D O McGregor, K L Lynn, R R Bailey, R A Robson, J Gardner
Clinical audit of the use of renal biopsy in the management of isolated microscopic hematuria.
Clin Nephrol. 1998 Jun;49(6):345-8.
Abstract/Text
Whether renal biopsies are indicated for the investigation of microscopic hematuria is a subject of debate. In this retrospective study we evaluated our use of renal biopsy in patients who presented between 1985 and 1995 with microscopic hematuria but without proteinuria, hypertension or renal insufficiency. Of 111 patients, 75 had a renal biopsy. Histological diagnoses included thin membrane nephropathy (TMN) (36%), IgA nephropathy (IgAN) (23%), non-IgA mesangioproliferative glomerulonephritis (MPGN) (9%), mild glomerular abnormalities (11%), focal global glomerulosclerosis (FGS) (4%) and normal (17%). After 85 patients had been followed for a mean of 43 months there were no deaths, 3 patients had proteinuria (IgAN 2, no biopsy 1), 1 had proteinuria and renal insufficiency (immune negative MPGN) and 11 were hypertensive (TMN 3, IgAN 2, normal 2, FGS 1, no biopsy 3). Hematuria resolved in 23 patients. Only 11 patients were still attending the nephrology clinic and 27% of the patients who were advised to continue annual follow-up with family doctors had not done so. In summary, the information obtained from renal biopsy rarely altered clinical management. Hypertension developed in 13% of the patients followed but it was not predicted by the biopsy result. Although a renal biopsy will usually be diagnostic it is difficult to justify in patients who have isolated microscopic hematuria.
C L Hall, R Bradley, A Kerr, R Attoti, D Peat
Clinical value of renal biopsy in patients with asymptomatic microscopic hematuria with and without low-grade proteinuria.
Clin Nephrol. 2004 Oct;62(4):267-72.
Abstract/Text
BACKGROUND: The decision whether to perform renal biopsy on patients with persistent asymptomatic microscopic hematuria (AMH) with and without low-grade proteinuria (LGP) remains controversial as, although often diagnostic, the information gained seldom alters clinical management. Our study investigates the clinical value of renal biopsy in patients with isolated AMH versus those with AMH and LGP.
METHODS: Between 1996 and 2002, we identified 89 patients with AMH and 46 with AMH and LGP. The patients were asymptomatic, free from systemic illness, had a sterile urine, normal serum creatinine, normal renal and bladder ultrasound, less than 2.5 g proteinuria/day, underwent successful renal biopsy and were followed-up for a mean period of 46 +/- 12 months.
RESULTS: In patients with isolated AMH, thin basement membrane nephropathy (TBMN) was diagnosed in 43%, IgA nephropathy in 20%, minor abnormalities in 19% and normal biopsies in 18%. In patients with AMH and LGP, IgA nephropathy was diagnosed in 46%, other major nephropathies in 26%, minor abnormalities in 17%, TBMN in 7% and normal biopsies in 4%. At follow-up, 32% of AMH patients and 38% of AMH with LGP patients had a GFR of less than 90 ml/min and 36% and 56%, respectively were hypertensive.
CONCLUSIONS: The results support the current consensus that routine renal biopsy is not indicated for isolated AMH but suggest that biopsy is indicated for AMH and LGP identifying major and potentially progressive nephropathies in 70% of patients, who should be managed by specialist nephrologists.
Byung Soo Kim, Yong Kyun Kim, Young Shin Shin, Young Ok Kim, Ho Cheol Song, Yong Soo Kim, Euy Jin Choi
Natural history and renal pathology in patients with isolated microscopic hematuria.
Korean J Intern Med. 2009 Dec;24(4):356-61. doi: 10.3904/kjim.2009.24.4.356. Epub 2009 Nov 27.
Abstract/Text
BACKGROUND/AIMS: No definite conclusions have been reached about the natural history of patients with isolated microscopic hematuria (IMH). In this study, we observed the natural history of patients with IMH and examined factors related to a pathologic diagnosis and subsequent prognosis.
METHODS: We retrospectively evaluated 156 subjects with IMH who had a renal biopsy performed. Of the 156 subjects, 33.3% were diagnosed with IgA nephropathy, 23.7% with mesangial proliferative glomerulonephritis, 15.4% with glomerular minor lesion, and 12.8% with thin basement membrane nephropathy; 6.4% had normal biopsies.
RESULTS: We followed up with 100 subjects for about 31 months. During this follow-up period, two subjects who had received a pathologic diagnosis of IgA nephropathy developed chronic kidney disease. During the course of the study, one of these subjects presented with proteinuria and hypertension and the other with proteinuria. The overall incidences of proteinuria and hypertension were 6% and 5% respectively.
CONCLUSIONS: The prognosis for patients with IMH was relatively favorable, but patients developing proteinuria and/or hypertension require careful observation and management during the follow-up period.
K M Chow, B C Kwan, P K Li, C C Szeto
Asymptomatic isolated microscopic haematuria: long-term follow-up.
QJM. 2004 Nov;97(11):739-45. doi: 10.1093/qjmed/hch125.
Abstract/Text
BACKGROUND: Evidence to support current diagnostic and management approaches to asymptomatic haematuria is lacking and based on short-term clinical observation.
AIM: To ascertain the natural history and long-term outcome of asymptomatic and isolated haematuria, and to determine the clinical correlates of adverse renal events.
DESIGN: Prospective observational referral-based study.
METHODS: We evaluated 90 consecutive patients with isolated microscopic haematuria, first seen between 1985 and 1996 at an out-patient nephrology clinic. We defined adverse renal events as the development of proteinuria (> 0.5 g/24 h) on two consecutive occasions, development of hypertension, or impaired renal function characterized by glomerular filtration rate (GFR) of <60 ml/min/1.73 m(2) for 3 months or more.
