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  • Review Article
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Complications associated with new-onset diabetes after kidney transplantation

Abstract

New-onset diabetes mellitus after kidney transplantation (NODAT) is widely acknowledged to be associated with increased morbidity and mortality, as well as poor quality of life. Clear evidence links the occurrence of NODAT to accelerated progression of some macrovascular and/or microvascular complications. However, the evidence that some complications commonly attributed to diabetes mellitus occur in the context of transplantation lacks robustness. Certain complications are transplantation-specific and prevalent, but others are not frequently observed or documented. For this reason, it is essential that clinicians are aware of the array of potential complications associated with NODAT in kidney allograft recipients. Rather than simply translating evidence from the general population to the high-risk transplant recipient, this Review aims to provide specific guidance on diabetes-related complications in the context of a complex transplantation environment.

Key Points

  • New-onset diabetes mellitus after kidney transplantation (NODAT) is associated with numerous short-term and long-term complications

  • Diabetes-related complications in patients with NODAT probably involve both general and transplant-specific components

  • The array of diabetes-related complications observed in the general population might not be directly applicable to the transplant population

  • Some evidence suggests that the evolution of diabetes-related complications is accelerated after kidney transplantation

  • Management of NODAT complications requires a multifactorial rather than glycemia-centered approach, conducted in partnership with established diabetes frameworks, to ensure optimal care for transplant recipients

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Figure 1: The range of complications attributed to NODAT and their evidence base.

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References

  1. Sharif, A. & Baboolal, K. Risk factors for new-onset diabetes after kidney transplantation. Nat. Rev. Nephrol. 6, 415–423 (2010).

    Article  PubMed  Google Scholar 

  2. Lechler, R. I., Sykes, M., Thomson, A. W. & Turka, L. A. Organ transplantation—how much of the promise has been realized? Nat. Med. 11, 605–613 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Lamb, K. E., Lodhi, S. & Meier-Kriesche, H. U. Long-term renal allograft survival in the United States: a critical reappraisal. Am. J. Transplant. 11, 450–462 (2011).

    Article  CAS  PubMed  Google Scholar 

  4. American Diabetes Association. Standards of medical care in diabetes—2006. Diabetes Care 29 (Suppl. 1), S4–S42 (2006).

  5. Woodward, R. S. et al. Incidence and cost of new onset diabetes mellitus among U. S. wait-listed and transplanted renal allograft recipients. Am. J. Transplant. 3, 590–598 (2003).

    Article  PubMed  Google Scholar 

  6. Davidson, J. et al. New-onset diabetes after transplantation: 2003 international consensus guidelines. Proceedings of an international expert panel meeting. Barcelona, Spain, 19 February 2003. Transplantation 75 (10 Suppl.), SS3–SS24 (2003).

    PubMed  Google Scholar 

  7. Davidson, J. A. & Wilkinson, A. New-onset diabetes after transplantation 2003 international consensus guidelines: an endocrinologist's view. Diabetes Care 27, 805–812 (2004).

    Article  PubMed  Google Scholar 

  8. Burroughs, T. E. et al. Diabetic complications associated with new-onset diabetes mellitus in renal transplant recipients. Transplantation 83, 1027–1034 (2007).

    Article  PubMed  Google Scholar 

  9. Kasiske, B. L., Snyder, J. J., Gilbertson, D. & Matas, A. J. Diabetes mellitus after kidney transplantation in the United States. Am. J. Transplant. 3, 178–185 (2003).

    Article  PubMed  Google Scholar 

  10. Kuo, H. T., Sampaio, M. S., 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. 56, 1127–1139 (2010).

    Article  PubMed  Google Scholar 

  11. Cosio, F. G. et al. Patient survival after renal transplantation: IV. Impact of post-transplant diabetes. Kidney Int. 62, 1440–1446 (2002).

    Article  PubMed  Google Scholar 

  12. Revanur, V. K. et al. Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation. Clin. Transplant. 15, 89–94 (2001).

    Article  CAS  PubMed  Google Scholar 

  13. Meisinger, C., Wölke, G., Brasche, S., Strube, G. & Heinrich, J. Postload plasma glucose and 30-year mortality among nondiabetic middle-aged men from the general population: the ERFORT study. Ann. Epidemiol. 16, 534–539 (2006).

