Plasma calcium oxalate supersaturation in children with primary hyperoxaluria and end-stage renal failure

Background. Children with primary hyperoxaluria type (PH 1) are at great ri sk to develop systemic oxalosis in endstage renal disease (ESRD), as endoge nous oxalate production exceeds oxalate removal by dialytic therapy. As oxa late accumulates, calcium oxalate (CaOx) tissue deposition occurs. Children with other causes of ESRD, however, are not prone to CaOx deposition despi te elevated plasma oxalate (P-Ox) levels. Methods. Our study objective was to examine the potential mechanisms for th ese observations. We measured P-Ox, sulfate, citrate, and calculated CaOx s aturation (beta(CaOx)) in 7 children with ESRD caused by PH 1 and in 33 chi ldren with non-PH-related ESRD. Maintenance hemodialysis (HD) was performed in 6 PH 1 and 22 non-PH patients: Pre- and post-HD levels were analyzed at this point and were repeated twice within 12 months in 5 PH 1 and 14 non-P H patients. Samples were obtained only once in 12 patients (one PH 1) on pe ritoneal dialysis (PD). After liver-kidney or kidney transplantation, plasm a levels were measured repetitively. Results. The mean P-Ox was higher in PH (125.7 +/- 17.9 mu mol/liter) than in non-PH patients (44.2 +/- 3.3 mu mol/liter, P < 10(-4)). All other deter mined anions did not differ between the two groups. beta(CaOx) was higher i n PH 1 (4.71 +/- 0.69 relative units) compared with non-PH children (1.56 /- 0.12 units, P < 10(-4)). P-Ox and beta(CaOx) were correlated in both the PH 1 (r = 0.98: P < 2 x 10(-4)) and the non-PH group (r = 0.98, P < 10(-4) ). P-Ox and beta(CaOx) remained stable over time in the non-PH children, wh ereas an insignificant decline was observed in PH 1 patients after six mont hs of more aggressive dialysis. beta(CaOx) was supersaturated (more than 1) in all PH 1 and in 25 out of 33 non-PH patients. Post-HD beta(CaOx) remain ed more than 1 in all PH 1, but in only 2 out of 22 non-PH patients. In non PH children. P-Ox and beta(CaOx) decreased to normal within three weeks af ter successful kidney transplantation. whereas the levels still remained el evated seven months after combined liver-kidney transplantation in two PH p atients. Conclusion. Systemic oxalosis in PH 1 children with ESRD is due to higher P -Ox and beta(CaOx) levels. As beta(CaOx) remained supersaturated in PH 1 ev en after aggressive HD, oxalate accumulation increases, and CaOx tissue dep osition occurs. Therefore, sufficient reduction of P-Ox and beta(CaOx) is c rucial in PH 1 and might only be achieved by early, preemptive, combined li ver-kidney transplantation or liver transplantation alone.