Cardiovascular risk factors following renal transplant

Jill Neale, Alice C Smith, Jill Neale, Alice C Smith

Abstract

Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Non-traditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population.

Keywords: Atherosclerosis; Cardiovascular disease; Diabetes mellitus; Immunosuppression; Kidney transplantation.

References

    1. Jha V, Wang AY, Wang H. The impact of CKD identification in large countries: the burden of illness. Nephrol Dial Transplant. 2012;27 Suppl 3:iii32–iii38.
    1. Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375:2073–2081.
    1. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–1305.
    1. Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN, Kasiske BL, Klag MJ, Mailloux LU, Manske CL, Meyer KB, et al. Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis. 1998;32:853–906.
    1. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, Port FK. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341:1725–1730.
    1. Rao PS, Merion RM, Ashby VB, Port FK, Wolfe RA, Kayler LK. Renal transplantation in elderly patients older than 70 years of age: results from the Scientific Registry of Transplant Recipients. Transplantation. 2007;83:1069–1074.
    1. Oniscu GC, Brown H, Forsythe JL. How great is the survival advantage of transplantation over dialysis in elderly patients? Nephrol Dial Transplant. 2004;19:945–951.
    1. Bottomley MJ, Harden PN. Update on the long-term complications of renal transplantation. Br Med Bull. 2013;106:117–134.
    1. von der Lippe N, Waldum B, Brekke FB, Amro AA, Reisæter AV, Os I. From dialysis to transplantation: a 5-year longitudinal study on self-reported quality of life. BMC Nephrol. 2014;15:191.
    1. Liefeldt L, Budde K. Risk factors for cardiovascular disease in renal transplant recipients and strategies to minimize risk. Transpl Int. 2010;23:1191–1204.
    1. Meier-Kriesche HU, Schold JD, Srinivas TR, Reed A, Kaplan B. Kidney transplantation halts cardiovascular disease progression in patients with end-stage renal disease. Am J Transplant. 2004;4:1662–1668.
    1. Holdaas H, Fellström B, Jardine AG, Holme I, Nyberg G, Fauchald P, Grönhagen-Riska C, Madsen S, Neumayer HH, Cole E, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet. 2003;361:2024–2031.
    1. Willicombe M, Kumar N, Goodall D, Clarke C, McLean AG, Power A, Taube D. Incidence, risk factors, and outcomes of stroke post-transplantation in patients receiving a steroid sparing immunosuppression protocol. Clin Transplant. 2015;29:18–25.
    1. Sung RS, Althoen M, Howell TA, Merion RM. Peripheral vascular occlusive disease in renal transplant recipients: risk factors and impact on kidney allograft survival. Transplantation. 2000;70:1049–1054.
    1. Pruthi R, Casula A, MacPhee I. UK Renal Registry 17th Annual Report: Chapter 3 Demographic and Biochemistry Profile of Kidney Transplant Recipients in the UK in 2013: National and Centre-specific Analyses. Nephron. 2015;129 Suppl 1:57–86.
    1. Ghanta M, Kozicky M, Jim B. Pathophysiologic and treatment strategies for cardiovascular disease in end-stage renal disease and kidney transplantations. Cardiol Rev. 2014;23:109–118.
    1. Boerner BP, Shivaswamy V, Desouza CV, Larsen JL. Diabetes and cardiovascular disease following kidney transplantation. Curr Diabetes Rev. 2011;7:221–234.
    1. De Lima JJ, Gowdak LH, de Paula FJ, Arantes RL, Ianhez LE, Ramires JA, Krieger EM. Influence of coronary artery disease assessment and treatment in the incidence of cardiac events in renal transplant recipients. Clin Transplant. 2010;24:474–480.
    1. Farrugia D, Cheshire J, Begaj I, Khosla S, Ray D, Sharif A. Death within the first year after kidney transplantation--an observational cohort study. Transpl Int. 2014;27:262–270.
    1. Pilmore HL, Skeans MA, Snyder JJ, Israni AK, Kasiske BL. Cardiovascular disease medications after renal transplantation: results from the Patient Outcomes in Renal Transplantation study. Transplantation. 2011;91:542–551.
    1. Aalten J, Peeters SA, van der Vlugt MJ, Hoitsma AJ. Is standardized cardiac assessment of asymptomatic high-risk renal transplant candidates beneficial? Nephrol Dial Transplant. 2011;26:3006–3012.
    1. Lentine KL, Brennan DC, Schnitzler MA. Incidence and predictors of myocardial infarction after kidney transplantation. J Am Soc Nephrol. 2005;16:496–506.