    Article  PubMed  Google Scholar 

  14. The DECODE study group on behalf of the European Diabetes Epidemiology Group. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Diabetes epidemiology: collaborative analysis of diagnostic criteria in Europe. Lancet 354, 617–621 (1999).

  15. Shaw, J. E., Hodge, A. M., de Courten, M., Chitson, P. & Zimmet, P. Z. Isolated post-challenge hyperglycaemia confirmed as a risk factor for mortality. Diabetologia 42, 1050–1054 (1999).

    Article  CAS  PubMed  Google Scholar 

  16. Sorkin, J. D., Muller, D. C., Fleg, J. L. & Andres, R. The relation of fasting and 2-h postchallenge plasma glucose concentrations to mortality: data from the Baltimore Longitudinal Study of Aging with a critical review of the literature. Diabetes Care 28, 2626–2632 (2005).

    Article  PubMed  Google Scholar 

  17. Cosio, F. G. et al. New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation. Kidney Int. 67, 2415–2421 (2005).

    Article  PubMed  Google Scholar 

  18. Valderhaug, T. G. et al. The association of early post-transplant glucose levels with long-term mortality. Diabetologia 54, 1341–1349 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ekberg, H. et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N. Engl. J. Med. 357, 2562–2575 (2007).

    Article  CAS  PubMed  Google Scholar 

  20. Howard, R. J. et al. The changing causes of graft loss and death after kidney transplantation. Transplantation 73, 1923–1928 (2002).

    Article  PubMed  Google Scholar 

  21. Cole, E. H., Johnston, O., Rose, C. L. & Gill, J. S. Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival. Clin. J. Am. Soc. Nephrol. 3, 814–821 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Matas, A. J. et al. Posttransplant diabetes mellitus and acute rejection: impact on kidney transplant outcome. Transplantation 85, 338–343 (2008).

    Article  PubMed  Google Scholar 

  23. Miles, A. M. et al. Diabetes mellitus after renal transplantation: as deleterious as non-transplant-associated diabetes? Transplantation 65, 380–384 (1998).

    Article  CAS  PubMed  Google Scholar 

  24. Salifu, M. O. et al. Allograft diabetic nephropathy may progress to end-stage renal disease. Pediatr. Transplant. 8, 351–356 (2004).

    Article  PubMed  Google Scholar 

  25. Kasiske, B. L. Epidemiology of cardiovascular disease after renal transplantation. Transplantation 72 (6 Suppl.), S5–S8 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. de Mattos, A. M. et al. Cardiovascular events following renal transplantation: role of traditional and transplant-specific risk factors. Kidney Int. 70, 757–764 (2006).

    Article  CAS  PubMed  Google Scholar 

  27. Wheeler, D. C. & Steiger, J. Evolution and etiology of cardiovascular diseases in renal transplant recipients. Transplantation 70 (11 Suppl.), SS41–SS45 (2000).

    CAS  PubMed  Google Scholar 

  28. Marcén, R. Cardiovascular risk factors in renal transplantation—current controversies. Nephrol. Dial. Transplant. 21 (Suppl. 3), iii3–iii8 (2006).

    Article  PubMed  Google Scholar 

  29. Forsythe, J. L. Graft function and other risk factors as predictors of cardiovascular disease outcome. Transplantation 72 (6 Suppl.), S16–S19 (2001).

    Article  CAS  PubMed  Google Scholar 

  30. Kasiske, B. L., Guijarro, C., Massy, Z. A., Wiederkehr, M. R. & Ma, J. Z. Cardiovascular disease after renal transplantation. J. Am. Soc. Nephrol. 7, 158–165 (1996).

    CAS  PubMed  Google Scholar 

  31. Israni, A. K. et al. Predicting coronary heart disease after kidney transplantation: Patient Outcomes in Renal Transplantation (PORT) Study. Am. J. Transplant. 10, 338–353 (2010).

    Article  CAS  PubMed  Google Scholar 

  32. Hjelmesaeth, J. et al. The impact of early-diagnosed new-onset post-transplantation diabetes mellitus on survival and major cardiac events. Kidney Int. 69, 588–595 (2006).

    Article  CAS  PubMed  Google Scholar 

  33. Koselj, M. et al. De novo diabetic nephropathy on renal allografts. Transplant. Proc. 35, 2919–2921 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Owda, A. K. et al. De novo diabetes mellitus in kidney allografts: nodular sclerosis and diffuse glomerulosclerosis leading to graft failure. Nephrol. Dial. Transplant. 14, 2004–2007 (1999).

