TY - JOUR
T1 - Nodular lesions in diabetic nephropathy
T2 - Collagen staining and renal prognosis
AU - Mise, Koki
AU - Ueno, Toshiharu
AU - Hoshino, Junichi
AU - Hazue, Ryo
AU - Sumida, Keiichi
AU - Yamanouchi, Masayuki
AU - Hayami, Noriko
AU - Suwabe, Tatsuya
AU - Hiramatsu, Rikako
AU - Hasegawa, Eiko
AU - Sawa, Naoki
AU - Fujii, Takeshi
AU - Hara, Shigeko
AU - Wada, Jun
AU - Makino, Hirofumi
AU - Takaichi, Kenmei
AU - Ohashi, Kenichi
AU - Ubara, Yoshifumi
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Aims 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.
AB - Aims 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.
KW - Diabetic nephropathy
KW - Mesangiolysis
KW - Nodular lesion
KW - Renal pathology
KW - Renal prognosis
KW - Type IV collagen
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U2 - 10.1016/j.diabres.2017.03.006
DO - 10.1016/j.diabres.2017.03.006
M3 - Article
C2 - 28388509
AN - SCOPUS:85016809915
SN - 0168-8227
VL - 127
SP - 187
EP - 197
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
ER -
