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BACKGROUND: Up to 60% of pediatric renal transplant recipients with end-stage renal disease due to primary focal and segmental glomerulosclerosis (FSGS) may develop recurrent disease. Such recurrence is associated with poor prognosis if no remission is achieved. We report a single center experience with a protocol based on plasmapheresis and increased immunosuppression that resulted in a high long-lived remission rate. METHODS: This retrospective cohort study included consecutive pediatric renal transplant patients with recurrent FSGS treated with a standardized protocol using plasmapheresis and cyclophosphamide to supplement usual post-transplant immunosuppression with calcineurin inhibitors and steroids. Relapse was defined as urinary protein/creatinine ratio > 1.0 g/g and remission as < 0.5 g/g. RESULTS: Seventeen patients with FSGS recurrence post-transplant were treated. All had therapy resistant FSGS in native kidneys and had been on dialysis from 4 to 10 years. Of the 17, one died perioperatively from a pulmonary thromboembolism. Fifteen others achieved a complete remission within 3 months of treatment for FSGS recurrence. After a median follow-up period of 4 years, there were no recurrences of significant proteinuria. One patient achieved remission with rituximab. CONCLUSION: The addition of plasmapheresis and cyclophosphamide to a calcineurin- and steroid-based immunosuppression regime was highly successful in inducing high remission rates with recurrent FSGS. Prospective trials are needed to evaluate further the efficacy of increased immunosuppression along with plasmapheresis in this setting.
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Glomeruloesclerosis Focal y Segmentaria , Niño , Glomeruloesclerosis Focal y Segmentaria/terapia , Humanos , Terapia de Inmunosupresión , Plasmaféresis/métodos , Estudios Prospectivos , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Vizcarra-Vizcarra, Cristhian A., Eduardo Chávez-Velázquez, Carmen Asato-Higa, and Abdías Hurtado-Aréstegui. Treatment of focal and segmental glomerulosclerosis secondary to high altitude polycythemia with acetazolamide. High Alt Med Biol. 23:286-290, 2022.-Focal segmental glomerulosclerosis (FSGS) is a morphological pattern, caused by glomerular injury and is the leading cause of nephrotic syndrome in adults. We present the case of a 59-year-old female patient, resident of a high-altitude city (3,824 m), who had polycythemia and nephrotic syndrome. A renal biopsy was performed, and the findings were compatible with FSGS. The patient received phlebotomy 500 ml three times, which reduced, partially, the hemoglobin concentration. However, she had refractory proteinuria, despite the use of enalapril and spironolactone. We observed that proteinuria worsened with the increase in hemoglobin levels. So, she was treated with acetazolamide 250 mg bid for 4 months, which reduced proteinuria and hemoglobin. During the coronavirus disease 2019 (COVID-19) pandemic, the patient did not take acetazolamide and again, she had an increase in hemoglobin and proteinuria levels. We conclude that acetazolamide may be an effective treatment in FSGS due to high altitude polycythemia.
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Mal de Altura , COVID-19 , Glomeruloesclerosis Focal y Segmentaria , Síndrome Nefrótico , Policitemia , Acetazolamida/uso terapéutico , Adulto , Altitud , Mal de Altura/complicaciones , Mal de Altura/tratamiento farmacológico , Femenino , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Glomeruloesclerosis Focal y Segmentaria/etiología , Humanos , Persona de Mediana Edad , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/patología , Policitemia/complicaciones , Policitemia/etiología , Proteinuria/etiologíaRESUMEN
ABSTRACT Background: Primary focal and segmental glomerulosclerosis progresses to end-stage renal disease in every other patient, and therefore determinants of its long-term outcome have been extensively studied. Immediate response to treatment has been regarded as a positive prognostic predictor and short-term manifestation of the disease could affect its determinants. Therefore, we have sought to assess the early clinical course of primary adult focal and segmental glomerulosclerosis and analyze its prognostic factors. Methods: We have retrospectively assessed clinical course of primary focal and segmental glomerulosclerosis ("not otherwise specified" histological variant) in 84 adults. Renal function was expressed as serum creatinine concentration and equilibrated glomerular filtration rate (MDRD equation). Proteinuria was expressed as protein to urinary creatinine ratio, assessed in the morning voiding sample. The evaluation of these parameters was performed every 3 months after diagnosis. Statistical analysis was achieved using package Statistica. Results: As result of treatment, complete remission of proteinuria, was attained in 30 subjects (35.7%), partial remission in 37 persons (44%), whereas in 17 patients protein excretion rate remained unchanged (20.2%). The severity of glomerular injury, at initial presentation of the disease, correlated with its early (12 months) outcome: patients attaining early complete remission have had the lowest initial proteinuria, higher serum albumin and total protein concentrations than those who have failed to achieve remission. Pharmacotherapy with prednisone, but not with calcineurin inhibitors or mycophenolate mofetil was demonstrated to significantly affect achievement of remission. Conclusions: Early remission of proteinuria in response to treatment is feasible in 44% of patients with primary focal and segmental glomerulosclerosis, it is best achieved in subjects presenting with mild glomerular injury, and in patients treated with prednisone. Higher serum albumin and total protein concentrations predict better response to induction of remission.
