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

https://doi.org/10.14341/probl201662514-16

Abstract

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 markers

Parametrs

Group 1

Group 2

Group 3

Group 4

TGF 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)

About the Authors

Alexandra M. Glazunova
Endocrinology Research Centre
Russian Federation
MD, PhD, Endocrinologyst, department of chronic diabetes kidney disease and posttrsnsplanation reabilitation Institution of Diabetes


Larisa V. Nikankina
Endocrinology Research Centre
Russian Federation
MD, PhD, Doctor of clinical laboratory diagnostics


Alexandr V. Ilin
Endocrinology Research Centre
Russian Federation
MD, Head of clinical laboratory diagnostics


Minara S. Shamkhalova
Endocrinology Research Centre
Russian Federation
MD, PhD, Head of department of chronic diabetes kidney disease and post trsnsplanation reabilitation Institution of Diabetes


Gulya M. Musaeva
I.M. Sechenov First Moscow State Medical University
Russian Federation
MD, Ophthalmologist, the department of eye diseases


Marina V. Shestakova
Endocrinology Research Centre; I.M. Sechenov First Moscow State Medical University
Russian Federation
MD, PhD, Professor, Head of Diabetes Institute


Yan G. Moysyuk
Academician V.I. Shumakov federal research center of transplantology and artificial organs
Russian Federation
MD, PhD, Professor, Head of department of kidney and liver transplantation


Ivan I. Dedov
Endocrinology Research Centre
Russian Federation
MD, PhD, Professor, Director of Research Centre of Endocrinology


Review

For citations:


Glazunova A.M., Nikankina L.V., Ilin A.V., Shamkhalova M.S., Musaeva G.M., Shestakova M.V., Moysyuk Ya.G., Dedov I.I. Renal dysfunction markers in patients with diabetes mellitus type 1 after kidney or simultaneous kidney-pancreas transplantation. Problems of Endocrinology. 2016;62(5):14-16. https://doi.org/10.14341/probl201662514-16

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ISSN 0375-9660 (Print)
ISSN 2308-1430 (Online)