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: 7456371
• 负责人: RAJIV KUMAR
• 金额: $ 18.51万
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7456371
• 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）：胃旁路手术后，患者经常出现肾石器症，以进行医学上复杂的肥胖症。我们已经在有限的患者中表明，即使没有临床明显的肾石石症，胃旁路术后1年，在胃旁路尿后1年，诸如Hyperoxaluria，depocitraturia和Hypocalciuria等石头的代谢危险因素也很常见。该应用的目标是检查roux-en-y胃旁路（RYGB）手术后，患者中高黄油和肾结石病的患病率和机制。在此赠款期间获得的信息将使我们能够定义问题的范围，并获取适当的大规模试验的信息，以防止肾脏症，肾球钙经症和肾功能障碍的肾上石症，越来越多地接受与​​RYGB治疗的医学上复杂性肥胖的患者。我们的假设是，在RYGB手术治疗治疗肥胖症后，患者经常出现高黄油尿症，而这种代谢异常通常会导致肾石石症的发生。肾球身床病和肾功能受损是潜在的，甚至更严重的RYGB手术并发症。我们假设在这些患者中观察到的高氧钙是继发于肠子中草酸盐的高吸收的继发的。我们的具体目的是：1）估计一组正在进行RYGB手术的100例患者中肾物石症，肾球腺炎和肾功能受损的发病率和患病率，并比较这些手术患者的发现，并在这些手术患者中与30例非手术的肥胖对照组所见。 。患者将在RYGB手术之前接受广泛的生化和放射学评估，以进行医学上复杂的肥胖症，并在手术后6和12个月再次接受。 2）确定在RYGB手术治疗医学复杂的肥胖症后，患者在患者中发生高黄油的机制。为了洞悉可能是干预试验靶标的潜在机制，我们将通过口服13c草酸盐的口服给药前后评估草酸盐的吸收，并在尿液中测量13 C的Oxalate排泄13 C的测量。我们将确定此类患者是否患有脂肪吸收不良。我们将评估这些患者是否在RYGB手术前通过降解草酸盐的草酸杆菌甲酸造成甲酸杆菌定殖，以及该患者在手术后的定殖状态是否变化并导致高氧甲里的严重程度。我们研究的意义在于，它将确定RYGB手术后患者中高黄油，肾结石病和肾功能丧失的患病率，并将提出这些并发症发生的机制。根据这些发现，我们将能够定义可用于防止这种RYGB手术并发症的理性干预措施和疗法。由于与体重减轻有关的有益结果，胃旁路操作以越来越多的速率进行胃旁路操作。有证据表明，患者形成肾结石并因手术而降低肾脏功能。我们将确定在接受胃旁路手术的患者中，石头常见的石头和化学危险因素如何发生。最后，我们将研究为什么发生这些并发症的原因，我们将开发用于防止肾结石和胃旁路手术后肾功能丧失的方法。

项目成果

The regulation of parathyroid hormone secretion and synthesis.

• DOI: 10.1681/asn.2010020186
• 发表时间: 2011-03
• 期刊: Journal of the American Society of Nephrology : JASN
• 作者: Kumar R;Thompson JR
• 通讯作者: Thompson JR

ATM-dependent expression of IEX-1 controls nuclear accumulation of Mcl-1 and the DNA damage response.

• DOI: 10.1038/cdd.2010.56
• 发表时间: 2010-11
• 期刊: Cell death and differentiation
• 影响因子: 12.4

Quantification of urinary albumin by using protein cleavage and LC-MS/MS.

• DOI: 10.1373/clinchem.2008.115543
• 发表时间: 2009-06
• 期刊: Clinical chemistry
• 影响因子: 9.3
• 作者: Seegmiller JC;Barnidge DR;Burns BE;Larson TS;Lieske JC;Kumar R
• 通讯作者: Kumar R

Fat malabsorption and increased intestinal oxalate absorption are common after Roux-en-Y gastric bypass surgery.

• DOI: 10.1016/j.surg.2010.11.015
• 发表时间: 2011-05
• 期刊: SURGERY
• 影响因子: 3.8
• 作者: Kumar, Rajiv;Lieske, John C.;Collazo-Clavell, Maria L.;Sarr, Michael G.;Olson, Ellen R.;Vrtiska, Terri J.;Bergstralh, Eric J.;Li, Xujian
• 通讯作者: Li, Xujian

Increased expression of secreted frizzled-related protein 4 in polycystic kidneys.

• DOI: 10.1681/asn.2008040345
• 发表时间: 2009
• 期刊: Journal of the American Society of Nephrology : JASN
• 作者: Daniel Romaker;Michael Puetz;S. Teschner;J. Donauer;M. Geyer;P. Gerke;B. Rumberger;B. Dworniczak;P. Pennekamp;B. Buchholz;H. Neumann;R. Kumar;J. Gloy;K. Eckardt;G. Walz