Hyperoxaluria and Nephrolithiasis After Gastric Bypass Surgery for Obesity

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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.