Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics (Seventh Edition) - Chapter 4: Renal Tubular Disorders

The renal tubules are the primary mechanism by which the body can reabsorb small molecules. Disorders of renal tubular function are divided by the segment of the tubule involved and by the substrate(s) whose transport is affected. Molecules are reabsorbed by mechanisms that are both specific and saturable. Most of the transport proteins involved in specific transport systems have been identified and mapped. Most disorders of transport involve defects in the proximal tubule. The renal tubules reabsorb 80%–98% of filtered small molecules by energy-dependent mechanisms. Disorders, primary or secondary, that interfere with these mechanisms can cause loss in the urine of sugars, amino acids, bicarbonate, phosphorus, and other cations, as well as a variety of organic acids. Specific transport systems are under genetic control. Thus, inherited disorders can affect the reabsorption of only one or a small group of compounds. Defects altering energy metabolism can produce a more generalized loss of renal tubular mechanisms. With the notable exceptions of bicarbonate and phosphorus, unless an intestinal defect is also present, these disorders produce little systemic disease and have not yet been implicated in nutritional deficiencies, although there is now some suggestion that they may be import in seniors. Cystine transport deficiency produces problems primarily because of the low solubility of this compound. Nonetheless, these disorders are important to recognize because they cause confusion with defects in metabolism, where increased serum levels of a compound cause the filtered load to exceed the tubules' capacity for reabsorption.