Hyperoxaluria is the term for high levels of oxalate in the urine. It is normal to pass oxalate in the urine but these levels are lower than 40mg (milligrams) per day. In hyperoxaluria the urinary oxalate levels exceed 40mg within a 24 hour period. The oxalate is produced within the body and/or sourced from certain foods. High levels of oxalate greatly increases the risk of urinary stones. It can also progress to oxalosis where the blood levels of oxalate is raised and oxalate is deposited in various tissues throughout the body.
Oxalate (C2O4) is an organic salt that is considered to be endogenous when it is produced within the body or exogenous when it is sourced from food. It has no known beneficial role in the human body.
Oxalate is produced in the liver during glycolate metabolism. It is an end-product that is excreted in the urine as a waste since it does not have any known benefit to humans.
Oxalate is produced by plants in varying amounts. It is used as a means for the plant to get rid of excess calcium. Most of the oxalate can be found within the bark, fruit, nuts and leaves.
The amount of oxalate produced in the body and sourced from food varies on a daily basis and from person to person. Even the same species of plant may contain varying amounts of oxalate. There are many reasons why the oxalate levels may be elevated. Eating foods that are high in oxalate is one reason. Another possible mechanism is that there is greater than normal oxalate absorption from the gut. A rare mechanism arises when the pathway for glycolate metabolism that favors oxalate production is increased due to a loss of enzymes that catalyze other pathways . Lastly, excess levels of oxalate may occur for no clearly identifiable reason.
Although it has no known benefit, oxalate has a strong affinity for calcium. When it binds with calcium, it forms calcium oxalate. This compound has low solubility meaning that it does not dissolve very well in body fluids. Therefore it can increase the risk of stone formation. Since oxalate is passed out in the urine, it is in the kidney and urinary tract where stones are more likely to occur when there is excess oxalate in the urine. The effects of excess oxalate in the body is not limited to kidney stones. Excess oxalate that is not removed by the kidney can build up in the bloodstream and be deposited in tissues throughout the body. This is known as oxalosis.
Excessively high levels of oxalate may present in different ways depending on the part of the body where oxalate is deposited.
The formation of calcium oxalate kidney stones are the most common presentation. Small stones may not cause any symptoms and is passed out unnoticed in the urine. Medium-sized stones can cause severe flank pain once it enters the ureter. A burning sensation during urination is usually reported and there may be signs of blood in the urine (hematuria). Larger stones may not pass into the ureter and cause an accumulation of urine in the kidney. Oxalate build up in kidney tissue causes nephrocalcinosis.
Oxalate in the bones in high levels can reduce the deposition of bone by osteoblasts and increase bone resorption. This weakens the bones which may not cause any symptoms at the outset. Patients may be prone to fractures more easily than would be expected. It can lead to problems with growth in children.
A build up of oxalate in the small arteries impairs oxygen supply to the tissue. This is more prominent in the hands and feet. In more severe cases it can lead to the formation of ulcers on the skin, particularly on the fingers and toes.
Deposition of oxalate within the nerve cells and blood vessels supplying the nerves hampers its activity. It may lead to peripheral neuropathy that presents with a myriad of symptoms depending on the nerve(s) affected. Involvement of sensory nerves may present with pain, numbness and tingling while that of motor nerves may lead to muscle weakness, paralysis or poor coordination.
Oxalate accumulation within the bowels mainly causes diarrhea. It is usually persistent and therapeutic measures are usually not effective. Diarrhea can lead to dehydration which further increases the chances of kidney stone formation.
- Bone marrow – anemia
- Heart – arrhythmia and cardiac insufficiency
Hyperoxaluria may arise due to several mechanisms and the causes may therefore vary. It can arise with excessive consumption of oxalate-rich foods, increased production of oxalate within the body, higher than normal oxalate absorption from the gut or due to unknown reasons. Based on its etiology, hyperoxaluria can be classified according to four types :
- Primary hyperoxaluria
- Enteric hyperoxaluria
- Dietary hyperoxaluria
- Idiopathic hyperoxaluria
With primary hyperoxaluria, inherited genetic defects affect certain metabolic pathways as a result of enzyme deficiencies. Alternative pathways are utilized as a result of which higher levels of oxalate is produced. There are several subtypes.
- Type I is due to a deficiency of alanine-glyoxylate aminotransferase. It is the most common type.
- Type II is due to deficiency of D-glyceric dehydrogenase.
- Type III is where no known enzyme deficiency exists but the body overproduces oxalate.
This form of hyperoxaluria is usually a consequence of malabsorption. It arises when disruptions in the normal absorptive function of the small reduces the availability of calcium in the gut. This means that less oxalate is bound to calcium. Greater amounts of oxalate can then be absorbed from the gut. Any cause of chronic diarrhea can lead to enteric hyperoxaluria. This includes :
- Inflammatory bowel disease (IBD)
- Pancreatic disease
- Biliary tract disease
- Surgical resection of the small bowel
- Bariatric surgery (for weight loss)
Certain bacteria within the gut known as Oxalobacter formigenes can digest oxalate. When these bacteria are present in low numbers, it can allow for increased oxalate absorption.
This type of hyperoxaluria arises from consuming large amounts of oxalate-rich foods such as :
Idiopathic hyperoxaluria is the most common type. It is believed to be a consequence of primary hyperoxaluria where no specific enzyme deficiency can be identified (type III) or with increased consumption of oxalate-rich foods which cannot be conclusively identified.
Hyperoxaluria should be suspected in patients with recurrent calcium oxalate stones, especially if there is co-existent chronic diarrhea. Various tests can confirm the diagnosis of hyperoxaluria. This includes :
- Urinalysis with 24-hour urine collection
- Liver biopsy to identify deficient enzymes in primary hyperoxaluria
- Urea and electrolytes blood test
Imaging studies like a CT scan or ultrasound is useful to evaluate the consequences of hyperoxaluria and oxalosis. Levels of oxalate exceeding 40mg in a 24-hour urine collection sample is conclusive for hyperoxaluria. A level slightly higher than 40mg may be seen in males but is still considered normal.
The treatment measures utilized and long term management depends on the type of hyperoxaluria and severity of the condition.
- Primary hyperoxaluria :
- Vitamin B6 (pyridoxine) supplementation
- Magnesium supplementation
- Thiazide diuretics
- Gene therapy
- Liver-kidney transplantation is the only definitive cure.
- Enteric hyperoxaluria :
- Calcium supplementation
- Iron/aluminum supplementation
- Magnesium supplementation
- Potassium citrate
- Dietary modification
- Organic marine hydrocolloid
- Idiopathic hyperoxaluria :
- Restriction of dietary oxalate
- Phosphate or magnesium supplementation
- Calcium supplementation