Gitelman syndrome and glomerular proteinuria: a link between loss of sodium-chloride cotransporter and podocyte dysfunction?

Demoulin, Nathalie; Aydın, Selda; Cosyns, Jean‐Pierre; Dahan, Karin; Cornet, Georges; Auberger, Ines; Loffing, Johannes; Devuyst, Olivier

doi:10.1093/ndt/gfu075

Cited by 22 publications

(20 citation statements)

References 19 publications

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“…Isolated cases of focal segmental glomerulosclerosis (FSGS) and C1q nephropathy in Gitelman patients have been reported as well [ 14 , 15 ]. Devuyst also found that GS was related to glomerular proteinuria and abnormalities of the glomerular basement membrane (GBM) [ 16 ]; defects of the GBM and podocytes were also detected in the Slc12a3 knockout mouse model [ 17 ]. These studies suggest that the association between GS and secondary changes of the kidney is probably not coincidental.…”

Section: Discussionmentioning

confidence: 99%

A case of hypokalemia and proteinuria with a new mutation in the SLC12A3 Gene

Chen

Y²,

Zhao

et al. 2018

BMC Nephrol

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BackgroundGitelman syndrome is an autosomal recessive inherited renal disorder characterized by hypokalemia, hypomagnesemia, and hypocalciuria. Since the symptoms are not severe and laboratory results are not always clear, Gitelman syndrome can go unnoticed by physicians. Here, we report our experiences with a patient that presented with hypokalemia and proteinuria; genetic analysis revealed a new homozygous mutation in the SLC12A3 gene.Case presentationA 47-year-old man presented with hypokalemia and proteinuria. He had come to the hospital with the same symptoms 11 months and 3 years prior. His laboratory tests showed hypokalemia, hypocalciuria, and increased plasma angiotensin-2 activity. His renal pathology was consistent with the development of minimal lesions. Genetic analysis found a new homozygous mutation in exon 6 on the SLC12A3 gene (p.Trp281Arg) in the patient and in his brother; his mother and sister were diagnosed as heterozygous carriers of the same gene mutation. Finally, the patient was diagnosed with Gitelman syndrome.ConclusionsThis case is the first to report a homozygous mutation in the 841th nucleotide of exon 6 on the SLC12A3 gene (p.Trp281Arg), which may cause Gitelman syndrome. At the same time, this report might stimulate interest in discussing the relationship between different mutations in the SLC12A3 gene and renal pathology.

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Section: Discussionmentioning

confidence: 99%

A case of hypokalemia and proteinuria with a new mutation in the SLC12A3 Gene

Chen

Y²,

Zhao

et al. 2018

BMC Nephrol

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“…47,48 Reports suggest that GS may be associated with glomerular proteinuria due to abnormalities of the glomerular basement membrane. 22,49 Chronic kidney disease might develop in GS patients due to either chronic hypokalemia, which is associated with tubulointerstitial nephritis, tubule vacuolization, and cystic changes, or volume depletion and increased reninangiotensin-aldosterone, which may contribute to renal damage and fibrosis. 21,50,51 Many patients with GS present with abdominal pain, which may be due to intestinal paresis because of hypokalemia or intolerability of potassium and magnesium supplementation.…”

Section: Clinical Manifestations and Workupmentioning

confidence: 99%

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

Blanchard

Böckenhauer

Bolignano

et al. 2017

Kidney International

274

346

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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.

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“…Several recent studies have reported that some subsets of patients tend to show overt proteinuria 29 , 30 ) , which has received attention as an independent risk factor for cardiovascular and chronic kidney disease 31 ) . Empirical evidence available in the literature shows several glomerulopathies and concomitant proteinuria in patients with GS 32 , 33 , 34 ) . A few reports have even anecdotally described patients with severe progressive renal failure requiring renal replacement therapy 35 , 36 ) .…”

Section: Discussionmentioning

confidence: 99%

A case of Gitelman syndrome: our experience with a patient treated in clinical practice on a local island

Chinen

Saeki²,

Mori

et al. 2019

J Rural Med

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Background: Gitelman syndrome (GS) is an autosomal recessive salt-losing renal tubulopathy resulting from mutations in the thiazide-sensitive Na-Cl cotransporter (NCC) gene. Notably, lack of awareness regarding GS and difficulty with prompt diagnosis are observed in clinical practice, particularly in rural settings.Case presentation: We report a case of a 48-year-old man with GS who presented to a local clinic on a remote island. Occasional laboratory investigations incidentally revealed a reduced serum potassium level of 2.6 mmol/L. A careful medical interview revealed episodes of intermittent paralysis of the lower extremities and muscular weakness for >30 years. Subsequent laboratory investigations revealed hypomagnesemia, hypocalciuria, and hypokalemic metabolic alkalosis. Based on the patient’s history, clinical presentation, and laboratory investigations, we suspected GS. Genetic testing revealed a rare homozygous in-frame 18 base insertion in the NCC gene that might have resulted from the founder effect, consequent to his topographically isolated circumstances.Conclusion: More case studies similar to our study need to be added to the literature to gain a deeper understanding of the functional consequences of this mutation and to establish optimal management strategies for this condition, particularly in rural clinical settings.

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Gitelman syndrome and glomerular proteinuria: a link between loss of sodium-chloride cotransporter and podocyte dysfunction?

Cited by 22 publications

References 19 publications

A case of hypokalemia and proteinuria with a new mutation in the SLC12A3 Gene

A case of hypokalemia and proteinuria with a new mutation in the SLC12A3 Gene

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

A case of Gitelman syndrome: our experience with a patient treated in clinical practice on a local island

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