Abstract
Nephrolithiasis in children is increasing in prevalence and tends to be recurrent. In adults, recognized risk factors for stone formation include familial hypercalciuria, hyperoxaluria, hypocitraturia, low urine volume and hyperuricosuria. Few studies have looked at risk factors in stone-forming children and compared them to healthy children or their non-stone-forming siblings.
This study obtained 24-h urine collections from 417 children: 129 had calcium stones, 105 were non-stone-forming siblings from the same families and 183 were age- and sex-matched healthy children whose families did not have calcium stone disease. The mean 24-h excretions of calcium, oxalate, phosphorous and citrate were measured, along with urine volume and pH. The ability of the urine to inhibit growth of calcium oxalate (CaOx) crystals was also measured.
Compared with normal children (NN), stone-formers (SF) and their non-stone-forming siblings (NS) excreted more calcium. Significant differences were found in mean calcium excretion between SF and NS (P< 0.0001) and SF versus NN (P< 0.0001). The NS group also had significantly higher calcium excretion than the NN (P< 0.03). Unlike calcium, there were no significant differences for urine oxalate, phosphorous, volume, pH or citrate.
Calcium oxalate supersaturation increases from NN to NS to SF. The supersaturation required to experimentally induce crystal formation (upper limit of metastability [ULM]) also rose in the same manner. Both urine calcium and CaOx supersaturation rose with increasing stone number, and this trend was significant (P< 0.001). Calcium-phosphate supersaturation increased from NN to NS to SF but the ULM did not. Therefore the supersaturation–ULM distance decreased (SF<NN or NS, P< 0.01). This decrease could promote stone formation as the ambient supersaturation resides closer to the supersaturation needed to initiate crystallization.
This shows that hypercalciuria and a reduction in the gap between calcium phosphate ULM and supersaturations are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones.