Hyperoxaluria and Nephrolithiasis After Gastric Bypass Surgery for Obesity

描述（由申请人提供）：患者经常在胃旁路手术后发生肾结石，以治疗医学上复杂的肥胖症。我们已经在有限的患者中发现，即使没有临床上明显的肾结石，在胃旁路手术后1年，结石的代谢危险因素如高尿酸、低柠檬酸尿和低钙尿也是常见的。本申请的目的是检查Roux-en-Y胃旁路（RYGB）手术治疗医学并发性肥胖症后患者高尿酸和肾结石的患病率和机制。在此资助期间获得的信息将使我们能够确定问题的范围，并获得适当的大规模试验的信息，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治疗的医学复杂性肥胖症。我们的假设是，高血压尿经常发生在因医学上复杂的肥胖症而接受RYGB手术的患者中，这种代谢异常通常导致肾结石的发生。肾钙质沉着和肾功能受损是RYGB手术的潜在甚至更严重的并发症。我们推测，在这些患者中观察到的高尿酸是继发于肠草酸盐的过度吸收。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、肾钙质沉着和肾功能受损的发生率和患病率，并将这些手术患者的结果与30例非手术肥胖对照者的结果进行比较。患者将在RYGB手术前接受广泛的肾结石生化和放射学评估，以治疗医学上复杂的肥胖症，并在手术后6个月和12个月再次进行评估。2)确定RYGB手术治疗医学并发性肥胖患者发生高尿症的机制。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13 C草酸盐和测量尿液中排泄的13 C草酸盐来评估RYGB前后的肠道草酸盐吸收。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手术前是否被草酸盐降解细菌Oxalciumformigenes定植，以及患者的定植状态在手术后是否发生变化并导致高尿酸的严重程度。我们研究的意义在于，它将确定RYGB手术后患者高尿酸血症、肾结石和肾功能丧失的患病率，并将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，可用于预防RYGB手术的此类并发症。胃旁路手术正在越来越多的肥胖患者中进行，因为与体重减轻相关的有益结果。有证据表明，病人形成肾结石，并遭受肾功能下降，作为手术的结果。我们将确定结石和结石的化学危险因素在胃旁路手术患者中的发生率。最后，我们将研究这些并发症发生的原因，并研究预防肾结石和胃旁路手术后肾功能丧失的方法。

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.