nutrition

INFLAMMATORY
issues
BOWEL
in gastroenterology,
DISEASE: A PRACTICAL
series
APPROACH,
#107 SERIES #73
Carol Rees Parrish, M.S., R.D., Series Editor

When the Bowel Becomes the Bladder:

Changes in Metabolism
After Urinary Diversion

Frank Van der Aa Dirk De Ridder Hendrik Van Poppel

Urinary diversion is performed on a regular basis in urological practice. Surgeons and general
practitioners are not always aware of the metabolic effects of any type of diversion. From the
patient’s perspective, diarrhea is the most bothersome complaint after urinary diversion. Rarely,
this is accompanied by other malabsorption syndromes. Hyperchloremic metabolic acidosis is
the “baseline” metabolic state of diverted patients. Other electrolyte disturbances are infrequent.
Partly due to the acidotic state, bone health is at risk in patients with urinary diversion. Many
patients are also subject to urinary calculus formation, both at the upper and lower urinary
tract. The kidney function has to be monitored prior to, and lifelong after, urinary diversion
and screening for reversible causes of renal deterioration is an integral part of the follow up.

Introduction

I
n urological practice, several conditions can lead continence mechanism. The occurrence of ureteral
to untreatable problems of the lower urinary tract. strictures, stone formation, ascending infections
High-risk non-muscle invasive bladder cancers, after with sepsis and peritonitis lead to an early, and high,
failure of intravesical therapy or muscle invasive bladder mortality rate. At the clinical level, urinary incontinence
cancer mandating cystectomy, comprise the majority was frequent. Both advances in surgical techniques and
of patients. Other reasons to perform cystectomy are in medical therapy (antibiotics, fluid management) have
neurogenic bladder disease, urinary incontinence and resulted in long life expectancy after urinary diversion
vesicovaginal fistulae (see Table 1). In our high volume at present. This means that we will not only have to
tertiary referral center, about 1 in 6 cystectomies will address evident and severe metabolic problems after
be performed for non-oncological reasons. urinary diversion, but that we also have to pay attention
Historically, initial urinary diversion was performed to more discrete changes in metabolism that can affect
by formation of a fistulous tract between the ureters quality of life in the long run.
and the bowel. Such derivations used the anus as the Urinary diversions can be divided into non-
continent diversions, continent diversions and
Frank Van der Aa, MD, PhD, Dirk De Ridder, MD, PhD, orthotopic neobladders. When a bowel segment is
Hendrik Van Poppel, MD, PhD, Department of Urology, incorporated into the urinary tract, not only does the
University Hospitals Leuven, Leuven, Belgium direct metabolic consequence need to be considered,

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but also the consequence of removing the segment Table 1. Indications for Cystectomy
from the gastrointestinal tract. The majority of urinary
diversions are constructed from terminal ileum or • N
 on muscle invasive bladder cancer after
ileocolonic segments of the intestine. The rationale failure of intravesical therapy
to take these bowel segments are: good mobility with
relatively long and anatomically constant vessels, the • Muscle invasive bladder cancer
caecum rarely has diverticula, easy harvesting and re-
anastomosis of these bowel segments, and finally, when • Neurogenic bladder disease caused by:
creating continent diversion the appendix can be used
as a conduit or the ileocaecal valve can be used as o Spinal cord injury
continence mechanism. There is no ‘proof’ however that
these segments are superior to other bowel segments. o Multiple sclerosis
The nature and the grade of metabolic effects will
be determined by the duration of contact between urine o Meningomyelocoele
and bowel and by the segment and length of bowel used.
Metabolic changes begin immediately after diversion. • Bladder pain syndrome
In the immediate postoperative phase however, urinary
catheters and stents drain urine from the diversion and • Radiation cystitis
diminish the contact with the intestinal mucosa. At the
time of catheter removal (around postoperative day 10) • Urinary incontinence
the metabolic changes occur fully. Many complications,
however, will only become clear months or years after • Vesicovaginal fistulae
the surgical procedure. Therefore, long-term follow-up
and prevention of complications is mandatory. Although • F ailed reconstruction after congenital
diversions have been performed for decades, many anomalies (such as extrophia vesicalis)
aspects regarding follow up and prevention of metabolic
changes remain under debate. This field of study is
hampered by a plethora of confounding variables (such
as concomitant chemotherapy, neurogenic diseases, short bowel segment and the fact that the segment does
congenital anomalies, etc.). Therefore, good clinical not function as a reservoir, implicates less metabolic
studies are lacking and most recommendations are effects. Nevertheless, about 10% of patients with ileal
based on expert opinion and low quality data. conduits will have metabolic disturbances requiring
In this review article we will describe the relevant therapy (2).
short and long-term metabolic changes in urinary Several pouches to create continent diversions
diversion using ileal and ileocolonic segments. We or orthotopic neobladders can be constructed
will suggest a scheme for clinical follow up, treatment by detubularizing (i.e. opening the bowel at the
of metabolic changes and prevention of complications antimesenterial side in order to abolish functional bowel
(see table 2 and 3). contractions) a certain length of ileum. The W-pouch
or Hautmann pouch, the Stüder pouch, the N-pouch
Surgical Aspects and the Kock pouch are some popular variants on this
Non-continent ileocutaneostomy or Bricker diversion is theme (3-7) (table 4). In contrast to the ileal conduit, 40-
the most frequently used type of diversion worldwide. 80 centimeters of preterminal ileum are used for these
This procedure was popularized by Eugene M. Bricker types of diversion. The ileal segment is detubularized
(1). In this procedure, 15 to 25 centimeters of preterminal in order to create a larger, low pressure reservoir. In
ileum is harvested. Reasons for its popularity over other this way reservoirs can be made with capacities that
types of diversion are the relative ease and simplicity are similar to the native bladder. As a consequence,
of the procedure. It gives predictable functional results. urine will have a long contact time with the intestinal
There is no risk for unexpected incontinence, for urinary segment, allowing extensive metabolic exchange. The
retention or for catheterization problems. The use of a (continued on page 19)

