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Urinary Angiotensinogen in addition to Imaging Classification in the Prediction of Renal Outcome in Autosomal Dominant Polycystic Kidney Disease

Journal of Korean Medical Science 2020년 35권 22호 p.165 ~ 165
박혜인조 ( Park Hayne-Cho ) - Hallym University College of Medicine Department of Internal Medicine

김주희 ( Kim Ju-Hee ) - Hallym University College of Medicine Department of Internal Medicine
조아진 ( Cho A-Jin ) - Hallym University College of Medicine Department of Internal Medicine
김도형 ( Kim Do-Hyoung ) - Hallym University College of Medicine Department of Internal Medicine
이영기 ( Lee Young-Ki ) - Hallym University College of Medicine Department of Internal Medicine
류현진 ( Ryu Hyun-Jin ) - Seoul National University Hospital Department of Internal Medicine
김현숙 ( Kim Hyun-Suk ) - Hallym University College of Medicine Department of Internal Medicine
오국환 ( Oh Kook-Hwan ) - Seoul National University Hospital Department of Internal Medicine
오윤규 ( Oh Yun-Kyu ) - SMG-SNU Boramae Medical Center Department of Internal Medicine
황영환 ( Hwang Young-Hwan ) - Truewords Dialysis Clinic
이규백 ( Lee Kyu-Beck ) - Sungkyunkwan University School of Medicine Kangbuk Samsung Hospital Department of Internal Medicine
김수완 ( Kim Soo-Wan ) - Chonnam National University Medical School Department of Internal Medicine
김영훈 ( Kim Yeong-Hoon ) - Inje University Busan Paik Hospital Department of Internal Medicine
이중엽 ( Lee Joong-Yub ) - Inha University Hospital Department of Prevention and Management
안규리 ( Ahn Curie ) - Seoul National University Hospital Department of Internal Medicine

Abstract


Background: Intrarenal renin-angiotensin system (RAS) is known to play the major role in the development of hypertension and renal progression in autosomal dominant polycystic kidney disease (ADPKD). Urinary angiotensinogen to creatinine ratio (AGT/Cr) was suggested as a novel biomarker to reflect intrarenal RAS activity. This study was performed to evaluate urinary AGT/Cr as a predictive biomarker for renal function decline in addition to imaging classification in a prospective ADPKD cohort.

Methods: From 2011 to 2016, a total of 364 ADPKD patients were enrolled in the prospective cohort called the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Among them, a total of 207 subjects in chronic kidney disease stage 1?4 with baseline urinary AGT and total kidney volume and subsequent renal function follow-up data over more than 1 year were included in the analysis. Patients were defined as slow progressors (SP) if they are classified as 1A or 1B by imaging classification whereas rapid progressors (RP) if they are classified as 1C?1E. Patients were divided according to AGT/Cr quartiles and annual estimated glomerular filtration rate (eGFR) slope was compared among highest quartile (hAGT group) and the rest of quartiles (lAGT group). Patients were divided into 4 groups to evaluate the predictive value of urinary AGT/Cr in addition to imaging classification: SP/lAGT, SP/hAGT, RP/lAGT, and RP/hAGT. The Cox regression model was used to evaluate the hazard ratio (HR) between groups.

Results: The mean age was 45.9 years and 88.9% had hypertension. Baseline eGFR was 79.0 ± 28.4 mL/min/1.73 m2 and median height-adjusted total kidney volume was 788.2 (471.2; 1,205.2) mL/m. The patients in the hAGT group showed lower eGFR (72.4 ± 24.8 vs. 81.1 ± 29.2 mL/min/1.73 m2,P = 0.039), lower plasma hemoglobin (13.0 ± 1.4 vs. 13.7 ± 1.6 g/dL, P = 0.007), higher urinary protein to creatinine ratio (0.14 [0.09, 0.38] vs. 0.07 [0.04, 0.12] g/g, P = 0.007) compared to the lAGT group. The hAGT group was an independent risk factor for faster eGFR decline after adjusting for gender, RP, baseline eGFR, and other known risk factors. During median follow-up duration of 4.6 years, a total of 29 renal events (14.0%) occurred. The SP/hAGT group showed significantly higher risk of developing renal outcome compared to SP/lAGT group (HR, 13.4; 95% confidence interval, 1.282?139.324; P = 0.03).

Conclusion: Urinary AGT/Cr can be a useful predictive marker in the patients with relatively small ADPKD. Various biomarkers should be considered to define RP when implementing novel treatment in the patients with ADPKD.

키워드

Angiotensinogen; Biomarkers; Glomerular Filtration Rate; Autosomal Dominant Polycystic Kidney
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