title: Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-d-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy-Proven Diabetic Nephropathy.
abstract: OBJECTIVE
  Some biomarkers of renal tubular injury are reported to be useful for predicting renal prognosis in the early stage of diabetic nephropathy (DN). Our study compared predictions of the renal prognosis by such biomarkers and by histologic tubulointerstitial damage.
  
  
  METHODS
  Among 210 patients with type 2 diabetes and biopsy-proven DN managed from 1985 to 2011, 149 patients with urinary N-acetyl-β-d-glucosaminidase (NAG) and urinary β2-microglobulin (β2-MG) data at the time of renal biopsy were enrolled. The primary outcome was a decline in eGFR of ≥50% from baseline or commencement of dialysis for ESRD.
  
  
  RESULTS
  The median follow-up period was 2.3 years (interquartile range, 1.1-5.3), and the primary outcome was noted in 94 patients. Mean eGFR was 46.3±23.2 ml/min per 1.73 m(2), and 132 patients (89%) had overt proteinuria at baseline. Cox proportional hazards analysis revealed that the association of urinary NAG and β2-MG with the outcome was attenuated after adjustment for known promoters of progression (+1 SD for log NAG: hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 0.84 to 1.55; +1 SD for log β2-MG: HR, 1.23; 95% CI, 0.94 to 1.62). In contrast, the interstitial fibrosis and tubular atrophy (IFTA) score was still significantly correlated with the outcome after adjustment for the same covariates (+1 for IFTA score: HR, 2.31; 95% CI, 1.56 to 3.43). Moreover, adding the IFTA score to a model containing known progression indicators improved prediction of the outcome (increase of concordance index by 0.02; 95% CI, 0.00 to 0.05; category-free net reclassification improvement by 0.54; 95% CI, 0.03 to 1.05; and relative integrated discrimination improvement by 0.07; 95% CI, -0.08 to 0.22).
  
  
  CONCLUSIONS
  Adding urinary NAG and β2-MG excretion to known promoters of progression did not improve prognostication, whereas adding the IFTA score did. The IFTA score may be superior to these tubulointerstitial markers for predicting the renal prognosis in advanced DN.
authors.affiliation: Nephrology Center, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan; Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; and kokims-frz@umin.ac.jp jhoshino-ind@umin.ac.jp.
authors.forename: Koki
authors.initials: K
authors.lastname: Mise
authors.affiliation: Nephrology Center.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hoshino
authors.affiliation: Nephrology Center.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Nephrology Center.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hazue
authors.affiliation: Nephrology Center.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Hasegawa
authors.affiliation: Nephrology Center.
authors.forename: Akinari
authors.initials: A
authors.lastname: Sekine
authors.affiliation: Nephrology Center.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sumida
authors.affiliation: Nephrology Center.
authors.forename: Rikako
authors.initials: R
authors.lastname: Hiramatsu
authors.affiliation: Nephrology Center.
authors.forename: Eiko
authors.initials: E
authors.lastname: Hasegawa
authors.affiliation: Nephrology Center.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamanouchi
authors.affiliation: Nephrology Center.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hayami
authors.affiliation: Nephrology Center.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suwabe
authors.affiliation: Nephrology Center.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sawa
authors.affiliation: Department of Pathology, and.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Nephrology Center, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan;
authors.forename: Shigeko
authors.initials: S
authors.lastname: Hara
authors.affiliation: Department of Pathology, and Department of Pathology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Nephrology Center, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan;
authors.forename: Kenmei
authors.initials: K
authors.lastname: Takaichi
authors.affiliation: Nephrology Center, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan;
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ubara
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine*; D015415:Biomarkers; D001706:Biopsy; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000652:urine*; D018450:Disease Progression; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology*; D011379:Prognosis; D014551:Urinary Tract; D001613:beta 2-Microglobulin / Q000652:urine*
chemical_list: D015415:Biomarkers; D001613:beta 2-Microglobulin; D000118:Acetylglucosaminidase
keywords: diabetes mellitus, type 2; diabetic nephropathy; disease progression; follow-up studies; humans; kidney failure, chronic; renal pathology; renal prognosis; tubulointerstitial lesion; urinary biomarker