    1. Aftab W, Varadarajan P, Rasool S, Pai RG. Predictors and prognostic implications of major adverse cardiovascular events after renal transplant: 10 years outcomes in 321 patients. Int J Angiol. 2014;23:131–138.
    1. Carpenter MA, Weir MR, Adey DB, House AA, Bostom AG, Kusek JW. Inadequacy of cardiovascular risk factor management in chronic kidney transplantation - evidence from the FAVORIT study. Clin Transplant. 2012;26:E438–E446.
    1. Lindholm A, Albrechtsen D, Frödin L, Tufveson G, Persson NH, Lundgren G. Ischemic heart disease--major cause of death and graft loss after renal transplantation in Scandinavia. Transplantation. 1995;60:451–457.
    1. Sundström J, Arima H, Woodward M, Jackson R, Karmali K, Lloyd-Jones D, Baigent C, Emberson J, Rahimi K, MacMahon S, et al. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet. 2014;384:591–598.
    1. Kidney disease: Improving global outcomes (KDIGO) blood pressure work group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Inter. 2012;2 Suppl:337–414.
    1. UK Renal Association Clinical Practice Guidelines Committee. Guideline: Post-operative care of the kidney transplant recipient, 5th ed. 2011; Available from: .
    1. Muntner P, Anderson A, Charleston J, Chen Z, Ford V, Makos G, O’Connor A, Perumal K, Rahman M, Steigerwalt S, et al. Hypertension awareness, treatment, and control in adults with CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2010;55:441–451.
    1. Kasiske BL, Anjum S, Shah R, Skogen J, Kandaswamy C, Danielson B, O’Shaughnessy EA, Dahl DC, Silkensen JR, Sahadevan M, et al. Hypertension after kidney transplantation. Am J Kidney Dis. 2004;43:1071–1081.
    1. Zhang H, Li X. The risk factors of cardiovascular disease in patients with renal transplantation. Pak J Med Sci. 2014;30:1228–1231.
    1. Mangray M, Vella JP. Hypertension after kidney transplant. Am J Kidney Dis. 2011;57:331–341.
    1. Mange KC, Cizman B, Joffe M, Feldman HI. Arterial hypertension and renal allograft survival. JAMA. 2000;283:633–638.
    1. Opelz G, Döhler B. Improved long-term outcomes after renal transplantation associated with blood pressure control. Am J Transplant. 2005;5:2725–2731.
    1. Zhang R, Leslie B, Boudreaux JP, Frey D, Reisin E. Hypertension after kidney transplantation: impact, pathogenesis and therapy. Am J Med Sci. 2003;325:202–208.
    1. Artz MA, Boots JM, Ligtenberg G, Roodnat JI, Christiaans MH, Vos PF, Blom HJ, Sweep FC, Demacker PN, Hilbrands LB. Improved cardiovascular risk profile and renal function in renal transplant patients after randomized conversion from cyclosporine to tacrolimus. J Am Soc Nephrol. 2003;14:1880–1888.
    1. Vincenti F, Jensik SC, Filo RS, 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.
    1. Webster A, Woodroffe RC, Taylor RS, Chapman JR, Craig JC. Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients. Cochrane Database Syst Rev. 2005;5:CD003961.
    1. Dawidson I, Rooth P, Lu C, Sagalowsky A, Diller K, Palmer B, Peters P, Risser R, Sandor Z, Seney F. Verapamil improves the outcome after cadaver renal transplantation. J Am Soc Nephrol. 1991;2:983–990.
    1. Rump LC, Oberhauser V, Schwertfeger E, Speidel L, Zimmerhackl L, Kirste G, Grotz W. Dihydropyridine calcium antagonists and renal function in hypertensive kidney transplant recipients. J Hypertens. 2000;18:1115–1119.
    1. Kuypers DR, Neumayer HH, Fritsche L, Budde K, Rodicio JL, Vanrenterghem Y. Calcium channel blockade and preservation of renal graft function in cyclosporine-treated recipients: a prospective randomized placebo-controlled 2-year study. Transplantation. 2004;78:1204–1211.
    1. Halimi JM, Giraudeau B, Buchler M, Al-Najjar A, Etienne I, Laouad I, Bruyère F, Lebranchu Y. Enalapril/amlodipine combination in cyclosporine-treated renal transplant recipients: a prospective randomized trial. Clin Transplant. 2007;21:277–284.