RESULTS: There were 24 males and 66 females, median follow-up 5.2 years (total 442 patient-years). Mean age at presentation was 39 +/- 13 years. Fifteen (17%) had complete resolution of microscopic haematuria. One (1%) had transitional cell carcinoma of urinary bladder 20 months after initial presentation. Twelve (13%) developed hypertension, and 10 (11%) proteinuria. Only one developed chronic renal failure, 2.3 years after initial presentation. Altogether, 16 (19%) developed at least one adverse event, after a mean 42 months. Neither history of renal biopsy nor histological diagnosis of glomerular disease was predictive of renal events. Three independent variables were predictive of adverse renal events: baseline proteinuria (RR per 0.1 g/day 2.04; 95%CI 1.13-3.68; p = 0.018); MDRD-estimated GFR at presentation (RR per 10 ml/min/1.73 m(2) decrement 2.01; 95%CI 1.09-3.71; p = 0.025); and baseline serum urate (RR per 100 micromol/l 1.02; 95%CI 1.01-1.03; p = 0.009).
DISCUSSION: Asymptomatic microscopic haematuria can lead to adverse renal events, and warrants nephrologist evaluation and regular follow-up. Its isolated microscopic haematuria is closely related to early hints of chronic kidney disease, such as low-grade proteinuria and renal insufficiency, as well as hyperuricaemia.
Hae Min Lee, Ji In Hyun, Ji-Won Min, Kyungsoo Lee, Yong Kyun Kim, Euy Jin Choi, Ho Cheol Song
The Natural Course of Biopsy-Proven Isolated Microscopic Hematuria: a Single Center Experience of 350 Patients.
J Korean Med Sci. 2016 Jun;31(6):909-14. doi: 10.3346/jkms.2016.31.6.909. Epub 2016 Apr 18.
Abstract/Text
The increasing interest in healthcare and health screening events is revealing additional cases of asymptomatic isolated microscopic hematuria (IMH). However, a consensus of the evaluation and explanation of the IMH prognosis is controversial among physicians. Here, we present the natural course of IMH together with the pathological diagnosis and features to provide supportive data when approaching patients with IMH. We retrospectively evaluated 350 patients with IMH who underwent a renal biopsy between 2002 and 2011, and the pathological diagnosis and chronic histopathological features (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) were reviewed. Deterioration of renal function was examined during follow up. The patients with IMH were evaluated for a mean of 86 months. IgA nephropathy was the most common diagnosis in 164 patients (46.9%). Chronic histopathological changes were observed in 166 (47.4%) but was not correlated with proteinuria or a decline in renal function. Ten patients developed proteinuria, and all of them had IgA nephropathy. Three patients progressed to chronic kidney disease with an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) but none progressed to end stage renal disease. In conclusion, IMH had a generally benign course during 7-years of observation, although IgA nephropathy should be monitored if it progresses to proteinuria. Future prospective randomized studies may help conclude the long-term prognosis and lead to a consensus for managing IMH.
Z Kovacević, D Jovanović, V Rabrenović, J Dimitrijević, J Djukanović
Asymptomatic microscopic haematuria in young males.
Int J Clin Pract. 2008 Mar;62(3):406-12. doi: 10.1111/j.1742-1241.2007.01659.x.
Abstract/Text
AIM: The study involved 120 young males (aged 20.5 +/- 2.5 years) having undergone successful kidney biopsy because of asymptomatic haematuria with the aims to assess the prevalence of histological diagnosis and the natural history of the disease.
METHODS: The patients were selected from the population of conscripts who were referred to our clinic as a result of asymptomatic microhaematuria. All patients had a negative history of kidney disease, normal creatinine clearance (Ccr), while extrarenal causes of microhaematuria were excluded. The patients were divided into a group of 62 patients with isolated microhaematuria (IMH; proteinuria < 0.3 g/day) and a group of 58 patients with asymptomatic microhaematuria and proteinuria (AMHP; proteinuria > 0.3 g/day). After kidney biopsy patients were monitored for 3-9 years.
RESULTS: Normal biopsies and minor abnormalities were more frequent in IMH than in AMHP patients, who had IgA nephritis more frequently and significantly higher total pathohistological score. Based on the clinical and histological features, recommendations on patients' ability for military service were made. During the follow-up period, normal Ccr maintained in all patients. Macrohaematuria appeared in 42 patients and proteinuria worsened in eight patients (seven with AMHP). Urinary abnormalities disappeared in 20 patients with IMH and in eight with AMHP (p = 0.04).
CONCLUSION: Minimal histological changes and disappearance of urinary abnormalities were more frequent in IMH than in AMHP patients. Kidney biopsy is useful only in patients with AMHP but it is not necessary in IMH patients.
K Yamagata, Y Yamagata, M Kobayashi, A Koyama
A long-term follow-up study of asymptomatic hematuria and/or proteinuria in adults.
Clin Nephrol. 1996 May;45(5):281-8.
