To use receiver operator characteristic curve methodology to determine the test characteristics of microscopic hematuria for identifying urologic injuries in children who underwent computed tomography (CT) of the abdomen and pelvis as part of a trauma evaluation.
We performed a retrospective medical record review of all children from 0 to 12 years of age who presented to our pediatric emergency department within a Level 1 trauma center, had an abdominal and pelvic CT and a microscopic urinalysis as part of an initial evaluation for trauma. Urologic injury was defined as any injury to the kidneys, ureters or bladder. We defined hematuria from the microscopic urinalysis and reported by the clinical laboratory as the exact number of red blood cells per high power field (RBC/hpf).
Of the 502 children in the study group, 17 (3%; 95% CI [2%–5.4%]) had evidence of urologic injury on the abdominal or pelvic CT. Microscopic urinalysis for those children with urologic injury ranged from 0 to15,544 RBC/hpf. The remaining 485 children without urologic injury had a range of hematuria from 0 to 20,596 RBC/hpf. A receiver operating characteristic curve was generated and the area under the curve is 0.796 (95% CI [0.666–0.925]).
If the abdominal and pelvic CT is used as the criterion standard for identifying urologic trauma, the microscopic urinalysis has moderate discriminatory power to predict urologic injury.
Hematuria is one of the most common findings on urinalysis in patients encountered by primary care physicians. In many instances it can also be the first presentation of a serious urological problem. As such, we sought to evaluate current practices adopted by primary care physicians in the workup and screening of hematuria.
Questionnaires were mailed to all registered primary care physicians across Quebec. Questions covered each physician’s personal approach to men and postmenopausal women with painless gross hematuria or with asymptomatic microscopic hematuria, as well as screening techniques, general knowledge with regards to urine collection and sampling, and referral patterns.
Of the surveys mailed, 599 were returned. Annual routine screening urinalysis on all adult male and female patients was performed by 47% of respondents, regardless of age or risk factors. Of all the respondents, 95% stated microscopic hematuria was associated with bladder cancer. However, in an older male with painless gross hematuria, only 64% of respondents recommended further evaluation by urology. On the other hand, in a postmenopausal woman with 2 consecutive events of significant microscopic hematuria, only 48.6% recommended referral to urology. Findings were not associated with the gender of the respondent, experience or geographic location of practice (urban vs. rural).
There seems to be reluctance amongst primary care physicians to refer patients with gross or significant microscopic hematuria to urology for further investigation. A higher level of suspicion and further education should be implemented to detect serious conditions and to offer earlier intervention when possible.
Eosinophilic cystitis is a rare inflammatory lesion of the bladder, characterized by massive eosinophilic infiltration of the bladder wall. Its cause is not known definitely. A 49-year-old man consulted our department with a miction pain, gross hematuria, and frequent micturition. Urinalysis showed combined hematuria and pyuria, but urine culture was sterile. Abnormal findings of laboratory examination included an elevated white blood cell (WBC) count (15,700/μL) and the proportion of eosinophils in the peripheral blood was 12% of the WBCs (normal 0–5%). Cystoscopy revealed a solid mass with severe edematous mucosa. Magnetic resonance imaging (MRI) also indicated marked bladder wall thickening, which was suspected for invasive bladder cancer. Transurethral biopsy of the bladder mass was performed with pathological examination revealing features of eosinophilic cystitis. After administration of a combination of prednisolone and suplatast tosilate, followed by monotherapy with suplatast tosilate, regression of the bladder mass, and normalization of the count of peripheral eosinophils were achieved. Fourteen months after steroid therapy, under treatment with suplatast tosilate, there was no relapse of urinary symptoms and the bladder mass.
Bladder cancer is the most common malignancy in the urinary tract. Urothelial carcinoma is the most common histologic type of bladder cancer in the United States, accounting for approximately 90%. Squamous cell carcinoma is less common, making up 3-5% of bladder cancers. We present a case of squamous cell carcinoma in a female associated with multiple bladder stones.