    Article  CAS  PubMed  Google Scholar 

  35. Gimenez, L. F. et al. De novo diabetic nephropathy with functional impairment in a renal allograft. Am. J. Nephrol. 6, 378–381 (1986).

    Article  CAS  PubMed  Google Scholar 

  36. Sharma, U. K., Jha, V., Gupta, K. L., Joshi, K. & Sakhuja, V. De novo diabetic glomerulosclerosis in a renal allograft recipient. Am. J. Kidney Dis. 23, 597–599 (1994).

    Article  CAS  PubMed  Google Scholar 

  37. Kelly, J. J., Walker, R. G. & Kincaid-Smith, P. De novo diabetic nodular glomerulosclerosis in a renal allograft. Transplantation 53, 688–689 (1992).

    Article  CAS  PubMed  Google Scholar 

  38. Cervera, C. et al. The influence of innate immunity gene receptors polymorphisms in renal transplant infections. Transplantation 83, 1493–1500 (2007).

    Article  CAS  PubMed  Google Scholar 

  39. Joshi, N., Caputo, G. M., Weitekamp, M. R. & Karchmer, A. W. Infections in patients with diabetes mellitus. N. Engl. J. Med. 341, 1906–1912 (1999).

    Article  CAS  PubMed  Google Scholar 

  40. Muller, L. M. et al. Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus. Clin. Infect. Dis. 41, 281–288 (2005).

    Article  CAS  PubMed  Google Scholar 

  41. Kornum, J. B. et al. Diabetes, glycemic control, and risk of hospitalization with pneumonia: a population-based case-control study. Diabetes Care 31, 1541–1545 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Geerlings, S. E. et al. Risk factors for symptomatic urinary tract infection in women with diabetes. Diabetes Care 23, 1737–1741 (2000).

    Article  CAS  PubMed  Google Scholar 

  43. Gleckman, R. A. & al-Wawi, M. A review of selective infections in the adult diabetic. Compr. Ther. 25, 109–113 (1999).

    Article  CAS  PubMed  Google Scholar 

  44. Venmans, L. M., Hak, E., Gorter, K. J. & Rutten, G. E. Incidence and antibiotic prescription rates for common infections in patients with diabetes in primary care over the years 1995 to 2003. Int. J. Infect. Dis. 13, e344–e351 (2009).

    Article  CAS  PubMed  Google Scholar 

  45. Matarese, G. & La Cava, A. The intricate interface between immune system and metabolism. Trends Immunol. 25, 193–200 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Pietrzak-Nowacka, M. et al. Impact of posttransplant diabetes mellitus on graft function in autosomal dominant polycystic kidney disease patients after kidney transplantation. Ann. Acad. Med. Stetin. 54, 41–48 (2008).

    PubMed  Google Scholar 

  47. Siraj, E. S., Abacan, C., Chinnappa, P., Wojtowicz, J. & Braun, W. Risk factors and outcomes associated with posttransplant diabetes mellitus in kidney transplant recipients. Transplant. Proc. 42 1685–1689 (2010).

    Article  CAS  PubMed  Google Scholar 

  48. von Kiparski, A., Frei, D., Uhlschmid, G., Largiadèr, F. & Binswanger, U. Post-transplant diabetes mellitus in renal allograft recipients: a matched-pair control study. Nephrol. Dial. Transplant. 5, 220–225 (1990).

    Article  CAS  PubMed  Google Scholar 

  49. Bouchta, N. B. et al. Conversion from tacrolimus to cyclosporin is associated with a significant improvement of glucose metabolism in patients with new-onset diabetes mellitus after renal transplantation. Transplant. Proc. 37, 1857–1860 (2005).

    Article  CAS  PubMed  Google Scholar 

  50. Butani, L. & Makker, S. P. Conversion from tacrolimus to neoral for postrenal transplant diabetes. Pediatr. Nephrol. 15, 176–178 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Oberholzer, J. et al. Immediate conversion from tacrolimus to cyclosporine in the treatment of posttransplantation diabetes mellitus. Transplant. Proc. 37, 999–1000 (2005).

    Article  CAS  PubMed  Google Scholar 

  52. Sharif, A. et al. Complex interplay between insulinemia, glycemia, and glomerular filtration rate in nondiabetic renal transplant recipients. Transplantation 88, 290–292 (2009).

