Nodular lesions in diabetic nephropathy: Collagen staining and renal prognosis

Koki Mise, Toshiharu Ueno, Junichi Hoshino, Ryo Hazue, Keiichi Sumida, Masayuki Yamanouchi, Noriko Hayami, Tatsuya Suwabe, Rikako Hiramatsu, Eiko Hasegawa, Naoki Sawa, Takeshi Fujii, Shigeko Hara, Jun Wada, Hirofumi Makino, Kenmei Takaichi, Kenichi Ohashi, Yoshifumi Ubara

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)187-197
Number of pages11
JournalDiabetes Research and Clinical Practice
Volume127
DOIs
Publication statusPublished - May 1 2017

Fingerprint

Diabetic Nephropathies
Collagen
Staining and Labeling
Kidney
Periodic Acid
Collagen Type VI
Collagen Type V
Methenamine
Collagen Type IV
Patient Selection
Chronic Kidney Failure
Dialysis
Regression Analysis
Confidence Intervals
Biopsy

Keywords

  • Diabetic nephropathy
  • Mesangiolysis
  • Nodular lesion
  • Renal pathology
  • Renal prognosis
  • Type IV collagen

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Mise, K., Ueno, T., Hoshino, J., Hazue, R., Sumida, K., Yamanouchi, M., ... Ubara, Y. (2017). Nodular lesions in diabetic nephropathy: Collagen staining and renal prognosis. Diabetes Research and Clinical Practice, 127, 187-197. https://doi.org/10.1016/j.diabres.2017.03.006

Nodular lesions in diabetic nephropathy : Collagen staining and renal prognosis. / Mise, Koki; Ueno, Toshiharu; Hoshino, Junichi; Hazue, Ryo; Sumida, Keiichi; Yamanouchi, Masayuki; Hayami, Noriko; Suwabe, Tatsuya; Hiramatsu, Rikako; Hasegawa, Eiko; Sawa, Naoki; Fujii, Takeshi; Hara, Shigeko; Wada, Jun; Makino, Hirofumi; Takaichi, Kenmei; Ohashi, Kenichi; Ubara, Yoshifumi.

In: Diabetes Research and Clinical Practice, Vol. 127, 01.05.2017, p. 187-197.

Research output: Contribution to journalArticle

Mise, K, Ueno, T, Hoshino, J, Hazue, R, Sumida, K, Yamanouchi, M, Hayami, N, Suwabe, T, Hiramatsu, R, Hasegawa, E, Sawa, N, Fujii, T, Hara, S, Wada, J, Makino, H, Takaichi, K, Ohashi, K & Ubara, Y 2017, 'Nodular lesions in diabetic nephropathy: Collagen staining and renal prognosis', Diabetes Research and Clinical Practice, vol. 127, pp. 187-197. https://doi.org/10.1016/j.diabres.2017.03.006
Mise, Koki ; Ueno, Toshiharu ; Hoshino, Junichi ; Hazue, Ryo ; Sumida, Keiichi ; Yamanouchi, Masayuki ; Hayami, Noriko ; Suwabe, Tatsuya ; Hiramatsu, Rikako ; Hasegawa, Eiko ; Sawa, Naoki ; Fujii, Takeshi ; Hara, Shigeko ; Wada, Jun ; Makino, Hirofumi ; Takaichi, Kenmei ; Ohashi, Kenichi ; Ubara, Yoshifumi. / Nodular lesions in diabetic nephropathy : Collagen staining and renal prognosis. In: Diabetes Research and Clinical Practice. 2017 ; Vol. 127. pp. 187-197.
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abstract = "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.",
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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

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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