scholarly journals 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

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Irina Larina ◽  
Anastasia Severina ◽  
Minara Shamhalova ◽  
Marina Shestakova ◽  
Larisa Nikankina ◽  
...  

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.

2020 ◽  
Vol 23 (3) ◽  
pp. 275-282
Author(s):  
A. S. Severina ◽  
I. I. Larina ◽  
A. S Shutovа ◽  
M. S. Shamkhalova ◽  
I. V. Dmitriev ◽  
...  

Simultaneous pancreas-kidney transplantation (SPKT) is the most promising treatment option for patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease (ESRD) due to diabetic nephropathy (DN). Successful SPKT eliminates uremic intoxication and hyperglycemia the leading trigger of vascular diabetic complications. Therefore, euglycemia is an important metabolic change in patients after surgery and remains only one of the factors for the saved renal allograft functioning. In the case of resuming renal replacement therapy by dialysis after SPKT, the management and monitoring of the pancreatic graft remains open. Special attention to the pancreatic grafts function is due to both the potential risk of surgical complications, and some probability of T1DM relapse with the need to resume insulin therapy. In patients with saved function of both transplants, the assessment of the dynamics of diabetic complications in general becomes more important. The results of few studies in this regard remain contradictory. Thus, clinical options can be unpredictably diverse and require not only search for the root cause, but also optimization of rehabilitation tactics, even if the expected results are achieved.


2016 ◽  
Vol 88 (10) ◽  
pp. 25-34
Author(s):  
A M Glazunova ◽  
M S Arutyunova ◽  
E V Tarasov ◽  
L V Nikankina ◽  
A V Ilyin ◽  
...  

Aim. To study the markers of renal graft dysfunction in patients with type 1 diabetes mellitus (T1DM) after kidney transplantation (KT) and simultaneous pancreas-kidney transplantation (SPKT). Subjects and methods. The investigation enrolled 20 patients after successful SPKT and 41 patients after KT (of them 21 received continuous subcutaneous insulin infusion with an insulin doser; 20 had multiple insulin injections). The periods after KT and SPKT at patient inclusion were 8 (7; 8) and 11 (8; 18) months, respectively. A control group comprised 15 patients with T1DM without diabetic nephropathy. The patients were matched for gender, age, and T1DM duration. At a 9-month follow-up, the main biomarkers of kidney graft dysfunction were identified using the standard kits: Cystatin C (Cys C; serum; urine), NGAL, KIM-1, Podocin, Nephrin, IL-18, MMP-9 (urine), TGF-β1, VEGF-A, and Osteopontin (OPN; serum). Fasting blood was taken; a morning urinary portion was examined. Results. The posttransplantation glomerular filtration rate (GFR) in the patients corresponded to Stage C2; albuminuria did to Category A1 chronic kidney disease. Despite successful SPKT in the group of patients with T1DM, as in that of patients after isolated KT, there was a statistically significant increase in the level of kidney dysfunction markers (Cys C, NGAL, Podocin, and OPN) versus the control group regardless of the compensation for glucose metabolism. compensation. It was found that the level of Cys C was high and correlated negatively with GFR (r=–0.36; p


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Irina Larina ◽  
Anastasia Severina ◽  
Minara Shamhalova ◽  
Marina Shestakova ◽  
Larisa Nikankina ◽  
...  

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.


2018 ◽  
Vol 5 (4) ◽  
pp. 295-303
Author(s):  
George W. Burke ◽  
Gaetano Ciancio ◽  
Mahmoud Morsi ◽  
Jose Figueiro ◽  
Linda Chen ◽  
...  

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