Pregnancy and severely reduced renal mass: A stress model showing renal hyperfiltration.

Pregnancy may increase signs of renovascular stress. We compared pregnant sham operated (S) and 5/6 nephrectomy (NX) rats to examine the effect of pregnancy on reduced nephron number. Blood pressure (BP), heart rate (HR), body weight (BW), food/water intake, serum creatinine (Cr), urinalyses were assessed weekly, and end pregnancy renal histology examined. NX showed decreased BW, elevated BP and Cr, and proteinuria. Histology revealed increased glomerular volume, increased tubular diameter and interstitial inflammation and fibrosis. This pilot shows that a pregnant 5/6th nephrectomy rat is a reliable model in which to evaluate renovascular stress with reduced nephrons.

New and developing diagnostic technologies for urinary tract infections.

Timely and accurate identification and determination of the antimicrobial susceptibility of uropathogens is central to the management of UTIs. Urine dipsticks are fast and amenable to point-of-care testing, but do not have adequate diagnostic accuracy or provide microbiological diagnosis. Urine culture with antimicrobial susceptibility testing takes 2-3 days and requires a clinical laboratory. The common use of empirical antibiotics has contributed to the rise of multidrug-resistant organisms, reducing treatment options and increasing costs. In addition to improved antimicrobial stewardship and the development of new antimicrobials, novel diagnostics are needed for timely microbial identification and determination of antimicrobial susceptibilities. New diagnostic platforms, including nucleic acid tests and mass spectrometry, have been approved for clinical use and have improved the speed and accuracy of pathogen identification from primary cultures. Optimization for direct urine testing would reduce the time to diagnosis, yet these technologies do not provide comprehensive information on antimicrobial susceptibility. Emerging technologies including biosensors, microfluidics, and other integrated platforms could improve UTI diagnosis via direct pathogen detection from urine samples, rapid antimicrobial susceptibility testing, and point-of-care testing. Successful development and implementation of these technologies has the potential to usher in an era of precision medicine to improve patient care and public health.

Dietary fructose in pregnancy induces hyperglycemia, hypertension, and pathologic kidney and liver changes in a rodent model.

PURPOSE: The incidence of pregnancies complicated by hyperglycemia and hypertension is increasing along with associated morbidities to mother and offspring. The high fructose diet is a well-studied model that induces hyperglycemia and hypertension in male rodents, but may not affect females. We hypothesized that the physiologic stress of pregnancy may alter metabolic responses to dietary fructose. MATERIALS AND METHODS: In this study female Sprague-Dawley rats were divided into two gestational dietary groups: (1) 60% carbohydrate standard rat chow (Pregnant-S-controls) and (2) 60% fructose enriched chow (Pregnant-F). Body weight, blood pressure, blood glucose, triglycerides, and insulin were measured in pregnancy and during the post-partum period. Maternal organ weight and histological changes were also assessed after delivery. RESULTS: By midpregnancy Pregnant-F rats had increased weight, elevated blood pressure, higher fasting glucose, and elevated triglycerides compared with Pregnant-S rats. Both groups demonstrated elevated gestational insulin levels with signs of insulin resistance (increased HOMA-IR). Pregnant-F rats showed significant histopathologic hepatic steatosis and renal tubular changes characterized by tubular dilation and glomerulosclerosis. CONCLUSION: Our study provides a model in which dietary change during pregnancy can be examined. We demonstrate, moreover, that high dietary fructose ingestion in pregnant rats may result in profound systemic and pathologic changes not appreciated during routine pregnancy.

Testosterone changes bladder and kidney structure in juvenile male rats.

PURPOSE: Testosterone affects male development, maturation and aging but limited data exist on testosterone effects on the juvenile genitourinary system. We hypothesized that testosterone has bladder and kidney developmental effects, and investigated this in juvenile male rats. MATERIALS AND METHODS: To examine the testosterone effect 21-day-old prepubertal male Wistar rats were divided into 3 groups of 12 each, including sham orchiectomy as controls, and bilateral orchiectomy with vehicle and bilateral orchiectomy with testosterone. Starting at age 28 days (week 0) testosterone enanthate (5 mg/100 gm) or vehicle was injected weekly. Testosterone was measured at study week 0 before injection, and at weeks 1, 6 and 16. Whole bladders and kidneys were evaluated for androgen receptor, bladder collagen-to-smooth muscle ratio, and renal morphometry and immunohistochemistry. RESULTS: Testosterone was not detectable at week 0 in all groups. It remained undetectable at weeks 1, 6 and 16 in the orchiectomy plus vehicle group. Testosterone levels were physiological in controls and rats with orchiectomy plus testosterone but levels were higher in the latter than in the former group. Rats with orchiectomy plus testosterone had increased bladder-to-body and kidney-to-body weight ratios (p<0.01 and <0.05, respectively), and decreased collagen-to-smooth muscle ratio than the orchiectomy plus vehicle and control groups. Rats with orchiectomy plus testosterone had a lower renal total glomerular count (p<0.01) but increased androgen receptor density. CONCLUSIONS: In juvenile male rats testosterone was associated with increased bladder and renal mass, and increased bladder smooth muscle. Testosterone associated kidneys also appeared to have fewer but larger glomeruli. These data support an important role for sex hormones in structural and functional development of the bladder and kidney.

