Rapidly progressive glomerulonephritis caused by tegafur/gimeracil/oteracil resulted in diabetes nephropathy, in a patient with minor risk of diabetes nephropathy: a case report

Toriu, Naoya; Sawa, Naoki; Imafuku, Aya; Hasegawa, Eiko; Sekine, Akinari; Mizuno, Hiroki; Yamanouchi, Masayuki; Hiramatsu, Rikako; Hayami, Noriko; Hoshino, Junichi; Kawada, Manabu; Suwabe, Tatsuya; Ohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi

doi:10.1007/s13730-020-00485-7

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…Clinically, there is a case report of an early stage DN patient with rapidly progressing diabetic kidney disease due to previously developed advanced rectal cancer, treated with a tegafur/gimeracil/oteracil [ 7 ], and a case series in which the appearance of renal TMA lesions and decreased VEGF expression in the glomeruli was associated with progressive worsening of DN [ 5 , 6 ]. Hyperplasia of the mesangial matrix, a hallmark of early DN, involves accelerated HB-EGF production in the mesangial cells and its downstream EGFR-mediated transforming growth factor-β1 expression [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

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A Case of Rapidly Progressive Diabetic Nephropathy Induced by Osimertinib

Karasawa,

Akiyama,

Akihisa

et al. 2023

Case Rep Nephrol Dial

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The number of patients with diabetic nephropathy is increasing worldwide and it is important to understand the underlying pathological mechanisms of the disease. In early stage diabetic nephropathy, the hyperglycemic environment leads to vascular endothelial cell damage, resulting in overexpression of vascular endothelial growth factor (VEGF) in podocytes and renal pathology of glomerular hypertrophy, glomerular basement membrane thickening, and mesangial hyperplasia. In diabetic nephropathy, renal thrombotic microangiopathy (TMA) develops and the nephropathy progressively worsens in some cases of severe glomerular podocyte damage. Further, receptor tyrosine kinase inhibitors (RTKIs) may suppress VEGF secretion via VEGF receptor-2 tyrosine kinase inhibition in podocytes, which results in renal TMA and rapid deterioration of diabetic nephropathy. Osimertinib, a third-generation irreversible epidermal growth factor receptor (EGFR)-TKI, is approved as a first-line treatment agent for metastatic or locally advanced EGFR mutation-positive non-small cell lung cancer. We encountered a case of a patient with diabetic nephropathy with lung adenocarcinoma treated with osimertinib, whose condition deteriorated from early nephropathy to end-stage renal disease in approximately 4 months. The patient had early diabetic nephropathy, but the use of a RTKI suppressed VEGF expression in podocytes, resulting in the induction of renal TMA and the development of rapidly progressive diabetic nephropathy.

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Section: Discussionmentioning

confidence: 99%

“…While it is well known that the use of anti-VEGF agents is associated with TMA, a rare case of drug-induced renal TMA in a patient with early stage DN resulting in rapidly progressive diabetic nephropathy (RPDN) has been reported [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

A Case of Rapidly Progressive Diabetic Nephropathy Induced by Osimertinib

Karasawa,

Akiyama,

Akihisa

et al. 2023

Case Rep Nephrol Dial

Self Cite

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“…However, the pathogenesis of DN, which involves numerous factors, remains unclear so far, and the treatment for DN is relatively limited at present. The currently available clinical treatment only alleviates disease progression but not reverses or cures the disease [3]. Therefore, it is of great significance to investigate the pathogenesis of DN and identify the novel therapeutic targets for the early prevention and clinical treatment of DN.…”

Section: Introductionmentioning

confidence: 99%

XCL1 Aggravates Diabetic Nephropathy-Mediated Renal Glomerular Endothelial Cell Apoptosis and Inflammatory Response via Regulating p53/Nuclear Factor-Kappa B Pathway

