Clinical Information

Oxalate is an insoluble dicarboxylic acid, which is an end product of liver metabolism of glyoxalate and glycerate. Humans lack an enzyme to degrade oxalate, and thus it must be eliminated by the kidney. Oxalate is a strong anion and tends to precipitate with calcium, especially in the urinary tract. Consequently, about 75% of all kidney stones contain calcium oxalate in some proportion. In renal failure oxalate is retained in the body and it can precipitate in tissues causing tissue toxicity, a condition called oxalosis.

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 oxalate contained in various foods. However, in the presence of gastrointestinal diseases that cause fat malabsorption the percentage absorbed from food can be much greater. The oxalate content of fruits and vegetables is quite variable, some being quite high and others virtually zero.

Oxalate is freely filtered by the glomerulus. A smaller amount is also secreted in the proximal tubule. If the glomerular filtration rate (GFR) is decreased, oxalate begins to be retained in the body. However, in persons without primary hyperoxaluria (PH) or enteric hyperoxaluria (EH) plasma levels do not exceed the normal range until the GFR decreases below 10-20 mL/min/1.73 m(2).

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 3 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 type1).

Glycolate reductase / hydroxypyruvate reductase deficiency in the liver and elsewhere in the body results in increased glyceric acid formation, which leads to increased oxalate production (primary hyperoxaluria type 2).

A third type of PH was recently shown to be due to mutations of HOGA1 that encodes the enzyme
4-hydroxy-2-oxaloglutarate aldolase that is found in hepatic mitochondria (primary hyperoxaluria type 3).

Increased oxalate load can be caused by increased absorption from the intestines after consuming large amounts of oxalate-rich foods such as rhubarb, spinach, or nuts.

Certain abnormalities of the gastrointestinal tract can cause fat malabsorption including short bowel syndromes, inflammatory bowel disease, gastric bypass for obesity, and pancreatic insufficiency. All of these gastrointestinal abnormalities result in increased oxalate absorption from the intestinal tract. This is due to saponification of calcium by fatty acids in the colon, which in turn frees up oxalate anions for absorption.

Decreased urinary oxalate excretion in chronic kidney disease (CKD) also caused oxalate retention in the body.

Management of patients with PH and renal failure is difficult. Intensive dialyses are undertaken in an attempt to keep plasma levels below the level at which supersaturation and crystallization can occur in body tissues such as heart and bones (called oxalosis).

PH 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. Although plasma oxalate increases in CKD patients without PH, values are much higher in those CKD patients who do have PH. Plasma oxalate is often used to monitor these patients during critical periods in and around kidney transplantation, dialysis, or liver transplantation.

Oxalate concentration in dialysate fluid is a reflection of the oxalate removed during dialysis.