Diagnostic and therapeutic strategies in hyperoxaluria: a plea for early intervention

Oxalic acid is an end product of human metabolism and does not appear to be needed for any process in the body. Under normal conditions the daily load of oxalate deriving from endogenous production and intestinal absorption is fully excreted by the kidneys. Up to a certain extent renal oxalate excretion may even keep pace with an elevated oxalate load, yet at the expense of hyperoxaluria, a major risk factor for recurrent nephrolithiasis and nephrocalcinosis [1,2]. Unfortunately, hyperoxaluria is all too often overlooked at this stage. The situation becomes far more serious if renal function is impaired (e.g. from complications of hyperoxaluria): the amount of oxalate excreted in the urine will no longer match its production and absorption, resulting in progressive oxalate retention with renal and extrarenal deposition of calcium oxalate, i.e. systemic oxalosis [3]. In a recent survey from the US 30% of patients with primary hyperoxaluria (PH) were only diagnosed after having reached end-stage renal failure (ESRF [4]). Late diagnosis is a particular problem in adult patients. In a recent Dutch study, 59% of those patients older than 18 years had already reached ESRF at the time of diagnosis of PH I [5]. Two forms of autosomal-recessive inherited PHs have been characterized at the molecular level, both being due to defects of glyoxylate metabolism [6–8]. One or several other types of PH are likely to exist, and there is a certain overlap with severe forms of secondary hyperoxaluria [9,10].