Bariatric Surgery and Kidney Stones

Wisit Cheungpasitporn

August 21, 2015

Disclosure• None

Increasing proportion of adults with obesity, United States, 1990 to 2010

*obesity was defined as a BMI ≥ 30 kg/m2

In 2012, more than one-third (34.9% or 78.6 million) of U.S. adults are obese.

Indications for Bariatric Surgery• Bariatric surgery is a treatment option for people with obesity if all

of the following criteria are fulfilled:• BMI ≥40 kg/m2, or • BMI 35 - 40 kg/m2 and other significant diseases (for example,

such as type 2 DM, HTN or OSA) that could be improved if they lost weight.

• All appropriate non-surgical measures have been tried but the person has not achieved or maintained adequate, clinically beneficial weight loss.

• The person is generally fit for anesthesia and surgery.

• The person commits to the need for long-term follow-up.

NICE clinical guideline. Issued: November 2014Fried, M. et al. Obes. Surg. 24, 42–55 (2014).

Classification of Bariatric Surgery

• Purely Restrictive• Adjustable gastric banding [AGB]• Vertical banded gastroplasty [VBG]• Sleeve gastrectomy

• Purely Malabsorptive • jejuno–ileal bypass

Frühbeck G. Nat Rev Endocrinol. 2015;11(8):465-77

Classification of Bariatric Surgery

• Mixed restrictive and malabsorptive• Restrictive > Malabsorptive

• Roux-en-Y gastric bypass [RYGB]

• Malabsorptive > Restrictive• Biliopancreatic diversion with or without

duodenal switch • Very, very long limb RYGB

Frühbeck G. Nat Rev Endocrinol. 2015;11(8):465-77

Mechanick JI et al. Obesity. 2013;21 Suppl 1:S1-27.

Laparoscopic adjustable gastric banding

Sleeve gastrectomy

Tarplin S et al. Nat Rev Urol. 2015;12(5):263-270

Roux-en‑Y gastric bypass

Tarplin S et al. Nat Rev Urol. 2015;12(5):263-270

Lieske JC et al. Semin Nephrol. 2008;28(2):163-73.

Roux-en‑Y gastric bypass

Biliopancreatic diversion with duodenal switch

Lieske JC et al. Semin Nephrol. 2008;28(2):163-73.

Association Between Bariatric Surgeryand Long-term Survival

Arterburn DE et al. JAMA . 2015;313(1):62-70.

2.4%6.4%

1.7%

10.4%

23.9%

13.8%

Matched control

Surgical patients

Bariatric procedures: 74% gastric bypass, 15% sleeve gastrectomy, 10% adjustable gastric banding, and 1% other.

Matched age, sex, geographic region, BMI, diabetes, and Diagnostic Cost Group

Frühbeck G. Nat Rev Endocrinol. 2015;11(8):465-77

Chang SH et al. JAMA Surg. 2014;149(3):275-87

BMI loss within 5 years after surgery

Number of bariatric surgeries performed in the U.S.

Gonzalez RD et al. Curr Urol Rep;2014:15:401

Trends in number of procedures worldwide: from 2003 to 2008 to 2011 to 2013

Angrisani L. et al. Obesity surgery (2015): 1-11.

Trends in percentage of procedures worldwide: from 2003 to 2008 to 2011 to 2013

Angrisani L. et al. Obesity surgery (2015): 1-11.

Countries where >10,000 procedures were performed in 2013 include• United States and Canada (n = 154,276)

• Brazil (n = 86,840)

• France (n = 37,300)

• Argentina (n =30,378)

• Saudi Arabia(n =13,194)

• Belgium(n = 12,000)

• Israel (n =11,452)

• Australia/New Zealand (n =10,467)

• India (n =10,002)

Angrisani L. et al. Obesity surgery (2015): 1-11.

Powell CR et al. Urology. 2000;55(6):825-30.

Currie A et al. Obes Surg. 2011;21(4):528-39.

Asplin JR. Adv Chronic Kidney Dis. 2009;16(1):11-20.

Currie A et al. Obes Surg. 2011;21(4):528-39.

Currie A et al. Obes Surg. 2011;21(4):528-39.

Obesity

CKD

Kidney Stones

Bariatric Surgery

??

