Clinical and genetic features of Gitelman syndrome patients with hyperuricemia

Gitelman syndrome (GS) is a rare inherited salt-losing tubulopathy caused by dysfunction of the thiazide-sensitive sodium-chloride cotransporter (NCC). Hyperuricemia is frequently observed in patients with GS, yet its risk factors and associations with GS remain unclear. This study aimed to investigate the percentage, clinical characteristics, and genetic mechanisms in GS patients with hyperuricemia.

We reanalyzed the GS cohort at Peking Union Medical College Hospital, investigated the baseline clinical, laboratory, and genetic data of GS patients, and utilized the Illumina Human Asian Screening Array-24+v1.0 gene chip and IMPUTE2 for single nucleotide polymorphism (SNP) analysis.

The average serum uric acid of 132 GS patients was 352.3 ± 96.9 μmol/l (5.9 ± 1.6 mg/dl), with 21.2% hyperuricemia [mean 486.1 μmol/l (8.2 mg/dl)] and two cases of gout. The GS patients with hyperuricemia had higher body mass index (BMI) (24.3 ± 3.9 vs 21.7 ± 3.5 kg/m², P = .001), lower fractional excretion of uric acid (FEUA) (median 4.22% vs 6.17%, P < .001), and urinary calcium/creatinine ratio (0.05 vs 0.12 mmol/mmol, P = .004). In GS patients with or without hyperuricemia, the impairment of NCC function indicated by the value of increase of chloride excretion fraction (△FECl) in the hydrochlorothiazide test was median 0.49% vs 0.82% (P = .10). We focused on the SLC12A3 genotype and 33 SNPs linked to uric acid levels and found no significant genetic differences between patients with or without hyperuricemia.

Hyperuricemia is common in patients with GS in China, associated with elevated BMI and potentially more severe NCC dysfunction.