Urinary N-acetyl-β-D glucosaminidase as a surrogate marker for renal function in autosomal dominant polycystic kidney disease: 1 year prospective cohort study

Park, Hayne Cho; Hwang, Jin Ho; Kang, Ah Young; Ro, Han; Kim, Myung Gyu; An, Jung Nam; Park, Ji In; Kim, Seung Hyup; Yang, Jaeseok; Oh, Yun Kyu; Oh, Kook Hwan; Noh, Jung Woo; Cheong, Hae Il; Hwang, Young Hwan; Ahn, Curie

doi:10.1186/1471-2369-13-93

Cited by 29 publications

(21 citation statements)

References 21 publications

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“…Finally, few studies have investigated the association of urinary NAG with ESRD events, but our study is consistent with prior reports in the Pima Indians and adults with autosomal dominant polycystic kidney disease, where urinary NAG was not associated with CKD progression or eGFR decline after adjustment for traditional risk factors for CKD progression (15,18).…”

Section: Discussionsupporting

confidence: 81%

Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study

Foster

Coresh

Bonventre

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Liver fatty acid binding protein (L-FABP), kidney injury molecule 1 (KIM-1), N-acetylb-D-glucosaminidase (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) are urinary markers of tubular injury that may also be markers of chronic kidney damage. We evaluated the association of these markers with incident ESRD in a community-based sample from the Atherosclerosis Risk in Communities Study.Design, setting, participants, & measurements This was a matched case-control study of 135 patients with ESRD and 186 controls who were matched on sex, race, kidney function, and diabetes status at baseline (Atherosclerosis Risk in Communities Study visit 4, 1996Study visit 4, -1998. Urinary KIM-1 indexed to creatinine (Cr), NAG/Cr, NGAL/Cr, and L-FABP/Cr were measured in stored spot urine samples from the baseline examination. Associations of KIM-1/Cr, NAG/Cr, and NGAL/Cr with patients with incident ESRD through 2008 were modeled continuously and categorically (quartiles) using conditional logistic regression. L-FABP/Cr was modeled only categorically because of a large number of measurements below the lower limit of detection for the assay (2.4 ng/ml).Results No significant associations were observed for NAG/Cr, NGAL/Cr, or L-FABP/Cr with ESRD. Those in the highest category for KIM-1/Cr had a higher risk of ESRD compared with those with undetectable biomarker levels (reference group) in unadjusted models (odds ratio, 2.24; 95% confidence interval, 1.97 to 4.69; P=0.03) or adjustment for age (odds ratio, 2.23; 95% confidence interval, 1.06 to 4.67; P=0.03). This association was attenuated with additional adjustment for baseline kidney function (odds ratio, 2.02; 95% confidence interval, 0.95 to 4.31; P=0.07 after additional adjustment for eGFR and natural log of the urinary albumin-to-creatinine ratio). No association between KIM-1/Cr and ESRD was found when KIM-1/Cr was analyzed as a continuous variable.Conclusions Elevated urinary KIM-1/Cr may be associated with a higher risk of incident ESRD, but it does not add to risk prediction after accounting for traditional markers of kidney function in this population.

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Section: Discussionsupporting

confidence: 81%

Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study

Foster

Coresh

Bonventre

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…2 Increased urinary NAG activity has been described in various disease states such as heavy metal poisoning and renal diseases. [3][4][5][6][7] Most authors consider increased urinary NAG to be a sensitive marker of tubular injury, 8 related to inflammation and oxidative stress. Albumin in the urine is traditionally considered to be of glomerular origin, 9 although impaired tubular reabsorption may contribute in the pathogenesis of increased urinary albumin excretion (UAE).…”

mentioning

confidence: 99%

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

Solbu

Toft

Løchen

et al. 2016

Journal of the American Society of Nephrology

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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.

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“…Interestingly, the urinary NGAL levels in each mouse were correlated with KW. It was also reported that NGAL is abundant in the cyst fluid of patients with ADPKD Park et al, 2012). Therefore, elevated NGAL might be a common feature of PKD in human patients and rodent models.…”

Section: Discussionmentioning

confidence: 99%

Tolvaptan Delays the Onset of End-Stage Renal Disease in a Polycystic Kidney Disease Model by Suppressing Increases in Kidney Volume and Renal Injury

Aihara

Fujiki

Mizuguchi

et al. 2014

J Pharmacol Exp Ther

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Tolvaptan, a selective vasopressin V 2 receptor antagonist, slows the increase in total kidney volume and the decline in kidney function in patients with the results of the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Outcome (TEMPO) 3:4 trial. However, it was unclear which dose of tolvaptan was optimal or whether tolvaptan was able to delay progression to end-stage renal disease (ESRD). Here we examined the relationship with aquaresis and the inhibitory effect on cyst development in short-term treatment and mortality as an index of ESRD in long-term treatment with tolvaptan using DBA/2FG-pcy mice, an animal model of nephronophthisis. With short-term treatment from 5 to 15 weeks of age, tolvaptan (0.01-0.3% via diet) dose-dependently enhanced aquaresis, prevented increases in kidney weight and cyst volume, and was associated with significant reductions in kidney cAMP levels and extracellular signal-regulated kinase activity. Maximal effects of tolvaptan on aquaresis and the prevention of development of polycystic kidney disease (PKD) were obtained at 0.1%. Interestingly, tolvaptan also dose-dependently reduced urinary neutrophil gelatinase-associated lipocalin levels in correlation with the kidney volume. With long-term treatment from 5 to 29 weeks of age, tolvaptan significantly attenuated the increase in kidney volume by up to 50% and reduced urinary albumin excretion. Furthermore, tolvaptan significantly reduced the mortality rate to 20%, compared with 60% in the control group. These data indicate that tolvaptan may delay the onset of ESRD in PKD by suppressing the increases in kidney volume and renal injury, providing a promising treatment for PKD.

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Urinary N-acetyl-β-D glucosaminidase as a surrogate marker for renal function in autosomal dominant polycystic kidney disease: 1 year prospective cohort study

Cited by 29 publications

References 21 publications

Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study

Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study

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

Tolvaptan Delays the Onset of End-Stage Renal Disease in a Polycystic Kidney Disease Model by Suppressing Increases in Kidney Volume and Renal Injury

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