↑↑

Nazzal L, Puri S, Goldfarb DS. Nephrol Dial Transplant. 2015 [Epub ahead of print]

Sinha MK et al. Kidney Int. 2007;72(1):100-7.

Semins MJ et al. Urology. 2010;76(4):826-9.

54 subjects after RYGB; 18 patients after restrictive bariatric; 14 gastric banding and 4 sleeve gastrectomy The mean time from restrictive surgical procedure to urine collection was 12.4 months (range: 7-30)

Semins MJ et al. Urology. 2010;76(4):826-9.

35.4

60.7

32.9

37.2

Gonzalez RD et al. Curr Urol Rep (2014) 15:401

Kidney Stone incidence following Bariatric Surgery

Obesity

CKD

Kidney Stones

Bariatric Surgery

↑↑↑?

↑

↑

Ahmed MH et al. Nephrol Dial Transplant. 2010;25(10):3142-7.

Ahmed MH et al. Nephrol Dial Transplant. 2010;25(10):3142-7.

Neff KJ et al. Nephrol Dial Transplant. 2013;28 Suppl 4:iv73-82.

Obesity

CKD

Kidney Stones

Bariatric Surgery

↑↑↑?

↑

↑

Lieske JC et al. Kidney Int. 2015 Apr;87(4):839-45.

Objective

• To compare the incidence of stones in patients after bariatric surgery with that in comorbidity-matched obese controls in a population based study

Methods – Study population

• Bariatric surgery group• Olmsted County residents with BMI > 35 kg/m2, who

underwent bariatric surgery at Mayo Clinic between the year 2000 and 2011

• Control group• Sampled from among all Olmsted County residents with

BMI > 35 kg/m2 who were seen at Mayo Clinic during study period

• Matched for sex, index year* and BMI with ± 3.

• 759 of 762 surgery cases were matched, with 95% having an age within 5 years

*index year (BMI date in controls closest to preoperative BMI in surgery patients)

Methods - Outcomes• Using REP* data to capture kidney stone and CKD events for

both surgery and control groups

• EMR for 24-hr urine studies• Bariatric surgery group: as part of routine follow-up visits

beginning 6 months post surgery or at the time of a nephrology stone clinic visit if they developed stones

• Control group: available only at the time of a nephrology stone clinic visit

Outcome ICD-9Kidney/bladder stone

592, 594, 274.11

CKD 250.4, 274.10, 274.19, 403, 404, 446.21, 453.3, 572.4, 581, 582, 583, 585, 586, 587, 593.89, 593.9, 753.1, 753.0, 753.3, 791.0

*REP= Rochester Epidemiology Project

Methods – Statistical Analysis

• Association between bariatric surgery with a subsequent kidney stone event and CKD

• Kaplan-Meier plots• Cox proportional hazard models with adjustment for

age, sex, and other baseline comorbidities• Subjects with prevalent kidney stones were excluded

from analysis of incident stones

Results

2683 bariatric surgery

-63 no research authorization-1832 non-OC residents-26 BMI < 35

762 bariatric surgery studied

13256 OC residents with BMI > 35

-699 bariatric surgery-63 no research authorization

12494 potential control

759 matched bariatric surgery patients

759 matched control

*OC = Olmsted County

Type of bariatric surgery 2000-2011

• Standard RYGB (n=591): most common (78%)• Majority: open surgery before 2007, laparoscopic after 2004

• Malabsorptive procedure (n=105)• Very, very long limb RYGB (n=55)• Biliopancreatic diversion/switch (n=50)

• Restrictive procedure (n=56)• Laparoscopic banding (n=43)• Laparoscopic sleeve gastrectomy (n=13)

P=0.02 for comparison between post-bariatric group and obese stone former

Univariate and multivariate models of hazard ratios for kidney stones

Risk Factor HR 95% CI PUnivariate      Age at time of surgery 1.003 0.986-1.020 0.72

