Magnesium lactate in the treatment of Gitelman syndrome: patient-reported outcomes

Abstract

Background: Gitelman syndrome (GS) is a rare recessively inherited renal tubulopathy associated with renal potassium (K) and magnesium (Mg) loss. It requires lifelong K and Mg supplementation at high doses that are at best unpalatable and at worst, intolerable. In particular, gastrointestinal side effects often limit full therapeutic usage. Methods: We report here the analysis of a cohort of 28 adult patients with genetically proven GS who attend our specialist tubular disorders clinic, in whom we initiated the use of a modified-release Mg preparation (slow-release Mg lactate) and who were surveyed by questionnaire. Results: Twenty-five patients (89%) preferred the new treatment regimen. Of these 25, 17 (68%) regarded their symptom burden as improved and seven reported no worsening. Of the 25 who were not Mg-treatment naïve, 13 (59%) patients reported fewer side effects, 7 (32%) described them as the same and only 2 (9%) considered side effects to be worse. Five were able to increase their dose without ill-effect. Overall, biochemistry improved in 91% of the 23 patients switched from therapy with other preparations who chose to continue the modified-release Mg preparation. Eleven (48%) improved both their Mg and K mean levels, 3 (13%) improved Mg levels only and in 7 cases (30%), K levels alone rose. Conclusions: Patient-reported and biochemical outcomes using modified-release Mg supplements were very favourable, and patient choice should play a large part in choosing Mg supplements with GS patients.

Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

“…Persistent diarrhea may mandate a drop in dosage, which paradoxically may improve serum levels thanks to increased bioavailability or decreased intestinal transit time or both. 65 A list of magnesium-rich foods is provided in Supplementary Table S5.…”

Persistent severe hypokalemia: Gitelman syndrome and differential diagnosis

“…Standard treatment includes a diet with high levels of salt, potassium and magnesium, as well as oral magnesium and potassium supplements, sometimes together with K-sparing diuretics (if hypotension permits). 6,9 In summary, in our case report, the patient had concurrent THPP and GS, two simultaneous pathological mechanisms triggered by hypokalemia. 15 Clinical findings did not provide clues for a pathological condition other than thyrotoxicosis.…”

“…Its main clinical features of this disease are hypokalemia, hypomagnesemia, low urinary calcium, and high aldosterone and renin levels with normal blood pressure. 6,[9][10][11] GS is a rare inherited autosomal recessive tubulopathy that causes loss of salt, characterized by hypokalemic metabolic alkalosis, hypomagnesemia, hypocalciuria, and secondary hyperaldosteronism. 11,12 It is mainly related to mutations in the SLC12A3 gene encoding for the thiazide-sensitive NaCl cotransporter of the distal convoluted tubule.…”

“…5,8,12,15 The phenotypic variations and the absence of a standard diagnostic method make a definite diagnosis of GS more difficult. 9,16 Nevertheless, even without a genetic report, clinicians should be able to make correct clinical diagnosis, predict prognosis, and manage the condition correctly. 10 The aims of treatment are to improve patient symptoms, quality of life and serum electrolyte levels, and to ensure cardiac rhythm stability.…”

The challenges of diagnosis and management of Gitelman syndrome

“…Similarly, a variety of magnesium treatments are available and should be titrated in the same fashion. Though magnesium aspartate, citrate and lactate have better bioavailability, magnesium chloride can be used to compensate for urinary chloride losses. The use of slow‐release tablets is again preferred (eg Mag‐Tab SR), as recommended by consensus guidance, which can be taken with meals.…”