Changes in Serum and Urinary Potassium Handling Associated with Renin-Angiotensin-Aldosterone System Inhibitors in Advanced Chronic Kidney Disease Patients

Abstract

ObjectiveThis study aimed to (i) compare the extent of urinary potassium (K+) excretion in addition to the changes in serum K+ concentration: and (ii) clarify the association between changes in serum K+ concentration, urinary K+ excretion, and acid-base status with or without renin-angiotensin-aldosterone system (RAAS) inhibitors in patients with advanced chronic kidney disease (CKD) stages.MethodsSix hundred and ninety-one patients with advanced CKD (CKD G3b, 161; G4, 271; G5, 259) were retrospectively evaluated. Differences in serum K+ concentration, urinary K+ excretion, and serum sodium and chloride differences (Na+−Cl-) were compared among patients with RAAS inhibitors, RAAS inhibitors and diuretic agents, and without either medication in each CKD stage.ResultsSerum K+ concentrations in patients with RAAS inhibitors were significantly higher than in those with RAAS inhibitors and diuretics in CKD stage G3b and the other two treatment groups in CKD stage G4. Urinary K+ excretion among the three groups did not differ significantly in each CKD stage. Serum Na+−Cl- differences in patients with RAAS inhibitors were significantly smaller than in those with RAAS inhibitors and diuretics in CKD stages G3b (p = 0.006) and the other two groups in CKD stage G4 (vs. RAAS inhibitors and diuretics, p <0.001; vs. without either medication, p = 0.008).ConclusionOur study demonstrated that RAAS inhibitor use might be associated with hyperkalemia via not decreased urinary K+ excretion but rather K+ redistribution from intracellular to extracellular fluid induced by the progression of metabolic acidosis in patients with advanced CKD, particularly stages G3b and G4.

Potential kidney protective effects of glucagon‐like peptide‐1 receptor agonists

“…28,29,31 GLP-1, when administered as a 7-36 amide (an active form of GLP-1) at physiologic levels, also induces a significant reduction in circulating levels of angiotensin II, without corresponding changes in renin or aldosterone in healthy adults, an important finding given the well-established kidney-protective effects of RAS blockade. 31,32 The mechanism of angiotensin II suppression in this setting is not yet known. The natriuretic effect and suppression of angiotensin II, as described above, depends on GLP-1 receptor activation as demonstrated by the fact that these effects are abolished by coadministration of a GLP-1 receptor antagonist.…”

“…GLP‐1, when administered as a 7–36 amide (an active form of GLP‐1) at physiologic levels, also induces a significant reduction in circulating levels of angiotensin II, without corresponding changes in renin or aldosterone in healthy adults, an important finding given the well‐established kidney‐protective effects of RAS blockade 31,32 . The mechanism of angiotensin II suppression in this setting is not yet known.…”

Long-Term Impact of Renin-Angiotensin System Inhibitors for Secondary Prevention in Patients with Chronic Kidney Disease Who Underwent Percutaneous Coronary Intervention

“…In addition, the incidence rates of end-stage kidney disease, myocardial infarction (MI), HF, and mortality are especially relevant in patients with lower estimated GFR [7]. In the nephrology, many studies on the clinical outcomes affected by RAS inhibitors have recently been reported [8–12]. Both studies showed that RAS inhibitors for patients with CKD significantly prevented the adverse cardiovascular events, but the progression to end-stage kidney disease and introduction of kidney replacement therapy caused by RAS inhibitors were inconsistent, whereas RAS inhibitor use has been recommended for purpose of myocardial protection even when coexisting CAD [13, 14].…”