Hyperoxaluria

Under hyperoxaluria (also: oxaluria, oxalosis ) refers to the rise and increased excretion of oxalic acid in the urine.

Molding

There are two forms of hyperoxaluria: on the rare primary hyperoxaluria is an enzyme defect that occurs secondary hyperoxaluria other underlying diseases in the frame.

Primary hyperoxaluria

Oxalate is an end product of metabolism and is, as long as renal function is sufficient to almost completely excreted in the urine. Usual case of extremely high oxalate excretion, as in primary hyperoxaluria (PH), the urine calcium oxalate always ( CaOx ) is supersaturated. This leads to deposits of these crystals in renal tissue ( nephrocalcinosis ) or to stone formation in the urinary tract. Both triggers chronic inflammation and scarring, and finally a renal impairment.

In addition to the deposition of calcium oxalate in the kidney occurs in increasing renal function in systemic oxalosis, which relates, inter alia, eye, heart muscle, vascular walls, skin, bone and central nervous system. As a result, it comes in addition to the renal impairment at different Oxalosis typical organ diseases such as blindness, heart rhythm disturbances, no longer treatable anemia and oxalate bone disease and possibly death.

The clinical course of primary hyperoxaluria is very different, a real genotype / phenotype correlation does not exist. The severity ranges from the mere occurrence of individual kidney stones in old age to a neonatal renal impairment. Even within the family can be high variability.

In primary hyperoxaluria three types (Type I, Type II and Type III) are distinguished and they are still there in unclassified form.

Primary hyperoxaluria type I

In primary hyperoxaluria type I is a rare, autosomal recessive metabolic disease. The incidence is 0,4-1:10.000 where the disease is most commonly occur in Arabs and Iran. This is a defect of the peroxisomal liver enzyme glyoxylate aminotransferase ( locus 2q36 - q37 ). The enzyme converts glyoxylate into glycine. In consequence there is an increase of oxalic acid. There are massive deposits of oxalic acid in different tissues, including, inter alia in the kidney, suggests it comes to chronic renal failure. Oxalic acid can precipitate in the urine and then lead to urolithiasis. These can then be accompanied by fever, hematuria and renal colic. In the course may lead to a complete closure of the urinary tract and acute renal failure. About half of patients recover within 15 years of ESRD. It then comes to a rise in the concentration of oxalic acid in the blood. Now it is increasingly deposited in various tissues. As a result of the deposits it comes to the following disorders:

  • In the heart conduction disturbances,
  • In the vascular system hypertension, distal gangrene,
  • Limited mobility in the joints and pain.

The first symptoms may occur as early as 1 year of age, half of the patients in the age of 5 symptomatic.

Primary hyperoxaluria type II

The PH II is a deficiency in the whole body occurring Glyoxylat-Reductase/Hydroxypyruvat-Reductase based ( GRHPR ). Again, oxalate accumulates as a result of a lack of degradation of glyoxylate. In addition, there are at most PH II elevated levels of L- glycerate in the urine.

Other subtypes of PH occur probably because up to 20% of patients with typical PH phenotype normal AGT and GRHPR activities and unobtrusive sequence findings for AGXT and GRHPR have (11, 3). The etiology of these subtypes was completely unknown. Recently, a new PH III gene has now been localized on chromosome 10 described ( DHDPSL, Hydroxyprolinstoffwechsel ).

There was another PH gene found.

Secondary hyperoxaluria

In most cases, the secondary hyperoxaluria in metabolic disorder is associated with hypercalcemia and hypercalciuria on. In about half the cases, a cause can not be found ( idiopathic), although it can occur after consumption of products of large amounts of spinach, rhubarb and cocoa -containing, as these foods contain very much oxalic acid. Rare is the hyperoxaluria due to an overactive parathyroid gland ( hyperparathyroidism ). Other causes of secondary hyperoxaluria are sarcoidosis, vitamin D overdose, Cushing's disease, bone metastases, multiple myeloma, or confinement to bed.

Therapy

The treatment consists first in high fluid intake and administration of inhibitors of crystal formation, such as citrate, bicarbonate and magnesium. In addition, an attempt is made to keep the urine alkaline, so that oxalate does not precipitate in the urinary tract. By substitution of pyridoxine oxalate production can potentially be reduced in patients sensitive vitamin B6. Through early and aggressive conservative therapy, the course of the disease can be delayed.

A sole kidney transplantation as a therapy is not enough, there needs to be a combined liver and kidney transplantation, which probably is the treatment of choice in young children.

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