Systemic autoinflammatory disease, IgA glomerulonephritis and renal cortical necrosis: coincidence or causation?

We present a patient with a rare systemic autoinflammatory disease (mevalonate kinase deficiency -MKD-) with the identification of two heterozygous variants (c.1129G>A and c.32C>T) in the Mevalonate Kinase gene, detected by next generation sequencing and a highly prevalent glomerulonephritis (IgA nephropathy). The patient presents clinically with a monthly recurrent periodic fever from 12 days of age, accompanied by mucocutaneous lesions (maculopapular rash in extremities, aphthous stomatitis), joint (arthralgias in ankles, wrists and knees), lymphoid (cervical lymphadenopathy, splenomegaly), gastrointestinal (diarrhea, abdominal pain) and kidney (hematuria and proteinuria) with repeated biopsies showing IgA nephropathy alternating activity with chronicity. During follow-up. The patients presented a poor therapeutic response to multiple immunosuppressive regimens used for 7 years (corticosteroids, azathioprine, mycophenolate, cyclophosphamide, rituximab and tocilizumab), and finally a good response to canakinumab. Four years after starting canakinumab, during the course of an infection due to a muscle abscess, the clinical presentation is complicated by a severe renal microvascular event (renal cortical necrosis -RCN-) with acute kidney injury and dialysis requirement. Therecurrent episodes of inflammation due to MKD could act as triggers for the reactivation of glomerulonephritis (which would explain the poor response to immunosuppressants and the rapid progression to histological chronicity) and to generate a microenvironment that predisposes the development of RCN in the face of a non-serious infection. A defect in IgA molecules has been described in MKD, a phenomenon also observed in IgA nephropathy. This raises the challenging hypothesis of a common pathogenetic link between all the patient's clinical manifestations.

Presentamos un paciente con una rara enfermedad autoinflamatoria sistémica (deficiencia de mevalonato quinasa -DMQ-) con la identificación de dos variantes heterocigotas (c.1129G>A y c.32C>T) en el gen Mevalonato Quinasa, detectadas por secuenciación masiva en paralelo y una glomerulonefritis de alta prevalencia (nefropatía por IgA). El paciente presentó un cuadro de fiebre periódica recurrente mensual desde los 12 días de vida, acompañada de lesiones mucocutáneas (rash maculopapular en extremidades, estomatitis aftosa), compromiso articular (artralgias en tobillos, muñecas y rodillas), linfoideo (linfoadenopatía cervical, esplenomegalia), gastrointestinal (diarrea, dolor abdominal) y renal (hematuria y proteinuria) con repetidas biospias mostrando nefropatía por IgA alternando actividad y cronicidad. Durante el seguimiento, tuvo una pobre respuesta terapéutica a múltiples esquemas inmunosupresores utilizados durante 7 años (corticoides, azatrioprina, micofenolato, ciclofosfamida, rituximab y tocilizumab), y buena respuesta finalmente a canakinumab. Cuatro años posteriores al inicio de canakinumab, durante el curso de una infección por un absceso muscular, el cuadro clínico se complica con un evento microvascular renal grave (necrosis cortical renal -NCR-) con fallo renal agudo y necesidad de diálisis. Los episodios recurrentes de inflamación por la DMQ podrían actuar como gatillos para la reactivación de su glomerulonefritis (lo que explicaría la escasa respuesta a inmunosupresores y la progresión rápida a cronicidad histológica) y para generar un microambiente que predisponga el desarrollo de una NCR ante una infección no grave. En la DMQ se ha descripto un defecto en las moléculas de IgA, fenómeno también observado en la nefropatía por IgA. Esto plantea la desafiante hipótesis de un vínculo patogénico común entre todas las manifestaciones clínicas del paciente.

Systemic autoinflammatory disease, IgA glomerulonephritis and renal cortical necrosis: coincidence or causation? / Enfermedad autoinflamatoria sistémica, glomerulonefritis por IgA y necrosis cortical renal: ¿causalidad o casualidad?

Abstract We present a patient with a rare systemic autoinflam matory disease (mevalonate kinase deficiency -MKD-) with the identification of two heterozygous variants (c.1129G>A and c.32C>T) in the Mevalonate Kinase gene, detected by next generation sequencing and a highly prevalent glomerulonephritis (IgA nephropathy). The patient presents clinically with a monthly recurrent periodic fever from 12 days of age, accompanied by mucocutaneous lesions (maculopapular rash in ex tremities, aphthous stomatitis), joint (arthralgias in ankles, wrists and knees), lymphoid (cervical lymph adenopathy, splenomegaly), gastrointestinal (diarrhea, abdominal pain) and kidney (hematuria and protei-nuria) with repeated biopsies showing IgA nephropathy alternating activity with chronicity. During follow-up. The patients presented a poor therapeutic response to multiple immunosuppressive regimens used for 7 years (corticosteroids, azathioprine, mycophenolate, cyclo phosphamide, rituximab and tocilizumab), and finally a good response to canakinumab. Four years after starting canakinumab, during the course of an infection due to a muscle abscess, the clinical presentation is complicated by a severe renal microvascular event (renal cortical necrosis -RCN-) with acute kidney injury and dialysis requirement. Therecurrent episodes of inflammation due to MKD could act as triggers for the reactivation of glomerulonephritis (which would explain the poor response to immunosuppressants and the rapid pro gression to histological chronicity) and to generate a microenvironment that predisposes the development of RCN in the face of a non-serious infection. A defect in IgA molecules has been described in MKD, a phenom enon also observed in IgA nephropathy. This raises the challenging hypothesis of a common pathogenetic link between all the patient's clinical manifestations.

