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

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.

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.

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.

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.