Kidney and metabolic complications following urinary diversion

INTRODUCTION — Urinary diversion is a surgical procedure in which the normal flow of urine out of the body is rerouted away from the bladder. In adults this procedure is most commonly performed following cystectomy due to medically refractory invasive bladder cancer [1]. Other indications for cystectomy include neurogenic bladder disease due to spinal cord lesions, urinary incontinence, vesicovaginal fistulae, scarring due to infection or chemotherapy. In infants and children, urinary diversion is required to treat bladder exstrophy disorders, various congenital anomalies, and failed reconstruction of congenital anomalies [2,3].

There are three major forms of urinary diversion performed in patients requiring a cystectomy (see "Urinary diversion and reconstruction following cystectomy" and "Radical cystectomy"):

●Intestinal conduit – A non-continent cutaneous diversion in which the urine flows from the ureters through an isolated segment of vascularized bowel (usually from the ileum [termed ileal conduit] and less commonly from the jejunum or colon) to the skin surface as a stoma, where it is collected in an external bag or other appliance.

●Continent cutaneous diversion – A cutaneous continent reservoir may be constructed to avoid the need for an external appliance (usually using a segment of right colon and terminal ileum). The patient self-catheterizes at regular intervals to empty the reservoir [4].

●Orthotopic neobladder – An orthotopic neobladder may be formed from several segments of bowel and attached to the urethra. This enables patients to void through their urethra. Continent diversions can greatly improve patient quality of life and self-image and also increase acceptance of radical cystectomy.

Ureterosigmoidostomy was more commonly used in the past but is now used infrequently due to a high rate of complications. However, it is still performed in some complex pediatric cases in resource-limited settings. Also, clinicians may still encounter patients who have had this procedure. Although infrequent, a segment of bowel can be interposed between the pelvis of the kidney and the bladder when the ureter is damaged beyond repair.

These techniques and their complications are discussed elsewhere in detail:

●(See "Urinary diversion and reconstruction following cystectomy".)

●(See "Radical cystectomy".)

The interposition of bowel into the urinary tract is associated with a variety of potential kidney and metabolic complications [5,6]:

●Deterioration of kidney function due primarily to obstruction of urine flow (see 'Kidney function decline' below)

●Urinary tract infections (see "Urinary diversion and reconstruction following cystectomy", section on 'Complications')

●Nephrolithiasis (see 'Nephrolithiasis' below)

●Metabolic disturbances (see 'Metabolic disturbances' below)

KIDNEY FUNCTION DECLINE — Kidney function decline is relatively common in patients following urinary diversion, as discussed elsewhere. (See "Urinary diversion and reconstruction following cystectomy", section on 'Impaired renal function'.)

The major causes of kidney injury in such patients include:

●Reflux nephropathy

●Infection

●Stenosis of the ureteral-intestinal anastomosis

●Nephrolithiasis

●Prerenal azotemia

It is important that continent urinary diversions have low storage and emptying pressures since high pressures can lead to reflux nephropathy and pressure-induced kidney injury [7]. Reflux of urine into the urinary pelvis can also predispose to ascending urinary tract infections and pyelonephritis, further contributing to progressive loss of kidney function.

To ensure a low-pressure system, all bowel segments used for diversion are usually detubularized and then refashioned into a more spherical shape. This maneuver allows for greater holding capacity and reduced luminal pressures compared with unaltered segments. (See "Urinary diversion and reconstruction following cystectomy", section on 'Continent cutaneous diversions'.)

In addition to reflux nephropathy, stenosis of the ureteral-intestinal or intestinal-cutaneous anastomosis and nephrolithiasis may cause urinary obstruction resulting in kidney function decline.

Prerenal kidney dysfunction may develop because some patients who undergo extensive resection of the terminal ileum during ileal conduit creation can develop diarrhea due to malabsorption of bile salts and fat as well as bacterial overgrowth. (See "Urinary diversion and reconstruction following cystectomy", section on 'Nutritional and metabolic abnormalities'.)

NEPHROLITHIASIS — Patients with urinary diversion are at increased risk for development of upper tract calculi, particularly those composed of struvite. (See "Kidney stones in adults: Struvite (infection) stones".)

Important risk factors for this complication are chronic bacteriuria with urease-producing organisms and upper urinary tract dilatation associated with urinary stasis. The maintenance of sterile urine is important in minimizing the risk of stones in these patients. In patients with recurrent struvite stones, antibiotic prophylaxis and surveillance may be warranted.

METABOLIC DISTURBANCES — The nature and severity of metabolic disturbances are primarily a function of the duration of contact time between the urine and bowel, the total surface area of bowel exposed to urine, and the anatomic origin of the bowel segment utilized for the anastomosis (table 1).

