Karyomegalic interstitial nephritis with focal segmental glomerulosclerosis: A rare association

Radha, Sistla; Tameem, A; Rao, B. Sanjiva

doi:10.4103/0971-4065.127905

Cited by 15 publications

(11 citation statements)

References 6 publications

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“…[ 5 ] One case report of KIN associated with focal segmental glomerulosclerosis (FSGS) has been described by Radha. et al [ 6 ] The natural course of the disease is either nonprogressive or progression to end-stage kidney disease requiring renal replacement therapy. Recurrence of KIN in the allograft kidney is also reported.…”

Section: Introductionmentioning

confidence: 99%

Novel homozygous FAN1 mutation in a familial case of karyomegalic interstitial nephritis

et al. 2020

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Karyomegalic interstitial nephritis (KIN) is a rare genetic kidney disease associated with a mutation in FAN1 gene and is often underdiagnosed. The histomorphology demonstrates chronic interstitial nephritis with tubular epithelial cells showing bizarre enlarged nuclei. We present a case report of a 47-year-old multiparous South-Indian woman presenting with bilateral pitting pedal oedema and mild hypertension. At the time of presentation, her serum creatinine was 1.52 mg/dL and urine analysis showed mild proteinuria. Kidney biopsy showed features of tubular injury with bizarre enlarged nuclei and focal mild chronic tubulointerstitial nephritis. Immunohistochemistry was negative for cytomegalovirus (CMV) Ag and SV40 Ag. Real-time polymerase chain reaction (PCR) done for CMV and BK virus genomes was negative. Relevant family history was that her older brother was also diagnosed with kidney failure and is on renal replacement therapy. Genetic analysis for FAN1 gene of the proband and her sibling showed two rare mutations of the FAN1 gene in the exon 4, of which, one is non-synonymous mutation and the other is a stop-gain mutation in the proband. This case illustrates a rare presentation of karyomegalic interstitial nephritis in siblings with previous unknown FAN1 gene mutations.

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Section: Introductionmentioning

confidence: 99%

Novel homozygous FAN1 mutation in a familial case of karyomegalic interstitial nephritis

et al. 2020

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“…However, it is possible that different DNA lesions may play a role in KIN pathogenesis. Generally, cases of KIN described in the literature exclude exposure to environmental genotoxins such as ochratoxin A, heavy metals, or herbal medicines (Mihatsch et al 1979;Bhandari et al 2002;Uz et al 2011;Radha et al 2014), leaving endogenously derived toxins as more likely candidates. Given the recent data implicating acetaldehyde and formaldehyde in the pathogenesis of FA (Langevin et al 2011;Garaycoechea et al 2012;Hira et al 2013;Pontel et al 2015), the contribution of aldehydes to the pathogenesis of KIN needs to be examined.…”

Section: Fan1 and Organ Dysfunctionmentioning

confidence: 99%

Fan1 deficiency results in DNA interstrand cross-link repair defects, enhanced tissue karyomegaly, and organ dysfunction

et al. 2016

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Deficiency of FANCD2/FANCI-associated nuclease 1 (FAN1) in humans leads to karyomegalic interstitial nephritis (KIN), a rare hereditary kidney disease characterized by chronic renal fibrosis, tubular degeneration, and characteristic polyploid nuclei in multiple tissues. The mechanism of how FAN1 protects cells is largely unknown but is thought to involve FAN1's function in DNA interstrand cross-link (ICL) repair. Here, we describe a Fan1-deficient mouse and show that FAN1 is required for cellular and organismal resistance to ICLs. We show that the ubiquitinbinding zinc finger (UBZ) domain of FAN1, which is needed for interaction with FANCD2, is not required for the initial rapid recruitment of FAN1 to ICLs or for its role in DNA ICL resistance. Epistasis analyses reveal that FAN1 has cross-link repair activities that are independent of the Fanconi anemia proteins and that this activity is redundant with the 5 ′ -3 ′ exonuclease SNM1A. Karyomegaly becomes prominent in kidneys and livers of Fan1-deficient mice with age, and mice develop liver dysfunction. Treatment of Fan1-deficient mice with ICL-inducing agents results in pronounced thymic and bone marrow hypocellularity and the disappearance of c-kit + cells. Our results provide insight into the mechanism of FAN1 in ICL repair and demonstrate that the Fan1 mouse model effectively recapitulates the pathological features of human FAN1 deficiency.

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“…9 d e s c r i b e d g l o m e r u l a r changes which included mesangial thickening and nuclear enlargement in epithelial cells lining the Bowman's capsule in three of six patients. In 2014, Rhada et al 2 presented the case of an eight-yearold male, likely the youngest patient with KIN in the literature, whose biopsy showed, typical nuclear changes of KIN in the tubular epithelial cells and segmental sclerosis in four out of 23 glomeruli. To our knowledge, this is the first case in the literature in which KIN and FSGS are described together, raising the question of a common link to the underlying genetic abnormality between KIN and FSGS.…”

Section: Discussionmentioning

confidence: 99%

“…1 This disease has a prevalence of less than 1% and has no defined treatment guidelines. 2 It is characterized by progressive renal failure, proteinuria, and a history of recurrent respiratory infections. 1 Histologically, KIN reveals hyperchromatic and enlarged nuclei of tubular epithelial cells accompanied by marked interstitial fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Association of karyomegalic interstitial nephritis with focal segmental glomerulosclerosis

Chand¹,

Zaka²,

Qin³

2021

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Karyomegalic interstitial nephritis with focal segmental glomerulosclerosis: A rare association

Cited by 15 publications

References 6 publications

Novel homozygous FAN1 mutation in a familial case of karyomegalic interstitial nephritis

Novel homozygous FAN1 mutation in a familial case of karyomegalic interstitial nephritis

Fan1 deficiency results in DNA interstrand cross-link repair defects, enhanced tissue karyomegaly, and organ dysfunction

Association of karyomegalic interstitial nephritis with focal segmental glomerulosclerosis

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