RESUMEN Antecedentes: La glomeruloesclerosis focal y segmentaria se convierteennefropatía terminal enuno de cada dos pacientes, por lo que losfactoresdeterminantes de susdesenlaces a largo plazohansidoobjeto de muchosestudios. La respuestainmediata al tratamiento se considera un factor pronóstico favorable, y las manifestaciones a cortoplazo de la enfermedadpuedenafectarlosfactoresdeterminantes. Portodoello, hemosbuscadoevaluar la evoluciónclínicatemprana de la glomeruloesclerosis focal y segmentariaprimaria, y analizarsusfactorespronósticos. Material y métodos: Hemosrealizado un estudioretrospectivo para evaluar la evoluciónclínica de la glomeruloesclerosis focal y segmentariaprimaria (variantehistológica "sin otraespecificación") en 84 pacientesadultos. Se evaluó la función renal a través de la creatininasérica y filtrado glomerular equilibradocalculadomediante la ecuación MDRD. La proteinuria se expresócomorelaciónproteína/creatininaurinaria, evaluadaen la muestramiccionalmatutina. La evaluación de estosparámetros se realizócada 3 mesesdespués del diagnóstico. El análisisestadístico se logróutilizando el paqueteStatistica. Resultados: Como resultado del tratamiento, se obtuvounaremisióncompleta de la proteinuria en 30 sujetos (35,7%), unaremisiónparcialen 37 personas (44%), mientras que, en 17 pacientes, la tasa de excreción de proteínas se mantuvo sin cambios (20,2%). En la presentacióninicial de la enfermedad, la gravedad de la lesión glomerular se correlacionó con suresultadotemprano (12 meses): lospacientes que lograronunaremisióncompletatempranamostraronlosnivelesmásbajos de proteinuria inicial, y concentracionesmásaltas de albúminasérica y proteínastotales que aquellos que no alcanzaron la remisión. Se demostró que la farmacoterapia con prednisona -pero no con inhibidores de calcineurina o micofenolato de mofetilo- condiciona de forma significativa el logro de la remisión. Conclusiones: La remisióntemprana de la proteinuria enrespuesta al tratamientoesfactibleen el 44% de lospacientes con glomeruloesclerosis focal y segmentariaprimaria; se obtienenmejoresresultadosensujetos que presentanunalesión glomerular leve y enpacientestratados con prednisona. Las concentracionesmásaltas de albúminasérica y proteínastotalespredicenunamejorrespuesta para inducir la remisión.
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Resumen Presentamos el caso de una paciente de 35 años, que cursó su última gestación con preeclampsia y falla renal aguda oligúrica, requiriendo ser intervenida mediante cesárea de emergencia y apoyo dialítico con un total de 16 sesiones de hemodiálisis, evolución favorable. Después de cuatro meses de alta desarrolló síndrome nefrótico, por lo que se la hospitalizó para un mejor manejo y una exhaustiva investigación de la etiología. Se tomaron medidas de soporte sin nuevo requerimiento de terapia de reemplazo renal, se descartó secundarismo y se le realizó biopsia renal. El estudio anatomopatológico concluyó que se trataba de una glomeruloesclerosis focal y segmentaria, en su variante perihiliar. La paciente evolucionó favorablemente durante su hospitalización y al darle el alta se la citó para continuar manejo por consulta externa. La aparición de síndrome nefrótico meses después del embarazo nos debe sugerir la presencia de una glomerulopatía subyacente o una glomerulopatía de novo.
Abstract We describe the case of a 35-year-old patient, who experienced preeclampsia and oliguric acute renal injury during her last pregnancy, requiring intervention by emergency cesarean section and dialysis support with a total of 16 hemodialysis sessions; she responded favorably. Four months after discharge, she developed nephrotic syndrome, so she was hospitalized for better management and a thorough etiologic research. Support measures were taken with no need for renal replacement therapy; secondary lesions were ruled out and a renal biopsy was performed. The pathological study concluded that it was a focal segmental glomerulosclerosis, in its perihilar variant. The patient responded favorably during her hospitalization and when discharged, she was summoned to continue management by external consultation. The appearance of nephrotic syndrome months after pregnancy may suggest the presence of an underlying glomerulopathy or de novo glomerulopathy.
