Evaluation of markers for renal graft dysfunction in patients with type 1 diabetes mellitus after kidney transplantation and simultaneous pancreas-kidney transplantation

Abstract

Aim. To study the markers of renal graft dysfunction in patients with type 1 diabetes mellitus (T1DM) after kidney transplantation (KT) and simultaneous pancreas-kidney transplantation (SPKT). Subjects and methods. The investigation enrolled 20 patients after successful SPKT and 41 patients after KT (of them 21 received continuous subcutaneous insulin infusion with an insulin doser; 20 had multiple insulin injections). The periods after KT and SPKT at patient inclusion were 8 (7; 8) and 11 (8; 18) months, respectively. A control group comprised 15 patients with T1DM without diabetic nephropathy. The patients were matched for gender, age, and T1DM duration. At a 9-month follow-up, the main biomarkers of kidney graft dysfunction were identified using the standard kits: Cystatin C (Cys C; serum; urine), NGAL, KIM-1, Podocin, Nephrin, IL-18, MMP-9 (urine), TGF-β1, VEGF-A, and Osteopontin (OPN; serum). Fasting blood was taken; a morning urinary portion was examined. Results. The posttransplantation glomerular filtration rate (GFR) in the patients corresponded to Stage C2; albuminuria did to Category A1 chronic kidney disease. Despite successful SPKT in the group of patients with T1DM, as in that of patients after isolated KT, there was a statistically significant increase in the level of kidney dysfunction markers (Cys C, NGAL, Podocin, and OPN) versus the control group regardless of the compensation for glucose metabolism. compensation. It was found that the level of Cys C was high and correlated negatively with GFR (r=–0.36; p<0.05) and positively with the level of albuminuria (r=0.40; p<0.05). There was also a direct correlation of urinary podocin concentrations with blood creatinine levels (r=0.35; p<0.05) and that of NGAL with albuminuria (r=0.35; p<0.05) in recipients after transplantation. Conclusion. The high levels of biomarkers for kidney graft dysfunction in the examinees (including subjects after SPKT) reflect the persistence of graft microstructural injuries in clinically stable function.

