Hyperoxaluria and Nephrolithiasis After Gastric Bypass Surgery for Obesity

描述(申请人提供)：患者通常在胃旁路手术后发生肾结石，原因是医学上有复杂的肥胖。我们在有限数量的患者中表明，即使在没有临床明显肾结石的情况下，高草酸尿、低柠檬酸尿和低钙尿等结石的代谢危险因素在胃旁路手术后1年也很常见。该应用程序的目标是检查Roux-en-Y胃旁路手术(RYGB)治疗内科复杂性肥胖症患者术后高草酸尿和肾结石的患病率和机制。在此赠款期间获得的信息将使我们能够确定问题的范围，并为适当的更大规模的试验获取信息，以预防肾结石、肾钙质沉着症和可能的肾功能障碍，这些患者越来越多地接受RYGB的医学复杂性肥胖治疗。我们的假设是，对于内科复杂性肥胖的RYGB手术后的患者，经常会出现高草酸尿，这种代谢异常通常会导致肾结石的发生。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症是继发于肠道草酸的高吸收。我们的具体目标是：1)评估100例接受RYGB手术的患者中肾结石、肾钙质沉着症和肾功能受损的发生率和患病率，并将这些手术患者的发现与30例非手术肥胖者的结果进行比较。这些患者将在RYGB手术之前接受广泛的生化和放射学评估，以治疗医学上复杂的肥胖症，并在术后6个月和12个月再次接受评估。2)探讨RYGB手术治疗内科复杂性肥胖症后高草酸尿的发生机制。为了深入了解可能成为干预试验目标的潜在机制，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前后的肠道草酸盐吸收。我们将确定这类患者是否存在脂肪吸收不良。我们将评估这些患者在RYGB手术前是否被草酸降解细菌形成草酸杆菌定植，以及手术后患者的定植状态是否发生变化并导致高草酸尿的严重程度。我们的研究的意义在于，它将确定RYGB手术后患者高草酸尿、肾结石和肾功能丧失的患病率，并提出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和治疗方法，可用于预防RYGB手术的此类并发症。由于与减肥相关的有益结果，胃旁路手术正以越来越快的速度在肥胖症患者中进行。有证据表明，患者会形成肾结石，并因手术而导致肾功能下降。我们将确定结石和结石的化学危险因素在接受胃旁路手术的患者中发生的常见程度。最后，我们将研究这些并发症发生的原因，并开发预防胃旁路手术后肾结石和肾功能丧失的方法。

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.