Síndrome de cascanueces: una causa infrecuente de hematuria / Nutcracker Syndrome: a Rare Cause of Hematuria

La hematuria en pediatría responde habitualmente a etiologías benignas. Una causa poco frecuente es el síndrome de cascanueces, que se define como la compresión de la vena renal izquierda entre la aorta y la arteria mesentérica superior, que deriva en una presión elevada en la vena renal izquierda con el desarrollo de venas colaterales y dilataciones varicosas. La prevalencia de este síndrome se desconoce. Cuando es sintomático ocasiona hematuria, proteinuria y dolor pélvico crónico. En la pubertad, el crecimiento rápido y el desarrollo de los cuerpos vertebrales pueden producir un estrechamiento del ángulo entre la aorta y la arteria mesentérica superior. Se describe el caso de una adolescente con diagnóstico de carcinoma mucoepitelial metastásico óseo múltiple que presenta hematuria anemizante. Se arribó al diagnóstico de síndrome de cascanueces y se discutieron las opciones de tratamiento. Finalmente, con el uso de realce del calzado para corrección de la escoliosis, se atenuó significativamente la hematuria. (AU)

In pediatrics, hematuria usually responds to benign etiologies. A rare cause is nutcracker syndrome, defined as compression of the left renal vein between the aorta and the superior mesenteric artery, resulting in elevated pressure in the left renal vein with the development of collateral veins and varicose dilatation. The prevalence of this syndrome is unknown. When symptomatic, it causes hematuria, proteinuria, and chronic pelvic pain. At puberty, the rapid growth and development of the vertebral bodies can produce a narrowing of the angle between the aorta and the superior mesenteric artery.We describe the case of a teenage girl diagnosed with multiple metastatic mucoepithelial carcinoma of bone who presented anemia-producing hematuria. The diagnosis of nutcracker syndrome was arrived at with consideration of the therapeutic options. Finally, with shoe enhancement for scoliosis correction, hematuria was significantly lessened. (AU)

How to define and assess the clinically significant causes of hematuria in childhood.

Given the wide diversity of causes of hematuria, ranging from simple urinary tract infections with rapid recovery to severe glomerulonephritis with fast decline in kidney function, it is essential to recognize the underlying disease. The first objective of the assessment is to determine whether the cause of the hematuria is medically significant. The combination of hematuria with proteinuria, the presence of hypertension, or worsening kidney function can represent signs of progressive kidney disease. Differentiating the various causes of hematuria is often simple and obvious based on the clinical signs and gross appearance of the urine. However, in some instances, additional non-invasive investigations, such as ultrasound imaging, urinary red cell morphology, measurement of calcium and other solutes in the urine, evaluation of kidney function, and protein excretion, are needed to elucidate the nature of the hematuria. Taking a detailed family history can help in establishing the underlying cause in cases of familial hematuria. On the other hand, the decision to perform a kidney biopsy in children with asymptomatic hematuria remains a challenging issue for clinicians. Ultimately, the frequency of diagnosis of glomerular involvement causing hematuria may depend on the threshold for performing a kidney biopsy. The following review will focus on the diagnostics of hematuria, starting with difficulties regarding its definition, followed by various means to differentiate between urinary, glomerular, and other causes, and finally reviewing the most common diseases that, due to their frequency or their effect on kidney function, present a diagnostic challenge in everyday practice.

The impact of Coronavirus disease 2019 (COVID-19) on urinalysis parameters.

