Association of karyomegalic interstitial nephritis with focal segmental glomerulosclerosis

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.

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.