A 76-year-old Caucasian woman presented to the emergency department with gross hematuria and dysuria for one month. Urinalysis showed many RBCs and WBCs with positive nitrite. She was admitted with an initial impression of urinary tract infection and intravenous ceftriaxone was started. Urine culture grew greater than 100,000 cfu/ml of Enterococcus species. Computed tomographic imaging of the abdomen/pelvis with oral contrast revealed a markedly distended bladder with hemorrhage, multiple calculi, and diffuse bladder wall thickening. Cystoscopy was performed for diffuse bladder wall thickening and demonstrated numerous bladder stones, a bladder mass, and organized blood clots. Biopsy of the mass was consistent with high-grade carcinoma with squamous differentiation. The bladder cancer was not surgically resectable and radical cystectomy was not recommended due to old age and poor functional status. The patient refused chemotherapy and she died in 6 months.
The association between foreign bodies in the bladder and sqaumous cell carcinoma is well established. Long-standing bladder stones have been implicated as a cause of squamous cell carcinoma of the bladder. Our female patient’s unusual presentation with multiple bladder stones and sqaumous cell carcinoma of the bladder highlights the association between these two conditions.
Squamous cell carcinoma; Urinary bladder calculi; Cystoscopy
Patients presenting with painless hematuria form a large part of the urological patient population. In many cases, especially in younger patients, the cause of hematuria is harmless. Nonetheless, hematuria could be a symptom of malignant disease and hence most patients will be subject to cystoscopy. In this study, we aimed to develop a prediction model based on methylation markers in combination with clinical variables, in order to stratify patients with high risk for bladder cancer.
Material and Methods
Patients (n=169) presenting with painless hematuria were included. 54 patients were diagnosed with bladder cancer. In the remaining 115 patients, the cause of hematuria was non-malignant. Urine samples were collected prior to cystoscopy. Urine DNA was analyzed for methylation of OSR1, SIM2, OTX1, MEIS1 and ONECUT2. Methylation percentages were calculated and were combined with clinical variables into a logistic regression model.
Logistic regression analysis based on the five methylation markers, age, gender and type of hematuria resulted in an area under the curve (AUC) of 0.88 and an optimism corrected AUC of 0.84 after internal validation by bootstrapping. Using a cut-off value of 0.307 allowed stratification of patients in a low-risk and high-risk group, resulting in a sensitivity of 82% (44/54) and a specificity of 82% (94/115). Most aggressive tumors were found in patients in the high-risk group. The addition of cytology to the prediction model, improved the AUC from 0.88 to 0.89, with a sensitivity and specificity of 85% (39/46) and 87% (80/92), retrospectively.
This newly developed prediction model could be a helpful tool in risk stratification of patients presenting with painless hematuria. Accurate risk prediction might result in less extensive examination of low risk patients and thereby, reducing patient burden and costs. Further validation in a large prospective patient cohort is necessary to prove the true clinical value of this model.
The aim of this study was to determine the relationship between hematuria and volume, position of stone, and hydronephrosis in patients with a solitary stone, using unenhanced multidetector computed tomography (MDCT).
This retrospective study evaluated the clinical and radiological records of 83 patients undergoing MDCT for the evaluation of acute flank pain and suspected renal colic, who also underwent a microscopic urinalysis at the emergency department of our hospital during a 1-year period. Inclusion criteria of the MDCT study were solitary urolithiasis and cumulative stone diameter under 1 cm.
A total of 83 patients were included in the study, with a mean age of 42.1±14.4 years; 48 (57.8%) were females and 35 (42.2%) were males. Detection of 5 or more red cells on urinalysis was regarded as microscopic hematuria, and was positive in 46 patients (55.4%). There was a positive correlation between the position of the stone (especially upper two-thirds ureteral stones) and microhematuria rate (r: 0.28, p=0.009). There was a statistically significant difference in presence of hydronephrosis between the microhematuria (36 patients, 78%) and non-microhematuria (12 patients, 32%) groups (p<0.001). The median stone volume between the microhematuria and non-microhematuria groups were not statistically different, 37.5 mm3 (range 5–425) and 28 mm3 (range 4–412), respectively (p=0.39).
Although stone volume is one of the best indicators of stone burden, it was not correlated with microhematuria. However, in patients with renal colic, microhematuria requires ultrasound examination whether hydronephrosis and ureteral stones are present or not. Further studies with larger sample sizes are warranted.
renal colic; hematuria; multidetector computed tomography; urolithiasis
Aim. In this study we report our experience with microhematuria and its relation with bladder tumors in Iranian women.
