Koki Mise , * , † , ‡ , Junichi Hoshino * , Toshiharu Ueno * , Ryo Hazue * , Jumpei Hasegawa * , Akinari Sekine * , Keiichi Sumida * , Rikako Hiramatsu * , Eiko Hasegawa * , Masayuki Yamanouchi * , Noriko Hayami * , Tatsuya Suwabe * , Naoki Sawa * , Takeshi Fujii § , Shigeko Hara * , † , Kenichi Ohashi § , ‖ , Kenmei Takaichi * , † , Yoshifumi Ubara * , †
22 January 2016
diabetic nephropathy, renal pathology, renal prognosis, tubulointerstitial lesion, urinary biomarker, diabetes mellitus, type 2, disease progression, follow-up studies, humans, kidney failure, chronic
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.
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).