Autopsy and Case Reports
Autopsy and Case Reports
Clinical Case Report

Association of karyomegalic interstitial nephritis with focal segmental glomerulosclerosis

Momal Tara Chand; Awais Zaka; Hong Qu

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Karyomegalic interstitial nephritis (KIN), first described in 1974, is a rare form of chronic tubulointerstitial nephritis. It is defined by the presence of markedly enlarged, hyperchromatic nuclei with prominent nucleoli, mainly involving tubular epithelial cells of the kidney, accompanied by marked interstitial fibrosis. The disease presents as asymptomatic proteinuria, gradually progresses to chronic kidney disease and eventually leads to end-stage renal disease by 30-40 years. The etiology of the disease remains unclear; however, genetic risk factors and possible association with HLA (B27/35) is proposed by some. It has also been linked to FAN1 (FANCD2/FANC1- associated nuclease 1) mutation.

Case Report: We present two cases of KIN with associated focal segmental glomerulosclerosis. Both patients presented with nephrotic range proteinuria. The biopsies demonstrated marked enlargement of tubular nuclei (3-5x larger than the uninvolved tubular nuclei, a metric used by some authors in previous studies) in some tubules, meeting the diagnostic criteria of KIN.. Interestingly, case one had a prior biopsy that showed minimal change disease. In the biopsies done at our institution, H&E sections showed patchy tubular attenuation with readily recognizable tubular cell mitotic figures, indicating concurrent acute tubular injury. Electron microscopy showed diffuse podocyte foot process effacement, along with microvillous transformation, podocyte hypertrophy, and cytoplasmic vacuoles, suggesting podocyte injury. This cytoplasmic vacuolization was also observed in the tubular epithelial cells. In both cases, the injury factor appeared to target both podocytes and tubular cells.


Glomerulosclerosis, Focal Segmental, Kidney, Nephritis, Interstitial


1 Isnard P, Rabant M, Labaye J, Antignac C, Knebelmann B, Zaidan M. Karyomegalic interstitial nephritis: a case report and review of the literature. Medicine. 2016;95(20):e3349. PMid:27196444.

2 Radha S, Tameem A, Rao BS. Karyomegalic interstitial nephritis with focal segmental glomerulosclerosis: a rare association. Indian J Nephrol. 2014;24(2):117-9. PMid:24701046.

3 Peterson JE, Samuel A, Jago MV. Pathological effects of dehydroheliotridine, a metabolite of heliotridine-based pyrrolizidine alkaloids, in the young rat. J Pathol. 1972;107(3):175-89. PMid:5084932.

4 Burry AF. Extreme dysplasia in renal epithelium of a young woman dying from hepatocarcinoma. J Pathol. 1974;113(3):147-50. PMid:4372331.

5 Mihatsch MJ, Gudat F, Zollinger U, Heierli C, Tholen H, Reutter FW. Systemic karyomegaly associated with chronic interstitial nephritis. A new disease entity? Clin Nephrol. 1979;12(2):54-62. PMid:527271.

6 Spoendlin M, Moch H, Brunner F, et al. Karyomegalic interstitial nephritis: further support for a distinct entity and evidence for a genetic defect. Am J Kidney Dis. 1995;25(2):242-52. PMid:7847351.

7 Godin M, Francois A, Le Roy FL, et al. Karyomegalic interstitial nephritis. Am J Kidney Dis. 1996;27(1):166. PMid:8546134.

8 Vadiaka M, Sotsiou F, Koufos C. A case of systemic karyomegaly associated with interstitial nephritis. Ann Med Interne. 1998;149(5):291-4. PMid:9791564.

9 Bhandari S, Kalowski S, Collett P, et al. Karyomegalic nephropathy: an uncommon cause of progressive renal failure. Nephrol Dial Transplant. 2002;17(11):1914-20. PMid:12401846.

10 Baba F, Nanovic L, Jaffery JB, Friedl A. Karyomegalic tubulointerstitial nephritis: a case report. Pathol Res Pract. 2006;202(7):555-9. PMid:16678356.

11 Zhou W, Otto EA, Cluckey A, et al. FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair. Nat Genet. 2012;44(8):910-5. PMid:22772369.

12 Wang R, Persky NS, Yoo B, et al. Mechanism of DNA interstrand cross-link processing by repair nuclease FAN1. Science. 2014;346(6213):1127-30. PMid:25430771.

13 Chaki M, Airik R, Ghosh AK, et al. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell. 2012;150(3):533-48. PMid:22863007.

14 Monga G, Banfi G, Salvadore M, Amatruda O, Bozzola C, Mazzucco G. Karyomegalic interstitial nephritis: report of 3 new cases and review of the literature. Clin Nephrol. 2006;65(5):349-55. PMid:16724656.

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