Background: Immunoglobulin A nephropathy (IgAN) is the most frequent recurrent disease in kidney transplant recipients and its recurrence contributes to reducing graft survival. Several variables at the time of recurrence have been associated with a higher risk of graft loss. The presence of clinical or subclinical inflammation has been associated with a higher risk of kidney graft loss, but it is not precisely known how it influences the outcome of patients with recurrent IgAN. Methods: We performed a multicentre retrospective study including kidney transplant recipients with biopsy-proven recurrence of IgAN in which Banff and Oxford classification scores were available. 'Tubulo-interstitial inflammation' (TII) was defined when 't' or 'i' were ≥2. The main endpoint was progression to chronic kidney disease (CKD) stage 5 or to death censored-graft loss (CKD5/DCGL). Results: A total of 119 kidney transplant recipients with IgAN recurrence were included and 23 of them showed TII. Median follow-up was 102.9 months and 39 (32.8%) patients reached CKD5/DCGL. TII related to a higher risk of CKD5/DCGL (3 years 18.0% vs 45.3%, log-rank 7.588, P = .006). After multivariate analysis, TII remained related to the risk of CKD5/DCGL (HR 2.344, 95% CI 1.119-4.910, P = .024) independently of other histologic and clinical variables. Conclusions: In kidney transplant recipients with IgAN recurrence, TII contributes to increasing the risk of CKD5/DCGL independently of previously well-known variables. We suggest adding TII along with the Oxford classification to the clinical variables to identify recurrent IgAN patients at increased risk of graft loss who might benefit from intensified immunosuppression or specific IgAN therapies.
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.
Kidney Transplantation , Tacrolimus , Humans , Delayed-Action Preparations , Drugs, Generic/adverse effects , Graft Rejection/epidemiology , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Prospective Studies , Tacrolimus/adverse effects
Background: 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. Methods: We performed a multicenter, retrospective cohort study of 82 KT patients with SARS-CoV-2 infection {coronavirus disease 2019 [COVID-19]} treated with sotrovimab. Results: 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 (<5 days from the onset of the symptoms) in 46 patients (56%). Early-treated patients showed less likely progression to severe COVID-19 than those treated later, represented as a lower need for ventilator support (2.2% vs 36.1%; P < .001) or intensive care admission (2.2% vs 25%; P = .002) and COVID-19-related mortality (2.2% vs 16.7%; P = .020). In the multivariable analysis, controlling for baseline risk factors to severe COVID-19 in KT recipients, early use of sotrovimab remained as a protective factor for a composite outcome, including need for ventilator support, intensive care, and COVID-19-related mortality. No anaphylactic reactions, acute rejection episodes, impaired kidney function events, or non-kidney side effects related to sotrovimab were observed. Conclusions: 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.
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)
Humans , Lung Transplantation , Pancreas Transplantation , Diabetes Mellitus, Type 1 , Retrospective Studies , Epidemiology, Descriptive , Spain
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.
Diabetes Mellitus, Type 1 , Kidney Transplantation , Pancreas Transplantation , Adult , Diabetes Mellitus, Type 1/surgery , Female , Humans , Kidney , Male , Pancreas , Retrospective Studies , Treatment Outcome
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.
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.
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/epidemiology , Graft Rejection/prevention & control , Kidney Transplantation , Pandemics , SARS-CoV-2 , Adult , Comorbidity , Female , Follow-Up Studies , Graft Rejection/epidemiology , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Spain/epidemiology , Treatment Outcome , Young Adult
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.
Autonomic Nervous System/physiopathology , Diabetes Mellitus, Type 1/surgery , Diabetic Neuropathies/surgery , Kidney Transplantation , Pancreas Transplantation , Adult , Diabetes Mellitus, Type 1/physiopathology , Diabetic Neuropathies/physiopathology , Female , Follow-Up Studies , Graft Survival , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome
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 AND 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.
Diabetes Mellitus, Type 1/surgery , Pancreas Transplantation , Adult , Autoantibodies/blood , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnosis , Female , Glutamate Decarboxylase/immunology , Graft Rejection/diagnosis , Graft Rejection/etiology , Humans , Kidney Transplantation , Male , Prospective Studies , Recurrence , Reoperation
OBJECTIVE: To report on 2 patients with alcoholic cirrhosis who were treated with transjugular intrahepatic portosystemic shunt (TIPS) placement. CLINICAL PRESENTATION AND INTERVENTION: The 2 patients had a history of alcoholic cirrhosis, and TIPS surgery was performed on them. In both cases, 4 months after TIPS placement, proteinuria was observed along with histological alterations characteristic of immune complex membranoproliferative glomerulonephritis (MPGN). CONCLUSION: The TIPS in one patient was successful without immediate complications, while the other patient was referred for a combined liver-kidney transplant. In both cases, immune complex MPGN might have developed after TIPS placement probably due to a reduced immune complex clearance.
Glomerulonephritis, Membranoproliferative/etiology , Immune Complex Diseases/etiology , Liver Cirrhosis, Alcoholic/surgery , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Antigen-Antibody Complex/immunology , Female , Glomerulonephritis, Membranoproliferative/immunology , Humans , Immune Complex Diseases/immunology , Male , Middle Aged
Levamisole is illicitly employed as a cocaine adulterant. The consumption of levamisole-adulterated cocaine can provoke anti-neutrophil cytoplasmic antibody (ANCA)-associated syndromes. Patients carrying an HLAB27 allele are known to be at higher risk of developing agranulocytosis when treated with levamisole. Likewise, patients with ANCA-associated vasculitis (AAV) and internal organ involvement have typically been exposed to offending agents for prolonged periods of time, often on the order of years. Here, we report an unusual case of a patient in which kidney biopsy showed membranous glomerulonephritis with cellular crescents associated with levamisole-contaminated cocaine use.