    1. Cross NB, Webster AC, Masson P, O’connell PJ, Craig JC. Antihypertensives for kidney transplant recipients: systematic review and meta-analysis of randomized controlled trials. Transplantation. 2009;88:7–18.
    1. Hiremath S, Fergusson D, Doucette S, Mulay AV, Knoll GA. Renin angiotensin system blockade in kidney transplantation: a systematic review of the evidence. Am J Transplant. 2007;7:2350–2360.
    1. Duerr M, Glander P, Diekmann F, Dragun D, Neumayer HH, Budde K. Increased incidence of angioedema with ACE inhibitors in combination with mTOR inhibitors in kidney transplant recipients. Clin J Am Soc Nephrol. 2010;5:703–708.
    1. Gonyea JE, Anderson CF. Weight change and serum lipoproteins in recipients of renal allografts. Mayo Clin Proc. 1992;67:653–657.
    1. Ong CS, Pollock CA, Caterson RJ, Mahony JF, Waugh DA, Ibels LS. Hyperlipidemia in renal transplant recipients: natural history and response to treatment. Medicine (Baltimore) 1994;73:215–223.
    1. Tse KC, Lam MF, Yip PS, Li FK, Lai KN, Chan TM. A long-term study on hyperlipidemia in stable renal transplant recipients. Clin Transplant. 2004;18:274–280.
    1. Pannu HS, Singh D, Sandhu JS. Lipid profile before and after renal transplantation--a longitudinal study. Ren Fail. 2003;25:411–417.
    1. Roodnat JI, Mulder PG, Zietse R, Rischen-Vos J, van Riemsdijk IC, IJzermans JN, Weimar W. Cholesterol as an independent predictor of outcome after renal transplantation. Transplantation. 2000;69:1704–1710.
    1. Jardine AG, Fellström B, Logan JO, Cole E, Nyberg G, Grönhagen-Riska C, Madsen S, Neumayer HH, Maes B, Ambühl P, et al. Cardiovascular risk and renal transplantation: post hoc analyses of the Assessment of Lescol in Renal Transplantation (ALERT) Study. Am J Kidney Dis. 2005;46:529–536.
    1. Manitpisitkul W, McCann E, Lee S, Weir MR. Drug interactions in transplant patients: what everyone should know. Curr Opin Nephrol Hypertens. 2009;18:404–411.
    1. Lemahieu WP, Hermann M, Asberg A, Verbeke K, Holdaas H, Vanrenterghem Y, Maes BD. Combined therapy with atorvastatin and calcineurin inhibitors: no interactions with tacrolimus. Am J Transplant. 2005;5:2236–2243.
    1. Holdaas H, Kobashigawa J, Fellstrom JA, Jardine A. Special transplant populations: Transplant recipients. Clin Lipidol. 2009:486–499.
    1. de Sévaux RG, Hilbrands LB, Tiggeler RG, Koene RA, Hoitsma AJ. A randomised, prospective study on the conversion from cyclosporine-prednisone to cyclosporine-azathioprine at 6 months after renal transplantation. Transpl Int. 1998;11 Suppl 1:S322–S324.
    1. Spinelli GA, Felipe CR, Park SI, Mandia-Sampaio EL, Tedesco-Silva H, Medina-Pestana JO. Lipid profile changes during the first year after kidney transplantation: risk factors and influence of the immunosuppressive drug regimen. Transplant Proc. 2011;43:3730–3737.
    1. Vathsala A, Weinberg RB, Schoenberg L, Grevel J, Goldstein RA, Van Buren CT, Lewis RM, Kahan BD. Lipid abnormalities in cyclosporine-prednisone-treated renal transplant recipients. Transplantation. 1989;48:37–43.
    1. Claes K, Meier-Kriesche HU, Schold JD, Vanrenterghem Y, Halloran PF, Ekberg H. Effect of different immunosuppressive regimens on the evolution of distinct metabolic parameters: evidence from the Symphony study. Nephrol Dial Transplant. 2012;27:850–857.
    1. Kasiske BL, de Mattos A, Flechner SM, Gallon L, Meier-Kriesche HU, Weir MR, Wilkinson A. Mammalian target of rapamycin inhibitor dyslipidemia in kidney transplant recipients. Am J Transplant. 2008;8:1384–1392.
    1. Palmer SC, Navaneethan SD, Craig JC, Perkovic V, Johnson DW, Nigwekar SU, Hegbrant J, Strippoli GF. HMG CoA reductase inhibitors (statins) for kidney transplant recipients. Cochrane Database Syst Rev. 2014;1:CD005019.