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Focal and segmental glomerulosclerosis (FSGS) is one of the most important renal diseases related to end-stage renal failure. Bradykinin has been implicated in the pathogenesis of renal inflammation, whereas the role of its receptor 2 (B2RBK; also known as BDKRB2) in FSGS has not been studied. FSGS was induced in wild-type and B2RBK-knockout mice by a single intravenous injection of Adriamycin (ADM). In order to further modulate the kinin receptors, the animals were also treated with the B2RBK antagonist HOE-140 and the B1RBK antagonist DALBK. Here, we show that the blockage of B2RBK with HOE-140 protects mice from the development of FSGS, including podocyte foot process effacement and the re-establishment of slit-diaphragm-related proteins. However, B2RBK-knockout mice were not protected from FSGS. These opposite results were due to B1RBK expression. B1RBK was upregulated after the injection of ADM and this upregulation was exacerbated in B2RBK-knockout animals. Furthermore, treatment with HOE-140 downregulated the B1RBK receptor. The blockage of B1RBK in B2RBK-knockout animals promoted FSGS regression, with a less-inflammatory phenotype. These results indicate a deleterious role of both kinin receptors in an FSGS model and suggest a possible cross-talk between them in the progression of disease.
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Glomeruloesclerosis Focal y Segmentaria/patología , Receptores de Bradiquinina/fisiología , Animales , Bradiquinina/análogos & derivados , Bradiquinina/farmacología , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Ratones , Ratones Noqueados , Receptores de Bradiquinina/efectos de los fármacos , Receptores de Bradiquinina/genéticaRESUMEN
Primary focal and segmental glomerulosclerosis (FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.
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Focal and segmental glomerulosclerosis is classified as either primary or secondary. We present a patient with a past history of biopsy-proven focal and segmental glomerulosclerosis. Despite initial response to dual blockade and steroids, proteinuria raised when steroids were decreased. After the patient was restarted on steroids, proteinuria did not improve. Another biopsy confirmed the previous diagnosis but suggested Fabry's disease, later confirmed by electron microscopy, α-galactosidase A serum and leukocyte deficiency as well as genetic studies. Proteinuria decreased when agalsidase ß was prescribed in parallel with steroid tapering, increased with steroid discontinuation and improved with meprednisone administration. This report highlights the relevance of electron microscopy in kidney biopsy. In glomerulosclerosis, despite specific treatment, secondary hemodynamic and immunologic pathways may contribute to the development of proteinuria and accelerate the renal disease progression due to the primary disease. We discuss possible pathophysiologic pathways involved in proteinuria in Fabry's disease according to the biopsy and the therapeutic response.
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La esclerosis focal y segmentaria glomerular primaria es una causa frecuente de sindrome nefrótico con alta morbilidad que con frecuencia lleva a la insuficiencia renal terminal debido a que sus esquemas terapeúticos no son exitosos, ya que sus mecanismos fisiopatológicos a la actualidad han sido parcialmente descifrados. Estos son heterogéneos, complejos de integrar, y además el término agrupa bajo la misma denominación -la cual evoca una descripción histológica- a un variado número de causas moleculares con distinta fisiopatogenia. En esta revisión se describen los últimos adelantos respecto a la fisiopatología de esta compleja entidad y los últimos adelantos en su terapéutica.(AU)
Primary focal and segmental glomerulosclerosis is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure as the different available therapeutic approaches are unsuccessful, due in part to the fact that the pathophysiological mechanisms have not been fully deciphered, are heterogeneous and complex to integrate, and more important, the denomination employed evokes a histological description shared by a number of different causes with different molecular pathogenesis. This review describes the latest developments regarding the pathophysiology of this complexentity and describes recent advances in therapy.(AU)
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria , Proteinuria , Podocitos , Activador de Plasminógeno de Tipo UroquinasaRESUMEN
La esclerosis focal y segmentaria glomerular primaria es una causa frecuente de sindrome nefrótico con alta morbilidad que con frecuencia lleva a la insuficiencia renal terminal debido a que sus esquemas terapeúticos no son exitosos, ya que sus mecanismos fisiopatológicos a la actualidad han sido parcialmente descifrados. Éstos son heterogéneos, complejos de integrar, y además el término agrupa bajo la misma denominación -la cual evoca una descripción histológica- a un variado número de causas moleculares con distinta fisiopatogenia. En esta revisión se describen los últimos adelantos respecto a la fisiopatología de esta compleja entidad y los últimos adelantos en su terapéutica.
Primary focal and segmental glomerulosclerosis is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure as the different available therapeutic approaches are unsuccessful, due in part to the fact that the pathophysiological mechanisms have not been fully deciphered, are heterogeneous and complex to integrate, and more important, the denomination employed evokes a histological description shared by a number of different causes with different molecular pathogenesis. This review describes the latest developments regarding the pathophysiology of this complexentity and describes recent advances in therapy.