Focal and segmental glomerulosclerosis in adults: early clinical course and prognostic factors for short-term outcome / Glomeruloesclerosis focal y segmentariaenadultos: evoluciónclínicatemprana y factorespronósticos de resultados a cortoplazo

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.

Glomeruloesclerosis Focal y Segmentaria luego de Embarazo Complicado con Preeclampsia y Falla Renal Aguda. Reporte de Caso / Focal Segmental Glomerulosclerosis after Pregnancy Complicated with Preeclampsy and Acute Renal Injury. Case Report

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.

Esclerosis focal y segmentaria glomerular primaria: ubi sumus et quo eamus? / Primary focal segmental glomerulosclerosis: ubi sumus et quo eamus?

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.

A Clinical Analysis of Primary Focal and Segmental Glomerulosclerosis in Adults / 대한신장학회잡지

PURPOSE: Primary focal and segmental glomerulosclerosis(FSGS) is a clinicopathological entity defined by the segmental sclerosis involving glomeruli in a focal distribution with poor prognosis. Approximately 50% to 70% of adults with FSGS manifests nephrotic syndrome, and the others show mild to moderate proteinuria. In this study, we intended to figure out the clinical course, treatments and possible prognostic factors of FSGS in adults. METHODS: We retrospectively reviewed the clinical characteristics of 54 adult patients diagnosed as primary focal segmental glomerulo-sclerosis(FSGS) by renal biopsy in Chungnam National University Hospital. from Dec. 1989 to Jan. 2000. RESULTS: Mean age of 54 patients was 36.8+/-24.6 (15-75) years. Male to female ratio of them was 1.08 : 1. Thirty one patients(57%) of them were manifested as nephrotic syndrome and their male to female ratio was 1.4 : 1. In all of 54 primary FSGS patients, generalized edema(59%), microscopic hematuria (44%), hypertension(39%) and azotemia(15%) were noted as clinical manifestations at the time of diagnosis. Median duration of follow-up was 48.7(6-123) months. Except generalized edema, serum cholesterol and albumin level, and 24 hour urine protein excretion, there was no significant difference in hypertension, hematuria, serum creatinine, duration of follow- up and progression to chronic renal failure between 31 nephrotic and 23 non-nephrotic patients. Sixteen (52%) of 31 nephrotic patients with primary FSGS showed complete remission. Seven(22%) of them showed partial remission and eight(26%) of them showed no response after 8 weeks of first steroid treatment. No response group of primary FSGS nephrotic patients progressed significantly more to chronic renal failure than remission group including complete or partial remission patients. No response groups showed significantly higher serum creatinine, lower creatinine clearance, higher degree of glomerular global sclerosis and interstitial fibrosis than remission group at the time of diagnosis. Eleven patients(8 nephrotic and 3 non-nephrotic patients) of 54 primary FSGS patients progressed to CRF during follow-up period, and they showed significantly lower creatinine clearance and higher degree of global glomerular sclerosis at the time of diagnosis than normal renal function maintaining group. CONCLUSION: It is speculated that initial renal function and degree of global glomerular sclerosis at the time of diagnosis in primary FSGS patients, and additively response to initial steroid therapy and the degree of interstitial fibrosis at the time of diagnosis in nephrotic primary FSGS patients are thought to be significant long-term prognostic factors.