Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00169793 |
| Other study ID # |
05-076 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
September 9, 2005 |
| Last updated |
March 4, 2014 |
| Start date |
August 2005 |
| Est. completion date |
December 2012 |
Study information
| Verified date |
March 2014 |
| Source |
Indiana Kidney Stone Institute |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
Test the hypothesis that the new bariatric surgical procedures (BSP) increase stone risk,
and will result in an increased incidence and prevalence of stone disease; the purpose is to
determine if BSP patients require special management for stone prevention. This study does
not include the bariatric surgery but enrolls subjects who are already scheduled for surgery
with an affiliated surgeon. The study procedure is to collect 24 hour urines pre-and post
surgically to evaluate the risk of kidney stone procedure after surgery.
Description:
Surgical therapy for the morbidly obese began when the jejunocolic anastomosis procedure was
performed in 1956 but was modified to a jejunoileal technique years later after intolerable
metabolic complications ensued.1, 2 In 1969, Payne recommended that the end to side
jejunal-ileal bypass (JIB) procedure which preserved 37cm of jejunum and 10cm of ileum
should replace the jejunocolic bypass.2 In 1970, Scott modified JIB by increasing the length
of intestine used and by fashioning an end-to-end anastomosis between the jejunum and
ileum3; this modified procedure soon became the preferred procedure for weight reduction.
This foray into bariatric surgery was quickly embraced and JIB was widely adopted. However,
in the mid to late 1970's, about 10 years after the first JIB was performed, concern
developed regarding the long-term adverse effects of anemia, vitamin deficiencies,
nephrolithiasis and ultimately even renal and liver failure.4-14 It was not until a number
of patients had end organ failure that the full impact of the complications of JIB were
recognized. Much of the complications stem from the malabsorptive component that results
from JIB. As fat is malabsorbed, fat-soluble vitamins and calcium are saponified.
Subsequently, nutrients are lost and an increased oxalate load is delivered to the large
intestine as the calcium that would normally bind oxalate is lost with the malabsorbed fat.
In addition, bile salts normally reabsorbed in the ileum are delivered to the colon,
increasing the permeability of the colonic mucosa to oxalate. These factors result in
increased uptake of oxalate in the large intestine. Oxalate, which cannot be metabolized by
humans, is rapidly cleared by the kidney resulting in "intestinal" hyperoxaluria and calcium
oxalate nephrolithiasis4-6, 12, 15 and nephrotoxicity.7, 10, 11, 13, 16 The probability of a
severe renal complication after JIB was calculated to be about 21% at 5 years and increased
to 37% at 15 years; there is also a 28.7% risk of nephrolithiasis at 15 years.13 It was not
until 1980 that the Food and Drug Administration placed a moratorium on JIB for obesity
surgery. Prior to that approximately 25,000 such procedures had been performed in the United
States. A large number of these patients had the JIB reversed or succumbed to its
complications.10 Those patients with the JIB intact remain at risk for complications such as
cirrhosis, arthritis, urolithiasis, oxalate nephropathy, and bypass enteritis—of which only
the latter three respond when the JIB is reversed.10 The lessons learned from this previous
experience with bariatric surgical procedures must not be repeated. Although the
cardiopulmonary risks of obesity are significant, the catastrophic long-term consequences
that were unrecognized initially with JIB should not be forgotten. Many patients not only
necessitated treatment for kidney stones but some have lost renal function requiring
dialysis and transplantation from oxalate nephropathy.10, 11, 13 Currently, the Roux-en-Y
bariatric procedure (REY) is the most widely utilized procedure for the surgical treatment
of obesity. REY results in rapid weight loss17 compared to restrictive procedures16, 17,
18-20 but the long-term effects of the malabsorptive component of this operation on the risk
of nephrolithiasis and renal loss is currently unknown. With REY, fat malabsorption is one
of the primary mechanisms by which weight loss is accomplished and, therefore, intestinal
hyperoxaluria, as occurs with JIB, is theoretically possible. Although the long-term
metabolic consequences of REY have yet to be studied, some recent data from LithoLink is
concerning. LithoLink Corporation, located in Chicago IL, is a clinical laboratory/disease
management company that provides testing for kidney stone patients. Physicians from all
across the United States refer stone patients to the LithoLink laboratory for evaluation.
