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Vesicoureteral reflux (VUR) is the most common disease of the urinary tract in children. In order to identify gene(s) involved in this complex disorder, we performed a genome-wide search in a selected sample of 31 patients with primary VUR from eight families originating from southern Italy. Sixteen additional families with 41 patients were included in a second stage. Nonparametric, affected-only linkage analysis identified four genomic areas on chromosomes 1, 3, and 4 (p < 0.05); the best result corresponded to the D3S3681-D3S1569 interval on chromosome 3 (nonparametric linkage score, NPL = 2.75, p = 0.008). This region was then saturated with 26 additional markers, tested in the complete group of 72 patients from 24 families (NPL = 2.01, p = 0.01). We identified a genomic area on 3q22.2-23, where 26 patients from six multiplex families shared overlapping haplotypes. However, we did not find evidence for a common ancestral haplotype. The region on chromosome 1 was delimited to 1p36.2-34.3 (D1S228-D1S255, max. NPL = 1.70, p = 0.03), after additional fine typing. Furthermore, on chromosome 22q11.22-12.3, patients from a single family showed excess allele sharing (NPL = 3.35, p = 0.015). Only the chromosome 3q region has been previously reported in the single genome-wide screening available for primary VUR. Our results suggest the presence of several novel loci for primary VUR, giving further evidence for the genetic heterogeneity of this disorder.

The aim of this study was to evaluate the relationship between blood pressure (BP), measured with ambulatory blood pressure monitoring (ABPM), and the progression of renal damage in 100 (70 females, 30 males) normotensive children with reflux nephropathy (RN). The patients, mean age of 13.5+/-5 years and almost 5 years of follow-up, were divided according to degree of RN into group A (I/II) and group B (III/IV). For each subject, 24-h systolic and diastolic BP (SBP-DBP), load (percentage of BP readings that exceeded the age- and sex-specific 95th percentile), and biochemical parameters were recorded. There was no significant difference in casual BP between the groups. The mean 24-h SBP-DBP and load were significantly higher in group B than A. There was a significant difference in creatinine (Cr) levels between the groups, and Cr correlated with BP in both groups. In group B, microalbuminuria correlated with ambulatory BP, and plasma renin activity failed to decrease with chronological age. Elevated load was shown in 8 of 50 patients in group A and in 21 of 50 in group B. In 3 of 12 patients of group B, with increased load BP, left ventricular geometry, by integrated backscatter, was abnormal. ABPM was useful in selected children at risk of hypertension.