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Kidney Week

Abstract: TH-PO0401

Clinical Characteristics, Symptoms, and Long-Term Outcomes in Gitelman Syndrome

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

  • Hoorn, Ewout J., Erasmus MC, Rotterdam, ZH, Netherlands
  • Wieërs, Michiel L.a.j., Erasmus MC, Rotterdam, ZH, Netherlands
  • Salih, Mahdi, Erasmus MC, Rotterdam, ZH, Netherlands
  • Imenez Silva, Pedro Henrique, Erasmus MC, Rotterdam, ZH, Netherlands

Group or Team Name

  • Gitelman Survey Study Authors.
Background

Gitelman syndrome (GS) is an autosomal recessive salt-losing tubulopathy caused by SLC12A3 variants. Because GS is a rare disease, knowledge gaps include effects on growth, genotype-phenotype correlations, sex differences, patient-related and long-term outcomes. To address this, we performed an observational study within the European Reference Network for Rare Kidney Diseases (ERKNet).

Methods

ERKNet members were invited to provide data on patients with a clinical or genetic diagnosis of GS. A patient survey was circulated among GS patients to analyze patient-reported outcomes. The data were compared with the general population using two age- and sex-matched cohorts.

Results

Data from 587 patients (25% pediatric) across 13 countries showed 93% were genotyped, with 94% having SLC12A3 variants. Children with GS were shorter and lighter than the general population, with lower body weight persisting into adulthood. The sex distribution was uneven, with more males in childhood and more females in adulthood. GS patients had the expected electrolyte disorders, but also significantly lower blood phosphate levels. Positive correlations were found between blood magnesium and potassium, and potassium and aldosterone. GS patients scored worse than the general population in fatigue, physical and cognitive function, and ranked salt craving and polydipsia-polyuria as most severe symptoms. Symptom burden was higher in adult females and patients with lower blood magnesium. Treatment consisted of potassium (94%) and magnesium (50%) supplementation. Potassium-sparing medication (used in 33%) slightly increased blood potassium levels (3.2 vs. 3.1 mmol/l). More potassium supplementation increased kaliuresis but not blood potassium levels. Adult GS patients had a high prevalence of chondrocalcinosis (15%) and elevated blood cell counts (26%). Compared to the general population, adult GS patients had lower rates of chronic kidney disease and hypertension, a similar rate of diabetes, but a higher rate of albuminuria or proteinuria (28%).

Conclusion

Our study reveals new aspects of GS, including lower body weight, sex differences, reduced blood phosphate levels, and a higher prevalence of albuminuria. In addition, there was significant burden of disease with both general and GS-specific symptoms. Our findings have implications for clinical care and future research.

Digital Object Identifier (DOI)