Bartter's and Gitelman's syndromes: their relationship to the actions of loop and thiazide diuretics

The wider recognition of inherited Bartter's and Bartter's-like syndromes, especially Gitelman's, has come largely as a result of the advances in, and application of, molecular genetics. By exploiting pre-existing renal cell models of ion transport, specifically for sodium and potassium, the known mechanisms and sites of action of loop and thiazide diuretics and the similarity of their chronic effects to these syndromes, it was possible for geneticists to take a candidate gene approach. This was initially successful but, when not all cases could be explained on this basis, it forced a more detailed clinical appraisal and better phenotyping, resulting in the discovery of novel genes involved in controlling renal sodium, potassium and chloride transport, and new insights into renal tubular physiology. This is a good example of one form of ‘translational research’, the message being the importance of our ability to link (in this instance) basic renal physiology and pharmacology, with clinical nephrology and genetics.