Death as a Cause of Late Allograft Loss thereafter.21
Diagnosis of NODAT is defined according to the current American Diabetes Association (ADA) and World Health Organization (WHO) criteria. Lifestyle changes to modify diet and exercise should be taught to all obese patients. Consideration can be given to bariatric surgery in those patients who have difficulty with weight loss. A USRDS analysis did show that 30-day mortality rates were comparable for pre- and post-kidney transplant recipients undergoing bariatric surgery.38
However, there was a
higher mortality rate in the post-transplant patients 31–90 days post- operatively. Further studies need to be performed to analyze the risk–benefit ratio.
Immunosuppressive regimens can also be individualized according to the patient’s clinical conditions and risk factors. Patients with high risk for developing NODAT should be considered for early withdrawal of corticosteroids and/or maintenance immunosuppression with cyclosporine rather than tacrolimus. High risk of dyslipidemia may necessitate choosing tacrolimus over cyclosporine. However, there are no studies showing that these changes decrease CVD mortality. Patients who are at high risk for malignancy can also be converted to sirolimus. The Sirolimus renal conversion trial (CONVERT) show a significantly decreased rate of overall malignancy and skin carcinomas at two years after conversion to sirolimus from CNI.39
A new immunosuppressive agent still
Mean blood pressure, incidence of NODAT, and lipid profile were all lower in belatacept patients compared with cyclosporine
1. Ojo AO, Hanson JA, Wolfe RA, et al., Long-term survival in renal transplant recipients with graft function, Kidney Int, 2000; 57(1):307–13.
2. Howard RJ, Patton PR, Reed AI, et al., The changing causes of graft loss and death after kidney transplantation, Transplantation, 2002;73(12):1923–8.
3. Meier-Kriesche HU, Arndorfer JA, Kaplan B, Association of antibody induction with short- and long-term cause-specific mortality in renal transplant recipients, J Am Soc Nephrol, 2002;13(3):769–72.
4. Mazuecos A, Munoz Terol JM, Garcia Alvarez T, et al., Increase in malignancies as cause of death in renal transplant patients, Transplant Proc, 2009;41(6):2159–62.
5. Ojo AO, Cardiovascular complications after renal transplantation and their prevention, Transplantation, 2006;82(5):603–11.
6. Young JB, Neumayer HH, Gordon RD, Pretransplant cardiovascular evaluation and posttransplant cardiovascular risk, Kidney Int;78(Suppl.) 118:S1–7.
7. Lenfant C, Chobanian AV, Jones DW, Roccella EJ, Seventh report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7): resetting the hypertension sails, Hypertension, 2003;41(6):1178–9.
8. 2007 Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1998–2007, Rockville, MD: Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation, 2008.
9. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients, Am J Kidney Dis, 2005;45(4 Suppl. 3):S1–153.
10. Courivaud C, Kazory A, Simula-Faivre D, et al., Metabolic syndrome and atherosclerotic events in renal transplant recipients, Transplantation, 2007;83(12):1577–81.
11. Meier-Kriesche HU, Arndorfer JA, Kaplan B, The impact of body mass index on renal transplant outcomes: a significant independent risk factor for graft failure and patient death, Transplantation, 2002;73(1):70–4.
12. Gaston RS, Danovitch GM, Adams PL, et al., The report of a national conference on the wait list for kidney transplantation, Am J Transplant, 2003;3(7):775–85.
13. Meier-Kriesche HU, Port FK, Ojo AO, et al., Effect of waiting time on renal transplant outcome, Kidney Int, 2000;58(3):1311–7.
14. Schold JD, Sehgal AR, Srinivas TR, et al., Marked variation of the association of ESRD duration before and after wait listing on kidney transplant outcomes, Am J Transplant, 10(9):2008–16.
15. Rao PS, Merion RM, Ashby VB, et al., Renal transplantation in elderly patients older than 70 years of age: results from the
undergoing US Food and Drug Administration (FDA) trials, belatacept, shows promise in reducing cardiovascular risk factors at two years of follow-up.40
patients. Guidelines for screening for malignancies are unclear at this time. However, patients should be reminded to have age-appropriate malignancy screenings. Patients can be taught to perform monthly self-exams of their skin to evaluate for skin carcinomas. They should also have a physician exam of their skin every three years during ages 20–39 and annually for patients over 40.32
Prophylaxis with antivirals for
cytomegalovirus (CMV) has also been shown to decrease mortality. A meta-analysis of 32 trials examining the use of antivirals versus placebo for CMV prophylaxis in solid organ transplant recipients found that it decreases CMV disease and CMV-associated mortality. CMV prophylaxis is recommended for all CMV-positive recipients and CMV-negative recipients receiving CMV-positive organs.41
Conclusion
Outcomes in kidney transplantation have improved, but DWGF continues to be a significant contributor to allograft loss. CVD, the main contributor to DWGF, remains important both in the pre- and post-transplant period. Attempts should be made to aggressively reduce the significant risk factors for CVD through medical, and surgical if necessary, management. Immunosuppression can also be tailored to each patient as there is no standard regimen that fits all recipients. Appropriate malignancy screening should also be provided to all at-risk patients. Although risk factors for DWGF are well known, there is a paucity of evidence showing that modification of risk factors decreases mortality. Further studies with randomized controlled trials need to be performed to clarify recommendations. n
Scientific Registry of Transplant Recipients, Transplantation, 2007;83(8):1069–74.
