BackgroundFocal segmental glomerulosclerosis (FSGS) lesions have often been discussed as a negative predictor in idopathic membranous nephropathy (MN). The mechanism of the development of FSGS lesion in MN is still uncertain.MethodsFrom 250 cases of MN, 26 cases contained FSGS lesion. We compared the clinicopathological characteristics between MN cases with FSGS lesion [MN-FSGS(+)] and MN without FSGS lesion [MN-FSGS(−)], matched for gender, age, stage of MN.ResultsThe glomerular filtration rate (eGFR) was significantly lower in MN-FSGS(+) cases compared to MN-FSGS(−), although nephrotic syndrome, hematuria, and systolic blood pressure levels were not significantly different between the two groups. Pathologically, glomeruli in MN-FSGS(+) cases showed narrowing and loss of glomerular capillaries with separating from GBM or disappearance of CD34+ endothelial cells, and accumulation of extracellular matrix (ECM) in capillary walls, indicating the development of glomerular capillary injury. These findings of endothelial injury were seen even in MN-FSGS(−) cases, but they were more prominent in MN-FSGS(+) than MN-FSGS(−) by computer assessed morphometric analysis. In MN-FSGS(+) cases, 44 out of 534 glomeruli (8.2%) contained FSGS lesions (n = 31, NOS lesion; n = 13, perihilar lesion). Significant thickness of GBM with ECM accumulation was evident in MN-FSGS(+) cases. Podocyte injury with effacement of foot processes was also noted, but the expression of VEGF on podocytes was not different between the two groups, which suggests that the significant thickness of capillary walls may influence the function of VEGF from podocyte resulting in the glomerular capillary injury that contribute to the development of FSGS lesion in MN.ConclusionGlomerular capillary injury was seen in all MN cases. Furthermore, the prominent injuries of glomerular capillaries may be associated with the deterioration of eGFR and the formation of FSGS lesions in MN.

The loss of glomerular capillaries with endothelial cell injury is commonly associated with the formation of necrotizing and cellular crescentic lesions, regardless of the pathogeneses associated with different types of crescentic GN, such as pauci-immune type ANCA-associated GN, anti-GBM GN, and immune-complex type GN. In addition, impaired capillary regeneration and a loss of endothelial cells contribute to the development of glomerular sclerosis with fibrous crescents and glomerular collapse.

Focal segmental glomerulosclerosis (FSGS) is associated with various clinicopathological conditions, including hypertension. We report here a case of secondary FSGS associated with malignant hypertension. A 33-yearold man with a 1-month history of visual impairment and headache visited the Department of Ophthalmology at our hospital and was found to have hypertensive retinopathy and severe hypertension (230/160 mmHg). He was referred to our department based on suspected renal dysfunction. His blood pressure on admission was 250/130 mmHg. Physical examination and laboratory tests revealed hypertensive cardiac dysfunction, focal brain edema, renal dysfunction (serum creatinine, Cr 7.07 mg/dl, blood urea nitrogen, BUN 49.9 mg/dl), massive proteinuria (10.7 g/day), and thrombotic microangiopathy. Funduscopy showed exudate, hemorrhage, and papilledema. The cause of secondary hypertension could not be identified. He was treated for primary malignant hypertension, but required hemodialysis 3 days after admission due to anuria. Treatment with antihypertensive agents resulted in the gradual recovery of renal function, although heavy proteinuria continued with nephrotic syndrome. Renal biopsy performed 1 month after admission showed features of malignant nephrosclerosis with secondary FSGS. Hemodialysis was discontinued following further improvement in renal function and the most recent laboratory tests showed proteinuria 1.8 g/day and persistent renal dysfunction (BUN 36.5 mg/dl, Cr 3.14 mg/ dl). Malignant hypertension may cause various injuries, including glomerular endothelial and epithelial cell injuries in glomerular hypertension and hyperfiltration, increase of the renin-angiotensin-aldosterone system, and endothelialepithelial interaction, resulting in the development of secondary FSGS and heavy proteinuria.

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