Materials and Methods. Overall 249 women were evaluated. Microscopic hematuria was defined as three or more red blood cells per high-power field on at least two different occasions. Patients with a history of gross hematuria or coagulation disorders, having organic diseases, urinary stones, urinary tract infections, nephrological diseases, and local lesions such as urethral caruncle were excluded from the study population. Final diagnosis of malignant tumors was done with cystoscopy and biopsy specimen pathological assessment in all cases. Results. Age for the study population was 49.7 ± 11.8 years. 95 (38%) of patients were identified during routine check up and presenting symptoms in other patients were frequency, dysuria, stress urge incontinence, urge incontinence, feeling of incomplete urine emptying, and flunk pain, respectively. Finally, 7 (2.8%) of study subjects were confirmed as having bladder tumors. One of tumor cases was diagnosed 24 months after initial assessments. Patients with bladder tumor were significantly older; more frequently had diverticulum in their bladder wall (P < .05). Conclusion. Female microscopic hematuria is relevant and deserves evaluations, especially in elderly patients. Patients whose reason for microhematuria would not be diagnosed at the initial evaluations should be followed.
Bladder cancer kills more women than cervical cancer and is also a significant cause of mortality in men. Little progress has been made in improving survival in patients with advanced bladder cancer. Two pilot studies using microhematuria screening have shown that screening for bladder cancer results in close to 80% downstaging, with high-grade cancers being detected before they have invaded the bladder wall. Results of long-term follow-up even suggest a striking reduction in bladder cancer mortality. The main obstacles to screening for bladder cancer may be overcome if a higher-risk population is identified by designing a risk scale for exposure to cigarette smoke and occupational carcinogens, and through genetic testing for susceptibility to cancer and home hematuria screening, which in itself identifies a population with approximately 3% to 4% risk of bladder cancer. The feasibility and cost effectiveness of screening for bladder cancer can be significantly improved by incorporating a secondary screening strategy using a more sensitive and specific bladder cancer marker that is currently available, and by limiting urological evaluations to patients who show positive results on one or more of these tests. Bladder cancer is the most costly cancer to treat in the United States and pharmacoeconomic studies suggest that screening for bladder cancer could not only save lives but also reduce costs per year-life saved. A pilot study is underway and the urology community should be very supportive of studies to validate this opportunity.
The World Health Organization classifies lupus nephritis as class I to V or VI. However, a few cases of minimal change glomerulopathy have been reported in association with systemic lupus erythematosus (SLE). Mycophenolate mofetil has been shown to be effective for treatment of minimal change disease and lupus nephritis. A 24-year-old woman diagnosed with SLE five years prior to presentation complained of a mild generalized edema. The urinalysis showed microscopic hematuria and proteinuria. The assessed amount of total proteinuria was 1,618 mg/24 hours. A renal biopsy demonstrated diffuse fusion of the foot processes of podocytes on electron microscopy. Mycophenolate mofetil was started in addition to the maintenance medications of prednisolone 10 mg/day and hydroxychloroquine 400 mg/day. After six months of treatment, the microscopic hematuria and proteinuria resolved, and the total urine protein decreased to 100 mg/24 hours.
Nephrosis, lipoid; Lupus erythematosus, systemic; Mycophenolate mofetil
Introduction. Several point-of-care tests (POCT) are available for the diagnosis of bladder cancer (BC). We evaluate the impact of HU (hematuria) on performance of POCTs. Materials and Methods. Urine from 10 donors was diluted with blood from 0.5 to 0.00625%. BladderCheckR, BTAstatR, BCMR, and BTAR tests were applied. Tests were additionally conducted in 54 patients with HU. HU was stratified according to the amount of erythrocytes (RBC)/μL using two systems: (1) no HU; mild microscopic HU; severe microscopic HU; gross HU; (2) I <25 RBCs; <250
III. Results were compared to HU status and histopathology.
Results. Gross HU became evident between 2090 RBCs/μL and 1065/μL. Addition of blood led to default tests in all 4: BladderCheckR 0.25%; BCM 0.025%, BioNexia 0.00625%, and BTAstat <0.00625%. Rates of false positives for BladderCheck, BTAstat, BCM, and BioNexia were 5.9, 11.8, 0, and 1.8% without HU and 0, 66.7, 44.4, and 66.7% with HU. BTAstat, BCM, and BioNexia were independently influenced by HU (P < 0.0002).
