Improvement in karyomegalic interstitial nephritis three years after ifosfamide and cisplatin therapy by corticosteroid

Matsuura, Tomokazu; Wakino, Shu; Yoshifuji, Ayumi; Nakamura, Toshifumi; Tokuyama, Hirobumi; Hashiguchi, Akinori; Konishi, Konosuke; Iwasa, Takeshi; Shoji, Masaaki; Hosono, Ako; Ohashi, Ken; Chuman, Hirokazu; Itoh, Hiroshi

doi:10.1007/s13730-014-0124-3

Cited by 13 publications

(18 citation statements)

References 20 publications

(31 reference statements)

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“…Several studies have reported KIN in patients treated for childhood cancer as a rare event related to ifosfamide treatment, a nephrotoxic drug that is known to cause tubulopathy, reduced glomerular filtration and renal Fanconi syndrome, but details on clinical features and pathology are lacking. Matsuura et al, 2014;Jaysurya et al, 2016; Despite the small sample size, our observations confirm that tubular injury after ifosfamide therapy is responsible for the clinical picture and suggest that KIN and cellular senescence should be considered as underlying cause of early CKD in childhood cancer patients.…”

Section: Discussionsupporting

confidence: 71%

Senescent cell accumulation & Research-based undergraduate education

Valentijn¹

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Chapter 1 General introduction Chapter 2 Cellular senescence in the aging and diseased kidney Chapter 3 CCN2 aggravates acute DNA damage and the subsequent DDR-Senescence-Fibrosis sequence following renal ischemiareperfusion injury Chapter 4 CCN2 aggravates the immediate Oxidative Stress-DNA Damage Response following renal ischemia-reperfusion injury Chapter 5 Acute kidney injury is aggravated in aged mice by the exacerbation of proinflammatory processes Chapter 6 Oxidative stress and cellular senescence are involved in the aging kidney Chapter 7 A human conditionally immortalized proximal tubule epithelial cell line as a novel model for studying senescence and response to senolytics Chapter 8 Cellular senescence and the kidney: potential therapeutic targets and tools Chapter 9 Cellular senescence in kidney biopsies is associated with tubular dysfunction and predicts CKD progression in childhood cancer patients with KIN Bridging research (part 1) and education (part 2) Chapter 10 Proposal for a research-based bachelor course design to provide insight into underlying mechanisms of the rare, genetic renal disease KIN Part 2. Research-based education in undergraduate biomedicine education Chapter 11 A challenge-based interdisciplinary undergraduate concept fostering translational medicine Chapter 12 A novel undergraduate biomedical laboratory course concept in synergy with ongoing faculty research Chapter 13 Hybrid PhD tracks with synergy between education and research Chapter 14 Summarizing discussion and future perspectives Appendices Nederlandse samenvatting Dankwoord Curriculum vitae CHAPTER 1 General introductionChapter 1. General introduction Chronic kidney disease is a major health burden lacking effective treatment Chronic kidney disease (CKD) is a common, progressive and irreversible disorder. In 2016, the global prevalence of CKD was estimated to be 13.4%. In the Netherlands, the prevalence of CKD is estimated to be around 10%. (Nierstichting-a) People with CKD have an increased risk of end-stage kidney disease (ESKD) and cardiovascular disease. Lifestyle and drug interventions (e.g. ACE inhibition or angiotensin II receptor type 2 inhibition) are currently the cornerstone for treatment for CKD, but do not sufficiently prevent CKD progression. A large number of CKD patients (approximately 2000 patients per year in the Netherlands (Nierstichting-b)) develop ESKD and will need to switch to renal replacement therapy such as dialysis or transplantation. During dialysis, quality of life is poor and morbidity and mortality are high. ESRD patients who start dialysis between the ages of 45 and 65 have a 5-year survival rate of under 50% in the United States and Europe. (Robinson et al. 2016) Donor kidneys are scarce and long-term renal allograft survival is poor. The halflife of kidney transplants is approximately 9 years for deceased donor grafts and 12 years for living donor grafts. (Lamb et al. 2011) Thus, the demand for better treatment options to stop CKD progression and improve survival of a graft kidney i...

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Section: Discussionsupporting

confidence: 71%

Senescent cell accumulation & Research-based undergraduate education

Valentijn¹

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“…Tomokazu Matsuura et al reported a case of a 15-year-old boy presented with progressive nephrotoxicity 3 years after systemic chemotherapy with ifosfamide and cisplatin for the treatment of osteosarcoma. This case suggests the possibility that cisplatin may have a synergetic effect with ifosfamide for producing KIN [7].…”

Section: Discussionmentioning

confidence: 89%

Karyomegalic interstitial nephritis

Guebessi¹,

Karkouri

2015

CEN Case Rep

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Karyomegalic interstitial nephritis is a singular type of progressive chronic interstitial nephritis. The pathogenesis of this disease is unknown. The present study reported the case of a 22-year-old man who presented with a long history of recurrent upper respiratory tract infection episodes secondary to bronchiectasis and with progressive renal failure. Renal biopsy revealed chronic tubulointerstitial nephritis and a surprisingly marked karyomegaly specifically of the tubular epithelium.

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“…described a 15-year-old boy who developed renal failure and fanconi's syndrome 3 years after receiving IFO. [ 3 ] In spite of significant chronicity in the biopsy, the patient showed improvement in GFR following corticosteroid therapy. It is postulated that IFO-induced DNA damage prevents the normal cellular regenerative process resulting in karyomegaly.…”

Section: Discussionmentioning

confidence: 99%

“…Later similar lesions were described in long-term survivors of malignancies treated with the alkylating agent ifosfamide (IFO). [ 2 3 ] To the best of our knowledge, only four cases of IFO-induced KIN (one case series and a single case report) have been published so far, and the optimal therapeutic strategies are unclear.…”

Section: Introductionmentioning

confidence: 99%

Karyomegalic interstitial nephropathy following ifosfamide therapy

et al. 2016

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Ifosfamide (IFO), an alkylating agent used for the management of solid organ tumors, can cause reversible Fanconi's syndrome and acute kidney injury. Karyomegalic interstitial nephropathy (KIN) is a rare form of chronic tubulointerstitial nephritis, initially described as a familial nephropathy in adults. So far, four cases of KIN have been reported in pediatric and adolescent population following treatment with IFO. We report a 22-year-old man who developed renal dysfunction following IFO therapy for relapsed Hodgkin's lymphoma. Renal biopsy revealed chronic tubulointerstitial nephritis with atypical tubular epithelial cells showing nuclear enlargement and hyperchromasia, consistent with a diagnosis of KIN. The renal function improved following a short course of corticosteroids.

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Improvement in karyomegalic interstitial nephritis three years after ifosfamide and cisplatin therapy by corticosteroid

Cited by 13 publications

References 20 publications

Senescent cell accumulation & Research-based undergraduate education

Senescent cell accumulation & Research-based undergraduate education

Karyomegalic interstitial nephritis

Karyomegalic interstitial nephropathy following ifosfamide therapy

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