    1. Hjelmesaeth J, Hartmann A, Leivestad T, Holdaas H, Sagedal S, Olstad M, Jenssen T. The impact of early-diagnosed new-onset post-transplantation diabetes mellitus on survival and major cardiac events. Kidney Int. 2006;69:588–595.
    1. Pham PT, Pham PM, Pham SV, Pham PA, Pham PC. New onset diabetes after transplantation (NODAT): an overview. Diabetes Metab Syndr Obes. 2011;4:175–186.
    1. Davidson J, Wilkinson A, Dantal J, Dotta F, Haller H, Hernández D, Kasiske BL, Kiberd B, Krentz A, Legendre C, et al. New-onset diabetes after transplantation: 2003 International consensus guidelines. Proceedings of an international expert panel meeting. Barcelona, Spain, 19 February 2003. Transplantation. 2003;75:SS3–S24.
    1. American Diabetes Association. Standards of medical care in diabetes--2010. Diabetes Care. 2010;33 Suppl 1:S11–S61.
    1. Balla A, Chobanian M. New-onset diabetes after transplantation: a review of recent literature. Curr Opin Organ Transplant. 2009;14:375–379.
    1. Elmagd MM, Bakr MA, Metwally AH, Wahab AM. Clinicoepidemiologic study of posttransplant diabetes after living-donor renal transplant. Exp Clin Transplant. 2008;6:42–47.
    1. Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003;3:178–185.
    1. Cosio FG, Pesavento TE, Osei K, Henry ML, Ferguson RM. Post-transplant diabetes mellitus: increasing incidence in renal allograft recipients transplanted in recent years. Kidney Int. 2001;59:732–737.
    1. Miles AM, Sumrani N, Horowitz R, Homel P, Maursky V, Markell MS, Distant DA, Hong JH, Sommer BG, Friedman EA. Diabetes mellitus after renal transplantation: as deleterious as non-transplant-associated diabetes? Transplantation. 1998;65:380–384.
    1. Moore R, Boucher A, Carter J, Kim SJ, Kiberd B, Loertscher R, Mongeau JG, Prasad GV, Vautour L. Diabetes mellitus in transplantation: 2002 consensus guidelines. Transplant Proc. 2003;35:1265–1270.
    1. Hjelmesaeth J, Hartmann A, Kofstad J, Stenstrøm J, Leivestad T, Egeland T, Fauchald P. Glucose intolerance after renal transplantation depends upon prednisolone dose and recipient age. Transplantation. 1997;64:979–983.
    1. Meigs JB, Mittleman MA, Nathan DM, Tofler GH, Singer DE, Murphy-Sheehy PM, Lipinska I, D’Agostino RB, Wilson PW. Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study. JAMA. 2000;283:221–228.
    1. Garg N, Weinberg J, Ghai S, Bradauskaite G, Nuhn M, Gautam A, Kumar N, Francis J, Chen JL. Lower magnesium level associated with new-onset diabetes and pre-diabetes after kidney transplantation. J Nephrol. 2014;27:339–344.
    1. Bloom RD, Lake JR. Emerging issues in hepatitis C virus-positive liver and kidney transplant recipients. Am J Transplant. 2006;6:2232–2237.
    1. Boots JM, Christiaans MH, van Hooff JP. Effect of immunosuppressive agents on long-term survival of renal transplant recipients: focus on the cardiovascular risk. Drugs. 2004;64:2047–2073.
    1. Boots JM, van Duijnhoven EM, Christiaans MH, Wolffenbuttel BH, van Hooff JP. Glucose metabolism in renal transplant recipients on tacrolimus: the effect of steroid withdrawal and tacrolimus trough level reduction. J Am Soc Nephrol. 2002;13:221–227.
    1. Vincenti F, Schena FP, Paraskevas S, Hauser IA, Walker RG, Grinyo J. A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients. Am J Transplant. 2008;8:307–316.
    1. Pascual J, Zamora J, Galeano C, Royuela A, Quereda C. Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev. 2009;(1):CD005632.
    1. Palepu S, Prasad GV. New-onset diabetes mellitus after kidney transplantation: Current status and future directions. World J Diabetes. 2015;6:445–455.
    1. Santos L, Rodrigo E, Piñera C, Quintella E, Ruiz JC, Fernández-Fresnedo G, Palomar R, Gómez-Alamillo C, de Francisco A, Arias M. New-onset diabetes after transplantation: drug-related risk factors. Transplant Proc. 2012;44:2585–2587.
