Hoppe B, Kemper M J, Bökenkamp A, Portale A A, Cohn R A, Langman C B
Department of Pediatrics, Northwestern University Medical School, Children's Memorial Hospital, Chicago, Illinois 60614, USA.
Kidney Int. 1999 Jul;56(1):268-74. doi: 10.1046/j.1523-1755.1999.00546.x.
Children with primary hyperoxaluria type 1 (PH 1) are at great risk to develop systemic oxalosis in end-stage renal disease (ESRD), as endogenous oxalate production exceeds oxalate removal by dialytic therapy. As oxalate accumulates, calcium oxalate (CaOx) tissue deposition occurs. Children with other causes of ESRD, however, are not prone to CaOx deposition despite elevated plasma oxalate (POx) levels.
Our study objective was to examine the potential mechanisms for these observations. We measured POx, sulfate, citrate, and calculated CaOx saturation (betaCaOx) in 7 children with ESRD caused by PH 1 and in 33 children 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-PH patients. Samples were obtained only once in 12 patients (one PH 1) on peritoneal dialysis (PD). After liver-kidney or kidney transplantation, plasma levels were measured repetitively.
The mean POx was higher in PH 1 (125.7 +/- 17.9 micromol/liter) than in non-PH patients (44.2 +/- 3.3 micromol/liter, P < 10(-4)). All other determined anions did not differ between the two groups. betaCaOx was higher in PH 1 (4.71 +/- 0.69 relative units) compared with non-PH children (1.56 +/- 0.12 units, P < 10(-4)). POx and betaCaOx 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)). POx and betaCaOx remained stable over time in the non-PH children, whereas an insignificant decline was observed in PH 1 patients after six months of more aggressive dialysis. betaCaOx was supersaturated (more than 1) in all PH 1 and in 25 out of 33 non-PH patients. Post-HD betaCaOx remained more than 1 in all PH 1, but in only 2 out of 22 non-PH patients. In non-PH children, POx and betaCaOx decreased to normal within three weeks after successful kidney transplantation, whereas the levels still remained elevated seven months after combined liver-kidney transplantation in two PH 1 patients.
Systemic oxalosis in PH 1 children with ESRD is due to higher POx and betaCaOx levels. As betaCaOx remained supersaturated in PH 1 even after aggressive HD, oxalate accumulation increases, and CaOx tissue deposition occurs. Therefore, sufficient reduction of POx and betaCaOx is crucial in PH 1 and might only be achieved by early, preemptive, combined liver-kidney transplantation or liver transplantation alone.
1型原发性高草酸尿症（PH 1）患儿在终末期肾病（ESRD）时发生全身性草酸osis的风险极大，因为内源性草酸盐生成超过了透析治疗对草酸盐的清除能力。随着草酸盐的蓄积，草酸钙（CaOx）组织沉积随之发生。然而，患有其他ESRD病因的儿童尽管血浆草酸盐（POx）水平升高，但并不容易发生CaOx沉积。
我们的研究目的是探究这些观察结果的潜在机制。我们测定了7例由PH 1导致ESRD的患儿以及33例非PH相关ESRD患儿的POx、硫酸盐、柠檬酸盐，并计算了CaOx饱和度（βCaOx）。6例PH 1患儿和22例非PH患儿接受维持性血液透析（HD）：此时分析HD前后的水平，并在12个月内对5例PH 1患儿和14例非PH患儿重复进行两次。12例患者（1例PH 1）接受腹膜透析（PD），仅采集一次样本。肝肾或肾移植后，重复测定血浆水平。
PH 1患儿的平均POx（125.7±17.9微摩尔/升）高于非PH患儿（44.2±3.3微摩尔/升，P<10⁻⁴）。两组间其他测定的阴离子无差异。与非PH儿童（1.56±0.12单位，P<10⁻⁴）相比，PH 1患儿的βCaOx更高（4.71±0.69相对单位）。POx与βCaOx在PH 1组（r = 0.98，P<2×10⁻⁴）和非PH组（r = 0.98，P<10⁻⁴）均呈正相关。非PH儿童的POx和βCaOx随时间保持稳定，而在更积极透析6个月后，PH 1患儿的POx和βCaOx出现轻微下降。所有PH 1患儿以及33例非PH患儿中的25例，βCaOx均处于过饱和状态（大于1）。HD后，所有PH 1患儿βCaOx仍大于1，但22例非PH患儿中只有2例如此。在非PH儿童中，成功肾移植后3周内POx和βCaOx降至正常，而在2例PH 1患儿接受肝肾联合移植7个月后，其水平仍保持升高。
ESRD的PH 1患儿发生全身性草酸osis是由于较高的POx和βCaOx水平。由于即使在积极HD后，PH 1患儿的βCaOx仍处于过饱和状态，草酸盐蓄积增加，进而发生CaOx组织沉积。因此，充分降低POx和βCaOx对PH 1患儿至关重要，可能只有通过早期、预防性的肝肾联合移植或单独肝移植才能实现。
