Focal and Segmental Glomerulosclerosis and Membranous Nephropathy overlapping in a patient with Nephrotic Syndrome: a case report / Glomeruloesclerose Segmentar e Focal e Nefropatia Membranosa sobrepostas em paciente com Síndrome Nefrótica: relato de caso

Abstract Introduction: Some cases of membranous nephropathy (MGN) present focal segmental glomerulosclerosis (FSGS) typically associated with disease progression. However, we report a case of a patient who seemed to have MGN and FSGS, both primary. Case presentation: A 17-year-old female, Caucasian, presenting lower extremity edema associated with episodes of foamy urine and high blood pressure, had physical and laboratorial exams indicating nephrotic syndrome. A renal biopsy was performed and focal and segmental glomerulosclerosis were observed under light microscopy in some glomeruli presented as tip lesion, and in others it was accompanied by podocyte hypertrophy and podocyte detachment in urinary space, compatible with podocytopathy FSGS. Besides, there were thickened capillary loops with basement membrane irregularities due to "spikes" compatible with MGN stage II. Immunofluorescence showed finely granular IgG, IgG4, and PLA2R deposits in capillary loops and, in electron microscopy, subepithelial deposits and foot process effacement. These morphological findings are compatible with FSGS and MGN stage II. Conclusions: In the present case, clinical and morphological characteristics showed a possible overlap of primary FSGS and MGN as focal and segmental glomerulosclerosis does not seem to be related with MGN progression but with the podocytopathy FSGS.

Resumo Introdução: Alguns casos de nefropatia membranosa (NM) apresentam glomeruloesclerose segmentar e focal (GESF) tipicamente associada a progressão da doença. Contudo, relatamos o caso de uma paciente que parece ter NM e GESF, ambas primárias. Apresentação do caso: Uma jovem branca de 17 anos de idade com edema de membros inferiores associado a episódios de urina espumosa e hipertensão apresentou-se com achados físicos e laboratoriais sugestivos de síndrome nefrótica. Foi realizada biópsia renal. GESF foi observada por microscopia de luz em alguns glomérulos que apresentavam lesões de ponta, enquanto em outros o achado era acompanhado por hipertrofia podocitária e descolamento de podócitos no espaço urinário, compatíveis com podocitopatia GESF. Além disso, as alças capilares estavam espessadas com irregularidades na membrana basal devido a "espículas" compatíveis com NM estágio II. Imunofluorescência revelou depósitos finamente granulares de IgG, IgG4 e PLA2R nas alças capilares. Microscopia eletrônica exibiu depósitos subepiteliais e apagamento de pedicelos. Tais achados morfológicos são compatíveis com GESF e NM estágio II. Conclusões: No presente caso, as características clínicas e morfológicas revelaram uma possível sobreposição de GESF primária e NM, uma vez que a glomeruloesclerose segmentar e focal não parece estar relacionada com a progressão da NM, mas com a podocitopatia GESF.

The metabolomics signature associated with responsiveness to steroid therapy in focal segmental glomerulosclerosis: a pilot study

Abstract Background Focal segmental glomerulosclerosis (FSGS) is considered one of the most severe glomerular diseases and around 80% of cases are resistant to steroid treatment. Since a large proportion of steroid-resistant (SR) FSGS patients progress to end-stage renal disease, other therapeutic strategies may benefit this population. However, identification of non-invasive biomarkers to predict this high-risk population is needed. Objective We aimed to identify the biomarker candidates to distinguish SR from steroid-sensitive (SS) patients using metabolomics approach and to identify the possible molecular mechanism of resistance. Methods Urine was collected from biopsy-proven FSGS patients eligible for monotherapy with prednisolone. Patients were followed for 6-8 weeks and categorized as SS or SR. Metabolite profile of urine samples was analyzed by one-dimensional 1H-nuclear magnetic resonance (1H-NMR). Predictive biomarker candidates and their diagnostic importance impaired molecular pathways in SR patients, and the common target molecules between biomarker candidates and drug were predicted. Results Homovanillic acid, 4-methylcatechol, and tyrosine were suggested as the significant predictive biomarker candidates, while L-3,4-dihydroxyphenylalanine, norepinephrine, and gentisic acid had high accuracy as well. Tyrosine metabolism was the most important pathway that is perturbed in SR patients. Common targets of the action of biomarker candidates and prednisolone were molecules that contributed in apoptosis. Conclusion Urine metabolites including homovanillic acid, 4-methylcatechol, and tyrosine may serve as potential non-invasive predictive biomarkers for evaluating the responsiveness of FSGS patients.

