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Oxalate is a dicarboxylic acid, which is an end-product of liver metabolism of glyoxalate and glycerate. Humans have no enzyme capable of degrading oxalate, which is quite insoluble, particularly when precipitated with calcium. Oxalate is important primarily because it affects kidney stone formation. About 85% of all kidney stones contain calcium oxalate in some proportion. Oxalate also may precipitate in tissues, causing tissue toxicity.
In the absence of disease, up to 90% of the body pool of oxalate is produced by hepatic metabolism and the other 10% is provided by the oxalate in food. However, in the presence of gastrointestinal disease, the percentage absorbed from food can be much greater.
Oxalate is filtered by the glomerulus and efficiently secreted by the renal tubules. Once the glomerular filtration rate (GFR) begins to decrease, the pool size increases, but plasma levels do not increase out of the normal range until the GFR decreases to <10 mL/min to 20 mL/min.
Plasma oxalate concentration is a reflection of the body pool size. When the pool increases, oxalate may precipitate in tissues and cause toxicity. Plasma oxalate pool size can be increased in various situations:
-Increased production and accumulation results from an abnormality in at least 2 different enzymes. Alanine glyoxalate transferase is necessary for the conversion of glycolate to alanine. A deficiency or intracellular mistargeting of this hepatic enzyme results in increased oxalate production (primary hyperoxaluria I). Hepatic glycolate reductase/hydroxypyruvate reductase deficiency results in increased glyceric acid formation, which eventually leads to increased oxalate production (primary hyperoxaluria II).
-Pool size of oxalate can be increased by increased absorption from the intestine after consuming foods such as rhubarb, nuts, chocolate, or tea.
-Certain abnormalities of the gastrointestinal tract, including fat malabsorption, short bowel syndromes, and abnormal bile salt metabolism, all result in increased oxalate absorption from the intestinal tract.
-Increased pool size can result from decreased urinary excretion as occurs in chronic renal insufficiency.
Management of patients with primary hyperoxaluria and renal failure is difficult. Intensive dialyses are undertaken in an attempt to keep plasma levels below the level at which supersaturation is thought to occur.
Primary hyperoxaluria is typically diagnosed by measuring oxalate levels in urine. However, as kidney function decreases, the renal excretion of oxalate also decreases. In such situations, plasma oxalate levels may be informative. Plasma oxalate is often used to monitor these patients during critical periods in and around kidney transplantation, dialysis, or liver transplantation.
High value suggestive of primary hyperoxaluria. However if the patient has chronic kidney disease (GFR <30 mL/min/1.732m) plasma oxalate values up to 30 mcM/L can be normal.
Assessing the body pool size of oxalate. The settings in which it has been most useful include patients with enzyme deficiencies, such as primary hyperoxaluria, which result in overproduction of oxalate.
In the presence of renal insufficiency, 3 uses of plasma oxalate are:
-In those patients with renal insufficiency from indeterminate causes and in whom the question of primary hyperoxaluria has arisen and urinary oxalate is not available, plasma oxalate has been used for diagnosis of primary hyperoxaluria
-Monitoring patients with renal failure who are thought to have primary hyperoxaluria
-As an aid to maintaining plasma oxalate at levels below that which supersaturation occurs
In nonacidified plasma specimens values near the reference range increase an average of 50% due to spontaneous oxalate generation.
In patients with normal renal function, the presence of increased plasma oxalate concentration is good evidence for overproduction of oxalate (primary hyperoxaluria).
In the presence of renal insufficiency, plasma oxalate levels are markedly elevated. Increased levels of plasma oxalate can be found in dialysis patients.
In patients with possible primary hyperoxaluria and renal insufficiency, the diagnosis often can be made by knowing the plasma level of oxalate. However, ancillary tests, such as the demonstration of oxalate crystals in tissues (other than the kidney) or increased glycolate in dialysate (for patients on dialysis) often are necessary to make an accurate diagnosis.
Because increased production and decreased excretion rates of oxalate can increase the plasma oxalate concentration, the interpretation of any given plasma value must consider the patient's clinical setting.
Proper specimen processing and acidification are essential to obtain a quality result (see Specimen Required).
For external clients only, non-acidified specimens can be accepted if the heparinized plasma is promptly frozen. However, in non-acidified plasma oxalate values may increase spontaneously (average 50% increase for plasma oxalate <15 mcmol/L; average 10% increase for plasma oxalate >15 mcmol/L).
1. Milliner DS, Eickholt JT, Bergstralh EJ, et al: Results of long-term treatment with orthophosphate and pyridoxine in patients with primary hyperoxaluria. N Engl J Med 1994;331:1553-1558
2. Kuiper JJ: Initial manifestation of primary hyperoxaluria type I in adults--recognition, diagnosis, and management. West J Med 1996;164:42-53