16. Shah T, Bunnapradist S, Hutchinson I, et al., The evolving notion of "senior" kidney transplant recipients, Clin Transplant, 2008;22(6):794–802.
17. Maluf DG, Fisher RA, King AL, et al., Hepatitis C virus infection and kidney transplantation: predictors of patient and graft survival, Transplantation, 2007;83(7):853–7.
18. Morales JM, Dominguez-Gil B, Sanz-Guajardo D, et al., The influence of hepatitis B and hepatitis C virus infection in the recipient on late renal allograft failure, Nephrol Dial Transplant, 2004;19(Suppl. 3):iii72–6.
19. Rike AH, Mogilishetty G, Alloway RR, et al., Cardiovascular risk, cardiovascular events, and metabolic syndrome in renal transplantation: comparison of early steroid withdrawal and chronic steroids, Clin Transplant, 2008;22(2):229–35.
20. Vincenti F, Schena FP, Paraskevas S, et al., A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients, Am J Transplant, 2008;8(2):307–16.
21. Gill JS, Cardiovascular disease in transplant recipients: current and future treatment strategies, Clin J Am Soc Nephrol, 2008;3 (Suppl. 2):S29–37.
22. Margreiter R, Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study, Lancet, 2002;359(9308):741–6.
23. Burroughs TE, Swindle J, Takemoto S, et al., Diabetic complications associated with new-onset diabetes mellitus in renal transplant recipients, Transplantation, 2007;83(8):1027–34.
24. Cole EH, Johnston O, Rose CL, Gill JS, Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival, Clin J Am Soc Nephrol, 2008;3(3):814–21.
25. Kuo HT, Sampaio MS, Vincenti F, Bunnapradist S, Associations of Pretransplant Diabetes Mellitus, New-onset diabetes after transplant, and acute rejection with transplant outcomes: an analysis of the Organ Procurement and Transplant Network/United Network for Organ Sharing (OPTN/UNOS) database, Am J Kidney Dis.
26. Meier-Kriesche HU, Baliga R, Kaplan B, Decreased renal function is a strong risk factor for cardiovascular death after renal transplantation, Transplantation, 2003;75(8):1291–5.
27. Narayanan R, Cardella CJ, Cattran DC, et al., Delayed graft function and the risk of death with graft function in living donor kidney transplant recipients, Am J Kidney Dis.
28. Tapiawala SN, Tinckam KJ, Cardella CJ, et al., Delayed graft function and the risk for death with a functioning graft, J Am Soc
Nephrol, 21(1):153–61.
29. Meier-Kriesche HU, Ojo AO, Hanson JA, Kaplan B, Exponentially increased risk of infectious death in older renal transplant recipients, Kidney Int, 2001;59(4):1539–43.
30. Dharnidharka VR, Caillard S, Agodoa LY, Abbott KC, Infection frequency and profile in different age groups of kidney transplant recipients, Transplantation, 2006;81(12):1662–7.
31. Briggs JD, Causes of death after renal transplantation, Nephrol Dial Transplant, 2001;16(8):1545–9.
32. Kasiske BL, Vazquez MA, Harmon WE, et al., Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation, J Am Soc Nephrol, 2000;11 Suppl. 15:S1–86.
33. Bustami RT, Ojo AO, Wolfe RA, et al., Immunosuppression and the risk of post-transplant malignancy among cadaveric first kidney transplant recipients, Am J Transplant, 2004;4(1):87–93.
34. Opelz G, Dohler B, Improved long-term outcomes after renal transplantation associated with blood pressure control, Am J Transplant, 2005;5(11):2725–31.
35. Holdaas H, Fellstrom B, Cole E, et al., Long-term cardiac outcomes in renal transplant recipients receiving fluvastatin: the ALERT extension study, Am J Transplant, 2005;5(12):2929–36.
36. Holdaas H, Fellstrom B, Jardine AG, et al., Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial, Lancet, 2003;361(9374): 2024–31.
37. Jardine AG, Holdaas H, Fellstrom B, et al., Fluvastatin prevents cardiac death and myocardial infarction in renal transplant recipients: post-hoc subgroup analyses of the ALERT Study, Am J Transplant, 2004;4(6):988–95.
38. Modanlou KA, Muthyala U, Xiao H, et al., Bariatric surgery among kidney transplant candidates and recipients: analysis of the United States renal data system and literature review, Transplantation, 2009;87(8):1167–73.
39. Schena FP, Pascoe MD, Alberu J, et al., Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial, Transplantation, 2009;87(2):233–42.
40. Larsen CP, Grinyo J, Medina-Pestana J, et al., Belatacept-based regimens versus a cyclosporine A-based regimen in kidney transplant recipients: 2-year results from the BENEFIT and BENEFIT-EXT studies, Transplantation.
41. Hodson EM, Craig JC, Strippoli GF, Webster AC, Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients, Cochrane Database Syst Rev, 2008(2):CD003774
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