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.

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.

[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.

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.

Enfermedad renal crónica y aparición de metástasis posterior a nefrectomía radical y parcial por carcinoma renal de células claras / Chronic kidney disease and clear renal cell carcinoma metastasis following radical or partial nephrectomy

RESUMEN Introducción: El uso de la nefrectomía parcial para el tratamiento del carcinoma de células renales en estadios tempranos se ha convertido en una de las intervenciones preferidas para estos pacientes en la Argentina. Sin embargo, sus resultados en el país a largo plazo aún se desconocen. En este estudio analizamos la progresión a enfermedad renal crónica y aparición de metástasis posterior a nefrectomía parcial y radical, en pacientes con carcinoma de células renales. Material y métodos: Se realizó un estudio de cohorte retrospectivo. Se incluyeron a todos los pacientes con carcinoma renal de células claras en estadio T1 que, entre 2006 y 2012, se sometieron a nefrectomía parcial en nuestro hospital. Se realizó un seguimiento hasta enero del 2018. Resultados: Se incluyeron 32 pacientes (19 con nefrectomía radical y 13 con nefrectomía parcial). Comparado con el grupo de nefrectomía parcial, los individuos sometidos a nefrectomía radical presentaron mayor progresión a enfermedad renal crónica (nefrectomía radical 63,2% vs nefrectomía parcial 15,4%; p=0,007). No existieron diferencias en el tiempo de seguimiento de ambos grupos (nefrectomía radical 69,3 ± 23,8 vs nefrectomía parcial 72,5 ± 26,9 meses; p=0,73). Los sujetos sometidos a nefrectomía radical tuvieron 11 veces mayor riesgo de progresión a enfermedad renal crónica que los de nefrectomía parcial (HR ajustado 11,12, IC95 1,24-99,9; p=0,031) ajustado por los demás factores de riesgo tradicionales. Ningún paciente con estadio T1a presentó metástasis durante todo el seguimiento, independientemente del tipo de cirugía. Conclusión: En nuestro estudio, la nefrectomía parcial preserva mejor la función renal a largo plazo que la nefrectomía radical y tiene un excelente perfil de seguridad oncológico en pacientes con carcinoma de células renales en estadio T1a. La nefrectomía radical fue un factor de riesgo independiente de progresión a enfermedad renal crónica.

ABSTRACT Introduction: Partial nephrectomy to treat early-stage renal cell carcinoma has become one of the surgeries of choice for patients in Argentina. However, long-term results in the country are unknown. In this study, we analyzed the progression to chronic kidney disease and the appearance of metastasis after partial or radical nephrectomy in renal cell carcinoma patients. Methods: A retrospective, cohort study was conducted. We included all patients suffering from T1 stage clear cell renal carcinoma who, between 2006 and 2012, underwent partial nephrectomy in our hospital. Follow-up continued until January 2018. Results: Thirty-two patients were included (19 had undergone radical nephrectomy and 13, partial nephrectomy). Subjects who had radical nephrectomy showed a more rapid progression to chronic kidney disease as compared to the subjects in the partial nephrectomy group (radical nephrectomy 63.2% vs. partial nephrectomy 15.4%; p=0.007). There were no differences in the follow-up period in both groups (radical nephrectomy 69.3% ± 23.8 months vs. partial nephrectomy 72.5 ± 26.9 months; p=0.73). Risk of progression to end-stage chronic kidney disease was 11 times higher for subjects who had undergone radical nephrectomy as compared to subjects who had had partial nephrectomy (adjusted HR 11.12; 95% CI: 1.24-99.9; p=0.031), adjusted by the rest of traditional risk factors. None of the T1a patients had metastasis during follow-up, regardless of the type of surgery. Conclusion: According to the findings of our study, partial nephrectomy preserves long-term renal function better than radical nephrectomy and has an excellent oncologic safety profile in T1a stage renal cell carcinoma patients. Radical nephrectomy was an independent risk factor of progression to chronic kidney disease.

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.

Post-kidney donation glomerular filtration rate measurement and estimation.

