What is Hyperoxaluria and Oxalosis?
Hyperoxaluria is a condition where too much oxalate is present in the urine. Oxalate is the salt form of oxalic acid, and is a natural end product of metabolism. Oxalate does not appear to be needed for any human body process and normally, more than 90% is excreted by the healthy kidney, with a small amount of excretion into the lower gut. Since oxalate and calcium are continuously excreted by the kidney into the urine, it can combine with calcium causing formations of calcium-oxalate crystals and grow into a kidney stone.

Kidney stones are more common in adults, occurring in 10% of men and 3% of women during their lifetimes. Kidney stones are rare in children and uncommon in teenagers, though can occur at any age. Calcium oxalate stones are the most common type of stone formed by individuals who have kidney stone disease. Increased oxalate in the urine can come from eating too much oxalate in foods, over-absorption of oxalate from the intestinal tract associated with intestinal diseases (enteric hyperoxaluria) and abnormalities of oxalate production (primary hyperoxaluria).

Hyperoxaluria is uncommon. In some people the cause of the excess urine oxalate is not known but may result from changes in the way kidneys handle normal amounts of body oxalate. In its many forms it can be found among all ages, from infants to people in their 70's. The highest amounts of oxalate in the urine however are seen in diseases in which the liver produces too much oxalate - this occurs in primary hyperoxaluria.

Because of the low solubility of oxalate, increased concentrations of oxalate in body fluids, including the urine, can lead to the deposition of calcium oxalate (oxalosis) in the kidney tissue (nephrocalcinosis) or urinary tract (urolithiasis, nephrolithiasis, kidney stones). Oxalosis occurs after the kidneys fail and the excess oxalate builds up in the blood and then deposits oxalate salts in the eyes, blood vessels, bones, muscles, heart and other major organs.

Primary Hyperoxaluria Type I and Type II
Primary Hyperoxaluria (PH) is a rare genetic (inherited) disorder that is present at birth. Primary hyperoxaluria comes in many forms, of which only two, Type I and Type II are well characterized. Type I and Type II are both autosomal recessive diseases. Although Type I is more common than Type II, it is still a rare disease with an estimated frequency of somewhere between 1 in 100,000 and 1 in 1,000,000.

In Type I and Type II PH, the enzyme in the liver is defective but the organ that suffers is the kidney. In a person with Type I, the liver creates too little of the enzyme alanine: glyoxylate aminotransferase or AGT. In patients with Type I, the deficiency of AGT causes increased amounts of oxalate and glycolate to be formed in the body. Unfortunately, oxalate cannot be further metabolized, and it can only be eliminated from the body by the kidney by urinary excretion. This leads to an increase in urinary excretion, producing both hyperoxaluria and hyperglycolic aciduria.

In Type II, the liver is missing a different enzyme called glyoxylate reductase or GR also called, hydroxpyruvate reductase or HPR. Like AGT, GR is also found mainly in liver cells. Very large amounts of oxalate are produced when there is too little of the enzyme in the liver which leads to increased urinary excretion. Type II patients frequently have high concentrations of glyceric acid in the urine in addition to hyperoxaluria. Over time, large amounts of oxalate in the urine can cause kidney stones.

Patients with primary hyperoxaluria typically present kidney stones, anywhere from birth to the mid -20's. But hyperoxaluria may go unrecognized until age 30 to 40. When very large amounts of oxalate are present in the urine, such as in primary hyperoxaluria, the kidneys can be damaged to the point that they stop working (renal failure). In some patients the first symptom may be kidney failure. Oxalosis occurs after the kidneys fail and the excess oxalate builds up in the blood, and then spreads to the eyes, bones, muscles, blood vessels, heart and other major organs.

Milder forms of hyperoxaluria can cause kidney stones without other associated problems. Severe hyperoxaluria not only causes kidney stones but if left untreated, can lead to serious illness and even death. Among patients with primary hyperoxaluria, about 50% will have kidney failure by age 15, and about 80% will have kidney failure by age 30. For that reason, it is critical that primary hyperoxaluria be diagnosed and treated as early as possible.

Other forms of Primary Hyperoxaluria
Other forms of PH certainly exist and a number of individuals have been described with very high urine oxalate who have normal AGT and GR activities. However, reasons for the marked increase in oxalate in these patients (whether it is due to a different liver enzyme defect or to problems in the kidney) has not yet been identified.

Chronic Kidney Disease, Kidney Failure, and Oxalosis
The kidneys, when working normally, are very efficient at eliminating excess oxalate that is produced by the liver or absorbed from the intestinal tract. In patients with good kidney function, blood concentrations of oxalate are kept normal or near the normal range, and it is only in the urine and the kidney tissue that high concentrations of oxalate occur. It is the high concentration of oxalate in the urine (hyperoxaluria) that causes stones to form, and over time causes damage to kidney tissue.

As time passes, kidney function may be reduced by 50% or more. When that occurs, and the kidney can no longer eliminate excess oxalate efficiently and blood levels of oxalate begin to rise. When blood oxalate concentrations reach a critical level, the amount of oxalate in the blood is high enough to form complexes with calcium leading to calcium oxalate deposits in multiple body tissues (called oxalosis).

Oxalosis can involve many different organs. Most common in patients with primary hyperoxaluria with associated kidney failure are deposits in small blood vessels which can cause painful skin ulcers that do not heal, deposits in bone marrow causing anemia, deposits in bone tissue causing failure to grow in children and fractures in adults and children, and calcium oxalate deposits in the heart causing abnormalities of heart rhythm or poor heart function.

Oxalosis will become progressively more severe as long as the blood oxalate concentration remains high, and can lead to death. For this reason, prompt recognition of the problem and prompt treatment are essential. Kidney dialysis can remove oxalate from the blood, but in most patients with primary hyperoxaluria dialysis cannot keep pace with the very large amount of oxalate produced. Definitive treatment of kidney failure and oxalosis in patients with primary hyperoxaluria is transplantation.

Overview | Symptoms | Diagnosis | Treatment | Transplantation | Future of OHF