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.

Persistent Hematuria and Kidney Disease Progression in IgA Nephropathy: A Cohort Study.

RATIONALE & OBJECTIVE: Hematuria is the most typical presentation of immunoglobulin A nephropathy (IgAN); however, its role in disease progression is still controversial. This study aimed to evaluate the association of hematuria and progression of IgAN. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A cohort of 1,333 patients with IgAN treated at a Chinese referral hospital with a median follow-up of 45 months. PREDICTORS: Microhematuria was evaluated in fresh urine using a fully automated urine particle analyzer (automated method) and urine sediment examination by a skilled examiner (manual method). Hematuria was characterized as a time-varying attribute; namely, average hematuria level was calculated for every 6-month period for each patient during follow-up. Remission was defined as average red blood cell count ≤5/high-power field (manual method) or ≤28 red blood cells/µL (automated method) during the first 6 months of follow-up. OUTCOMES: Composite event of 50% decline in estimated glomerular filtration rate or development of kidney failure. ANALYTICAL APPROACH: Multivariable cause-specific hazards models to analyze the relationship between hematuria and the composite kidney disease progression event. RESULTS: Time-varying hematuria during follow-up was an independent risk factor for the composite kidney disease progression event (HR, 1.46; 95% CI, 1.13-1.87; P = 0.003). Hematuria remission during the 6 months after diagnosis was associated with a significantly lower rate of the composite kidney disease progression event (HR, 0.41; 95% CI, 0.28-0.61; P < 0.001). A significant interaction was detected between remission of proteinuria and remission of hematuria during the first 6 months (P < 0.001). The association between remission of hematuria and kidney disease progression was detectable (HR, 0.46; 95% CI, 0.32-0.68) within the subpopulation with persistent proteinuria (protein excretion > 1.0 g/d during the first 6 months), but not among patients whose proteinuria had remitted (HR, 0.64; 95% CI, 0.31-1.29; P = 0.2). The 2 techniques for hematuria evaluation were strongly and significantly linearly correlated (r = 0.948; P < 0.001), and results using these 2 methods were consistent. LIMITATIONS: A single-center retrospective study. Proportional hazards regression incorporating time-varying covariates may create time-varying confounding. The predictive value of reductions in hematuria was not directly evaluated. CONCLUSIONS: Level of hematuria was independently associated with kidney disease progression, whereas hematuria remission was associated with improved kidney outcomes in IgAN among patients with persistent proteinuria. Additionally, to monitor IgAN progression, automated methods to evaluate hematuria hold promise as a replacement for manual evaluation of urinary sediment.

Association between vitamin D level and hematuria from a dipstick test in a large scale population based study: Korean National Health and nutrition examination survey.

BACKGROUND: Vitamin D deficiency is an important health concern because it is related to several comorbidities and mortality. However, its relationship with the risk of hematuria remains undetermined in the general population. In this study, we analyzed the association between vitamin D deficiency and hematuria. METHODS: We conducted cross-sectional analysis using data of participants from the Korean National Health and Nutrition Examination Survey (KNHANES) 2010-2014. A total of 20,240 participants, aged ≥18 years old, were analyzed. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in a central laboratory and hematuria was defined as ≥1+ on a dipstick test. Multivariate logistic regression was conducted to calculate the odds ratio (OR) of hematuria risk according to serum 25(OH)D quartiles, after adjusting several covariates. RESULTS: A total 3144 (15.5%) participants had hematuria. The mean 25(OH)D level was 17.4 ± 6.2 ng/mL (median, 16.6 ng/mL (interquartile range, 13.1-20.8 ng/mL)). The 3rd and 4th quartiles had a higher risk of hematuria than the 1st quartile, with adjusted ORs 1.26 (1.114-1.415) and 1.40 (1.240-1.572) in the 3rd and 4th quartiles, respectively. However, this relationship was only significant in women, not in men. When stratified analyses were conducted according to menopausal status, there was a significant increase of hematuria risk according to quartiles in postmenopausal but not in premenopausal women. CONCLUSION: We found that vitamin D deficiency is correlated with hematuria in women, particularly after menopause. Further interventional studies are warranted to address whether correcting vitamin D deficiency can lower the risk of hematuria.

Characteristics and Histological Types of Lupus Nephritis in a Jordanian Tertiary Medical Center.

