Glomerulopatía por invaginación podocítica; reporte del primer caso en Latinoamérica y revisión de la literatura / Podocyte infolding glomerulopathy; report of the first case in Latin America and review of the literatura

ANTECEDENTES: La glomerulopatía por invaginación podocítica (GIP) es una enfermedad de origen incierto, frecuentemente asociada a enfermedades autoinmunes, de la que se desconoce el tratamiento específico y su evolución. Caracterizada por engrosamiento de paredes capilares por la presencia de burbujas no argirofílicas intramembanosas similares a las encontradas en la glomerulopatía membranosa, pero sin depósitos de inmunocomplejos electrodensos en la ultraestructura, donde se observan microesferas traslúcidas generadas por invaginación del citoplasma podocítico dentro de las membranas basales. OBJETIVOS: Generalmente descrito en pacientes jóvenes de sexo femenino. Hasta la fecha, han sido reportados escasos casos en pacientes de origen asiático. Nuestro caso constituiría el primer reporte en paciente latinoamericano de raza blanca. MÉTODOS: Mujer de 38 años con LES. En el año 2014 presentó síndrome nefrótico tratado empíricamente con corticoides (CO) y ciclofosfamida intravenosa (CF) con buena respuesta. Presenta recaída en abril del 2015 con función renal normal y sin actividad lúpica extrarrenal, por lo que es derivada a nuestro hospital para ser biopsiada. RESULTADOS: La biopsia informó esclerosis glomerular focal y segmentaria sin depósitos de inmunocomplejos en la inmunofluorescencia, pero con técnica de metenamina plata se detectaron en las paredes capilares, espacios claros acompañados de marcadas alteraciones podocíticas. Al microscopio electrónico, se observaron agregados de ultraestructuras microvesiculares y cilíndricas unidas a las membranas sin evidencia de depósitos densos y borramiento difuso de pies pedicelares, confirmando el diagnóstico sospechado. CONCLUSIONES: Reportamos el primer caso de lo que puede ser considerada, una nueva entidad patológica glomerular, en una paciente de raza blanca latinoamericana, cuya evolución y terapéutica aún se desconocen

BACKGROUND: Podocyte infolding glomerulopathy (PIG) is a condition of uncertain origin, frequently associated with autoimmune diseases. Its specific treatment and clinical course are unknown. It is characterised by thickening of the capillary walls due to the presence of non-argyrophilic intramembranous bubbles similar to those found in membranous glomerulopathy, but without electron-dense deposits of immune complexes in the ultrastructure, where translucent microspheres generated by invagination of the podocyte cytoplasm into the basement membranes are observed. OBJECTIVES: Generally reported in young females patients. To date, few cases in Asian patients have been reported. Our case is the first to be reported in a Latin American Caucasian patient. METHODS: A 38-year-old woman with SLE. In 2014 she presented with nephrotic syndrome empirically treated with corticosteroids (CO) and intravenous cyclophosphamide with good response. She had a relapse in April 2015 with normal renal function and no extrarenal lupus activity, so she was referred to our hospital to be biopsied. RESULTS: The biopsy reported focal segmental glomerular sclerosis without deposits of immune complexes in the immunofluorescence. However, methenamine silver staining revealed clear spaces in the capillary walls accompanied by marked podocyte alterations. On electron microscope study, numerous aggregates of microvesicular and cylindrical ultrastructures bound to the membranes were observed, without evidence of dense deposits, and diffuse effacement of pedicel foot processes, confirming the suspected diagnosis. CONCLUSIONS: This is the first reported case of what can be considered a new pathological glomerular entity in a Latin American Caucasian patient, whose clinical course and therapy are still unknown

Podocyte infolding glomerulopathy; report of the first case in Latin America and review of the literature. / Glomerulopatía por invaginación podocítica; reporte del primer caso en Latinoamérica y revisión de la literatura.

