CASE REPORT | RELATO DE CASO 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 Authors ABSTRACT RESUMO 1 Crislaine Aparecida da Silva Introduction: Some cases of membra- Introdução: Alguns casos de nefropatia Fabiano Bichuette Custódio1 nous nephropathy (MGN) present focal membranosa (NM) apresentam glomeru- Maria Luíza Gonçalves dos Reis segmental glomerulosclerosis (FSGS) ty- loesclerose segmentar e focal (GESF) tipi- 1 Monteiro pically associated with disease progres- camente associada a progressão da doença. 2 Stanley de Almeida Araújo sion. However, we report a case of a Contudo, relatamos o caso de uma paciente 1 Liliane Silvano Araújo patient who seemed to have MGN and que parece ter NM e GESF, ambas primárias. 1 Rosana Rosa Miranda Côrrea FSGS, both primary. Case presentation: A Apresentação do caso: Uma jovem branca 1 Marlene Antônia dos Reis 17-year-old female, Caucasian, presenting de 17 anos de idade com edema de membros Juliana Reis Machado1 lower extremity edema associated with inferiores associado a episódios de urina episodes of foamy urine and high blood espumosa e hipertensão apresentou-se com 1 Universidade Federal do pressure, had physical and laboratorial achados físicos e laboratoriais sugestivos de Triângulo Mineiro, Instituto de exams indicating nephrotic syndrome. síndrome nefrótica. Foi realizada biópsia Ciências Biológicas e Naturais, Uberaba, MG, Brasil. A renal biopsy was performed and focal renal. GESF foi observada por microscopia 2 Universidade Federal de Minas and segmental glomerulosclerosis were de luz em alguns glomérulos que apresen- Gerais, Hospital das Clínicas, Belo observed under light microscopy in some tavam lesões de ponta, enquanto em outros Horizonte, MG, Brasil. glomeruli presented as tip lesion, and in o achado era acompanhado por hipertrofia others it was accompanied by podocyte podocitária e descolamento de podócitos no hypertrophy and podocyte detachment espaço urinário, compatíveis com podoci- in urinary space, compatible with po- topatia GESF. Além disso, as alças capila- docytopathy FSGS. Besides, there were res estavam espessadas com irregularidades thickened capillary loops with basement na membrana basal devido a “espículas” membrane irregularities due to “spikes” compatíveis com NM estágio II. Imunofluo- compatible with MGN stage II. Immuno- rescência revelou depósitos finamente granu- fluorescence showed finely granular IgG, lares de IgG, IgG4 e PLA2R nas alças capila- IgG4, and PLA2R deposits in capillary res. Microscopia eletrônica exibiu depósitos loops and, in electron microscopy, sube- subepiteliais e apagamento de pedicelos. pithelial deposits and foot process efface- Tais achados morfológicos são compatíveis ment. These morphological findings are com GESF e NM estágio II. Conclusões: No compatible with FSGS and MGN stage II. presente caso, as características clínicas e Conclusions: In the present case, clinical morfológicas revelaram uma possível sobre- and morphological characteristics showed posição de GESF primária e NM, uma vez a possible overlap of primary FSGS and que a glomeruloesclerose segmentar e focal MGN as focal and segmental glomerulos- não parece estar relacionada com a pro- clerosis does not seem to be related with gressão da NM, mas com a podocitopatia MGN progression but with the podocyto- GESF. Submitted on: 11/19/2018. pathy FSGS. Approved on: 12/07/2018. Keywords: Glomerulosclerosis, Focal Seg- Palavras-chave: Glomerulosclerose Segmen- mental; Glomerulonephritis, Membranous; tar e Focal; Glomerulonefrite Membranosa; Correspondence to: Juliana Reis Machado Nephrotic Syndrome. Síndrome Nefrótica. E-mail: [email protected] DOI: 10.1590/2175-8239-JBN-2018-0239 *The study was performed in the General Pathology and Nephropathology Service of Federal University of Triangulo Mineiro. 113 FSGS and membranous overlap INTRODUCTION There were 23 glomeruli for analysis by LM. All glo- meruli had thickened capillary loops due to epimem- Membranous nephropathy (MGN) is caused by branous deposits (Figure 1A). There were also base- the deposition of subepithelial immunocomplexes, ment membrane irregularities forming “spikes” in a accounts for about 20% of primary glomerulopathies global and diffuse pattern in glomeruli (Figure 1B). in adults and predominantly affects men between 40- Besides, 10 glomeruli had increased mesangial matrix 50 years old1. Patients present proteinuria, edema, with collapse of capillary loops in less than half of hypoalbuminemia and hyperlipidemia, and the pri- each glomerulus, characterizing segmental sclerosis; mary form (75%) is due to in situ immunoglobulin some had podocyte hypertrophy and podocyte