Renal hypouricemia is characterized by impaired uric acid reabsorption at the apical membrane of proximal renal tubule cells. Patients may be asymptomatic. However, it is accompanied by nephrolithiasis and exercise-induced acute renal failure in about 10% of patients. No other proximal tubular disorders are observed, although in some cases, can be be associated with hypercalciuria.
Although most patients are asymptomatic, they can occasionally have episodes of uric acid and/or calcium oxalate nephrolithiasis. More and more cases are described that, after exercise, develop acute renal failure due to intratubular deposits of uric acid.
To prove that the hypouricemia is renal tubular in origin, the fractional excretion of uric acid should be increased (EF uric acid>10%) and serum uric acid should be less than 2.0 mg/dl. Glomerular filtration rate and other parameters that assess renal tubular function are normal. Quite frequently, the renal hypouricemia is associated with hypercalciuria, which has been associated with the presence of elevated levels of calcitriol.
In 2002, a urate transporter, URAT1, was identified in human kidney. URAT1 is located in the apical tubular membrane, and is encoded by the SLC22A12 gene. Uricosuric drugs, probenecid and benzbromarone act on this transporter. Mutations in SLC22A12 are the cause of hereditary renal hypouricemia (Renal hypouricemia-1, RHUC1). Subsequently, a second gene, SLC2A9, was identified that encodes GLUT9 protein and belonging to a family of proteins facilitating the transport of hexoses (fructose, glucose). There is an isoform, GLUT9L, that is expressed primarily in the basolateral membrane of proximal tubule cells, and another isoform GLUT9S that is expressed exclusively in the apical membrane of these cells. This explain why in patients with the second variant of renal tubular hypouricemia (hypouricemia renal-2, RHUC2) the reduction in the urate reabsorption occurs on both sides of the proximal tubules cells and the urate fractional excretion is greater than 150%. GLUT9 is certainly the main regulator of urate levels in humans. For the genetic study it will be necessary samples of the index case and the parents.
The oral fluid intake should be increased in order to get an abundant diuresis. Thereby, the concentration and hipersaturación of uric acid in urine will decrease. It is necessary to maintain the urinary pH between 6 and 6.5, in order to increase the solubility of uric acid. At the same time, the dissolution of existing calculi will be facilitated. Alkalization is carried out with oral potassium citrate, sodium salts like bicarbonate should not be used since they increase the hypercalciuria and calcium stones. If the alkalization is excessive, there risk for formation calcium phosphate calculi.
It is in general good because it is usually a benign disease. Increased levels predispose for gout and, if very high, renal failure.
Some patients develop nephrolithiasis and exercise-induced acute renal failure.