BACKGROUND: Creatinine elevation and changes in urinalyse parameters may be seen due to acute kidney injury during COVID-19. In the present study, we aimed to investigate the changes in urinalysis of COVID-19 patients with normal kidney function. METHODS: The data of COVID-19 patients with normal renal functions were retrospectively analyzed. Urinalysis parameters of these patients were recorded. The patients were divided into three groups as mild, moderate and severe with respect to the clinical course of the disease. It was examined whether the urine analysis values in the groups were different from normal reference values and whether these values were different between the groups. In addition, possible relationship between the urinalysis parameters and the clinical severity of the disease was investigated. RESULTS: There are three groups; mild (N.=40), moderate (N.=38) and severe (N.=42). Mean age were significantly higher in the severe group, while gender distribution of the groups was similar (P=0.033, P=0.091) Creatinine values of all patients were normal. There were 6.7% glucose positivity, 13.4% protein positivity, 5.8% urobilinogen positivity and 7.5% ketone positivity in urine dipstick analysis and these changes were all significantly higher than the reference values (P=0.008, P<0.0001, P=0.016, P=0.016). Pyuria and hematuria were detected in 8.3% and 9.2%, respectively. The urinalysis parameters and urine microscopy findings were not affected by the severity of the disease. CONCLUSIONS: Glycosuria, proteinuria, pyuria and hematuria may occur during COVID-19 disease, regardless of comorbidity and renal dysfunction. However, these urine parameters were not correlated with the severity of the disease.

RNA-based urinary assays for non-muscle invasive bladder cancer.

PURPOSE OF REVIEW: To provide an overview of the recent literature on RNA-based molecular urine assays for the diagnosis and surveillance of non-muscle invasive bladder cancer (NMIBC). RECENT FINDINGS: Articles were eligible for inclusion if performance metrics sensitivity, specificity, and negative-predictive value (NPV) were reported or could be calculated. Only prospective studies published between 2020-2022 were included. Five out of fourteen studies addressed the primary diagnostic setting; the proportion of gross hematuria patients in all study populations was >50%. Only one study reported performance metrics within a microscopic hematuria subgroup. This study evaluated Xpert Bladder and reported a sensitivity: 73%, specificity: 84%, NPV: 99%, and PPV: 12%. Ten studies assessed test performance during surveillance for NMIBC. For the detection of high-grade (HG) and high-risk (HR) NMIBC, sensitivity, specificity, NPV, and PPV varied between 78-100%, 64-89%, 97.0-99.7%, and 9.2-39%. SUMMARY: Multiple RNA-based urine assays have been investigated for the detection of urothelial cancer in the primary or surveillance setting. However, studies included within this review have important limitations, hampering the interpretation of study results. As such, performance metrics should be interpreted with caution and further research is required to evaluate the clinical impact of RNA-based urine assays in daily practice.

Defining Properly Collected Urine: Thresholds to Improve the Accuracy of Urinalysis for Microscopic Hematuria Evaluation in Women.

PURPOSE: Microscopic hematuria is one of the most common office consults for urologists. While revised guidelines have risk-stratified patients to reduce unnecessary screening, they do not provide guidance concerning specimen quality. We sought to define "properly collected" specimens using catheterized urine samples as a reference to improve the utility of hematuria screening in women. MATERIALS AND METHODS: We prospectively acquired same-visit voided and catheterized urine samples from 46 women referred for microscopic hematuria from September 2016 to March 2020. Characteristics of pre-referral urinalysis were compared to the matched specimens. True microscopic hematuria was defined as ≥3 red blood cells per high power field on catheterization. RESULTS: Catheterized urinalyses had significantly fewer red blood and squamous epithelial cells in comparison to both referral urinalyses (p=0.006, p=0.001, respectively) and same-day void urinalyses (p=0.02, p=0.04, respectively). As no catheterized sample had >2 squamous epithelial cells, we applied this squamous epithelial cell threshold to referral urinalyses for analysis. Addition of this criterion for "properly collected specimen" increased the positive predictive value of referral urinalyses from 46.1% to 68.8% for true microscopic hematuria. Fewer than 2 squamous epithelial cells with elevated RBC was a significant predictor for true microscopic hematuria (p=0.003). CONCLUSIONS: Voided specimens in the urology clinic had significantly lower red blood cells than referral samples, indicating improved collection technique may reduce false positive urinalyses. Matched collection suggested that repeat collection by catheterization in women who present with >2 squamous epithelial cells per high power field on referral urinalysis may prevent unnecessary future work-up.

Comparing Urine Specimen Collection Methods for Urinalysis and Culture Agreement: A Paired Sample Design.