Evaluation of dynamic contrast-enhanced MRI in detecting renal scarring in a rat injury model.

PURPOSE: To create a reliable rat model with small renal cortical scars and evaluate the accuracy and sensitivity of dynamic contrast-enhanced MRI in detecting the kinds of lesions that are associated with reflux nephropathy. MATERIALS AND METHODS: In 16 rats, three unilateral renal cortical lesions were created using either electrocautery or pure alcohol with the contralateral kidney serving as control. MRI on a 1.5 Tesla GE Signa was performed 10-14 days after surgery. After bolus injection of 0.2 mM/Kg Gd-DTPA, sequential MRI acquisitions were performed using a 4-inch quadrature birdcage coil. Renal and scar volumes and pathology were compared after scanning and killing. RESULTS: Of the 48 points of injury, 40 (83%) in the 16 rats were detected grossly. Under microscopy, 36 injuries (75%) were detected on mid-kidney cross-sections. The average lesion was 4.2 mm(3) corresponding to 0.5% of the kidney volume. Using pathological findings as the gold standard, the sensitivity and specificity of scar detection using MRI was 69% and 93%, respectively. CONCLUSION: A rat model was created to demonstrate the sensitivity of dynamic contrast-enhanced MRI for detecting renal scars. Alcohol and electrocautery created reliable renal scars that were confirmed pathologically. MRI detected these lesions that averaged 4.2 mm(3) (0.5% total renal volume) with sensitivity and specificity of 69% and 93%, respectively.

Urinary tract infection in children: etiology and epidemiology.

The urinary tract is a relatively common site of infection in infants and young children. Urinary tract infection (UTI) may result in significant acute morbidity, as well as longterm medical complications. Recent advances elucidating the pathogen-host interaction have broadened the understanding of the pathogenesis and clinical progression of pediatric UTI. This article focuses on the epidemiology and pathogenesis of pediatric UTI, and briefly discusses UTI-related complications.

Urinary tract infection at the age extremes: pediatrics and geriatrics.

Urinary tract infections (UTIs) are common and generally benign conditions among healthy, sexually active young women without long-term medical sequelae. In contrast, UTIs are more complicated among those individuals at either end of the age spectrum: infants/young children and geriatrics. UTI in children younger than 2 years has been associated with significant morbidity and long-term medical consequences, necessitating an extensive and somewhat invasive imaging evaluation to identify possible underlying functional or anatomic abnormalities. Pediatric UTI should be considered complicated until proved otherwise, and treatment should reflect the severity of signs and symptoms. Management in the acutely ill child frequently involves parenteral broad-spectrum antimicrobial agents, and less ill children can be treated with trimethoprim- sulfamethoxazole (TMP-SMX), beta-lactams, and cephalosporins.UTI among older patients (>65 years) may be complicated by comorbidities, the baseline presence of asymptomatic bacteriuria, and benign urinary symptoms that can complicate diagnosis. The etiology of UTI encompasses a broader spectrum of infecting organisms than is seen among younger patients and includes more gram-positive organisms. Symptomatic UTI is generally more difficult to treat than among younger populations. Management should be conservative, of longer treatment durations, and cover a broad spectrum of possible uropathogens. Oral or parenteral treatment with a fluoroquinolone for 7 days is the preferred empiric approach. TMP-SMX can also be considered a first-line agent in women only, but only if the pathogen is known to be TMP-SMX sensitive.

Prospective study of urinary tract infections and urinary antibodies after radical prostatectomy and cystoprostatectomy.

