Urinary N-Acetyl-β-D-Glucosaminidase (NAG) Index in Cats with Variable Azotaemia and as a Predictor of Kidney Disease
Diagnosis of feline chronic kidney disease is based on the development of azotaemia and inadequate urine concentrating ability by which time substantial damage to the kidney will already have occurred. NAG is a lysosomal enzyme expressed at high levels in the proximal tubular cells (PTC). Increased protein processing or damage to the PTC may increase NAG release and activity in the urine. NAG activity may therefore be an early marker of kidney damage.
Geriatric (>9 years) cats with variable plasma creatinine concentration were recruited from 2 first opinion practices in central London. Cats received a physical examination, plasma biochemistry, measurement of systolic blood pressure, urinalysis and evaluation of urine protein to creatinine ratio (UP/C). Total T4 concentration was evaluated in all non-azotaemic cats. A colorimetric enzymatic assay involving the conversion of 3-Cresolsulfonphthaleinyl-N-acetyl-β-glucosaminide to 3-cresol-purple was used to assess NAG activity. Non-azotaemic cats were offered re-examinations at 12 months and were classified according to their renal status at this time (non-azotaemic or azotaemic (plasma creatinine > 2.0mg/dL)).
NAG activity was standardised to urine creatinine concentration to give the NAG index. Results are reported as median [25th, 75th percentile]. NAG index and UP/C were logarithmically transformed for parametric statistical analysis. Cats were grouped according to their plasma creatinine concentration; I <1.6mg/dL, IIa 1.6-2.0mg/dL, IIb 2.0-2.8mg/dL, III 2.8-5.0mg/dL, IV >5.0mg/dL and according to their magnitude of proteinuria; UP/C<0.2 non-proteinuric, UP/C 0.2-0.4 borderline proteinuric, UP/C>0.4 proteinuric. A one-way ANOVA was used to compare groups and where necessary a Bonferroni post-test was applied. Pearson's correlation was used to assess the relationship between plasma creatinine and log UP/C with log NAG index. A student t-test was used to compare log NAG index between non-azotaemic cats that remained non-azotaemic at 12 months and those which developed azotaemia.
NAG index was evaluated in 197 cats of which 93 were non-azotaemic. No significant difference was found in log NAG index when cats were grouped according to plasma creatinine concentration (p=0.06). The correlation between plasma creatinine and log NAG index was poor (r=0.154, p=0.031). A significant difference was found in log NAG index when cats were grouped by magnitude of proteinuria (p<0.001) and a significant positive correlation was found between log UP/C and log NAG index (r=0.499, p<0.001). In non-azotaemic cats NAG index was significantly higher in those cats that developed azotaemia (n=19, 1.52 [0.82, 5.32] U/g) than in those that remained non-azotaemic at 12 months (n=56, 0.64 [0.21, 1.30] U/g; p=0.0014).
NAG index may indicate early tubular damage in the cat before the onset of azotaemia and correlates with the magnitude of proteinuria and potentially tubular processing of protein in cats with variable azotaemia.