OBJECTIVES: The primary aim of this study was to determine if results from clean catch urine specimens agree with results from catheterized specimens in a urogynecology patient population. The secondary aim was to identify clinical scenarios in which catheterized specimens are preferred over clean catch specimens. METHODS: Both a midstream clean catch and a catheterized specimen were obtained for each participant. Dipstick urinalysis was performed. If either specimen was positive for nitrites, leukocyte esterase, or blood then both were sent for urine culture.Kappa statistics were calculated to measure agreement between the paired specimen data for the total sample and for stratified samples. We agreed to accept clean catch results as preferable to catheterized results if the κ statistic was 0.7 or greater. RESULTS: Three hundred forty-two participants were enrolled. For all participants, the agreement between the paired samples was strong for nitrite (κ = 0.884), moderate for blood and colony count (both κ = 0.656), weak for culture species (κ = 0.566), and minimal for leukocyte esterase (κ = 0.382). When data were stratified for menopause, vaginal estrogen use, body mass index, and prolapse, there were no clinical scenarios in which the κ values were consistently greater than our accepted value of 0.7. CONCLUSIONS: Our data indicate that catheterized urine specimens should be used in the evaluation of urinary tract infection or microscopic hematuria in the typical patient presenting to a urogynecology office who is often menopausal, overweight, and may have prolapse.

Utility of remission criteria for the renal prognosis of IgA nephropathy.

BACKGROUND: Novel criteria for the remission of Immunoglobulin A nephropathy (IgAN) based on an opinion survey of Japanese nephrologists and literature review were proposed in 2013. This single-center, longitudinal retrospective cohort study was conducted to validate this criteria. METHODS: Present study included the IgAN patients diagnosed between 2001 and 2005 in the Juntendo University Hospital. Remission of hematuria was defined as three consecutive dipstick test results of ( -) to ( ±) or a red blood cell count < 5 in urinary sediment per high-power field during at least 6 months. Remission of proteinuria was defined as three consecutive dipstick results of ( -) to ( ±) during at least 6 months. We categorized four groups according to the remission status which was assessed 2 years after the renal biopsy. The primary outcome was a 50% increase in the serum creatinine over the baseline. We evaluated the slope of eGFR decline (mL/min/1.73 m2/year) and a decrease in the eGFR of 30% from baseline eGFR as the secondary outcome, respectively. RESULTS: A total of 74 patients (male: 47.3%, median age: 30 years) were included and were followed for a median of 86.5 months. During the period, forty-one patients achieved neither remission of proteinuria nor hematuria (NR). Twelve patients met the primary study outcome. A survival analysis revealed that the NR had the worst prognosis and the steepest slope of eGFR decline. CONCLUSION: Although further validation in a large cohort is necessary, these novel remission criteria for IgAN patients appear to predict the renal prognosis.

Laboratory Reporting Parameters of Microhematuria: Implications for Interpreting the 2020 AUA Guideline.

OBJECTIVE: To explore how laboratories in the United States (U.S.) report red blood cell per high powered field (RBC/HPF) counts on urinalysis and to evaluate whether this methodology permits effective risk stratification in accordance with the 2020 AUA/SUFU microhematuria guidelines. MATERIALS AND METHODS: Reporting methods for RBC/HPF counts (ranges, or actual counts) were collected by querying urologists in U.S. academic medical institutions or commercial laboratories. We explore whether (1) the reporting schemes were concordant with the risk strata in the new microhematuria guideline (3-10 [low risk], 11-25 [intermediate risk], and more than 25 [high risk]), and (2) evaluate the potential for risk group misclassification based on reporting methodology. RESULTS: Data were available for 141 laboratories. Seventy-two (51%) use RBC/HPF ranges, while the remainder use actual counts (or counts to a threshold). Sixty (42%) report range cutoffs which are not concordant with the microhematuria guidelines risk groups. Furthermore, fifty-six (40%) do not include the cutoff of 25 RBC/HPF which could potentially misclassify intermediate and high risk groups. Finally, sixteen (11%) do not include the cut-off of 3 RBC/HPF that defines the presence of microhematuria. CONCLUSION: A significant number of laboratories report RBC/HPF counts in ranges that differ from thresholds in the 2020 AUA/SUFU guideline. The implication is potential misclassification of microhematuria both at minimum threshold diagnosis (3 RBC/HPF), and additionally between intermediate and high risk groups. Standardization of reporting schemes to actual RBC/HPF counts may allow improved adherence to guidelines while providing data for future guideline development.

