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Abstract: FR-PO657

Persistent Proteinuria Associated with CUBN Variants in Korean Children

Session Information

  • Pediatric Nephrology - II
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Choi, Yun Young, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Choi, Naye, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
  • Min, Jeesu, Chungnam National University Sejong Hospital, Sejong, Korea (the Republic of)
  • Park, Eujin, Korea University Guro Hospital, Seoul, Korea (the Republic of)
  • Ahn, Yo Han, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
  • Kang, Hee Gyung, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
  • Lee, Hyun Kyung, Kangwon National University Hospital, Chuncheon, Kangwon, Korea (the Republic of)
Introduction

Persistent proteinuria is a risk factor of progression for chronic kidney disease (CKD). However, the recent discovery suggests that not all proteinuria is damaging. CUBN, encoding the membrane glycoprotein cubilin, forms cubilin-amnionless-megalin complex that is responsible for the receptor-mediated endocytosis of albumin in the proximal tubules. A defect of cubilin decreases albumin reuptake, consequently resulting in proteinuria. Interestingly, variants located at the N-terminal of CUBN result in severe proteinuria and megaloblastic anemia, whereas variants at the C-terminal are associated with benign, isolated proteinuria.

Case Description

Here, we report 6 Korean patients (M:F=3:3) presented with persistent proteinuria with homozygous or compound heterozyous C-terminal CUBN variants. All patients presented with incidentally found isolated asymptomatic proteinuria, at their median age of 5 years (range 18 months ~ 9years). Their mean urine protein creatinine ratios was 1.13 (range 0.94 ~ 1.5) mg/mg at presentation and laboratory findings were unremarkable at presentation for eGFR, serum albumin, lipid, hemoglobin, urine 2-microglobulin and N-acetyl-beta-D-glucosaminidase. None had hypertension, and kidney ultrasound was normal. Two patients underwent kidney biopsy, which revealed non-specific findings. Their median follow-up duration was 4 years (range 6 months ~ 12 years) , median age at the last follow-up was 8.5 years (range 2 years ~21 years) and the amount of proteinuria and the kidney function did not change significantly over time regardless of renin-angiotensin-aldosterone system (RAS) inhibition with mean urine protein creatinine ratio at the last follow up of 0.965 (range 0.75 ~ 1.175).

Discussion

These cases are similar to previously reported cases, indicating that asymptomatic subnephrotic range proteinuria patients should be suspected of C-terminal variants of CUBN gene. There are still debates on whether CUBN C-terminal mutation is truly benign proteinuria, and whether clinicians should treat these patients with RASi.