Immunohistochemical Distribution of Endothelin in Biopsies of Pediatric Nephrotic Syndrome

Abstract

In a retrospective, double-blind study, we analyzed, utilizing an immunohistochemical technique, the distribution of Endothelin (Et) in 20 renal biopsies of 17 children with nephrotic syndrome (NS): 9 cases of steroid-responsive and 8 of steroid-resistant minimal-change disease (MCD) and 3 cases of focal segmental glomerulosclerosis (FSGS). Thirteen out of 20 biopsies (9/9 steroid-responsive MCD and 4/8 steroid-resistant MCD) showed a weak positivity of the vascular endothelial cells, as the normal renal tissue samples obtained from tumor nephrectomies. Seven out of 20 biopsies, all steroid-resistant NS, showed a marked positivity of the vascular endothelium and of the tubules and/or interstitial cells. In 4 of these 7 cases (1 MCD, 3 FSGS) a positivity of glomeruli was also revealed. The positivity of vascular endothelium seems to confirm its central role in Et production. The marked immunoreactivity detected in the endothelial cells and other renal components reveals a local increase in Et in some steroid-resistant MCD and, particularly, in FSGS. These preliminary observations suggest that Et may participate (cause or epiphenomon) in the mechanisms underlying the development of glomerulosclerosis and the progression of renal damage.

Impact of endothelin-1 Lys198Asn polymorphism on coronary artery disease and endorgan damage in hypertensives

“…Several studies documented that renal synthesis of ET-1 is increased either in animal or in human chronic nephropathies [12,21]. Interestingly, Murer et al [22] demonstrated a correlation between glomerulonephritis/ glomerulosclerosis and an activated renal ET system. It has been shown that no significant higher risk for increased urinary albumin excretion, microalbuminuria, decreased glomerular filtration rate, or reduced filtration could be observed for a single-nucleotide polymorphism.…”

Endothelin-1 transgenic mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension.

“…Various studies have demonstrated a correlation between an activated renal endothelin system and renal injury (7)(8)(9). However, clear evidence showing that kidney ET-1 overexpression results in renal injury has been lacking.…”

“…However, clear evidence showing that kidney ET-1 overexpression results in renal injury has been lacking. In humans, as well as in animals with kidney diseases, an activated renal endothelin system (namely ET-1) due to hypoxia, renal mass reduction, cyclosporine, or inflammatory kidney diseases like lupus nephritis, seems to correlate with renal injury (7,8,28,29).…”

Mechanisms of Scarring in Focal Segmental Glomerulosclerosis

“…55 In some steroid-resistant FSGS patients, increased endothelin expression in glomeruli was demonstrated. 56 In patients with membranous nephropathy, more GEC injury, with nuclear and cytoplasmic swelling and loss of fenestrae, was found in those patients who, in addition to the membranous lesions, had secondary segmental sclerosis. 57 These findings suggest podocyte injury in FSGS may lead to endothelial cell dysfunction.…”