A 30 year old man is referred for a medical check up before taking a life insurance policy. He is asymptomatic, gives no relevant history, is on no treatment and physical examination is unremarkable. Routine dip-stick analysis of a mid­stream specimen of urine reveals traces of blood. What is to be done?peer-reviewe

Vella, Mario P.

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42 Malta Medical Journal    Volume 17   Issue 01   March 2005A 30 year old man is referred for a medical check up beforetaking a life insurance policy. He is asymptomatic, gives norelevant history, is on no treatment and physical examinationis unremarkable. Routine dip-stick analysis of a mid–streamspecimen of urine reveals traces of blood. What is to be done?IntroductionThis is an all too common problem. The causes ofmicroscopic haematuria range from minor to life threatening.They vary with age. Not all cases require urgent and in-depthinvestigation. On the other hand one must be careful not to missconditions, particularly neoplasia, where early diagnosis andmanagement can make a real difference to outcomes and toquality of patient life.1  Patients with glomerular disease alsohave better outcomes when referred early for specialistmanagement.2Definitions and Concepts Many subjects will have microscopic haematuria at somestage in their lives. In the overall population, the pointprevalence is around 4%.3  Grossfield and Carroll carried out ametanalysis in 1998 and put the  overall incidence at 0.2 to21.1%. A relatively high proportion were found to have a specificcause, and of these 3.4-56% had moderately or highly significantlesions at the time of diagnosis.1The American Urological Association (AUA) Best PracticePolicy Panel on Asymptomatic Microscopic Haematuria definesmicroscopic haematuria as three or more red blood cells (RBCs)per high power microscopic field (HPF) of urinary sedimentfrom two or three properly collected urinalysis specimens.4  Mostindividuals will have 1 RBC or less per HPF or per ml. This isequivalent to a loss of 1-10 RBCs per nephron daily. These cellsare mostly dysmorphic. 5 mls. of blood per litre or 25,000 RBCsper ml will produce visible or gross haematuria, and twice thisamount will produce persistent gross haematuria. Dip-sticksdetect blood from lysed RBC’s, which lyse more easily in alkalineurine. Their active reagent is usually orthotoluidine. This alsoMicroscopic HaematuriaIn PracticeMario P Vellagives a positive test in intravascular haemolysis withhaemoglobinuria, in myoglobinuria and when there is infectionwith certain peroxidase producing bacteria. Many healthyindividuals with urinary RBC losses at the upper limits of normalwill have positive tests at some time in their lives. False negativetests occur with urine containing high concentrations of ascorbicacid. Dip-stick analysis is 100% sensitive, but only 62% specific.Hence, a persistently positive test must always be corroboratedby urinalysis and microscopy.5  Table 1 summarises theprevalence of microscopic haematuria by age.CausesThe two questions to be kept in mind when investigatingmicroscopic haematuria are:1. Is the haematuria glomerular, non-glomerular(parenchymal) or extrarenal in origin?2. Depending on the patient’s age, what is the main differentialdiagnosis? 6It is worth remembering that diseases and lesions of theurinary tract do not automatically cause haematuria, and thisis often intermittent. Sugimura et al (2001) noted haematuria(microscopic or gross) in only 35% of 113 patients with renalcell carcinoma (RCC), while 94% of 236 patients with urothelialmalignancies had haematuria at some stage. Of 823 patientswith asymptomatic microscopic haematuria only 2.1% hadurothelial malignancies and only 0.2% had RCC. However, ofthose aged over 50 years 6.2% had urothelial malignancies.7 Ofabout 100 young male military recruits investigated forMario P Vella MRCP (UK) MScDepartment of MedicineSt Luke’s Hospital, Guardamangia, MaltaEmail: mariopio@maltanet.netTable 1: Prevalence of microscopic haematuria by age.