SUN-199 URINARY ANGIOTENSINOGEN TO CREATININE RATIO (UAGT/CR) IS NOT A PREDICTIVE BIOMARKER FOR RENAL PROGRESSION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: KNOW-CKD STUDY

Abstract

Decreased renal blood flow by cystic compression and subsequent hypertension has been suggested as one of the main mechanisms for renal progression in autosomal dominant polycystic kidney disease (ADPKD) and intrarenal renin-angiotensin-aldosterone system (RAAS) is known to play the major role in this process. Urinary angiotensinogen to creatinine ratio (UAGT/Cr) was suggested as a novel biomarker to reflect intrarenal RAAS activity. Previous study demonstrated that ADPKD patients have 5- to 6- fold higher level of UAGT/Cr compared to non-ADPKD CKD patients and the level of UAGT/Cr was associated with decreased renal function. However, whether UAGT/Cr can predict renal function decline or kidney growth has not been elucidated. This study was performed to evaluate UAGT/Cr in a prospective ADPKD cohort and demonstrate its usefulness as a predictive biomarker in ADPKD patients. From April 2011 to February 2016, a total of 364 ADPKD patients were enrolled in the prospective cohort called KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). UAGT was measured by commercial sandwich enzyme-linked immunosorbent assay (ELISA) (Immuno-Biological Laboratories, Co., Ltd., Gunma, Japan) and adjusted by urinary creatinine (Cr) content. Serum Cr was measured by IDMS-traceable method at a central laboratory and glomerular filtration rate (GFR) was estimated by CKD-EPI(Cr) equation. Annual GFR decline rate was calculated from the difference between final and initial Cr divided by follow-up years. Total kidney volume (TKV) was measured upon enrollment and every two years afterwards. HtTKV was calculated by TKV divided by the height of the patient. The annual eGFR decline rate and HtTKV growth rate was compared among UAGT/Cr quartile groups. The variables that do not follow normal distribution was natural log-transformed before analysis. The mean age was 47 years and male were 184 (50.5%). Most of the patients were taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers (85.9%). Baseline estimated GFR was 68.1±33.3 mL/min/1.73m2 and HtTKV was 740.7±541.6 cc/m. Mean UAGT.Cr was 16.3±45.3 μg/g. Ln(UAGT/Cr) was negatively correlated with estimated GFR (r2=0.03, p=0.001) and positively correlated with Ln(HtTKV) (r2=0.03, p=0.004). UAGT/Cr was significantly increased as CKD stage progressed (8.1±20.9 in stage 1 vs. 8.9±16.4 in stage 2 vs. 12.9±16.2 in stage 3 vs. 28.6±74.1 in stage 4 vs. 125.2±138.4 in stage 5, p<0.001). A total of 246 patients with relatively preserved GFR (>30 mL/min/1.73m2) were evaluated for the effect of UAGT/Cr upon prospective eGFR decline rate and HtTKV growth rate. The mean follow-up duration was 45.3±14.8 months. The highest quartile UAGT/Cr group showed higher systolic and diastolic blood pressure (131.9±13.6 and 83.0±10.9 mmHg, p<0.05), lower GFR at baseline (63.9±20.9 mL/min/1.73m2, p<0.001) and higher HtTKV (816.5±499.2 cc/m, p=0.079). However, neither annual GFR decline rate or HtTKV growth rate was statistically different among UAGT/Cr quartile groups. Ln(UAGT/Cr) was not associated with either annual GFR decline rate (r2=0.01, p=0.876) or Ln(HtTKV growth rate) (r2=0.036, p=0.761). UAGT/Cr is a marker of concurrent renal function and HtTKV. However, UAGT/Cr cannot predict renal progression in ADPKD.