Prevalence of Hyperkalemia and Familial Hyperkalemic Hypertension in 5100 Patients Referred to a Tertiary Hypertension Unit

Abstract

Background: Hyperkalemia is a frequent electrolyte alteration whose prevalence varies widely, depending on the adopted cutoff, the setting (inpatients versus outpatients), and the characteristics of the study population. Familial hyperkalemic hypertension (FHH) is a rare cause of hypertension, hyperkalemia, and hyperchloremic metabolic acidosis.

Methods: In this retrospective observational study, we investigated the prevalence of hyperkalemia (serum K⁺ >5.2 mmol/L on 2 repeated measurements) in 5100 referred patients affected by arterial hypertension, the potential causes, and the associated cardiovascular risk profile.

Results: Overall, 374 (7.3%) patients had hyperkalemia. This was associated with drugs known to increase K⁺ levels (74.6%), chronic kidney disease (33.7%), or both (24.3%). Among the 60 patients with unexplained hyperkalemia, 3 displayed a clinical and biochemical phenotype suggestive of FHH that was genetically confirmed in 2 of them (0.04% in the entire cohort). FHH prevalence rose to 3.3% in patients with unexplained hyperkalemia and up to 29% (2/7) if they had serum K⁺>5.8 mmol/L. The genetic cause of FHH was a missense variant affecting the acidic motif of WNK1 in 1 family and a rare CUL3 splicing variant, whose functional significance was confirmed by a minigene assay, in another. Finally, we observed a significant association between hyperkalemia and the occurrence of cardiovascular events, metabolic syndrome, and organ damage, independent of potential confounding factors.

Conclusions: The identification of hyperkalemia in patients with hypertension has prognostic implications. A timely diagnosis of FHH is important for effective management of hypertension, electrolyte imbalance correction with tailored treatment, and genetic counseling.

Keywords: cardiovascular diseases; electrolytes; hyperkalemia; hypertension; prevalence.