Blog entry by Meguid El Nahas

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by Meguid El Nahas - Monday, 20 October 2014, 8:40 AM
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Am J Kidney Dis. 2014 Oct 10. pii: S0272-6386(14)01163-9. doi: 10.1053/j.ajkd.2014.07.025. [Epub ahead of print]

Urine Neutrophil Gelatinase-Associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study.

 

BACKGROUND:

Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria).

STUDY DESIGN:

Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study.

SETTING & PARTICIPANTS:

3,386 participants with estimated glomerular filtration rate of 20 to 70mL/min/1.73m2 enrolled from June 2003 through August 2008.

PREDICTOR:

Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration.

OUTCOMES:

Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011.

MEASUREMENTS:

Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories).

RESULTS:

There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5ng/mL] vs lowest [≤6.9ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths.

LIMITATIONS:

Urine NGAL was measured only once.

CONCLUSIONS:

Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths.

Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.

COMMENTS:

What seems to be overlooked by one track Nephrologists and CKD aficonados is that HNAG/Lipocalin has many sources other than the renal tubules including neutrophils known to be a risch source of NGAL and involved in atherosclerosis.

http://www.ncbi.nlm.nih.gov/pubmed/22813613

In fact, leukocytosis and a high neutrophil count is alo a risk factor for CVD along with a number of neutrophils release products:

http://www.ncbi.nlm.nih.gov/pubmed/12718482

This is also the case for monocytes/monocytosis like releasers of NGAL:

http://www.ncbi.nlm.nih.gov/pubmed/16612453

So NEPHROLOGISTS  need to take their blinkers off and realise that NGAL, like previous factors before, thought to be relased from a single cell or organ, are pleomorphic factors almost universally released by numerous cells within the body...

Remember Vitamin D and its 1alpha hydroxylation..thought for generations to be unique to the kidney and noiw found to take place in numerous extra-renal cells...

Sio regardless of the kidney, its injury or otherwise, inflammatory markers including Leukocytosis, ESR, CRP, hiyerfibrogenemia, etc...and raised NGLA...are all predictors of CVD and CAD.

 

 

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