Sex 1.243 0.791-1.951 0.34Hypertension 1.092 0.756-1.577 0.64Diabetes 1.797 1.226-2.635 0.003Arthritis 2.227 1.538-3.223 <0.001Sleep apnea 1.617 1.118-2.341 <0.001RYGB 2.554 1.655-3.940 <0.001Malabsorptive 5.292 3.038-9.221 <0.001Restrictive 0.588 0.080-4.317 0.60Multivariate      Age 0.999 0.980-10.18 0.94Sex 1.085 0.674-1.748 0.74Hypertension 0.852 0.562-1.291 0.45Diabetes 1.656 1.096-2.502 0.02Arthritis 1.312 0.844-2.040 0.23Sleep apnea 1.084 0.716-1.642 0.70

RYGB 2.140 1.291-3.547 0.003Malabsorptive 4.036 2.073-7.860 <0.001Restrictive 0.521 0.070-3.875 0.52

Risk of recurrent stone

• Patients with history of a prior stone at the time of bariatric surgery were more likely to develop a stone after surgery than non-prevalent cases (42% vs. 14% at 10 years; HR 4.1, P<0.001)

• The risk of prevalent obese patients forming a second stone was slightly higher (52% at 10 year)

• This reflect stone event risk to increase as the number of prior event increases

• This does not suggest that bariatric surgery disproportionately augments stone risk among those with past stone events

Bariatric surgery was not a risk factor for developing CKD (HR 0.95; 95% CI 0.67-1.35)

Univariate and multivariate models of hazard ratios for CKD

Risk Factor HR 95% CI PUnivariate      Age at time of surgery 1.040 1.023-1.058 <0.001

Sex 1.716 1.716-1.143 0.009Hypertension 2.058 1.437-2.947 <0.001Diabetes 3.609 2.541-5.125 <0.001Arthritis 1.075 0.747-1.547 0.70Sleep apnea 1.470 1.036-2.085 0.03RYGB 0.775 0.523-1.149 0.20Malabsorptive 2.018 1.197-3.402 0.009Restrictive 0.793 0.193-3.263 0.75Multivariate      Age 1.026 1.006-1.045 0.01Sex 1.219 0.788-1.886 0.37Hypertension 1.335 0.899-1.985 0.15Diabetes 2.903 2.003-4.207 <0.001Arthritis 0.931 0.587-1.477 0.76Sleep apnea 0.975 0.658-1.446 0.90RYGB 0.750 0.469-1.201 0.23Malabsorptive 2.044 1.087-3.843 0.03Restrictive 0.918 0.219-3.845 0.91

Changes in urine oxalate and CaOx SS after surgery

Discussion • The risk for kidney stones is approximately doubled in

patients after RYGB compared with matched, non-operated, obese controls.

• The risk for kidney stones • Malabsorptive > Standard RYGB> Restrictive

Discussion

• The mechanism(s) by which RYGB patients develop hyperoxaluria is yet to be fully explained.

• The distal malabsorptive so-called very, very long limb RYGB or the biliopancreatic diversion/duodenal switch, may predispose to clinically important fat malabsorption, leading to enteric hyperoxaluria.

Discussion• The extent of hyperoxaluria corresponds to the

degree of steatorrhea.

• In the one stone clinic patient in whom fat malabsorption was assessed, 72-h fecal fat excretion was increased (57 g; normal <7 g), despite the absence of diarrhea.

McLeod RS, Churchill DN. J Urol 1992; 148: 974–978

Sinha MK et al. Kidney Int 2007; 72: 100–107.

Discussion

• The prevalence and risk factors for oxalate nephropathy after RYGB are less certain.

• The presence of CKD before RYGB may be an important predisposing factor.

Nasr SH et al. Clin J Am Soc Nephrol. 2008;3(6):1676-83.

Limitations

• Kidney stones, CKD, and comorbidities were determined by diagnosis codes, and laboratory data were available for only a subset of all patients with or without kidney stones.

• The incidence and prevalence of CKD post-bariatric surgery might also have been underestimated because of the effects of weight loss on creatinine generation and serum creatinine levels.

Conclusion

• Obese patients who undergo RYGB have an increased risk for kidney stones that is approximately double that of obese, nonoperated controls.

• Patients with malabsorptive bariatric procedures appear at greatest risk for stones but are also at increased risk for new-onset CKD.

Questions & Discussion

Tarplin S et al. Nat Rev Urol. 2015;12(5):263-270

Cossey LN et al. Am J Kidney Dis 2013; 61: 1032–1035

Canales BK et al. Surg Obes Relat Dis. 2014;10(4):734-42.