Abstract/Text
Between January 1, 1983 and December 31, 1992, 805 patients with asymptomatic proteinuria and/or hematuria were selected in the mass screening of 56,269 adults. We conducted prospective long-term follow-up studies of these patients and evaluated their clinical findings and renal histology. They were divided into three groups according to the first dipstick urinalysis findings: 478 patients with pure hematuria (H), 150 patients with concomitant hematuria and proteinuria (H & P), and 177 patients with proteinuria (P). The mean follow-up period was 5.80 +/- 4.42 years. Of the 478 patients with H, a specific cause of hematuria was found in 46 (9.6%), the remaining 432 (90.4%) patients were diagnosed as having asymptomatic hematuria (ASH). During the follow-up period, in the ASH patients, hematuria disappeared in 44.2%, 43.7% had persistent microhematuria without proteinuria, and 10.6% manifested proteinuria, none of the patients showed renal insufficiency. Of the 150 patients with H & P, 134 were diagnosed as having asymptomatic H & P. During the follow-up period, the hematuria and proteinuria disappeared in 16.4% of these patients, the proteinuria disappeared in 8.2%, and 14.9% of the patients showed renal insufficiency. Of the 177 patients with P, 151 were diagnosed has having asymptomatic P. During the follow-up period, proteinuria disappeared in 23.2%, and 10.6% showed renal insufficiency. Renal biopsy was performed in 151 patients in the study population who had a moderate degree of proteinuria; 68.2% of these patients had IgA nephropathy, 12.6% had non-IgA mesangial proliferative GN, 6.0% had membranous nephropathy, 5.3% had minimal change, and 2.6% had focal and segmental glomerular sclerosis. This study of the mass screening of urinalysis in asymptomatic adults showed that although the patients with pure hematuria did not exhibit renal insufficiency, 10.6% of these patients were proteinuric during the follow-up period. Therefore, careful observation and management are needed in these patients.
M H Khadra, R S Pickard, M Charlton, P H Powell, D E Neal
A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice.
J Urol. 2000 Feb;163(2):524-7.
Abstract/Text
PURPOSE: The commonly accepted diagnostic algorithm for hematuria includes excretory urography (IVP) and cystoscopy. Some have suggested that ultrasound of the upper urinary tract is adequate and that cystoscopy is not necessary in younger patients with microscopic hematuria. We ascertain whether a less intensive algorithm could be adopted while retaining diagnostic efficacy.
MATERIALS AND METHODS: A total of 1,930 patients were enrolled prospectively in the study at a hematuria clinic between October 1994 and March 1997. Evaluation consisted of basic demographics, history and examination, routine blood tests, urinalysis and cytology. All patients underwent plain abdominal radiography, renal ultrasound, IVP and flexible cystoscopy.
RESULTS: A total of 1,194 males and 736 females with a mean age of 58 years (range 17 to 96) were included in the study. Overall, 61% of patients had no basis found for hematuria, 12% had bladder cancer, 13% had urinary tract infection and 2% had stones. Kidney and upper tract tumors were noted in 14 patients (0.7%), including 4 who presented with microscopic hematuria. If only ultrasound or IVP had been performed 4 of these cases would have been missed. Of 982 patients presenting with microscopic hematuria 51 had cancer. Bladder cancer was found in 7 patients younger than 40 years.
CONCLUSIONS: Our findings suggest that cystoscopy cannot be safely avoided even in younger patients with microscopic hematuria. Only a combination of ultrasound and IVP detected all upper tract tumors.
S Murakami, T Igarashi, S Hara, J Shimazaki
Strategies for asymptomatic microscopic hematuria: a prospective study of 1,034 patients.
J Urol. 1990 Jul;144(1):99-101.
Abstract/Text
To establish strategies for treatment of asymptomatic microscopic hematuria we conducted a prospective study of 1,034 patients with this disease. The patients were examined by cystoscopy, urine cytology, abdominal ultrasound and excretory urography. On initial examination 30 highly significant lesions, including 24 cases of urological malignancies, 195 moderately significant lesions and 246 insignificant lesions were detected. In the remaining 563 patients no underlying lesion could be found. Of the 246 patients with insignificant lesions and 563 with unexplained asymptomatic microscopic hematuria followup was done in 421 at 6-month intervals for more than 1 year. A diagnosis became clear within 3 years in 22 patients, including 3 cases of bladder carcinoma and 1 of prostatic carcinoma.
A J Mariani, M C Mariani, C Macchioni, U K Stams, A Hariharan, A Moriera
The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis.
J Urol. 1989 Feb;141(2):350-5.
Abstract/Text
Between March 1976 and June 1985, 1,000 consecutive adults with asymptomatic gross or microscopic hematuria in the absence of proteinuria were evaluated urologically. Lesions that could account for the hematuria were detected in 88.3 per cent of the patients. Life-threatening lesions were diagnosed in 9.1 per cent of the patients, while lesions requiring at least observation were present in 22.8 per cent. The incidence of life-threatening lesions increased with age, with a sharp increase after age 50 years. Life-threatening lesions were more common in men (13.6 per cent) than in women (4.9 per cent). In general, as the degree of hematuria increased so did the yield of life-threatening lesions; however, there was no "safe" lower limit of hematuria. Of the patients with life-threatening lesions 18.6 per cent had at least 1 urinalysis with less than 3 red blood cells per high power field within 6 months of the diagnosis. The direct medical cost of a hematuria evaluation was $777. The difference in direct medical costs to diagnose and treat localized versus metastatic genitourinary cancer was $48,070 in 3 matched pairs of patients. In this study group 77 of 84 patients (92 per cent) diagnosed with genitourinary cancer had localized disease. A hematuria evaluation was cost-effective for all groups studied. A literature-based estimate of the life-threatening risks of diagnostic studies applied to the study data resulted in a 1.1 per cent life-threatening risk per hematuria evaluation. For all categories studied, except for women less than 40 years old with microscopic hematuria, the risk of a hematuria evaluation was less than the incidence of life-threatening lesions discovered as a result of the evaluation. Asymptomatic hematuria, whether gross or microscopic, is a significant finding and warrants evaluation from a risk-benefit and cost-effectiveness standpoint.
