What is the pathophysiology of Fanconi syndrome?

Updated: Feb 09, 2018
  • Author: Sahar Fathallah-Shaykh, MD; Chief Editor: Craig B Langman, MD  more...
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Numerous mechanisms can result in diminished reabsorption of solutes by the proximal tubule. The 3 main categories in which they can be classified are (1) alterations in the function of the carriers that transport substances across the luminal membrane, (2) disturbances in cellular energy metabolism, and (3) changes in permeability characteristics of the tubular membranes.

Numerous symporters and antiporters affect the transport of solutes across the apical membrane of proximal tubule cells. The energy required for the function of these carriers is provided by the sodium-potassium (Na+/K+)–adenosine triphosphatase (ATPase) pump, which is located at the basolateral membrane.

Because of the large number of transport abnormalities observed in Fanconi syndrome, these anomalies are not likely due to alterations in the carriers, which are specific for each of the substances reabsorbed in the proximal tubule. A defect in cellular energy metabolism appears to be a more plausible cause. Under the scenario of a defective cellular energy metabolism, any process that results in a decrease in the level of ATP impairs the performance of secondary active transport mechanisms, such as those of glucose, phosphate, or amino acids. Evidence supporting this hypothesis can be found in various experimental models and clinical forms of Fanconi syndrome.

One of the most extensively studied models of Fanconi syndrome is that induced by maleic acid. Rats and dogs injected with this substance develop glucosuria, phosphaturia, aminoaciduria, bicarbonaturia, and proteinuria, associated with decreases in Na+/K+ -ATPase and ATP levels. Similar changes develop in animals injected with heavy metals, such as cadmium, lead, and mercury.

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