    1. Meier-Kriesche HU, Baliga R, Kaplan B. Decreased renal function is a strong risk factor for cardiovascular death after renal transplantation. Transplantation. 2003;75:1291–1295.
    1. Hariharan S, McBride MA, Cherikh WS, Tolleris CB, Bresnahan BA, Johnson CP. Post-transplant renal function in the first year predicts long-term kidney transplant survival. Kidney Int. 2002;62:311–318.
    1. Abbott KC, Yuan CM, Taylor AJ, Cruess DF, Agodoa LY. Early renal insufficiency and hospitalized heart disease after renal transplantation in the era of modern immunosuppression. J Am Soc Nephrol. 2003;14:2358–2365.
    1. Abbott KC, Bucci JR, Cruess D, Taylor AJ, Agodoa LY. Graft loss and acute coronary syndromes after renal transplantation in the United States. J Am Soc Nephrol. 2002;13:2560–2569.
    1. Edmunds M, Russell G, Swales J. Hypertension in renal failure. Textbook of Hypertension. London, Blackwell. 1994. pp. 798–810.
    1. Sechi LA, Catena C, Zingaro L, Melis A, De Marchi S. Abnormalities of glucose metabolism in patients with early renal failure. Diabetes. 2002;51:1226–1232.
    1. Ardhanari S, Alpert MA, Aggarwal K. Cardiovascular disease in chronic kidney disease: risk factors, pathogenesis, and prevention. Adv Perit Dial. 2014;30:40–53.
    1. Rigatto C, Foley R, Jeffery J, Negrijn C, Tribula C, Parfrey P. Electrocardiographic left ventricular hypertrophy in renal transplant recipients: prognostic value and impact of blood pressure and anemia. J Am Soc Nephrol. 2003;14:462–468.
    1. Paoletti E, Cannella G. Reducing the risk of left ventricular hypertrophy in kidney transplant recipients: the potential role of mammalian target of rapamycin. Transplant Proc. 2009;41:S3–S5.
    1. Ibernon M, Moreso F, Ruiz-Majoral A, Sarrias X, Sarrias M, Grinyó JM, Serón D. Contribution of anemia and hypertension to left ventricular hypertrophy during the initial 2 years after renal transplantation. Transplant Proc. 2011;43:2199–2204.
    1. Turkmen F, Emre A, Ozdemir A, Sevinc C, Erisken E, Yesilcimen K. Relationship between aortic valve sclerosis and left ventricular hypertrophy in chronic haemodialysis patients. Int Urol Nephrol. 2008;40:497–502.
    1. Zolty R, Hynes PJ, Vittorio TJ. Severe left ventricular systolic dysfunction may reverse with renal transplantation: uremic cardiomyopathy and cardiorenal syndrome. Am J Transplant. 2008;8:2219–2224.
    1. Ferreira SR, Moisés VA, Tavares A, Pacheco-Silva A. Cardiovascular effects of successful renal transplantation: a 1-year sequential study of left ventricular morphology and function, and 24-hour blood pressure profile. Transplantation. 2002;74:1580–1587.
    1. Rigatto C, Foley RN, Kent GM, Guttmann R, Parfrey PS. Long-term changes in left ventricular hypertrophy after renal transplantation. Transplantation. 2000;70:570–575.
    1. Patel RK, Mark PB, Johnston N, McGregor E, Dargie HJ, Jardine AG. Renal transplantation is not associated with regression of left ventricular hypertrophy: a magnetic resonance study. Clin J Am Soc Nephrol. 2008;3:1807–1811.
    1. Midtvedt K, Ihlen H, Hartmann A, Bryde P, Bjerkely BL, Foss A, Fauchald P, Holdaas H. Reduction of left ventricular mass by lisinopril and nifedipine in hypertensive renal transplant recipients: a prospective randomized double-blind study. Transplantation. 2001;72:107–111.
    1. Paoletti E, Cassottana P, Amidone M, Gherzi M, Rolla D, Cannella G. ACE inhibitors and persistent left ventricular hypertrophy after renal transplantation: a randomized clinical trial. Am J Kidney Dis. 2007;50:133–142.
    1. Paoletti E, Amidone M, Cassottana P, Gherzi M, Marsano L, Cannella G. Effect of sirolimus on left ventricular hypertrophy in kidney transplant recipients: a 1-year nonrandomized controlled trial. Am J Kidney Dis. 2008;52:324–330.
    1. Friedman AN, Miskulin DC, Rosenberg IH, Levey AS. Demographics and trends in overweight and obesity in patients at time of kidney transplantation. Am J Kidney Dis. 2003;41:480–487.
