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  • Title: Tubular reabsorption of high, middle and low molecular weight proteins according to the tubulo-interstitial damage marker N-acetyl-β-D-glucosaminidase in glomerulonephritis.
    Author: Bazzi C, Rizza V, Olivieri G, Casellato D, D'Amico G.
    Journal: J Nephrol; 2015 Oct; 28(5):541-8. PubMed ID: 25227764.
    Abstract:
    BACKGROUND: Proteinuria, the hallmark of glomerular diseases, is an independent predictor of end-stage renal disease (ESRD) progression. Proteinuria is a mixture of proteins of different molecular weight (MW) dependent on alterations of glomerular filtration barrier (GFB) and reabsorption impairment by proximal tubular epithelial cells (PTECs). We aimed to evaluate the excretion of different-MW proteins according to the tubulo-interstitial damage marker N-acetyl-β-D-glucosaminidase (NAG) in glomerulonephritides (GNs). METHODS: In 189 patients [idiopathic membranous nephropathy (IMN) n = 84, primary focal segmental glomerulosclerosis (FSGS) n = 48, crescentic IgA nephropathy (CIgAN) n = 37, minimal change disease (MCD) n = 20] several urinary proteins were measured at biopsy: α2-macroglobulin/creatinine ratio; fractional excretion of IgG, transferrin, albumin and α1-microglobulin, and the NAG/creatinine ratio divided by estimated glomerular filtration rate (eGFR) (NAG/C/eGFR), as NAG excretion is dependent on functioning nephron mass. Protein excretion was compared between 4th vs. 1st quartile of NAG/C/eGFR. RESULTS: In IMN, FSGS and CIgAN high-MW proteins excretion (α2-macroglobulin, IgG) was greater than that of middle- (transferrin, albumin) and low-MW proteins (α1-microglobulin) in 4th vs. 1st quartile of NAG/C/eGFR; the mean fold excretion increase of high-MW proteins in 3 GNs was 74.9, higher than that of middle- (34.8) and low-MW proteins (12.0). Higher excretion of high-MW proteins may be dependent on lower reabsorption by PTECs. By contrast, in MCD the difference in excretion of different-MW proteins is probably due to high GFB selectivity. CONCLUSION: High-MW protein excretion is dependent on GFB alteration and reduced reabsorption; its prognostic significance is ominous because in several glomerular diseases progression is associated with high-MW protein excretion.
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