Fluorescence In Situ Hybridization in Urine Samples (UroVysion Kit).

Cystoscopy is considered the standard approach to the diagnostic workup of urinary symptoms. It has high sensitivity and specificity for papillary tumors of the bladder but low sensitivity and specificity for flat lesions. It is also expensive and may cause discomfort and complications. Urine cytology, in contrast, has the advantage of being a noninvasive test with high specificity but suffers from low sensitivity in low-grade and early-stage tumors, possibly due to the low number of exfoliated cells in urine. Numerous new noninvasive tests have been proposed. Among these, fluorescence in situ hybridization (FISH) has been studied for long time and in 2005 UroVysion Bladder Cancer Kit (UroVysion Kit) (Abbott/Vysis) received FDA approval for initial diagnosis of bladder carcinoma in patients with hematuria and subsequent monitoring for tumor recurrence in patients previously diagnosed with bladder cancer. The UroVysion Kit is designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus by FISH in urine specimens from symptomatic patients, those with hematuria suspected of having bladder cancer. Here, the approach for FISH assay by using UroVysion Bladder Cancer kit according to manufacturer's instructions is described.

The clinical research of 5 steps sequential method for whole treatment of hemorrhagic radiation cystitis in china.

Background: Curing hemorrhagic cystitis remains a challenge. We explore a continuous and effective treatment for hemorrhagic radiation cystitis. Methods: The data of patients in 6 provincial cancer hospital urology departments between April 2015 and December 2019 was reviewed retrospectively. Patients were classified as moderate and severe groups. The 5-steps sequential method was adopted. Two groups were initiated with step 1 and step 3 respectively. Step 1 was symptomatic treatment. Thrombin solution or sodium hyaluronate was administrated for bladder irrigation in step 2. Step 3 was transurethral electrocoagulation. Step 4 was interventional embolization. Step 5 was HBO therapy. OABSS was used to assess the improvement of patients' symptoms. The outcome was evaluated after at least 6 months of follow-up. Results: A total of 650 patients (56 men and 594 women), mean age 71.2 years, were enrolled in the 5 steps sequential method. 582 patients were classified as moderate and 68 severe group. In moderate group, the cure rate of step 1 was 61.2% (356/582), 80.4% (468/582) after step 2, 93.1% (542/582) after step 3, 96.2% (560/582) after step 4, and 99.8% (581/582) after step 5. In severe group, the cure rate was 54.4% (37/68) after step 3, 76.5% (52/68) after step 4, and 94.1% (64/68) after the step 5 respectively. The mean OABSS scores of both groups significantly decreased after 5 steps sequential method treatment (P<0.01). Conclusions: Our results show hemorrhagic radiation cystitis can be cured in 5 steps, and the 5 steps sequential method is welcomed and effective. Therapy efficacy depends on the number of steps adopted and the severity of hematuria.

The feasibility of multiple-tract mini-percutaneous nephrolithotomy as an overnight surgery for the treatment of complex kidney stones.

To demonstrate the feasibility of applying multiple-tract percutaneous nephrolithotomy (PCNL) as an overnight surgery for treatment of complex kidney stones. We reviewed a prospectively collected database of all multiple-tract PCNL planned as overnight surgery performed by a single surgeon since 2018. A clinical pathway including the removal of nephrostomy tube and discharge on the morning after surgery was carried out. A definition for tube removal was outlined. Ability to adhere to the pathway and achieving the described parameters and whether any resulting complications occurred were determined. A total of 136 consecutive patients were enrolled with mean stone burden of 960.5 mm2 and 5.1 cm. Mean operative time was 71.7 ± 30.7 min. The average hemoglobin drop was 17.6 ± 12.2 g/L, and the incidence of drop > 25 g/L was 21.9%. Overall, 125 patients (91.9%) but 11 patients were discharge on postoperative day 1. One case required readmission. Among the 11 patients, 7 patients (5.1%) underwent a delayed tube removal (≥ 2 days) and 4 patients underwent complications after next-day nephrostomy tube removal, including renal colic (2 cases), hydrothorax (1 case), and fever (1 case). Postoperative fever or severe hematuria was the major reason for delayed nephrostomy tube removal. The total complication rate was 8.8% (n = 12). Multiple-tract PCNL as an overnight surgery can be safely performed by experienced surgeons in most patients. An early nephrostomy tube removal could be achieved in nearly 95% patients.