(Adapted from “Oxford Textbook of Clinical Nephrology”;2nd Edition). 5Age Category Prevalencechildren < 12 years 1-4%Young Males 18-33 years(Military recruits) 5.2%Older Adults > 50 years 4-18% males; 14% femalesElderly > 75 years 13% males; 9% femalesMalta Medical Journal    Volume 17   Issue 01   March 2005 43ManagementOne must confirm that microscopic haematuria is reallypresent by repeating dip-stick urine analysis once or twice,always using a clean-catch mid-stream specimen. Women ofreproductive age should produce their sample before or severaldays after their menses. If the presence of microscopichaematuria is corroborated, one should immediately perform aformal urine analysis and microscopy on a fresh, early morningunspun and acidic urine sample. A Fuchs-Rosenthal countingchamber is used, ideally utilising phase-contrast microscopy.5If bacteria are present, a urine culture is essential. 10 It isimportant that when submitting urine to a laboratory,transportation times should be kept as short as possible. It isessential to take a full history with particular attention tosymptoms, present and past history of diabetes, hypertension,Table 2: Causes of Microscopic Haematuria (Adapted from the “Oxford Textbook of Clinical Nephrology” 2 nd Edition, and“Primer on Kidney Diseases” 2 nd Edition). 5,6A. Glomerular• Proliferative Glomerulopathies:1. Primary  (IgA Nephropathy,Postinfective, Mesangiocapillary, Rapidly Progressive/Crescentic)2. Secondary ( SLE, Anti glomerular basement membrane disease, systemic vasculitis, associated with bacteraemiaeg SBE, associated with Hepatitis B and C, Essential Mixed Cryoglobulinaemia).• Non-proliferative Glomerulopathies: (Minimal Change, Focal Segmental  Glomerulosclerosis, Membranous, HaemolyticUraemic Syndrome)• Familial Glomerular Disease: (Alport’s, Thin glomerular basement membrane disease, Fabry’s disease, Nail-patellasyndrome)B. Non-glomerular• Neoplasia (RCC, Wilm’s tumour, Benign cysts, Angiomyolipoma of Tuberous Sclerosis, Multiple Myeloma)• Vascular (Renal infarction, Renal vein thrombosis, Malignant hypertension, Arteriovenous malformation, Loin-painHaematuria Syndrome)• Metabolic (Hypercalcuria, Hyperoxaluria, Hyperuricosuria, Cystinuria)• Familial (Autosomal dominant polycystic kidney disease, Medullary cystic disease, Medullary sponge kidney)• Papillary Necrosis (Analgesia, Infection, Diabetes, Obstruction, Sickle cell anaemia and trait, Tuberculosis, AnkylosingSpondylitis, Alcohol Abuse)• Hydronephrosis (All causes)• Drug Induced (NSAID’s, Aminoglycosides)• Trauma (Renal and extrarenal; including exercise induced haemolysis as in “Jogger’s Haematuria”)C. Extrarenal• Urolithiasis• Urothelial neoplasia• Prostatic Adenocarcinoma• Benign Prostatic Hypertrophy (BPH)• Infective (Bacterial, Chlamydial, Fungal, Tuberculosis, Schistosomiasis)• Drug Induced (Cyclophosphamide, Anticoagulants)• Trauma to Lower Urinary Tract and Genitalia.• Genital Bleeding.• Factitious (Deliberate addition of blood to urine sample)SLE – systemic lupus erythematosus; SBE – subacute bacterial endocarditis; NSAIDS – non-steroidal anti-inflammatorydrugs; RCC – renal cell carcinomaasymptomatic microscopic haematuria by Sparwasser et alin1994, 31.2 % had pathology and this was almost equallydivided between glomerular disease (16.5% and most commonlyIgA Nephropathy), and urothelial disease, of which only 2 hadurothelial carcinomas.8By far the greatest cause at all ages is infection of the urinarytract, followed by urolithiasis. A great age divide thus emerges;with those over 50 years having a higher incidence