The authors have prospectively documented that men who undergo orthotopic bladder substitution more frequently experience bacteriuria than do normal men [19] or men with carcinoma of the prostate scheduled to have radical prostatectomy (see Table 1). Because the frequency of bacteriuria in men after prostatectomy was also lower than that after orthotopic bladder substitution (see Table 1), removal of the prostate and any of its presumed antibacterial properties probably does not account for this difference. Furthermore, the authors' data (see Table 5 ) and that of Woodside and associates [23] demonstrate that intestine incorporated into the genitourinary tract generates a local antibody response against urinary bacteria. Although others have suggested that the incorporation of bowel in the urinary tract may be associated with increased bacteriuria, this effect has never been documented prospectively. The mechanism of this increased frequency of bacteriuria is unknown. Because the anatomy of the male secretory genitourinary system may be altered after radical prostatectomy and orthotopic bladder substitution, the authors evaluated local antibody production before and after these operations. More than 20 years ago, Burdon [5] found that the initial portion of the VB1 sample in men had significantly higher levels of IgA compared with the VB2 specimen, whereas the levels of IgG were similar in the two portions. This latter finding was confirmed by Shorliffe and co-workers [22] when they examined prostatic secretion. Other investigators have found high levels of IgA in human prostatic tissue and fluid. [24,25]. On the basis of these findings, it was believed that, in men, the prostate produces most of the urinary IgA, whereas the bladder or upper urinary tracts make most of the urinary IgG. Although the authors' study confirms that most local urinary tract IgG is produced by the bladder or upper urinary tracts, this study documents that the prostate is not the only source of urethral IgA in men. Despite almost complete removal or prostate secretory epithelium by radical prostatectomy, as evidenced by a dramatic fall in postoperative VB1 and VB2 PSA compared with preoperative levels (Table 3). men who had this operation had only slightly decreased IgA levels after the operation (Table 4, Fig I). The source of this IgA must be urethral because the VB1 urinary stream contains more IgA than the VB2 urine even after radical prostatectomy. The authors have not determined whether the urinary IgA concentrations observed after radical prostatectomy are the true baseline values for a man without a prostate, or whether they actually reflect abnormal production of local IgA stimulated by radical prostatectomy. Because post-prostatectomy bacteriuris occurred frequently during urethral catheter drainage, the authors screened for postoperative IgA titers to mix 1 and mix 2 to determine whether specific production of antibody against gram-negative organisms might account for some of the postoperative IgA measured. Postradical prostatectomy mix 1 and mix 2 titers were not elevated, compared with preoperative measurements. Because urethral glandular tissue other than prostatic tissue is present in the male urethra, these glands also might be responsible for significant local antibody production. The high levels of urinary IgA and IgG after cystoprostatectomy with ileal orthotopic bladder substitution document that intestine incorporated into the urinary tract is still capable of producing local antibody. This observation corresponds with the findings of Mansson and associated [26] of elevated IgA and IgG in ileal reservoir urine compared with normal urinary tracts. It has been estimated that 1 m of intestine may secrete up to 780 mg/d of IgA [27], indicating that normal intestine production of antibody alone can account for the high IgA and IgG levels found in the patients who underwent bladder substitution. Interestingly, the ratio of IgA to IgG concentration in smal intestine fluid is 2:129, similar to the ratio of IgA to IgG in bladder substitution urine (2.92.1:52, Table 4). Because mix 1 and mix 2 IgA concentrations were elevated in VB1 and VB2 urine after ileal bladder substitution (see Table 5), some of this antibody was produced by the ileal bladder substitution in response to the inevitable bacteriuria that occurs during the prolonged postoperative catheter drainage. The findings is absent after radical prostatectomy alone. In addition, some of this increased antibody might be a result of the increased bacteriuria noted in the patients who underwent ileal bladder substitution after the initial postoperative period. The significance of the increased bacteriuria and elevated antibody levels after ileal bladder substitution is unclear. Because most of these episodes of bacteriuria were asymptomatic, whether they represent clinical infections that should be treated is not known. Bishop and associates [28] found that the bacterial flora of ileal conduits with asymptomatic bacteriuria had bacterial counts of 1000 or fewer colonies, and they noted that the healthy ileum in situ may contain more than 10,000 organisms per milliliter [29]. Because the normal urinary tract is usually sterile, it is possible that the bacteriuria found by the authors after ileal bladder substitution represents some form of bowel colonization more commonly associated with the bowel rather than clinical urinary tract infection and has limited clinial importance. Trinchieri and associated [30] found that urinary from patients with ileocystoplasty prevented attachment of E. coli to human uroepithelial cells more effectively that urine from patients with recurrent urinary infections. This observation suggests that the relatively large quantities of Iga produced by the ileal bladder substitution may, in fact, prevent clinical infection by preventing tissue invasion by the bacteria. Only long-term follow-up of patients with ileocystoplasty or ileal bladder substitution will determine the clinical significance of the bacteriuria. The authors' study had documented an increased incidence of bacteriuria in men after ileal bladder substitution and no such increase after radical prostatectomy. Analysis of the data shows that male sources other than the prostate--probably urethral glands-- must produce significant quantities of local urinary tract IgA. After ileal bladder substitution, the incorporated ileum may produce volumes of local antibody that may exceed the amounts ordinarily produce by the normal urinary tract. The clinical significance of the increased incidence of bacteriuria and elevated antibody levels in patients after illeal bladder substitution is unclear.