Resumen Presentamos un paciente con una rara enfermedad autoinflamatoria sistémica (deficiencia de mevalonato quinasa -DMQ-) con la identificación de dos variantes heterocigotas (c.1129G>A y c.32C>T) en el gen Meval onato Quinasa, detectadas por secuenciación masiva en paralelo y una glomerulonefritis de alta prevalencia (nefropatía por IgA). El paciente presentó un cuadro de fiebre periódica recurrente mensual desde los 12 días de vida, acompañada de lesiones mucocutáneas (rash maculopapular en extremidades, estomatitis aftosa), compromiso articular (artralgias en tobillos, muñecas y rodillas), linfoideo (linfoadenopatía cervical, esplenome galia), gastrointestinal (diarrea, dolor abdominal) y renal (hematuria y proteinuria) con repetidas biospias most rando nefropatía por IgA alternando actividad y cronic idad. Durante el seguimiento, tuvo una pobre respuesta terapéutica a múltiples esquemas inmunosupresores utilizados durante 7 años (corticoides, azatrioprina, micofenolato, ciclofosfamida, rituximab y tocilizumab), y buena respuesta finalmente a canakinumab. Cuatro años posteriores al inicio de canakinumab, durante el curso de una infección por un absceso muscular, el cuadro clínico se complica con un evento microvascular renal grave (necrosis cortical renal -NCR-) con fallo renal agudo y necesidad de diálisis. Los episodios recurrentes de inflamación por la DMQ podrían actuar como gatil los para la reactivación de su glomerulonefritis (lo que explicaría la escasa respuesta a inmunosupresores y la progresión rápida a cronicidad histológica) y para gen erar un microambiente que predisponga el desarrollo de una NCR ante una infección no grave. En la DMQ se ha descripto un defecto en las moléculas de IgA, fenómeno también observado en la nefropatía por IgA. Esto plantea la desafiante hipótesis de un vínculo patogénico común entre todas las manifestaciones clínicas del paciente.

[Clinical and microbiological characteristics of urinary tract infections in the first year after renal transplantation]. / Infecciones urinarias en el primer año postrasplante renal.

Introduction: Urinary tract infections (UTI) are the most frequent infection in kidney transplant (KT) patients. The main objective was to determine the clinical and microbiological characteristics of UTIs that occur during the first year after KT. Methods: Retrospective cohort study that included patients over 18 years of age who received KT between 2009-2020 in two hospitals in Córdoba city, Argentina. Patients were followed up during the first year after the transplant by recording them in the medical records, and those who presented at least one episode of UTI were analyzed. Results: During the study period, 568 KTs were performed, of which 207 (36.4%) had at least one episode of UTI. In total, there were 419 UTI episodes, 6 (1.4%) polymicrobial UTI episodes, so a total of 426 microorganisms were identified in the urine cultures. Of the total number of episodes, 206 (49.2%) occurred between 31 and 180 days post-transplant. The main etiological agent was E. coli with 225 isolates (52.8%) followed by Klebsiella sp. with 94 (22.1%). 52.1% of all episodes were caused by multi-resistant microorganisms (MRM). Among the E. coli isolates, 94 (41.8%) were MRM. In the multivariate analysis, the risk factors associated with UTI due to MRM were a history of recurrent UTI (Odds ratio 2.43; 95% CI: 1.37-4.30) and induction with basiliximab (Odds ratio 1.53; 95% CI: 1.029-2.29). Main conclusion: UTIs occurred in more than a third of kidney transplant patients, being slightly more than half caused by MOR.

Introducción: Las infecciones del tracto urinario (ITU) constituyen la infección más frecuente en los trasplantados renales (TR). El objetivo principal fue determinar las características clínicas y microbiológicas de las ITU que ocurren durante el primer año posterior al TR. Metodología: Estudio de cohorte retrospectivo, donde se incluyeron pacientes mayores 18 años que recibieron un TR entre 2009-2020 en dos hospitales de la ciudad de Córdoba. A través del registro en las historias clínicas se realizó seguimiento de los pacientes durante el primer año postrasplante y se analizaron los que presentaron al menos un episodio de ITU. Resultados: En el período de estudio, se realizaron 568 TR, de los cuales 207(36,4%) tuvieron al menos un episodio de ITU. En total hubo 419 episodios de ITU, 6(1,4%) episodios de ITU polimicrobianos, se identificaron un total de 426 microorganismos en total en los urocultivos. Del total de episodios 206(49,2%) ocurrieron entre los 31-180 días postrasplante. El principal agente etiológico fue E. coli con 225 aislamientos (52,8%) seguido de Klebsiella sp. con 94(22,1%). El 52,1% del total de episodios fueron causados por microorganismos multirresistentes (MOR). Entre los aislamientos de E. coli, 94(41,8%) fueron MOR. En el análisis multivariado los factores de riesgo asociados a ITU por MOR fueron el antecedente de ITU recurrente (Odds ratio 2.43; IC95%: 1.37-4.30) e inducción con basiliximab (Odds ratio 1.53; IC95%: 1.029-2.29). Conclusión: Las ITU se presentaron en más de un tercio de los pacientes trasplantados renales siendo un poco más de la mitad causados por MOR.