OBJECTIVES: Few reports of lupus nephritis (LN) from Jordan and the Middle East exist. This study assessed the demographic, clinical, and basic laboratory characteristics of Jordanian patients with LN and correlations with the histological class of LN. METHODS: This was a retrospective study of all patients who underwent kidney biopsy between 2007 and 2018 at a tertiary medical center in Jordan. Patients' demographic, clinical, laboratory, and pathological data were reviewed. RESULTS: In total, 79 patients were included in this study [mean age, 29.95 ± 12.16 years; 11 men (13.9%), 68 women (86.1%)]. Asymptomatic proteinuria and hematuria were the most common presentations in LN patients at biopsy (59.5%). The study revealed a significant difference in frequency of nephritic syndrome (p= 0.01) between sexes (10.3% female vs. 45.5% male). Class IV was the most common pathological class of LN [37 (46.8%)], followed by class V [15 (19%)] and class III [10 (12.7%)]. Post hoc analysis of the associations between laboratory values and histopathological patterns revealed a significant correlation between class IV lupus and renal failure (p= 0.018) and class IV lupus and anti-DNA antibodies p= 0.030). End-stage renal disease (ESRD) occurred in 25% of lupus nephritis cases. There was an increased likelihood of ESRD among men than women (45% vs. 22%). Overall mortality was 10%. CONCLUSION: Although some clinical and laboratory findings correlate with histological types of LN, clinical and laboratory parameters of Jordanian patients with LN are not predictive of the histological type, although differences with regional studies were noted.

Hirudin ameliorates immunoglobulin A nephropathy by inhibition of fibrosis and inflammatory response.

Immunoglobulin A nephropathy (IgAN) is characterized by mesangial IgA and IgG co-deposition. As the clinical course of IgAN is highly variable, a lot of patients will eventually develop to end-stage renal disease (ESRD) within years. Hirudin, a potent and specific thrombin inhibitor, has been reported to treat IgAN with hematuria, but the mechanism is unclear. Our study aims to explore the potential of hirudin and the underlying mechanism in the treatment of IgAN. The establishment of IgAN model was set up in rats through oral and intravenous immunization with bovine gamma-globulin (BGG). Results suggested that hirudin could reduce the increased level of proteinuria, serum creatinine and urea nitrogen in IgAN models. Besides that, hirudin ameliorated the elevated number of apoptotic bodies and expressions of apoptosis-related proteins (caspase-3 and caspase-9) in IgAN model. The fibrosis indexes (transforming growth factor ß-1 (TGF-ß1), Collagen-IV (CoI-IV) and Fibronectin-1) of kidney were remarkably suppressed in IgAN rats treated with hirudin compared with IgAN rats with no further treatment. IgAN rats exhibited remarkably increased inflammatory factors (IL-1ß, IL-6, and IL-18), while hirudin treatment significantly alleviated these alterations. Moreover, the reduced levels of CD4+CD25+Foxp3+ Treg and CD4+IFN-γ+ Th1/CD4+IL-4+ Th2 could be reversed by hirudin in IgAN model. Furthermore, in the process of IgAN, hirudin could inactivate various pathways (IκBα, NF-κB, TNF-α, and VCAM-1) compared with IgAN model group. Taken together, our study indicated that hirudin could ameliorate IgAN through suppressing fibrosis and inflammatory response. These findings provide a new therapeutic method to treat IgAN.

Hyperuricemia, urine uric excretion, and associated complications in thalassemia patients.

Thalassemia patients have a high cell turnover rate due to chronic hemolysis and ineffective erythropoiesis; therefore, hyperuricemia is anticipated. This study aimed to identify the prevalence of hyperuricemia, gout and nephrolithiasis, conditions associated with serum uric acid (SUA), and urine uric acid excretion (UUA) in thalassemia patients. This was a cross-sectional study in patients aged 15 years or older at Chiang Mai University Hospital. All patients had blood and 24-h urine collection test. We enrolled 112 thalassemia patients in which 67.0% were female, 64.3% had beta thalassemia/Hb E, 76.8% were transfusion dependent, and 59.8% were post splenectomy. The median age was 29 (16-58) years. Mean SUA was 6.7 ± 2.0 mg/dl and hyperuricemia (SUA > 6.8 mg/dl) was found in 47 cases (45.2%). Intact spleen (ORs 4.3, 95%CI 1.55-12.50, p = 0.01) and lower FEuric (ORs 2.08, 95%CI 1.35-3.33, p < 0.01) were associated with hyperuricemia significantly. Seven (6.3%) had gouty arthritis and nine (8%) had microscopic hematuria, one case being confirmed nephrolithiasis. The mean UUA excretion was 981.3 ± 335.0 mg/day and UUA hyperexcretion (> 700 mg/24 h) was found in 83.3%. UUA hyperexcretion patients had renal hyperfiltration 46%, glomerular dysfunction 84%, and tubular dysfunction 7.7%. From our study, hyperuricemia was found in approximately 40% of thalassemia patients but gouty arthritis occurred only in few patients (6%). This may be explained by urinary uric hyperexcretion which is found in over 80%. The significant risk factors for hyperuricemia were intact spleen and lower fraction excretion of uric acid.

