Early Urinary Markers of Diabetic Kidney Disease: A Nested Case-Control Study From the Diabetes Control and Complications Trial (DCCT)

Kern, Emily; Erhard, Penny; Sun, Wanjie; Genuth, Saul; Weiss, Miriam F.

doi:10.1053/j.ajkd.2009.11.009

Cited by 92 publications

(74 citation statements)

References 42 publications

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“…reported that urinary NAG predicted the occurrence of albuminuria in patients with diabetes mellitus (36). We are, to our knowledge, the first to investigate how a panel of markers associated with damage to different parts of the nephron relates to progression of albuminuria.…”

Section: Discussionmentioning

confidence: 87%

Glomerular and Tubular Damage Markers in Individuals with Progressive Albuminuria

Nauta

Scheven

Meijer

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Albuminuria is associated with risk for renal and cardiovascular disease. It is difficult to predict which persons will progress in albuminuria. This study investigated whether assessment of urinary markers associated with damage to different parts of the nephron may help identify individuals that will progress in albuminuria.Design, setting, participants, & measurements Individuals were selected from a prospective community-based cohort study with serial follow-up and defined as "progressors" if they belonged to the quintile of participants with the most rapid annual increase in albuminuria, and reached an albuminuria $150 mg/d during follow-up. Patients with known renal disease or macroalbuminuria at baseline were excluded. Each progressor was matched to two control participants, based on baseline albuminuria, age, and sex. Furthermore, damage markers were measured in a separate set of healthy individuals.Results After a median follow-up of 8.6 years, 183 of 8394 participants met the criteria for progressive albuminuria. Baseline clinical characteristics were comparable between progressors and matched controls (n=366). Both had higher baseline albuminuria than the overall population. Urinary excretion of the glomerular damage marker IgG was significantly higher in progressors, whereas urinary excretion of proximal tubular damage markers and inflammatory markers was lower in these individuals compared with controls. Healthy individuals (n=109) had the lowest values for all urinary damage markers measured.Conclusions These data suggest that albuminuria associated with markers of glomerular damage is more likely to progress, whereas albuminuria associated with markers of tubulointerstitial damage is more likely to remain stable.

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Section: Discussionmentioning

confidence: 87%

Glomerular and Tubular Damage Markers in Individuals with Progressive Albuminuria

Nauta

Scheven

Meijer

et al. 2013

Clinical Journal of the American Society of Nephrology

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“…[32][33][34][35] In the present study, increased NAG ratio was found in the same risk groups, which is in line with the existing literature. 20,22,[36][37][38][39][40][41] The associations with the end points may therefore in part be explained by the more adverse risk profile among individuals with increased NAG ratio. However, because the associations were independent from the traditional cardiovascular risk factors, ACR, and hsCRP, explanations other than NAG ratio solely reflecting an adverse risk profile and inflammation should be sought.…”

Section: Discussionmentioning

confidence: 99%

“…The relationship between urinary NAG and end-organ damage has been assessed mainly in cross-sectional studies of diabetic patients [16][17][18][19] and in hypertension. 20 Prospective studies of the association between urinary NAG excretion and future development of disease are scarce and have only been carried out in patients with diabetes 21,22 and chronic heart failure. 23 To our knowledge, the role of urinary NAG as a risk factor for myocardial infarction, ischemic stroke, and all-cause mortality has never been investigated, either in patient groups or in the general population.…”

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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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“…On the other hand, a small study in patients with T1D suggested that low urinary levels of KIM-1 and Nacetyl-β-D-glucosaminidase (NAG) are independently associated with regression from moderate albuminuria to normoalbuminuria [87]. A nested case-control study in DCCT also reported that elevated urinary NAG levels independently predict the development of moderate and severe albuminuria [88].…”

Section: Novel Markers For the Early Diagnosis Of Diabetic Nephropathymentioning

confidence: 99%

Diabetic Nephropathy: New Risk Factors and Improvements in Diagnosis

2015

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■ AbstractDiabetic nephropathy is the leading cause of end-stage renal disease. Patients with diabetic nephropathy have a high cardiovascular risk, comparable to patients with coronary heart disease. Accordingly, identification and management of risk factors for diabetic nephropathy as well as timely diagnosis and prompt management of the condition are of paramount importance for effective treatment. A variety of risk factors promotes the development and progression of diabetic nephropathy, including elevated glucose levels, long duration of diabetes, high blood pressure, obesity, and dyslipidemia. Most of these risk factors are modifiable by antidiabetic, antihypertensive, or lipid-lowering treatment and lifestyle changes. Others such as genetic factors or advanced age cannot be modified. Therefore, the rigorous management of the modifiable risk factors is essential for preventing and delaying the decline in renal function. Early diagnosis of diabetic nephropathy is another essential component in the management of diabetes and its complications such as nephropathy. New markers may allow earlier diagnosis of this common and serious complication, but further studies are needed to clarify their additive predictive value, and to define their cost-benefit ratio. This article reviews the most important risk factors in the development and progression of diabetic nephropathy and summarizes recent developments in the diagnosis of this disease.

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Early Urinary Markers of Diabetic Kidney Disease: A Nested Case-Control Study From the Diabetes Control and Complications Trial (DCCT)

Abstract: Background-Urinary markers were tested as predictors of macroalbuminuria or microalbuminuria in type 1 diabetes.

Cited by 92 publications

References 42 publications

Glomerular and Tubular Damage Markers in Individuals with Progressive Albuminuria

Glomerular and Tubular Damage Markers in Individuals with Progressive Albuminuria

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

Diabetic Nephropathy: New Risk Factors and Improvements in Diagnosis

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