Renal Transplantation in the Elderly: Are They All the Same? A Multicenter, Comorbidity-Based Study.

INTRODUCTION: The age for kidney transplantation (KT) is no longer a limitation and several studies have shown benefits in the survival of elderly patients. The aim of this study was to examine the relationship of the baseline Charlson comorbidity index (CCI) score to morbidity and mortality after transplantation. METHODS: In this multicentric observational retrospective cohort study, we included patients older than 60 years admitted on the waiting list (WL) for deceased donor KT from January 01, 2006, to December 31, 2016. The CCI score was calculated for each patient at inclusion on the WL. RESULTS: Data for analysis were available of 387 patients. The patients were divided in tertiles of CCI: group 1 (CCI: 1-2) n = 117, group 2 (CCI: 3-4) n = 158, and group 3 (CCI: ≥5) n = 112. Patient survival was significantly different between CCI groups at 1, 3, and 5 years, respectively: 90%, 88%, and 84% for group 1, 88%, 80%, and 72% for group 2, and 87%, 75%, and 63% for group 3 (p < 0.0001). Variables associated with mortality were CCI score (p < 0.0001), HLA mismatch (p = 0.014), length of hospital stay (p < 0.0001), surgical complications (p = 0.048). CONCLUSION: Individualized strategies to modify these variables may improve patient's morbidity and mortality after KT.

Estimation of Glomerular Filtration Rate in Obese Patients: Utility of a New Equation.

There is no consensus on the best equation to estimate glomerular filtration rate (eGFR) in obese patients (OP). Objective: to evaluate the performance of the current equations and the new Argentinian Equation ("AE") to estimate GFR in OP. Two validation samples were used: internal (IVS, using 10-fold cross-validation) and temporary (TVS). OP whose GFR was measured (mGFR) with clearance of iothalamate between 2007/2017 (IVS, n = 189) and 2018/2019 (TVS, n = 26) were included. To evaluate the performance of the equations we used: bias (difference between eGFR and mGFR), P30 (percentage of estimates within ±30% of mGFR), Pearson's correlation (r) and percentage of correct classification (%CC) according to the stages of CKD. The median age was 50 years. Sixty percent had grade I obesity (G1-Ob), 25.1% G2-Ob and 14.9% G3-Ob, with a wide range in mGFR (5.6-173.1 mL/min/1.73 m2). In the IVS, AE obtained a higher P30 (85.2%), r (0.86) and %CC (74.4%), with lower bias (-0.4 mL/min/1.73 m2). In the TVS, AE obtained a higher P30 (88.5%), r (0.89) and %CC (84.6%). The performance of all equations was reduced in G3-Ob, but AE was the only one that obtained a P30 > 80% in all degrees. AE obtained better overall performance to estimate GFR in OP and could be useful in this population. Conclusions from this study may not be generalizable to all populations of obese patients since they were derived from a study in a single center with a very specific ethnic mixed population.

The incidence, risk factors and impact of acute kidney injury in hospitalized patients due to COVID-19.

The incidence of acute kidney injury (AKI) in hospitalized patients with COVID-19 is variable, being associated with worse outcomes. The objectives of the study were to evaluate the incidence, risk factors (considering demographic characteristics, comorbidities, initial clinical presentation and associated complications) and impact of AKI in subjects hospitalized for COVID-19 in two third-level hospitals in Córdoba, Argentina. A retrospective cohort study was conducted. We included 448 adults who were consecutively hospitalized for COVID-19 between March 3 and October 31, 2020 and were followed throughout the hospitalization. The incidence of AKI was 19% (n = 85; stage I = 43, stage II = 17, and stage III = 25, 18 required renal replacement therapy). In the multivariate analysis, the variables that were independently associated with AKI were: age (for every 10 years, adjusted odd ratio [95%CI] = 1.30 [1.04-1.63], p = 0.022), history of chronic kidney disease -CKD- (9.92 [4.52-21.77], p < 0.001), blood neutrophil count at admission -BNCA- (for every increase of 1000 BNCA, 1.09 [1.01-1.18], p = 0.037) and requirement for mechanical ventilation -MV- (6.69 [2.24-19.90], p = 0.001). AKI was associated with longer hospitalization, higher admission (63.5 vs. 29.7%; p < 0.001) and longer stay in the intensive care unit, a positive association with respiratory bacterial superinfection, sepsis, respiratory distress syndrome, MV requirement and mortality (mortality without AK I = 12.4% vs with AKI = 47.1%; stage I = 26%, stage II = 41% and stage III = 88%; p < 0.001). AKI was independently associated with higher mortality (3.32 [1.6-6.9], p = 0.001). In conclusion, the incidence of AKI in adults hospitalized for COVID-19 was 19% and had a clear impact on morbidity and mortality. The independent risk factors for AKI were: Age, CKD, BNCA and MV.