Conclusions. NMP22-BladderCheck was most resistant to blood. The diagnostic yield of all others was significantly influenced by HU. A well-defined HU grading helps to define limits of HU for a reliable interpretation of BC-POCTs.
To determine the point prevalence of urine bilirubin, urine hemoglobin and urobilinogen in blunt trauma patients, and to evaluate its utility as a screening tool for intra-abdominal injury.
Data analysis of 986 consecutive trauma patients of which 698 were adult blunt trauma patients. Five-hundred sixteen subjects had a urinalysis and a CT scan of the abdomen/pelvis or exploratory laparotomy. We reviewed initial urinalysis results from trauma patients in the emergency department (ED) for the presence of urine hemoglobin, uroblinogen and urine bilirubin. Computed tomography (CT) scan results and operative reports were reviewed from the trauma registry for evidence of liver laceration, spleen laceration, bowel or mesenteric injuries.
There were 73 injuries and 57/516 patients (11%) with intra-abdominal injury. Urinalysis was positive for urobilinogen in 28/516 (5.4%) patients, urine bilirubin in 15/516 (2.9%) patients and urine hemoglobin in 313/516 (61%) patients. Nineteen/forty-seven (4%) subjects had liver lacerations, 28/56 (5%) splenic lacerations, and 15/5 (3%) bowel or mesenteric injury. Comparing the proportion of patients that had urobilinogen detected in the group with and without intra-abdominal injury, 8/28 (29%) subjects with urobilinogen, 5/15 (33%) subjects with bilirubin and 47/313 (15%) subjects with urine hemoglobin were found to have liver lacerations, spleen lacerations, or bowel/mesenteric injuries. Preexisting liver or biliary conditions were not statistically associated with elevation of urine bilirubin, urine hemoglobin or urobilinogen on initial urinalysis after blunt abdominal trauma. Point prevalence for urobilinogen, urine bilirubin and urine hemoglobin are 5.43% (28/516), 2.91% (15/516) and 60.7% (313/516) respectively.
The utility of the initial routine urinalysis in the ED for adult blunt abdominal trauma patients should not be used as a screening tool for the evaluation of intra-abdominal injury.
When urine infections are missed in febrile young infants with normal urinalysis, clinicians may worry about the risk – hitherto unverified – of concomitant invasion of blood and cerebrospinal fluid by uropathogens. In this study, we determine the extent of this risk.
In a retrospective cohort study of febrile 0–89 day old infants evaluated for sepsis in an urban academic pediatric emergency department (1993–1999), we estimated rates of bacteriuric sepsis (urinary tract infections complicated by sepsis) after stratifying infants by urine leukocyte counts higher, or lower than 10 cells/hpf. We compared the global accuracy of leukocytes in urine, leukocytes in peripheral blood, body temperature, and age for predicting bacteruric sepsis. The global accuracy of each test was estimated by calculating the area under its receiver operating characteristic curve (AUC). Chi-square and Fisher exact tests compared count data. Medians for data not normally distributed were compared by the Kruskal-Wallis test.
Two thousand two hundred forty-nine young infants had a normal screening dipstick. None of these developed bacteremia or meningitis despite positive urine culture in 41 (1.8%). Of 1516 additional urine specimens sent for formal urinalysis, 1279 had 0–9 leukocytes/hpf. Urine pathogens were isolated less commonly (6% vs. 76%) and at lower concentrations in infants with few, compared to many urine leukocytes. Urine leukocytes (AUC: 0.94) were the most accurate predictors of bacteruric sepsis. Infants with urinary leukocytes < 10 cells/hpf were significantly less likely (0%; CI:0–0.3%) than those with higher leukocyte counts (5%; CI:2.6–8.7%) to have urinary tract infections complicated by bacteremia (N = 11) or bacterial meningitis (N = 1) – relative risk, 0 (CI:0–0.06) [RR, 0 (CI: 0–0.02), when including infants with negative dipstick]. Bands in peripheral blood had modest value for detecting bacteriuric sepsis (AUC: 0.78). Cases of sepsis without concomitant bacteriuria were comparatively rare (0.8%) and equally common in febrile young infants with low and high concentrations of urine leukocytes.
