Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons.
Urinary neutrophil gelatinase-associated lipocalin (Ngal or lipocalin 2) is a very early and sensitive biomarker of kidney injury. Here we determined the origin and time course of Ngal appearance in several experimental and clinically relevant renal diseases. Urinary Ngal levels were found to be markedly increased in lipoatrophic- and streptozotocin-induced mouse models of diabetic nephropathy. In the latter mice, the angiotensin receptor blocker candesartan dramatically decreased urinary Ngal excretion. The reabsorption of Ngal by the proximal tubule was severely reduced in streptozotocin-induced diabetic mice, but upregulation of its mRNA and protein in the kidney was negligible, compared to those of control mice, suggesting that increased urinary Ngal was mainly due to impaired renal reabsorption. In the mouse model of unilateral ureteral obstruction, Ngal protein synthesis was dramatically increased in the dilated thick ascending limb of Henle and N was found in the urine present in the swollen pelvis of the ligated kidney. Five patients with nephrotic syndrome or interstitial nephritis had markedly elevated urinary Ngal levels at presentation, but these decreased in response to treatment. Our study shows that the urinary Ngal level may be useful for monitoring the status and treatment of diverse renal diseases reflecting defects in glomerular filtration barrier, proximal tubule reabsorption, and distal nephrons.
Kuwabara
Takashige
T
Department of Medicine and Clinical Science, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
Mori
Kiyoshi
K
Mukoyama
Masashi
M
Kasahara
Masato
M
Yokoi
Hideki
H
Saito
Yoko
Y
Yoshioka
Tetsuro
T
Ogawa
Yoshihisa
Y
Imamaki
Hirotaka
H
Kusakabe
Toru
T
Ebihara
Ken
K
Omata
Mitsugu
M
Satoh
Noriko
N
Sugawara
Akira
A
Barasch
Jonathan
J
Nakao
Kazuwa
K
D058186:Acute Kidney Injury / Q000378:metabolism; D000209:Acute-Phase Proteins / Q000378:metabolism* / Q000652:urine; D000418:Albumins / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use; D015415:Biomarkers / Q000652:urine; D001713:Biphenyl Compounds; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000652:urine; D004195:Disease Models, Animal; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism* / Q000652:urine; D008138:Loop of Henle / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009395:Nephritis, Interstitial / Q000378:metabolism / Q000652:urine; D009399:Nephrons / Q000378:metabolism*; D009404:Nephrotic Syndrome / Q000378:metabolism / Q000652:urine; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D012680:Sensitivity and Specificity; D013777:Tetrazoles / Q000627:therapeutic use; D013997:Time Factors; D014517:Ureteral Obstruction / Q000378:metabolism
D000209:Acute-Phase Proteins; D000418:Albumins; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D013777:Tetrazoles; C081643:candesartan