Los objetivos del estudio fueron evaluar la incidencia, los factores de riesgo (considerando características demográficas, comorbilidades, presentación clínica inicial y complicaciones asociadas) y el impacto de la lesión renal aguda ­LRA­ en sujetos hospitalizados por COVID-19 en dos instituciones de alta complejidad de Córdoba, Argentina. Se realizó un estudio de cohorte retrospectivo. Se incluyeron 448 adultos que fueron hospitalizados por COVID-19 entre el 3 de marzo y el 31 de octubre del 2020 con seguimiento durante toda la hospitalización. La incidencia de LRA fue 19% (estadio I = 43, estadio II = 17 y estadío III = 25, 18 requirieron diálisis). Las variables que se asociaron de manera independiente con el LRA fueron: edad (por cada 10 años, odd ratio ajustado [IC95%] = 1.30 [1.04-1.63], p = 0.022), enfermedad renal crónica ­ERC­ (9.92 [4.52-21.77], p < 0.001), recuento de neutrófilos sanguíneos al ingreso ­NSI­ (por cada incremento de 1000 NSI, 1.09 [1.01­1.18], p = 0.037) y asistencia respiratoria mecánica ­ARM­ (6.69 [2.24­19.90], p = 0.001). Los sujetos con LRA presentaron una internación más prolongada, mayor requerimiento (63.5 vs. 29.7%; p < 0.001) y estadía más prolongada en unidad de cuidados intensivos, una asociación positiva con sobreinfección respiratoria bacteriana, sepsis, síndrome de distrés respiratorio, requerimiento de ARM y mortalidad (mortalidad sin LRA 12.4% vs. con LRA 47.1%; estadio I = 26%, estadio II = 41% y estadio III = 88%; p < 0.001). LRA se asoció de manera independiente a mayor mortalidad (3.3 [1.6­6.9], p = 0.001). En conclusión, la incidencia de LRA en adultos hospitalizados por COVID-19 fue del 19% y tuvo un claro impacto en la morbi-mortalidad. Los factores de riesgo independientes de LRA fueron: edad, ERC, NSI y ARM.

[ABO incompatible living donor kidney transplantation in a center in Córdoba, Argentina]. / Trasplante renal donante vivo ABO incompatible en un centro de Córdoba, Argentina.

The ABO incompatible (ABOi) living donor (LD) kidney transplant allows increasing the number of donors and reducing the time on the waiting list. The objectives of this study were to compare graft survival, patient survival, rejection risk factors and complications during the first year p ost-transplantation in patients who received an ABOi LD kidney transplant between 2014 and 2019 in our institution, matched according to sex, age and immunological risk with a control group of ABO compatible (ABOc) LD kidney transplants in the same period. Thirteen patients were included in each group. No significant differences were found between ABOi and ABOc in the incidence of delayed graft function (n = 0 vs. 1), bleeding (0 vs. 0), infections (13 vs. 13), cellular rejection (1 vs. 3) and humoral rejection (4 vs. 3) in the first year after transplantation. The rejection rate in ABOi do not seem to be related to blood incompatibility. No risk factors associated with rejection were found. Overall survival of patients was 100% in both groups, and graft survival was 92.3% in ABOi and 100% in ABOc (p = 1). ABOi kidney transplantation is an adequate feasible option in our environment for those who do not have compatible donors.

El trasplante renal con donante vivo (DV) ABO incompatible (ABOi) permite aumentar el número de donantes y reducir el tiempo en lista de espera. Los objetivos de este estudio fueron: comparar la supervivencia del injerto, del paciente, los factores de riesgo de rechazo y las complicaciones durante el primer año post-trasplante en los pacientes que recibieron un trasplante DV ABOi entre 2014 y 2019 en nuestra institución, emparejados según sexo, edad y riesgo inmunológico con un grupo control de trasplantados DV ABO compatibles (ABOc) en el mismo periodo. Se incluyeron 13 pacientes en cada grupo. No se hallaron diferencias significativas entre los ABOi vs ABOc en la incidencia de retardo de la función del injerto (n = 0 vs. 1), sangrado (0 vs. 0), infecciones (13 vs. 13), rechazo celular (1 vs. 3) y rechazo humoral (4 vs. 3) en el primer año posttrasplante. La tasa de rechazo en los pacientes ABOi no parece tener relación con la incompatibilidad sanguínea, ni se hallaron otros factores de riesgo asociados a rechazo. La supervivencia global de los pacientes fue del 100% en ambos grupos, y la del injerto fue del 92.3% en ABOi y 100% en ABOc (p = 1). El trasplante renal ABOi es una adecuada opción factible en nuestro medio para quienes que no cuentan con donantes compatibles.

The incidence, risk factors and impact of acute kidney injury in hospitalized patients due to COVID-19 / Incidencia, factores de riesgo e impacto de la lesión renal aguda en pacientes hospitalizados por COVID-19

Abstract The incidence of acute kidney injury (AKI) in hospitalized patients with COVID-19 is variable, being associated with worse outcomes. The objectives of the study were to evaluate the incidence, risk factors (considering demographic characteristics, comorbidities, initial clinical presentation and associated complications) and impact of AKI in subjects hospitalized for COVID-19 in two third-level hospitals in Córdoba, Argentina. A retrospective cohort study was conducted. We included 448 adults who were consecutively hospitalized for CO VID-19 between March 3 and October 31, 2020 and were followed throughout the hospitalization. The incidence of AKI was 19% (n = 85; stage I = 43, stage II = 17, and stage III = 25, 18 required renal replacement therapy). In the multivariate analysis, the variables that were independently associated with AKI were: age (for every 10 years, adjusted odd ratio [95%CI] = 1.30 [1.04-1.63], p = 0.022), history of chronic kidney disease -CKD- (9.92 [4.52-21.77], p < 0.001), blood neutrophil count at admission -BNCA- (for every increase of 1000 BNCA, 1.09 [1.01-1.18], p = 0.037) and requirement for mechanical ventilation -MV- (6.69 [2.24-19.90], p = 0.001). AKI was associated with longer hospitalization, higher admission (63.5 vs. 29.7%; p < 0.001) and longer stay in the intensive care unit, a positive association with respiratory bacterial superinfection, sepsis, respiratory distress syndrome, MV requirement and mortality (mortality without AK I = 12.4% vs with AKI = 47.1%; stage I = 26%, stage II = 41% and stage III = 88%; p < 0.001). AKI was independently associated with higher mortality (3.32 [1.6-6.9], p = 0.001). In conclusion, the incidence of AKI in adults hospitalized for COVID-19 was 19% and had a clear impact on morbidity and mortality. The independent risk factors for AKI were: Age, CKD, BNCA and MV.