    1. Aalten J, Christiaans MH, de Fijter H, Hené R, van der Heijde JH, Roodnat J, Surachno J, Hoitsma A. The influence of obesity on short- and long-term graft and patient survival after renal transplantation. Transpl Int. 2006;19:901–907.
    1. Lentine KL, Rocca-Rey LA, Bacchi G, Wasi N, Schmitz L, Salvalaggio PR, Abbott KC, Schnitzler MA, Neri L, Brennan DC. Obesity and cardiac risk after kidney transplantation: experience at one center and comprehensive literature review. Transplantation. 2008;86:303–312.
    1. Wissing KM, Pipeleers L. Obesity, metabolic syndrome and diabetes mellitus after renal transplantation: prevention and treatment. Transplant Rev (Orlando) 2014;28:37–46.
    1. Bayer ND, Cochetti PT, Anil Kumar MS, Teal V, Huan Y, Doria C, Bloom RD, Rosas SE. Association of metabolic syndrome with development of new-onset diabetes after transplantation. Transplantation. 2010;90:861–866.
    1. Ducloux D, Kazory A, Simula-Faivre D, Chalopin JM. One-year post-transplant weight gain is a risk factor for graft loss. Am J Transplant. 2005;5:2922–2928.
    1. de Vries AP, Bakker SJ, van Son WJ, van der Heide JJ, Ploeg RJ, The HT, de Jong PE, Gans RO. Metabolic syndrome is associated with impaired long-term renal allograft function; not all component criteria contribute equally. Am J Transplant. 2004;4:1675–1683.
    1. Israni AK, Snyder JJ, Skeans MA, Kasiske BL. Clinical diagnosis of metabolic syndrome: predicting new-onset diabetes, coronary heart disease, and allograft failure late after kidney transplant. Transpl Int. 2012;25:748–757.
    1. Sung RS, Althoen M, Howell TA, Ojo AO, Merion RM. Excess risk of renal allograft loss associated with cigarette smoking. Transplantation. 2001;71:1752–1757.
    1. Kasiske BL, Klinger D. Cigarette smoking in renal transplant recipients. J Am Soc Nephrol. 2000;11:753–759.
    1. Corbett C, Armstrong MJ, Neuberger J. Tobacco smoking and solid organ transplantation. Transplantation. 2012;94:979–987.
    1. Nielens H, Lejeune TM, Lalaoui A, Squifflet JP, Pirson Y, Goffin E. Increase of physical activity level after successful renal transplantation: a 5 year follow-up study. Nephrol Dial Transplant. 2001;16:134–140.
    1. Zelle DM, Corpeleijn E, Stolk RP, de Greef MH, Gans RO, van der Heide JJ, Navis G, Bakker SJ. Low physical activity and risk of cardiovascular and all-cause mortality in renal transplant recipients. Clin J Am Soc Nephrol. 2011;6:898–905.
    1. Painter PL, Hector L, Ray K, Lynes L, Dibble S, Paul SM, Tomlanovich SL, Ascher NL. A randomized trial of exercise training after renal transplantation. Transplantation. 2002;74:42–48.
    1. Mazzoni D, Cicognani E, Mosconi G, Totti V, Roi GS, Trerotola M, Nanni Costa A. Sport activity and health-related quality of life after kidney transplantation. Transplant Proc. 2014;46:2231–2234.
    1. Miller TD, Squires RW, Gau GT, Ilstrup DM, Frohnert PP, Sterioff S. Graded exercise testing and training after renal transplantation: a preliminary study. Mayo Clin Proc. 1987;62:773–777.
    1. Painter PL, Hector L, Ray K, Lynes L, Paul SM, Dodd M, Tomlanovich SL, Ascher NL. Effects of exercise training on coronary heart disease risk factors in renal transplant recipients. Am J Kidney Dis. 2003;42:362–369.
    1. You HS, Chung SY, So HS, Choi SJ. Effect of a DanJeon Breathing Exercise Program on the quality of life in patients with kidney transplants. Transplant Proc. 2008;40:2324–2326.
    1. Juskowa J, Lewandowska M, Bartłomiejczyk I, Foroncewicz B, Korabiewska I, Niewczas M, Sierdziński J. Physical rehabilitation and risk of atherosclerosis after successful kidney transplantation. Transplant Proc. 2006;38:157–160.
