Hyperoxaluria and Nephrolithiasis After Gastric Bypass Surgery for Obesity

肥胖胃绕道手术后高草酸尿和肾结石

• 批准号: 7231530
• 负责人: RAJIV KUMAR
• 金额: $ 22.67万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7231530
• 关键词: Affect; Bacteria; Biochemical; Body Weight decreased; Calcium Oxalate; Calculi; Chemicals; Clinical Research; Condition; Data; Evaluation; Frequencies; Functional disorder; Future; Gastric Bypass; Goals; Grant; Hyperoxaluria; Impaired Renal Function; Incidence; Intervention Trial; Intestines; Kidney; Kidney Calculi; Malabsorption Syndromes; Measurement; Measures; Metabolic; Morbidity - disease rate; Nephrocalcinosis; Nephrolithiasis; Numbers; Obesity; Operative Surgical Procedures; Oral Administration; Outcome; Oxalates; Oxalobacter formigenes; Patients; Physicians; Prevalence; Procedures; Rate; Renal function; Research; Research Project Grants; Risk Factors; Secondary to; Severities; Testing; Therapeutic Intervention; United States National Institutes of Health; Urine; Urologic Diseases; absorption; bariatric surgery; base; design; insight; prevent; response; symposium

DESCRIPTION (provided by applicant): Patients often develop nephrolithiasis after gastric bypass surgery for medically-complicated obesity. We have shown in a limited number of patients that metabolic risk factors for stones such as hyperoxaluria, hypocitraturia, and hypocalciuria are common 1 year after gastric bypass procedures, even without clinically apparent nephrolithiasis. The goals of this application are to examine the prevalence and mechanisms of hyperoxaluria and nephrolithiasis in patients after Roux-en-Y Gastric Bypass (RYGB) operations for medically- complicated obesity. Information obtained during this grant period will allow us to define the scope of the problem and acquire information for appropriate larger-scale trials to prevent nephrolithiasis, nephrocalcinosis and possibly renal dysfunction in patients who are increasingly being treated for medically-complicated obesity with RYGB. Our hypothesis is that hyperoxaluria frequently develops in patients after RYGB operations for medically-complicated obesity, and this metabolic abnormality often results in the occurrence of nephrolithiasis. Nephrocalcinosis and impaired renal function are potential and even more serious complications of RYGB surgery. We hypothesize that hyperoxaluria observed in these patients is secondary to the hyper-absorption of oxalate from the bowel. Our specific aims are: 1) To estimate the incidence and prevalence of nephrolithiasis, nephrocalcinosis and impaired renal function in a group of 100 patients undergoing RYGB operations, and to compare the findings in these operated patients with those seen in 30 non-operated obese controls. The patients will undergo extensive biochemical and radiological evaluation for nephrolithiasis prior to the RYGB operation for medically-complicated obesity, and again at 6 and 12 months after the operation. 2) To determine the mechanism by which hyperoxaluria occurs in patients after RYGB procedures for medically complicated obesity. To develop insight into potential mechanisms that could be targets of intervention trials, we will assess intestinal oxalate absorption before and after RYGB by oral administration of 13C oxalate and the measurement of excreted 13 C oxalate in the urine. We will determine whether such patients have fatty malabsorption. We will assess whether these patients are colonized by the oxalate-degrading bacterium Oxalobacter formigenes prior to the RYGB procedure, and if the patients' colonization status changes after the procedure and contributes to the severity of hyperoxaluria. The significance of our study is that it will determine the prevalence of hyperoxaluria, nephrolithiasis and loss of renal function in patients following RYGB surgery and it will suggest mechanisms by which these complications occur. Based on these findings we will be able to define rational interventions and therapies that can be used to prevent such complications of RYGB surgery. Gastric bypass operations are being performed at an increasing rate in patients with obesity because of the beneficial outcomes associated with weight loss. There is evidence that patients form kidney stones and suffer reductions in kidney function as a result of the surgery. We will determine how commonly stones and chemical risk factors for stones occur in patients who have had gastric bypass surgery. Finally, we will study why these complications occur and we will develop ways in which to prevent kidney stones and loss of kidney function after gastric bypass surgery.

描述（由申请人提供）：内科并发症性肥胖患者常在胃旁路手术后发生肾结石。我们已经在有限数量的患者中表明，即使没有临床上明显的肾结石，胃旁路手术后1年的结石代谢危险因素如高草酸尿、低尿和低钙尿是常见的。本应用程序的目的是研究Roux-en-Y胃旁路手术（RYGB）后医学并发症性肥胖患者高草酸尿和肾结石的患病率和机制。在此拨款期间获得的信息将使我们能够确定问题的范围，并为适当的大规模试验获取信息，以预防肾结石、肾钙化症和可能的肾功能障碍，这些患者越来越多地接受RYGB治疗医学并发症性肥胖。我们的假设是，在RYGB手术后，伴有内科并发症的肥胖患者经常出现高草酸尿，这种代谢异常经常导致肾结石的发生。肾钙质沉着和肾功能受损是RYGB手术潜在的甚至更严重的并发症。我们假设在这些患者中观察到的高草酸尿是继发于肠道对草酸盐的过度吸收。我们的具体目的是：1)估计100例RYGB手术患者的肾结石、肾钙化症和肾功能损害的发病率和患病率，并将这些手术患者与30例未手术的肥胖对照进行比较。患者将在RYGB手术前接受广泛的肾结石生化和放射学评估，并在手术后6个月和12个月再次进行评估。2)探讨医源性肥胖患者RYGB手术后高草酸尿发生的机制。为了深入了解干预试验的潜在机制，我们将通过口服13C草酸盐和测量尿液中13C草酸盐的排泄来评估RYGB前后肠道草酸盐的吸收。我们将确定这些患者是否有脂肪吸收不良。我们将评估这些患者在RYGB手术前是否被草酸降解菌草酸杆菌定植，以及患者的定植状态是否在手术后发生变化并导致高草酸尿的严重程度。本研究的意义在于，它将确定RYGB手术后患者高血氧症、肾结石和肾功能丧失的患病率，并提示这些并发症发生的机制。基于这些发现，我们将能够确定合理的干预措施和治疗方法，可用于预防RYGB手术的此类并发症。胃旁路手术在肥胖患者中的应用越来越多，因为与减肥相关的有益结果。有证据表明，手术后患者会形成肾结石，肾功能下降。我们将确定在胃旁路手术患者中发生结石的常见程度和结石的化学危险因素。最后，我们将研究这些并发症发生的原因，并研究预防胃旁路手术后肾结石和肾功能丧失的方法。