Zhang¹,

Chen²,

Fan³

et al. 2021

Nephron

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Background: Glomerular endothelial cell damage plays an important role in the occurrence and development of diabetic nephropathy (DN). Objectives: This study aimed to clarify the role of XCL1 in DN-mediated glomerular endothelial cell apoptosis and whether the function was related to the activation of the p53/nuclear factor-kappa B (NF-κB) signaling pathway. Methods: Candidate biomarkers were identified by least absolute shrinkage and selection operator (LASSO) regression model analysis. The area under the receiver operating characteristic curve value was calculated and used to evaluate the discriminating ability. Cell viability, apoptosis, and interleukin-1β and tumor necrosis factor-α expression at messenger RNA and protein levels were detected by using the Cell Counting Kit-8, flow cytometry, ELISA, real-time polymerase chain reaction, and Western blotting assays. In vivo studies were conducted in the DN mice. Results: The LASSO regression model displayed good discriminating performance, with a C-index of 0.803 and good calibration, and high XCL1 expression was identified as the predicting factor for DN in diabetes mellitus patients. XCL1 expression was upregulated in glomeruli of db/db mice, which was closely related to the expression of its receptor (XCR1). XCL1 overexpression played an important role in the apoptosis and inflammatory response of high glucose (HG)-treated human renal glomerular endothelial cells. Meanwhile, the expression of p53 and the levels of inflammatory cytokines were upregulated upon XCL1 overexpression. p53 silencing with its inhibitor blocked the apoptotic response and inflammatory response in XCL1-overexpressed cells exposed to HG. Besides, the XCL1 overexpression-induced downregulation of NF-κB was reversed by pifithrin-α pretreatment. Conclusions: Our findings in this work provided the mechanistic insights into the effects of XCL1 on the modulation of DN development, illustrating that XCL1 might serve as an essential prognostic indicator and therapeutic target for DN progression.

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Multiple drugs

2021

Reactions Weekly

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Multiple drugs Various toxicities: case reportA 79-year-old man developed rapidly progressive glomerulonephritis due to thrombotic microangiopathy during treatment with gimeracil/oteracil/tegafur for advanced colorectal cancer (stage IIIa). Additionally, he exhibited lack of efficacy while being treated with furosemide, prednisolone and plasma for rapidly progressive glomerulonephritis [not all routes, dosages and outcomes not stated; duration of treatment to reaction onset not stated].The man had type-2 diabetes mellitus and was well controlled without any diabetes medication. Additionally, he had mild diabetic neuropathy. At the age of 78 years, he diagnosed with advanced colorectal cancer (stage IIIa) and was initiated treatment with oral gimeracil/oteracil/tegafur [S-1] 80mg twice daily for 6 months (28 days of 42-day cycle). However, during the treatment, his weight was increased, and leg oedema and abdominal swelling also noticed. Following 6 months of therapy, his serum creatinine level and proteinuria were elevated, and his serum albumin was decreased. Thereby, his gimeracil/oteracil/tegafur therapy was discontinued.Consequently, the man was initiated treatment with 180mg furosemide and 30mg of prednisolone. Although, his serum creatinine continued to elevate, and proteinuria remained in the nephrotic range. Hence, he was hospitalised. During the hospitalisation, he was conscious, and his leg oedema and abdominal swelling also noted. Therefore, he underwent several laboratory investigations, which showed decreased haemoglobin, haematocrit, platelet, total protein, albumin, sodium, calcium and Fe, and increased lactate dehydrogenase, alkaline phosphate, urea nitrogen, uremic acid, glycoalbumin, triglyceride, phosphorus, ferritin, C reactive protein, B-type natriuretic peptide, vascular endothelial growth factor, proteinuria, N-acetyl-beta-Dglucosaminidase and Alpha1-microglobuline. All other laboratory test were with in the normal range. Additionally, serum protein electrophoresis no M-peak, hepatitis B virus and hepatitis C virus antibody found negative; microscopic haematuria 2 +, proteinuria 4.2 g/day and Bence Jones proteinuria was negative. Therefore, a CT scan was performed, which revealed severe ascites, liver atrophy and mildly enlarged spleen. An abdominal ultrasound revealed ascites and liver atrophy with a highly irregular surface, highly blunted edge and mildly coarse texture, the portal vein blows towards the liver, and there was no space occupying lesion was detected. An echocardiogram showed an ejection fraction of 72% and normal wall motion. Subsequently, an aspiration of ascites was performed, which revealed total protein 1.0 g/dL, albumin 0.3 g/dL, and lactate dehydrogenase 68 IU/L, which suggested that ascites were transudative. Eventually, a renal biopsy was performed to understand the reason for proteinuria. Meanwhile, a light microscopic examination of the renal biopsy specimen was performed, which revealed global sclerosis in 2 out of 8 glomeruli which confirmed cores Kimmelstiel-Wil...

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Rapidly progressive glomerulonephritis caused by tegafur/gimeracil/oteracil resulted in diabetes nephropathy, in a patient with minor risk of diabetes nephropathy: a case report

Cited by 4 publications

References 15 publications

A Case of Rapidly Progressive Diabetic Nephropathy Induced by Osimertinib

A Case of Rapidly Progressive Diabetic Nephropathy Induced by Osimertinib

XCL1 Aggravates Diabetic Nephropathy-Mediated Renal Glomerular Endothelial Cell Apoptosis and Inflammatory Response via Regulating p53/Nuclear Factor-Kappa B Pathway

Multiple drugs

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