Renal dysfunction markers in patients with diabetes mellitus type 1 after kidney or simultaneous kidney-pancreas transplantation

Objective. To examine kidney transplant dysfunction markers in patients with diabetes mellitus type 1 (T1DM) after kidney transplantation (KT) and simultaneous kidney-pancreas transplantation (SPK).Materials and methods. The study included 20 patients after successful SPK (group 1) and 41 patients after KT (21 received insulin pump therapy (group 2), 20 –multiple daily injections of insulin (group 3). Post transplantation period at the time of inclusion in the KT group was 8 months [7;8], in SPK-11 months [8;18]. The control group consisted of 15 patients with DM1 without diabetic nephropathy (group 4). Sex, age and duration of T1DM were comparable. Donors of SPK were younger than KT: 29 [25; 33] vs 46[30; 51] years p<0,01 and transplant cold ischemia time was less 8[7;10] vs 11,5 [1; 17] hours respectively, p<0,01. After 9 months of observation biomarkers of dysfunction of renal transplant: Cystatin C (serum, urine); NGAL, KIM-1, podocin, nephrin, IL-18, IP-10 (urine), TGF-β1, MMP-9, VEGF-A, Osteopontin – (OPN) (serum) were defined.Results. the level of GFR in patients after transplantation was C2 stage, albuminuria A1 of chronic kidney disease. In the group of patients with T1DM after successful SPK and KT revealed a significant increase in markers of renal dysfunction (cystatin C (serum), NGAL, Podocin, OPN) compared with the control group despite of carbohydrate metabolism compensation (Tabl.1). High level and a negative associated of blood cystatin C with GFR (r = - 0,36, p<0.05) and positive with albuminuria (r=0,40, p<0,05), as well as a direct link of podocin urine-with blood creatinine (r = 0,35, p<0.05) and NGAL with albuminuria (r = 0,35, p<0.05) in recipients after transplantation were defined. Association between podocin with MMP-9 (r = 0,46, p<0,05) and NGAL (r = 0,33, p<0,05) indicated correlation of stress factors of renal microstructures in posttransplantation patients.Conclusion. High levels of renal graft dysfunction biomarkers in the examined patients (including those after SPK) show the persistence of damage to the microstructures with stable graft function and demonstrate the need to control all factors in the preservation of renal function.Table 1. Renal transplant dysfunction markersParametrsGroup 1Group 2Group 3Group 4TGF b1 (serum, pg/ml)32999[24514;3917]24473[21752;33330]25139[11367;2862]26986[17347;4266]VEGF A (serum, pg/ml)471,9[296;530,6]#407,6[301,6;522,2] #226,6[177,8;367,4]467,4[288,3;474,8]CYS C, (serum, ng/ml)1047[985;1295]*∞1252,9[1151;1540]#∞1113,32[986;1257] §728,8[592,9;765,3]Osteopontin (serum, ng/ml)3,51[2,7;4,9] #∞4,28[2,8;8,2] ∞4,71[3,6;12,7] §2,86[2,2;3,1]MMP-9 (urine, ng/ml)1,15[1,1;1,7]1,30[1,2;1,9] #1,10[0,9;1,3]1,22[1,0;1,3]IP-10 (urine, ng/ml)17,83[17,32;18,36]17,83[17,32;18,36]18,36[17,83;18,90]18,36[17,83;18,90]CYS C (urine, ng/ml)10407[5812;16306]15574[7518;28397]13329[7006;24624]14701[3643;26666]Podocin (urine, ng/ml)0,41[0,18;0,51] #0,49[0,26;0,69]0,56[0,38;0,79]§0,36[0,1;0,51]Nephrin (urine, ng/ml)0,0[0,0;0,1]0,0[0,0;01]0,0[0,0;0,07]0,07[0,0;0,1]KIM-1 (urine, ng/ml)211,8[83,3;368,4]314,9[152,1;508,6]338,7[191,3;594,0]359,2[204,4;494,5]NGAL (urine, ng/ml)2,4[1,7;6,7] *7,8[2,8;14,5] ∞2,9[1,8;12,0]§2,3[1,7;7,3]* р<0,01 (1-2); # р<0,01 (1,2-3); ∞ р<0,01 (1,2-4); § р<0,01 (3–4)