Problems in the investigation of urine from patients suffering from primary hyperoxaluria type 1

Regular calculation of urinary crystallization risk indices in patients suffering from urolithiasis is a recommended measure for treatment adjustment. The more the patient experiences either extensive stone formation or an enhanced recurrence rate, the more important risk index calculations. In patients suffering from primary hyperoxaluria type 1 (PH1), both criteria are met. Different methods of risk determination are known. All strategies for measuring the calcium oxalate (CaOx) crystallization risk of a given urine principally determine this parameter from voided urine. This "bladder urine", however, has possibly passed stone material located in the urinary tract and thus may be depleted in lithogenic components. This is commonly the case for patients with PH1, who mostly experience a massive stone burden or severe nephrocalcinosis. Hence, the question arises as to whether we can adequately determine the crystallization risk in the urine of stone-bearing PH1-patients or not. Based on model calculations, we show that the determination of CaOx formation risk in PH1-patients requires knowledge of the restrictions in risk index interpretation: risk indices calculated from urinalysis (e.g. EQUIL) still indicate, even after strong in vivo stone formation, an enhanced but in fact strongly underestimated risk value. However, the outcome "enhanced" masks the patient's true risk situation. The BONN Risk Index (BRI), in contrast, discloses the process of extreme in vivo crystal formation. As determined, inter alia, from the urinary concentration of free ionized calcium ([Ca(2+)]), BRI approaches abnormally low values, as, in consequence of CaOx - formation, [Ca(2+)] tends to values close to zero. Thus, calculations of urinalysis-based risk indices alone are insufficient strategies for the quantification of a PH1 patient's CaOx crystallization risk.