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Abstract：
OBJECTIVE: To investigate the incidence of nephrolithiasis in a cohort of children with congenital adrenal hyperplasia (CAH), and to study if there is an association with the metabolic control of the disease.
METHODS: This study was designed as a multicenter 1 year-prospective study involving 52 subjects (35 males) with confirmed molecular diagnosis of CAH due to 21-hydroxylase deficiency (21-OHD). Each patient was evaluated at three different time-points: T0, T1 (+6 months of follow-up), T2 (+12 months of follow up). At each follow up visit, auxological data were collected, and adrenocorticotrophic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), Δ4-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and urinary excretion of creatinine, calcium, oxalate and citrate were assayed. Moreover, a renal ultrasound was performed.
RESULTS: The incidence of nephrolithiasis, assessed by ultrasound was 17.3% at T0, 13.5% at T1 and 11.5% at T2. At T0, one subject showed nephrocalcinosis. In the study population, a statistically significant difference was found for 17-OHP [T0: 11.1 (3.0-25.1) ng/mL; T1: 7.1 (1.8-19.9) ng/mL; T2: 5.9 (2.0-20.0) ng/mL, p < 0.005], and Δ4-androstenedione [T0: 0.9 (0.3-2.5) ng/mL; T1: 0.3 (0.3-1.1) ng/mL; T2: 0.5 (0.3-1.5) ng/mL, p < 0.005] which both decreased over the follow up time. No statistically significant difference among metabolic markers was found in the group of the subjects with nephrolithiasis, even if 17-OHP, DHEAS and Δ4-androstenedione levels showed a tendency towards a reduction from T0 to T2. Principal component analysis (PCA) was performed to study possible hidden patterns of associations/correlations between variables, and to assess the trend of them during the time. PCA revealed a decrease in the amount of the variables 17-OHP, Δ4-androstenedione, and ACTH that occurred during follow-up, which was also observed in subjects showing nephrolithiasis.
CONCLUSIONS: our data demonstrated that children affected with 21-OHD can be at risk of developing nephrolithiasis. Additional studies are needed to clarify the pathogenesis and other possible risk factors for this condition, and to establish if regular screening of kidney ultrasound in these patients can be indicated.
METHODS: This study was designed as a multicenter 1 year-prospective study involving 52 subjects (35 males) with confirmed molecular diagnosis of CAH due to 21-hydroxylase deficiency (21-OHD). Each patient was evaluated at three different time-points: T0, T1 (+6 months of follow-up), T2 (+12 months of follow up). At each follow up visit, auxological data were collected, and adrenocorticotrophic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), Δ4-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and urinary excretion of creatinine, calcium, oxalate and citrate were assayed. Moreover, a renal ultrasound was performed.
RESULTS: The incidence of nephrolithiasis, assessed by ultrasound was 17.3% at T0, 13.5% at T1 and 11.5% at T2. At T0, one subject showed nephrocalcinosis. In the study population, a statistically significant difference was found for 17-OHP [T0: 11.1 (3.0-25.1) ng/mL; T1: 7.1 (1.8-19.9) ng/mL; T2: 5.9 (2.0-20.0) ng/mL, p < 0.005], and Δ4-androstenedione [T0: 0.9 (0.3-2.5) ng/mL; T1: 0.3 (0.3-1.1) ng/mL; T2: 0.5 (0.3-1.5) ng/mL, p < 0.005] which both decreased over the follow up time. No statistically significant difference among metabolic markers was found in the group of the subjects with nephrolithiasis, even if 17-OHP, DHEAS and Δ4-androstenedione levels showed a tendency towards a reduction from T0 to T2. Principal component analysis (PCA) was performed to study possible hidden patterns of associations/correlations between variables, and to assess the trend of them during the time. PCA revealed a decrease in the amount of the variables 17-OHP, Δ4-androstenedione, and ACTH that occurred during follow-up, which was also observed in subjects showing nephrolithiasis.
CONCLUSIONS: our data demonstrated that children affected with 21-OHD can be at risk of developing nephrolithiasis. Additional studies are needed to clarify the pathogenesis and other possible risk factors for this condition, and to establish if regular screening of kidney ultrasound in these patients can be indicated.