In young infants evaluated for fever, leukocytes in urine reflect the likelihood of bacteriuric sepsis. Infants with urinary tract infections missed because of few leukocytes in urine are at relatively low risk of invasive bacterial sepsis by pathogens isolated from urine.
Dysuria is a common presenting complaint of women and urinalysis is a valuable tool in the initial evaluation of this
presentation. Clinicians need to be aware that pyuria is the best determinate of bacteriuria requiring therapy and
that values significant for infection differ depending on the method of analysis. A hemocytometer yields a value of
≥ 10 WBC/ mm3
significant for bacteriuria, while manual microscopy studies show ≥ 8 WBC/high-power field
reliably predicts a positive urine culture. In cases of uncomplicated symptomatic urinary tract infection, a positive
value for nitrites and leukocyte esterase by urine dipstick can be treated without the need for a urine culture. Automated
urinalysis used widely in large volume laboratories provides more sensitive detection of leukocytes and
bacteria in the urine.With automated microscopy, a value of > 2 WBC/hpf is significant pyuria indicative of inflammation
of the urinary tract. In complicated cases such as pregnancy, recurrent infection or renal involvement,
further evaluation is necessary including manual microscopy and urine culture with sensitivities.
Hypercalciuria is a risk factor for nephrolithiasis. We hypothesized that children with recurrent stones in 1 but not both kidneys and a normal 24-hour bladder urine calcium-to-creatinine ratio might exhibit isolated hypercalciuria of the affected kidney.
Materials and Methods
Patients 18 years or younger with symptomatic urolithiasis who had undergone ureteroscopic stone removal were included. All subjects underwent 24-hour bladder urinalysis. Subjects with an increased urine calcium-to-creatinine ratio from the 24-hour urine collection were excluded. The 4 subject cohorts defined were 1) single stone episode in 1 kidney, 2) single stone episode in both kidneys, 3) recurrent stone episodes on 1 side and 4) recurrent stone episodes on both sides. All urine collections were obtained at ureteroscopy. Urine was obtained from the bladder and from the renal pelvis of the kidney forming the stone. Spot urine calcium-to-creatinine ratio was determined from these samples.
A total of 329 patients were included. Nine of 74 subjects (12%) with recurrent stone episodes on 1 side had increased spot urine calcium-to-creatinine ratio from the affected kidney. No patients in the other cohorts had increased spot urine calcium-to-creatinine ratio. Patients who formed recurrent stones in 1 kidney had increased spot urine calcium-to-creatinine ratio in the affected kidney vs other stone formers (ANOVA p <0.001).
Unilateral hypercalciuria can occur in children with normal calcium levels in bladder urine. Unilateral hypercalciuria should be considered as a risk factor for nephrolithiasis in children with recurrent stone episodes in 1 kidney only.
hypercalciuria; nephrolithiasis; pediatrics
A 91-year-old female presented with lower extremity swelling and shortness of breath. Laboratory analysis revealed elevations in blood urea nitrogen and creatinine along with microscopic hematuria on urinalysis. Computed tomography imaging showed moderate right hydronephrosis with dilatation of the proximal ureter with a soft tissue density at a transition point. Endoscopic evaluation revealed multiple raised, fleshy, and hemorrhagic masses throughout the bladder which are present in both ureters. Biopsy of these lesions revealed malignant melanoma invading the lamina propria. No dermatologic lesions were identified suggesting a primary malignant melanoma of the genitourinary system.
To test whether a noninvasive urine-based multianalyte diagnostic readout assay that uses protein and DNA biomarkers can risk stratify patients with hematuria into those who are or are not likely to have bladder cancer and those who should receive standard care.
Patients and Methods
This prospective, observational, multicenter, single-assessment study was conducted between June 12, 2009, and April 15, 2011. Eligible patients presented with hematuria and as part of their evaluation underwent cystoscopy. Urine samples were analyzed for the presence of mutant FGFR3 and quantified matrix metalloproteinase 2 and the hypermethylation of TWIST1 and NID2. A patient's chance of having (positive predictive value [PPV]) or not having (negative predictive value [NPV]) cancer was determined by FGFR3 alone or by all 4 biomarkers, respectively.