    1. Winkelmayer WC, Kramar R, Curhan GC, Chandraker A, Endler G, Födinger M, Hörl WH, Sunder-Plassmann G. Fasting plasma total homocysteine levels and mortality and allograft loss in kidney transplant recipients: a prospective study. J Am Soc Nephrol. 2005;16:255–260.
    1. Ducloux D, Motte G, Challier B, Gibey R, Chalopin JM. Serum total homocysteine and cardiovascular disease occurrence in chronic, stable renal transplant recipients: a prospective study. J Am Soc Nephrol. 2000;11:134–137.
    1. Bostom AG, Carpenter MA, Kusek JW, Levey AS, Hunsicker L, Pfeffer MA, Selhub J, Jacques PF, Cole E, Gravens-Mueller L, et al. Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial. Circulation. 2011;123:1763–1770.
    1. Jardine MJ, Kang A, Zoungas S, Navaneethan SD, Ninomiya T, Nigwekar SU, Gallagher MP, Cass A, Strippoli G, Perkovic V. The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: systematic review and meta-analysis. BMJ. 2012;344:e3533.
    1. Nutritional anaemias. Report of a WHO scientific group. World Health Organ Tech Rep Ser. 1968;405:5–37.
    1. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis. 2006;47:S11–S145.
    1. Mix TC, Kazmi W, Khan S, Ruthazer R, Rohrer R, Pereira BJ, Kausz AT. Anemia: a continuing problem following kidney transplantation. Am J Transplant. 2003;3:1426–1433.
    1. Molnar MZ, Novak M, Ambrus C, Kovacs A, Pap J, Remport A, Szeifert L, Mucsi I. Anemia in kidney transplanted patients. Clin Transplant. 2005;19:825–833.
    1. McClellan W, Aronoff SL, Bolton WK, Hood S, Lorber DL, Tang KL, Tse TF, Wasserman B, Leiserowitz M. The prevalence of anemia in patients with chronic kidney disease. Curr Med Res Opin. 2004;20:1501–1510.
    1. Augustine JJ, Knauss TC, Schulak JA, Bodziak KA, Siegel C, Hricik DE. Comparative effects of sirolimus and mycophenolate mofetil on erythropoiesis in kidney transplant patients. Am J Transplant. 2004;4:2001–2006.
    1. Kreis H, Cisterne JM, Land W, Wramner L, Squifflet JP, Abramowicz D, Campistol JM, Morales JM, Grinyo JM, Mourad G, et al. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation. 2000;69:1252–1260.
    1. Choukroun G, Kamar N, Dussol B, Etienne I, Cassuto-Viguier E, Toupance O, Glowacki F, Moulin B, Lebranchu Y, Touchard G, et al. Correction of postkidney transplant anemia reduces progression of allograft nephropathy. J Am Soc Nephrol. 2012;23:360–368.
    1. Walker AM, Schneider G, Yeaw J, Nordstrom B, Robbins S, Pettitt D. Anemia as a predictor of cardiovascular events in patients with elevated serum creatinine. J Am Soc Nephrol. 2006;17:2293–2298.
    1. Kadambi PV, Javaid B. Cardiovascular diseases in kidney transplant recipients: the role of anemia. Adv Chronic Kidney Dis. 2004;11:328–333.
    1. EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.9.1. Haematological complications. Anaemia. Nephrol Dial Transplant. 2002;17 Suppl 4:48–49.
    1. Linde T, Ekberg H, Forslund T, Furuland H, Holdaas H, Nyberg G, Tydén G, Wahlberg J, Danielson BG. The use of pretransplant erythropoietin to normalize hemoglobin levels has no deleterious effects on renal transplantation outcome. Transplantation. 2001;71:79–82.
    1. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9 Suppl 3:S1–S155.
    1. Bakri RS, Afzali B, Covic A, Sriskantharan R, Bharma-Ariza P, Park WH, Sriharan M, Dalton N, Wierzbicki AS, Crook MA, et al. Cardiovascular disease in renal allograft recipients is associated with elevated sialic acid or markers of inflammation. Clin Transplant. 2004;18:201–204.
    1. Dahle DO, Mjøen G, Oqvist B, Scharnagl H, Weihrauch G, Grammer T, März W, Abedini S, Norby GE, Holme I, et al. Inflammation-associated graft loss in renal transplant recipients. Nephrol Dial Transplant. 2011;26:3756–3761.
    1. Stojanovic D, Cvetkovic T, Stojanovic M, Bojanic V, Stefanovic N, Radenkovic S, Ljubisavljevic S, Pavlovic D. Crosstalk of inflammatory mediators and lipid parameters as early markers of renal dysfunction in stable renal transplant recipients with regard to immunosuppression. Ann Transplant. 2013;18:414–423.