摘要：
目的：探讨先天性肾上腺皮质增生症（CAH）患儿的肾结石发生率。并研究是否与疾病的代谢控制有关。
方法：本研究设计为一项多中心1年前瞻性研究，涉及52名受试者（35名男性），其分子诊断为21-羟化酶缺乏症（21-OHD）所致的CAH。每个患者在三个不同的时间点进行评估：T0，T1（随访6个月），T2(+12个月随访)。每次随访时，收集了营养数据，和促肾上腺皮质激素（ACTH），17-羟基孕酮（17-OHP），Δ4-雄烯二酮，硫酸脱氢表雄酮（DHEAS）血清水平，和尿肌酐的排泄，钙，测定草酸盐和柠檬酸盐。此外，进行了肾脏超声检查.
结果：肾结石的发病率，超声评估T0为17.3%，T1为13.5%，T2为11.5%。在T0时，一名受试者显示肾钙质沉着。在研究人群中，17-OHP的差异具有统计学意义[T0：11.1（3.0-25.1）ng/mL;T1：7.1（1.8-19.9）ng/mL;T2：5.9（2.0-20.0）ng/mL，p<0.005],和Δ4-雄烯二酮[T0：0.9（0.3-2.5）ng/mL；T1：0.3（0.3-1.1）ng/mL；T2：0.5（0.3-1.5）ng/mL，p<0.005]，在随访时间内均下降。在肾结石患者组中，代谢标志物之间没有统计学上的显着差异。即使17-OHP,DHEAS和Δ4-雄烯二酮水平显示出从T0到T2降低的趋势。进行了主成分分析(PCA)来研究变量之间可能隐藏的关联/相关性模式，并评估它们在此期间的趋势。PCA显示变量17-OHP的数量减少，Δ4-雄烯二酮，以及在随访期间发生的ACTH，在显示肾结石的受试者中也观察到了这一点。
结论：我们的数据表明，患有21-OHD的儿童可能有发生肾结石的风险。需要更多的研究来阐明这种情况的发病机理和其他可能的危险因素。并确定是否可以对这些患者进行定期肾脏超声筛查。
方法：本研究设计为一项多中心1年前瞻性研究，涉及52名受试者（35名男性），其分子诊断为21-羟化酶缺乏症（21-OHD）所致的CAH。每个患者在三个不同的时间点进行评估：T0，T1（随访6个月），T2(+12个月随访)。每次随访时，收集了营养数据，和促肾上腺皮质激素（ACTH），17-羟基孕酮（17-OHP），Δ4-雄烯二酮，硫酸脱氢表雄酮（DHEAS）血清水平，和尿肌酐的排泄，钙，测定草酸盐和柠檬酸盐。此外，进行了肾脏超声检查.
结果：肾结石的发病率，超声评估T0为17.3%，T1为13.5%，T2为11.5%。在T0时，一名受试者显示肾钙质沉着。在研究人群中，17-OHP的差异具有统计学意义[T0：11.1（3.0-25.1）ng/mL;T1：7.1（1.8-19.9）ng/mL;T2：5.9（2.0-20.0）ng/mL，p<0.005],和Δ4-雄烯二酮[T0：0.9（0.3-2.5）ng/mL；T1：0.3（0.3-1.1）ng/mL；T2：0.5（0.3-1.5）ng/mL，p<0.005]，在随访时间内均下降。在肾结石患者组中，代谢标志物之间没有统计学上的显着差异。即使17-OHP,DHEAS和Δ4-雄烯二酮水平显示出从T0到T2降低的趋势。进行了主成分分析(PCA)来研究变量之间可能隐藏的关联/相关性模式，并评估它们在此期间的趋势。PCA显示变量17-OHP的数量减少，Δ4-雄烯二酮，以及在随访期间发生的ACTH，在显示肾结石的受试者中也观察到了这一点。
结论：我们的数据表明，患有21-OHD的儿童可能有发生肾结石的风险。需要更多的研究来阐明这种情况的发病机理和其他可能的危险因素。并确定是否可以对这些患者进行定期肾脏超声筛查。
