NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease

被引:105
作者
Nickolas, Thomas L. [1 ]
Forster, Catherine S. [1 ]
Sise, Meghan E. [2 ]
Barasch, Nicholas [1 ]
Sola-Del Valle, David [1 ]
Viltard, Melanie [1 ]
Buchen, Charles [1 ]
Kupferman, Shlomo [1 ]
Carnevali, Maria Luisa [3 ]
Bennett, Michael [4 ]
Mattei, Silvia [3 ]
Bovino, Achiropita [3 ]
Argentiero, Lucia [3 ]
Magnano, Andrea [3 ]
Devarajan, Prasad [4 ]
Mori, Kiyoshi [5 ]
Erdjument-Bromage, Hediye [6 ]
Tempst, Paul [6 ]
Allegri, Landino [3 ]
Barasch, Jonathan [1 ]
机构
[1] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA
[2] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA
[3] Univ Parma, Nephrol Sect, Dept Med, I-43100 Parma, Italy
[4] Univ Cincinnati, Dept Med, Cincinnati Childrens Hosp, Nephrol Sect, Cincinnati, OH 45221 USA
[5] Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Kyoto, Japan
[6] Mem Sloan Kettering Canc Ctr, Dept Med, Program Mol Biol, New York, NY 10021 USA
基金
美国国家卫生研究院;
关键词
Biomarker; chronic kidney disease; pathology; GELATINASE-ASSOCIATED LIPOCALIN; ALPHA-2-MACROGLOBULIN RECEPTOR; MASS-SPECTROMETRY; SERUM CREATININE; RENAL-FUNCTION; PROTEIN; INJURY; IDENTIFICATION; NEPHROPATHY; PROGRESSION;
D O I
10.1038/ki.2012.195
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase-associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r = -0.53, P < 0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167 mu g uNGAL/g Cr, P < 0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164 mu g uNGAL/g Cr, P < 0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD.
引用
收藏
页码:718 / 722
页数:5
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