Cystoscopy/biopsy diagnosed 690 of 748 patients as negative and 58 as positive for bladder cancer. Of 21 patients identified by FGFR3 as highly likely to have cancer, 20 were also positive by cystoscopy/biopsy, resulting in a PPV of 95.2% (20 of 21), with specificity of 99.9% (689 of 690). The 4-marker combination identified 395 patients as having a low likelihood of cancer. Of these, 56.2% (388 of 690) also had negative biopsy/cystoscopy findings, resulting in an NPV of 98.2% (388 of 395). In total, 416 of the 748 patients with hematuria (55.6%) were identified with extremely high NPV and PPV to have or not have bladder cancer.
This multianalyte assay accurately stratified patients with high confidence into those who likely do or do not have bladder cancer. This test was developed to enhance and not to eliminate referrals for urologic evaluation.
AUA, American Urological Association; CIDD, Clinical Intervention Determining Diagnostic; MADR, multianalyte diagnostic readout; MMP-2, matrix metalloproteinase 2; NPV, negative predictive value; PCR, polymerase chain reaction; PPV, positive predictive value
Current urine-based assays for bladder cancer (BCa) diagnosis lack accuracy, so the search for improved biomarkers continues. Through genomic and proteomic profiling of urine, we have identified a panel of biomarkers associated with the presence of BCa. In this study, we evaluated the utility of three of these biomarkers, interleukin 8 (IL-8), Matrix metallopeptidase 9 (MMP-9) and Syndecan in the diagnosis of BCa through urinalysis.
Voided urines from 127 subjects, cancer subjects (n = 64), non-cancer subjects (n = 63) were analyzed. The protein concentrations of IL-8, MMP-9, and Syndecan were assessed by enzyme-linked immunosorbent assay (ELISA). Data were also compared to a commercial ELISA-based BCa detection assay (BTA-Trak©) and urinary cytology. We used the area under the curve of a receiver operating characteristic (AUROC) to compare the performance of each biomarker.
Urinary protein concentrations of IL-8, MMP-9 and BTA were significantly elevated in BCa subjects. Of the experimental markers compared to BTA-Trak©, IL-8 was the most prominent marker (AUC; 0.79; 95% confidence interval [CI], 0.72-0.86). Multivariate regression analysis revealed that only IL-8 (OR; 1.51; 95% CI, 1.16-1.97, p = 0.002) was an independent factor for the detection of BCa.
These results suggest that the measurement of IL-8 in voided urinary samples may have utility for urine-based detection of BCa. These findings need to be confirmed in a larger, prospective cohort.
IL-8; Biomarkers; Diagnosis; Bladder cancer
Regardless of the availability of newer and more sophisticated modalities of investigation, urinary tract cytology still remains the most commonly used non-invasive test for the diagnosis of bladder cancer.
As hematuria is the commonest presenting symptom in patients with malignancy of urinary tract, we undertook this study to know the usefulness of urine cytology in evaluation of the hematuric patients for malignancy.
Materials and Methods:
A total of 21,557 fresh voided urine samples received at our tertiary care referral centre over a period of three years were included in the study. Of these, 1428 cases had hematuria, criteria of either gross or microscopic.
Among these hematuric cases included in the study, 32.5% (464 cases) were found to have positive finding of atypical cells. In these cases with atypia, 9.5% (136 cases) were proved to have malignancy both with the histopathological biopsy and cystoscopic findings. Other cases of atypia were found to be of reactive origin, either due to instrumentation or foreign body. A large number of hematuric cases, that is, 964 cases (67.5%) were negative for atypical cells.
The limited ability of urine cytology to detect low grade bladder tumors, its subjectivity and lack of uniformity in reporting, all render urine cytology a less than perfect tool. With added collaboration between clinician and cytopathologist, urine cytology can be used an adjunct tool in evaluation of patients with hematuria.
