Etiology of Increased Enzymuria in Different Morphological Forms of Glomerulonephritis

Abstract

Background: High urinary excretion of lysosomal enzymes is thought to reflect tubulointerstitial damage and is observed both in the acute and chronic phases of various morphological forms of glomerulonephritis (GN). It is related to the degree of proteinuria and secondary interstitial inflammatory process. N-acetyl-β-D-glucosaminidase (NAG) and β-glucuronidase (β-GR) are the most commonly used markers of tubulointerstitial injury. NAG and β-GR are also contained in azurophilic granulations of polymorphonuclear leukocytes (PMNs) and may be released during the activation of PMNs. Aims: The aim of this study was to elucidate the role of PMN degranulation in causing the increase of urinary excretion of lysosomal enzymes that is observed in glomerulonephritis. Material and Methods: We analyzed the urinary excretion of NAG, its B isoenzyme NAG-B, β-GR and leukocyte elastase (EL), in 91 patients with morphologically different primary and secondary glomerulopathies, and in 12 healthy controls. Results: Excretion of NAG, NAG-B and β-GR were statistically significantly higher in all GN patients in comparison to healthy controls. In the whole analyzed GN population significant correlations between amount of proteinuria and excretion of NAG, NAG-B and β-GR were ascertained. In subgroup analysis NAG excretion was significantly correlated with proteinuria in patients with diffuse proliferative GN (PGN), mesangiocapillary GN (MCGN), and minimal change disease (MCD). There was a significant correlation between NAG-B and proteinuria in MCD and PGN patients. There was a significant relationship of β-GR and EL with proteinuria and EL with NAG in the PGN group. Significant relationships between serum creatinine and excretion of EL but not NAG, NAG-B, or β-GR were observed in the whole examined group. Conclusions: Increased urinary excretion of elastase, with concomitant high proteinuria and NAG excretion in patients with proliferative GN may indicate that leukocyte degranulation is an additional source of enzymuria in the primary i.e. glomerular inflammatory process. Significant relationship between EL excretion and serum creatinine may indicate that EL released from PMN may also participate in the secondary i.e. interstitial injury that is decisive in the progression of GN.

Enzymuria and low molecular weight protein excretion as the differentiating marker of complications in the early post kidney transplantation period

“…NAG-B isoenzyme has been used in determining the source of increased enzymuria. Contrary to NAG, released also from degranulated neutrophils [1,2], NAG-B specifically originates from the kidney [13]. In our study the NAG and NAG-B excretion was significantly higher in AGR and ATN groups than in SGF patients; the highest NAG and NAG-B excretion was observed in the AGR group.…”

“…Most extensively studied markers include a lysosomal enzyme-N-acetyl-b-D-glucosaminidase (NAG), which is released mainly from the proximal tubule epithelial cells, but also from degranulated leucocytes [1,2], its tubule-specific isoenzyme NAG-B, brush border enzymes-alanylaminopeptidase (AAP) and c-glutamyltransferase (GGT) [3][4][5], a-glutathione-S-transferase (a-GST) originating from proximal tubule cells cytoplasm, and p-GST originating from distal tubule cells [6,7]. Among various LMWP, retinol binding protein (RBP) and b 2 -microglobulin (b 2 M) have been measured to assess reabsorptive and catabolic functions of the tubules.…”

Urinary Markers in Healthy Young and Aged Dogs and Dogs with Chronic Kidney Disease

“…As in the present study, a report on urinary enzymes in humans with glomerulonephritis also demonstrated a correlation between uNAG/c and proteinuria and the absence of an association between uNAG/c and sCr. 44 The current hypothesis is that urinary enzymes correlate better with tubulointerstitial damage than with an indirect measurement of glomerular filtration rate such as sCr.…”

Renal biomarkers in domestic species

“…Of note, both NAG‐A and B are detectable in healthy cats . Although present in the serum and other tissues and cells, urinary NAG, GGT, and ALP originate from the renal tubules in the absence of glomerular damage …”