BACKGROUND: Podocyte infolding glomerulopathy (PIG) is a condition of uncertain origin, frequently associated with autoimmune diseases. Its specific treatment and clinical course are unknown. It is characterised by thickening of the capillary walls due to the presence of non-argyrophilic intramembranous bubbles similar to those found in membranous glomerulopathy, but without electron-dense deposits of immune complexes in the ultrastructure, where translucent microspheres generated by invagination of the podocyte cytoplasm into the basement membranes are observed. OBJECTIVES: Generally reported in young females patients. To date, few cases in Asian patients have been reported. Our case is the first to be reported in a Latin American Caucasian patient. METHODS: A 38-year-old woman with SLE. In 2014 she presented with nephrotic syndrome empirically treated with corticosteroids (CO) and intravenous cyclophosphamide with good response. She had a relapse in April 2015 with normal renal function and no extrarenal lupus activity, so she was referred to our hospital to be biopsied. RESULTS: The biopsy reported focal segmental glomerular sclerosis without deposits of immune complexes in the immunofluorescence. However, methenamine silver staining revealed clear spaces in the capillary walls accompanied by marked podocyte alterations. On electron microscope study, numerous aggregates of microvesicular and cylindrical ultrastructures bound to the membranes were observed, without evidence of dense deposits, and diffuse effacement of pedicel foot processes, confirming the suspected diagnosis. CONCLUSIONS: This is the first reported case of what can be considered a new pathological glomerular entity in a Latin American Caucasian patient, whose clinical course and therapy are still unknown.

Manejo de la Hiperuricemia en Pacientes en Argentina. Una Encuesta Mediante Cuestionario / Hyperuricemia Management in Patients from Argentina. A Questionnaire Survey

Resumen Introducción: Durante muchos años el ácido úrico se ha considerado como un producto metabólico inerte del metabolismo de las purinas, sin embargo, ha sido recientemente asociado a una serie de estados de enfermedad crónica. No hay hallazgos concluyentes disponibles en la actualidad para tomar una conducta activa clara respecto al tratamiento de ácido úrico sérico, y cuál sería su objetivo terapéutico. Material y métodos: Debido a esta controversia, se decidió llevar a cabo una encuesta para evaluar cuáles son las decisiones que se toman en este contexto, en el ámbito médico de la Argentina. Se consultó en qué pacientes se evaluaba en forma rutinaria el ácido úrico sérico, resultando en un 53.2% de todos los pacientes, sin diferenciar patologías, y un 11.5% refirió que no lo realiza rutinariamente. Con respecto al tratamiento sólo refirieron tratarlo con enfermedad renal un 62.5%; con diabetes 61.7%; con síndrome metabólico 60.4%; con enfermedad cardiovascular un 50.3%; con gota, cálculos renales o dolor articular, un 91.3%, 74% y 36.1% respectivamente. Resultados: Los datos de la encuesta confirman la falta de evidencia en el criterio para la selección de pacientes, a los fines de evaluar los niveles de ácido úrico sérico y su tratamiento. Conclusiones: De esta forma, se concluye que prima la necesidad de realizar estudios prospectivos y randomizados de las patologías con alta incidencia de uricemia elevada, para poder determinar normativas que orienten una conducta a los especialistas según los resultados obtenidos, y que dicha decisión no esté basada solo en la opinión de los expertos.

Abstract Introduction: For many years, uric acid was considered to be an inert product of purine metabolism; however, it has recently been associated with a number of chronic diseases. Nowadays, there are no conclusive findings available regarding a clear action plan to treat serum uric acid or which specific therapeutic goals it would have. Methods: Given this controversy, a survey was conducted in order to evaluate which decisions are taken regarding this situation within the Argentinian medical community. The question was in which cases serum uric acid was routinely assessed and the result was 53.2% no matter the pathology; 11,5% of physicians did not assess it routinely. Regarding its treatment, 62.5% of them reported to have treated it as part of kidney disease; 61.7 % as part of diabetes; 60.4% as part of metabolic syndrome; 50.3% as part of cardiovascular disease; 91.3 % as part of gout; 74% as part of renal stones, and 36.1% as part of joint pain. Results: The data collected by means of the survey show a lack of evidence for establishing the patient selection criteria when evaluating levels of serum uric acid and its treatment. Conclusions: Therefore, it is concluded that it is necessary to conduct prospective and randomized studies of conditions with a high incidence of elevated uricemia in order to develop guidelines for specialists according to results; this decision should not be based on experts' opinion alone.

