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 (HbA1c 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

Pharmacotherapy of Ischemia-Reperfusion Injury of Transplanted Kidneys in Children: Comparative Study

Background. Prevention of ischemia-reperfusion injury of the allograft (IRIA) is an urgent problem in transplantology, which largely determines the prognosis for both the transplanted organ and the patient as a whole.Objective. Our aim was to study the effectiveness of eculizumab in comparison with plasmapheresis during induction  immunosuppressive therapy in kidney transplantation in children.Methods. The retrospective study includes children with terminal phase of chronic renal failure who have received kidney transplants from either a living relative or deceased donor. The age of patients is from 1 year to 18 years. Induction immunosuppression in both groups was performed with alemtuzumab. Group 1 (main) included children who were treated with eculizumab to prevent IRIA, Group 2 (comparison) included children who were treated with plasmapheresis for the same purpose. The comparative analysis was carried out according to the following criteria: the rate of blood creatinine subnormalization (in days), the rate of glomerular filtration (in ml/min) 30 days after the operation; daily protein excretion (mg/24 h) 30 days after organ transplantation; morphological characteristics of renal biopsy samples by Banff 30 days after surgery.Results. During the comparative analysis from December 2012 to November 2016, eculizumab was administered to 32 patients, 24 patients underwent plasmapheresis. In Group 1, blood creatinine normalized almost 4 days earlier than in Group 2 (p=0.0049); the glomerular filtration rate in Group 1 was 4.5 times higher than in Group 2 (p=0.0018). Daily proteinuria in Group 1 was 4 times lower than in Group 2 (p=0.0019).Conclusion. The carried out study showed better indices of renal allograft function when using eculizumab in comparison with plasmapheresis: consequently, eculizumab more effectively suppresses IRIA than plasmapheresis

Outcome of renal transplantation in small infants:a match-controlled analysis

BACKGROUND Infants with a body weight of less than 10 kg are often not considered to be suitable candidates for renal transplantation (RTx). The objective of this study was to evaluate this arbitrary weight threshold for pediatric RTx. METHODS We conducted a multicenter, retrospective, match-controlled cohort study on infants weighing less than 10 kg at time of engrafting (low-weight group [LWG], n = 38) compared to a matched control group (n = 76) with a body weight of 10-15 kg, using data from the first 2 years post-transplant derived from the CERTAIN Registry. RESULTS Patient survival was 97 and 100% in the LWG and control groups, respectively (P = 0.33), and death-censored graft survival was 100 and 95% in the LWG and control groups, respectively (P = 0.30). Estimated glomerular filtration rate at 2 years post-transplant was excellent and comparable between the groups (LWG 77.6 ± 34.9 mL/min/1.73 m; control 74.8 ± 29.1 mL/min/1.73 m; P = 0.68). The overall incidences of surgery-related complications (LWG 11%, control 23%; P = 0.12) and medical outcome measures (LWG 23%, control 36%, P = 0.17) were not significantly different between the groups. The medical outcome measures included transplant-related viral diseases (LWG 10%, control 21%; P = 0.20), acute rejection episodes (LWG 14%, control 29%; P = 0.092), malignancies (LWG 3%, control 0%; P = 0.33) and arterial hypertension (LWG 73%, control 67%; P = 0.57). CONCLUSIONS These data suggest that RTx in low-weight children is a feasible option, at least in selected centers with appropriate surgical and medical expertise

Outcome of renal transplantation in small infants:a match-controlled analysis

BACKGROUND Infants with a body weight of less than 10 kg are often not considered to be suitable candidates for renal transplantation (RTx). The objective of this study was to evaluate this arbitrary weight threshold for pediatric RTx. METHODS We conducted a multicenter, retrospective, match-controlled cohort study on infants weighing less than 10 kg at time of engrafting (low-weight group [LWG], n = 38) compared to a matched control group (n = 76) with a body weight of 10-15 kg, using data from the first 2 years post-transplant derived from the CERTAIN Registry. RESULTS Patient survival was 97 and 100% in the LWG and control groups, respectively (P = 0.33), and death-censored graft survival was 100 and 95% in the LWG and control groups, respectively (P = 0.30). Estimated glomerular filtration rate at 2 years post-transplant was excellent and comparable between the groups (LWG 77.6 ± 34.9 mL/min/1.73 m; control 74.8 ± 29.1 mL/min/1.73 m; P = 0.68). The overall incidences of surgery-related complications (LWG 11%, control 23%; P = 0.12) and medical outcome measures (LWG 23%, control 36%, P = 0.17) were not significantly different between the groups. The medical outcome measures included transplant-related viral diseases (LWG 10%, control 21%; P = 0.20), acute rejection episodes (LWG 14%, control 29%; P = 0.092), malignancies (LWG 3%, control 0%; P = 0.33) and arterial hypertension (LWG 73%, control 67%; P = 0.57). CONCLUSIONS These data suggest that RTx in low-weight children is a feasible option, at least in selected centers with appropriate surgical and medical expertise