Abstract
BackgroundGuidelines for general hypertension treatment do not recommend the combined use of renin-angiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia. However, a recent clinical trial showed that polycystic kidney disease (PKD) patients had infrequent episodes of hyperkalemia despite receiving combined RAAS inhibitors. Because intrarenal RAAS is a main component for renal potassium handling, we further investigated the association between intrarenal RAAS activity and serum potassium level in patients with chronic kidney disease, particularly in PKD patients, and examined whether intrarenal RAAS activity has a prognostic role in patients with PKD.MethodsA total of 1788 subjects from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) were enrolled in this study. Intrarenal RAAS activity was assessed by the measurement of urinary angiotensinogen (AGT). The primary outcome was the composite of all-cause mortality and renal function decline.ResultsPatients with PKD had a significantly lower serum potassium level in chronic kidney disease stages 1 to 3b than non-PKD patients. In logistic regression analysis, after adjusting for multiple confounders, PKD patients had a significantly lower risk of hyperkalemia than non-PKD patients. 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 correlated with the transtubular potassium gradient (TTKG, β = 0.087, P = 0.001). In propensity score matching analysis, after matching factors associated with serum potassium and TTKG, PKD patients had a significantly higher TTKG (P = 0.021) despite a lower serum potassium level (P = 0.004). Additionally, the urinary AGT/Cr ratio was significantly higher in PKD patients than in non-PKD patients (P = 0.011). In 293 patients with PKD, high urinary AGT/Cr ratio was associated with increased risk of the composite outcome (hazard ratio 1.29; 95% confidence interval, 1.07–1.55; P = 0.007).ConclusionsHigh activity of intrarenal RAAS is associated with increased urinary potassium excretion and low serum potassium level in patients with PKD. In addition, intrarenal RAAS activity can be a prognostic marker for mortality and renal function decline in these patients.
Highlights
Guidelines for general hypertension treatment do not recommend the combined use of reninangiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia
It was expected that dual inhibition using an angiotensin-converting enzyme inhibitor (ACEi) and angiotensin-II receptor blocker (ARB) would be more effective in inhibiting the progression of chronic kidney disease (CKD); three randomized controlled trials have failed to demonstrate this [12,13,14]
The urinary AGT/Cr ratio was negatively correlated with the serum potassium level (β = − 0.058, P = 0.017) and positively correlated with Transtubular potassium gradient (TTKG) (β = 0.087, P = 0.001)
Summary
Guidelines for general hypertension treatment do not recommend the combined use of reninangiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia. A recent clinical trial showed that polycystic kidney disease (PKD) patients had infrequent episodes of hyperkalemia despite receiving combined RAAS inhibitors. It was expected that dual inhibition using an ACEi and ARB would be more effective in inhibiting the progression of CKD; three randomized controlled trials have failed to demonstrate this [12,13,14]. These trials demonstrated that dual inhibition significantly increased the incidence of hyperkalemia and renal impairment. Two of the trials involving dual RAAS inhibition in patients with type 2 diabetes mellitus (DM) were terminated early because of an increased risk of hyperkalemia and acute kidney injury [13, 14]
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