Effect of Gastric Bypass Surgery on Kidney Stone Disease

Article Outline

• Abstract
• Materials and Methods
• Results
• Discussion
• Conclusions
• Acknowledgments
• Appendix 1. Codes Used to Define Bariatric Surgical Procedures
• Appendix 2. Codes Used to Define Urological Procedures and Conditions
• References
• Copyright

Purpose

Recent studies have demonstrated that mineral and electrolyte abnormalities develop in patients who undergo bariatric surgery. While it is known that these abnormalities are a risk factor for urolithiasis, the prevalence of stone disease after bariatric surgery is unknown. We evaluated the likelihood of being diagnosed with or treated for an upper urinary tract calculus following Roux-en-Y gastric bypass surgery.

Materials and Methods

We identified 4,639 patients who underwent Roux-en-Y gastric bypass surgery and a control group of 4,639 obese patients who did not have surgery in a national private insurance claims database in a 5-year period (2002 to 2006). All patients had at least 3 years of continuous claims data. Our 2 primary outcomes were the diagnosis and the surgical treatment of a urinary calculus.

Results

After Roux-en-Y gastric bypass surgery 7.65% (355 of 4,639) of patients were diagnosed with urolithiasis compared to 4.63% (215 of 4,639) of obese patients in the control group (p <0.0001). Subjects in the treatment cohort more commonly underwent shock wave lithotripsy (81 [1.75%] vs 19 [0.41%], p <0.0001) and ureteroscopy (98 [2.11%] vs 27 [0.58%], p <0.0001). Logistic regression demonstrated that Roux-en-Y gastric bypass surgery was a significant predictor of being diagnosed with a urinary calculus (OR 1.71, CI 1.44–2.04) as well as undergoing a surgical procedure (OR 3.65, CI 2.60–5.14).

Conclusions

Roux-en-Y gastric bypass surgery is associated with an increased risk of kidney stone disease and kidney stone surgery in the postoperative period. Clinicians should be aware of this hazard and inform patients of this potential complication. Future studies are needed to evaluate preventive measures in the high risk population.

Key Words: kidney, calculi, bariatric surgery, epidemiology

Abbreviations and Acronyms: BCBS, Blue Cross Blue Shield, BMI, body mass index, JI, jejunoileal, RYGB, Roux-en-Y gastric bypass

Obesity has become a leading public health epidemic with recent estimates that 30% of American adults are obese (BMI greater than 30).¹ Even more alarming is the trend that prevalence rates are increasing rapidly,¹ creating a deferred societal burden of type II diabetes, heart disease, hypertension, pregnancy complications, sleep apnea and other health problems.² Bariatric surgery is the only therapy to date to our knowledge that has been shown to result in sustained and significant weight loss in the majority of candidate morbidly obese patients. In fact, the number of bariatric procedures performed in the United States increased 5-fold from 1998 to 2002.³

The earliest surgical therapy for the treatment of obesity was the malabsorptive JI bypass procedure. Although JI bypass did induce rapid and lasting weight loss, increasing experience with the procedure led to the recognition of serious postoperative sequelae such as liver failure, osteomalacia, nephrolithiasis and renal failure.⁴ Nephrolithiasis and renal failure were induced by over-absorption of dietary oxalate, which resulted in severe hyperoxaluria.⁵ As a consequence of these metabolic consequences the JI bypass was abandoned and in 1979 the Food and Drug Administration requested a moratorium on the procedure.⁶

The Roux-en-Y gastric bypass overcame many of the malabsorptive problems associated with JI bypass, and is recognized as a safe and effective therapy.³, ⁷ However, some reports have suggested that patients undergoing certain types of bariatric surgery such as RYGB are at increased risk for postoperative hyperoxaluria. It is not known whether this hyperoxaluria will ultimately result in symptomatic renal calculi as it did in patients undergoing JI bypass.⁸, ⁹, ¹⁰ To address this question we designed a study to measure the prevalence of kidney stone disease following modern RYGB surgery performed for bariatric indications.