deta- deposits against phospholipase A2 receptor (PLA2R) chment in urinary space, with a glomerulus showing a podocyte antigen. In stage I of the disease, glomeruli tip lesion (Figure 1C). Interstitial fibrosis and tubu- are normal in light microscopy (LM) and diagnosis lar atrophy were mild. Vascular compartment was is possible only through immunofluorescence which unremarkable. showed IgG subepeithelial deposits (IF) and trans- IF showed marked granular global and diffu- mission electron microscopy (TEM), which evidence se staining for IgG, IgG4, and PLA2R, in glomeruli IgG subepithelial deposits. Stage II presents glomeru- (Fig.1D), as well as Kappa and Lambda light chains. lar basement membrane (GBM) projections between C3 had mild granular segmental positivity in glome- deposits, named “spikes”, better visualized by silver ruli and segmental positivity in Bowman’s capsule. stain. As the disease progresses, deposits are incorpo- IgA, IgM, C1q and fibrinogen were negative. rated in GBM, which results in a pinhole aspect (stage TEM showed electron-dense amorphous subepi- III) and are posteriorly reabsorbed, creating a thicker thelial deposits, with some deposits separated from GBM (stage IV)2. each other by basement membrane spikes (Figure The coexistence of MGN with other renal disea- 1E), areas of immune complex reabsorption and foot ses was already reported3-6 including MGN and FSGS process effacement (Fig.1F). There was no mesangial, 7, 8, with FSGS cellular9 and collapsing variants10,11. subendothelial, or other glomerular deposits. Therefore, we report the case of a patient with mor- After the diagnosis was confirmed, treatment with phological characteristics of two primary glomerular angiotensin-converting enzyme inhibitor (ACEI) was diseases, MGN and FSGS. started and the patient presented spontaneous remis- sion for 1 year. After this period, there was an in- CASE PRESENTATION crease in proteinuria (5712 mg/24h) and cyclosporine A 17 year-old female, Caucasian, investigating treatment was started. Due to lack of response for 3 proteinuria, presented lower extremity edema asso- months, treatment with cyclophosphamide alternated ciated with episodes of foamy urine and high blood with prednisone was started, with improvement of pressure. The patient reported no use of medications, proteinuria. no arthralgia, arthritis, or skin lesions, and no family history of nephropathy. Laboratorial exams at admis- DISCUSSION sion showed serum creatinine: 0.8 mg/dL; urea: 22 This is a case report of a patient with nephrotic mg/dL; glycemia: 82 mg/dL; total cholesterol: 460 syndrome (NS), which renal biopsy showed mor- mg/dL; LDL cholesterol: 340 mg/dL; triglycerides: phological pattern of two different diseases. GBM 243 mg/dL; and serum albumin: 2.59 g/dL. Her pro- irregularities by LM, IgG, and PLA2R deposits by IF, teinuria was 4370 mg/24h and urinalysis had 300 and subepithelial electron-dense deposits by TEM are mg/dL of proteins, 10,000 leucocytes and 22,000 characteristic of membranous nephropathy stage II2. erythrocytes. Rheumatoid factor was 13 UL/mL and In addition, LM findings of focal and segmental glo- plasma complement particles C3 and C4 were nor- merulosclerosis, podocyte hypertrophy and tip lesion, mal. Dosages of FAN, anti-DNA, and serology for and TEM findings of foot process effacement charac- HIV, HCV, HBV, and VDRL were negative. After terize the podocytopathy FSGS12. There was no evi- exams, she started using 40 mg/day furosemide and dence of secondary diseases. 20 mg/day Simvastatin. MGN and FSGS are important causes of NS in The patient underwent renal biopsy without any adults, MGN being responsible for 20% of cases and intercurrence, and LM, IF, and TEM were performed. FSGS for 40% of cases. MGN pathogenesis involves Braz. J. Nephrol. (J. Bras. Nefrol.) 2020;42(1):113-117 114 FSGS and membranous overlap Figure 1. Histological sections of renal biopsy with morphological diagnosis of membranous glomerulopathy (MGN) concurrent with focal segmental glomerulosclerosis (FSGS). Light microscopy shows (A) thickening of capillary loops due to epimembranous deposits (HE). (B) Segmental sclerosis tip lesion, podocyte hypertrophy, and podocyte detachment in urinary space (HE). (C) Irregularities in glomerular basement membrane forming “spikes” (PAMS). Immunofluorescence for (D) IgG, (E) IgG4, and (F) PLA2R in a marked positive, finely granular, subepithelial, global and diffuse pattern. Electron microscopy showing a capillary loop with electron-dense subepithelial deposits with “spikes” formation in GBM (G) and foot process effacement with areas with deposits reabsorption (F). 115 Braz. J. Nephrol. (J.