早产儿尿液对一水合草酸钙结晶动力学的调节作用

Schell-Feith E A, Que I, Kok D J, Kist-Van Holthe J E, Kühler E, Brand R, Papapoulos S E, van der Heijden B J

Departments of Pediatrics and Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.

Am J Kidney Dis. 2001 Dec;38(6):1229-34. doi: 10.1053/ajkd.2001.29218.

Preterm neonates frequently develop nephrocalcinosis (NC). However, the cause has not yet been elucidated. This study focuses on the effects of urine from preterm neonates on crystallization kinetics. Urine samples were collected and renal ultrasound examinations of preterm neonates (gestational age < 32 weeks) were performed during the first weeks of life, at term, and ages 6, 12, and 24 months. The effect of urine on crystallization was determined using a seeded crystal growth system, which measures the square root of solubility product ( radicalLc), percentage of growth inhibition (GI), and agglomeration inhibition ([tm]) of calcium oxalate crystals. Data for preterm neonates in the first weeks of life (n = 19) were compared with those for full-term neonates (n = 17) and healthy adults. Moreover, the correlation between [tm] and urinary (U)citrate level was studied. Mean radicalLc (0.27 +/- 0.1 versus 0.36 +/- 0.08 mmol/L) and mean [tm] (81 +/- 32 versus 143 +/- 97 minutes) were lower and mean Ucalcium-creatinine (2.20 +/- 1.74 versus 0.46 +/- 0.73 mol/mol) and Uoxalate-creatinine ratios (0.39 +/- 0.21 versus 0.16 +/- 0.09 mol/mol) were greater in preterm neonates in the first weeks of life compared with full-term neonates (p < 0.05). Furthermore, [tm] was less than the lower limit for healthy adults for all but one preterm neonate; [tm] increased and Ucalcium-creatinine and Uoxalate-creatinine ratios decreased with age (p < 0.005). There was a correlation between [tm] and citrate excretion (coefficient of 38; P < 0.001). Patients with and without NC at term did not differ statistically in mean radicalLc, percentage of GI, or [tm]. In conclusion, urine from preterm neonates in the first weeks of life is highly supersaturated and has a defective ability to inhibit calcium oxalate crystal agglomeration. This ability improves with age and is citrate mediated. We suggest that both the high level of supersaturation and defective ability to inhibit calcium oxalate crystal agglomeration contribute to the high incidence of NC.

早产儿经常会发生肾钙质沉着症（NC）。然而，其病因尚未阐明。本研究聚焦于早产儿尿液对结晶动力学的影响。收集了尿液样本，并在早产儿（胎龄<32周）出生后的头几周、足月时以及6、12和24个月龄时对其进行了肾脏超声检查。使用接种晶体生长系统测定尿液对结晶的影响，该系统可测量草酸钙晶体的溶解度积平方根（radicalLc）、生长抑制百分比（GI）和团聚抑制（[tm]）。将出生后头几周的早产儿（n = 19）的数据与足月儿（n = 17）和健康成年人的数据进行了比较。此外，还研究了[tm]与尿柠檬酸水平之间的相关性。与足月儿相比，出生后头几周的早产儿的平均radicalLc（0.27±0.1对0.36±0.08 mmol/L）和平均[tm]（81±32对143±97分钟）较低，而平均尿钙肌酐（2.20±1.74对0.46±0.73 mol/mol）和草酸尿酸肌酐比值（0.39±0.21对0.16±0.09 mol/mol）较高（p<0.05）。此外，除一名早产儿外，所有早产儿的[tm]均低于健康成年人的下限；[tm]随年龄增加，而尿钙肌酐和草酸尿酸肌酐比值随年龄降低（p<0.005）。[tm]与柠檬酸排泄之间存在相关性（系数为38；P<0.001）。足月时有和没有NC的患者在平均radicalLc、GI百分比或[tm]方面无统计学差异。总之，出生后头几周的早产儿尿液高度过饱和，抑制草酸钙晶体团聚的能力存在缺陷。这种能力随年龄增长而改善，且由柠檬酸介导。我们认为，过饱和水平高和抑制草酸钙晶体团聚的能力缺陷均导致了NC的高发病率。