Atypical cells; hematuria; urine cytology
Hematuria is one of the most common conditions confronting clinical urologists and is present in many genitourinary pathology conditions. Although researchers have studied hematuria symptoms in an effort to determine the best diagnostic pathway, the existing lack of scientific evidence has created variations in clinical practice. The literature does not provide enough evidence to significantly alter the need to assess these patients. Consequently, many patients with microscopic or gross hematuria undergo low-yield workups that include invasive testing and imaging with radiation. In 2007, a national group of Kaiser Permanente (KP) urology chiefs agreed that national practice recommendations were needed to address existing variations in the management and workup of hematuria. Using a KP guideline methodology, the group reached a consensus agreement on the following recommendations: 1) referral to urology is recommended for all people with gross hematuria or high-grade hematuria (>50 red blood cells per high-power field [RBCs/HPF]) on a single urinalysis (UA); 2) referral to urology and urologic evaluation is recommended for men or women with asymptomatic microscopic hematuria or symptomatic hematuria that produces >3 RBCs/HPF on two of three properly performed and collected urinalyses; and 3) voided urinary cytology should be eliminated from asymptomatic hematuria screening protocol. The test is not sensitive enough to obviate further workup if findings are negative, and elimination of this screening test is estimated to save millions of dollars across the US. Hematuria on a UA should be reported as 0 to 3 RBC/HPF, 4 to 10 RBC/HPF, 11 to 25 RBC/HPF, 26 to 50 RBC/HPF, >50 RBC/HPF, or gross hematuria. This approach will also reduce radiation exposure.
To compare the urine protein–creatinine ratio with urinalysis to predict significant proteinuria (≥300 mg per day).
A total of 116 paired spot urine samples and 24-h urine collections were obtained prospectively from women at risk for preeclampsia. Urine protein–creatinine ratio and urinalysis were compared to the 24-h urine collection.
The urine protein–creatinine ratio had better discriminatory power than urinalysis: the receiver operating characteristic curve had a greater area under the curve, 0.89 (95% confidence interval (CI) 0.83 to 0.95) vs 0.71 (95% CI 0.64 to 0.77, P<0.001). When matched for clinically relevant specificity, urine protein–creatinine ratio (cutoff ≥0.28) is more sensitive than urinalysis (cutoff ≥1+): 66 vs 41%, P = 0.001 (with 95 and 100% specificity, respectively). Furthermore, the urine protein–creatinine ratio predicted the absence or presence of proteinuria in 64% of patients; urinalysis predicted this in only 19%.
The urine protein–creatinine ratio is a better screening test. It provides early information for more patients.
pregnancy; urinalysis; urine protein; creatinine ratio; proteinuria; preeclampsia; sensitivity and specificity
In this study, we investigated the influence of hematuria on the performance of the BTA tests in a clinical cohort and in an experimental model.
Materials and Methods
Analysis of urine samples from a cohort of 126 subjects (64 with BCa and 62 controls) were analyzed by ELISA for hemoglobin and BTA. The experimental model involved the spiking of urine with blood from the same subject, and hemoglobin, red blood cell count, and BTA levels (BTA stat© and BTA-TRAK©). BTA-TRAK© analyses were also performed on serum samples obtained from 40 subjects (20 with confirmed with BCa).
In the 126-subject cohort, correlation between hemoglobin and BTA was 0.732. Of the 64 BCa samples, 72% had a positive BTA assay, but 47% of controls were also positive. The sensitivity and specificity of BTA to detect BCa was 72% and 53%, respectively. Hematuria, measured by urinary hemoglobin, was a better indicator of BCa with 75% sensitivity and 90% specificity. Spiking of BTA-negative urine samples with as little as 1μl/10ml was enough to produce positive a BTA test. High levels of BTA were found equally in the serum of subjects with, or without BCa (mean BTA levels 355,159 U/ml vs. 332,329 U/ml, respectively).
Rather than detecting a bladder tumor antigen, urinary BTA assays may be measuring serum cFH introduced by bleeding, a common presenting factor in BCa subjects. The presence of hematuria in subjects without malignant disease can result in false-positive BTA assays.
complement factor H; hematuria; BTA; bladder cancer; diagnosis
OBJECTIVE: To review the clinical classification of childhood diurnal enuresis, to describe the evaluation process, and to discuss principles of management. QUALITY OF EVIDENCE: An extensive literature review was performed with a MEDLINE search. Articles were selected according to date of publication, clinical relevance, and availability. Recent articles, cohort studies of at least 50 patients, and randomized clinical trials were preferred. Recent editions of classic textbooks were consulted. Evaluation and management activities discussed in this article are supported by original and relevant literature. MAIN MESSAGE: Most causes of childhood diurnal enuresis can be determined by a thorough history coupled with a complete physical examination and urinalysis and culture. Supplementary investigations include ultrasonography of the kidneys and bladder to screen for neurogenic bladder and urethral obstruction. When obstruction, ectopic ureter, or bladder dysfunction is suspected, voiding cystourethrography and urodynamic studies are needed. Evaluation of neurogenic bladder includes magnetic resonance imaging of the spine. Treatment is aimed at correcting poor toilet habits, preventing or treating urinary tract infections, and using appropriate medication. CONCLUSIONS: In most instances, diurnal enuresis in childhood is a benign condition with an easily identifiable cause and an excellent prognosis with time and appropriate treatment.