Co-Inheritance of Autosomal Dominant Polycystic Kidney Disease and Naevoid Basal Cell Carcinoma Syndrome: Effects on Renal Progression.

The calcium signalling and hedgehog (HH) signalling pathways operate in the primary cilium. Abnormalities in these pathways cause autosomal dominant polycystic kidney disease (ADPKD) and naevoid basal cell carcinoma syndrome (NBCCS) respectively. Several reports have proposed that hyperactivation of the HH pathway in animal models of polycystic kidney disease affects normal renal development and renal cyst phenotype. A family with 2 cases (a proband and her sister) of ADPKD and NBCCS coinheritance led us to investigate whether interactions may be present in the 2 pathways. The effect of HH pathway hyperactivation (due to c.573C>G mutation on PTCH1 gene that cause NBCCS) on renal ADPKD progression in the proband was compared to 18 age- and sex-matched ADPKD patients in a 9-year, prospective, follow-up study. Blood pressure, total kidney volume, estimated glomerular filtration rate, plasma copeptin, urine excretion of albumin, total protein and monocyte chemoattractant protein-1 (MCP-1) were analysed. Data for the sibling was not available. In the ADPKD group, blood pressure and estimated glomerular filtration rate were within normal values, and total kidney volume and MCP-1 increased (p < 0.01) throughout the study. In comparison, during the 9-year follow-up, the proband showed persistent hypertension (from 125/85 to 140/95 mm Hg), low total kidney volume (75 and 61% of median ADPKD), and a ninefold increase in urine MCP-1. We found no differences in urine excretion of albumin or plasma copeptin values. These results suggest that HH hyperactivation may play a minimal role in ADPKD progression. These observations can help to clarify the clinical impact of affected pathways in renal development and cystogenesis in humans.

Tratamiento de las hiperuricemias / Treatment of hyperuricemias

El manejo de la hiperuricemia (HU) asintomática y los trastornos asociados al ácido úrico (AU) difieren de acuerdo al contexto clínico del paciente y/o al estadio de la enfermedad renal (ER). Existe uma asociación entre los niveles de AU y la hipertensión arterial (HTA),(1) la edad, la enfermedad cardiovascular (ECV) y ER.(2) La causalidad de esta relación es aún hoy un tema controversial,(3) así como el rol del AU en la iniciación, progresión y desarrollo de la ER(4-5) y en el trasplante.(6) Las modalidades farmacológicas empleadas en el tratamiento de las alteraciones del AU pueden clasificarse según su efecto antiinflamatorio en el ataque agudo, profiláctico para evitar recurrencia o considerar las drogas hipouricemiantes para prevenir o revertir las complicaciones generadas por depósitos de cristales de urato en articulaciones (artropatía gotosa), tracto urinario (litiasis, nefritis tubulointersticial) y tejidos (tofos). Es vital que los valores plasmáticos de uratos sean mantenidos por debajo de 6.8 mg/dl, un nivel por encima del cual podría precipitar; niveles bajos se relacionan a mejor evolución en pacientes con gota, incluyendo menores ataques, mayor rapidez en reducción del tamaño de los tofos y desaparición de cristales de urato monosódico en líquido sinovial

Asymptomatic hyperuricemia (AH) and other disorders associated with uric acid (UA) are treated differently according to the patient's clinical state and to the stage of renal disease (RD). There is a relation between UA level, high blood pressure (HBP), age, cardiovascular disease (CVD) and RD. The causation of this relation is still controversial, as well as the role of UA in the onset, progression and development of RD and transplantation. The different drugs used for UA disorders therapy may be classified according to their anti-inflammatory effect in an acute episode; their prophylaxis to avoid recurrence, and their action to prevent or reverse complications caused by urate crystal depositions in the joints (gouty arthritis), in the urinary tract (lithiasis, tubulointerstitial nephritis) and in the tissues (tophi). It is vital to keep plasma urate levels below 6.8 mg/dL; lower concentrations may be associated with better progress in gouty patients: fewer episodes, faster reduction of tophus size and absence of monosodium urate crystals in synovial fluid