Hematuria and Renal Outcomes in Patients With Diabetic Chronic KidneyDisease.

BACKGROUND: Hematuria may indicate nondiabetic renal disease in diabetic chronic kidney disease (CKD). However, some studies have reported that hematuria is noted in diabetic nephropathy and is associated with albuminuria. Hematuria is a risk factor for end-stage renal disease in glomerulonephritis, but its prognostic value in diabetic CKD is unknown. We investigated the factors associated with hematuria and the prognostic value of hematuria in patients with diabetic CKD. MATERIAL AND METHODS: We included 1958 patients with type 2 diabetes and CKD stages 1-5, and 111 patients underwent renal biopsy. Patients in the biopsied cohort were younger and had more severe proteinuria, compared with those in the total cohort; hematuria was associated with nondiabetic renal disease. RESULTS: In the total cohort, hematuria was observed in 15.0% of the patients and was associated with young age, a lower estimated glomerular filtration rate, proteinuria, high blood pressure and short diabetes duration. Hematuria was significantly associated with an increased risk (hazard ratio 1.39, 95% CI: 1.10-1.76, P < 0.001) of end-stage renal disease, particularly in patients with CKD stages 1-3 or a urine protein-to-creatinine ratio of <1,500mg/g (P for interaction < 0.05). The odds ratio of hematuria for rapid renal progression was 1.81 (95% CI: 1.29-2.53, P < 0.001). CONCLUSIONS: Hematuria is associated with nondiabetic renal disease in biopsied patients with diabetic CKD and is associated with an increased risk of end-stage renal disease in patients with early diabetic CKD.

CYP1A1 expression and organochlorine pesticides level in the etiology of bladder cancer in North Indian population.

Urinary bladder cancer (UBC) is one of the most common malignancies worldwide. The etiology of UBC is multifactorial and includes both exogenous and endogenous factors. Exogenous risk factors include exposure to heavy metals, aromatic amines, and environmental pollutants including pesticides such as organochlorine pesticides (OCPs). Environmental factors alone are incapable of directly producing DNA damage and may require activation by phase I metabolizing enzymes like cytochrome P450 in order to become active carcinogen. The present study is designed to study CYP1A1 gene expression, OCP level in cases of UBC, as well as to explore the plausible role of gene-environment interaction in the etiology of UBC among North Indian population. A total of 60 cases with equal number of controls were enrolled under this study, the OCP levels were estimated using gas chromatography, CYP1A1 mRNA expression was quantified by real-time quantitative polymerase chain reaction, and fold change was calculated using the ΔΔCt method. In the present study, the levels of OCP were found to be significantly higher with the upregulation of CYP1A1 mRNA expression among UBC cases as compared to controls. While putting multiple linear regression, it has been observed that there is a significant interaction between the levels of OCPs and ΔCt value of CYP1A1 gene taken into account hematuria episodes as dependent variable. The study concludes that when there is predisposition of OCPs and upregulation of CYP1A1 gene, then the result will be an increment in hematuria episodes which indicates that gene-environment interaction plays a significant role in the causation of UBC among North Indian population.

Safety and Efficacy of Flexible Ureteroscopy in Combination with Holmium Laser Lithotripsy for the Treatment of Bilateral Upper Urinary Tract Calculi.

OBJECTIVE: To retrospectively evaluate the safety and efficacy of flexible ureteroscopy (FURS) in combination with holmium laser lithotripsy for the treatment of bilateral upper urinary calculi. MATERIALS AND METHODS: The stone-free status was defined as the absence of any stones or asymptomatic status, or the presence of clinically insignificant residual fragments <4 mm, and was assessed by plain kidney, ureter, and bladder X-ray. The operative time, stone-free rates (SFRs), serum creatinine (SCr), and complications were recorded. RESULTS: During the operation, there was no bleeding, ureteral perforation, avulsion, and rupture. Postoperative hematuria was observed in 2 patients. SCr increased significantly on the first day after the procedure compared with the preoperative SCr, but after 4 weeks, the renal function significantly improved (p < 0.05). The SFR was 71.6% (63/88) on the first day after the first surgical procedure; it then increased to 86.4% (76/88) in the fourth week, and rose to 97.4% (76/78) after the second operation. CONCLUSION: The results demonstrated that FURS in combination with holmium laser lithotripsy represented a favorable less-invasive alternative with high SFR and acceptable complication rates in the treatment of bilateral upper urinary tract calculi.

