title: Clinical and pathological predictors of estimated GFR decline in patients with type 2 diabetes and overt proteinuric diabetic nephropathy.
abstract: BACKGROUND
  The effect of clinical and pathological parameters on the estimated glomerular filtration rate (eGFR) decline has not been investigated in patients with type 2 diabetes and overt proteinuric biopsy-proven diabetic nephropathy.
  
  
  METHODS
  Among 198 patients with type 2 diabetes who underwent renal biopsy and were confirmed to have pure diabetic nephropathy according to the recent classification, 128 patients with overt proteinuria were enrolled. Receiver operating characteristic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were performed using models adjusted for various clinical and pathological covariates to determine the best predictors of rapid eGFR decline [defined as >14.9%/year (median eGFR decline)].
  
  
  RESULTS
  A model that incorporated proteinuria showed the largest area under the curve (AUC) among clinical models, which suggested that proteinuria was the best clinical predictor. Although a model incorporating interstitial fibrosis and tubular atrophy (IFTA) score did not display a significantly larger AUC than the model with proteinuria (0.843 vs 0.812, respectively, p = 0.47), a model with both IFTA score and proteinuria had a significantly larger AUC than the model with proteinuria alone (0.875 vs 0.812, respectively, p = 0.014). Similarly, the addition of IFTA score resulted in a significantly greater net reclassification improvement and integrated discrimination improvement than the model with proteinuria alone [NRI: 0.78 (95% CI: 0.43-1.13; p < 0.001), IDI: 0.13 (95% CI: 0.07-0.19; p < 0.001)].
  
  
  CONCLUSIONS
  Our results suggest that not only proteinuria but also tubulointerstitial lesions should be assessed to predict rapid eGFR decline in patients with type 2 diabetes who have overt proteinuria and biopsy-proven diabetic nephropathy.
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Mise
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hoshino
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hazue
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sumida
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Rikako
authors.initials: R
authors.lastname: Hiramatsu
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Hasegawa
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamanouchi
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hayami
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suwabe
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sawa
authors.affiliation: Department of Pathology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.|Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Shigeko
authors.initials: S
authors.lastname: Hara
authors.affiliation: Department of Pathology, Toranomon Hospital, Tokyo, Japan.|Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.|Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Kenmei
authors.initials: K
authors.lastname: Takaichi
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.|Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ubara
mesh_terms: D000368:Aged; D001284:Atrophy / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers; D001707:Biopsy, Needle; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000473:pathology / Q000503:physiopathology; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000150:complications* / Q000209:etiology; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers
keywords: diabetic nephropathy; eGFR decline; integrated discrimination improvement analysis; net reclassification improvement analysis; receiver operating characteristic analysis; renal pathology