Karyomegalic interstitial nephritis: Further support for a distinct entity and evidence for a genetic defect

Spoendlin, Martin; Moch, H.; Brunner, Felix; Brunner, W; Burger, H R; Kiss, D; Wegmann, W; Dalquen, Peter; Oberholzer, M.; Thiel, G; Mihatsch, Michael J.

doi:10.1016/0272-6386(95)90005-5

Cited by 45 publications

(38 citation statements)

References 16 publications

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“…Karyomegalic interstitial nephritis is sometimes regarded as the heredity disease [16], so there is the possibility that this patient had the subclinical karyomegalic interstitial nephritis before initiation of the chemotherapy. However, it is not the case because there were no sign of renal dysfunction and Fanconi's syndrome at least before the initiation of the chemotherapy.…”

Section: Discussionmentioning

confidence: 97%

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

et al. 2014

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Long-term nephrotoxicity of ifosfamide is occasionally progressive, and, in such case, there has been no specific treatment to prevent progression. It has been reported that the presence of karyomegalic interstitial nephritis, which is rare type of interstitial nephritis, may be related to ifosfamide-induced nephropathy with poor prognosis and resistant to the immunosuppressive therapy. A 15-year-old boy presented with progressive nephrotoxicity 3 years after systemic chemotherapy with ifosfamide and cisplatin for the treatment of osteosarcoma. Renal biopsy revealed the severe tubulointerstitial nephritis with tubular atrophy and focal global and segmental glomerular sclerosis. It also showed tubular epithelial cells with variably sized nuclei, some of which were massively enlarged, abnormal hyperchromatic, irregular shaped, and bizarreappearing. These morphological changes were suggestive of the histology of karyomegalic interstitial nephritis. Corticosteroid retarded the progression of nephrotoxicity. The present case is the first report, suggesting that corticosteroid was effective against the late-onset renal toxicity by ifosfamide therapy. Our case also suggests that karyomegalic interstitial nephritis may be the result of long-term nephrotoxicity of ifosfamide. Since concurrent treatment with cisplatin is one of the risk factors for ifosfamide nephrotoxicity, there is a possibility that cisplatin may have a synergetic effect with ifosfamide for producing karyomegalic interstitial nephritis.

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Section: Discussionmentioning

confidence: 97%

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

et al. 2014

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“…Renal insufficiency was associated with the rare histological diagnosis of KIN. There appear to be only two other paediatric cases of karyomegalic nephropathy reported: a 9-year-old who presented with microscopic haematuria, did not have renal impairment at presentation and was lost to follow-up; and a 12-year-old girl who was diagnosed on the basis of positive urine cytology [3,5]. Recent reports have further described karyomegalic nephropathy, and suggest that it is under-recognised [6,7].…”

Section: Discussionmentioning

confidence: 99%

Karyomegalic-like nephropathy, Ewing’s sarcoma and ifosfamide therapy

et al. 2011

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Karyomegalic interstitial nephropathy has been reported as a rare interstitial nephritis in adult patients. Histology shows atypical epithelial cells and large abnormal hyperchromatic nuclei with irregular outlines. We report 3 adolescent patients who all recovered from their initial treatment for Ewing's sarcoma but developed a tubulopathy attributed to ifosfamide therapy. Renal impairment resulted in biopsy, which showed features of karyomegalic nephropathy in all 3. One patient has progressed to haemodialysis. Recognition of the pathology may be important in similar patients. It is surmised that the unusual histological findings in these patients stem from a common pathogenesis which may be related to chemotherapeutic agent related nuclear damage. At present there is no specific treatment to prevent progressive renal impairment.

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“…KIN is a rare NPHP-like chronic kidney disease caused by renal tubular degeneration and fibrosis, but specifically also associated with renal cell karyomegaly (enlarged nuclei) (Burry 1974;Mihatsch et al 1979). Interestingly, polyploidy is not restricted to renal tissue in KIN patients but is often also observed in the lung, liver, and brain (Spoendlin et al 1995;Monga et al 2006). Lymphoblast and fibroblast cell lines from FAN1-mutated KIN patients showed hypersensitivity to killing and elevated chromosome aberration formation in response to ICLforming agents, although quantitatively less so than cells from FANCA and FANCD2 patients .…”

Section: Fan1 and Karyomegalic Interstitial Nephritismentioning

confidence: 99%

Diseases Associated with Defective Responses to DNA Damage

O’Driscoll

2012

Cold Spring Harbor Perspectives in Biology

109

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Within the last decade, multiple novel congenital human disorders have been described with genetic defects in known and/or novel components of several well-known DNA repair and damage response pathways. Examples include disorders of impaired nucleotide excision repair, DNA double-strand and single-strand break repair, as well as compromised DNA damage-induced signal transduction including phosphorylation and ubiquitination. These conditions further reinforce the importance of multiple genome stability pathways for health and development in humans. Furthermore, these conditions inform our knowledge of the biology of the mechanics of genome stability and in some cases provide potential routes to help exploit these pathways therapeutically. Here, I will review a selection of these exciting findings from the perspective of the disorders themselves, describing how they were identified, how genotype informs phenotype, and how these defects contribute to our growing understanding of genome stability pathways.

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Karyomegalic interstitial nephritis: Further support for a distinct entity and evidence for a genetic defect

Cited by 45 publications

References 16 publications

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

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

Karyomegalic-like nephropathy, Ewing’s sarcoma and ifosfamide therapy

Diseases Associated with Defective Responses to DNA Damage

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