Sodium-glucose cotransporter-2 inhibitor therapy in kidney transplant patients with type 2 or post-transplant diabetes: an observational multicentre study.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. Methods: This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results: Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63-17.21]} and female sex [OR 2.46 (CI 1.19-5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [-2.22 kg (95% CI -2.79 to -1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [-0.36% (95% CI -0.51 to -0.21)], serum uric acid [-0.44 mg/dl (95% CI -0.60 to -0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11-0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28-0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions: SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.

Comparative Study of 2 Extended-Release Tacrolimus Formulations in Kidney Transplantation.

BACKGROUND: During the 1900s, tacrolimus became the mainstay immunosuppressive agent to prevent rejection after kidney transplant. Subsequently, an extended-release tacrolimus (ER-Tac) formulation was developed to improve adherence, and its generic version has been marketed over the last years. This study examines the differences in efficacy and safety between the generic ER-Tac (Conferoport) and the reference brand-name drug (Advagraf). METHODS: Prospective, randomized and parallel single-center study (May 2020 to June 2021) with 52 kidney transplant recipients who were randomly assigned to 1 of the following groups: study group (Conferoport, n = 31) and control group (Advagraf, n = 21). The variables of interest were collected and analyzed to compare tacrolimus efficacy and safety between them. Demographic characteristics of the patients and clinical donor data were homogeneous in both groups (P > .05). RESULTS: No statistically significant differences were found among treatments regarding dosage used, levels, creatinine, and proteinuria (P > .05), with these variables presenting a downward trend during follow-up and, consequently, the improvement of graft function. Analyses also revealed the absence of differences concerning the incidence of acute rejection and intrapatient variability (coefficient of variation) throughout the first year of evolution between both formulations (P > .05). A total of 5 graft losses occurred, 2 resulting from patient death. CONCLUSIONS: In our experience, we found no significant differences between the measured parameters in relation to the efficacy and safety profile of both drugs, with generic ER-Tac being an alternative comparable with the reference brand-name ER-Tac.

Resultados tras 13 años del inicio del trasplante simultáneo de páncreas-riñón en pacientes con diabetes mellitus tipo 1 en la Comunidad Valenciana / Results after 13 years of kidney-pancreas transplantation in type 1 diabetic patients in Comunidad Valenciana

Introducción: El trasplante simultáneo de páncreas-riñón (SPK, por simultaneous pancreas kidney) es una opción terapéutica válida en pacientes afectos de diabetes mellitus tipo 1 con enfermedad renal crónica terminal que son candidatos a trasplante renal. Se presentan los resultados desde el inicio del programa de trasplante SPK en la Comunidad Valenciana. Métodos: Estudio descriptivo, retrospectivo y unicéntrico de los trasplantes de páncreas realizados en el Hospital Universitari i Politècnic La Fe, desde septiembre de 2002 a diciembre de 2015. Se recogieron variables clínicas de los donantes y receptores, variables peri-operatorias y supervivencia del paciente y del injerto pancreático. Resultados: Ochenta y un pacientes con diabetes mellitus tipo 1 (48 hombres y 33 mujeres, de 37,4±5,7 años, IMC de 24,1±3,4kg/m2, con una duración de su diabetes de 25,5±6,5 años) recibieron un trasplante SPK. La supervivencia global del paciente a uno, 3 y 5 años fue del 91,3, el 91,3 y el 89,5%, respectivamente. Sin embargo, la supervivencia del paciente en los periodos 2002-2008 y 2009-2015 fue del 88,2 y el 93,6% al año, del 88,2 y el 93,7% a los 3 años, y del 85,3 y el 93,7% a los 5 años, respectivamente (p=1). La supervivencia global del injerto pancreático a uno, 3 y 5 años fue del 75,2, el 69,1 y el 63,2%, respectivamente. Por otra parte, la supervivencia del injerto pancreático en los periodos 2002-2008 y 2009-2015 fue del 67,5 y el 80,6% al año, del 64,7 y el 71,8% a los 3 años, y del 58,8 y el 65,3% a los 5 años, respectivamente (p=0,0109). Las complicaciones postrasplante fueron: rechazo del injerto en un 8,6%, trombosis venosa del injerto en un 7,4% y pancreatitis del injerto en un 4,9%. (AU)

