Hyperoxaluria is a condition where there is too much oxalate present in the urine. It can be caused by inherited (genetic) disorders, an intestinal disease or eating too many oxalate-rich foods.
Oxalate is an end product from the metabolism in vertebrates. It is primarily derived from the amino acid and glyoxalate metabolism. Oxalate can also be absorbed from oxalate-rich food such as rhubarb, spinach, coffee and chocolate.
Although nature has provided oxalate degrading machinery in the form of enzymes in several bacteria and fungi, vertebrate animals including humans do not have the capacity to degrade oxalate. The oxalate has to be excreted through the kidneys and through the intestines. Oxalate forms insoluble calcium oxalate at physiological pH and the growth of calcium oxalate crystals can result in severe damage to the kidneys. Consistent high levels of oxalate is known as hyperoxaluria.
PH is a rare autosomal recessive disorder of the glyoxalate metabolism, caused by a deficient or absent activity of specific enzymes. It is a genetic disease that primarily affects children. PH has a prevalence of 1-3 cases per million inhabitants and an incidence of 1: 120,000 live births. Three types of PH exist, types I, II and III; type I is the most common variant accounting for 70-80% of all cases. All types of PH are characterised by severe hyperoxaluria.
The human body tries to excrete oxalate through the intestines via specific secretory proteins and through the kidneys. Oxalate forms an insoluble salt together with calcium and results in the formation of crystals of calcium oxalate.. Recent findings indicate that very small crystals get internalized in the parenchymal cells in the kidney and causes inflammation. PH-patients suffer from a progressive kidney damage and calcification of the kidneys and the disease leads to kidney failure. With advancing renal failure, patients experience progressive systemic deposition of calcium- oxalate, also referred to as oxalosis.This can lead to multiple organ dysfunction and cause severe morbidity and mortality.
There is currently no approved drug available that can significantly decrease the oxalate load in plasma and urine for these patients. A combined liver and kidney transplantation is the only curative treatment.
SH is caused either by a defect secretion of oxalate to the intestine or by a defect absorption of oxalate from the intestine.
In patients with a disturbed function of the small intestine, both the oxalate secretion from plasma and the oxalate absorption from diet can be disturbed and cause elevated levels of oxalate in plasma and urine. The malfunctioning small intestine can be a result of many different diseases such as, but not limited to, inflammatory bowel disease, Chron’s disease, gastric surgery or cancer. The course of the disease can be either a slow progression or a faster process, where patients eventually develop Chronic Kidney Disease (CKD) and kidney failure.