Specific Developmental Profiles of Lysosomal and Brush Border Enzymuria in the Human

Abstract

Various enzymatic urinary activities have been proposed to assess renal proximal tubule damage in children, including neonates. Nevertheless comprehensive knowledge on the developmental aspects of physiological enzymuria is limited, particularly with regard to lysosomal and brush border enzymuria. Urinary activities of two lysosomal enzymes, N-acetyl-β-D-glucosaminidase (NAG) and β-galactosidase (GAL), and of two brush border enzymes, alanine aminopeptidase (AAG) and γ-glutamyltransferase (GGT) were comparatively investigated in normal prematures (n = 28), term neonates (n = 52), infants aged less than 2 years (n = 19) and children (n = 33), and compared to urinary excretion of β₂-microglobulin (B2M). Enzymatic activities were assayed using either spectrophotometrical (NAG, AAP, GGT) fluorimetrical (GAL) or radioimmunological (B2M) methods, and were related to urinary creatinine excretion. Developmental profiles of both the studied lysosomal enzymes and of B2M were similarly characterized with significantly decreasing values from prematures (NAG 9.29 ± 1.44, GAL 2.26 ± 0.26 IU/mmol creatinine, indicated as mean ± SEM) to term neonates (6,94 ± 0.58 and 1.76 ± 0.15 IU/ mmol creatinine, respectively) and older infants and children. Lysosomal enzymatic urinary activities correlated linearly with a coefficient of r = 0.75, (p < 0.05), while correlations between each lysosomal enzymatic activity and B2M urinary excretion were weaker. Profiles of both the studied brush border enzymes were characterized with lower activities in prematures (AAP 4.45 ± 0.44, GGT 5.52 ± 0.49 IU/mmol creatinine) than in term neonates (5.62 ± 0.92 and 9.1 ± 1.73 IU/mmol creatinine, respectively) or even in infants with respect to GGT (AAP 4.06 ± 0.72 and GGT 11.54 ± 1.71 IU/mmol creatinine), with a consecutive decrease of activities in older infants or children. It is concluded that lysosomal and brush border enzymuria follow different developmental profiles in the normal human. Studies involving enzymuria as a marker of tubular lesion should include the measurements of at least one lysosomal and one brush border enzymatic activity, and should be interpreted with reference to the respective, specific developmental profiles.

Renal injury in perinatal hypoxia: ultrasonography and changes in renal function

“…As to the tubular markers, FE Na values on both days and urinary NAG activities on day 3 were signi®cantly higher in the hypoxaemic neonates than in the control group (Tables 2 and 3). In the case of premature infants this results can partially be explained by the immaturity of tubular function [12]. Healthy control neonates did not exhibit appreciable changes in the measured parameters.…”

Targeted design of a recombinant tracer for SPECT renal imaging

“…In PBT-Fc, we emphasize that the Fc module of the tracer directs protein reuptake at the proximal tubule through a different mechanism than protein sorting by megalin and cubilin. Megalin and cubilin direct their respective ligands such as β2M to lysosomal degradation in tubular cells 38 , leading to the release and subsequent urinary excretion of any radionuclide attachments. In contrast, FcRn mediates transcytotic recycling that can circumvent lysosomal degradation of its 'cargo' proteins such as albumin and IgG 39 .…”

Urinary N-Acetyl-β-<i>D</i>-Glucosaminidase Excretion in Newborns

“…Dear Sir, We read with much interest the article of Simeoni et al [1] about the specific developmental profiles of lysosomal and brush border enzymuria in the human. Preterm urinary N-acetyl-P-D-glucosaminidase (NAG) activity was greater than that in term neonates in their study.…”