Introduction: Simultaneous pancreas-kidney (SPK) transplant is a proven option of treatment for patients with type 1 diabetes mellitus and related end-stage renal disease, who are candidates for kidney transplantation. The results from the beginning of SPK transplant program in Comunidad Valenciana are presented. Methods: Descriptive, retrospective, and single-center study of the pancreas transplant performed at the Hospital Universitari i Politècnic La Fe, from September 2002 to December 2015. Clinical variables from donors and recipients, peri-operative variables, patient survival, and pancreatic graft survival were collected. Results: Eighty-one patients with type 1 diabetes mellitus (48 males and 33 females, mean age 37.4±5.7 years, mean BMI 24.1±3.4kg/m2, mean duration of diabetes 25.5±6.5 years) received SPK transplantation. The overall patient survival at one, 3, and 5 years were 91,3, 91,3 and 89,5%, respectively. However, patient survival in the periods 2002-2008 and 2009-2015 were 88.2 and 93.6% at one year, 88.2 and 93.7% at 3 years, and 85.3 and 93.7% at 5 years, respectively (P=1). The overall pancreatic graft survival at one, 3, and 5 years were 75.2, 69.1 and 63.2%, respectively. On the other hand, pancreatic graft survival in the periods 2002-2008 and 2009-2015 were 67.5 and 80.6% at one year, 64.7 and 71.8% at 3 years, and 58.8% and 65.3% at 5 years, respectively (P=.0109). Postransplant complications were: graft rejection 8.6%, venous graft thrombosis 7.4%, graft pancreatitis 4.9%. (AU)

Results after 13 years of kidney-pancreas transplantation in type 1 diabetic patients in Comunidad Valenciana.

INTRODUCTION: Simultaneous pancreas-kidney (SPK) transplant is a proven option of treatment for patients with type 1 diabetes mellitus and related end-stage renal disease, who are candidates for kidney transplantation. The results from the beginning of SPK transplant program in Comunidad Valenciana are presented. METHODS: Descriptive, retrospective, and single-center study of the pancreas transplant performed at the Hospital Universitari i Politècnic La Fe, from September 2002 to December 2015. Clinical variables from donors and recipients, peri-operative variables, patient survival, and pancreatic graft survival were collected. RESULTS: Eighty-one patients with type 1 diabetes mellitus (48 males and 33 females, mean age 37.4 ± 5.7 years, mean BMI 24.1 ± 3.4 kg/m2, mean duration of diabetes 25.5 ± 6.5 years) received SPK transplantation. The overall patient survival at one, 3, and 5 years were 91.3%, 91.3% and 89.5%, respectively. However, patient survival in the periods 2002-2008 and 2009-2015 were 88.2% and 93.6% at one year, 88.2% and 93.7% at 3 years, and 85.3% and 93.7% at 5 years, respectively (P = 1). The overall pancreatic graft survival at one, 3, and 5 years were 75.2%, 69.1% and 63.2%, respectively. On the other hand, pancreatic graft survival in the periods 2002-2008 and 2009-2015 were 67.5% and 80.6% at one year, 64.7% and 71.8% at 3 years, and 58.8% and 65.3% at 5 years, respectively (P = .0109). Post-transplant complications were: graft rejection 8.6%, venous graft thrombosis 7.4%, graft pancreatitis 4.9%. CONCLUSIONS: In 13 years' experience of SPK transplantation, patient and pancreatic graft survival and the rate of complications after pancreas transplantation were similar to those of other larger series. The medical-surgical team experience improves pancreatic graft survival without influencing patient survival.

Results after 13 years of kidney-pancreas transplantation in type 1 diabetic patients in Comunidad Valenciana. / Resultados tras 13 años del inicio del trasplante simultáneo de páncreas-riñón en pacientes con diabetes mellitus tipo 1 en la Comunidad Valenciana.