Resumen Los objetivos del estudio fueron evaluar la incidencia, los factores de riesgo (consi derando características demográficas, comorbilidades, presentación clínica inicial y complicaciones asociadas) y el impacto de la lesión renal aguda -LRA- en sujetos hospitalizados por COVID-19 en dos instituciones de alta complejidad de Córdoba, Argentina. Se realizó un estudio de cohorte retrospectivo. Se incluyeron 448 adul tos que fueron hospitalizados por COVID-19 entre el 3 de marzo y el 31 de octubre del 2020 con seguimiento durante toda la hospitalización. La incidencia de LRA fue 19% (estadio I = 43, estadio II = 17 y estadío III = 25, 18 requirieron diálisis). Las variables que se asociaron de manera independiente con el LRA fueron: edad (por cada 10 años, odd ratio ajustado [IC95%] = 1.30 [1.04-1.63], p = 0.022), enfermedad renal crónica -ERC- (9.92 [4.52-21.77], p < 0.001), recuento de neutrófilos sanguíneos al ingreso -NSI- (por cada incremento de 1000 NSI, 1.09 [1.01-1.18], p = 0.037) y asistencia respiratoria mecánica -ARM- (6.69 [2.24-19.90], p = 0.001). Los sujetos con LRA presentaron una internación más prolongada, mayor requerimiento (63.5 vs. 29.7%; p < 0.001) y estadía más prolongada en unidad de cuidados intensivos, una asociación positiva con sobreinfección respi ratoria bacteriana, sepsis, síndrome de distrés respiratorio, requerimiento de ARM y mortalidad (mortalidad sin LRA 12.4% vs. con LRA 47.1%; estadio I = 26%, estadio II = 41% y estadio III = 88%; p < 0.001). LRA se asoció de manera independiente a mayor mortalidad (3.3 [1.6-6.9], p = 0.001). En conclusión, la incidencia de LRA en adultos hospitalizados por COVID-19 fue del 19% y tuvo un claro impacto en la morbi-mortalidad. Los factores de riesgo independientes de LRA fueron: edad, ERC, NSI y ARM.

Trasplante renal donante vivo ABO incompatible en un centro de Córdoba, Argentina / ABO incompatible living donor kidney transplantation in a center in Córdoba, Argentina

Resumen El trasplante renal con donante vivo (DV) ABO incompatible (ABOi) permite aumentar el número de donantes y reducir el tiempo en lista de espera. Los objetivos de este estudio fueron: comparar la supervivencia del injerto, del paciente, los factores de riesgo de rechazo y las complicaciones durante el primer año post-trasplante en los pacientes que recibieron un trasplante DV ABOi entre 2014 y 2019 en nuestra ins titución, emparejados según sexo, edad y riesgo inmunológico con un grupo control de trasplantados DV ABO compatibles (ABOc) en el mismo periodo. Se incluyeron 13 pacientes en cada grupo. No se hallaron diferencias significativas entre los ABOi vs ABOc en la incidencia de retardo de la función del injerto (n = 0 vs. 1), sangrado (0 vs. 0), infecciones (13 vs. 13), rechazo celular (1 vs. 3) y rechazo humoral (4 vs. 3) en el primer año post-trasplante. La tasa de rechazo en los pacientes ABOi no parece tener relación con la incompatibilidad sanguínea, ni se hallaron otros factores de riesgo asociados a rechazo. La supervivencia global de los pacientes fue del 100% en ambos grupos, y la del injerto fue del 92.3% en ABOi y 100% en ABOc (p = 1). El trasplante renal ABOi es una adecuada opción factible en nuestro medio para quienes que no cuentan con donantes compatibles.

Abstract The ABO incompatible (ABOi) living donor (LD) kidney transplant allows increasing the number of donors and reducing the time on the waiting list. The objectives of this study were to compare graft survival, patient survival, rejection risk factors and complications during the first year p ost-transplantation in patients who received an ABOi LD kidney transplant between 2014 and 2019 in our institution, matched according to sex, age and immunological risk with a control group of ABO compatible (ABOc) LD kidney transplants in the same period. Thirteen patients were included in each group. No significant differences were found between ABOi and ABOc in the incidence of delayed graft function (n = 0 vs. 1), bleeding (0 vs. 0), infections (13 vs. 13), cellular rejection (1 vs. 3) and humoral rejection (4 vs. 3) in the first year after transplantation. The rejection rate in ABOi do not seem to be related to blood incompatibility. No risk factors associated with rejection were found. Overall survival of patients was 100% in both groups, and graft survival was 92.3% in ABOi and 100% in ABOc (p = 1). ABOi kidney trans plantation is an adequate feasible option in our environment for those who do not have compatible donors.