Plasma and urine DNA levels are related to microscopic hematuria in patients with bladder urothelial carcinoma.

a) Objective: An increase in cell-free DNA was observed in the plasma of many cancer patients. This major biomarker can be used to differentiate patients with malignant neoplasms from those with benign neoplasms or healthy patients. Depending on the characteristic of the tumor, there are qualitative variations in the circulating cell-free DNA. Today, studies on the concentration of fragments of circulating cell-free DNA and their respective sizes in patients with bladder cancer are not plentiful in the literature. A 100% effective plasma tumor marker, which would help in the diagnosis and follow-up of bladder cancer, is yet to be developed; therefore, cell-free DNA levels in the plasma may represent a valuable biomarker for the diagnosis, prognosis and follow-up of patients with this type of tumor. b) Design and methods: In this study we analyze the kinetics of plasma and urine DNA concentrations in patients with bladder cancer, relating them to the other clinical laboratory variables. c) Results: Patients with hematuria showed a positive correlation with urine DNA. d) Conclusion: An increase in plasma and urine DNA was unprecedentedly reported over time, a fact that may come in handy in the prognosis of patients. Furthermore, microscopic haematuria is correlated with plasma and urinary DNA levels.

Diagnostic impact of dysmorphic red blood cells on evaluating microscopic hematuria: the urologist's perspective.

PURPOSE: Dysmorphic red blood cells (dRBCs) are indicative of glomerular disease and considered a first step in evaluating microscopic hematuria (MH). The predominance of dRBCs does not preclude urological disease; however, some contemporary guidelines advise nephrological evaluation without further urological evaluation, in contrast to the American Urological Association guideline. We investigated the feasibility and safety of omitting urological evaluation in patients presenting with MH. METHODS: A retrospective analysis was performed on 411 consecutive patients who presented with MH between January 2012 and December 2014. MH was defined as ≥3 RBCs per high-power field. All patients received full urological and nephrological evaluations including history and physical assessment, renal function, urine cytology, %dRBC, cystoscopy, computed tomography (CT) imaging, and renal biopsy when indicated. RESULTS: The median %dRBC was higher in patients with glomerular disease than in those with urological disease (40.4 vs. 21.1 %; p < 0.001). Among patients exhibiting %dRBC ≥ 40, 33/97 (34.0 %) had urological and 28/97 (28.9 %) had glomerular diseases. Urological diseases included 9/33 (27.3 %) clinically meaningful malignancies and 17/33 (51.5 %) conditions requiring immediate treatment. The rate of malignancy was comparable between %dRBC groups (p = 0.087). Among patients with final diagnoses who exhibited %dRBC ≥ 40, 32/61 (52.5 %) treatment-requiring conditions would have been unrecognized had cystoscopy and/or CT not been performed. For predicting glomerular disease, the presence of proteinuria demonstrated higher AUC than %dRBC ≥ 40 (0.77 vs. 0.65; p < 0.001). CONCLUSIONS: Identification of %dRBC ≥ 40 had modest diagnostic value in identifying glomerular disease, and concomitant presence of proteinuria was more indicative of glomerular origin in patients presenting with MH. Urological evaluation should not be omitted in these patients considering the prevalence of treatment-requiring urological disease.

Dysmorphic erythrocytes are superior to hematuria for indicating non-diabetic renal disease in type 2 diabetics.

AIMS/INTRODUCTION: There are sparse and limited studies on erythrocyte morphology in renal biopsy identifying nephropathic patients among type 2 diabetics. The present study sought to clarify the predictive value of dysmorphic erythrocytes in type 2 diabetics with non-diabetic renal disease and influences on hematuria. MATERIALS AND METHODS: We examined 198 patients with type 2 diabetes who underwent kidney biopsies between 2012 and 2013. Hematuria was defined as >3 or >10 red blood cells per high-power field (RBCs/hpf) in urine sediment. If >80% of the erythrocytes were dysmorphic, glomerular hematuria was diagnosed. Clinical findings and predictive value of dysmorphic erythrocytes were compared between patients with hematuria (n = 19) and those without (n = 61). The potential risk factors for hematuria among diabetic nephropathy patients were also screened. RESULTS: There was a statistically significant difference between the diabetic nephropathy group and the non-diabetic renal disease group (6.6 vs 16.8%; P = 0.04) when the demarcation point of hematuria was 10 RBCs/hpf. When the definition of hematuria was based on an examination of urinary erythrocyte morphology, a marked difference was seen (3.3 vs 24.8%; P < 0.001). Glomerular hematuria showed high specificity and a positive predictive value (0.97 and 0.94, respectively) in non-diabetic renal disease. A multivariate analysis showed that nephrotic syndrome was significantly associated with hematuria (odds ratio 3.636; P = 0.034). CONCLUSIONS: Dysmorphic erythrocytes were superior to hematuria for indicating non-diabetic renal disease in type 2 diabetics. Nephrotic syndrome was an independent risk factor for hematuria.