INTRODUCTION: Simultaneous pancreas-kidney (SPK) transplant is a proven option of treatment for patients with type 1 diabetes mellitus and related end-stage renal disease, who are candidates for kidney transplantation. The results from the beginning of SPK transplant program in Comunidad Valenciana are presented. METHODS: Descriptive, retrospective, and single-center study of the pancreas transplant performed at the Hospital Universitari i Politècnic La Fe, from September 2002 to December 2015. Clinical variables from donors and recipients, peri-operative variables, patient survival, and pancreatic graft survival were collected. RESULTS: Eighty-one patients with type 1 diabetes mellitus (48 males and 33 females, mean age 37.4±5.7 years, mean BMI 24.1±3.4kg/m2, mean duration of diabetes 25.5±6.5 years) received SPK transplantation. The overall patient survival at one, 3, and 5 years were 91,3, 91,3 and 89,5%, respectively. However, patient survival in the periods 2002-2008 and 2009-2015 were 88.2 and 93.6% at one year, 88.2 and 93.7% at 3 years, and 85.3 and 93.7% at 5 years, respectively (P=1). The overall pancreatic graft survival at one, 3, and 5 years were 75.2, 69.1 and 63.2%, respectively. On the other hand, pancreatic graft survival in the periods 2002-2008 and 2009-2015 were 67.5 and 80.6% at one year, 64.7 and 71.8% at 3 years, and 58.8% and 65.3% at 5 years, respectively (P=.0109). Postransplant complications were: graft rejection 8.6%, venous graft thrombosis 7.4%, graft pancreatitis 4.9%. CONCLUSIONS: In 13-year's experience of SPK transplantation, patient and pancreatic graft survival and the rate of complications after pancreas transplantation were similar to those of other larger series. The medical-surgical team experience improves pancreatic graft survival without influencing patient survival.

Simultaneous Pancreas Kidney Transplantation Improves Cardiovascular Autonomic Neuropathy with Improved Valsalva Ratio as the Most Precocious Test.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation is a proven option of treatment for patients with type 1 diabetes mellitus (T1DM) and related end-stage renal disease. There is discrepancy between the results of different studies about the impact of prolonged normalization of glucose metabolism achieved by SPK on the course of diabetic complications including severe forms of diabetic neuropathy. The objective of the study was to evaluate the prevalence of cardiovascular autonomic neuropathy (CAN) in patients undergoing SPK transplantation and its evolution 10 years after transplantation. METHODS: Prospective study of 81 patients transplanted in a single center from year 2002 to 2015. Autonomic function was assessed using cardiovascular autonomic reflex tests (CARTs). CARTs were made before SPK transplantation and during the follow-up. Evolution of tests after SPK transplantation was evaluated by contrasting hypotheses (paired tests). Multiple testing was adjusted with the Benjamini-Hochberg procedure with a false discovery rate of 10%. RESULTS: 48 males and 33 females, mean age 37.4 ± 5.7 years, mean BMI 24.0 ± 3.4 kg/m2, and mean duration of diabetes 25.5 ± 6.5 years, received SPK transplantation. Ten years after SPK transplantation, 56 patients re tained the pancreatic graft (42 of them with normofunctioning pancreas and 14 with low doses of insulin therapy). These 42 patients were selected for the autonomic study. Before transplant procedure, all CART results were abnormal. After SPK transplantation, paired test analysis showed an improvement of systolic blood pressure (SBP) response to orthostasis at the 5th year after SPK (p = 0.03), as well as improvement of the Valsalva ratio at the 3rd (p < 0.001) and 5th (p = 0.001) year after SPK. After correcting for the false discovery rate, all the variables of autonomic study reached significance at different time points. CONCLUSIONS: Prevalence of CAN in patients who are candidates for SPK transplantation is high and is generally advanced. SPK transplantation improves CAN with improved Valsalva ratio as the most precocious test.

The effects of hyperlipidaemia on graft and patient outcome in renal transplantation.

Hyperlipidaemia is a frequent complication after renal transplantation. As to whether total cholesterol (TC) and triglyceride levels are risk factors for cardiovascular disease and graft survival is controversial. The prevalence of hypercholesterolaemia in the transplanted population in Spain has increased over the years, going from 38.8% in 1990 to 48% in 1998. In contrast, the prevalence of hypertriglyceridaemia being approximately 20%, has not shown any significant variation. Transplant recipients with high cholesterol were characterized by increased age, lower proportion of males, higher mean body mass index, lower proportion of HCV antibodies, reduced time on dialysis and diabetes. Patients with high cholesterol were more frequently treated with cyclosporine + MMF + prednisone and less frequently treated with tacrolimus + MMF + prednisone. Hypertriglyceridaemia was more frequent in patients treated with cyclosporine + MMF + prednisone, and these patients showed significantly higher creatinine plasma levels at 1 year and were more frequently treated with lipid-lowering agents. Hypertriglyceridaemia at 3 months after transplantation is associated with worse graft survival (RR 1.078; CI 1.07-1.143; P = 0.011) and greater cardiovascular mortality (RR 1.265; CI 1.20-1.428; P = 0.0002), while treatment with statins has a protective effect on the graft survival (RR 0.64; CI 0.512-0.888; P = 0.0051). In conclusion, in the renal transplant population in Spain, hypertriglyceridaemia rather than hypercholesterolaemia, may exert a deleterious effect on graft and patient survival.