Pathological significance of a panel of urinary biomarkers in patients with drug-induced tubulointerstitial nephritis.
OBJECTIVE
Although a renal biopsy is indispensable for depicting the severity of pathologic lesions in drug-induced tubulointerstitial nephritis (DTIN), it is not acceptable in some cases and cannot be performed serially because of its invasive nature. Therefore, the discovery of noninvasive markers that are closely related to the pathology of DTIN is of great value.


METHODS
In this study, the urinary levels of monocyte chemotactic peptide-1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-d-glucosaminidase, and α1-microglobulin were measured in 40 DTIN subjects, and the performances of these parameters for distinguishing different pathologic lesions were compared.


RESULTS
Linear correlation and receiver operating characteristic curve analyses showed that urinary MCP-1 levels were able to identify serious interstitial edema and inflammatory infiltration with greater accuracy than the other biomarkers (r = 0.501, P < 0.001 and r = 0.768, P < 0.001, respectively), whereas urinary NGAL levels showed the highest correlation coefficient with tubular atrophy (r = 0.692, P < 0.001).


CONCLUSIONS
These results suggest that these biomarker levels were higher in patients with DTIN than in controls. Urinary MCP-1 levels correlated and were predictive of the gradated severity of acute lesions in DTIN, whereas the roles of NGAL and α1-microglobulin in chronic alterations require further study.
Wu
Yu
Y
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
Yang
Li
L
Su
Tao
T
Wang
Chen
C
Liu
Gang
G
Li
Xiao-mei
XM
D000118:Acetylglucosaminidase / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000510:Alpha-Globulins / Q000652:urine; D001284:Atrophy; D015415:Biomarkers / Q000652:urine; D001706:Biopsy; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000652:urine; D002681:China; D005260:Female; D005355:Fibrosis; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000652:urine; D012372:ROC Curve; D012720:Severity of Illness Index; D055815:Young Adult
D000209:Acute-Phase Proteins; D000510:Alpha-Globulins; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C016001:alpha-1-microglobulin; D000118:Acetylglucosaminidase
Curr Opin Nephrol Hypertens. 2003 Nov;12(6):639-43
14564202
Clin Chem. 2004 Mar;50(3):552-8
14709451
Kidney Int. 1999 Feb;55(2):713-23
9987096
J Clin Invest. 1987 Feb;79(2):319-26
3543052
Ann Acad Med Singap. 2001 Mar;30(2):112-7
11379406
J Am Soc Nephrol. 1996 Jun;7(6):906-13
8793800
Clin Chim Acta. 1981 Oct 8;116(1):25-34
6172216
Lancet. 2005 Apr 2-8;365(9466):1231-8
15811456
Kidney Int. 2008 Apr;73(7):863-9
18059454
Am J Kidney Dis. 2003 Sep;42(3):497-506
12955677
Pediatr Nephrol. 2007 Jan;22(1):101-8
17072653
Am J Nephrol. 2004 May-Jun;24(3):307-15
15148457
Kidney Int. 2006 Jul;70(1):199-203
16710348
J Immunol. 2003 Dec 15;171(12):6630-9
14662866
Kidney Blood Press Res. 2008;31(4):255-8
18600028
J Am Soc Nephrol. 2003 Oct;14(10):2534-43
14514731
Am J Kidney Dis. 2003 Apr;41(4):760-6
12666062
Toxicol Lett. 2003 Aug 28;143(3):279-90
12849688
Ren Fail. 1997 Jan;19(1):15-22
9044448