    Article  PubMed  Google Scholar 

  53. Gerich, J. E., Meyer, C., Woerle, H. J. & Stumvoll, M. Renal gluconeogenesis: its importance in human glucose homeostasis. Diabetes Care 24, 382–391 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Meyer, C., Dostou, J. M. & Gerich, J. E. Role of the human kidney in glucose counterregulation. Diabetes 48, 943–948 (1999).

    Article  CAS  PubMed  Google Scholar 

  55. Stumvoll, M., Meyer, C., Mitrakou, A. & Gerich, J. E. Important role of the kidney in human carbohydrate metabolism. Med. Hypotheses 52, 363–366 (1999).

    Article  CAS  PubMed  Google Scholar 

  56. Arem, R. Hypoglycemia associated with renal failure. Endocrinol. Metab. Clin. North Am. 18, 103–121 (1989).

    Article  CAS  PubMed  Google Scholar 

  57. Rabkin, R., Ryan, M. P. & Duckworth, W. C. The renal metabolism of insulin. Diabetologia 27, 351–357 (1984).

    Article  CAS  PubMed  Google Scholar 

  58. Sharif, A. Current and emerging antiglycaemic pharmacological therapies: the renal perspective. Nephrology (Carlton) 16, 468–475 (2011).

    Article  CAS  Google Scholar 

  59. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352, 837–853 (1998).

  60. Mann, D. M., Woodward, M. & Muntner, P. Preventing diabetes complications: are we too glucocentric? Int. J. Clin. Pract. 64, 1024–1027 (2010).

    Article  CAS  PubMed  Google Scholar 

  61. Laupacis, A. et al. A study of the quality of life and cost-utility of renal transplantation. Kidney Int. 50, 235–242 (1996).

    Article  CAS  PubMed  Google Scholar 

  62. Rubin, R. R. & Peyrot, M. Quality of life and diabetes. Diabetes Metab. Res. Rev. 15, 205–218 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Vileikyte, L. et al. The development and validation of a neuropathy- and foot ulcer-specific quality of life instrument. Diabetes Care 26, 2549–2555 (2003).

    Article  PubMed  Google Scholar 

  64. Rubin, R. R. & Peyrot, M. Patient-reported outcomes and diabetes technology: a systematic review of the literature. Pediatr. Endocrinol. Rev. 7 (Suppl. 3), 405–412 (2010).

    PubMed  Google Scholar 

  65. Nouwen, A. et al. Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis. Diabetologia 53, 2480–2486 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hu, G., Jousilahti, P., Bidel, S., Antikainen, R. & Tuomilehto, J. Type 2 diabetes and the risk of Parkinson's disease. Diabetes Care 30, 842–847 (2007).

    Article  PubMed  Google Scholar 

  67. Palumbo, P. J. Metabolic risk factors, endothelial dysfunction, and erectile dysfunction in men with diabetes. Am. J. Med. Sci. 334, 466–480 (2007).

    Article  PubMed  Google Scholar 

  68. Sandberg, G. E., Sundberg, H. E., Fjellstrom, C. A. & Wikblad, K. F. Type 2 diabetes and oral health: a comparison between diabetic and non-diabetic subjects. Diabetes Res. Clin. Pract. 50, 27–34 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. Dorko, E. et al. Diabetes mellitus and candidiases. Folia Microbiol. (Praha) 50, 255–261 (2005).

    Article  CAS  Google Scholar 

  70. Conwell, L. S. et al. Dermatological complications of continuous subcutaneous insulin infusion in children and adolescents. J. Pediatr. 152, 622–628 (2008).

    Article  CAS  PubMed  Google Scholar 

  71. Romano, G. et al. Skin lesions in diabetes mellitus: prevalence and clinical correlations. Diabetes Res. Clin. Pract. 39, 101–106 (1998).

    Article  CAS  PubMed  Google Scholar 

  72. Hegde, K. R., Kowluru, R. A., Mohr, S., Nagaraj, R. H. & Petrash, J. M. New horizons in research on diabetic complications of the eye: special emphasis on diabetic cataracts and retinopathy. J. Ophthalmol. 2010, 979040 (2010).