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(continued from page 16)

Table 2. Clinical Problems with Practical Considerations

Clinical Problem Advise Discourage Intervention

Diarrhea • High fiber intake • H
 igh fat intake • Quantify stool output
if bile salt
• High fluid intake • C
 heck for infectious
deficient
etiologies
• Cholestyramine
• Loperamide

Urolithiasis • H
 igh fluid intake • Urine culture
(achieve urine
• Check for acidosis
output of 2000 mL)
• Consider fat malabsorption

Metabolic Acidosis • S
 odium bicarbonate • Monitor potassium
(1 to 2g t.i.d.)
• C
 onsider calcium
• Sodium citrate supplements
(1 to 3g t.i.d.)
• Nicotinic acid
(500 mg to 2g q.d)
• Chlorpromazine
(25 to 50 mg q.i.d.)

Altered • Lactulose • Check for hyperammonemia

Sensorium/Coma
• Neomycin • C
 heck for infection with
urease producing bacteria
• Rifaximin
• Check for obstruction
Low Vitamin • Daily oral supplement
B12 Level
• M
 onthly
intramuscular or
subcutaneous
supplements
Renal Function • Strictly monitor • N
 SAIDs, toxic • Perform renal ultrasound
Impairment blood pressure substances
• Consider nuclear scans
• Appropriate
Diabetes mellitus
control
Need for New • C
 onsider possible
Medical Treatment reabsorption in the
intestinal segment

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longer part of bowel used to create these diversions prove to be insufficient, gastrointestinal motility
will also influence gastrointestinal absorption more inhibitors such as loperamide 4 mg q.d. to 16 mg q.d.
extensively as compared to an ileal conduit. can be added. It is best not to advise fluid restriction,
For ileocolonic pouches, the terminal ileum, together since patients with urinary diversion are subject to
with caecum, are detubularized to create a reservoir. dehydration (10).
One of the most popular examples of these techniques
is the Mainz pouch (8, 9). Metabolic consequences Renal Function
of these pouches are in general comparable to ileal From the age of 40 onwards, glomerular filtration
pouches, although some differences exist. One of the rate (GFR) of adults decreases progressively with
main differences is the incorporation of the ileocaecal approximately 1 mL/min/1,73m² from an initial
valve in the urinary tract, which will increase the rate normal value of 100 to 130 ml/min/1,73m². After
of diarrhea in diverted patients. urinary diversion, several factors may amplify renal
deterioration. Stenosis of uretero-intestinal anastomosis
Bowel Dysfunction/Malabsorption results in ureteric obstruction with gradual kidney
Harvesting a part of preterminal ileum can result in damage. Also recurrent infections and urinary lithiasis
diminished bile salt and fat absorption. The longer will have a negative impact on renal function. In theory,
the segment needed to create a urinary diversion, the the incorporation of a bowel segment into the urinary
more likely clinically important malabsorption will tract induces urinary metabolite absorption and thus
occur. After food ingestion, bile salts are secreted into a variable and immediate decline in renal function.
the duodenum. They emulsify fats and are almost The exact impact of urinary diversion as such on renal
completely reabsorbed in the preterminal ileum, function is not known (11). It has been shown that GFR
entering the enterohepatic cycle. When large amounts of decreases 15-25% after urinary diversion with a follow
bile salts reach the colon, they act as mucosal irritants, up of 11 years (12).
directly causing diarrhea. When the absorbing part of In a clinical setting, it is important to screen for
ileum is resected, even removing a relatively small part reversible causes of upper urinary tract deterioration in
can cause bile salt malabsorption. Fat malabsorption every patient and to treat these causes accordingly. It is
only occurs when larger portions of small intestine equally important to know the level of renal function
are resected resulting in steatorrhea. Resection of the prior to urinary diversion, as this may have an impact
ileocaecal valve can result in bacterial overgrowth of on future decisions. Long-term monitoring of renal
the ileum. This further reduces the absorptive capacity, function, at least annually, is advisable. Serum creatinine
resulting again in bile salt and fat malabsorption. is not a sensitive parameter of renal function. The use
Resection of larger parts of the colon can diminish of renal ultrasound together with serum creatinine is to
absorptive capacity for the alkaline ileal content and be considered a screening method of the upper urinary
can manifest in dehydration and metabolic acidosis. The tract. When in doubt, or when a more precise idea of
above described bowel dysfunctions seem to be more renal function is required, nuclear scans to determine
prevalent in patients with underlying neurogenic disease. the GFR or diuretic renograms should be performed,
Diarrhea is clinically the most important element to or 24h creatinine clearance should be determined. In
diminish quality of life after urinary diversion (6). In patients with diminished renal function, baseline renal
general, nutritional deficiencies are rare since large function should be determined prior to diversion.
portions of jejunum are not used for urinary diversions.
The treatment of persisting bothersome diarrhea Acid Base Abnormalities
after urinary diversion consists of increased dietary In the bowel lumen, sodium (Na+) is secreted in
fiber intake (in general in fruits, vegetables, whole exchange for hydrogen (H+); bicarbonate (HCO3-) in
grain products), diminished fat intake and adding exchange for chloride (Cl-). Since urine generally has
cholestyramine if necessary. The dose of cholestyramine high concentrations of ammonia (NH3), ammonium
has to be increased gradually from 4 g b.i.d. to 8 g b.i.d. (NH4+), hydrogen and chloride, these substances
and should be taken separately from other medication. are reabsorbed in bowel segments exposed to urine.
Long term, high dose use of cholestyramine can induce Inevitably, the presence of ileal and/or colonic urinary
deficiency of fat soluble vitamins. If these measures (continued on page 24)