[Molecular mechanisms of individual platelet reactivity in hematuria secondary to lithotripsy].

AIM: To investigate the mechanisms of individual platelet reactivity to ADP and adrenaline associated with the variability of hematuria after lithotripsy in patients with chronic obstructive pyelonephritis (COPN). MATERIALS AND METHODS: The study included 41 COPN patients admitted to the Department of Urology for lithotripsy (LT). The contact ultrasonic LT was performed using the Karl Storz Calcuson Ultrasonic Lithotripsy System. Postoperative hematuria was assessed by microscopic red blood cell count. Platelets were separated from the citrated peripheral blood by centrifugation. Platelet aggregation was measured by Chrono-log aggregometer using agonists (ADP, adrenaline) at a concentration of EC50 and EU10. RESULTS: There were three types of platelet functional response to ADP and adrenaline after LT (increased, unchanged and decreased aggregation), but the predominant type of individual response was increased platelet aggregation. Testing 24 hours after LT revealed 7 platelet phenotypes differing in functional activity of 2-adrenoceptor agonist and purine receptors (R2Y1 and R2Y12). Normal purine receptor activity was associated with the ability of platelets to respond to adrenaline by increasing the functional activity aimed at limiting hematuria. Reduced platelet response to ADP after LT reaching the level of hyporesponsiveness may be viewed as a predictor of severe hematuria after surgery. CONCLUSION: Individual platelet reactivity, manifested by the interaction of ADP and adrenaline agonist, determines the effectiveness of the increase in pro-aggregation capacity of platelets in developing postoperative hematuria.

Molecular characterization of novel splice site mutation causing protein C deficiency.

Congenital protein C deficiency is an inherited coagulation disorder associated with an elevated risk of venous thromboembolism. A Saudi Arabian male from a consanguineous family was admitted to neonatal intensive care unit in his first days of life because of transient tachypnea and hematuria. Laboratory investigations determined low platelet and protein C deficiency. Direct sequencing of PROC gene and RNA analysis were performed. Analysis of factor V Leiden (G1691A) and factor II (G20210A) mutations was also done. Novel homozygous splice site mutation c.796+3A>T was detected in the index case and segregation was confirmed in the family. RNA analysis revealed the pathogenicity of the mutation by skipping exon 8 of PROC gene and changing the donor splice site of the exon. Detection of the molecular cause of protein C deficiency reduces life threatening and facilitates inductive carrier testing, prenatal and preimplantation genetic diagnosis for families.

Manual bladder washouts for urinary clot retention: a survey of knowledge among healthcare workers.

INTRODUCTION: Manual bladder washouts (MBWs) are an integral skill for healthcare workers dealing with urological patients. Despite this they are often overlooked by educators and omitted from formal teaching curricula. We aimed to determine the level of competence and training among healthcare workers in performing a MBW. MATERIALS AND METHODS: Following a literature review for correct MBW technique, a 15-question survey was developed to assess knowledge and self-reported competency of doctors and nurses in performing a MBW. Two hundred paper and email-based surveys were distributed to doctors and nurses in the urology wards of Australian public and private hospitals. RESULTS: The survey response rate was 79% with the majority of responses received from senior nurses and surgical registrars, comprising a final study population of 133 respondents. Reported levels of education pertaining to MBW were poor, with only 5% of doctors and 35% of nurses claiming to have been taught the skill as a student. Opinions surrounding the technical aspects of MBW varied significantly across both clinician and nursing subgroups. Interpretation of completion of a MBW was inconsistent, with 72% of nurses stating this occurred when continuous irrigation ran freely compared to only 25.3% of registrars. Despite this, confidence in performance of a MBW in clinicians was high (> 95% agree or strongly agree). Confidence levels in knowledge and procedural skills were significantly lower in the nurse cohort than the registrar cohort (p < 0.01). CONCLUSIONS: The indications and technique for MBW are poorly described in the literature. Despite high self-reported competency, MBW appears poorly understood by both doctors and nurses. This valuable and common skill is rarely taught to healthcare students, suggesting better education may improve expertise and patient outcomes.