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The glomeruli filter approximately 150 liters of ultrafiltrate daily that are delivered to the renal tubules. The renal tubules reabsorb organic solutes, salt, and water to maintain a constant extracellular fluid volume and composition. In addition, organic anions and cations, which are protein bound and not filtered by the glomerulus, are secreted by the proximal tubule. The final urine contains about one hundredth of the volume and sodium as that in the original glomerular filtrate, but contains all waste products. There are 12 nephron segments that have different transport properties to perform this task. Disorders of tubular function can be due to inherited defects in transporters or mutations in factors that regulate transport, or result from inherited or acquired disorders that cause tubular injury. Renal transport disorders can be mild with little to no clinical consequences, or life threatening, depending on the transporters and nephron segments affected.

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Fanconi syndrome is a generalized proximal tubule transport disorder.1 The proximal tubule is responsible for the reabsorption of all filtered glucose and amino acids, and 80% of the filtered bicarbonate and phosphate. Patients with Fanconi syndrome have hypophosphatemia, hypokalemia, and hyperchloremic metabolic acidosis.

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Pathophysiology

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The luminal fluid entering the proximal tubule is an ultrafiltrate of plasma. Most solutes are transported across the apical membrane in conjunction with sodium. The driving force for solute transport is the low intracellular sodium generated by the basolateral Na+-K+-ATPase. A generalized decrease in proximal tubular transport could result from a primary injury to the Na+-K+-ATPase pump or a decrease in intracellular adenosine triphosphate (ATP) that fuels the pump. Theoretically, an increase in the permeability of the proximal tubule paracellular pathway could result in Fanconi syndrome, but this theory has been discounted. Although the cellular basis for most causes of Fanconi syndrome has not been determined, most studies have demonstrated that the proximal tubule transport defect in Fanconi syndrome is the result of a decrease in intracellular ATP.

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Differential Diagnosis

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The causes for Fanconi syndrome are listed in Table 474-1. Diagnosis of Fanconi syndrome is usually made due to the presence of symptoms, including failure to thrive, severe rickets, and sometimes bouts of polydipsia, polyuria, and dehydration. Laboratory findings include hypophosphatemia, hypokalemia, and acidosis.2 Evaluation of the urine reveals glucosuria, generalized aminoaciduria, and hyperphosphaturia, despite the hypophosphatemia, a stimulus that increases proximal tubule phosphate absorption.

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Table 474-1. Causes of Fanconi Syndrome

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