Doença de lesões mínimas e glomeruloesclerose segmentar e focal em adultos: resposta a corticoide e risco de insuficiência renal / Minimal change disease and focal segmental glomerulosclerosis in adults: response to steroids and risk of renal failure

Resumo Introdução: O perfil clínico de pacientes brasileiros adultos com síndrome nefrótica por doença de lesões mínimas (LM) e glomeruloesclerose segmentar e focal (GESF) é pouco conhecido. Objetivo: Avaliamos as características clínico-laboratoriais e resposta a tratamento em pacientes adultos com síndrome nefrótica e diagnósticos histológicos de LM ou GESF. Métodos: Fez-se a análise retrospectiva de 50 pacientes adultos com LM e 120 com GESF. Todos os pacientes foram inicialmente tratados com corticosteroide. Os desfechos do estudo foram: resposta a corticosteroide, prevalência de remissão total, progressão para doença renal crônica estágio 5 (DRC5) e necessidade de terapia de substituição renal por DRC5. Resultados: Níveis iniciais de creatinina sérica foram 24% mais elevados entre pacientes com GESF (p = 0,02) e os de proteinúria foram 36% mais altos em LM (p < 0,001). Pacientes com LM foram córtico-sensíveis em 80% dos casos, com remissão total em 74%, e os pacientes com GESF em 58% (p = 0,01), com remissão total em 30% (p = 0,002). A prevalência de insuficiência renal aguda em pacientes com GESF foi de 39% (vs. 12%, p = 0,013) e DRC5 de 10% (vs. 0%, p < 0,001). Remissão completa ou parcial com o uso de corticosteroide reduziu em 83% o risco de DRC5 (p < 0,001) e remissão total associou-se a redução no risco de DRC5 de 89% (p < 0,001). Conclusão: A resposta positiva à corticoterapia foi o fator mais importante relacionado à preservação da função renal ao longo de mais de uma década de seguimento, e GESF relacionou-se a menor índice de resposta a corticosteroide.

Abstract Introduction: There is scarce data on the clinical profile of adult Brazilian patients with nephrotic syndrome caused by minimal change disease (MCD) and focal segmental glomerulosclerosis. Objective: We evaluated the clinical characteristics and response to treatment in adult patients with nephrotic syndrome having a histological diagnosis of MCD or FSGS. Methods: This is a retrospective analysis of 50 patients with MCD and 120 with FSGS. All patients were initially treated with steroids. The study outcomes were: steroid responsiveness, prevalence of total remission, progression to chronic renal failure and need of renal replacement therapy due to end-stage renal disease (ESRD). Results: Initial serum creatinine level was 24% higher among patients with FSGS (p = 0.02), and proteinuria levels were 36% higher in MCD (p < 0.001). Patients with MCD were sensitive to steroid therapy in 80% of the cases, with total remission in 74%, while patients with FSGS were sensitive in 58% (p = 0.01), with total remission in 30% (p = 0.002). Patients with FSGS had an acute renal failure prevalence of 39% (vs. 12%, p = 0.013) and ESRD of 10% (vs. 0%, p < 0.001). Steroid responsiveness reduced in 83% the risk of ESRD (p < 0.001), while total remission was associated to a reduction in risk of 89% (p < 0.001). Conclusion: A positive response to steroid therapy was the most important factor related with preservation of renal function and FSGS was related with less steroid responsiveness.

