FP040
PATIENTS WITH POLYCYSTIC KIDNEY DISEASE ARE MORE RESISTANT TO HYPERKALEMIA THAN THOSE WITH OTHER CAUSES OF KIDNEY DISEASES: THE ROLE OF INTRARENAL RENIN-ANGIOTENSIN ACTIVITY

INTRODUCTION AND AIMS: Increased activity of the intrarenal renin-angiotensin-aldosterone system (RAAS) is the main pathogenic mechanism for the development of early hypertension in patients with autosomal dominant polycystic kidney disease (ADPKD). Moreover, intrarenal RAAS is an important component for renal potassium handling and maintaining potassium balance. The recent HALT-PKD trial for ADPKD showed that episodes of hyperkalemia were infrequently observed despite dual blocking in RAAS. The aims of this study were to investigate whether high intrarenal RAAS activity affects serum potassium levels and whether it acts as a prognostic marker in patients with ADPKD.

METHODS: This prospective longitudinal study was conducted with 1788 subjects from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). The baseline urinary angiotensinogen (AGT) level was measured using a commercially available enzyme-linked immunosorbent assay kit. Propensity score matching (PSM) analysis was performed to compare potassium handling between the ADPKD and non-PKD groups. The primary outcome of this study was the composite of all-cause mortality and renal function decline.

RESULTS: Patients’ mean age was 54.0 ± 12.2 years, and 690 (38.6%) were women. The average estimated glomerular filtration rate was 50.1 ± 29.9 mL/min/1.73 m². The risk of hyperkalemia was significantly lower in ADPKD than in other causes of chronic kidney disease after adjusting the covariables. In multivariable linear regression analysis, the urinary AGT/creatinine (Cr) ratio was negatively correlated with the serum potassium level (β = -0.058, P = 0.017) and positively associated with the transtubular potassium gradient (TTKG, β = 0.087, P = 0.001). After PSM, patients with ADPKD had significantly lower serum potassium levels (P < 0.001) with oppositely elevated TTKGs (P = 0.024). Additionally, the urinary AGT/Cr ratio was significantly higher in ADPKD than in non-PKD (P = 0.003). These results were much prominent in the comparison between ADPKD and diabetic nephropathy. In 293 patients with ADPKD, the urinary AGT/Cr ratio was a significant risk factor of the composite outcome (hazard ratio, 1.33; 95% confidence interval, 1.10-1.62; P = 0.004).

CONCLUSIONS: Increasing activity of intrarenal RAAS represented by a high urinary AGT level is associated with high tubular potassium excretion and a low serum potassium level, and is a prognostic marker in patients with ADPKD. The present study suggests that a higher degree of RAAS blockade may be needed to inhibit intrarenal RAAS activity in patients with ADPKD.