of urothelialdisease and those of a younger age being less likely to haveserious conditions and these being predominantly glomerularin origin.5,6  Small children below the age of three represent aspecial category where glomerular causes predominate but withWilm’s tumour, congenital abnormalities of the genitourinarytract and rhabdomyosarcoma of the bladder must be kept inmind.9  Table 2 lists the causes of microscopic haematuria.44 Malta Medical Journal    Volume 17   Issue 01   March 2005Key: UTI – urinary tract infection; U/E – urea and electrolytesFigure 1: Algorithm for the management of microscopic haematuriadocumented nephrological and urological problems; familyhistory; medications (including analgesics, anticoagulants, over-the-counter and herbal preparations) and social andoccupational history. A full physical examination must beperformed, including blood-pressure measurement,fundoscopy, a rectal examination and examination of theexternal genitalia.When to Refer? A majority of positively screening subjects will not havemajor pathology. Chow et al (2004) followed 90 consecutivepatients with isolated microscopic haematuria between 1985and 1996. The median follow-up time was 5.2 years. 17% ofthese had complete resolution of the problem. 13% developedhypertension and 11% developed proteinuria. Only onepatient developed a malignancy, and another one went onto end-stage renal failure. Predictors for a poor outcome atstart of follow-up were proteinuria, diminished glomerularfiltration rate and hyperuricaemia.11 Eardley et al (2004)carried out a retrospective study of a series of patients whounderwent renal biopsy for microscopic haematuria andcompared those without albuminuria with patients who hadMalta Medical Journal    Volume 17   Issue 01   March 2005 45micro- or macro-albuminuria. It was noted that the latter had asignificantly higher incidence of severe glomerular disease andsignificantly worse outcomes.12  Microalbuminuria is anindependent marker for an increased risk of cardiac events.13Not all glomerular disease automatically produces microscopichaematuria, especially if secondary to systemic illness such asdiabetes and hypertension.14There is general agreement that patients over 50 years ofage should be referred for urological assessment.15   It thustranspires that certain categories of patients are more “at risk”of having significant pathology (Table 3). These should bereferred for specialist assessment, with age, symptoms andclinical findings guiding one to refer to a urologist or to anephrologist. Asymptomatic patients who do not fall within thehigh risk category and who have a normal urine microscopycan be investigated and followed up at primary care level withfull blood count, urea, electrolytes and creatinine, blood glucose,calcium, uric acid and coagulation screen. Where the findingscan be reasonably explained away by the presence of a lowerurinary tract infection (UTI), this can be similarly investigated,treated and followed up. Figure 1 is an algorithm for themanagement of this clinical problem.Special InvestigationsOne should proceed to a straight penetrated X-ray of theabdomen (KUB), renal ultrasonography, and in selectedpatients, intravenous urography and computerized tomographyof the urinary tract. All patients with a history of grosshaematuria, and those with microscopic haematuria aged over50, require flexible cystourethroscopy. In children, invasiveinvestigations and radiation hazards should be kept to aminimum.16The role of renal biopsy is controversial and yields verylittle information when there is asymptomatic haematuria ormicroscopic haematuria with low-grade haematuria. It isrequired where there is significant proteinuria (over 0.5-1.0gdaily) or impaired renal function besides microscopichaematuria.17In