Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM1) in patients with diabetic nephropathy: a cross-sectional study and the effects of lisinopril

• Published in: Diabetic medicine Vol. 27; no. 10; pp. 1144 - 1150
• Main Authors: Nielsen, S. E., Schjoedt, K. J., Astrup, A. S., Tarnow, L., Lajer, M., Hansen, P. R., Parving, H.-H., Rossing, P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2010; Blackwell
• Subjects: ACE inhibition; Acute-Phase Proteins - urine; albuminuria; Albuminuria - urine; Associated diseases and complications; Biological and medical sciences; Creatinine; Cross-Sectional Studies; Diabetes mellitus; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - urine; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - urine; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Hepatitis A Virus Cellular Receptor 1; Humans; Injuries; Kidney; Leukocytes (neutrophilic); Lipocalin; Lipocalin-2; Lipocalins - urine; Lisinopril - therapeutic use; Male; Medical sciences; Membrane Glycoproteins - drug effects; Membrane Glycoproteins - urine; Middle Aged; nephrology; Nephropathy; Proto-Oncogene Proteins - urine; Receptors, Virus - drug effects; Statistical analysis; tubular damage; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Nephrology; Kidney; Peptidyl-dipeptidase A; Cross sectional study; Metastasis suppressor gene; Diabetic nephropathy; Inhibition; Nutritional status; Kidney disease; Human; Urine; Obesity; Urinary system disease; Lisinopril; Nutrition; Enzyme; ACE inhibition; Diabetes mellitus; Nutrition disorder; Enzyme inhibitor; Albumin; tubular damage; Patient; Metabolic diseases; Trauma; Peptidases; albuminuria; Concomitant disease; Urinary system; Hydrolases; Peptidyl-dipeptidases; Antihypertensive agent; Lesion; Neutrophil gelatinase associated lipocalin; ACE inhibitor; Endocrinology; Proteinuria
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2010.03083.x

Diabet. Med. 27, 1144–1150 (2010) Aims  Our aim was to evaluate the markers of tubulointerstitial damage, neutrophil gelatinase‐associated lipocalin (NGAL) and kidney injury molecule 1 (KIM1) in Type 1 diabetic patients with different levels of albuminuria and in control subjects. In addition, the effect of renoprotective treatment on urinary NGAL was evaluated in diabetic nephropathy. Methods  This was a cross‐sectional study in 58 normoalbuminuric (u‐albumin < 30mg/24 h), 45 microalbuminuric (30–300 mg/24 h) and 45 macroalbuminuric (> 300 mg/24 h) Type 1 diabetic patients and 55 non‐diabetic control subjects. Furthermore, in a second study, urine‐NGAL was measured in a randomized cross‐over study of 56 Type 1 diabetic patients with diabetic nephropathy treated with lisinopril 20, 40 and 60 mg daily. Results  Urine‐NGAL levels were [geometric mean (95% CI)]: control subjects 74 (52–104) (pg/mmol creatinine), normoalbuminuric 146 (97–221), microalbuminuric 222 (158–312) and macroalbuminuric group 261 (175–390). Urine‐NGAL increased significantly from the normo‐ to the micro‐ and further to the macroalbuminuric group (P < 0.05). Urine‐NGAL was higher in normoalbuminuric vs. control subjects (P < 0.01). Plasma‐NGAL was significantly higher in the normoalbuminuric and macroalbuminuric groups than in the control group. Urine‐KIM1 was higher in all diabetic groups than in the control group (P < 0.001), with no difference between diabetic groups. During lisinopril treatment, urine‐NGAL was reduced (95% CI) 17% (11–50) (not significant). Conclusions  Urine‐NGAL and urine‐KIM1 (u‐KIM1) are elevated in Type 1 diabetic patients, with or without albuminuria, indicating tubular damage at an early stage. Urine‐NGAL increases significantly with increasing albuminuria. The ACE inhibitor lisinopril reduced urine‐NGAL, but this was not statistically significant.