Metabolic acidosis — A hyperchloremic (normal anion gap) metabolic acidosis develops in up to 80 percent of patients who underwent ureterosigmoidostomy [8-10]. In such patients, urine is exposed to a large surface area of colonic mucosa for a prolonged period of time. The colon has an abundant luminal anion exchanger (SLC26A3) that absorbs chloride and secretes bicarbonate. Thus, when chloride-rich urine enters the colon, the chloride is absorbed in exchange for bicarbonate, resulting in bicarbonate loss, and chloride retention.

Metabolism of urinary urea by intestinal bacteria is another potential mechanism for metabolic acidosis in patients with a ureterosigmoidostomy [8]. Urea delivered to the colon is metabolized to ammonium and bicarbonate. Bicarbonate generated from urea may be excreted unchanged in the stool, or it may react with organic acids such as lactate or butyrate, and those anions are excreted instead of bicarbonate. Intestinal absorption of the ammonium ions, either in exchange for sodium or together with chloride, represents an acid load. The absorbed ammonium ions are transported via the portal circulation to the liver where they are metabolized to urea. The process of urea synthesis generates two hydrogen ions per molecule of urea synthesized. The net effect is the loss of NaHCO₃ or the addition of hydrochloric acid to body fluids.

Metabolic acidosis is much less likely to develop in patients who have a well-functioning ileal, jejunal, or colonic conduit. Rapid drainage of urine into an external collection bag limits the contact time between the urine and intestinal mucosa, thereby preventing significant changes in urinary composition [9,11]. However, metabolic acidosis can develop if contact time is increased due to malfunction of the loop (most often the result of a stomal [anastomotic] stenosis). Thus, a loopogram should be performed when an otherwise unexplained metabolic acidosis develops in a patient with an intestinal loop conduit. When acidosis occurs in such patients, ileal absorption of urinary ammonium may be a more important mechanism of metabolic acidosis than chloride-bicarbonate exchange [10,12].

Hypokalemia — Hypokalemia is common with ureterosigmoidostomy and sigmoid loop bladders, although the mechanism is unclear [13]. Hypokalemia is less common with ileal as compared with sigmoid diversions, perhaps because the sigmoid secretes potassium while the ileum does not.

Hypokalemia may also result from renal losses. First, systemic acidosis can lead to renal potassium wasting [14]. Metabolic acidosis is associated with decreased net proximal Na⁺ reabsorption [14,15]. The subsequent increase in distal delivery leads to volume contraction and activation of the renin-angiotensin-aldosterone system. The renin-angiotensin-aldosterone system may also be activated by the "inappropriate" loss of HCO₃ salts generated by the intestinal segment. The combination of increased distal Na⁺ delivery and aldosterone increases renal K⁺ excretion.

The metabolic acidosis associated with a ureteral diversion can usually be corrected by the administration of sodium bicarbonate or potential bicarbonate salts such as sodium or potassium citrate. When patients present with severe potassium deficits, it is important that the potassium replacement be initiated before the administration of any bicarbonate salts. Otherwise, correction of the acidosis can further reduce the serum potassium concentration to dangerous levels. There are case reports of patients with ureterosigmoidostomy developing severe muscle weakness due to hypokalemia and mistakenly diagnosed with Guillain-Barré syndrome [16,17].

Hyperammonemic encephalopathy — Hyperammonemic encephalopathy is an unusual complication of ureteral diversion that typically develops in patients who also have chronic liver disease or acute hepatic dysfunction. In such patients, the ammonia that is derived from intestinal metabolism of urine urea is absorbed and cannot be efficiently metabolized. This may generate hyperammonemia and encephalopathy.

Stomal obstruction may also exacerbate hyperammonemia by increasing exposure time of the urine with intestinal mucosa. In addition, urinary infection caused by bacteria that hydrolyze urea to ammonium, such as Proteus mirabilis and Klebsiella oxytoca, can markedly increase ammonia levels, even in the absence of liver dysfunction [18].

Thus, patients with a ureteral diversion who develop high ammonia levels should be evaluated and, if necessary, treated for acute or chronic liver disease, urinary tract obstruction, and urinary tract infection.

Hyperkalemia and hyponatremia with ureterojejunostomy — Anastomosis of the ureter to a segment of jejunum can lead to hyperkalemia since the jejunum normally absorbs potassium [8,11]. This complication developed in a 77-year-old man undergoing extensive pelvic surgery for treatment of rectal carcinoma [19]. Due to the presence of multiple pelvic adhesions, the ureters were inadvertently diverted into a section of the jejunum. Upon institution of enteral feedings containing a high-potassium content, the patient quickly developed hyperkalemia.

