Glomerular basement membrane lipidosis in Alagille syndrome

Abstract

Alagille syndrome is characterized by a paucity of interlobular bile ducts with chronic cholestasis, cardiac, skeletal, and eye abnormalities and is associated predominantly with JAG1 mutations. Various renal abnormalities have been sporadically described. The classic renal histopathology described in Alagille syndrome is mesangiolipidosis, with lipid deposits predominately confined to the mesangium and minimal deposition within the glomerular basement membrane (GBM). We report a 5-year-old girl with Alagille syndrome who presented with persistent subnephrotic proteinuria and renal tubular acidosis. A renal biopsy showed GBM irregularities (mimicking membranous glomerulonephritis), mesangial sclerosis, and focal segmental glomerulosclerosis (FSGS) on light microscopy. Electron microscopy revealed few lipid inclusions within the mesangium but extensive inclusions along the GBM. These findings are mostly consistent with those reported previously in Alagille syndrome. However, the histologic distribution of lipid vacuoles is seemingly reversed in this patient and is uniquely accompanied by FSGS, emphasizing the spectrum of renal histopathology seen in Alagille syndrome. The proteinuria observed in this patient is likely attributed to significant GBM lipid deposition, which over time may contribute to the development of FSGS.

Developmental abnormalities and liver disease in childhood

“…Renal abnormalities, such as tubulointerstitial nephropathy, membranous nephropathy, single kidney and renovascular hypertension, may be prominent. [373][374][375] The most frequent finding is mesangiolipidosis. 376 Nephrolithiasis may occur, and various types of renal cystic disease have been reported.…”

Endoplasmic reticulum stress participates in inflammation‐accelerated, lipid‐mediated injury of human glomerular mesangial cells

“…In 1982, Moorhead and colleagues suggested that lipid accumulation induces kidney injury and can cause progressive renal disease. Recently, studies demonstrated that lipid abnormalities contribute to disease progression and GS …”

Anomalías renales en niños con síndrome de Alagille

“…4 M u y r a r a m e n t e , puede encontrarse glomeruloesclerosis focal y segmentaria, aunque solo ha sido descrita en 2 pacientes adultos. 2,8 A pesar de que, en ninguno de nuestros pacientes, se realizó biopsia renal, podría especularse que este grupo presentaba dichas lesiones histológicas como responsables de la disfunción renal. Esto destaca la importancia de la búsqueda de afectación renal en todos los pacientes, incluyendo aquellos sin patología estructural.…”

“…2,4,7 También han sido descritos cambios glomerulares, como la mesangiolipidosis y la glomeruloesclerosis focal y segmentaria. 2,8 La hipertensión arterial secundaria a estenosis de la arteria renal y otros compromisos vasculares, como el síndrome de aorta media, anomalías vasculares intraabdominales y del sistema nervioso central, también han sido descritos. 3 Los accidentes cerebrovasculares han sido reportados hasta en el 15%.…”