References

  1. Kim SC, Page EK, Knechtle SJ. Urine proteomics in kidney transplantation. Transplantat Rev. 2014;28(1):15-20. doi: 10.1016/j.trre.2013.10.004
  2. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl 1):S1-266.
  3. First MR. Renal function as a predictor of long-term graft survival in renal transplant patients. Nephrol Dial Transplant. 2003;18(suppl 1):i3-i6. doi: 10.1093/ndt/gfg1027
  4. Rosner MH. Biomarker in renal disease. Chapter 6. Biomarker in kidney transplantation. Nova science Publisher inc; 2008.
  5. Hariharan S, McBride MA, Cohen EP. Evolution of Endpoints for Renal Transplant Outcome. Am J Transplant. 2003;3(8):933-941. doi: 10.1034/j.1600-6143.2003.00176.x
  6. Ge F, Dai Q, Gong W. Biomarkers for renal transplantation: where are we? Int J Nephrol Renovasc Dis. 2013;6:187-191. doi: 10.2147/IJNRD.S39806
  7. Gong W, Whitcher GH, Townamchai N, et al. Biomarkers for Monitoring Therapeutic Side Effects or Various Supratherapeutic Confounders after Kidney Transplantation. Transplant Proceed. 2012;44(5):1265-1269. doi: 10.1016/j.transproceed.2011.11.069
  8. Stevens LA, Schmid CH, Greene T et al. Factors Other than GFR Affecting Serum Cystatin C Levels. Kidney Int. 2009;75(6):652-660. doi: 10.1038/ki.2008.638
  9. Данович Г.М. Трансплантация почки. Глава 9. Первые три месяца после трансплантации почки. М.: ГЭОТАР-Медиа; 2013.
  10. Dupont PJ, Psimenou E, Lord R et al. Late Recurrent Urinary Tract Infections May Produce Renal Allograft Scarring Even in the Absence of Symptoms or Vesicoureteric Reflux. Transplantation. 2007;84(3):351-355. doi: 10.1097/01.tp.0000275377.09660.fa
  11. Locke JE, Zachary AA, Warren DS et al. Proinflammatory Events Are Associated with Significant Increases in Breadth and Strength of HLA-Specific Antibody. Am J Transplant. 2009;9(9):2136-2139. doi: 10.1111/j.1600-6143.2009.02764.x
  12. Thrailkill KM, Moreau CS, Cockrell GE et al. Disease and gender-specific dysregulation of NGAL and MMP-9 in type 1 diabetes mellitus. Endocrine. 2010;37(2):336-343. doi: 10.1007/s12020-010-9308-6
  13. Mårtensson J, Bell M, Oldner A, et al. Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury. Intensive Care Med. 2010;36(8):1333-1340. doi: 10.1007/s00134-010-1887-4
  14. van Timmeren MM, Vaidya VS, van Ree RM et al. High Urinary Excretion of Kidney Injury Molecule-1 Is an Independent Predictor of Graft Loss in Renal Transplant Recipients. Transplantation. 2007;84(12):1625-1630. doi: 10.1097/01.tp.0000295982.78039.ef
  15. Данович Г.М. Трансплантация почки. Глава 1. Возможности лечения пациентов в терминальной стадии хронической почечной недостаточности. М.: ГЭОТАР-Медиа; 2013.
  16. Pippin J, Kumar V, Stein A et al. The Contribution of Podocytes to Chronic Allograft Nephropathy. Nephron Exper Nephrol. 2009;111(1):e1-e10. doi: 10.1159/000178762
  17. Forbes JM, Cooper ME. Mechanisms of Diabetic Complications. Physiol Revi. 2013;93(1):137-188. doi: 10.1152/physrev.00045.2011
  18. Opdenakker G, Van den Steen PE, Dubois B et al. Gelatinase B functions as regulator and effector in leukocyte biology. J Leukocyte Biol. 2001;69(6):851-859.
  19. Hartmann A, Sagedal S, Hjelmesæth J. The Natural Course of Cytomegalovirus Infection and Disease in Renal Transplant Recipients. Transplantation. 2006;82:S15-S17. doi: 10.1097/01.tp.0000230460.42558.b0
  20. Zhang Z-X, Shek K, Wang S, et al. Osteopontin Expressed in Tubular Epithelial Cells Regulates NK Cell-Mediated Kidney Ischemia Reperfusion Injury. J Immunol. 2010;185(2):967-973. doi: 10.4049/jimmunol.0903245
  21. Lorenzen JM, Hafer C, Faulhaber-Walter R, et al. Osteopontin predicts survival in critically ill patients with acute kidney injury. Nephrol DialTransplant. 2010. doi: 10.1093/ndt/gfq498
  22. Gordin D, Forsblom C, Panduru NM et al. Osteopontin Is a Strong Predictor of Incipient Diabetic Nephropathy, Cardiovascular Disease, and All-Cause Mortality in Patients With Type 1 Diabetes. Diabetes Care. 2014;37(9):2593-2600. doi: 10.2337/dc14-0065
  23. Jin Z-K, Tian P-X, Wang X-Z et al. Kidney injury molecule-1 and osteopontin: New markers for prediction of early kidney transplant rejection. Mol Immunol.2013;54(3-4):457-464. doi: 10.1016/j.molimm.2013.01.013
  24. Lorenzen JM, Martino F, Scheffner I et al. Fetuin, Matrix-Gla Protein and Osteopontin in Calcification of Renal Allografts. PLoS ONE. 2012;7(12):e52039. doi: 10.1371/journal.pone.0052039

Copyright (c) 2016 Glazunova A.M., Arutyunova M.S., Tarasov E.V., Nikankina L.V., Ilyin A.V., Shamkhalova M.S., Shestakova M.V., Moysyuk Y.G.

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