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      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

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          Background and objectives

          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.

          Design, setting, participants, & measurements

          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.


          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).


          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.

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          Author and article information

          Clin J Am Soc Nephrol
          Clin J Am Soc Nephrol
          Clinical Journal of the American Society of Nephrology : CJASN
          American Society of Nephrology
          7 April 2016
          22 January 2016
          : 11
          : 4
          : 593-601
          [* ]Nephrology Center,
          [§ ]Department of Pathology, and
          []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
          []Department of Pathology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
          Author notes
          Correspondence: Dr. Koki Mise, Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan, or Dr. Junichi Hoshino, Nephrology Center, Toranomon Hospital Kajigaya, 1-3-1, Kajigaya, Takatu-ku, Kawasaki-shi, Kanagawa-ken 213-0015, Japan: Email: kokims-frz@ 123456umin.ac.jp or jhoshino-ind@ 123456umin.ac.jp
          PMC4822660 PMC4822660 4822660 04980515
          Copyright © 2016 by the American Society of Nephrology
          Page count
          Pages: 9
          Original Articles
          Diabetes and the Kidney
          Custom metadata
          April 07, 2016


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