Pattern, clinical features and response to corticoids of glomerular diseases in a Brazilian population. An analytical cross-sectional study / Perfil, características clínicas e resposta a corticoides das doenças glomerulares em uma população brasileira. Um estudo transversal analítico

CONTEXT AND OBJECTIVE: Glomerular disease registries are increasing all around the world. The aim of this study was to evaluate the clinical characteristics and treatment response among patients with glomerular diseases followed up in a tertiary hospital in Brazil. DESIGN AND SETTING: Analytical cross-sectional study; tertiary-level public hospital. METHODS: This study included patients with glomerular diseases followed up at a tertiary hospital in Fortaleza, northeastern Brazil. Clinical and laboratory data on each patient were registered. The response to specific treatment was evaluated after 3, 6 and 12 months. RESULTS: The study included 168 patients of mean age 37 ± 14 years. The most prevalent glomerular diseases were focal segmental glomerulosclerosis FSGS] (19.6%), minimal change disease MCD] (17.9%), membranous nephropathy MN] (16.7%) and lupus nephritis LN] (11.9%). The main clinical presentations were nephrotic proteinuria (67.3%) and renal insufficiency (17.9%). The mean proteinuria value decreased after the treatment began. Regarding 24-hour proteinuria on admission, there was no significant difference between patients with a good response and those with no response (7,448 ± 5,056 versus 6,448 ± 4,251 mg/24 h, P = 0.29). The glomerular disease with the highest remission rate was MCD (92%). Absence ...

CONTEXTO E OBJETIVO: Registros de glomerulopatias estão aumentando em todo o mundo. O objetivo deste estudo é avaliar as características clínicas e a resposta do tratamento de pacientes com glomerulopatias acompanhados em um hospital terciário no Brasil. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico. Hospital público terciário. MÉTODOS: O estudo incluiu pacientes com glomerulopatias acompanhados em um hospital terciário de Fortaleza, Ceará, Brasil. Foi realizado registro dos dados clínicos e laboratoriais para cada paciente. A resposta ao tratamento específico foi avaliada após 3, 6 e 12 meses. RESULTADOS: Foram incluídos 168 pacientes, com média de idade de 37 ± 14 anos. A glomerulopatia mais prevalente foi a glomerulosclerose segmentar e focal GESF] (19,6%), seguida pela doença de lesão mínima DLM] (17,9%), nefropatia membranosa NM] (16,7%) e nefrite lúpica NL] (11,9%). As principais manifestações clínicas foram proteinúria nefrótica (67,3%) e insuficiência renal (17,9%). A média dos valores de proteinúria diminuiu após o início do tratamento. Com relação à proteinúria de 24 horas na admissão, não houve diferença significativa entre os pacientes com boa resposta ao tratamento ...

Alkali Therapy Attenuates the Progression of Kidney Injury via Na/H Exchanger Inhibition in 5/6 Nephrectomized Rats

Metabolic acidosis is a cause of renal disease progression, and alkali therapy ameliorates its progression. However, there are few reports on the role of renal acid-base transporters during alkali therapy. We evaluated the effect of sodium bicarbonate therapy and the role of acid-base transporters on renal disease progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary sodium bicarbonate (NaHCO3) or sodium chloride (NaCl) with 20% casein after a 5/6 nephrectomy. After being provided with a casein diet, the NaHCO3-treated group had higher levels of serum bicarbonate than the control group. At week 4, the glomerular filtration rate in the NaHCO3 group was higher than that in the NaCl group, and the difference became prominent at week 10. The glomerulosclerosis and tubulointerstitial damage indices in the NaHCO3 group were less severe compared with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was decreased, and apical reactivity was decreased in the NaHCO3 group, compared with the NaCl group. Endothelin-1 levels in the kidney were also decreased in the NaHCO3 group. Dietary sodium bicarbonate has the effects of ameliorating renal disease progression, which may be related to the altered expression of NHE in the remaining kidney.

