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

Background. Obstructive nephropathy is characterized at the histologic leve l by tubular atrophy and interstitial monocyte infiltration. The molecular mechanisms underlying these histologic changes are still poorly defined. Ep idermal growth factor (EGF) produced by tubular cells seems to play a pivot al role in the modulation of tubular cell growth, while monocyte chemotacti c peptide-1 (MCP-1) is a powerful and specific chemotactic and activating f actor for monocytes. Methods. Twenty-four patients with congenital ureteropelvic junction obstru ction [UPJO; 10 with recurrent urinary tract infection (UTI) and 10 with no UTI] and 15 healthy children were studied. Diagnosis was made by renal ult rasound, intravenous pielography, and MAG3 scan. Urinary samples were colle cted before and after surgery. In 10 patients, urine was also collected dir ectly 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, wherea s MCP-1 mRNA was undetectable. MCP-1 gene expression was strikingly increas ed at the tubulointerstitial level in UPJO biopsies compared with controls and was directly correlated with the extent of monocyte infiltration. In ad dition, UPJO kidney sections showed a marked reduction in EGF gene expressi on that was directly correlated with the degree of tubular damage. EGF urin e concentration was significantly reduced in UPJO when compared with contro l 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 be tween the MCP-1 concentration in the urine collected from the obstructed pe lvis and the MAG3 clearance of the obstructed kidney (r = -0.76). The prese nce of recurrent UTI was associated with a significantly higher MCP-I excre tion and a slight reduction in EGF urine concentration. The surgical correc tion 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 ur ine concentrations. Interestingly, EGF urine concentration measured before surgery was significantly correlated with the difference between the MAG3 c learance of the obstructed kidney before and after surgery. Conclusions. MCP-1 and EGF seem to be involved in the pathogenesis of tubul ointerstitial damage in congenital obstructive nephropathy, and their urine excretion may represent a powerful prognostic marker in this form of renal disease.