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

[EN] 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 5(th) year after SPK (p=0.03), as well as improvement of the Valsalva ratio at the 3(rd) (p<0.001) and 5(th) (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.Argente-Pla, M.; Pérez-Lázaro, A.; Martinez-Millana, A.; Del Olmo-García, MI.; Espí-Reig, J.; Beneyto-Castello, I.; López-Andújar, R.... (2020). Simultaneous Pancreas Kidney Transplantation Improves Cardiovascular Autonomic Neuropathy with Improved Valsalva Ratio as the Most Precocious Test. Journal of Diabetes Research. 2020:1-10. https://doi.org/10.1155/2020/7574628S1102020Freeman, R. (2014). Diabetic autonomic neuropathy. Handbook of Clinical Neurology, 63-79. doi:10.1016/b978-0-444-53480-4.00006-0Maser, R. E., Mitchell, B. D., Vinik, A. I., & Freeman, R. (2003). The Association Between Cardiovascular Autonomic Neuropathy and Mortality in Individuals With Diabetes: A meta-analysis. Diabetes Care, 26(6), 1895-1901. doi:10.2337/diacare.26.6.1895Dimitropoulos, G. (2014). 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Use of tocilizumab in kidney transplant recipients with COVID-1

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed

Autoimmune Diabetes Recurrence After Pancreas Transplantation: Diagnosis, Management, and Literature Review

[EN] Background: Pancreas transplantation can be a viable treatment option for patients with type 1 diabetes mellitus (T1DM), especially for those who are candidates for kidney transplantation. T1DM may rarely recur after pancreas transplantation, causing the loss of pancreatic graft. The aim of this study was to describe the prevalence of T1DM recurrence after pancreas transplantation in our series. Material/Methods: Eighty-one patients transplanted from 2002 to 2015 were included. Autoantibody testing (GADA and IA-2) was performed before pancreas transplantation and during the follow-up. Results: The series includes 48 males and 33 females, mean age 37.4+5.7 years and mean duration of diabetes 25.5 +/- 6.5 years. Patients received simultaneous pancreas kidney (SPK) transplantation. After SPK transplantation, 56 patients retained pancreatic graft, 8 patients died, and 17 patients lost their pancreatic graft. T1DM recurrence occurred in 2 of the 81 transplanted patients, yielding a prevalence of 2.5%, with an average time of appearance of 3.3 years after transplant. Pancreatic enzymes were normal in the 2 patients, ruling out pancreatic rejection. T1DM recurrence was confirmed histologically, showing selective lymphoid infiltration of the pancreatic islets. Conclusions: T1DM recurrence after pancreas transplantation is infrequent; however, it is one of the causes of pancreatic graft loss that should always be ruled out. Negative autoimmunity prior to transplantation does not ensure that T1DM does not recur.Argente-Pla, M.; Martinez-Millana, A.; María Isabel Del Olmo-García; Espí-Reig, J.; Pérez-Rojas, J.; Traver Salcedo, V.; Merino-Torres, JF. (2019). Autoimmune Diabetes Recurrence After Pancreas Transplantation: Diagnosis, Management, and Literature Review. Annals of Transplantation. 24:608-616. https://doi.org/10.12659/AOT.920106S6086162

Treatment with sotrovimab for SARS-CoV-2 infection in a cohort of high-risk kidney transplant recipients.

Sotrovimab is a neutralizing monoclonal antibody (mAb) that seems to remain active against recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. The evidence on its use in kidney transplant (KT) recipients, however, is limited. We performed a multicenter, retrospective cohort study of 82 KT patients with SARS-CoV-2 infection {coronavirus disease 2019 [COVID-19]} treated with sotrovimab. Median age was 63 years. Diabetes was present in 43.9% of patients, and obesity in 32.9% of patients; 48.8% of patients had an estimated glomerular filtration rate under 30 mL/minute/1.73 m2. Additional anti-COVID-19 therapies were administered to 56 patients, especially intravenous steroids (65.9%). Sotrovimab was administered early ( Sotrovimab had an excellent safety profile, even in high-comorbidity patients and advanced chronic kidney disease stages. Earlier administration could prevent progression to severe disease, while clinical outcomes were poor in patients treated later. Larger controlled studies enrolling KT recipients are warranted to elucidate the true efficacy of monoclonal antibody therapies