Tratamiento de la glomeruloesclerosis focal y segmentaria / Focal segmental glomerulosclerosis treatment

La glomeruloesclerosis focal y segmentaria, es un padecimiento que fue descrito en 1957, su prevalencia varía entre el 2.5 y 18.7 por ciento entre los pacientes a quienes se les hace biopsia renal, su etiología se desconoce. El cuadro clínico se inicia con microhematuria, proteinuria o síndrome nefrótico, pudiendo llegar hasta la insuficiencia renal crónica. Los autores recomiendan iniciar el tratamiento con prednisona a dosis de 60 mgs diario durante 6 meses, quienes no respondan al tratamiento, se pueden beneficiar de: ciclosporina, azatioprina, ciclofosfamida o clorambicil. El padecimiento puede presentar recurrencia en el riñón trasplantado con no poca frecuencia, estos pacients se peuden beneficiar de la pasmaféresis, para lograr una emisión

Survival analysis of Thai patients with IgM nephropathy, focal segmental glomerulosclerosis and membranous nephrotic syndrome.

Long term outcome of 124 Thai adult nephrotic patients was determined. Nephrotic syndrome affects the young more often than the old (median age 29 years). The most common pathology was IgM nephropathy (45.2%), membranous nephropathy (31.5%) and FSGS (23.4%). Sixty-four per cent of patients with IgM nephropathy respond to corticosteroid within 4-8 weeks while twenty three per cent were late responders. However, more than half of these patients were relapsers or steroid dependent. Response to corticosteroid occurred in 48.2 per cent of patients with FSGS while the response rate of patients with membranous nephropathy was only 23.1 per cent. Survival analysis revealed that five and ten years renal survival of IgM nephropathy was 98 per cent. Five and ten years renal survival of FSGS was 83.7 per cent and 76.8 per cent while those of membranous nephropathy was 95 per cent and 63.3 per cent. The response to corticosteroid was associated with better prognosis in FSGS. Our results show that patients with IgM nephropathy and membranous nephropathy have a generally good prognosis. Renal function is usually well preserved for at least ten years. The prognosis of patients with FSGS varied and correlated with the degree of steroid responsiveness.

Intravenous pulse cyclophosphamide--a new regime for steroid resistant focal segmental glomerulosclerosis.

OBJECTIVE: A prospective study was conducted to evaluate the role of intravenous pulse cyclophosphamide (IVCP) infusions in the management of children with steroid resistant (SR) idiopathic focal segmental glomerulosclerosis (FSGS). METHODS: The study group comprised of 20 consecutive children with idiopathic nephrotic syndrome secondary to FSGS who were SR. All of them were subjected to standard baseline investigations. They were started on monthly infusions of IVCP in a dose of 500-750 mg/m2. Adjunctive prednisolone was given in a dose of 60 mg/m2/day for 4 weeks followed by 40 mg/m2/alternate day for another 4 weeks and tapered off over next 4 weeks. RESULTS: The study group comprised of 15 boys and 5 girls with mean age of onset of disease of 5.5 +/- 3.5 years. Two of these children had chronic renal insufficiency prior to starting therapy. At the end of the study, after a mean duration of disease (since onset of NS) of 77 +/- 55 months, all 20 children had normal renal functions. After a mean follow up post IVCP therapy of 21.2 +/- 13.4 months, 13 of the 20 children (65%) had attained a complete remission. Of these, 10 children were infrequent relapsers, 2 frequent relapsers and 1 steroid dependent. The mean duration of remission following last dose of IVCP in these children was 12.5 +/- 11.9 months. Of the 7 children who continued to be proteinuric, 3 became edema free and have not required any albumin infusion or diuretics. One other died due to peritonitis 2 years after the last dose of IVCP. The mean total protein and serum albumin levels following the IVCP infusion were significantly higher than those prior to therapy (6.5+/-1.0 mg/dl Vs 5.0+/-0.8) (p=0.0004) and (3.5+/-0.7 g/dl Vs 2.3+/0.7) (p = 0.000007) respectively. The serum creatinine levels following IVCP therapy (0.8+/-0.2 mg/dl) were significantly lower than those prior to treatment (1.0+/-0.6 mg/dl) (p=0.02). The only side effects that were observed were transient nausea and vomiting during infusion (n=2) and alopecia (n=1). None of the children developed leukopenia or hemorrhagic cystitis. CONCLUSION: IVCP infusions appear to be safe, effective and economical therapeutic modality in steroid resistant children with idiopathic FSGS.

