N-Acetyl-β-D-Glucosaminidase Does Not Enhance Prediction of Cardiovascular or All-Cause Mortality by Albuminuria in a Low-Risk Population

Abstract

Albuminuria is a well known risk factor for cardiovascular disease and mortality, but focus on renal tubular dysfunction as a potential risk factor is growing also. The association between the urinary activity of N-acetylb-D-glucosaminidase (NAG) and cardiovascular risk has been assessed mostly in cross-sectional studies. We studied the cross-sectional associations between urinary NAG and cardiovascular risk factors and the longitudinal associations between NAG, cardiovascular disease, and all-cause mortality in a general population. Urinary NAG/creatinine ratio (NAG ratio) and albumin/creatinine ratio (ACR) were measured in 6834 participants of the Tromsø Study in 1994-1995. During the median 17.5 years of follow-up, 958 myocardial infarctions, 726 ischemic strokes, and 2358 deaths were registered. In multivariable analyses adjusted for albuminuria and cardiovascular risk factors, a baseline NAG ratio in the highest quartile was associated with an increased risk of myocardial infarction (hazard ratio [HR], 1.43; 95% confidence interval [95% CI], 1.16 to 1.76), ischemic stroke (HR, 1.41; 95% CI, 1.10 to 1.80), and all-cause mortality (HR, 1.60; 95% CI, 1.39 to 1.84). Combined, ACR and NAG ratio above median associated with a 48%-80% increased risk for the three end points. However, the NAG ratio did not add significantly to the baseline risk-prediction models when assessed by area under the receiver operating characteristics curve or net reclassification improvement. In conclusion, the nonsignificant improvement of risk prediction does not support the clinical use of NAG ratio in cardiovascular risk assessment in a low-risk group.

The Association Between Adiponectin, Serum Uric Acid and Urinary Markers of Renal Damage in the General Population: Cross-Sectional Data from the Tromsø Study

“…Therefore, NAG is considered a marker of tubular dysfunction or damage [54,55]. NAG has been demonstrated to predict vascular disease in patients with diabetes [56], and we recently published that NAG-CR was independently, though weakly, associated with CVD and all-cause mortality in the general population [41]. We also showed that increasing NAG-CR was related to a more adverse cardiovascular risk profile.…”

“…Leisure physical activity was dichotomised as active (≥1 hour of physical activity with prominent perspiration or breathlessness per week), or inactive (all others). Verified information about previous myocardial infarction and/or ischaemic stroke was obtained from the Tromsø Study Cardiovascular Disease Registry [41]. Blood pressure was recorded in triplets, and the mean of the two last readings was used in the analyses.…”

Electrochemical N-Acetyl-β-D-glucosaminidase Urinalysis: Toward Sensor Chip-Based Diagnostics of Kidney Malfunction

“…B plots of the anodic 4NP peak current magnitudes, ip, as a function of the GlcNAc centration and trial time, t, show the marked difference between the voltammetr Lysosomal GlcNAcase in circulating blood is too large to pass through the filtration system of the renal glomeruli into the urine; however, it might enter urine in tiny amounts by, for instance, lysosomal exocytosis. The urine of healthy people with normal kidney function is thus not entirely free of GlcNAcase, but its level is low with 5-10 U/L having been reported for control populations in clinical studies [36,37]. The elevated and critical levels are 20 and 100 U/L or higher, respectively.…”

The renal tubular damage marker urinary N-acetyl-β-d-glucosaminidase may be more closely associated with early detection of atherosclerosis than the glomerular damage marker albuminuria in patients with type 2 diabetes

“…In a study including a low-risk general population, urinary NAG and ACR were independently associated with first-ever myocardial infarction, first-ever ischemic stroke, and all-cause mortality. However, NAG did not add to the risk predicted by traditional cardiovascular risk factors, such as eGFR and ACR [ 24 ].…”

“…There is evidence that chronic tubulointerstitial hypoxia and increased oxidative stress may play a pathogenic role in early stages of DKD [ 28 ], which in turn is related to the development of CVD. Furthermore, increased urinary NAG is a sensitive marker of tubular injury related to inflammation and oxidative stress [ 24 ]. Therefore, the elevation of urinary NAG, a renal interstitial marker, might reflect the severity of interstitial changes that result from atherosclerosis and subsequent ischemic injury [ 23 ].…”