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up / Biomarcadores del metabolismo mineral óseo (FGF-23, fetuína-A) y calcificaciones vasculares como herramientas predictivas de muerte cardiovascular de pacientes en diálisis, a 10 años de seguimiento

Abstract Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary stud ies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Resumen Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad car diovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p<0.001). El mejor punto de corte fue de 5 (sensibili dad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up.

Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary studies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad cardiovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p < 0.001). El mejor punto de corte fue de 5 (sensibilidad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Infections in the first year after renal transplant / Infecciones en el primer año post-trasplante renal

Abstract Infections are frequent complications of kidney transplants. We aimed at determining the frequency and type of infections that occur in renal transplant recipients during the early (0-1 month), intermediate (1-6 months) and late (6-12 months) post-transplant period and analyzing the risk factors for infection. To this aim, we conducted a retrospective cohort study on 1-year post-transplant follow-up in two third-level university hospitals in Cordoba city. All consecutive recipients of renal transplants performed between 2009 and 2015 were included, except those with multiple solid organ transplantation and pediatric patients. We included 375 recipients, of which 235 (62.7%) had at least one episode of infection during follow-up. There were 504 episodes of infection, of which 131 (26%) occurred in the early, 272 (53.9%) in the intermediate, and 101 (20.1%) in the late post-transplant period. The most frequent infections in all periods were caused by bacteria (mainly urinary tract infections), and the most frequent viral infection was caused by Cytomegalovirus (mainly in the second and third period). In the multivariate analysis, infection risk factors were: age > 60 years (adjusted odds ratio [aOR] = 1.92; 95% CI = 1.05-3.49), organ transplantation from deceased donor (aOR = 8.19; 95% CI = 2.32-28.9), use of pigtail catheter for urinary tract drainage (aOR = 4.06; 95% CI = 1.27-12.9), and number of days in hospital after transplant (aOR = 1.05; 95% CI = 1.01-1.11). In conclusion, infections in renal transplant recipients represent a very frequent health problem in our hospitals. Understanding the local epidemiology of infection and the potential risk factors for infection acquires utmost importance.

Resumen Las infecciones son complicaciones frecuentes de los trasplantes renales. Los objetivos del estudio fueron determinar la frecuencia y el tipo de infecciones que ocurren en el período post-trasplante temprano (0-1 mes), intermedio (1-6 meses) y tardío (6-12 meses) en nuestro medio y analizar los factores de riesgo de infección. Se realizó un estudio de cohorte retrospectivo que incluyó todos los pacientes con trasplantes renales realizados entre 2009 y 2015 en dos hospitales universitarios de tercer nivel de la ciudad de Córdoba, excluidos los receptores de trasplante simultáneo de múltiples órganos sólidos y los menores de 18 años. Fueron incluidos 375 pacientes, de los cuales 235 (62.7%) tuvieron al menos un episodio de infección. Hubo 504 episodios de infección: 131 (26%) ocurrieron en el período temprano, 272 (53.9%) en el intermedio y 101 (20.1%) en el tardío. La mayoría de las infecciones fueron de origen bacteriano (principalmente del tracto urinario). La mayoría de las infecciones virales ocurrieron en el segundo y el tercer período y Citomegalovirus fue el responsable más frecuente. En el análisis multivariado, los factores de riesgo de infección post-transplante renal fueron: edad > 60 años (odds ratio ajustado [aOR] 1.92; IC95% 1.05-3.49), donante cadavérico (aOR 8.19; IC95% 2.32-28.9), uso de catéter pigtail (aOR 4.06; IC95% 1.27-12.9) y número de días internado postrasplante (aOR 1.05; IC95% 1.01-1.11). En conclusión, confirmamos que las infecciones en pacientes con trasplante renal son muy frecuentes en nuestro medio, por lo cual es importante conocer la epidemiología local y los factores de riesgo.

Infections in the first year after renal transplant.

Infections are frequent complications of kidney transplants. We aimed at determining the frequency and type of infections that occur in renal transplant recipients during the early (0-1 month), intermediate (1-6 months) and late (6-12 months) post-transplant period and analyzing the risk factors for infection. To this aim, we conducted a retrospective cohort study on 1-year post-transplant follow-up in two third-level university hospitals in Cordoba city. All consecutive recipients of renal transplants performed between 2009 and 2015 were included, except those with multiple solid organ transplantation and pediatric patients. We included 375 recipients, of which 235 (62.7%) had at least one episode of infection during follow-up. There were 504 episodes of infection, of which 131 (26%) occurred in the early, 272 (53.9%) in the intermediate, and 101 (20.1%) in the late post-transplant period. The most frequent infections in all periods were caused by bacteria (mainly urinary tract infections), and the most frequent viral infection was caused by Cytomegalovirus (mainly in the second and third period). In the multivariate analysis, infection risk factors were: age > 60 years (adjusted odds ratio [aOR] = 1.92; 95% CI = 1.05-3.49), organ transplantation from deceased donor (aOR = 8.19; 95% CI = 2.32-28.9), use of pigtail catheter for urinary tract drainage (aOR = 4.06; 95% CI = 1.27-12.9), and number of days in hospital after transplant (aOR = 1.05; 95% CI = 1.01-1.11). In conclusion, infections in renal transplant recipients represent a very frequent health problem in our hospitals. Understanding the local epidemiology of infection and the potential risk factors for infection acquires utmost importance.