Hialinosis focal y segmentaria / Focal segmental glomeruloesclerosis

La Hialinosis Focal y Segmentaria (HFS), idiopática o secundaria, es una afección frecuente. Su patogenia no es aún bien conocida, en los últimos años, al mecanismo de hiperfiltración e hipertensión glomerular se asocia el rol patogénico de los factores de crecimiento e hipertrofia glomerular. La presentación clínica más habitual es el Sindrome Nefrótico con pobre respuesta al tratamiento esteroideo y evolución en plazos variables a la insuficiencia renal extrema. Los factores predictivos de evolución a la pérdida de la función renal, son el rango nefrótico de la proteinuria, los niveles elevados de creatinina sérica inicial y la severidad de las lesiones túbulointersticiales. La mejor evolución de la función renal de los pacientes cuya proteinuria responde al tratamiento, justifica tratarlos

Idiopathic foca and segmental glomerulosclerosis in Jamaica: a 10 year review

Idiopathic focal and segmental glomerulosclerosis (IFSGS) in a predominantly black population does not appear to behave any differently than in Caucasian patients. Response to steroid therapy and cyclophosphamide had favourable prognostic significance. There may be a subgroup of IFSGS which responds more slowly to steroids. The duration of steroid therapy should extend beyond four months

Intrarenal hemodynamic abnormality in severe form of glomerulonephritis: therapeutic benefit with vasodilators.

Intrarenal hemodynamic and tubular function has been assessed in 16 patients who presented clinically with hypertension, hematuria and severe renal functional impairment. Twelve of these 16 patients had histopathologic classification as DPGN (3 cases), MPGN (3 cases) and FSGS (6 cases). The initial assessment of intrarenal hemodynamics in 11 patients revealed strikingly increased afferent (RA) and efferent arterioles (RE), filtration fraction (FF), intraglomerular capillary hydrostatic pressure (PG), whereas, there was marked reduction in renal plasma flow (RPF), in ultrafiltration coefficient (KFG) and in glomerular filtration rate (GFR). Tubular transporting defect as being reflected by enhanced fractional excretions of solutes was also observed. Both enhanced TXB2 production and diminished PGI2 may be in part responsible for the marked reduction of RPF and elevated intrarenal resistance. In light of the preceding intrarenal hemodynamics alteration, therapeutic intervention with vasodilators consisting of dipyridamole, calcium channel blocker and angiotensin convertase inhibitor has been accomplished with clinical improvement in glomerular and tubular functions following the improvement in intrarenal hemodynamics. Thus, this abnormal intrarenal hemodynamics renders a supportive view of the hemodynamically mediated glomerulo-tubulo-interstitial injury to be central to the pathogenetic mechanism.

Hialinosis focal y segmentaria / Focal and segmentary hyalinosis

Se refiere que la hialinosis focal y segmentaria es una causa frecuente de glomerulopatía en el adulto joven y que en nuestro país la frecuencia entre las glomerulopatías primarias del adulto es 22,7 por ciento. Se describe la lesion histológica característica con esclerosis segmentraria del glomérulo y acumulación de depósitos hialinos acelulares, que afectan solamente algunos glomérulos (focal), predominantemente los yuxtaglomerulares. Se discute la etiopatogenia y la interrelación con la lesión glomerular mínima y la proliferación mesangial. Se destaca la importancia de la hiperfiltración en la génesis y progresión de la lesión. Se refiere que la presentación clínica más habitual es el síndrome nefrótico, con microhematuria e hipertensión arterial y evolución progresiva a la pérdida de la función renal. En 38 pacientes se observó que la sobrevida actuarial a los 5 años fue 57 por ciento. Se destaca que la respuesta al tratamiento corticoideo e inmunosupresor es pobre y que son índices de mal pronóstico la hipertensión arterial y la corticorresistencia