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Materials and Methods 

The data and in-kind database development support and guidance were provided by the Blue Cross/Blue Shield Association, BCBS of Tennessee, BCBS of Hawaii, BCBS of Michigan, BCBS of North Carolina, Highmark, Inc. (of Pennsylvania), Independence Blue Cross (of Pennsylvania), Wellmark BCBS of Iowa and Wellmark BCBS of South Dakota. All individuals with 1 of these 7 plans as primary insurer were eligible for inclusion in the data set.

The claims data used in this study were de-identified in accordance with the Health Insurance Portability and Accountability Act of 1996 definition of a limited data set and were used in accordance with federal standards for protecting the confidentiality of the personal health information of the enrollee. The institutional review board of The Johns Hopkins University found this analysis to be exempt from the requirement for review. The data set includes approximately 2.4 million insured lives during a 5-year period (2002 to 2006) with information on enrollee age, sex, enrollment dates and claims for reimbursement for billable health care services. Included in these data are patient diagnoses as identified by ICD-9 codes and Diagnosis Related Groups, and medical procedures classified by CPT codes and ICD-9 procedure codes.

Subjects undergoing RYGB surgery with enrollment for 3 years following the date of bariatric surgery were selected for the treatment group. The codes used to define these procedures are found in Appendix 1. There were 18 patients with cancers of the esophagus, stomach, small intestine or pancreas who were excluded from analysis as some of the relevant gastric procedure codes for cancer could be mistaken for bariatric operations. A comparison control group of obese patients meeting the criteria for bariatric surgery was drawn from a subset of the database with BMI data from the Health Risk Assessment, a medical history document completed online or based on data collected from physician encounters. Control subjects with a BMI greater than 35 and 3 continuous years of followup data were selected and assigned an index date of 7 months after the first month of enrollment to match the median interval between first enrollment and surgery in the treatment group. We excluded from the treatment and control groups female subjects who were pregnant the year before, the year of or the year following an obese BMI value. We also excluded anyone with a preexisting renal disease diagnosis or who had undergone treatment of an upper urinary tract calculus (64 and 62 patients, respectively).

The 2 groups were matched using the SurveySelect procedure (SAS®, 2003) on the basis of age (18 to 24, 25 to 34, 45 to 54, 55 to 64, 65 to 74 and 75 to 84 years), gender, diagnosis of diabetes or prescription for an antihyperglycemic agent at any time before the date of surgery or index date, and presence of a diagnosis of hypertension or a claim for an antihypertensive medication within 6 months of the surgery/index date. One-to-one sampling with probability proportional to size was used.

The main dependent variables examined in this study were a stone removal procedure (shock wave lithotripsy, ureteroscopy, nephrolithotomy) and a diagnosis of urinary calculi (an exclusion criterion if preexisting). The codes used to define these procedures and conditions can be found in Appendix 2. In terms of analysis simple chi-square tests and logistic regression were performed. SAS® version 9.13 was used for all analyses.

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Results 

We identified 4,639 patients who had undergone RYGB surgery and met the criteria for the treatment group as well as a matched control group (table 1). Females outnumbered males 5-to-1 and the majority (64%) of subjects were 35 to 54 years old. An upper urinary tract calculus was diagnosed in 355 subjects (7.65%) in the bariatric surgery group compared to 215 (4.63%) in the comparison cohort (p <0.0001). Mean time from RYGB to diagnosis of an upper tract calculus was 558.65 days. In the subsample who experienced kidney stone events subjects who underwent RYGB were not more likely to have experienced multiple stone events than those in the control cohort (OR 1.03, 95% CI 0.736–1.437, p = 0.871).

