Mesangial sclerosis in a patient with type 1 diabetes following simultaneous pancreas-kidney transplantation despite maintenance of normoglycemia: a case report

Background Simultaneous pancreas-kidney transplantation is considered a curative treatment for type 1 diabetes complicated by end-stage kidney disease. We report herein a case of mesangial sclerosis in a patient who underwent successful kidney-pancreas transplantation despite well-controlled glucose and excellent pancreatic allograft function. Case presentation A 76-year-old type 1 diabetic man who underwent a simultaneous pancreas-kidney transplantation 19 years prior presented with persistent nephrotic range proteinuria although creatinine was at his baseline (normal) level. Hemoglobin A1c and fasting glucose were well controlled without the use of insulin or oral antihyperglycemic agents. Serum lipase and amylase were within the reference range and there was no evidence of donor-specific antibodies. Kidney allograft biopsy was performed to evaluate proteinuria and showed diffuse capillary loop thickening and diffuse moderate to severe mesangial sclerosis resembling diabetic nephropathy. Conclusions This case demonstrates a case of mesangial sclerosis resembling diabetic nephropathy in a patient with good glucose control after simultaneous pancreas-kidney transplantation with excellent pancreatic allograft function.

Cardiovascular outcomes after simultaneous pancreas kidney transplantation compared to kidney transplantation alone: a propensity score matching analysis

Background Coronary heart disease due to arteriosclerosis is the leading cause of death in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to evaluate the effect of simultaneous pancreas kidney transplantation (SPKT) compared to kidney transplantation alone (KTA) on survival, cardiovascular function and metabolic outcomes. Methods A cohort of 127 insulin-dependent diabetes mellitus (IDDM) patients with ESRD who underwent either SPKT (n = 100) or KTA (n = 27) between 1998 and 2019 at the University Hospital of Leipzig were retrospectively evaluated with regard to cardiovascular and metabolic function/outcomes as well as survival rates. An additional focus was placed on the echocardiographic assessment of systolic and diastolic cardiac function pretransplant and during follow-up. To avoid selection bias, a 2:1 propensity score matching analysis (PSM) was performed. Results After PSM, a total of 63 patients were identified; 42 patients underwent SPKT, and 21 patients received KTA. Compared with the KTA group, SPKT recipients received organs from younger donors (p < 0.05) and donor BMI was higher (p = 0.09). The risk factor-adjusted hazard ratio for mortality in SPKT recipients compared to KTA recipients was 0.63 (CI: 0.49–0.89; P < 0.05). The incidence of pretransplant cardiovascular events was higher in the KTA group (KTA: n = 10, 47% versus SPKT: n = 10, 23%; p = 0.06), but this difference was not significant. However, the occurrence of cardiovascular events in the SPKT group (n = 3, 7%) was significantly diminished after transplantation compared to that in the KTA recipients (n = 6, 28%; p = 0.02). The cardiovascular death rate was higher in KTA recipients (19%) than in SPK recipients with functioning grafts (3.3%) and comparable to that in patients with failed SPKT (16.7%) (p = 0.16). In line with pretransplant values, SPKT recipients showed significant improvements in Hb1ac values (p = 0.001), blood pressure control (p = < 0.005) and low-density lipoprotein/high-density lipoprotein (LDL/HDL) ratio (p = < 0.005) 5 years after transplantation. With regard to echocardiographic assessment, SPKT recipients showed significant improvements in left ventricular systolic parameters during follow-up. Conclusions Normoglycaemia and improvement of lipid metabolism and blood pressure control achieved by successful SPKT are associated with beneficial effects on survival, cardiovascular outcomes and systolic left ventricular cardiac function. Future studies with larger samples are needed to make predictions regarding cardiovascular events and graft survival.

Advanced glycation end products and oxidative stress as a basis for metabolic abnormalities in patients with type 1 diabetes after successful simultaneous pancreas-kidney transplantation

Aim. To compare advanced glycation end-products (AGE, RAGE) and 3-nitrotyrosine (3-HT) in patients with DM 1 after successful simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). To assess relationship between levels of AGE, RAGE, 3-HT and renal transplant (RT) function, carbohydrate and mineral metabolism. Materials and methods. The study included 58 patients who received kidney transplantation in end-stage renal disease (ESRD). 36 patients received SPK. There were performed routine laboratory, examination of AGE, RAGE, 3-NT, parathyroid hormone (PTH), 25(OH)vitamin D, calcium, phosphorus, FGF23, osteoprotegerin (OPG), and fetuin-A levels. Results. All patients after SPK reached normoglycemia (HbA1c 5.7 [5.3; 6.1] %; C-peptide 3.24 [2.29; 4.40] ng/ml) with the achievement of significant difference vs patients after KTA. Arterial hypertension (AH) was more frequent in recipients of SPK before transplantation than after (p=0.008). AH also persisted in greater number of cases in patients after KTA than after SPK. Patients after SPK had higher AGE (р=0.0003) and lower RAGE (р=0.000003) levels. OPG in patients after SPK was significantly higher (р=0.04). The correlation analysis revealed significant positive correlation between 3-HT and OPG (p0.05; r=0.30), RAGE and eGFR (r=-0.52), HbA1c (r=0.48), duration of AH (r=0.34), AGE with HbA1c (r=0.51). Conclusion. The results of the "metabolic memory" markers analysis may indicate their contribution to the persistence of the metabolic consequences of CKD and DM 1 after achievement of normoglycemia and renal function restoration and their possible participation in development of recurrent nephropathy, vascular calcification, and bone disorders.