P1777BIOMARKERS OF KIDNEY INJURY AS INDICATOR OF PRECLINICAL TRANSPLANT DYSFUNCTION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION AND THEIR RELATIONSHIP WITH EARLY REPARATIVE PROCESSES OF NONMYELINATED FIBERS

Abstract Background and Aims To evaluate the relationship of early kidney transplant dysfunction markers with complications of end-stage renal disease (ESRD) and corneal nerve structures in patients with type 1 diabetes mellitus (T1DM) аnd long-term history of diabetes, who reached stable euglycemia after simultaneous pancreas-kidney transplantation (SPKT). Method The study included 27 patients with T1DM duration for 21 [19; 28] years, diabetic nephropathy (DN) duration 7,0 [5,5; 13,5] years and duration of renal replacement therapy (dialysis) for 2 [1; 4] years after successful SPKT. The posttransplantation period at the time of inclusion was 61 [20; 90] months. Assessment included examination of level of the main kidney transplant dysfunction markers (KIM-1, NGAL, podocin), examination of state of corneal nerve structures according to corneal confocal microscopy (CCM) as indicator of early reparation processes, diabetes complications/ complications of ESRD with dynamic observation for 1 year. All patients received three-component immunosuppressive therapy. Results Despite of reached stable euglycemia (HbA1c 5.5 [5.1; 5.9] %, 5.5 [5.3; 5.7] % after 1 year of follow – up), the restoration of graft function to the rate of estimated glomerular filtration rate (eGFR) CKD-EPI stage C2, albuminuria stage A1, 41% of patients still needed antihypertensive therapy, 37% needed treatment with recombinant human erythropoietin and 30% - antiosteoporotic therapy. There were no statistically significant changes in NGAL, KIM-1, and podocin at baseline and after 1 year in assessment of early kidney transplant dysfunction markers. The results of the correlation analysis revealed associations of NGAL and indicators of CCM (CNFD & NGAL (R=0.61, p = 0.01), CNBD & NGAL (R=0.56, p=0.02), CNFL & NGAL (R=0.65, p=0.009) and vitamin D (R=-0.67, p = 0.008), correlation of KIM-1 with albumin-to-creatinine ratio (ACR) (R=0.43, p= 0.04), correlation of podocin with HbA1c (R=-0.46, p=0.03). Conclusion SPKT as the way to achieve euglycemia and compensation of uremia does not provide complete regress of DN and complications of ESRD. The revealed correlations of early, most sensitive kidney transplant dysfunction markers with degree of carbohydrate metabolism compensation, ACR and vitamin D level may reflect the persistence of microstructures damage with stable graft function and demonstrate need of multifactorial management in renal function preservation. At the same time, the statistically significant correlations of early kidney transplant dysfunction markers with the state of corneal nerve structures need more detailed investigation.