Las infecciones son complicaciones frecuentes de los trasplantes renales. Los objetivos del estudio fueron determinar la frecuencia y el tipo de infecciones que ocurren en el período post-trasplante temprano (0-1 mes), intermedio (1-6 meses) y tardío (6-12 meses) en nuestro medio y analizar los factores de riesgo de infección. Se realizó un estudio de cohorte retrospectivo que incluyó todos los pacientes con trasplantes renales realizados entre 2009 y 2015 en dos hospitales universitarios de tercer nivel de la ciudad de Córdoba, excluidos los receptores de trasplante simultáneo de múltiples órganos sólidos y los menores de 18 años. Fueron incluidos 375 pacientes, de los cuales 235 (62.7%) tuvieron al menos un episodio de infección. Hubo 504 episodios de infección: 131 (26%) ocurrieron en el período temprano, 272 (53.9%) en el intermedio y 101 (20.1%) en el tardío. La mayoría de las infecciones fueron de origen bacteriano (principalmente del tracto urinario). La mayoría de las infecciones virales ocurrieron en el segundo y el tercer período y Citomegalovirus fue el responsable más frecuente. En el análisis multivariado, los factores de riesgo de infección post-transplante renal fueron: edad > 60 años (odds ratio ajustado [aOR] 1.92; IC95% 1.05-3.49), donante cadavérico (aOR 8.19; IC95% 2.32-28.9), uso de catéter pigtail (aOR 4.06; IC95% 1.27-12.9) y número de días internado postrasplante (aOR 1.05; IC95% 1.01-1.11). En conclusión, confirmamos que las infecciones en pacientes con trasplante renal son muy frecuentes en nuestro medio, por lo cual es importante conocer la epidemiología local y los factores de riesgo.

Renal Transplantation in Patients Older Than 60 Years With High Comorbidity. Is There a Survival Benefit? A Multicenter Study in Argentina.

BACKGROUND: The impact of renal transplantation (RT) in the elderly with many comorbid conditions is a matter of concern. The aim of our study was to assess the impact of RT on the survival of patients older than 60 years compared with those remaining on the waiting list (WL) according to their comorbidities. METHODS: In this multicentric observational retrospective cohort study, we included all patients older than 60 years old admitted on the WL from 01 January 2006 to 31 December 2016. The Charlson comorbidity index (CCI) score was calculated for each patient at inclusion on the WL. Kidney donor risk index was used to assess donor characteristics. RESULTS: One thousand and thirty-six patients were included on the WL of which 371 (36%) received an RT during a median follow-up period of 2.5 (1.4-4.1) years. Patient survival was higher after RT compared to patients remaining on the WL, 87%, 80%, and 72% versus 87%, 55%, and 30% at 1, 3, and 5 years, respectively. After RT survival at 5 years was 37% higher for patients with CCI ≥ 3, and 46% higher in those with CCI < 3, compared with patients remaining on the WL. On univariate and multivariate analysis, patient survival was independently associated with a CCI of ≥3 (hazard ratio 1.62; confidence interval 1.09-2.41; P < 0.02) and the use of calcineurin-based therapy maintenance therapy (hazard ratio 0.53; confidence interval 0.34-0.82; P < 0.004). CONCLUSIONS: Our study showed that RT improved survival in patients older than 60 years even those with high comorbidities. The survival after transplantation was also affected by comorbidities.

[Nephrocalcinosis and proximal tubulopathy in Sjögren's Syndrome.] / Nefrocalcinosis y acidosis tubular renal proximal en síndrome de Sjögren.

Primary Sjögren's syndrome is a systemic and chronic autoimmune disease. Renal involvement may occur in up to 30% of patients. The incidence of tubulopathies ranges from 2.6 to 33%. They are manifested by defects in the urine concentration and hydroelectrolyte alterations, mainly distal tubular acidosis and exceptionally proximal tubular acidosis. These disorders can be associated with nephrocalcinosis and renal lithiasis. We report the case of a patient with primary Sjögren who presented proximal renal tubular acidosis associated with recurrent renal colic due to renal lithiasis and nephrocalcinosis. We highlight the importance of diagnosing renal tubular acidosis in patients with Sjögren's syndrome that present alterations in urinary sediment and electrolyte disorders to avoid nephrocalcinosis and nephrolithiasis. Acidosis correction treatment aims to prevent the progression of the disorder and preserve renal function.

El síndrome de Sjögren primario es una enfermedad autoinmune sistémica de evolución crónica. Puede presentar compromiso renal hasta en un 30% de los pacientes.La incidencia de tubulopatías varía de 2.6 a 33%. Se manifiestan por defectos en la concentración de la orina y alteraciones hidroelectrolíticas, principalmente acidosis tubular distal y de manera excepcional acidosis tubular proximal. Estos trastornos pueden asociarse a Nefrocalcinosis y litiasis renal. Reportamos el caso de una paciente con Sjögren primario que presentó acidosis tubular renal proximal asociada a cólicos renales recurrentes por litiasis renal y nefrocalcinosis. Destacamos la importancia de diagnosticar acidosis tubular renal en pacientes con síndrome de Sjögren que presenten alteraciones en el sedimento urinario y desórdenes electrolíticos para evitar la nefrocalcinosis medular y las nefrolitiasis asociadas. La terapia para la corrección de la acidosis tiene como objetivo evitar la progresión del trastorno y preservar la función renal.

