A case of secondary focal segmental glomerulosclerosis associated with malignant hypertension

Abstract

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-year-old 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 endothelial-epithelial interaction, resulting in the development of secondary FSGS and heavy proteinuria.

Keywords: Focal segmental glomerulosclerosis; Hypertensive emergency; Malignant hypertension; Malignant nephrosclerosis; Nephrotic syndrome; Thrombotic microangiopathy.

Fig. 1

Clinical course. Malignant hypertension, renal dysfunction, and nephrotic syndrome were present in the early period after admission. Hemodialysis was performed between days 3 and 39. Treatment of malignant hypertension resulted in a decrease in blood pressure and gradual recovery of renal function to mild-to-moderate renal dysfunction, allowing discontinuation of hemodialysis and resolution of the nephrotic syndrome to about 2.0 g/day of proteinuria

Fig. 2

Light microscopy (a, d Masson trichrome stain b, f periodic acid silver methenamine stain, c periodic acid-Schiff stain, e elastica Masson-Goldner stain; magnification: a ×200, b ×600, c–f ×800). Renal biopsy specimens showed marked thickening of the intima of the arterioles (arrow in a) and segmental sclerosis (arrowhead in a). About 60 % of the interstitium showed atrophy of the renal tubules with fibrosis. In one glomerulus, hyperplasia of epithelial cells was detected in Bowman’s space (arrowheads in b). Two glomeruli showed segmental endocapillary hypercellularity with infiltration of foam cells (arrows in c and d) and hyperplasia of epithelial cells in Bowman’s space (arrowheads in c and d). Arterioles showed marked intimal thickening without elastosis (e) but with intimal fibrosis (also known as onion-skin lesion) (f)

Fig. 3

Immunohistochemical examination of representative glomeruli with segmental sclerosis (a staining for CD34; b staining for CD68; c staining for α-smooth muscle actin, α-SMA; d staining for CD10; e staining for AE1/AE3; magnification: a–e ×800). The segmental sclerotic lesion was characterized by the loss of CD34⁺ glomerular capillaries (arrows in a) with increased deposition of glomerular extracellular matrix and presence of CD68⁺ macrophages (arrowheads in b) and α-SMA⁺ activated mesangial cells (arrowheads in c). Hyperplastic epithelial cells on segmental sclerosis were characterized by the loss of normal podocyte marker CD10 and the expression of Bowman’s epithelial cell marker cytokeratin (AE1/AE3)

Fig. 4

Electron microscopy (magnification: a ×8,000, b ×20,000, c, d ×7,000). Diffuse glomerular endothelial cell injury was detected, which was characterized by diffuse widening of the subendothelial space (arrowheads in a) with mesangial interposition (arrow in b), increased number of endothelial cells with swelling of the cytoplasm (arrowheads in c), and loss of fenestrae in glomerular capillaries. Segmental injury of glomerular epithelial cells was also noted, which was characterized by focal detachment of podocytes from the glomerular basement membrane (arrowheads in b), focal effacement of the foot processes, villi formation, two nuclei per podocyte (arrow in d), and vacuolar formation in the podocyte cytoplasm (arrowhead in d)