BACKGROUND: Long-term consequences associated with kidney donation are controversial. Pre- and post-donation glomerular filtration rates (GFRs) are determinants of renal and cardiovascular risk weighting. In Latin America, there is limited experience in evaluating kidney function using GFR measurement techniques in kidney donors. The MDRD 4-variable and CKD-EPI equations are considered reasonable options. The objective of this study was to evaluate the performance of the MDRD and CKD-EPI equations in post-nephrectomy GFR dynamics in kidney donors. MATERIALS AND METHODS: A prospective cohort study with GFR measurement and estimation in 189 kidney donors who underwent nephrectomy between 2007 and 2016 at the Hospital Privado Universitario de Córdoba [Private University Hospital of Córdoba] in Córdoba, Argentina. GFRs were evaluated before and after nephrectomy by iothalamate clearance determined by HPLC and by the MDRD and CKD-EPI equations for estimating GFR. Two groups were formed for this study: Group 1 (n=107), with an evaluation time subsequent to GFR stabilization (3 months) of up to 5 years, and Group 2 (n=82), with an evaluation time of 5-10 years following donation. Measured GFR (mGFR) was assessed by iothalamate clearance determined by HPLC. RESULTS: Renal compensation values were 61.9% (52.0%-71.1%) and 75.6% (64.9%-84.4%) for Group 1 (n=107) and Group 2 (n=82), respectively. MDRD underestimated the GFR in 3.2% (90ml/min/1.73m2) and 38.6% (60ml/min/1.73m2) compared to the mGFR, and CKD-EPI underestimated the GFR in 2.6% (90ml/min/1.73m2) and 13.8% (60ml/min/1.73m2). Diagnostic performance was evaluated with a ROC curve (mGFR<60ml/min/1.73m2) for MDRD (ABC=0.66; CI: 0.59-0.73; sensitivity: 98.7%; specificity: 63.3%) and for CKD-EPI (ABC=0.79 CI: 0.73-0.85; sensitivity: 96.9%; specificity: 76.4%. Estimated GFR (eGFR) showed poor performance for estimating the glomerular filtration rate in the post-nephrectomy follow-up of donors over 50 years of age. CONCLUSIONS: Equations for estimating GFRs showed poor performance for long-term follow-up of post-nephrectomy GFRs. Measuring GFRs to determine kidney function is recommended in the screening and follow-up of some donors under the current selection criteria.

Post-kidney donation glomerular filtration rate measurement and estimation. / Medición y estimación del filtrado glomerular posdonación renal.

BACKGROUND: Long-term consequences associated with kidney donation are controversial. Pre- and post-donation glomerular filtration rates (GFRs) are determinants of renal and cardiovascular risk weighting. In Latin America, there is limited experience in evaluating kidney function using GFR measurement techniques in kidney donors. The MDRD 4-variable and CKD-EPI equations are considered reasonable options. The objective of this study was to evaluate the performance of the MDRD and CKD-EPI equations in post-nephrectomy GFR dynamics in kidney donors. MATERIALS AND METHODS: A prospective cohort study with GFR measurement and estimation in 189 kidney donors who underwent nephrectomy between 2007 and 2016 at the Hospital Privado Universitario de Córdoba [Private University Hospital of Córdoba] in Córdoba, Argentina. GFRs were evaluated before and after nephrectomy by iothalamate clearance determined by HPLC and by the MDRD and CKD-EPI equations for estimating GFR. Two groups were formed for this study: Group 1 (n=107), with an evaluation time subsequent to GFR stabilization (3 months) of up to 5 years, and Group 2 (n=82), with an evaluation time of 5-10 years following donation. Measured GFR (mGFR) was assessed by iothalamate clearance determined by HPLC. RESULTS: Renal compensation values were 61.9% (52.0%-71.1%) and 75.6% (64.9%-84.4%) for Group 1 (n=107) and Group 2 (n=82), respectively. MDRD underestimated the GFR in 3.2% (90ml/min/1.73m2) and 38.6% (60ml/min/1.73m2) compared to the mGFR, and CKD-EPI underestimated the GFR in 2.6% (90ml/min/1.73 m2) and 13.8% (60ml/min/1.73 m2). Diagnostic performance was evaluated with a ROC curve (mGFR<60ml/min/1.73 m2) for MDRD (ABC=0.66; CI: 0.59-0.73; sensitivity: 98.7%; specificity: 63.3%) and for CKD-EPI (ABC=0.79 CI: 0.73-0.85; sensitivity: 96.9%; specificity: 76.4%. Estimated GFR (eGFR) showed poor performance for estimating the glomerular filtration rate in the post-nephrectomy follow-up of donors over 50 years of age. CONCLUSIONS: Equations for estimating GFRs showed poor performance for long-term follow-up of post-nephrectomy GFRs. Measuring GFRs to determine kidney function is recommended in the screening and follow-up of some donors under the current selection criteria.

[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.