    1. Winkelmayer WC, Lorenz M, Kramar R, Födinger M, Hörl WH, Sunder-Plassmann G. C-reactive protein and body mass index independently predict mortality in kidney transplant recipients. Am J Transplant. 2004;4:1148–1154.
    1. Winkelmayer WC, Schaeffner ES, Chandraker A, Kramar R, Rumpold H, Sunder-Plassmann G, Födinger M. A J-shaped association between high-sensitivity C-reactive protein and mortality in kidney transplant recipients. Transpl Int. 2007;20:505–511.
    1. Tripepi G, Mattace Raso F, Sijbrands E, Seck MS, Maas R, Boger R, Witteman J, Rapisarda F, Malatino L, Mallamaci F, et al. Inflammation and asymmetric dimethylarginine for predicting death and cardiovascular events in ESRD patients. Clin J Am Soc Nephrol. 2011;6:1714–1721.
    1. Abedini S, Holme I, März W, Weihrauch G, Fellström B, Jardine A, Cole E, Maes B, Neumayer HH, Grønhagen-Riska C, et al. Inflammation in renal transplantation. Clin J Am Soc Nephrol. 2009;4:1246–1254.
    1. Pihlstrøm H, Mjøen G, Dahle DO, Pilz S, Midtvedt K, März W, Abedini S, Holme I, Fellström B, Jardine A, et al. Symmetric dimethylarginine as predictor of graft loss and all-cause mortality in renal transplant recipients. Transplantation. 2014;98:1219–1225.
    1. Connolly GM, Cunningham R, McNamee PT, Young IS, Maxwell AP. Troponin T is an independent predictor of mortality in renal transplant recipients. Nephrol Dial Transplant. 2008;23:1019–1025.
    1. Wong BM, Huang M, Zaltzman JS, Prasad GV. Mycophenolate mofetil and C-reactive protein in renal transplant recipients. Transplantation. 2007;83:48–53.
    1. Peddi VR, Dean DE, Hariharan S, Cavallo T, Schroeder TJ, First MR. Proteinuria following renal transplantation: correlation with histopathology and outcome. Transplant Proc. 1997;29:101–103.
    1. Hohage H, Kleyer U, Brückner D, August C, Zidek W, Spieker C. Influence of proteinuria on long-term transplant survival in kidney transplant recipients. Nephron. 1997;75:160–165.
    1. Roodnat JI, Mulder PG, Rischen-Vos J, van Riemsdijk IC, van Gelder T, Zietse R, IJzermans JN, Weimar W. Proteinuria after renal transplantation affects not only graft survival but also patient survival. Transplantation. 2001;72:438–444.
    1. Fernández-Fresnedo G, Escallada R, Rodrigo E, De Francisco AL, Cotorruelo JG, Sanz De Castro S, Zubimendi JA, Ruiz JC, Arias M. The risk of cardiovascular disease associated with proteinuria in renal transplant patients. Transplantation. 2002;73:1345–1348.
    1. Cherukuri A, Welberry-Smith MP, Tattersall JE, Ahmad N, Newstead CG, Lewington AJ, Baker RJ. The clinical significance of early proteinuria after renal transplantation. Transplantation. 2010;89:200–207.
    1. Cherukuri A, Tattersall JE, Lewington AJ, Newstead CG, Baker RJ. Resolution of low-grade proteinuria is associated with improved outcomes after renal transplantation-a retrospective longitudinal study. Am J Transplant. 2015;15:741–753.
    1. Halimi JM, Buchler M, Al-Najjar A, Laouad I, Chatelet V, Marlière JF, Nivet H, Lebranchu Y. Urinary albumin excretion and the risk of graft loss and death in proteinuric and non-proteinuric renal transplant recipients. Am J Transplant. 2007;7:618–625.
    1. Heinze G, Mitterbauer C, Regele H, Kramar R, Winkelmayer WC, Curhan GC, Oberbauer R. 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. 2006;17:889–899.
    1. Opelz G, Zeier M, Laux G, Morath C, Döhler B. 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. 2006;17:3257–3262.
    1. Stephany BR, Augustine JJ, Krishnamurthi V, Goldfarb DA, Flechner SM, Braun WE, Hricik DE, Dennis VW, Poggio ED. Differences in proteinuria and graft function in de novo sirolimus-based vs. calcineurin inhibitor-based immunosuppression in live donor kidney transplantation. Transplantation. 2006;82:368–374.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren