Urinary beta2-microglobulin as a marker for vesicoureteral reflux

Abstract

To determine whether urinary beta 2-microglobulin (beta 2 M) excretion would be elevated in patients with severity of vesicoureteral reflux, urinary beta 2 M/creatinine (Cr) ratios were measured on random urine samples in 56 children with various grades of reflux. Results were compared with ratios of 39 nonrefluxing patients matched for age and gender. Patients with evidence of renal insufficiency or urinary tract infection were excluded. Bladder urine was obtained at the time of the vesicoureterogram. Reflux was graded using the International Reflux Classification System. The mean urinary beta 2 M/Cr ratio was higher in the refluxing group (1.82 +/- 0.6 micrograms/mg Cr) than in the nonrefluxing control group (0.54 +/- 0.09 microgram/mg Cr. P < 0.01). When the mean urinary beta 2 M/Cr ratios were compared for each grade of reflux with the nonrefluxing control group, patients with grade IV and V reflux had significantly higher urinary beta 2 M/Cr values than the nonrefluxing patients (2.83 +/- 0.71 micrograms/mg Cr and 4.61 +/- 0.65 micrograms/mg Cr, P < 0.001, respectively). No patient with grade I, II, or III reflux had a urinary beta 2 M/Cr ratio above 0.92 microgram/mg Cr. Statistical analysis revealed no significant differences among the mean beta 2 M/Cr ratio for grade I (0.53 +/- 0.08), II (0.51 +/- 0.09), or III (0.59 +/- 0.17) refluxers or the nonrefluxing controls. Therefore, urinary beta 2 M/Cr ratios are increased in children with a high grade of reflux. Such values may be useful in the early detection of tubular damage in patients with vesicoureteral reflux.

Prospective Study on Several Urinary Biomarkers as Indicators of Renal Damage in Children with CAKUT

“…These data are consistent with previous reports in patients with UPJO 3 and VUR. 25,26 One of the mechanisms suspected of being the cause of tubular damage was tubular apoptosis. Tubular cell apoptosis is a major event in the progression of tubular atrophy and renal mass loss in an experimental model of hydronephrosis.…”

Urinary excretion of EGF and MCP-1 in children with vesico-ureteral reflux

“…IL-6 seems to be associated with the presence of high grade VUR while IL-8 is linked to scar formation (23). Recent studies (24) point to a relationship between kidney injury molecule-1 (KIM-1), a trans-membrane protein and a marker of tubular damage, and severity of scar formation while urinary excretion of Beta 2-microglobin has been tested as a urinary marker of tubular damage and scar formation in VUR patients (25, 26). In addition, MCP-1 and macrophage colony stimulating factor (M-CSF) facilitate the homing of inflammatory cells to areas of tubular damage (27).…”

The ratios of urinary β2‐microglobulin and NAG to creatinine vary with age in children

“…In contrast, β2MG (11 800 Da) is a low-molecular-weight protein, freely filtered by the glomerular basement membrane and almost completely (99%) reabsorbed by proximal tubular epithelial cells. 3,7,24,[28][29][30] NAG (140 000 Da) is a lysosomal enzyme located in the proximal renal tubular cells and does not pass through intact glomeruli; thus, its excretion is increased when the renal proximal tubular cells are damaged. 24 Ca is filtered across the glomeruli and subsequently reabsorbed along the renal tubules.…”

“…Urinary β‐2‐microglobulin and U‐NAG have been reported to be influenced by urinary pH, with U‐β2MG generally decreasing at urinary pH under 5.5–6.0, and U‐NAG generally decreasing at urinary pH >8.0 . We therefore excluded subjects with urinary pH <5.5 when assaying U‐β2MG, and subjects with urinary pH >8.0 when assaying U‐NAG.…”