Karyomegalic nephropathy
(Karyomegalic interstitial nephritis)
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Karyomegalic nephropathy (KN) is a rare cause of interstitial nephritis with an estimated prevalence of <1% of kidney biopsies.
- KN is a slowly progressive interstitial disease eventually leading to end‐stage renal disease.
- KN typically presents in the third to fourth decade of life; however, the disease has also been reported in children.
- Clinically, patients usually present with mild to moderate renal dysfunction, and proteinuria with or without urinary sediment abnormalities.
- Extrarenal manifestations are usually subtle and may include recurrent respiratory tract infections and abnormal liver function tests.
- The pathogenesis of KN is largely unknown, tubular karyomegaly has been associated with viral infections, nephrotoxic medications (eg, ifosfamide, lithium, and cisplatin), heavy metals (eg, lead, bismuth), and mycotoxins, especially ochratoxin A.
- A genetic basis for KN has been proposed. Recent studies have indicated the role of Fanconi anemia associated–nuclease 1 (FAN1) gene mutations in the evolution of KN.
- Biopsy: KN is characterized by variable‐sized nuclei, many of which are large, irregularly shaped, with dark and smudged or indistinct chromatin pattern, and inconspicuous nucleoli. The nuclear size usually ranges from 10 μm to 30 μm. The karyomegaly is associated with progressive tubular atrophy and interstitial fibrosis.
- Pitfall: The large smudgy nuclei can be easily confused with viral cytopathy. However, the nuclei in KN are large, pleomorphic, and hyperchromatic, and usually with more extensive involvement, whereas the nuclei in viral‐infected cells show intranuclear inclusions, the nuclei do not appear pleomorphic, and the involvement is often focal.
- Management: There is no known treatment for this disease entity. Corticosteroids have been tried in the past with no improvement in renal outcomes.
References
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Fogo AB, Lusco MA, Najafian B, Alpers CE. AJKD Atlas of Renal Pathology: Karyomegalic Nephropathy. Am J Kidney Dis. 2016;68:e7.
- Ravindran A, Cortese C, Larsen CP. Karyomegalic interstitial nephritis in a renal allograft. Am J Transplant. 2019;19:285-290.
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