The jejunum also avidly absorbs electrolyte-free water, which can lead to hyponatremia in patients who drink large amounts of water. Although the urine excreted by the kidney may be dilute, as it passes through the jejunum, urinary osmolality rises to the level of plasma osmolality because electrolyte-free water is absorbed by the bowel mucosa.

Isolated loops of jejunum have been utilized as bladder replacement when the ileum or colon cannot be used [20]. The development of hyperkalemia, hyponatremia, and a normal gap acidosis following diversion of urine into the jejunum is referred to as the jejunal conduit syndrome. Its severity is related to the length of the jejunal segment that is used [20].

Metabolic alkalosis with gastrocystoplasty — Gastric acid loss leading to a metabolic alkalosis can result from gastrocystoplasty [21,22]. Although not commonly performed, this procedure involves implantation of a gastric patch onto the bladder. The gastric mucosa retains its normal secretory function and, depending upon the patch size, can produce significant acid loss from the body into the urine. Exposure of the gastric patch to an alkaline urine increases gastrin secretion, as does mechanical stretch of the patch. High gastrin levels stimulate hydrogen ion secretion. Thus, serum gastrin and serum bicarbonate concentrations are correlated in these patients [11]. Proton pump inhibitors can be used effectively to reduce acid secretion by the gastric patch.

In some patients, the markedly acid urine can damage the remaining bladder mucosa, resulting in dysuria and hematuria. Another long-term complication of gastric patch bladder augmentation procedures is an increased risk of malignancy in the gastric patch [23].

Effects on mineral metabolism — Chronic metabolic acidosis is partially buffered in the skeleton, which releases bone calcium. The combination of metabolic acidosis and loss of bone calcium can lead to both bone demineralization (with possible rickets or osteomalacia) and hypercalciuria. Metabolic acidosis also reduces urine citrate levels, which predisposes these patients to the development of calcium-containing kidney stones [9,11]. (See "Kidney stones in adults: Epidemiology and risk factors".)

However, struvite stones are also common as a result of chronic urinary infection with urease-producing organisms [24]. (See "Kidney stones in adults: Struvite (infection) stones".)

SUMMARY

●Types of urinary diversion – Urinary diversion is a surgical procedure in which the normal flow of urine out of the body is rerouted away from the bladder. This procedure is most commonly performed following cystectomy due to medically refractory invasive bladder cancer. There are three major forms of urinary diversion performed in patients requiring a cystectomy (see 'Introduction' above):

•Intestinal (usually ileal) conduit – A non-continent cutaneous diversion in which the urine flows from the ureters through a segment of bowel (usually ileum, termed ileal conduit) to the skin surface as a stoma, where it is collected in an external bag or other appliance.

•Continent cutaneous diversion – A cutaneous continent reservoir may be constructed to avoid the need for an external appliance (usually using the right colon and terminal ileum). The patient uses self-catheterization at regular intervals to empty the reservoir.

•Orthotopic neobladder – An orthotopic neobladder may be formed from a segment, or combined segments, of bowel and attached to the urethra. This enables the patient to void through the urethra. Continent diversions can greatly improve patient quality of life and self-image and can increase the acceptance of radical cystectomy. These neobladders can be created in both males and females.

Although ureterosigmoidostomy is now a rare procedure, clinicians still encounter patients with this form of urine diversion. This form of diversion generates the common and most severe metabolic complications (and risk of malignancy).

●Kidney and metabolic complications of urinary diversion – The interposition of bowel into the urinary tract is associated with a variety of potential kidney complications:

•Deterioration of kidney function is primarily due to obstruction of urine flow. Urinary tract infection and prerenal azotemia may also contribute to kidney dysfunction. Low pressure, high compliance diversions reduce this complication risk. (See 'Kidney function decline' above.)

•Urinary tract infections. (See "Urinary diversion and reconstruction following cystectomy", section on 'Complications'.)

•Nephrolithiasis, primarily upper tract calculi composed of struvite. (See 'Nephrolithiasis' above.)

•Metabolic disturbances, including (see 'Metabolic disturbances' above):

-Metabolic acidosis, most commonly a non-anion gap (hyperchloremic) acidosis (see 'Metabolic acidosis' above)

-Hypokalemia (see 'Hypokalemia' above)

-Hyperammonemic encephalopathy, typically in patients with acute or chronic liver disease (see 'Hyperammonemic encephalopathy' above)

-Hyperkalemia and hyponatremia if a ureterojejunostomy is created (see 'Hyperkalemia and hyponatremia with ureterojejunostomy' above)

-Metabolic alkalosis if a gastrocystoplasty is performed (see 'Metabolic alkalosis with gastrocystoplasty' above)

-Bone demineralization (see 'Effects on mineral metabolism' above)

Metabolic acidosis, hypokalemia, and hyperammonemic encephalopathy were most common with ureterosigmoidostomy diversion.