypertension and kidney function.
        J Hypertens Suppl. 1998; 16: S33-S38
        • Curtis J.J.
        • Laskow D.A.
        • Jones P.A.
        • Julian B.A.
        • Gaston R.S.
        • Luke R.G.
        Captopril-induced fall in glomerular filtration rate in cyclosporine-treated hypertensive patients.
        J Am Soc Nephrol. 1993; 3: 1570-1574
        • Hiremath S.
        • Fergusson D.
        • Doucette S.
        • Mulay A.V.
        • Knoll G.A.
        Renin angiotensin system blockade in kidney transplantation: a systematic review of the evidence.
        Am J Transplant. 2007; 7: 2350-2360
        • Amer H.
        • Fidler M.E.
        • Myslak M.
        • et al.
        Proteinuria after kidney transplantation, relationship to allograft histology and survival.
        Am J Transplant. 2007; 7: 2748-2756
        • Cross N.B.
        • Webster A.C.
        • Masson P.
        • O’connell P.J.
        • Craig J.C.
        Antihypertensives for kidney transplant recipients: systematic review and meta-analysis of randomized controlled trials.
        Transplantation. 2009; 88: 7-18
        • Hausberg M.
        • Barenbrock M.
        • Hohage H.
        • Müller S.
        • Heidenreich S.
        • Rahn K.H.
        ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients.
        Hypertension. 1999; 33: 862-868
        • Omoto K.
        • Tanabe K.
        • Tokumoto T.
        • Shimmura H.
        • Ishida H.
        • Toma H.
        Use of candesartan cilexetil decreases proteinuria in renal transplant patients with chronic allograft dysfunction.
        Transplantation. 2003; 76: 1170-1174
        • Paoletti E.
        • Bellino D.
        • Marsano L.
        • Cassottana P.
        • Rolla D.
        • Ratto E.
        Effects of ACE inhibitors on long-term outcome of renal transplant recipients: a randomized controlled trial.
        Transplantation. 2013; 95: 889-895
        • Philipp T.
        • Martinez F.
        • Geiger H.
        • et al.
        Candesartan improves blood pressure control and reduces proteinuria in renal transplant recipients: results from SECRET.
        Nephrol Dial Transplant. 2010; 25: 967-976
        • Roodnat J.I.
        • Mulder P.G.
        • Rischen-Vos J.
        • et al.
        Proteinuria after renal transplantation affects not only graft survival but also patient survival.
        Transplantation. 2001; 72: 438-444