Peritonitis en diálisis peritoneal. Epidemiología, factores de riesgo, incorporación del BACTECÕ a la recolección del cultivo tradicional y mortalidad a largo plazo / Peritonitis in peritoneal dialysis. Epidemiology, risk factors, inclusion of BACTECÕ in traditional culture systems, and long-term mortality

INTRODUCCIÓN: La peritonitis es la principal complicación en los pacientes en diálisis peritoneal (DP), con repercusión en su morbi-mortalidad. El objetivo de este estudio fue analizar la epidemiología, factores de riesgo, incorporación del BACTEC y mortalidad relacionada a peritonitis en DP. MATERIAL Y MÉTODOS: Estudio de cohorte retrospectivo. Se incluyeron todos los pacientes que iniciaron DP entre 1992 y 2017, en el Hospital Privado Universitario de Córdoba. RESULTADOS: En total se analizaron 159 pacientes, 63 (39.62%), tuvo por lo menos un episodio de peritonitis y 96 (60.38%), ninguno. La tasa global de peritonitis fue de 0.37 episodios/paciente-año. Los factores de riesgo para peritonitis fueron: antecedente de Hemodiálisis previo a DP (OR=3.18, IC95%=1.41-7.14; p=0.0051) e hipoalbuminemia(OR=3.10, IC95%=1.36-7.06; p=0.0071). La incorporación del BACTEC incrementó el porcentaje de cultivos positivos (de 73.55% a 96.55%; p=0.0076). Los aislamientos más frecuentes fueron: SAMS (23.66%) y BGN (20,61%). Existieron diferencias entre el periodo 1992-2006 y 2006-2017 en aislamientos de Candida (1.49% y 9.38%, p=0.0448) y el grupo otras bacterias (1.49% y 9.38%, p=0.0448). Los pacientes con peritonitis tuvieron mayor mortalidad (55.56% contra 38.58%, p=0.0480), aunque en el análisis multivariado, ésta no fue un factor de riesgo independiente de mortalidad. CONCLUSIÓN: Los factores de riesgo para peritonitis fueron haber recibido hemodiálisis previa a DP e hipoalbuminemia. La incorporación del BACTEC incrementó el porcentaje de cultivos positivos. Después del 2006 existió un incremento de aislamientos de cándidas y del grupo otras bacterias. La peritonitis no fue un factor de riesgo independiente de mortalidad a largo plazo

INTRODUCTION: Peritonitis is the most common complication in peritoneal dialysis (PD), with an effect on morbidity and mortality. The aim of this study was to analyze epidemiology, risk factors, implementation of the BACTEC™ blood culture system and mortality of peritoneal dialysis-associated peritonitis. METHODS: In this retrospective, cohort study, all the patients who started PD between 1992 and 2017 at Hospital Privado Universitario de Córdoba (Córdoba Private Medical College Hospital) were included. RESULTS: The total number of patients was 159, 63 (39.62%) of which had suffered from peritonitis at least once and 96 (60.38%) had never had it. The global peritonitis rate was 0.37 episodes per patient-year. The risk factors for peritonitis were the following: a history of hemodialysis before PD (OR=3.18; CI 95%=1.41-7.14; p=0.0051) and hypoalbuminemia (OR=3.10; CI 95%=1.36-7.06; p=0.0071). The implementation of the BACTEC™ system increased the percentage of positive blood cultures (from 73.55% to 96.55%; p=0.0076). The most frequent isolates were MSSA (23.66%) and GNB (20.61%). Differences were found between the 1992-2006 and 2006-2017 periods in the Candida isolates (1.49% and 9.38%; p=0.0448) and the "other bacteria" group (1.49% and 9.38%; p=0.0448). Although peritonitis patients showed a higher mortality rate (55.56% versus 38.58%; p=0.0480), the multivariate analysis revealed that this condition was not a mortality independent risk factor. CONCLUSION: The risk factors for peritonitis were hemodialysis prior to PD and hypoalbuminemia. The use of the BACTEC™ system increased the percentage of positive blood cultures. After 2006 the number of isolates from the Candida and the "other bacteria" groups was higher. Peritonitis was not a long-term mortality independent risk factor

[Inadequate doses of hemodialysis. Predisposing factors, causes and prevention]. / Dosis de hemodiálisis subóptima. Factores predisponentes, causas y prevención.

