Urinary excretion of β2-glycoprotein-1 (apolipoprotein H) and other markers of tubular malfunction in 'non-tubular' renal disease

Abstract

Aim: To determine whether urinary β2-glycoprotein-1 assays can provide improved discrimination between chronic renal diseases which are primarily of tubular or glomerular origin. Methods: Urinary β2-glycoprotein-1, retinol-binding protein, α1-microglobulin, β2-microglobulin, N-acetyl-β-D-glucosaminidase and albumin were measured in 51 patients with primary glomerular disease, 23 with obstructive nephropathy, and 15 with polycystic kidney disease, and expressed per mmol of creatinine. Plasma β2-glycoprotein-1 was assayed in 52 patients and plasma creatinine in all 89. The findings were compared between the diagnostic groups and with previously published data relating to primary tubular disorders. Results: All 31 patients with plasma creatinine greater than 200 μmol/l excreted increased amounts of β2-glycoprotein-1, retinol-binding protein, and α1-microglobulin, and 29 had increased N-acetyl-β-D-glucosaminidase; the quantities were generally similar to those found in comparable patients with primary tubular pathology. Among 58 with plasma creatinine concentations under 200 μmol/l, increases in β2-glycoprotein-1, retinol-binding protein, and α1-microglobulin excretion were less common and much smaller, especially in those with obstructive nephropathy and polycystic disease. The ratios of the excretion of albumin to the other proteins provided the clearest discrimination between the patients with glomerular or tubular malfunction, but an area of overlap was present which embraced those with obstructive nephropathy and polycystic disease. Conclusions: Increased excretion of β2-glycoprotein-1 due to a raised plasma concentration or diminution of tubular reabsorption, or both, is common in all the forms of renal disease investigated, and both plasma creatinine and urinary albumin must be taken into account when interpreting results. Ratios of urinary albumin: β2-glycoprotein-1 greater than 1000 are highly suggestive of primary glomerular disease and those less than 40 of primary tubular disease. Used in this way, β2-glycoprotein-1 assays provide superior discrimination between glomerular and tubular malfunction when compared with retinol binding protein but the best discrimination is provided by albumin: α1-microglobulin ratios.