MCP-1 and EGF renal expression and urine excretion in human congenital obstructive nephropathy.

BACKGROUND: Obstructive nephropathy is characterized at the histologic level by tubular atrophy and interstitial monocyte infiltration. The molecular mechanisms underlying these histologic changes are still poorly defined. Epidermal growth factor (EGF) produced by tubular cells seems to play a pivotal role in the modulation of tubular cell growth, while monocyte chemotactic peptide-1 (MCP-1) is a powerful and specific chemotactic and activating factor for monocytes. METHODS: Twenty-four patients with congenital ureteropelvic junction obstruction [UPJO; 10 with recurrent urinary tract infection (UTI) and 10 with no UTI] and 15 healthy children were studied. Diagnosis was made by renal ultrasound, intravenous pielography, and MAG3 scan. Urinary samples were collected before and after surgery. In 10 patients, urine was also collected directly from the affected pelvis at the time of surgery. Urinary EGF and MCP-1 levels were measured by enzyme-linked immunosorbent assay. MCP-1 and EGF gene expression were evaluated by in situ hybridization in 15 biopsies from congenital UPJO and in 10 normal kidneys. RESULTS: In normal kidneys, there was a high expression of EGF mRNA, whereas MCP-1 mRNA was undetectable. MCP-1 gene expression was strikingly increased at the tubulointerstitial level in UPJO biopsies compared with controls and was directly correlated with the extent of monocyte infiltration. In addition, UPJO kidney sections showed a marked reduction in EGF gene expression that was directly correlated with the degree of tubular damage. EGF urine concentration was significantly reduced in UPJO when compared with control and directly correlated with its renal gene expression. On the other hand, the MCP-1 urine concentration was strikingly increased in UPJO patients. It is noteworthy that a significant and inverse correlation was observed between the MCP-1 concentration in the urine collected from the obstructed pelvis and the MAG3 clearance of the obstructed kidney (r = -0.76). The presence of recurrent UTI was associated with a significantly higher MCP-1 excretion and a slight reduction in EGF urine concentration. The surgical correction of UPJO was followed by an improvement of renal function together with a significant reduction in MCP-1 excretion and a marked increase in EGF urine concentrations. Interestingly, EGF urine concentration measured before surgery was significantly correlated with the difference between the MAG3 clearance of the obstructed kidney before and after surgery. CONCLUSIONS: MCP-1 and EGF seem to be involved in the pathogenesis of tubulointerstitial damage in congenital obstructive nephropathy, and their urine excretion may represent a powerful prognostic marker in this form of renal disease.

Renal expression of monocyte chemotactic protein-1 and epidermal growth factor in children with obstructive hydronephrosis.

BACKGROUND/PURPOSE: The authors studied the potential role of ureteropelvic junction obstruction (UPJ-O) in causing progressive renal damage in children through the renal expression of epidermal growth factor (EGF) and monocyte chemotactic protein-1 (MCP-1) mRNA. METHODS: Renal tissues were harvested from 11 children with UPJ-O and from 10 normal kidneys to study the renal expression of EGF and MCP-1 detected by means of in situ hybridization. Five of the patients were found to have a history of urinary tract infection (UTI). RESULTS: Children with UPJ-O had marked reduction of EGF gene expression when compared with controls. Interstitial expression of MCP-1 mRNA was present in all UPJ-O cases. Both EGF and MCP-1 expression did not correlate with age, with differential renal function, and with renal thickness measured through MAG3 renal scan. Children with a history of UTI had a more severe reduction of the renal thickness of the affected kidney compared with those without UTI. MCP-1 expression was higher and EGF more reduced in children with a history of UTI. CONCLUSIONS: Our results suggest a potential role of EGF and MCP-1 in the pathogenesis of renal damage and growth failure in UPJ-O, especially in children with UTI. These important functional changes begin early in life, possibly during fetal life.