    PubMed  PubMed Central  Google Scholar 

  73. Boulton, A. J., Vileikyte, L., Ragnarson-Tennvall, G. & Apelqvist, J. The global burden of diabetic foot disease. Lancet 366, 1719–1724 (2005).

    Article  PubMed  Google Scholar 

  74. Camilleri, M. Clinical practice. Diabetic gastroparesis. N. Engl. J. Med. 356, 820–829 (2007).

    Article  CAS  PubMed  Google Scholar 

  75. Virally-Monod, M. et al. Chronic diarrhoea and diabetes mellitus: prevalence of small intestinal bacterial overgrowth. Diabetes Metab. 24, 530–536 (1998).

    CAS  PubMed  Google Scholar 

  76. Vinik, A. I. & Ziegler, D. Diabetic cardiovascular autonomic neuropathy. Circulation 115, 387–397.

  77. Casellini, C. M. & Vinik, A. I. Clinical manifestations and current treatment options for diabetic neuropathies. Endocr. Pract. 13, 550–566 (2007).

    Article  PubMed  Google Scholar 

  78. Tolman, K. G., Fonseca, V., Tan, M. H. & Dalpiaz, A. Narrative review: hepatobiliary disease in type 2 diabetes mellitus. Ann. Intern. Med. 141, 946–956 (2004).

    Article  PubMed  Google Scholar 

  79. Cusi, K. Nonalcoholic fatty liver disease in type 2 diabetes mellitus. Curr. Opin. Endocrinol. Diabetes Obes. 16, 141–149 (2009).

    Article  PubMed  Google Scholar 

  80. Fang, Z. Y., Prins, J. B. & Marwick, T. H. Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocr. Rev. 25, 543–567 (2004).

    Article  CAS  PubMed  Google Scholar 

  81. Guillausseau, P. J. et al. Abnormalities in insulin secretion in type 2 diabetes mellitus. Diabetes Metab. 34 (Suppl. 2), S43–S48 (2008).

    Article  CAS  PubMed  Google Scholar 

  82. Reaven, G. M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37, 1595–1607 (1988).

    Article  CAS  PubMed  Google Scholar 

  83. Nam, J. H. et al. Beta-cell dysfunction rather than insulin resistance is the main contributing factor for the development of postrenal transplantation diabetes mellitus. Transplantation 71, 1417–1423 (2001).

    Article  CAS  PubMed  Google Scholar 

  84. Elder, D. A., Prigeon, R. L., Wadwa, R. P., Dolan, L. M. & D'Alessio, D. A. Beta-cell function, insulin sensitivity, and glucose tolerance in obese diabetic and nondiabetic adolescents and young adults. J. Clin. Endocrinol. Metab. 91, 185–191 (2006).

    Article  CAS  PubMed  Google Scholar 

  85. Gerich, J. E. Contributions of insulin-resistance and insulin-secretory defects to the pathogenesis of type 2 diabetes mellitus. Mayo Clin. Proc. 78, 447–456 (2003).

    Article  PubMed  Google Scholar 

  86. van Hooff, J. P., Christiaans, M. H. & van Duijnhoven, E. M. Evaluating mechanisms of post-transplant diabetes mellitus. Nephrol. Dial. Transplant. 19 (Suppl. 6), vi8–vi12 (2004).

    PubMed  Google Scholar 

  87. Sharif, A. Metabolic syndrome and solid-organ transplantation. Am. J. Transplant. 10, 12–17 (2010).

    Article  CAS  PubMed  Google Scholar 

  88. Alberti, K. G., Zimmet, P. & Shaw, J. Metabolic syndrome—a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet. Med. 23, 469–480 (2006).

    Article  CAS  PubMed  Google Scholar 

  89. Laclaustra, M., Corella, D. & Ordovas, J. M. Metabolic syndrome pathophysiology: the role of adipose tissue. Nutr. Metab. Cardiovasc. Dis. 17, 125–139 (2007).

    Article  CAS  PubMed  Google Scholar 

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A. Sharif contributed to researching data for the article, discussion of the article content, writing the article, and reviewing and/or editing the manuscript before submission. K. Baboolal contributed to discussion of the article content and reviewing and/or editing the manuscript before submission.

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Correspondence to Adnan Sharif.

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Sharif, A., Baboolal, K. Complications associated with new-onset diabetes after kidney transplantation. Nat Rev Nephrol 8, 34–42 (2012). https://doi.org/10.1038/nrneph.2011.174

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