Dyskalemia in Chronic Kidney Disease: How Concerned Should We Be?

Abstract

Context: The widespread use of diuretics, potassium supplements, and medications that block renin angiotensin system puts the chronic kidney disease (CKD) population at high risk for dyskalemia, both hyperkalemia and hypokalemia. The optimal potassium level in a CKD patient is unknown. Subject of review: Two recent studies found conflicting results on the association of dyskalemia with outcomes. The Renal Research Institute CKD study [Clin J Am Soc Nephrol 2010; 5: 762–769] found increased mortality and incidence of end-stage renal disease (ESRD) with mild to moderate hypokalemia, whereas hyperkalemia was not significantly associated, compared to eukalemia. On the other hand, the Multi-Ethnic Study of Atherosclerosis (MESA)/Cardiovascular Health Study [Clin J Am Soc Nephrol 2017; 12: 245–252] showed both cardiovascular and noncardiovascular mortality to be higher with hyperkalemic patients, whereas associations with hypokalemic patients were statistically nonsignificant. Second opinion: If mild hypo- or hyperkalemia is associated with adverse outcomes, is it related to the hyperkalemia per se or to conditions associated with dyskalemia, such as kidney disease or cardiovascular disease? We interpret these articles in the context of criteria to support causality in epidemiologic studies. The cardiovascular effects of dyskalemia is well described and there is biological plausibility for increased cardiovascular mortality but the association of increased non-cardiovascular mortality with dyskalemia has little mechanistic basis. The explanation for a causal association of dyskalemia with ESRD is not adequate. Based on current evidence, targeting a potassium level of 4–5 mmol/L can be considered safe.

Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study

“…Although renin–angiotensin–aldosterone system inhibitors (RAASis) are mainstays of therapy among patients with proteinuric and diabetic CKD [ 6 ], use of maximum renoprotective RAASi dosages is limited due to RAASi-associated K + elevation risk [ 3 ]. Patients with severe CKD (Stages 4 and 5, eGFR <30 mL/min/1.73 m 2 ) often have strict dietary requirements, including restricted intake of fluids, protein, sodium, phosphate and K + .…”