MO056KARYOMEGALIC INTERSTITIAL NEPHRITIS: AN ENTITY ASSOCIATED WITH DIFFERENT GENETIC MUTATIONS
Authors: Özcan Şeyda Gül , Alay Mustafa Tarık , Kalaycı Yiğin Aysel , Trabulus Sinan , Seyahi Nurhan 
Published: May 2021

Background and Aims

Karyomegalic interstitial nephritis (KIN) is a rare hereditary cause of chronic interstitial nephritis, The disease manifests as a slowly progressive chronic kidney disease and it is an underdiagnosed cause of interstitial nephritis. The presence of karyomegalic tubular epithelial cells in a renal biopsy specimen is the primary marker that makes KIN distinguishable from other common causes of chronic tubulointerstitial nephritis. KIN has recently been associated with the FAN1 (FANCD2 / FANCI-Associated nuclease 1) gene involved in DNA repair.

In this article, we present two cases with KIN with different genetic associations.            

Methods

Clinical, laboratory, and kidney biopsy finding along with genetic examination is presented.

Results

The first case was a 42-year-old male, who was diagnosed with gout eight years ago and renal dysfunction was found in routine examinations. He was admitted to the nephrology clinic with pain in both feet and legs for the last six months. He had a history of frequent upper respiratory tract infections in his childhood. There was no family member with kidney disease. There was a ten pack/year smoking history. He did not use alcohol, nephrotoxic drugs, or herbal substances. Physical examination was unremarkable. On admission, serum creatinine was 2.71 mg/ dl and the estimated glomerular filtration rate (e-GFR) was 28 ml/min/1.73m2. Liver function tests, Hepatitis B, C, and HIV serologies, and serum complement levels were normal. Urinalysis, including microscopic examination, did not reveal any abnormality. In 24-hour collected urine, 182 mg proteinuria was detected. Kidney biopsy revealed the following findings; mild tubular atrophy, nucleomegaly in tubular epithelial nuclei, rare multinucleation, and prominence in nuclei. There were no immune deposits present in immunofluorescence microscopy. A pathological diagnosis of KIN was made. In the genetic analysis, we detected c.358T&gt;C (p.Cys120Arg) mutation in UMOD gene by using clinical exome sequencing. According to the Human Gene Mutation Database (HGMD) guideline, this variant is assessed as likely pathogenic. There was no mutation in the FAN1 gene.

The second case was a 64-year-old female, she had hypertension for eight years, and was referred to the nephrology clinic due to renal dysfunction. There was a history of pharyngitis four times a year. There was no history of smoking and alcohol use. She had been suffering from nocturia for eight years. She did not use alcohol, nephrotoxic drugs, or herbal substances. There was no history of kidney disease in her family. Serum creatinine on admission was 1.58 mg/dl and e-GFR was 35.2 ml/min/1.73m2. Liver function tests, Hepatitis B, C and HIV serologies, and serum complement levels were normal. Urinalysis, including microscopic examination, did not reveal any abnormality. In 24-hour collected urine 143 mg proteinuria was detected. Kidney biopsy revealed global sclerosis in glomeruli, nucleomegaly, intranuclear inclusions, and hyperchromasia in tubules epithelial cells and endothelial cells. A pathological diagnosis of KIN was made. The genetic analysis detected   c.1972 C&gt;T (p. Arg658Trp) mutation in the FAN1 gene. According to the HGMD guideline this variant is classified as an unknown significance. However, the clinical and pathological features of the patient were compatible with KIN, we concluded this specific FAN1 mutation was associated with the disease in our case.

Conclusion

Despite similar clinical features and histopathological findings, we found two different gene mutations in these two cases. It is especially interesting that UMOD mutation which was associated with hyperuricemia and uric acid nephropathy was associated with KIN. KIN should be included in the differential diagnosis of patients without a definite diagnosis of CKD, the genetic examination should be carried out to reveal the underlying mutation.