Christopher J D Wallis, Tristan Juvet, Yuna Lee, Rano Matta, Sender Herschorn, Ronald Kodama, Girish S Kulkarni, Raj Satkunasivam, William Geerts, Anne McLeod, Steven A Narod, Robert K Nam
Association Between Use of Antithrombotic Medication and Hematuria-Related Complications.
JAMA. 2017 Oct 3;318(13):1260-1271. doi: 10.1001/jama.2017.13890.
Abstract/Text
IMPORTANCE: Antithrombotic medications are among the most commonly prescribed medications.
OBJECTIVE: To characterize rates of hematuria-related complications among patients taking antithrombotic medications.
DESIGN, SETTING, AND PARTICIPANTS: Population-based, retrospective cohort study including all citizens in Ontario, Canada, aged 66 years and older between 2002 and 2014. The final follow-up date was December 31, 2014.
EXPOSURES: Receipt of an oral anticoagulant or antiplatelet medication.
MAIN OUTCOMES AND MEASURES: Hematuria-related complications, defined as emergency department visit, hospitalization, or a urologic procedure to investigate or manage gross hematuria.
RESULTS: Among 2 518 064 patients, 808 897 (mean [SD] age, 72.1 [6.8] years; 428 531 [53%] women) received at least 1 prescription for an antithrombotic agent over the study period. Over a median follow-up of 7.3 years, the rates of hematuria-related complications were 123.95 events per 1000 person-years among patients actively exposed to antithrombotic agents vs 80.17 events per 1000 person-years among patients not exposed to these drugs (difference, 43.8; 95% CI, 43.0-44.6; P < .001, and incidence rate ratio [IRR], 1.44; 95% CI, 1.42-1.46). The rates of complications among exposed vs unexposed patients (80.17 events/1000 person-years) were 105.78 for urologic procedures (difference, 33.5; 95% CI, 32.8-34.3; P < .001, and IRR, 1.37; 95% CI, 1.36-1.39), 11.12 for hospitalizations (difference, 5.7; 95% CI, 5.5-5.9; P < .001, and IRR, 2.03; 95% CI, 2.00-2.06), and 7.05 for emergency department visits (difference, 4.5; 95% CI, 4.3-4.7; P < .001, and IRR, 2.80; 95% CI, 2.74-2.86). Compared with patients who were unexposed to thrombotic agents, the rates of hematuria-related complications were 191.61 events per 1000 person-years (difference, 117.3; 95% CI, 112.8-121.8) for those exposed to both an anticoagulant and antiplatelet agent (IRR, 10.48; 95% CI, 8.16-13.45), 140.92 (difference, 57.7; 95% CI, 56.9-58.4) for those exposed to anticoagulants (IRR, 1.55; 95% CI, 1.52-1.59), and 110.72 (difference, 26.5; 95% CI, 25.9-27.0) for those exposed to antiplatelet agents (IRR, 1.31; 95% CI, 1.29-1.33). Patients exposed to antithrombotic agents, compared with patients not exposed to these drugs, were more likely to be diagnosed as having bladder cancer within 6 months (0.70% vs 0.38%; odds ratio, 1.85; 95% CI, 1.79-1.92).
CONCLUSIONS AND RELEVANCE: Among older adults in Ontario, Canada, use of antithrombotic medications, compared with nonuse of these medications, was significantly associated with higher rates of hematuria-related complications (including emergency department visits, hospitalizations, and urologic procedures to manage gross hematuria).
Nikita R Bhatt, Niall F Davis, William J Nolan, Robert J Flynn, Ted McDermott, Arun Z Thomas, Rustom P Manecksha
Incidence of Visible Hematuria Among Antithrombotic Agents: A Systematic Review of Over 175,000 Patients.
Urology. 2018 Apr;114:27-32. doi: 10.1016/j.urology.2017.11.023. Epub 2017 Nov 27.
Abstract/Text
OBJECTIVE: To determine the probability of visible hematuria with antithrombotic agents and to evaluate association of urologic etiology in antithrombotic-related hematuria.
METHODS: Preferred Reporting Items in Systematic Reviews and Meta-Analyses guidelines were followed to conduct a systematic review using search engines PUBMED and SCOPUS with the terms "(hematuria) OR (haematuria) OR urinary bleeding)) AND ((anticoagulants) OR anticoagulation) OR noac) OR novel anticoagulants) OR antiplatelet) OR dabigatran) OR rivaroxaban) OR apixaban) OR warfarin) OR aspirin) OR heparin) OR dipyridamole)." Raw data were used to perform a pooled analysis. Chi-square and logistic regression analysis were used for statistical analyses.
RESULTS: Twenty-two studies describing 175,114 patients met inclusion criteria. Odds ratio of hematuria with warfarin to rivoraxaban was 33 and warfarin to dabigatran was 16. The odds ratio of hematuria for oral anticoagulant (26.7%) to prophylactic parenteral anticoagulant (1.1%) agents was 9.6. Antiplatelet agents are 76 times less likely to cause hematuria compared to anticoagulants. Odds of hematuria with aspirin were 6.7 times the odds with clopidogrel and 3.5 times the odds with ticagrelor. Dabigatran was 198 times more likely to cause major hematuria compared to warfarin, whereas clopidogrel is 1.2 times more likely to cause major hematuria compared to aspirin. Urologic pathology was identified in 44% (234/532) of cases, malignancy in 24%.
CONCLUSION: Warfarin use poses the greatest risk for hematuria but is unlikely to cause major hematuria, whereas novel antithrombotic agents are more commonly associated with major hematuria. This review further characterizes the risk profile of antithrombotic agents and associated hematuria to equip clinicians with knowledge to choose an appropriate antithrombotic agent in patients with high-risk hematuria.
