Purpose of review: The study of inherited renal sodium (Na) transport disorders has greatly benefited from the use of new molecular biology research tools. This review discusses the recent findings that have expanded our knowledge and may impact clinical decision-making.
Recent findings: The genetic and molecular biology diagnostic tools have to a large extent validated conclusions drawn from physiologic studies that documented suppressed or enhanced Na transport in specific distal nephron segments in various disorders. However, many surprises were also encountered. In several conditions, no mutation in the Na transporter itself was found despite apparent dysfunction of the transporter. Further search has led to discovery of additional mechanisms. Some involve mutations in other transporters, especially potassium (K) and chloride (Cl) channels, which secondarily affect function of the Na transporter by altering electrochemical gradients across the cell membrane. Examples include certain types of Bartter syndrome. In other patients, search for mechanism has led to discovery of novel physiologic regulatory pathways that, if abnormal, will lead to up- or downregulation of an Na transporter. Examples include some types of Bartter syndrome and Gordon syndrome. Genetic diagnosis has also revealed hitherto unexplained phenotypic heterogeneity between patients carrying the same mutation, implying a contributory role for other factors.
Summary: Genetic and molecular diagnosis will have an expanding role in the understanding and management of the Na transport disorders. Predicting prognosis and inheritance pattern, as well as treatment plans will in the future be based on genetic diagnosis.