Neutrophil Gelatinase-Associated Lipocalin as an Early Biomarker of Nephropathy in Diabetic Patients

Bolignano, Davide; Lacquaniti, Antonio; Coppolino, Giuseppe; Donato, Valentina; Fazio, Maria Rosaria; Nicocia, Giacomo; Buemi, Michele

doi:10.1159/000209379

Cited by 164 publications

(149 citation statements)

References 41 publications

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“…At baseline, progressors as well as their matched controls had more albuminuria than the overall cohort population. We and others have found that albuminuria is positively associated with the urinary excretion of markers indicating damage to the proximal tubule (37,38). This is corroborated in this study, because we found such an association in patients as well as controls (Table 4).…”

Section: Discussionsupporting

confidence: 92%

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: Discussionsupporting

confidence: 92%

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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“…Biomarkers of AKI, such as NGAL, KIM‐1, and IL‐18, may be potentially beneficial for early detection, diagnosis, and prognosis of AKI after cardiac surgery 35, 36. However, in our study and others, these markers are commonly elevated at baseline, and thus a relatively large change from baseline (doubling or tripling) would be needed to detect AKI in this setting 37, 38, 39. In our study, the results in functional and novel injury markers were concordant in demonstrating no benefit of ABT‐719 treatment.…”

Section: Discussionmentioning

confidence: 66%

ABT‐719 for the Prevention of Acute Kidney Injury in Patients Undergoing High‐Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

McCullough

Bennett‐Guerrero

Chawla³

et al. 2016

JAHA

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BackgroundPatients undergoing cardiac surgeries with cardiopulmonary bypass (on‐pump) have a high risk for acute kidney injury (AKI). We tested ABT‐719, a novel α‐melanocyte‐stimulating hormone analog, for prevention of AKI in postoperative cardiac surgery patients.Methods and ResultsThis phase 2b randomized, double‐blind, placebo‐controlled trial included adult patients with stable renal function undergoing high‐risk on‐pump cardiac surgery in the United States and Denmark. Participants received placebo (n=61) or cumulative ABT‐719 doses of 800 (n=59), 1600 (n=61), or 2100 μg/kg (n=59). Primary outcome was development of AKI based on Acute Kidney Injury Network (AKIN) criteria, measured utilizing preoperative creatinine value and maximum value within 48 hours and urine output within the first 42 hours postsurgery. Secondary outcomes included incidence of AKI based on maximal changes from baseline in novel AKI biomarkers over a 72‐hour period after clamp release and length of intensive care unit stays through 90 days postsurgery. A total of 65.5%, 62.7%, and 69.6% of patients in the 800‐, 1600‐, and 2100‐μg/kg groups, respectively, developed AKI (stages 1, 2, and 3 combined) versus 65.5% in the placebo group (for each pair‐wise comparison with placebo, P=0.966, 0.815, and 0.605, respectively). Adverse events occurred at a similar rate in all treatment groups.Conclusions ABT‐719 treatment did not lower AKI incidence using AKIN criteria, influence the elevations of novel biomarkers, or change 90‐day outcomes in patients after cardiac surgery.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01777165.

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“…In patients with moderate kidney disease, serum and urine NGAL concentrations have been identified to be independent predictors of CKD progression [15]. Furthermore, urine NGAL can be used as an early biomarker of diabetic nephropathy [16]. However, urine NGAL was not found to be different between obese children and healthy controls in Goknar et al's study [11].…”

Section: Microalbuminuriamentioning

confidence: 95%

Early markers of obesity-related renal injury in childhood

Ding

Mak

2014

Pediatr Nephrol

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Childhood obesity has become a global epidemic. Recent epidemiological data suggest that obesity is associated with increased risk of renal injury in children. The onset of obesity-associated renal disease is insidious and asymptomatic, so early markers will be extremely useful in its prevention and treatment. Biomarker discovery can be focused on unbiased or biased (candidate) approaches. Unbiased approaches using innovative technologies, such as proteomics and metabolomics, have uncovered candidates that are emerging as plausible biomarkers for such renal disorders as obstructive uropathy and diabetic nephropathy. Biased approaches are based on hypotheses related to glomerular or tubular injury pathophysiology in obesity. Goknar et al. (Pediatric Nephrology 2014; doi: 10.1007/s00467-014-2829 recently evaluated early urine renal injury markers, namely, microalbuminuria, N-acetyl-beta-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and kidney injury molecule (KIM)-1, in obese children. They reported that obese children had higher urinary NAG and KIM-1 levels than healthy controls. Longitudinal observation studies are needed to evaluate whether these tubular damage markers are useful as early markers of renal injury in obese children.

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Neutrophil Gelatinase-Associated Lipocalin as an Early Biomarker of Nephropathy in Diabetic Patients

Cited by 164 publications

References 41 publications

Glomerular and Tubular Damage Markers in Individuals with Progressive Albuminuria

Glomerular and Tubular Damage Markers in Individuals with Progressive Albuminuria

ABT‐719 for the Prevention of Acute Kidney Injury in Patients Undergoing High‐Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

Early markers of obesity-related renal injury in childhood

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