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(continued from page 20) in accordance with serum bicarbonate levels and will
diversions implies a chronic acid load. Whether this be stopped in a large proportion of patients. Of course,
also results in important metabolic acidosis for the it will be restarted when low serum bicarbonate levels
patient depends on the specific patient (comorbidities), are encountered, even in conduit patients.
the bowel segment used, and the duration of contact of Alkalinizing therapy with oral sodium bicarbonate
the bowel segment with urine (13). A mild, subclinical (1 to 2 g t.i.d.) is our routine therapy in restoring normal
hyperchloremic metabolic acidosis is encountered in acid-base balance, but flatulence may diminish tolerance
all patients that undergo urinary diversion using ileal for this therapy. Sodium citrate (1 to 3 g q.i.d.) is a
and/or colonic segments. Probably, up to 20% of these valuable alternative, but has a bad taste. When sodium
patients will have episodes of severe acidosis (14); loads are to be avoided (fluid retention/pulmonary
reduced kidney function increases this problem. An edema, hypertension) nicotinic acid (500 mg q.d. to 2
ileal conduit uses much less bowel length and has a g q.d. extended release tablets) or chlorpromazine (25
much shorter contact time with urine when compared to 50 mg q.i.d.) can diminish the need for alkalinizing
to a neobladder or continent diversion. Therefore, the agents, through inhibition of cyclic AMP mediated
metabolic challenge to the patient is much smaller. chloride ion transport (15, 16).
Ten percent of patients with an ileal conduit have
been reported to have a clinically important metabolic Electrolyte Abnormalities
acidosis after a median follow up of 1 year (13). In Patients with urinary diversion suffer from depleted
severe cases, this can result in muscle weakness and body potassium loads due to intestinal loss (secretion)
bone demineralization. In prospective series, the rate of and renal wasting. In general, this hypokalemia will
metabolic acidosis in continent diversion and orthotopic not have important clinical consequences. One has
bladder replacement varies between 26 - 45%. to realize, however, that when metabolic acidosis is
The definition of metabolic acidosis is not treated, potassium is exchanged with the intracellular
universal; a venous sample bicarbonate level of < 21 space in the body resulting in further potassium
mmol/L is often used (11). It is important to take a depletion. Clinically, this can become apparent by
venous blood sample in the follow up of patients with muscle weakness. Several case reports of patients
urinary diversion. We will start alkalinizing therapy in presenting with general muscle weakness, mistaken for
all patients that undergo continent urinary diversion or a Guillain-Barré syndrome, after ureterosigmoïdostomy
neobladder on removal of the catheters in the immediate are reported in the literature (17-19). Therefore, one
postoperative phase. Patients with an ileal conduit will should not forget to supplement potassium (potassium
not receive routine alkalinizing therapy. In the first year citrate 15 mEq (approximately 1.6 g b.i.d. to q.i.d.)
we will see our patients for follow up at 6 weeks and at when correcting acidosis in urinary diversion (20).
2-3 month intervals. Alkalinizing therapy is diminished Chronic metabolic acidosis in patients with urinary
Table 3. Suggested Follow Up Scheme of Patients with Urinary Diversion
Parameter Pre 6W 3M 6M 12M 18M 24M Yearly

Bicarbonate X X X X X X X X

Ionogram X X X X X X X X

Creatinin X X X X X X X X

Vit B12 X X

Kidney Ultrasound X X X X

Bone Densitometry ? ? ? ?

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diversion is continuously buffered by bone carbonate. Radiotherapy may further predispose patients to this
This results in continuous calcium release from bone. kind of malabsorption (22). In the well-nourished
This excess of serum calcium is excreted by the kidneys, patient body stores of vitamin B12 are sufficient for
where the presence of acidosis and sulfate further 3 to 5 years. Clinically, insidious but irreversible
inhibit calcium reabsorption (21). Clinical important neurological deficits and megaloblastic macrocytic
hypocalcaemia is not frequent. More importantly, these anemia will occur. In our institution, we routinely check
metabolic changes will influence bone mineralization, serum vitamin B12 levels after urinary diversion on a
as will be discussed further in the article. Calcium yearly basis starting two years after diversion. When
supplements (500 mg to 1 g q.d.) are the treatment of vitamin B12 deficiency is suspected, supplementation is
choice. started. Oral supplementation with high doses (1 to 2 g
Hypomagnesaemia is a rare condition after urinary q.d.) might be as effective as parenteral (intramuscular
diversion. Nutritional depletion often plays an important or subcutaneous) administration (1 g monthly) (23).
role, with associated renal wasting since renal tubular
magnesium reabsorption is influenced by the altered Calculus Formation
calcium and sulfate metabolism, as well as by the A hyperchloremic metabolic acidosis results in an
acidosis (21). increased renal calcium and hydrogen excretion and
is often associated with hypocitraturia. The presence
Vitamin B12 of fat malabsorption can induce hyperoxaluria. Both
Vitamin B12 from food is bound to intrinsic factor will induce calcium phosphate and/or calcium oxalate
(secreted in the stomach) and this complex is absorbed stone formation. The tendency for dehydration in
in the terminal ileum. Loss of important portions of diverted patients further increases susceptibility to
stomach, or the use of the terminal ileum in urinary stone formation. Chronic colonization/infection of the
diversion, can result in vitamin B12 deficiency. diversion, especially with urease producing bacteria,

Table 4. Gastrointestinal Segments Used in Urinary Diversion

Type of Urinary Bowel Segments Used
Diversion (ileal and ileocolonic segments are the most frequently used segments)

Stomach Jejunum Ileum Ileo-colic Colon Rectum

Segment

Non-continent Jejunal Ileal conduit Colonic

conduit (Bricker) conduit
Continent

Pouch Gastric Mainz,

continent Le Bag, Indiana
urinary
reservoir
Neobladder Camey II, Mainz, Detubularized
Hautmann, Le Bag, Indiana right colon,
Kock,Stüder, sigmoid
N-pouch neobladder