Patients collect 24-hour urine samples at home and then send them via overnight air express
to LithoLink for analysis. As part of the disease management service, a medical history
pertinent to kidney stones is obtained from each patient via phone interview. Since 1998,
patients have specifically been asked if they have had weight reduction surgery and whether
the surgery was JIB or bariatric, and the answers are coded into the database. The LithoLink
database is the largest kidney stone database linking laboratory and clinical data in this
country, and perhaps the world. As part of an IRB approved research protocol, LithoLink
sought to ask the question whether modern bariatric procedures were associated with an
increase in urine oxalate excretion. They found normal non-stone forming controls have a
mean urinary oxalate excretion of 34.3mg/day while calcium oxalate stone formers from the
same laboratory have a mean urinary oxalate excretion of 37.3mg/day. In contrast, the
bariatric population, which includes both gastric banding (restrictive only) and REY
(restrictive and malabsorptive) patients, was found to have a mean urinary oxalate excretion
of 78.4mg/day (p<0.001 compared to both normal controls and stone formers). Figure 1 shows
the comparison of urine oxalate excretion of bariatric surgery patients to that of routine
stone formers. Note the significant right shift to higher oxalate excretion in the bariatric
surgery patients (open triangles). Most laboratories consider a urinary oxalate excretion of
>45mg/day to represent hyperoxaluria and primary hyperoxaluria (a rare inborn error of
metabolism resulting in marked endogenous production of oxalate) is suspected when the level
of urinary oxalate exceeds 100mg/day6. Given these definitions, the urine oxalate excretion
in patients having undergone bariatric surgery is striking. Nearly 3/4 of the bariatric
surgery cohort had urine oxalate levels above 45mg/day and about 1/4 had urinary oxalate
levels in excess of 100mg/day. Calcium oxalate supersaturation (Figure 2), the chemical
driving force for crystallization, is also dramatically elevated in bariatric surgery
patients compared to routine stone formers (12.5 vs. 7.3, p<0.001), highlighting the extreme
risk for stone formation and oxalate nephropathy in these patients. Finally, the data was
analyzed to see if there was an increase in the number of bariatric surgery patients being
referred for kidney stone evaluation. Since the number of new patients referred to Litholink
each year is increasing, the data is presented as the number of new bariatric surgery
patients per one thousand new stone patients per year. As can be seen in Figure 3, there is
a significant upward trend of bariatric surgery patients with kidney stones (r2= 0.86 for
the linear regression, p=0.01). This rise in bariatric surgery patients with kidney stones
parallels, but lags by several years, the rise in the number of bariatric surgeries in the
United States (Figure 3). Although bariatric procedures such as REY are performed with the
assumption that the resultant physiologic perturbations should be less severe than with JIB,
our preliminary data suggests that these contemporary bariatric surgical procedures result
in urinary oxalate levels comparable to that reported after JIB with the now well-known
long-term adverse sequela vis-à-vis nephrolithiasis and oxalate nephropathy.
Because Clarian, as well as many other medical institutions, is undertaking a large endeavor
to become a center of excellence in bariatric surgical treatment, the risk of stone
formation and renal disease in these patients should be carefully examined. It is hoped that
early recognition of adverse metabolic alterations will allow the patient and physician to
rapidly treat and even prevent some complications. Loss of renal function, as with the
previous experience with JIB, is much too late a phase in the consequences of hyperoxaluria
for the identification of such problems associated with bariatric surgery. Patients can also
be adequately counseled if they have a prior history of stone disease regarding the relative
risks of the various bariatric surgical procedures. As obesity is currently an important
national health issue, the examination of the surgical treatment for obesity and the
consequences of these procedures is timely. Scrutiny of the risks of bariatric surgery will
benefit both patient and surgeon in identify and preventing renal complications that may
arise.
