Primary, nonsyndromic vesicoureteric reflux and nephropathy in sibling pairs: a United Kingdom cohort for a DNA bank

Abstract

Background and objectives: Primary vesicoureteric reflux (VUR) can coexist with reflux nephropathy (RN) and impaired renal function. VUR appears to be an inherited condition and is reported in approximately one third of siblings of index cases. The objective was to establish a DNA collection and clinical database from U.K. families containing affected sibling pairs for future VUR genetics studies. The cohort's clinical characteristics have been described.

Design, setting, participants, & measurements: Most patients were identified from tertiary pediatric nephrology centers; each family had an index case with cystography-proven primary, nonsyndromic VUR. Affected siblings had radiologically proven VUR and/or radiographically proven RN.

Results: One hundred eighty-nine index cases identified families with an additional 218 affected siblings. More than 90% were <20 years at the study's end. Blood was collected and leukocyte DNA extracted from all 407 patients and from 189 mothers and 183 fathers. Clinical presentation was established in 122; 92 had urinary tract infections and 16 had abnormal antenatal renal scans. RN was radiologically proven in 223 patients. Four patients had been transplanted; none were on dialysis. In 174 others aged >1 year, estimated GFR (eGFR) was calculated. Five had eGFR 15 to 59 and 48 had eGFR 60 to 89 ml/min per 1.73 m(2). Values were lower in bilateral RN patients than in those with either unilateral or absent RN.

Conclusions: The large DNA collection from families with VUR and associated RN constitutes a resource for researchers exploring the most likely complex, genetic components predisposing to VUR and RN.

Figure 1.

Age (in years) distribution of 407 individuals.

Figure 2.

Mean (±95% confidence intervals) eGFR in VUR patients with bilateral, unilateral, and no reflux nephropathy (RN).

Figure 3.

Box plot of age (in years) in VUR patients with bilateral, unilateral, and no RN. The boundary of the box closest to zero indicates the 25th percentile, the line within the box shows the median, and the boundary of the box farthest from zero indicates the 75th percentile. Whiskers (error bars) above and below the box indicate the 90th and 10th percentiles. Outlying points are shown.