Copyright © 2017 Elsevier Inc. All rights reserved.
Emadouddin Moudi, Seyed-Reza Hosseini, Ali Bijani
Higher rate of microscopic hematuria in elderly patients who take regular doses of aspirin: Result from AHAP Study.
Caspian J Intern Med. 2016 Fall;7(4):278-282.
Abstract/Text
BACKGROUND: Aspirin is the most widely used drug in medicine for cardiovascular and as recently for its role in cancer prevention. Although the risk of bleeding events increased following regular use of aspirin, little is known about the association of aspirin and hematuria. The present study aimed to evaluate the association of regular aspirin use and microscopic hematuria in elderly.
METHODS: In this study, we have extracted the data of elderly people who participated in Amirkola Health and Aging Project (AHAP) and taking regular doses of aspirin. The prevalence of microscopic hematuria was compared between the elderly who took aspirin regularly and those who did not take it.
RESULTS: A total of 1243 individuals (54.22% males, 45.78% females) were entered in to the study. Two hundred and eighty-four (23%) elderly took regular doses of aspirin. Microscopic hematuria was seen in 305 (24.54%) elderly. The prevalence of microscopic hematuria was 27.27% in regular users of aspirin and 23.72% in non-users of aspirin (P=0.126). The prevalence of microscopic hematuria was significantly higher among the regular users of aspirin compared to non-users in multiple logistic regression analysis (P=0.035, OR=1.40, 95%CI: 1.02-1.92).
CONCLUSION: Taking regular doses of aspirin was accompanied with higher rate of microscopic hematuria in the elderly.
T F Culclasure, V J Bray, J A Hasbargen
The significance of hematuria in the anticoagulated patient.
Arch Intern Med. 1994 Mar 28;154(6):649-52.
Abstract/Text
BACKGROUND: There have been many case reports of substantial renal disease in association with anticoagulation, yet the intensity of anticoagulation has changed over the years. In 1986, the American College of Chest Physicians and the Heart, Lung, and Blood Institute recommended a decrease in anticoagulation intensity. In addition, a variety of new methods to investigate hematuria have evolved, including computed tomography and red blood cell morphologic analysis. Because of these developments, we initiated a prospective study to evaluate the relationship between anticoagulation, microscopic hematuria, and major genitourinary tract disease.
METHODS: To determine the incidence, prevalence, and cause of microscopic hematuria, patients receiving long-term anticoagulation therapy and controls not receiving such therapy were monitored with monthly urinalyses in a 2-year prospective study. Patients who developed hematuria were further studied for genitourinary tract disease. The incidence of hematuria was analyzed with regard to relative levels of anticoagulation.
RESULTS: The incidence of hematuria in the anticoagulated and control groups was 0.05 and 0.08 per 100 patient-months, respectively. The prevalence of hematuria was 3.2% in the anticoagulated group and 4.8% in the control group. Genitourinary tract disease was identified in 81% of patients with more than one episode of microscopic hematuria, and the cause of hematuria did not vary between groups. There was no correlation between the level of anticoagulation and the incidence of hematuria.
CONCLUSIONS: Anticoagulation at currently recommended levels does not predispose patients to hematuria. Identifiable genitourinary tract disease is present in the majority of anticoagulated patients with microscopic hematuria.
Chang Wook Jeong, Sangchul Lee, Seok-Soo Byun, Dong Ho Lee, Sang Eun Lee
No increase in risk of microscopic hematuria with aspirin use by asymptomatic healthy people.
JAMA Intern Med. 2013 Jun 24;173(12):1145-6. doi: 10.1001/jamainternmed.2013.567.
Abstract/Text
血尿診断ガイドライン改訂委員会（日本腎臓学会、日本泌尿器科学会、日本小児腎臓病学会、日本医学放射線学会、日本臨床検査医学会、日本臨床衛生検査技師会） 編：血尿診断ガイドライン2023. ライフサイエンス出版、2023年.
Said Fadel Mishriki, Ross Vint, Bhaskar K Somani
Half of visible and half of recurrent visible hematuria cases have underlying pathology: prospective large cohort study with long-term followup.
J Urol. 2012 May;187(5):1561-5. doi: 10.1016/j.juro.2011.12.100. Epub 2012 Mar 14.
Abstract/Text
PURPOSE: Visible hematuria has a cancer yield of up to 24.2%. A large proportion of cases will have no etiology. In this study we determined the incidence of pathology (benign and malignant) in patients with visible hematuria and those with persistent and recurrent visible hematuria, and evaluated the policy for investigations.
MATERIALS AND METHODS: Data were prospectively collected for 1,804 patients with visible hematuria at a United Kingdom teaching hospital from January 1999 to September 2007. In October 2010 the comprehensive hospital electronic database was checked for every individual patient to ensure no urological pathology was missed. All patients underwent standard hematuria investigations, including renal tract ultrasound and excretory urography or contrast enhanced computer tomography urogram, flexible cystoscopy and urine cytology.
RESULTS: The male-to-female ratio was 4.8:1. Median age ± SD was 67 ± 17.0 years (range 21 to 109). Median followup was 6.6 ± 2.5 years (range 1.5 to 11.6). No urological pathology was found in 965 (53.5%) patients. Malignant urological disease was found in 386 (21.4%) patients, of whom 329 had bladder tumors. There were 32 patients with persistent visible hematuria and no malignancy. Repeat investigation was performed in 69 patients reporting recurrence. Of these patients 35 received a significant urological diagnosis, including 12 (17.4%) urological malignancies, while 34 (49.3%) still had no diagnosis. Limitations include the possibility of missing pathology.