[Renal Transplantation in a patient with Recessive Dystrophic Epidermolysis Bullosa: a case report] / Reporte de caso: Trasplante Renal en un paciente con Epidermolisis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis characterized by abnormalities in the anchoring fibrils which attach the basal cell layer of the epidermis to the underlying structures. A characteristic feature of this disorder is the presence of recurrent blistering or erosions, the result of even minor traction to these tissues. Patients with RDEB frequently develop chronic renal failure, and require renal replacement therapy being a major cause of morbidity and mortality. The role of renal transplantation in these patients is scarcely known. We present the case of an end-stage renal disease patient with RDEB treated by renal transplantation and his follow-up during a period of 83 months after the transplant. In this period, there were very low frequency of serious infections as well as the absence of skin tumors. Renal transplantation could be an alternative to renal replacement therapy in epidermolysis bullosa patients with end-stage renal disease, reducing the comorbidities associated with this treatment.

La epidermolisis bullosa distrófica recesiva (EBDR) es una genodermatosis extremadamente infrecuente, caracterizada por la existencia de alteraciones a nivel de las fibras de anclaje que unen la membrana basal de la epidermis a las estructuras subyacentes. Un elemento característico de esta entidad es la formación recurrente de ampollas en piel y mucosas ante traumatismos mínimos, con posterior cicatrización. Los pacientes con EBRD frecuentemente desarrollan enfermedad renal crónica y requieren de terapia de reemplazo renal, constituyendo una importante causa de morbilidad y mortalidad en estos pacientes. El rol del trasplante renal es poco conocido en este tipo de pacientes.Se presenta el caso de un paciente con enfermedad renal terminal y EBDR que es tratado con trasplante renal y su seguimiento a lo largo de un período de 83 meses luego del trasplante. Durante dicho período se observó una baja frecuencia de intercurrencias infecciosas, así como la ausencia de desarrollo de neoplasias cutáneas. El trasplante renal podría ser una alternativa a la terapia de reemplazo dialítica en los pacientes con epidermolisis bullosa asociada a enfermedad renal terminal, reduciendo las comorbilidades asociadas a las terapias dialíticas.

[Recurrent atypical hemolytic uremic syndrome after renal transplantation: treatment with eculizumab]. / Síndrome urémico hemolítico atípico recurrente post-trasplante renal: tratamiento con eculizumab.

Atypical hemolytic uremic syndrome (aHUS) is a rare entity. It is characterized by a thrombotic microangiopathy (nonimmune hemolytic anemia, thrombocytopenia, and acute renal failure), with a typical histopathology of thickening of capillary and arteriolar walls and an obstructive thrombosis of the vascular lumen. The syndrome is produced by a genetic or acquired deregulation of the alternative pathway of the complement system, with high rates of end stage renal disease, post-transplant recurrence, and high mortality. Mutations associated with factor H, factor B and complement C3 show the worst prognosis. Even though plasma therapy is occasionally useful, eculizumab is effective both for treatment and prevention of post-transplant recurrence. We describe here an adult case of congenital aHUS (C3 mutation) under preventive treatment with eculizumab after renal transplantation, with neither disease recurrence nor drug-related adverse events after a 36-months follow-up.

Síndrome urémico hemolítico atípico recurrente post-trasplante renal: tratamiento con eculizumab / Recurrent atypical hemolytic uremic syndrome after renal transplantation: treatment with eculizumab

El síndrome urémico hemolítico atípico (SUHa) es una entidad rara que se presenta como una microangiopatía trombótica (anemia hemolítica no inmune, trombocitopenia e insuficiencia renal aguda), cuyas lesiones anatomopatológicas típicas son el engrosamiento de las paredes de capilares y arteriolas con trombosis obstructiva del lumen vascular. Se produce por desregulación de la vía alterna del complemento en la superficie celular, debido a causas genéticas o adquiridas, con una alta tasa de mortalidad, enfermedad renal crónica terminal y recurrencia post-trasplante renal. Las mutaciones de peor pronóstico son las asociadas a factor H, factor B y fracción C3 del complemento. La terapia plasmática resulta útil solo en algunos casos, mientras que el uso de eculizumab es altamente eficaz tanto para el tratamiento agudo como para prevenir las recurrencias en el post-trasplante. Comunicamos el caso de una mujer adulta con diagnóstico de SUHa congénito (mutación de C3) en tratamiento preventivo con eculizumab posterior al trasplante renal, sin recurrencia de la enfermedad, ni efectos adversos relacionados al medicamento a los 36 meses de seguimiento post-trasplante.

Atypical hemolytic uremic syndrome (aHUS) is a rare entity. It is characterized by a thrombotic microangiopathy (nonimmune hemolytic anemia, thrombocytopenia, and acute renal failure), with a typical histopathology of thickening of capillary and arteriolar walls and an obstructive thrombosis of the vascular lumen. The syndrome is produced by a genetic or acquired deregulation of the alternative pathway of the complement system, with high rates of end stage renal disease, post-transplant recurrence, and high mortality. Mutations associated with factor H, factor B and complement C3 show the worst prognosis. Even though plasma therapy is occasionally useful, eculizumab is effective both for treatment and prevention of post-transplant recurrence. We describe here an adult case of congenital aHUS (C3 mutation) under preventive treatment with eculizumab after renal transplantation, with neither disease recurrence nor drug-related adverse events after a 36-months follow-up.