Anal Uretero- Modified

Continence sigmoidostomy, rectal bladder
Mainz II

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will result in struvite and/or carbonate apatite stones. As and patients with impaired kidney function). At least,
a result, the incidence of renal stone formation increases increased attention to the risk of osteoporosis should be
in patients with intestinal urinary diversion. After 20 paid in these patient groups. Asymptomatic adults with
years of follow up, up to 20% of patients with ileal normal renal function probably do not need specific
conduits will have renal calculi (14). In routine follow bone density monitoring (27).
up of diverted patients, timely ultrasound of the kidney Treatment of metabolic acidosis by oral sodium
has to be incorporated to detect stone formation. bicarbonate or other alkalizing agents and administration
In the bowel segment used in the diversion, of vitamin C supplements (500 mg to 1g/24h) are able
calculus formation can occur, partly due to the above to avoid bone demineralization (28, 29). In severe
mentioned metabolic changes. In addition, the presence cases, supplemental vitamin D and calcium may also
of foreign materials (such as sutures and staples) will be necessary.
act as a nidus. Intestinal mucus can also function as
a nidus for calcifications as well as harbor chronic Hepatic Metabolism
infection, resulting again in struvite stone formation. Urinary diversion results in increased ammonia
The presence of residual urine after catheterization reabsorption from urine in the bowel segments. The
or micturition is an important risk factor for calculus normal liver can adapt easily to this increased load. A
formation and infection. Pouch calculi are reported in protein rich diet will further increase the ammonia load.
about 10% of patients with continent diversion. Initial The liver uses ammonia in the ornithine cycle to create
reports mentioned up to 25% of calculi in certain urea, which is in turn secreted through the kidneys.
pouches. Probably exposed staples in these techniques Preexisting hepatic disease can hinder the clearance of
were responsible for these very high rates (24-26). ammonia, resulting in hyperammonemia. Infection with
The number of calculi in orthotopic neobladders is urea producing bacteria (Proteus mirabilis, Klebsiella
generally lower, probably due to better emptying of oxytoca, etc.) further increases the ammonia load in an
these reservoirs. acute way. In addition, endotoxins significantly affect
hepatic transport and metabolism (30). Certainly in the
Bone Metabolism case of urinary obstruction, such an infection can lead to
In theory, a major effect of urinary diversion on bone hyperammonemic encephalopathy and even to hepatic
metabolism is demineralization and is to be expected. coma (31). This is the most frequent cause of altered
. The chronic metabolic hyperchloremic acidosis is sensorium in patients with urinary diversion. In the
buffered by bone minerals. Mobilization of calcium, absence of obstruction or in patients with non-continent
carbonate and sodium results in demineralization. diversion such as an ileal conduit, the occurrence of
Secondly, acidosis impairs renal activation of vitamin these complications is extremely rare.
D, which is necessary for normal bone mineralization. Treatment consists of drainage of the obstructed
Acidosis also activates osteoclasts, resulting in bone diversion along with antibiotics. The use of non-
resorption. Due to the use of bowel segments in urinary absorbable disaccharides (e.g. lactulose enemata) and
diversion, intestinal absorption of calcium and vitamin oral neomycin can diminish the nitrogen load for the
D can also be impaired. Parathormone does not seem to patient. Although protein restriction may be advised,
play a role in demineralization after urinary diversion. there is debatable evidence for this (32).
Severe bone demineralization leading to osteomalacia
in adults, or rickets in children, is not seen in current Abnormal Drug Kinetics
series of patients with urinary diversion. Every clinician that sees patients with urinary diversions
At the clinical level, asymptomatic adults with has to be aware that drug kinetics may be altered after
normal renal function do not seem to have major changes urinary diversion. Substances that are secreted in urine
in bone mineral density (27). However, patients with can be reabsorbed by the intestinal segments that are
diminished renal function are particularly at risk for incorporated into the urinary tract. This might have
bone demineralization, as well as women and children. consequences for both diagnostic and therapeutic
It is thus not clear to what extent patients should be purposes. The clinical significance of this process
screened (repeated bone densitometry) or prevention is difficult to summarize in general terms, since an
undertaken in groups at risk (such as women, children (continued on page 28)

26 Practical Gastroenterology  •  july 2012

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(continued from page 26)

important interindividual variability in ileal absorption 12. Kristjansson, A., L. Wallin and W. Mansson, Renal function up
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28 Practical Gastroenterology  •  july 2012