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학술저널
저자정보
김현숙 (한림대학교) 성진모 (서울대학교병원) 배주영 (기타기관) 이풍연 (농촌진흥청 국립축산과학원) 오윤규 (서울대학교) 김현호 (서울대학교)
저널정보
대한신장학회 Kidney Research and Clinical Practice Kidney Research and Clinical Practice Vol.41 No.6
발행연도
2022.11
수록면
730 - 740 (11page)
DOI
10.23876/j.krcp.21.303

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Background: Autosomal dominant polycystic kidney disease (ADPKD), one of the most common human monogenic diseases, is characterized by the presence of numerous fluid-filled renal cysts and is a leading cause of end-stage renal disease (ESRD). Urinary biomarkers may be useful for predicting the variable course of ADPKD progression from cyst growth to ESRD.Methods: To identify candidate urinary biomarkers of ADPKD progression, we used CRISPR/Cas9 genome editing to generate porcine fibroblasts with mono- and biallelic ADPKD gene knockout (PKD2+/ and PKD2/, respectively). We then performed RNA-sequencing analysis on these cells.Results: Levels of osteopontin (OPN), which is expressed by renal epithelial tubular cells and excreted into urine, were reduced in PKD2/ cells but not in PKD2+/ cells. OPN levels were also reduced in the renal cyst cells of ADPKD patients. Next, we investigated whether OPN excretion was decreased in patients with ADPKD via enzyme-linked immunosorbent assay. OPN levels excreted into renal cyst cell culture media and urine from ADPKD patients were decreased. To investigate whether OPN can predict the rate of ADPKD progression, we compared urinary excretion of OPN in ADPKD patients with slow progression and those with rapid progression. Those with rapid progression had an estimated glomerular filtration rate of >60 mL/min/1.73 m2. Urinary OPN excretion levels were lower in rapid progressors than in slow progressors.Conclusion: These findings suggest that OPN is a useful urinary biomarker for predicting ADPKD progression.

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