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BackgroundObservational 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.MethodsThis 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.ResultsKCl 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.ConclusionsIn 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

E.J.H.). A.N. has received consulting fees, speaking honoraria, or both from Daiichi-Sankyo, Taisho, AstraZeneca, Tanabe-Mitsubishi, and Kowa. A.N. received research funds from Boehringer-Ingelheim, Daiichi-Sankyo, Taisho, and Bayer. A.H.J.D. received research funds from Alnylam Pharmaceuticals. D.B. is coinventor of patents entitled "Active low molecular weight variants of angiotensin converting enzyme 2," "Active low molecular weight variants of angiotensin converting enzyme 2 (ACE2) for the treatment of diseases and conditions of the eye," and "Shorter soluble forms of angiotensin converting enzyme 2 (ACE2) for treating and preventing coronavirus infection." D.B. is founder of Angiotensin Therapeutics Inc. D.B. has received consulting fees from AstraZeneca, Relypsa, and Tricida, all unrelated to this work.1 H.L. and F.G. contributed equally to this work. dx.