Comparison of stone growth patterns and clinical outcomes of children presenting with Hypercalciuria, Hypocitraturia and Cystinuria as underlying metabolic renal stone disease
Fadi Zu’bi, Martin Sidler, Elizabeth Harvey, Asal Hojjat, Naimet Naoum, Roberto I Lopes, Martha Pokarowski, Walid Farhat, Frank Papanikolaou, Joana Dos Santos.
The Hospital for Sick Children, Toronto, ON, Canada.
Background: Hypercalciuria, hypocitraturia and cystinuria are the most common underlying metabolic stone abnormalities and account for more than 80% of all renal stones in children. Here we compare the impact of these underlying metabolic conditions on stone growth patterns and stone burden in the pediatric population.
Methods: After Research Ethics Board (REB) approval, we retrospectively reviewed the charts of children with renal stones at the Hospital for Sick Children (SickKids) between 2000 and 2015. Data captured included: Age, sex and weight; Renal imaging (ultrasounds and abdominal x-rays (KUB)); stone size, number and location; metabolic workup (24-hour and/or spot urine collection); new stone formation; stone related surgical procedures; and stone pathology. Differences among metabolic groups were determined using ANOVA. Independent samples T-Test was used to compare scale variables and chi-squared test for categorical variables. Logistic regression was performed to assess the effect of various parameters on the likelihood of needing surgery at any time point. Also, a receiver operating characteristic (ROC) analysis was applied to determine how baseline stone size predicts the need for surgery.
Results: During the study period 356 children were seen at SickKids. Mean age at presentation was 8.9 years (IQR = 3.0-13.1), 192 (54%) were boys. and 69/356 (19.4%) patients had congenital urinary tract anomalies. Mean stone size at baseline U/S was 7.6 mm (1-56) and 9 (2.9%) patients had their largest stone in the bladder. 140 (45.8%) stones were on the right side and 87/356 (24.4%) patients had bilateral renal stones. Stone-associated hydronephrosis was found in 86 patients (24.2%). Abdominal x-ray was done in 193 patients (54.2%), with a stone detected in 98 patients (50.7%). Mean initial stone size on x-ray was 10.33mm (SD 7.9mm, range 2-55.6), which correlated well with the initial stone size on ultrasound (paired sample correlation P<0.001). From our cohort of 356 patients, 280 (78.7%) children underwent metabolic workup at baseline or first follow up visit. Among these 280 patients, metabolic abnormality was identified in 154 (55%) children, with the most common being hypercalciuria in 86 (30.7 %), hypocitraturia in 20 (7.1%), cystinuria in 24 (8.6%) patients. Mixed and others abnormalities were found in 24 (8.6%) children. Hypercalciuria was significantly more prevalent in the younger age groups < 10 years. Cystinuria on the other hand was significantly more common in 11-18 year old patients. Stone analysis was done in 102 of 356 patients (28.7%). 1/3 had calcium oxalate stones. Stone composition was similar in both genders. Mean stone size at baseline was significantly larger in children with cystinuria compared to hypercalciuria (11.2 vs. 7.4, p=0.038), hypocitraturia (11.2 vs 7, p= 0.027), and the normal metabolic group (11.2 vs 7, P=0.003). Among our 356 patients, 123 (34.5%) had to undergo surgery. Median time from first clinic visit to surgery was 102 days (IQR 34-330 days). Mean growth rate in the operative group was 3.4mm/year, which was significantly higher than in the conservative group, where mean growth rate was 0.8mm/year (p=0.014). Stone growth rates were not statistically significant among metabolic groups. Larger stones, cysteine stones, and proximal ureteral stones were significantly more likely to require surgical treatment. Patients with a normal metabolic work-up, and lower pole stones were less than half as likely to have surgery than other patients. We performed a ROC analysis and found that among all patients with a stone of 5mm or more, surgery could be avoided in 50% of the cases, whereas with stones of 10mm or more, only 10% of patients could be treated conservatively.
Conclusions: To the best of our knowledge, this is the first study describing stone growth patterns associated with hypercalciuria, hypocitraturia and cystinuria in children. Stones in children with cystinuria were significantly larger than in the other metabolic groups. Our research also helps steer surgical decision making by informing the urologist that initial stone size, proximal ureteral stones and cystine stones are significant risk factors that predict the need for intervention. More than half of patients with normal metabolic workup and/or having their largest stone in the lower pole can be treated conservatively. Better understanding of the natural history ultimately helps surgeons and clinicians define prognosis, treatment and prevention plans for pediatric nephrolithiasis.
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