Advertisement

Diabetologia

, Volume 57, Issue 3, pp 554–561 | Cite as

Infection-related mortality is higher for kidney allograft recipients with pretransplant diabetes mellitus

  • Manvir K. Hayer
  • Daniela Farrugia
  • Irena Begaj
  • Daniel Ray
  • Adnan SharifEmail author
Article

Abstract

Aims/hypothesis

The risk of infection-related mortality in kidney allograft recipients with pre-existing diabetes mellitus is unknown. We determined the risk of infection-related mortality after kidney transplantation in a population-based cohort stratified by diagnosis of pre-existing diabetes mellitus.

Methods

We linked data between two national registries (Hospital Episode Statistics and the Office for National Statistics) to select all mortality events after kidney transplantation in England between April 2001 and March 2012. The primary outcome measure was infection-related mortality after transplantation comparing diabetic with non-diabetic recipients.

Results

A total of 19,103 kidney allograft recipients were analysed; 2,968 (15.5%) were known to have diabetes before kidney transplantation. After transplantation, 2,085 deaths (10.9%) occurred (median follow-up 4.4 years [interquartile range 2.2–7.3]), with 434 classified as secondary to infection (20.8% of all deaths). Risk of overall (16.0% vs 10.0%, p < 0.001) and infection-related (3.3% vs 2.1%, p < 0.001) mortality after kidney transplantation was higher for diabetic than non-diabetic recipients, respectively. No cytomegalovirus-related deaths occurred in diabetic recipients compared with 5.7% in non-diabetic recipients (p < 0.007), with a trend towards more unspecified sepsis in diabetic recipients (30.6% vs 22.6%, respectively, p = 0.070). Diabetes at the time of transplantation was an independent risk factor predicting infection-related mortality in kidney allograft recipients after transplantation (HR 1.71 [95% CI 1.36, 2.15], p < 0.001).

Conclusions/interpretation

Infection-related mortality is more common in kidney allograft recipients with pre-existing diabetes mellitus. Further work is required to determine whether attenuated immunosuppression is beneficial for diabetic kidney allograft recipients.

Keywords

Cytomegalovirus Diabetes mellitus Infection Kidney allograft Kidney transplantation Mortality Sepsis 

Abbreviations

CMV

Cytomegalovirus

ESRD

End-stage renal disease

HES

Hospital Episode Statistics

ONS

Office for National Statistics

OPCS-4

Office of Population Censuses and Surveys Classification of Interventions and Procedures, 4th revision

Notes

Acknowledgements

We thank S. Sutherland (Queen Elizabeth Hospital, Birmingham, UK) and J. Cheshire (University of Birmingham, UK) for their assistance in data classification as part of our analyses.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data. MKH, DF, IB, DR and AS were involved with drafting the article or revising it critically for important intellectual content; and all authors have given final approval of the version to be published.

References

  1. 1.
    Rich J, Lee JC (2005) The pathogenesis of Staphylococcus aureus infection in the diabetic NOD mouse. Diabetes 54:2904–2910PubMedCrossRefGoogle Scholar
  2. 2.
    Hirsch T, Spielmann M, Zuhaili B et al (2008) Enhanced susceptibility to infections in a diabetic wound healing model. BMC Surg 8:2482–2485CrossRefGoogle Scholar
  3. 3.
    Rees DA, Alcolado JC (2005) Animal models of diabetes mellitus. Diabet Med 22:359–370PubMedCrossRefGoogle Scholar
  4. 4.
    Bach JF (2005) Infections and autoimmune diseases. J Autoimmun 25:74–80PubMedCrossRefGoogle Scholar
  5. 5.
    Joshi N, Caputo GM, Weitekamp MR, Karchmer AW (1999) Infections in patients with diabetes mellitus. N Engl J Med 341:1906–1912PubMedCrossRefGoogle Scholar
  6. 6.
    Muller LM, Gorter KJ, Hak E, Goudzwaard WL et al (2005) Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus. Clin Infect Dis 41:281–288PubMedCrossRefGoogle Scholar
  7. 7.
    Peleg AY, Weerarathna T, McCarthy JS, Davis TM (2007) Common infections in diabetes: pathogenesis, management and relationship to glycaemic control. Diabetes Metab Res Rev 23:3–13PubMedCrossRefGoogle Scholar
  8. 8.
    Bertoni AG, Saydah S, Brancati FL (2001) Diabetes and the risk of infection-related mortality in the U.S. Diabetes Care 24(6):1044–1049PubMedCrossRefGoogle Scholar
  9. 9.
    Gu K, Cowie CC, Harris MI (1998) Mortality in adults with and without diabetes in a national cohort of the U.S. population, 1971–1993. Diabetes Care 21:1138–1145PubMedCrossRefGoogle Scholar
  10. 10.
    Moss SE, Klien R, Klein BEK (1991) Cause-specific mortality in a population-based study of diabetes. Am J Public Health 81:1158–1162PubMedCrossRefGoogle Scholar
  11. 11.
    US Renal Data System (2012) USRDS 2011 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. Am J Kidney Dis 59(Suppl 1):e1–e420Google Scholar
  12. 12.
    Briggs JD (2001) Causes of death after renal transplantation. Nephrol Dial Transplant 16:1545–1549PubMedCrossRefGoogle Scholar
  13. 13.
    Koh GC, Peacock SJ, van der Poll T, Wiersinga WJ (2012) The impact of diabetes on the pathogenesis of sepsis. Eur J Clin Microbiol Infect Dis 31:379–388Google Scholar
  14. 14.
    Kato S, Chmielewski M, Honda H et al (2008) Aspects of immune dysfunction in end-stage renal disease. Clin J Am Soc Nephrol 3:1526–1533PubMedCrossRefGoogle Scholar
  15. 15.
    Lansang MC, Ma L, Schold JD, Meier-Kriesche HU, Kaplan B (2006) The relationship between diabetes and infectious hospitalizations in renal transplant recipients. Diabetes Care 29:1659–1660PubMedCrossRefGoogle Scholar
  16. 16.
    OPCS-4 classification – NHS Connecting for Health. Available from www.connectingforhealth.nhs.uk. Accessed 12 June 2013
  17. 17.
    World Health Organization: International Classification of Diseases (ICD). Available from www.who.int/classifications/icd/en. Accessed 5 June 2013
  18. 18.
    Department for Communities and Local Government. The English Indices of Deprivation 2010. Available from www.gov.uk/government/publications/english-indices-of-deprivation-2010. Accessed17 June 2013
  19. 19.
    von Elm E, Altman DG, Egger M et al (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370(9596):1453–1457CrossRefGoogle Scholar
  20. 20.
    Steenkamp R, Shaw C, Feest T (2013) UK Renal Registry 15th Annual Report: Chapter 5, Survival and causes of death of UK adult patients on renal replacement therapy in 2011: national and centre-specific analyses. Nephron Clin Pract 123(Suppl 1):93–123PubMedCrossRefGoogle Scholar
  21. 21.
    Zykova SN, Jenssen TG, Berdal M et al (2000) Altered cytokine and nitric oxide secretion in vitro by macrophages from diabetic type II-like db/db mice. Diabetes 49:1451–1458PubMedCrossRefGoogle Scholar
  22. 22.
    Al-Mashat HA, Kandru S, Liu R et al (2006) Diabetes enhances mRNA levels of proapoptotic genes and caspase activity, which contribute to impaired healing. Diabetes 55:487–495PubMedCrossRefGoogle Scholar
  23. 23.
    Ilyas R, Wallis R, Soilleux EJ et al (2011) High glucose disrupts oligosaccharide recognition function via competitive inhibition: a potential mechanism for immune dysregulation in diabetes mellitus. Immunobiology 216:126–131PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Price CL, Hassi HO, English NR et al (2010) Methylglyoxal modulates immune responses: relevance to diabetes. J Cell Mol Med 14:1806–1815PubMedCrossRefGoogle Scholar
  25. 25.
    Benfield T, Jensen JS, Nordestgaard BG (2007) Influence of diabetes and hyperglycaemia on infectious disease hospitalisation and outcome. Diabetologia 50:549–554PubMedCrossRefGoogle Scholar
  26. 26.
    Marelli D, Laks H, Patel B et al (2003) Heart transplantation in patients with diabetes mellitus in the current era. J Heart Lung Transplant 22:1091–1097PubMedCrossRefGoogle Scholar
  27. 27.
    Thomas MC, Mathew TH, Russ GR et al (2001) Early peri-operative glycaemic control and allograft rejection in patients with diabetes mellitus: a pilot study. Transplantation 72:1321–1324PubMedCrossRefGoogle Scholar
  28. 28.
    Kotton CN, Fishman JA (2005) Viral infection in the renal transplant recipient. J Am Soc Nephrol 16:1758–1774PubMedCrossRefGoogle Scholar
  29. 29.
    Yoon JW (1990) The role of viruses and environmental factors in the induction of diabetes. Curr Top Microbiol Immunol 164:95–123PubMedGoogle Scholar
  30. 30.
    Pak CY, McArthur RG, Eun HM, Yoon JW (1988) Association of cytomegalovirus infection with autoimmune type 1 diabetes. Lancet 332:1–4CrossRefGoogle Scholar
  31. 31.
    Hjelmesaeth J, Muller F, Jenssen T, Rollag H, Sagedal S, Hartmann A (2005) Is there a link between cytomegalovirus infection and new-onset diabetes after transplantation? Potential mechanisms of virus induced beta-cell damage. Nephrol Dial Transplant 20:2311–2315PubMedCrossRefGoogle Scholar
  32. 32.
    Leung Ki EL, Venetz JP, Meylan P, Lamoth F, Ruiz J, Pascual M (2008) Cytomegalovirus infection and new-onset diabetes after transplantation. Clin Transplant 22:245–249Google Scholar
  33. 33.
    Sharif A, Baboolal K (2011) Complications of new onset diabetes after kidney transplantation. Nat Rev Nephrol 8:34–42PubMedCrossRefGoogle Scholar
  34. 34.
    Benavides FG, Bolumar F, Peris R (1989) Quality of death certificates in Valencia, Spain. Am J Public Health 79:1352–1354PubMedCrossRefGoogle Scholar
  35. 35.
    Pinner R, Tetutsh SM, Simonsen L et al (1996) Trends in infectious disease mortality in the United States. JAMA 275:189–193PubMedCrossRefGoogle Scholar
  36. 36.
    Kircher T, Nelson J, Burdo H (1985) The autopsy as a measure of accuracy of the death certificate. N Engl J Med 313:1263–1269PubMedCrossRefGoogle Scholar
  37. 37.
    Lloyd-Jones DM, Martin DO, Larson MG, Levy D (1998) Accuracy of death certificates for coding coronary heart disease as the cause of death. Ann Intern Med 129:1020–1026PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Manvir K. Hayer
    • 1
  • Daniela Farrugia
    • 1
  • Irena Begaj
    • 2
  • Daniel Ray
    • 2
  • Adnan Sharif
    • 1
    Email author
  1. 1.Department of Nephrology and Transplantation, Renal Institute of BirminghamQueen Elizabeth HospitalBirminghamUK
  2. 2.Department of Medical InformaticsQueen Elizabeth HospitalBirminghamUK

Personalised recommendations