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

Abstract

Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.

Two cases of hypokalaemic rhabdomyolysis: same but different

“…GS is caused by inactivating mutations in the NCC gene ( SLC12A3 ) 5. This results in a thiazide-like effect, consisting of salt wasting with secondary hypovolaemia and subsequent stimulation of the renin–angiotensin–aldosterone axis.…”

“…She was issued with a patient information chart including dietary advice and ‘Sick day rules’, as recommended in a recent review 5. Genetic screening has been offered to her parents and siblings.…”

Pathophysiology of Post Transplant Hypertension in Kidney Transplant: Focus on Calcineurin Inhibitors Induced Oxidative Stress and Renal Sodium Retention and Implications with RhoA/Rho Kinase Pathway

“…These animals developed salt-sensitive hypertension, hyperkalemia, renal tubular acidosis and hypercalciuria [39], a clinical picture similar to the Gordon syndrome a rare hereditary form of hypertension [47], which is caused by mutations in WNK kinases that activate NCC [48]. Of note, normo/ hypothension, hypokalemia, sodium wasting, metabolic alkalosis and hypocalciuria, clearly the opposite clinical picture of CNIs induced hypertension and Gordon syndrome, is presented by the Gitelman's syndrome, rare genetic tubulopathy caused by inactivating mutations in the gene coding for NCC, which lead to sodium and potassium wasting [49], further indirectly underlining the role of sodium retention via activation of NCC as contributing to CNI induced hypertension. Moreover, patients in whom NCC is genetically activated, such as Gordon syndrome, or inactivated, such as Gitelman's syndrome, show opposite changes in vascular reactivity with severe hypertension in the former and hypotension and reduced oxidative stress in the latter [8,48].…”

Predictors of Insulin Resistance in Obesity and Type 2 Diabetes Mellitus - The Role of Magnesium

“…For the current study, the collected data were retrospectively analyzed. All procedures followed were approved by the Ethics Committee of the Antwerp University Hospital [1,10,32] and were conducted in accordance with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.…”

“…Magnesium: Hypomagnesaemia was defined as a serum magnesium concentration <1.7 mg/dl [32][33][34][35]. The fractional excretion of magnesium (FE Mg 2+ ) was computed using the following equation: [6,36,37].…”