P1021MARKERS OF “METABOLIC MEMORY” AND KIDNEY GRAFT FUNCTION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION

Abstract

Abstract Background and Aims To evaluate the relationship between oxidative stress markers and advanced glycation end products receptor (RAGE) with kidney graft function and complications of end-stage renal disease (ESRD) in patients with type 1 diabetes mellitus (T1DM), 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 oxidative stress markers (3-nitrothyrosine (3-NT), superoxide dismutase (SOD) and RAGE, analysis of the main kidney transplant dysfunction markers (KIM-1, NGAL, podocin, IL-18) and state of carbohydrate metabolism with monitoring for 1 year. All patients received three-component immunosuppressive therapy. Results SPKT allowed to achieve stable euglycemia (HbA1c 5.5 [5.1; 5.9] %, 5.5 [5.3; 5.7] % and С-peptide 2,9 [2,1; 3,6] ng/ml, 2,6 [2,0; 3,4] ng/ml at baseline and after 1 year of follow – up, respectively) and the restoration of graft function to the rate of estimated glomerular filtration rate (eGFR) CKD-EPI stage C2, albuminuria stage A1 of chronic kidney disease (CKD). However, 22% of patients experienced an increase of albumin-to-creatinine ratio to A2 at different times after surgical treatment. There was a statistically significant increase in SOD level (p=0.0005) and RAGE level (p=0.011) after 12 months of observation. Significant correlations of kidney transplant function parameters with “metabolic memory" markers (oxidative stress and RAGE) were also found: RAGE & creatinine (R=0.50, p=0.02), RAGE & KIM-1 (R=0.43, p=0.047), 3-NT& eGFR (R= - 0.40, p=0.046), IL-18 & SOD baseline (R=0.43, p=0.047). Attention is drawn to the correlations of RAGE & HbA1c+12 month (R=0.47, p=0.01), podocin with HbA1c (R=-0.46, p=0.03), which may probably reflect the direct influence of carbohydrate metabolism compensation to the kidney graft condition and also the correlation of SOD baseline & RAGE +12 month (R= - 0.70, p=0.0008), which may demonstrate the relative influence of components of "metabolic memory”. Conclusion SPKT as the way to achieve compensation of carbohydrate metabolism remains just one of factors of stable kidney graft function. The results of analysis of “metabolic memory” markers could indicate not only their direct contribution to the persistence of metabolic consequences of DM and DN, but also their possible participation in the development of recurrent nephropathy.