Complications
In several of the heritable disorders, volume depletion and inanition are seen as early as infancy. They result from the massive loss of sodium, chloride, and other substrates caused by the generalized failure of the proximal tubule.
Many patients with hyperkalemic distal RTA develop this condition as a consequence of diabetes or chronic interstitial kidney disease. These individuals also have a high rate of cardiac disease including congestive heart failure, hypertension, and chronic kidney disease. When sodium reabsorption is stimulated, hypertension can worsen and fluid retention in the presence of heart failure or chronic kidney disease may cause worsening of edema and pulmonary edema. If these complications develop, furosemide can be used to reduce salt retention, but it may be necessary to discontinue the fludrocortisone.
Increased loads of filtered calcium arise because of the release of calcium phosphate and calcium carbonate during bone buffering. Accumulation of reabsorbed calcium leads to nephrocalcinosis.
Bone buffering of acidosis results in demineralization.
Acidosis is associated with muscle catabolism. Control of acidosis can restore normal growth.
In Fanconi syndrome, much of the growth retardation is due to the metabolic disorders that underlie most cases, although phosphate losses and abnormalities of vitamin D metabolism are important, and carnitine loss may also have a role.
Children with Fanconi syndrome of any cause are at risk of developing renal rickets, owing to the inability of the kidney to retain phosphate. Phosphate depletion results in inhibition of bone growth and remodeling. Loss of vitamin D in the urine and defective uptake and handling of vitamin D by the kidney impair the renal response to the hormone. Bones are poorly mineralized. Physical examination may detect genu valgum. Skeletal radiographs will define rickets. Aggressive phosphate replacement and vitamin D supplementation are useful in children.
Data indicate a significant risk for chronic kidney disease in primary distal RTA over time.[27][53] Chronic kidney disease may be a result of recurrent kidney stones, nephrocalcinosis, effects of hypokalemia or increased ammonia metabolism. In theory, control of acidosis and hypokalemia should diminish the risk, but there are currently insufficient data supporting this theory.
Direct consequence of genetic defect, not amenable to current treatment.
Distal RTA may result in hyperammonemia, which can cause neuronal dysfunction. A systematic review found hyperammonemia in several case reports of children who presented with poor feeding, vomiting, and failure to thrive and were found to have distal RTA. In these patients circulating ammonia levels were inversely related to bicarbonate levels (P <0.05).[150]
Because the distal nephron is the site of most critical potassium handling, it is clear that the potassium depletion in Fanconi syndrome is a secondary event. Most patients with proximal RTA have some degree of volume depletion and secondary hyperaldosteronism. When bicarbonate is aggressively replaced, bicarbonate is delivered to the distal nephron in quantity as sodium bicarbonate. In the presence of secondary hyperaldosteronism, sodium is absorbed and the lumen of the distal tubule and collecting duct becomes increasingly negatively charged relative to the peritubular tissue. This negative charge enhances potassium secretion by the tubule, leading to potassium depletion.
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