Shavit Linda, Girfoglio Daniela, Vijay Vivek, Goldsmith David, Ferraro Pietro Manuel, Moochhala Shabbir H, Unwin Robert
Centre for Nephrology, Royal Free Campus and Hospital, University College London Medical School, London, United Kingdom; Adult Nephrology Unit, Shaare Zedek Medical Center, Jerusalem, Israel;
Centre for Nephrology, Royal Free Campus and Hospital, University College London Medical School, London, United Kingdom;
Clin J Am Soc Nephrol. 2015 Feb 6;10(2):278-85. doi: 10.2215/CJN.06030614. Epub 2015 Jan 29.
Recent epidemiologic studies have provided evidence for an association between nephrolithiasis and cardiovascular disease, although the underlying mechanism is still unclear. Vascular calcification (VC) is a strong predictor of cardiovascular morbidity and the hypothesis explored in this study is that VC is more prevalent in calcium kidney stone formers (KSFs). The aims of this study were to determine (1) whether recurrent calcium KSFs have more VC and osteoporosis compared with controls and (2) whether hypercalciuria is related to VC in KSFs.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective, matched case-control study that included KSFs attending an outpatient nephrology clinic of the Royal Free Hospital (London, UK) from 2011 to 2014. Age- and sex-matched non-stone formers were drawn from a list of potential living kidney donors from the same hospital. A total of 111 patients were investigated, of which 57 were KSFs and 54 were healthy controls. Abdominal aortic calcification (AAC) and vertebral bone mineral density (BMD) were assessed using available computed tomography (CT) imaging. The prevalence, severity, and associations of AAC and CT BMD between KSFs and non-stone formers were compared.
Mean age was 47±14 years in KSFs and 47±13 in non-stone formers. Men represented 56% and 57% of KSFs and non-stone formers, respectively. The prevalence of AAC was similar in both groups (38% in KSFs versus 35% in controls, P=0.69). However, the AAC severity score (median [25th percentile, 75th percentile]) was significantly higher in KSFs compared with the control group (0 [0, 43] versus 0 [0, 10], P<0.001). In addition, the average CT BMD was significantly lower in KSFs (159±53 versus 194 ±48 Hounsfield units, P<0.001). A multivariate model adjusted for age, sex, high BP, diabetes, smoking status, and eGFR confirmed that KSFs have higher AAC scores and lower CT BMD compared with non-stone formers (P<0.001 for both). Among stone formers, the association between AAC score and hypercalciuria was not statistically significant (P=0.86).
This study demonstrates that patients with calcium kidney stones suffer from significantly higher degrees of aortic calcification than age- and sex-matched non-stone formers, suggesting that VC may be an underlying mechanism explaining reported associations between nephrolithiasis and cardiovascular disease. Moreover, bone demineralization is more prominent in KSFs. However, more data are needed to confirm the possibility of potentially common underlying mechanisms leading to extraosseous calcium deposition and osteoporosis in KSFs.
近期的流行病学研究已为肾结石与心血管疾病之间的关联提供了证据,尽管其潜在机制仍不明确。血管钙化(VC)是心血管疾病发病的有力预测指标,本研究探讨的假设是VC在含钙肾结石患者(KSF)中更为普遍。本研究的目的是确定:(1)与对照组相比,复发性含钙KSF患者是否有更多的VC和骨质疏松;(2)高钙尿症与KSF患者的VC是否相关。
设计、地点、参与者及测量方法:这是一项回顾性、匹配病例对照研究,纳入了2011年至2014年在英国伦敦皇家自由医院门诊肾病科就诊的KSF患者。年龄和性别匹配的非结石形成者来自同一家医院潜在活体肾供体名单。共调查了111例患者,其中57例为KSF患者,54例为健康对照。使用现有的计算机断层扫描(CT)成像评估腹主动脉钙化(AAC)和椎体骨密度(BMD)。比较了KSF患者和非结石形成者之间AAC和CT BMD的患病率、严重程度及相关性。
KSF患者的平均年龄为47±14岁,非结石形成者为47±13岁。男性分别占KSF患者和非结石形成者的56%和57%。两组的AAC患病率相似(KSF患者为38%,对照组为35%,P = 0.69)。然而,与对照组相比,KSF患者的AAC严重程度评分(中位数[第25百分位数,第75百分位数])显著更高(0[0,43]对0[0,10],P<0.001)。此外,KSF患者的平均CT BMD显著更低(159±53对194±48亨氏单位,P<0.001)。在对年龄、性别、高血压、糖尿病、吸烟状况和估算肾小球滤过率(eGFR)进行调整的多变量模型中,与非结石形成者相比,KSF患者的AAC评分更高,CT BMD更低(两者P均<0.001)。在结石形成者中,AAC评分与高钙尿症之间的关联无统计学意义(P = 0.86)。
本研究表明,含钙肾结石患者的主动脉钙化程度显著高于年龄和性别匹配的非结石形成者,提示VC可能是解释肾结石与心血管疾病之间报道关联的潜在机制。此外,KSF患者的骨质脱矿更为明显。然而,需要更多数据来证实导致KSF患者骨外钙沉积和骨质疏松的潜在共同机制的可能性。