Сhronic kidney disease complications in patients with type 1 diabetes mellitus after simultaneous pancreas-kidney transplantation – potential role of oxidative stress and glycation end products

BACKGROUND: Normoglycaemia in patients with diabetes mellitus type 1 (T1DM) after simultaneous pancreas-kidney transplantation (SPKT) is very interesting in regards to chronic kidney disease (CKD) complications dynamics depending of posttransplantation period and possible targets of potential treatment from the point of view “metabolic memory”

AIM: To evaluate the relationship between oxidative stress indicators and advanced glycation end products and complications of end-stage renal disease (ESRD) in patients with T1DM аnd a long-term history of diabetes decompensation, who reached stable euglycemia after SPKT.

MATERIALS AND METHODS: The study included 20 patients with compensation of carbohydrate metabolism after SPKT performed from November 2011 to September 2018. Assessment included examination of complications of ESRD (arterial hypertension, dyslipidemia, anemia, mineral and bone disorder) and analysis of "metabolic memory" markers: 3-nitrothyrosine (3-NT), superoxide dismutase (SOD), advanced glycation end products (AGE) and AGE receptor (RAGE). We performed follow-up examination of patients included in the early postoperative period (1st day/week) in 6-12 months after SPKT.

RESULTS: All patients with DM1 duration for 22 [19; 28] years, diabetic nephropathy (DN) 8 [6; 14] years and duration of renal replacement therapy (dialysis) for 3 [1.5; 4] years reached euglycemia (HbA_1c 5,5 [5,1; 5,8] %; С-peptide 3,2 [2,45; 3,63] ng/ml) after 6 month of surgical treatment. Despite of stable graft function (estimated glomerular filtration rate (eGFR) CKD-EPI 84 [69; 95] ml/min/1.73m²) 35% of patients still needed antihypertensive therapy, 40% needed treatment with recombinant human erythropoietin (RHuEPO) and 15% – ferrotherapy. With vitamin D deficiency, observed in 80% of cases (13.3 [9.3; 18.5] ng/ml), 55% of patients had secondary hyperparathyroidism, 45% – osteoporosis. The results of the correlation analysis revealed the association of the state of ESRD target organs with the studied "metabolic memory" markers: oxidative stress and AGE-RAGE system.

CONCLUSIONS: SPKT as the way to achieve compensation of carbohydrate metabolism and uremia does not provide regress of diabetes and complications of ESRD. Analysis of "metabolic memory" markers indicate their direct contribution to the persistence of metabolic consequences of diabetic nephropathy (DN). Found trends need more long-lasting observation and enlargement of study groups.

transplantation, diabetes mellitus type 1, chronic kidney disease complications, advanced glycation end products, oxidative stress, euglicemia

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