Document Detail


The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy: u-NGAL, u-KIM1 and u-LFABP.
MedLine Citation:
PMID:  22268365     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aim. Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid-binding protein (LFABP). Methods. A substudy of a double-masked, randomized, cross-over study including 52 patients with type 2 diabetes, hypertension and microalbuminuria. After 2 months washout of all antihypertensive medication except bendroflumethiazid, patients were treated in random order with irbesartan 300, 600 and 900 mg for 2 months. End points. Urinary tubular markers at baseline and after each treatment period (ELISA), 24-h blood pressure, glomerular filtration rate (GFR, (51)CrEDTA) and 24-h urine albumin excretion (UAER). Results. Fifty-two patients completed the study (41 male). Age (mean (SD)): 58(10) years and diabetes duration 13(8) years. Baseline GFR was 101(24) and UAER (geometric mean [95%CI]) 133 (103-172) mg/24 h. With increasing doses of irbesartan (300, 600, 900 mg) u-KIM1 was reduced with 15%, 10% and 15% (p = 0.07 between 300 mg vs. baseline and no difference between doses). Patients with high u-KIM1 at baseline (above median) had a 32% reduction in u-KIM1 during treatment (p = 0.01). No significant decline in U-NGAL compared to baseline. U-LFABP increased during treatment (p < 0.01). Conclusions. Irbesartan treatment reduced levels of the tubular marker u-KIM1 in patients with type 2 diabetes and microalbuminuria. u-NGAL changed insignificantly and u-LFABP increased. More studies with longer follow up are needed to determine the role of tubular markers in monitoring treatment effect and prediction of prognosis in diabetic nephropathy.
Authors:
Stine E Nielsen; Kasper Rossing; Georg Hess; Dietmar Zdunek; Berit R Jensen; Hans-Henrik Parving; Peter Rossing
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-24
Journal Detail:
Title:  Scandinavian journal of clinical and laboratory investigation     Volume:  -     ISSN:  1502-7686     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0404375     Medline TA:  Scand J Clin Lab Invest     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Steno Diabetes Center , Gentofte , Denmark.
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