Derivation of a clinical predicting rule for obstructive urolithiasis and alternative diagnosis requiring urgent intervention: the CLAD score.

Most patients with renal colic are discharged from the emergency department (ED) after evaluation and pain alleviation. These patients may not require urgent imaging by computed tomography. We derived a clinical prediction score in patients with renal colic to identify those at very low risk for complications and alternative diagnoses requiring urgent intervention. This retrospective chart review was carried out in 2 ED at an urban university hospital from January to December 2015. All patients with a diagnosis of renal colic were included. The primary outcome was an intervention required for renal colic or alternative diagnoses within 7 days of ED presentation. A stepwise logistic regression was used to assess factors associated with the outcome. A score was derived as a weighted sum of these predictors and its performance was calculated. The database was submitted to the French National Commission for Data Protection and Liberties (CNIL): declaration n°2164898v0 (03/22/2018). 871 with complete data were analyzed. In 94 (11%) patients, an intervention was performed for obstructive urolithiasis or alternative diagnosis. Five factors were most predictive of intervention: age > 45 years (1 point), a history of urologic surgery (1 point), pulse > 100 bpm (1 point), temperature > 37.8 °C (2 point), and urine dipstick negative for blood (1 point), yielding a score of 0-6 points (the Complicated uroLithiasis and Alternative Diagnosis (CLAD) score). The area under the curve of the receiver operating characteristic curve was 0.82 (95% CI 0.77-0.87). We derived a clinical score for renal colic that predicted the presence of obstructive urolithiasis and acute alternative diagnoses requiring intervention.

Bilateral renal haematuria and obstructive renal failure from acquired haemophilia A: a medical cause for a surgical problem.

A 55-year-old male presented to our emergency department with haematuria and abdominal pain. Investigations including a computed tomography (CT) scan revealed an intraluminal filling defect within the left collecting system, consistent in appearance with blood clot. With an initial working diagnosis of upper tract urothelial cell carcinoma, he was discharged with plans for an urgent cystoscopy and ureteroscopy. He subsequently represented with ongoing frank haematuria, anasarca, dropping haemoglobin and new right collecting system blood clot. Subsequent investigations showed that the patient had acquired haemophilia A resulting in the episodes of haematuria, highlighted after an elevated activated partial thromboplastic time prompted a thrombophilia screen. The patient was subsequently treated with factor eight inhibitor bypass activity, corticosteroids and cyclophosphamide.

Pediatric Donor Glomerulopathy Is a Possible Cause of Abnormal Urinalysis in Adults Receiving Small Pediatric Donor Kidneys.

BACKGROUND: Reports about prognosis of adults receiving small pediatric-donor kidneys (PDK) as compared to those receiving elder pediatric or adult donor kidneys (ADKs) are controversial. This study aimed to examine the outcomes of adults receiving small PDK and possible prognostic factors. METHODS: The records of adults who received kidneys from donors < 10 years old at our center from July 1, 2011 to June 30, 2018 were reviewed. RESULTS: A total of 121 adults were small PDK recipients. Twenty-three patients received 29 biopsies or nephrectomy between 6 and 896 days posttransplantation days. Seven patients (30.4%) had pediatric donor glomerulopathy (PDG), which developed from 113 to 615 days posttransplantation. The incidence of proteinuria and hematuria was significantly higher in the PDG group. The characteristic pathological finding in PDG was irregular lamination and splintering of the glomerular basement membrane (GBM). Donor age, donor weight, and donor kidney volume were significantly less in PDG cases compared with the non-PDG cases. For the risk factors of PDG, increasing urinary RBC count during follow-up was an independent predictor, while increasing donor age and body weight were protective factors. PDG was not a significant risk factor for Scr increasing of PDKs. CONCLUSIONS: PDG is a potential cause of abnormal urinalysis in adults receiving small PDKs. The pathological characteristic change of PDG is splitting and lamination of GBM. Persistent hematuria after transplantation in recipients of PDK is a predictor of PDG development.