Table 1. Demographic information

	RYGB Group	Control Group
Mean age (SE)	44.6(0.14)	45.0(0.15)
% Male/female	19.5/80.5	19.5/80.5
Median yrs observation (SE)	4.6(0.008)	4.1(0.005)
Total person-yrs studied	21,362	19,031

Of the bariatric surgery cohort 3.30% (153 of 4,639) underwent a urological procedure for an upper urinary tract calculus in the 3 years after bariatric surgery vs 0.93% (43 of 4,639) of the comparison group (p <0.0001) (table 2). Ureteroscopy and shock wave lithotripsy were used to a similar extent whereas nephrolithotomy was relied on less commonly.

Table 2. Summary of kidney stone procedures performed

	No. (%)		p Value (chi-square test)
	RYGB Group	Control Group
Shock wave lithotripsy	81(1.75)	19(0.41)	<0.0001
Ureteroscopy with or without lithotripsy	98(2.11)	27(0.58)	<0.0001
Percutaneous nephrolithotomy	6(0.13)	3(0.06)	0.5076⁎
Overall	153(3.30)	43(0.93)	<0.0001

When multivariate logistic regressions were performed to determine the strongest predictors of a surgical procedure for an upper tract calculus, having undergone RYGB bariatric surgery was consistently the most powerful predictor with odds ratios in the range of 3.55 to 4.06 (table 3). RYGB bariatric surgery was a significant predictor of being diagnosed with a urinary calculus (OR 1.76, CI 1.49–2.07) as well as undergoing a surgical procedure (OR 3.55, CI 2.58–4.89). A substantial increase in risk appeared to occur after the age of 45 years and males were more likely than females to undergo a stone removal procedure. However, the results for the male gender did not achieve statistical significance for those undergoing shock wave lithotripsy. Due to the small numbers of cases we did not present the results for nephrolithotomy, although they were included in the category any urological procedure. Neither diabetes nor hypertension was associated with the likelihood of undergoing a stone removal procedure, although hypertension was associated with the diagnosis of a urinary calculus independent of surgery status. All variables examined are included in table 3.

Table 3. Multivariate logistic regression of predictors of the diagnosis and treatment of a urinary calculus

	Diagnosis of Urinary Calculus		Shock Wave Lithotripsy		Ureteroscopy		Any Urological Procedure
	OR (95% CI)	p Value	OR (95% CI)	p Value	OR (95% CI)	p Value	OR (95% CI)	p Value
RYGB	1.76(1.49–2.07)	<0.0001	4.06(2.57–6.43)	<0.0001	4.01(2.62–6.13)	<0.0001	3.55 (2.58–4.89)	<0.0001
Age 45+ yrs	1.33(1.11–1.59)	0.0019	1.54(1.02–2.33)	0.0407	1.69(1.15–2.49)	0.0081	1.68 (1.24–2.28)	0.0009
Male	1.82(1.52–2.17)	<0.0001	1.39(0.91–2.14)	0.1274	2.30(1.59–3.32)	<0.0001	1.79 (1.33–2.4)	0.0001
Diabetes	1.19(0.98–1.44)	0.0761	1.26(0.81–1.96)	0.3135	0.91(0.60–1.40)	0.6774	1.08 (0.78–1.50)	0.6337
Hypertension	1.33(1.11–1.59)	0.0019	0.88(0.58–1.32)	0.5248	0.97(0.67–1.42)	0.8894	0.94 (0.70–1.27)	0.6773

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Discussion 

RYGB, the most commonly used modern bariatric procedure, causes weight loss by the 2 mechanisms of 1) surgically reducing the gastric reservoir and 2) bypassing a length of small intestine.³ The small size of the gastric reservoir limits the oral intake of calories by simple physical restriction, and the small bowel bypass results in shorter intestinal transit time and reduced absorptive surface area. The lithogenic effects of bariatric surgery likely stem from the bypass induced malabsorptive component of the surgery. As fat is malabsorbed fat soluble vitamins and calcium are saponified, leading to subsequent nutrient loss. Concomitantly an increased oxalate load is delivered to the colon as the calcium that would normally bind oxalate in the intestinal lumen is lost with the malabsorbed fat. Oxalate, which cannot be metabolized by humans, is cleared by the kidney, resulting in hyperoxaluria and calcium oxalate nephrolithiasis. Of patients who underwent JI bypass the risk of stone disease as a result of hyperoxaluria was estimated to be approximately 21% at 5 years after surgery.⁵

