title: Nodular lesions in diabetic nephropathy: Collagen staining and renal prognosis.
abstract: OBJECTIVE
  Nodular lesions are one of the most characteristic pathological changes of advanced diabetic nephropathy (DN). Previous studies have demonstrated that the pattern of both routine and collagen staining of nodular lesions changes during their development. However, the association between such changes of staining and the renal prognosis remains unclear.
  
  
  METHODS
  Among 252 patients with biopsy-proven DN, 67 met the selection criteria and were enrolled to investigate this relationship. In all patients, nodular lesions were stained with periodic acid Schiff, periodic acid methenamine silver, and Masson trichrome stains, and immunostaining was done for type I, III, IV, V, and VI collagen. The endpoint was commencement of dialysis due to end-stage renal disease.
  
  
  RESULTS
  At least one mesangiolytic nodular lesion (MNL) that showed faint staining for PAS and PAM was found in 61% of the patients. MNLs were negative for type IV collagen staining, unlike the strong positivity of non-MNLs, while type V and VI collagen staining were strongly positive in all nodular lesions. Cox proportional hazards regression analysis revealed that the hazard ratio (HR) for the endpoint was significantly higher in patients with at least one MNL than in patients with no MNLs after adjustment for known promoters of renal progression (HR: 2.94; 95% confidence interval: 1.24-7.07).
  
  
  CONCLUSIONS
  MNLs may reflect characteristic differences of collagen production and could be a useful prognostic indicator in patients with nodular lesions. Further investigation of the mechanism underlying these differences of collagen production could contribute to finding new therapeutic targets for DN.
authors.affiliation: Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan; 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, Okayama, Japan. Electronic address: kokims-frz@umin.ac.jp.
authors.forename: Koki
authors.initials: K
authors.lastname: Mise
authors.affiliation: Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hoshino
authors.affiliation: Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hazue
authors.affiliation: Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sumida
authors.affiliation: Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamanouchi
authors.affiliation: Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hayami
authors.affiliation: Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suwabe
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: 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 Kajigaya, Kanagawa, Japan; 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 Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.affiliation: Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
authors.affiliation: Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan; 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: Department of Pathology, Toranomon Hospital, Tokyo, Japan; 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, Toranomon Hospital Kajigaya, Kanagawa, Japan; 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; D001706:Biopsy; D024141:Collagen Type IV / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000473:pathology*; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D006435:Renal Dialysis / Q000379:methods*; D013194:Staining and Labeling / Q000379:methods*
chemical_list: D024141:Collagen Type IV
keywords: Diabetic nephropathy; Mesangiolysis; Nodular lesion; Renal pathology; Renal prognosis; Type IV collagen