Urinary excretion of β₂-microglobulin as a prognostic marker in immunoglobulin A nephropathy

Abstract

Background/Aimsβ2-microglobulin (β2-MG) is freely filtered at the glomerulus and subsequently reabsorbed and catabolized by proximal renal tubular cells. Urinary β2-MG is an early and sensitive biomarker of acute kidney injury; however, its utility as a biomarker of immunoglobulin A nephropathy (IgAN) is unclear.MethodsWe included urinary β2-MG levels in the routine laboratory examination of all inpatients with biopsy-proven IgAN at our hospital from 2006 to 2010. We retrospectively analyzed the correlation between β2-MG levels and clinical parameters as a prognostic biomarker of IgAN.ResultsA total of 51 patients (30 males, 21 females; mean age, 33.01 ± 12.73 years) with IgAN were included in this study. Initial demographic, clinical, and laboratory data for all patients are listed. The mean initial estimated glomerular filtration rate and 24-hour urine protein levels were 94.69 ± 34.78 mL/min/1.73 m2 and 1.28 ± 1.75 g/day, respectively. The mean level of urinary β2-MG was 1.92 ± 7.38 µg/mg creatinine. There was a significant correlation between initial serum creatinine (iSCr), urine protein creatinine ratio (UPCR), and the level of β2-MG (r = 0.744, r = 0.667, p < 0.01). There was also a significant correlation between renal function tests and the level of urinary β2-MG (p < 0.01). Cox regression analysis showed that albumin, β2-MG, iSCr, and UPCR were significant predictors of disease progression in IgAN.ConclusionsUrinary β2-MG levels showed a significant correlation with renal function and proteinuria in IgAN. Thus, we propose that urinary β2-MG may be an additional prognostic factor in patients with IgAN.

Proteinuria—take a closer look!

“…Although not documented histologically, their findings suggest that the prognostic value of the LMW protein markers in this setting reflects tubulointerstitial damage rather than impaired reabsorption due to overflow proteinuria. Although urinary ß2microglobulin was related to kidney function in patients with IgA nephropathy, Shin et al did not find a correlation between urinary ß2-microglobulin and tubulointerstitial inflammation or fibrosis [62].…”

“…Several authors have reported LMW proteinuria in patients with documented glomerular disease [19,56,[58][59][60][61][62]. Portman et al measured the fractional excretion of ß2-microglobulin in children with tubular and glomerular disease [58].…”

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

“…Collectively, the recent animal toxicology data raise important questions about both the specificity of urinary β 2 M for tubular lesions, i.e., this compound appears to detect glomerular injury better than tubular damage, and its overall utility relative to the more easily obtained assay for albuminuria. Interestingly, significant correlations between urinary β 2 M and other indices of renal damage (e.g., protein/Cr ratio) have been reported in IgA nephropathy ( 163 ) and systemic lupus erythematosus ( 164 ). Both these conditions are characterized by predominantly glomerular lesions.…”

“…Such studies are urgently needed, because the urinary β 2 M appears to have a much larger utility than previously recognized. Animal toxicology experiments conducted under rigorously controlled conditions ( 160 , 162 ) and provocative observations in glomerular diseases ( 163 , 164 ) suggest that urinary β 2 M may in fact be a better marker of glomerular than tubular damage. This finding, backed by controlled experiments in hundreds of animals and observations in a much smaller number of humans, seems to go against textbook dogma.…”

Urine Proteins and Fibrotic Lesions of Renal Compartments in Immune Glomerulopathies

“…В норме β2-МГ свободно фильтруется в клубочках, реабсорбируется и катаболизируется в проксимальных канальцах (ПК), в то время как при тубулярном повреждении ТИ уровень β2-МГ в моче повышается [7]. Вместе с тем, объяснения патогенетического и прогностического значения β2-МГ при иммунных гломерулопатиях могут выходить за пределы механистических представлений о его возможности быть маркером процесса тубулярного проксимального транспорта.…”