Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD

Abstract

Background: Observational studies suggest that adequate dietary potassium intake (90-120 mmol/day) may be renoprotective, but the effects of increasing dietary potassium and the risk of hyperkalemia are unknown.

Methods: This is a prespecified analysis of the run-in phase of a clinical trial in which 191 patients (age 68±11 years, 74% males, 86% European ancestry, eGFR 31±9 ml/min per 1.73 m², 83% renin-angiotensin system inhibitors, 38% diabetes) were treated with 40 mmol potassium chloride (KCl) per day for 2 weeks.

Results: KCl supplementation significantly increased urinary potassium excretion (72±24 to 107±29 mmol/day), plasma potassium (4.3±0.5 to 4.7±0.6 mmol/L), and plasma aldosterone (281 [198-431] to 351 [241-494] ng/L), but had no significant effect on urinary sodium excretion, plasma renin, BP, eGFR, or albuminuria. Furthermore, KCl supplementation increased plasma chloride (104±3 to 105±4 mmol/L) and reduced plasma bicarbonate (24.5±3.4 to 23.7±3.5 mmol/L) and urine pH (all P<0.001), but did not change urinary ammonium excretion. In total, 21 participants (11%) developed hyperkalemia (plasma potassium 5.9±0.4 mmol/L). They were older and had higher baseline plasma potassium.

Conclusions: In patients with CKD stage G3b-4, increasing dietary potassium intake to recommended levels with potassium chloride supplementation raises plasma potassium by 0.4 mmol/L. This may result in hyperkalemia in older patients or those with higher baseline plasma potassium. Longer-term studies should address whether cardiorenal protection outweighs the risk of hyperkalemia.Clinical trial number: NCT03253172.

Keywords: acidosis; aldosterone; chronic kidney disease; clinical trial; dietary supplements; electrolytes; hypertension; potassium chloride.

Graphical abstract

Figure 1.

Effects of 40 mmol KCl supplementation for 2 weeks. The effects are shown on (A) urine potassium (K⁺) excretion, (B) urine sodium (Na⁺) excretion, (C) plasma potassium (K⁺), (D) plasma aldosterone, (E) plasma renin, and (F) hematocrit (Hct). Data before and after KCl supplementation are shown in 191 patients. Data were analyzed by paired t test.

Figure 2.

Baseline characteristics that were associated with a smaller or larger increase in plasma potassium after KCl supplementation for 2 weeks. Data were analyzed by multivariable linear regression. See Supplemental Table 1 for univariable analysis. T2DM, type 2 diabetes mellitus; RAS-I, renin-angiotensin inhibitor; HCO₃⁻, bicarbonate; K⁺, potassium.

Figure 3.

Effects of 40 mmol KCl supplementation for 2 weeks. The effects are shown on (A) plasma bicarbonate (HCO₃⁻), (B) plasma chloride (Cl⁻), (C) venous pH, (D) urine ammonium (NH₄⁺) and (E) citrate excretion, and (G) urine pH. Data before and after KCl supplementation are shown in 191 patients (A), (B), (D), (G), 94 patients (C), and 126 patients (E). Data were analyzed by paired t test.

Figure 4.

Baseline characteristics associated with the development of hyperkalemia after KCl supplementation for 2 weeks. Data were analyzed by (A) univariable and (B) multivariable logistic regression.

Figure 5.

Effects of 40 mmol KCl supplementation for 2 weeks. The effects are shown on (A) eGFR, (B) urine albumin excretion, (C) office systolic BP, (D) office diastolic BP, and (E) heart rate. Data before and after KCl supplementation are shown in 191 patients. Data were analyzed by paired t test.