Gitelman Syndrome: A Rare Case of Hypokalaemia and a Novel Mutation

Gitelman syndrome (GS) is a hereditary renal tubulopathy caused by mutations in the SLC12A3 gene which encodes the thiazide-sensitive apical sodium-chloride cotransporter. GS is characterized by hypokalaemia, hypomagnesaemia and metabolic alkalosis. Treatment is based on potassium and magnesium replacement ad eternum. We present the case of a young man with palpitations and persistent hypokalaemia, who was diagnosed with GS. Genetic testing revealed 2 mutations in the gene SLC12A3 of combined heterozygosity, both considered pathological. Interestingly, 1 of these mutations was not yet described in the literature or in the reviewed databases. We also discuss the clinical approach and the specificities of managing this rare hereditary renal tubulopathy.

Advanced Oxidation Protein Products Contribute to Renal Tubulopathy via Perturbation of Renal Fatty Acids

BackgroundRenal proximal tubulopathy plays a crucial role in kidney disease, but its molecular mechanism is incompletely understood. Because proximal tubular cells consume a lot of energy during reabsorption, the relationship between fatty acids (FAs) and proximal tubulopathy has been attracting attention. The purpose of this study is to investigate the association between change in renal FA composition and tubulopathy.MethodsMice with cisplatin-induced nephrotoxicity were used as a model of AKI and 5/6-nephrectomized mice were used as a model of CKD. Renal FA composition in mice was measured by GC-MS. Human tubular epithelial cells (HK-2 cells) were used for in vitro studies.ResultsIn kidneys of AKI mice, increased stearic acid (C18:0) and decreased palmitic acid (C16:0) were observed, accompanied by increased expression of the long-chain FA elongase Elovl6. Similar results were also obtained in CKD mice. We show that C18:0 has higher tubular toxicity than C16:0 via induction of ER stress. Using adenovirus-expressing Elovl6 or siRNA for Elovl6 in HK-2 cells, we demonstrated that increased Elovl6 expression contributes to tubulopathy via increasing C18:0. Elovl6 knockout suppressed the increased serum creatinine levels, renal ER stress, and inflammation that would usually result after 5/6 nephrectomy. Advanced oxidation protein products (AOPPs), specifically an oxidized albumin, was found to induce Elovl6 via the mTORC1/SREBP1 pathway.ConclusionsAOPPs may contribute to renal tubulopathy via perturbation of renal FAs through induction of Elovl6. The perturbation of renal FAs induced by the AOPPs-Elovl6 system could be a potential target for the treatment of tubulopathy.