Patients receiving sub-optimal dose of hemodialysis have increased morbidity and mortality. The objectives of this study were to identify predisposing factors and causes of inadequate dialysis, and to design a practical algorithm for the management of these patients. A cross-sectional study was conducted. Ninety patients in chronic hemodialysis at Hospital Privado Universitario de Córdoba were included, during September 2015. Twenty two received sub-optimal dose of hemodialysis. Those with urea distribution volume (V) greater than 40 l (72 kg body weight approximately) are 11 times more likely (OR = 11.6; CI 95% = 3.2 to 51.7, p < 0.0001) to receive an inadequate dose of hemodialysis, than those with a smaller V. This situation is more frequent in men (OR = 3.5; 95% CI 1.01-15.8; p = 0.0292). V greater than 40 l was the only independent predictor of sub-dialysis in the multivariate analysis (OR = 10.3; 95% CI 2.8-37; p < 0.0004). The main cause of suboptimal dialysis was receiving a lower blood flow (Qb) than the prescribed (336.4 ± 45.8 ml/min vs. 402.3 ± 28.8 ml/min respectively, p < 0.0001) (n = 18). Other causes were identified: shorter duration of the session (n = 2), vascular access recirculation (n = 1), and error in the samples (n = 1). In conclusion, the only independent predisposing factor found in this study for sub-optimal dialysis is V greater than 40 l. The main cause was receiving a slower Qb than prescribed. From these findings, an algorithm for the management of these patients was developed.

Dosis de hemodiálisis sub-óptima: Factores predisponentes, causas y prevención / Inadequate doses of hemodialysis. Predisposing factors, causes and prevention

Los pacientes que reciben dosis sub-óptima de hemodiálisis tienen mayor morbimortalidad. El objetivo del trabajo fue identificar los factores predisponentes y las principales causas de diálisis inadecuada y diseñar un algoritmo para aplicar en estos casos. Se realizó un estudio de corte transversal. Se incluyeron 90 pacientes en hemodiálisis crónica, en el Hospital Privado Universitario de Córdoba, en septiembre 2015. Veintidós recibieron una dosis sub-óptima de hemodiálisis. Aquellos con un volumen de distribución de urea (V) mayor a 40 l (72 kg de peso corporal aproximadamente), tienen 11 veces mayores posibilidades (OR = 11.6; IC95% = 3.2-51.7, p < 0.0001) de recibir una dosis inadecuada de hemodiálisis que los que tienen un V menor a esa cifra; y los hombres 3 veces más probabilidad que las mujeres (OR = 3.5; IC95% 1.0-15.8; p = 0.0292). El V mayor a 40 l fue el único factor independiente predictor de sub-diálisis en el análisis multivariado (OR = 10.3; IC95% 2.8-37; p = 0.0004). La principal causa de diálisis sub-óptima fue recibir un flujo sanguíneo (Qb) menor al prescripto (336.4 ± 45.8 vs. 402.3 ± 28.8 ml/min, respectivamente, p < 0.0001) (n = 18). Otras causas fueron: menor duración de la sesión (n = 2), recirculación del acceso vascular (n = 1) y error en las muestras (n = 1). En conclusión, el único factor independiente predisponente de sub-diálisis fue el V mayor a 40 l. La principal causa de diálisis inadecuada fue recibir un Qb menor al prescripto. A partir de estos hallazgos, se desarrolla un algoritmo para aplicar en estos casos.

Patients receiving sub-optimal dose of hemodialysis have increased morbidity and mortality. The objectives of this study were to identify predisposing factors and causes of inadequate dialysis, and to design a practical algorithm for the management of these patients. A cross-sectional study was conducted. Ninety patients in chronic hemodialysis at Hospital Privado Universitario de Córdoba were included, during September 2015. Twenty two received sub-optimal dose of hemodialysis. Those with urea distribution volume (V) greater than 40 l (72 kg body weight approximately) are 11 times more likely (OR = 11.6; CI 95% = 3.2 to 51.7, p < 0.0001) to receive an inadequate dose of hemodialysis, than those with a smaller V. This situation is more frequent in men (OR = 3.5; 95% CI 1.01-15.8; p = 0.0292). V greater than 40 l was the only independent predictor of sub-dialysis in the multivariate analysis (OR = 10.3; 95% CI 2.8-37; p < 0.0004). The main cause of suboptimal dialysis was receiving a lower blood flow (Qb) than the prescribed (336.4 ± 45.8 ml/min vs. 402.3 ± 28.8 ml/min respectively, p < 0.0001) (n = 18). Other causes were identified: shorter duration of the session (n = 2), vascular access recirculation (n = 1), and error in the samples (n = 1). In conclusion, the only independent predisposing factor found in this study for sub-optimal dialysis is V greater than 40 l. The main cause was receiving a slower Qb than prescribed. From these findings, an algorithm for the management of these patients was developed.