Inflammatory bowel diseases (IBD), like ulcerative colitis (UC) and Crohn’s disease (CD), are associated with numerous extra-intestinal manifestations. Commonly studied urinary extra-intestinal manifestations found in CD include urolithiasis, urinary tract infections (UTI), and cystitis. However, these rates have not been well characterized in cross-race analyses.
The literature reviewed for this study identifies an association between CD and urolithiasis, specifically calcium oxalate stones and urate stones. Some have shown that the incidence of urolithiasis in CD ranges from 4 to 23% and that there is a 10-100 times increased risk of urolithiasis in CD patients as compared to the general population and UC patients [1]. The mechanism behind the increased calcium oxalate stone formation in CD is related to an increase in urinary oxalate excretion that is directly related to bile salt malabsorption. Under normal conditions oxalate is bound to calcium in the intestinal lumen, which limits the amount of oxalate absorbed in the intestines. In patients with a diseased or resected ileum, bile salts are poorly reabsorbed in the intestines leading to steatorrhea. The unabsorbed fats in the steatorrhea bind to the free calcium in the lumen and allow the intestines to absorb the excess oxalate [2]. Urate stones have been shown to be related to both lengthy diarrheal illnesses and surgeries that create small bowel ostomies. It is believed that the reason urate stones form after small bowel ostomies is due to dehydration and metabolic acidosis associated with the procedure. These stones form from acidic urine that results from intestinal fluid and bicarbonate loss allowing for urate stones to precipitate even if the patient’s urate concentration is not elevated [2, 3].
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UC is a chronic disease that is accompanied by intermittent diarrhea, which puts these patients at increased risk of urate renal calculi. Regardless of the disease severity, active UC represents a significant risk factor for the formation of renal calculi [4]. Studies have shown that asymptomatic nephrolithiasis in the UC and CD community is so common that IBD patients with renal dysfunction should be screened for kidney stones to prevent severe complications like UTIs, renal failure, and sepsis [4, 5].
Besides nephrolithiasis, uncomplicated UTIs, defined as cystitis and lower UTIs, are also associated with urinary extra-intestinal complications in IBD. Cystitis is the most common urinary problem in patients with CD. Furthermore, the most severe complications from cystitis occur in male patients, even though most of the affected patients are female [6, 7]. CD patients with perianal disease, which includes perianal abscesses and anal fistulas, have been shown to have an increased risk for UTIs by promoting bacterial translocation from the perineum to the bladder. In UC, independent predictors for UTI formation were disease duration over 11 months and age over 40 years old, possibly due to a degree of immunosuppression in elderly people. Even though IBD patients have an increased risk of UTIs, there were no significant differences between the rate of UTI diagnoses between CD and UC [8].
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Medications used to treat IBD can potentially influence the frequency of urinary extra-intestinal manifestations. It has been well documented that steroids increase the risk of infections and that their use in preoperative IBD patients undergoing elective bowel surgery have been associated with increased risk of infections [9, 10]. Other commonly used medications used to treat IBD include mesalamine, thiopurines, and anti-TNF monoclonal antibodies. Mesalamine is primarily active on the intestinal mucosa where it is believed to exerts its anti-inflammatory effect via the peroxisome proliferator-activated receptor (PPAR)-y [11]. Even though mesalamine is considered a relatively safe drug, it can lead to further precipitation of renal stones [12]. Anti-TNF monoclonal antibodies work differently by blocking the inflammatory molecule called tumor necrosis factor. Two of the most common anti-TNF antibodies are infliximab and adalimumab and it has been shown that the fourth most common site of infection in this class of medication was the urinary tract [13, 14].
Racial disparities in urinary comorbidities have not been well characterized in cross-race analysis and, when they have been studied, there are conflicting results. For instance, one study has shown that urolithiasis disproportionately affects Caucasian patients and that there is a 1.7% reduced risk of nephrolithiasis in African Americans [15]. Another study has shown that, after the age of 25, kidney stones become more common among men and that the incidence in African Americans increased 12% more than Caucasians every five years, regardless of gender [16]. When it comes to UTI incidence and prevalence among African Americans there has been little data examining the general population and most of the literature tends to examine the incidence in children, febrile infants, and pregnant mothers.
There are two purposes of this study and the first one is to establish the frequency of common urinary extra-intestinal manifestation in CD and UC. The second purpose is to determine at what rate these urinary extra-intestinal manifestations affect the African American and Caucasian IBD populations.
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