The autosomal recessive inherited primary hyperoxalurias types I, II and III are caused by defects in glyoxylate metabolism that lead to the endogenous overproduction of oxalate. Type III primary hyperoxaluria was first described in 2010 and further types are likely to exist. In all forms, urinary excretion of oxalate is strongly elevated (>1 mmol/1.73 m2 body surface area per day; normal <0.5 mmol/1.73 m2 body surface area per day), which results in recurrent urolithiasis and/or progressive nephrocalcinosis. All entities can induce kidney damage, which is followed by reduced oxalate elimination and consequent systemic deposition of calcium oxalate crystals. Systemic oxalosis should be prevented, but diagnosis is all too often missed or delayed until end-stage renal disease (ESRD) occurs; this outcome occurs in >30% of patients with primary hyperoxaluria type I. The fact that such a large proportion of patients have such poor outcomes is particularly unfortunate as ESRD can be delayed or even prevented by early intervention. Treatment options for primary hyperoxaluria include alkaline citrate, orthophosphate, or magnesium. In addition, pyridoxine treatment can be used to normalize or reduce oxalate excretion in about 30% of patients with primary hyperoxaluria type I. Time on dialysis should be short to avoid overt systemic oxalosis. Transplantation methods depend on the type of primary hyperoxaluria and on the particular patient, but combined liver and kidney transplantation is the method of choice in patients with primary hyperoxaluria type I and isolated kidney transplantation is the preferred method in those with primary hyperoxaluria type II. To the best of our knowledge, progression to ESRD has not yet been reported in any patient with primary hyperoxaluria type III.
The primary hyperoxalurias are rare genetic diseases caused by deficiencies in glyoxylate metabolism
The main first symptoms of primary hyperoxaluria are recurrent urolithiasis and/or progressive nephrocalcinosis, or early end-stage renal disease in the case of infantile oxalosis
Every child with a first kidney stone and all adults who have recurrent calcium oxalate kidney stones should be screened for primary hyperoxaluria
Primary hyperoxaluria type I in particular is a devastating disease that all too often leads to early end-stage renal disease
If the diagnosis of primary hyperoxaluria is made early, disease progression can be slowed
The transplantation procedure of choice is isolated kidney transplantation in patients with type II primary hyperoxaluria, and usually combined liver–kidney transplantation in type I disease
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The author declares no competing financial interests.
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Hoppe, B. An update on primary hyperoxaluria. Nat Rev Nephrol 8, 467–475 (2012). https://doi.org/10.1038/nrneph.2012.113
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