Serum adhesion molecule profiles in children with progressive renal disorders

Abstract

Dear Sirs, We read with great interest the article entitled “Serum VCAM-1, ICAM-1, and L-selectin levels in children and young adults with chronic renal failure” by Musial et al. [1]. In their research they showed that serum levels of VCAM-1 and ICAM-1 in children with chronic renal failure (CRF) were significantly higher than those in controls, and serum l-selectin level in CRF was significantly lower. As possible causes of higher concentrations of serum VCAM-1 they enumerated impaired renal clearance, increased proteolytic VCAM-1 cleavage, and blood-membrane contact during hemodialysis. Of the 61 children in their study, CRF had developed in 21 subjects (34%) because of reflux nephropathy (RN), which is an interesting point for us. Traditionally, RN is recognized as a major cause of CRF; this is supported by their study, because they showed that RN was the most common condition causing CRF. We also determined serum VCAM-1 levels in children with RN and found that serum VCAM-1 levels in RN were significantly higher than those in normal controls [2]. Although there are few reports about serum VCAM-1 levels in children with renal disease, tubular cell expression of VCAM-1 has been reported in many renal diseases causing tubulointerstitial inflammation and secondary glomerular inflammatory damage. This immuno-inflammatory response can thus reflect impaired tubular clearance and could be regarded as the cause of increased serum VCAM-1 levels in RN, because RN is primarily a tubulointerstitial disease [3]. RN is also associated with significantly higher levels of serum ICAM-1 [4], and Unemoto et al. [5] also reported that there is strong ICAM-1 immunoreactivity in the proximal tubules, interstitium, and glomeruli of refluxing kidneys. These reports suggest that ICAM-1 may also play a role in the pathogenesis of impaired renal clearance. Although Musial et al. showed that serum l-selectin values in CRF were significantly lower than in controls, there are no reports in the literature about l-selectin in RN. Reduced serum l-selectin in CRF is considered to reflect the disturbed leukocyte function or migration, and it may be valuable to determine serum l-selectin levels in RN subjects and confirm whether they are reduced. We believe that serum VCAM-1 level is a useful marker for disease activity in RN. If it is also increased in other conditions such as glomerulonephritis, lupus nephropathy, and hemolytic uremic syndrome, it could act as a valuable prognostic indicator of progression to CRF, and also become the basis for immunochemical therapy of progressive renal disorders. To develop the new therapeutics for inflammation-based disorders, a novel trial using a VCAM-1 inhibitor has already been commenced [6]. Thus, we suggest that further studies on children with progressive renal disorders are necessary to develop ways of preventing progression to CRF, for example novel immunochemical therapies.