CONCLUSIONS: Almost 50% of patients presenting with visible hematuria will have a diagnosis. Therefore, all cases of visible hematuria require full standard investigations. Patients with no diagnosis can be discharged from followup. Recurrent visible hematuria after full initial negative findings requires repeat full standard investigations because 11.6% will have malignant pathology.
Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
George C Willis, Semhar Z Tewelde
The Approach to the Patient with Hematuria.
Emerg Med Clin North Am. 2019 Nov;37(4):755-769. doi: 10.1016/j.emc.2019.07.011.
Abstract/Text
Hematuria is common; whether gross or microscopic, it is incumbent on emergency providers to consider life-threatening and benign processes when evaluating these patients. Most workup is driven by a focused history and physical, including laboratory studies and diagnostic imaging. The cause originates in the genitourinary tract and, as long as the patient remains stable, they can be discharged with close outpatient follow-up. The importance of this cannot be stressed enough because hematuria, especially in the elderly, frequently signals the presence of urologic malignancy. In addition, the workup occasionally yields a nongenitourinary tract cause, and these patients often require emergent management.
Copyright © 2019 Elsevier Inc. All rights reserved.
Richard Deji Akiboye, Davendra M Sharma
Haematuria in Sport: A Review.
Eur Urol Focus. 2019 Sep;5(5):912-916. doi: 10.1016/j.euf.2018.02.008. Epub 2018 Feb 27.
Abstract/Text
CONTEXT: Haematuria is a common urological presentation associated with patient anxiety and clinically relevant underlying pathology. However, the prevalence and pathophysiology of haematuria following sporting exercise is less well documented.
OBJECTIVES: This review paper seeks to clarify the prevalence of microscopic and macroscopic haematuria in association with sporting exercise reported in the literature, and the pathophysiology behind it. We review the relation of haematuria to injury to the urinary tract in sport, as well as the incidence of underlying disease, urological and incidental, following investigation for exercise-induced haematuria.
EVIDENCE ACQUISITION: A non-systematic literature review was conducted of articles and studies using the Pubmed database. Articles were selected with preference for the highest level of evidence available, with relevant data extracted, analysed, and summarised. Supplementary information was collected by cross-referencing the reference lists.
EVIDENCE SYNTHESIS: Multiple studies have shown that clinically significant haematuria is common after exercise. Physiological changes occurring during exercise result in increased glomerular permeability and microscopic haematuria in up to 95% of cases. The degree of haematuria is related to the intensity of the exercise. However, participating in contact sports increases the risk of macroscopic haematuria. Red cell haemolysis and rhabdomyolysis also play a role in urine discolouration following exercise and can be present in 30%. Haematuria following exercise-related trauma is regarded an important indication for further urological investigation. Haematuria may be absent in 44% of cases of urological injury. Renal trauma accounts for 80% of urological trauma, with 30% of these being due to sporting activity. Incidental findings on computed tomography for haematuria are common, with 50% showing positive extraurinary findings. Incidental malignancy, however, is rare.
CONCLUSIONS: Haematuria is common following exercise and results from physiological changes and contact-related trauma to the urinary tract. All cases of haematuria should be investigated as underlying trauma and extraurinary disease are common incidental findings on investigation.
PATIENT SUMMARY: Blood in the urine following exercise is a common phenomenon and occurs due to vascular responses to sports and trauma as well as blood and muscle cell breakdown. Although it may not be present in all cases of trauma, blood in the urine should be investigated due to the risk of discovering underlying injury to the urinary tract and other incidental findings.
Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.
Aart J Van Der Molen, Nigel C Cowan, Ullrich G Mueller-Lisse, Claus C A Nolte-Ernsting, Satoru Takahashi, Richard H Cohan, CT Urography Working Group of the European Society of Urogenital Radiology (ESUR)
CT urography: definition, indications and techniques. A guideline for clinical practice.
Eur Radiol. 2008 Jan;18(1):4-17. doi: 10.1007/s00330-007-0792-x. Epub 2007 Nov 1.
Abstract/Text
The aim was to develop clinical guidelines for multidetector computed tomography urography (CTU) by a group of experts from the European Society of Urogenital Radiology (ESUR). Peer-reviewed papers and reviews were systematically scrutinized. A summary document was produced and discussed at the ESUR 2006 and ECR 2007 meetings with the goal to reach consensus. True evidence-based guidelines could not be formulated, but expert guidelines on indications and CTU examination technique were produced. CTU is justified as a first-line test for patients with macroscopic haematuria, at high-risk for urothelial cancer. Otherwise, CTU may be used as a problem-solving examination. A differential approach using a one-, two- or three-phase protocol is proposed, whereby the clinical indication and the patient population will determine which CTU protocol is employed. Either a combined nephrographic-excretory phase following a split-bolus intravenous injection of contrast medium, or separate nephrographic and excretory phases following a single-bolus injection can be used. Lower dose (CTDIvol 5-6 mGy) is used for benign conditions and normal dose (CTDIvol 9-12 mGy) for potential malignant disease. A low-dose (CTDIvol 2-3 mGy) unenhanced series can be added on indication. The expert-based CTU guidelines provide recommendations to optimize techniques and to unify the radiologist's approach to CTU.
Acanthocyturia--a characteristic marker for glomerular bleeding.
Kidney Int. 1991 Jul;40(1):115-20.
Abstract/Text
Daniel A Barocas, Stephen A Boorjian, Ronald D Alvarez, Tracy M Downs, Cary P Gross, Blake D Hamilton, Kathleen C Kobashi, Robert R Lipman, Yair Lotan, Casey K Ng, Matthew E Nielsen, Andrew C Peterson, Jay D Raman, Rebecca Smith-Bindman, Lesley H Souter
Microhematuria: AUA/SUFU Guideline.
