Koki Mise1, Toshiharu Ueno2, Junichi Hoshino2, Ryo Hazue2, Keiichi Sumida2, Masayuki Yamanouchi2, Noriko Hayami2, Tatsuya Suwabe2, Rikako Hiramatsu3, Eiko Hasegawa3, Naoki Sawa3, Takeshi Fujii4, Shigeko Hara5, Jun Wada6, Hirofumi Makino6, Kenmei Takaichi5, Kenichi Ohashi7, Yoshifumi Ubara5. 1. 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. 2. Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan. 3. Nephrology Center, Toranomon Hospital, Tokyo, Japan. 4. Department of Pathology, Toranomon Hospital, Tokyo, Japan. 5. Nephrology Center, Toranomon Hospital Kajigaya, Kanagawa, Japan; Nephrology Center, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan. 6. Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 7. Department of Pathology, Toranomon Hospital, Tokyo, Japan; Department of Pathology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
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.
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.
Authors: Adriana Aparecida Ferraz Carbonel; Rafael André da Silva; Luiz Philipe de Souza Ferreira; Renata Ramos Vieira; Ricardo Dos Santos Simões; Gisela Rodrigues da Silva Sasso; Manuel de Jesus Simões; José Maria Soares Junior; Patrícia Daniele Azevedo Lima; Fernanda Teixeira Borges Journal: Nutrients Date: 2022-06-21 Impact factor: 6.706