Recently published laboratory analyses of the long-term effects of RYGB on the risk of nephrolithiasis are concerning. Asplin and Coe reported their experience from a commercial laboratory specializing in the urinary metabolic analyses of kidney stone formers.⁸ They found that stone formers who have undergone modern bariatric procedures are significantly hyperoxaluric to a greater extent than idiopathic calcium stone formers. In their laboratory analyses normal, nonstone formers have a mean urinary oxalate excretion of 34.3 mg daily, calcium oxalate stone formers have a mean urinary oxalate excretion of 37.3 mg daily and the bariatric population (patients who have undergone RYGB or gastric banding procedures) has a mean urinary oxalate of 78.4 mg daily. Importantly the urinary calcium oxalate supersaturation of the modern bariatric surgery cases was not significantly different from a cohort of historical cases treated with JI bypass. Sinha et al from the Mayo Clinic also evaluated a cohort of patients treated exclusively with RYGB for bariatric indications.⁹ In a cross-sectional study of patients who underwent bariatric surgery they found that hyperoxaluria was present in 7 of 13 and calcium oxalate supersaturation was significantly increased above the reference mean in 12 of 13. Duffey et al prospectively studied 24 patients who underwent bariatric surgery.¹⁰ Using the patients as their own control the authors found that there was a significant postoperative increase in urinary oxalate excretion. Urinary supersaturation of calcium oxalate was similarly increased. Taken together these data suggest that patients undergoing bariatric surgery are at increased risk for the formation of calcium oxalate renal calculi.

Until our present work it has been uncertain whether laboratory detected hyperoxaluria in patients treated with bariatric surgery would result in an increased incidence of kidney stone disease. In part this issue could not be resolved due to the lack of a large scale, comparative data set such as the one we have presented. However, what data have been previously published are suggestive of such a correlation. Encinosa et al reviewed the MarketScan Commercial Claims and Encounter Database and found that among the common diagnoses for postoperative conditions 180 days following bariatric surgery, calculus of urinary tract occurred with a frequency of 3.6%.⁷ Unfortunately the MarketScan data set has only limited patient demographic information and does not track patient BMI, precluding a comparison analysis such as we were able to perform.

The first case series commenting on stone disease following modern bariatric surgery was presented in 2005 by Nelson et al.¹¹ They identified 23 patients in whom hyperoxaluria and calcium oxalate stone disease developed following RYGB. Of these patients oxalate nephropathy and renal failure had developed in 2. Durrani et al subsequently reported a single institution, retrospective analysis of stone disease in patients undergoing bariatric surgery.¹² Of 972 patients identified 8.8% had a preoperative history of upper tract calculi and de novo stones developed in 3.2% in the postoperative period. Of the known stone formers 31% were diagnosed with a recurrent stone in the postoperative period. Overall stone prevalence was reported to be increased by approximately 70% in the bariatric surgery cohort compared with expected rates derived from the National Health and Nutrition Examination Survey III.

This report represents the largest analysis to our knowledge of the risk of kidney stone disease following modern bariatric surgery. As one might expect based on the previously reported laboratory studies of patients who had undergone bariatric surgery, we did find an increased incidence of stone disease in this population relative to our control population of obese patients who did not undergo bariatric surgery. However, one should not necessarily interpret our findings of an increased risk of stone disease following bariatric surgery as an indictment of this surgical intervention. The long-term health benefits of bariatric surgery are well characterized and significant.¹³ Rather our work should serve as a cautionary note to those physicians who treat patients undergoing bariatric surgery. The epidemiological findings presented here confirm previous laboratory studies and case series, and suggest that patients who undergo bariatric surgery are at significantly increased risk for stone disease and even oxalate nephropathy.¹⁴ Therefore, these patients should be counseled on maneuvers to attenuate kidney stone risk factors including fluid intake to maintain a urine output greater than 2 l daily, sufficient calcium intake, as well as restricted sodium, animal protein and oxalate intake. Should a patient treated with bariatric surgery ultimately be diagnosed with nephrolithiasis, a metabolic evaluation would be prudent as these patients are at increased risk for metabolic abnormalities, particularly hyperoxaluria.