J Urol. 2020 Oct;204(4):778-786. doi: 10.1097/JU.0000000000001297. Epub 2020 Jul 23.
Abstract/Text
PURPOSE: Patients presenting with microhematuria represent a heterogeneous population with a broad spectrum of risk for genitourinary malignancy. Recognizing that patient-specific characteristics modify the risk of underlying malignant etiologies, this guideline sought to provide a personalized diagnostic testing strategy.
MATERIALS AND METHODS: The systematic review incorporated evidence published from January 2010 through February 2019, with an updated literature search to include studies published up to December 2019. Evidence-based statements were developed by the expert Panel, with statement type linked to evidence strength, level of certainty, and the Panel's judgment regarding the balance between benefits and risks/burdens.
RESULTS: Microhematuria should be defined as ≥ 3 red blood cells per high power field on microscopic evaluation of a single specimen. In patients diagnosed with gynecologic or non-malignant genitourinary sources of microhematuria, clinicians should repeat urinalysis following resolution of the gynecologic or non-malignant genitourinary cause. The Panel created a risk classification system for patients with microhematuria, stratified as low-, intermediate-, or high-risk for genitourinary malignancy. Risk groups were based on factors including age, sex, smoking and other urothelial cancer risk factors, degree and persistence of microhematuria, as well as prior gross hematuria. Diagnostic evaluation with cystoscopy and upper tract imaging was recommended according to patient risk and involving shared decision-making. Statements also inform follow-up after a negative microhematuria evaluation.
CONCLUSIONS: Patients with microhematuria should be classified based on their risk of genitourinary malignancy and evaluated with a risk-based strategy. Future high-quality studies are required to improve the care of these patients.
E M Messing, T B Young, V B Hunt, J M Wehbie, P Rust
Urinary tract cancers found by homescreening with hematuria dipsticks in healthy men over 50 years of age.
Cancer. 1989 Dec 1;64(11):2361-7.
Abstract/Text
In a homescreening study 235 asymptomatic men, 50 years of age and older without known causes of hematuria, tested their urine each week with a chemical reagent strip for the presence of blood for 1 year. Forty-four men had hematuria at least once, and 31 had a full urologic evaluation. Of these, eight were found to have urinary cancers and seven had nonmalignant diseases warranting immediate treatment. In six of these 15 men (only two with cancer) hematuria occurred in over 1/3 of the testings, and in four hematuria was found on microscopic urinalysis at the time of urologic evaluation. The degree of hematuria was unrelated to the seriousness of its cause. We conclude that in this population hematuria occurs intermittently and when found, regardless of quantity or symptoms, serious underlying pathology must be ruled out. Furthermore, regular hematuria home testing offers a promising means of detecting urinary cancers and other diseases that warrant therapy in asymptomatic men 50 years of age and older.
E M Messing, T B Young, V B Hunt, E B Roecker, A M Vaillancourt, W J Hisgen, E B Greenberg, M E Kuglitsch, J D Wegenke
Home screening for hematuria: results of a multiclinic study.
J Urol. 1992 Aug;148(2 Pt 1):289-92.
Abstract/Text
The majority of urinary tract tumors cause bleeding in the urine. A program designed to detect hematuria before it is grossly apparent may contribute to earlier detection and more successful treatment of these malignancies. To test this hypothesis a hematuria home screening study was conducted. A total of 1,340 healthy men 50 years old or older used chemical reagent strips for 14 consecutive days to test the urine. Of the men 283 (21.1%) had at least 1 episode of hematuria. Of the 192 hematuria positive men who received a complete urological evaluation 16 (8.3%) had urological cancers and 47 (24.5%) had other hematuria-causing diseases that required immediate treatment. The quantity and frequency of hematuria were not related to disease severity. A hematuria home screening regimen is feasible and economical, and may promote the early detection of urinary tract cancers and other diseases in men more than 50 years old.
血尿診断ガイドライン編集委員会：血尿診断ガイドライン2013. ライフサイエンス出版、2013年.
Tim Wollin, Bruno Laroche, Karen Psooy
Canadian guidelines for the management of asymptomatic microscopic hematuria in adults.
Can Urol Assoc J. 2009 Feb;3(1):77-80.
Abstract/Text
Robert A Cohen, Robert S Brown
Clinical practice. Microscopic hematuria.
N Engl J Med. 2003 Jun 5;348(23):2330-8. doi: 10.1056/NEJMcp012694.
Abstract/Text
Howard Jung, Joseph M Gleason, Ronald K Loo, Hetal S Patel, Jeff M Slezak, Steven J Jacobsen
Association of hematuria on microscopic urinalysis and risk of urinary tract cancer.
J Urol. 2011 May;185(5):1698-703. doi: 10.1016/j.juro.2010.12.093. Epub 2011 Mar 21.
Abstract/Text
PURPOSE: We determined the incidence of urinary tract cancer in patients with hematuria, stratified risk by age, gender and hematuria degree, and examined current best policy recommendations.
MATERIALS AND METHODS: We performed a large, retrospective population based cohort study of patients who underwent microscopic urinalysis during 2004 and 2005 in a large managed care organization. Patients were followed for 3 years for urinary tract cancer.