The relationship between obesity and ketonuria is not well-established. We conducted a retrospective observational study to evaluate whether their body weight reduction response differed by the presence of ketonuria after fasting in the healthy obese. We used the data of 42 subjects, who had medical records of initial urinalysis at routine health check-up and follow-up urinalysis in the out-patient clinic, one week later. All subjects in the initial urinalysis showed no ketonuria. However, according to the follow-up urinalysis after three subsequent meals fasts, the patients were divided into a non-ketonuria group and ketonuria group. We compared the data of conventional low-calorie diet programs for 3 months for both groups. Significantly greater reduction of body weight (-8.6 ± 3.6 kg vs -1.1 ± 2.2 kg, P < 0.001), body mass index (-3.16 ± 1.25 kg/m2 vs -0.43 ± 0.86 kg/m2, P < 0.001) and waist circumference (-6.92 ± 1.22 vs -2.32 ± 1.01, P < 0.001) was observed in the ketonuria group compared to the non-ketonuria group. Fat mass and lean body mass were also more reduced in the ketonuria group. In addition, serum free fatty acid concentration after intervention in the ketonuria group showed significant more increment than in the non-ketonuria group. The presence of ketonuria after fasting may be a predicting factor of further body weight reduction.
Ketonuria; Body Weight; Fasting
The early detection of urological cancers is pivotal for successful patient treatment and management. The development of molecular assays that can diagnose disease accurately, or that can augment current methods of evaluation, would be a significant advance. Ideally, such molecular assays would be applicable to non-invasively obtained body fluids, enabling not only diagnosis of at risk patients, but also asymptomatic screening, monitoring disease recurrence and response to treatment. The advent of advanced proteomics and genomics technologies and associated bioinformatics development is bringing these goals into focus. In this article we will discuss the promise of biomarkers in urinalysis for the detection and clinical evaluation of the major urological cancers, including bladder, kidney and prostate. The development of urine-based tests to detect urological cancers would be of tremendous benefit to both patients and the healthcare system.
Biomarkers; body fluids; diagnosis; non-invasive; urinary; urological cancer
Although the performance of immunocytology has been established in the surveillance of patients with urothelial carcinoma of the bladder (UCB), its value in the initial detection of UCB in patients with painless hematuria remains unclear.
To determine whether immunocytology improves our ability to predict the likelihood of UCB in patients with painless hematuria. Further, to test the clinical benefit of immunocytology in this setting using decision curve analysis.
Design, setting, and participants
The subjects were 1182 consecutive patients without a history of UCB presenting with painless hematuria and were enrolled at three centres.
All patients underwent upper-tract imaging, cystourethroscopy, voided urine cytology, and immunocytology analysis. Bladder tumors were biopsied and histologically confirmed as UCB.
Multivariable regression models were developed. Area under the curve was measured and compared using the DeLong test. A nomogram was constructed from the full multivariable model. Decision curve analysis was performed to evaluate the clinical benefit associated with use of the multivariable models including immunocytology.
Results and limitations
Immunocytology had the largest contribution to a multivariable model for the prediction of UCB (odds ratio: 18.3; p < 0.0001), which achieved a 90.8% predictive accuracy. Decision curve analysis revealed that models incorporating immunocytology achieved the highest net benefit at all threshold probabilities.
Immunocytology is a strong predictor of the presence of UCB in patients who present with painless hematuria. Incorporation of immunocytology into predictive models improves diagnostic accuracy by a statistically and clinically significant margin. The use of immunocytology in the diagnostic workup of patients with hematuria appears promising and should be further evaluated.
Cystoscopy; Decision curve analysis; Early detection of cancer; Hematuria; Immunocytology; Nomograms; Urinary bladder neoplasms