Our present study has several limitations which merit mention. In general these limitations are inherent to the use of an administrative claims database. Erroneous and incomplete coding (ie failing to list codes for all diagnoses relevant to a given admission) may limit our ability to capture all outcomes. However, we would expect that incomplete coding and coding errors would affect both groups equally. BMI data were not available for the cohort of patients undergoing RYGB. The BMI threshold of 35 used to define the control cohort was selected to adequately capture the morbidly obese. It should be noted that although this value does represent a morbidly obese BMI, it is possible that certain bariatric surgical centers rely on a higher threshold for bariatric surgery.

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Conclusions 

Modern bariatric surgery is associated with an increased risk of kidney stone disease in the postoperative period. It is likely that hyperoxaluria, which has been reported to be prevalent following these surgical procedures, is one of the inciting factors in stone formation. As obesity is currently an important national health issue and bariatric surgery to treat it is increasing at a rapid rate, further studies are urgently required to better define the etiology of hyperoxaluria as well as other stone risk factors in this population. Thus, future efforts can be devoted to altering risk factors for this disorder, thereby attenuating kidney stone formation following bariatric surgery. However, until the pathophysiology of stone formation in this population is better understood it is incumbent upon physicians to maintain a high level of suspicion for underlying urinary metabolic abnormalities in the stone former after undergoing bariatric surgery.

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Acknowledgments 

Eric Bass and Jonathan Weiner provided study support.

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Appendix 1. Codes Used to Define Bariatric Surgical Procedures 

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Appendix 2. Codes Used to Define Urological Procedures and Conditions 

Indicator	Type of Code	Description
Urological Procedures
Shock wave lithotripsy	CPT code	50590 Lithotripsy, extracorporeal shock wave
		S0400 Global fee for extracorporeal shock wave lithotripsy treatment of kidney stone(s)
	ICD-9 procedure code	98.5 Extracorporeal shock wave lithotripsy
		98.51 Extracorporeal shock wave lithotripsy of the kidney, ureter and/or bladder
Ureteroscopy	CPT code	52352 Cystourethroscopy, with ureteroscopy and/or pyeloscopy; with removal or manipulation of calculus
		52353 Cystourethroscopy, with ureteroscopy and/or pyeloscopy; with lithotripsy
Nephrolithotomy (percutaneous and open)	CPT code	50060 Nephrolithotomy; removal of calculus
		50065 Nephrolithotomy; secondary surgical operation for calculus
		50070 Nephrolithotomy; complicated by congenital kidney abnormality
		50075 Nephrolithotomy; removal of large staghorn calculus filling renal pelvis and calices
		50080 Percutaneous nephrostolithotomy or pyelostolithotomy, up to 2 cm
		50081 Percutaneous nephrostolithotomy or pyelostolithotomy, over 2 cm
	ICD-9 procedure code	55.03 Nephrostomy
Renal Disease Indicators
Urinary calculi	Diagnosis Related Group	323 Urinary stones with complication or comorbidity and/or extracorporeal shock wave lithotripsy
		324 Urinary stones without complication or comorbidity
	ICD-9 diagnosis code	274.11 Uric acid nephrolithiasis
		592 Calculus of kidney and ureter
		592.0 Calculus of kidney—nephrolithiasis not otherwise specified
		592.1 Calculus of ureter
		592.9 Urinary calculus, unspecified

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