RESULTS: We identified 772,002 patients who underwent urinalysis during the study period. After exclusions due to previous hematuria, age less than 18 years, pregnancy, urinary tract infection, inpatient status and prior urinary tract cancer 309,402 patients were available for analysis, of whom 156,691 had hematuria. The overall 3-year incidence of urinary tract cancer in those with hematuria was 0.68%. Older age (greater than 40 years OR 17.0, 95% CI 11.2-25.7), greater hematuria (greater than 25 red blood cells per high power field OR 4.0, 95% CI 3.5-4.5) and male gender (OR 4.8, 95% CI 4.2-5.6) were associated with a higher risk of cancer. The American Urological Association definition of microhematuria had 50% sensitivity, 84% specificity and 1.3% positive predictive value.
CONCLUSIONS: The incidence of urinary tract cancer is low even in individuals with microhematuria. Thus, current best policy recommendations do not perform well. Since older age, male gender and greater hematuria are associated with a higher risk of cancer, future studies should evaluate strategies that target these populations.
Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Quinn K Lippmann, Jeff M Slezak, Shawn A Menefee, Casey K Ng, Emily L Whitcomb, Ronald K Loo
Evaluation of microscopic hematuria and risk of urologic cancer in female patients.
Am J Obstet Gynecol. 2017 Feb;216(2):146.e1-146.e7. doi: 10.1016/j.ajog.2016.10.008. Epub 2016 Oct 14.
Abstract/Text
BACKGROUND: Urologic cancer has a lower prevalence in women compared with men; however, there are no differences in the recommended evaluation for women and men with microscopic hematuria.
OBJECTIVES: The purpose of this study was to identify risk factors that are associated with urologic cancer in women with microscopic hematuria and to determine the applicability of a hematuria risk score for women.
STUDY DESIGN: We conducted a retrospective cohort study within an integrated healthcare system in Southern California. All urinalyses with microscopic hematuria (>3 red blood cells per high-power field) that were performed from 2009-2015 were identified. Women who were referred for urologic evaluation were entered into a prospective database. Clinical and demographic variables that included the presence of gross hematuria in the preceding 6 months were recorded. The cause of the hematuria, benign or malignant, was entered into the database. Cancer rates were compared with the use of chi-square and logistic regression models. Adjusted risk ratios of urologic cancer were estimated with the use of multivariate regression analysis. We also explored the applicability of a previously developed, gender nonspecific, hematuria risk score in this female cohort.
RESULTS: A total of 2,705,696 urinalyses were performed in women during the study period, of which 552,119 revealed microscopic hematuria. Of these, 14,539 women were referred for urologic evaluation; clinical data for 3573 women were entered into the database. The overall rate of urologic cancer was 1.3% (47/3573). In women <60 years old, the rate of urologic cancer was 0.6% (13/2053) compared with 2.2% (34/1520) in women ≥60 years old (P<.01). In women who reported a history of gross hematuria, the rate of urologic cancer was 5.8% (20/346) compared with a 0.8% (27/3227) in women with no history of gross hematuria (P<.01). In multivariate analysis, > 60 years old (odds ratio, 3.1; 95% confidence interval, 1.6-5.9), a history of smoking (odds ratio, 3.2; 95% confidence interval, 1.8-5.9), and a history of gross hematuria in the previous 6 months (odds ratio, 6.2; 95% confidence interval, 3.4-11.5) were associated with urologic cancers. A higher microscopic hematuria risk score was associated with an increased risk of cancer in this test cohort (P<.01). Women in the highest risk group had a urologic cancer rate of 10.8% compared with a rate of 0.5% in the lowest risk group.
CONCLUSIONS: In this female population, >60 years old and a history of smoking and/or gross hematuria were the strongest predictors of urologic cancer. Absent these risk factors, the rate of urologic cancer did not exceed 0.6%. A higher hematuria risk score correlated significantly with the risk of urologic cancer in this female test cohort.
Copyright © 2016 Elsevier Inc. All rights reserved.
Kunitoshi Iseki, Yoshiharu Ikemiya, Chiho Iseki, Shuichi Takishita
Proteinuria and the risk of developing end-stage renal disease.
Kidney Int. 2003 Apr;63(4):1468-74. doi: 10.1046/j.1523-1755.2003.00868.x.
Abstract/Text
BACKGROUND: Dipstick urinalysis for proteinuria and hematuria has been used to screen renal disease, but evidence of the clinical impact of this test on development of end-stage renal disease (ESRD) is lacking.
METHODS: We assessed development of ESRD through 2000 in 106,177 screened patients (50,584 men and 55,593 women), 20 to 98 years old, in Okinawa, Japan, who participated in community-based mass screening between April 1983 and March 1984. We used data from the Okinawa Dialysis Study Registry to identify ESRD patients. Multivariate logistic analyses were performed to calculate adjusted odds ratio and 95% confidence interval (95% CI) for the significance of proteinuria and hematuria on the risk of developing ESRD with confounding variables such as age, gender, blood pressure, and body mass index. A similar analysis was repeated in a subgroup of screened patients in whom serum creatinine data existed.
RESULTS: During 17 years of follow-up, 420 screened persons (246 men and 174 women) entered the ESRD program. We identified a strong, graded relationship between ESRD and dipstick urinalysis positive for proteinuria; adjusted odds ratio (95% CI) was 2.71 (2.51 to 2.92, P < 0.001). Similar trends were observed after adding serum creatinine data. Compared with dipstick-negative proteinuria, adjusted odds ratio (95% CI) of proteinuria (1+) was 1.93 (1.53 to 2.41, P < 0.001) in men and 2.42 (1.91 to 3.06, P < 0.001) in women.
CONCLUSION: Proteinuria was a strong, independent predictor of ESRD in a mass screening setting. Even a slight increase in proteinuria was an independent risk factor for ESRD. Therefore, asymptomatic proteinuria warrants further work-up and intervention.