Metabolic risk factors in children with kidney stone disease: an update.

BACKGROUND: The prevalence of kidney stones in children has significantly increased in the past few decades, with concomitant increased morbidity and healthcare costs worldwide. Assessing metabolic risk factors is essential for diagnosis and specific treatment. The objective of this retrospective study is to identify the epidemiological and clinical characteristics of children under 17 years of age, as well as the metabolic risk factors of nephrolithiasis. METHODS: A total of 300 children with kidney stone disease were included to undergo several clinical tests using a standardized protocol. RESULTS: The mean age was 11.2 years, and the male:female ratio was 1.15:1.0. Biochemical abnormalities were found in 89.3% of all cases. A single urine metabolic risk factor was present in 52.6% (n = 141) of the patients, and multiple risk factors were present in 36.7% (n = 106). Idiopathic hypercalciuria (alone or in combination) and hypocitraturia (alone or in combination) were the most frequent risk factors identified in 47.0% and 39.6% of these patients, respectively. Renal colic and/or unspecified abdominal pain were the most frequent forms of presentation (76.9%), followed by hematuria in 64.4% with 97.5% of stones located in the upper urinary tract. A positive family history in first-degree and second-degree relatives was found in 64.8% of boys and 61.8% of girls. CONCLUSIONS: We conclude that specific urinary metabolic risk factors can be found in most children with kidney stones, with hypercalciuria and hypocitraturia being the most common diagnoses. Graphical abstract .

Atypical cells parameter in an automated urine analyzer: Does it have a future?

Sysmex UN-Series automated urine analyzer has recently introduced "atypical cells" parameter. These cells are supposed to be epithelial cells with features of suspicion for a neoplastic proliferation. Atypical cells parameter in urinalysis should be considered to be as useful as the blast parameter in hematology. However, it has many disadvantages compared to its counterpart. I suggest it should be used as a caution flag rather than a quantitative value to appear in the patient result page. A decision limit must be defined; perhaps the color parameter should be matched to define patients with both hematuria and atypical cells.

Urine colour as an indicator for anastomotic leakage after robot-assisted radical prostatectomy.

Objectives: To determine whether macroscopic haematuria predicts urethrovesical anastomotic leakage after robot-assisted laparoscopic radical prostatectomy (RALP) as well as a cystogram.Patients and methods: Participants were recruited before cystogram and catheter removal 5-14 days after RALP surgery. Urine colour in the collection bag was classified according to a three-step scale (clear, light red and dark red) and leakages in cystogram were graded with a four-step scale (Grade 0-3). Diagnostic accuracy parameters were calculated for urine colour. A multivariate logistic regression model was used to evaluate other leakage risk factors.Results: Of 214 patients, 201 (94%) had clear, six (3%) had light red and seven (3%) had dark red coloured urine. In the cystogram, 20 (9%) patients had leakage; 14 had Grade 1, five Grade 2 and one Grade 3 leakage. Overall, specificity and sensitivity of urine colour in predicting anastomotic leakage were 0.97 (95% CI = 0.95-100) and 0.38 (95% CI = 0.17-0.59), respectively. Negative and positive predictive values were 94% and 62%, respectively. Other significant risk factors for anastomotic leakage were previous transurethral resection or radiation therapy to the prostate, non-waterproof anastomosis at surgery, postoperative pelvic haematoma, long catheterization and surgeon's inexperience. In patients with no other risk factors, test sensitivity improved to 0.80 (95% CI = 0.45-1.15) and negative and positive predictive values to 99% and 44%, respectively.Conclusion: This prospective single-arm trial indicates that in patients with clear urine and no other risk factors for anastomotic leakage, a cystogram examination before urethral catheter removal can be safely omitted.