Conclusion1. Microscopic haematuria is common.2. Not all patients require specialist referral but those at riskshould be referred.3. Patients aged over 50 years have a greater likelihood ofurological problems, while those below 40 years have amuch lower risk of problems, with these tending to beglomerular.References1. Grossfeld GD, Carroll PR. Evaluation of asymptomatic micro-scopic haematuria. Urol Clin North Am. 1998 Nov;25(4):661-76.2. Powe NR. Early referral in kidney diseases: an enormousopportunity for prevention. AJKD. 2003 Feb;41(2):505-507.3. Tomson CRV. Indications for renal biopsy in chronic renaldisease. Clinical Medicine. 2003 Vov/Dec;3(6):513-517.4. Grossfeld GD, Wolf JS Jr, Litwan MS, Hricak H, Shuler CL,Carroll PR et al. Asymptomatic microscopic haematuria inadults: summary of AUA best practice policy recommendations.Am Fam Physician. 2001 Mar 15;63(6):1145-54.5. Davison AM, Stewart Cameron J, Gruenfeld JP, Kerr DNS, RitzE, Winearls CG. Oxford Textbook of Clinical Nephrology OxfordMedical Publications 2nd Edition, Vol 1, Chapter 3.4:447-452.6. Greenberg A. Primer on Kidney Diseases (National KidneyFoundation) 2nd Edition, Chapter 4:36-41.7. Sugimura K, Ikemoto SI, Kawashima H, Nishisaka N, KishimotoT. Microscopic haematuria as a screening marker for urinarytract malignancies. Int J Urol. 2001 Jan;8(1):1-5.8. Sparwasser C, Cimniak HU, Treiber U, Pust RA. Significance ofthe evaluation of asymptomatic microscopic haematuria inyoung men. Br J Urol . 1994 Dec;74(6):723-729.9. Patel HP, Bissler JJ. Haematuria in children. Pediatr Clin NorthAm. 2001 Dec;48(6):1519-37.10. Misdraji J, Nguyen PL. Urinalysis. When— and when not—toorder. Postgrad Med. 1996 Jul;100(1):173-6, 181-2, 185-8.11. Chow KM, Kwan BC, Li PK, Szeto CC. Asymptomatic isolatedmicroscopic haematuria: long-term follow up. QJM.Nov;97(11):739-45.12. Eardley KS, Ferreira MA, Howie AJ, Gosling P, Lipkin GW.Urinary albumin excretion: a predictor of glomerular findings inadults with microscopic haematuria. QJM. 2004 May;97(5):297-301.13. Weiner DE, Sarnak MJ. Microalbuminuria: a marker ofcardiovascular risk. AJKD (Editorial). 2003 Sep;42(3):596-98.14. Waz WR, Quattrin T, Feld LG. Haematuria in children andadolescents with insulin dependent diabetes mellitus. J DiabetesComplications. 1995 Jul-Sep;9(3):194-7.15. Alishahi S, Byrne D, Goodman CM, Baxby K. Haematuriainvestigation based on a standard protocol: emphasis on thediagnosis of urological malignancy. J R Coll Surg Edinb. 2002Feb;47(1):422-7.16. Cilento BG Jr, Stock JA, Kaplan GW. Haematuria in Children. Apractical approach. Urol Clin North Am. 1995 Feb;22(1):43-55.17. Hall CL, Bradley R, Kerr A, Attoti, Peat D. Clinical value of renalbiopsy in patients with asymptomatic microscopic haematuriawith and without low-grade proteinuria. Clin Nephrol.Oct;62(4):267-72.Table 3: Markers of Increased Risk of SignificantPathology in Patients with Micorcopsic Haematuria1. Those over 50 years2. Children below 3 years3. Presence of gross haematuria at any stage (unlessalready investigated)4. Past history of renal disease5. Proteinuria (including microalbuminuria)6. Presence of diabetes and/or hypertension of more than3 year’s duration (even if well controlled)7. Family history of renal disease8. Presence of pain or systemic symptoms9. Smokers (because of association with bladder cancer),occupational exposure to chemicals, history of analgesicabuse or use of herb remedies.10. An abnormal urine microscopy, unless this is clearly dueto a lower UTIUTI – urinary tract infection

An abnormal urine microscopy, unless this is clearly due to a lower UTI UTI – urinary tract infection

Asymptomatic isolated microscopic haematuria: long-term follow up.

Asymptomatic microscopic haematuria in adults: summary of AUA best practice policy recommendations. Am Fam Physician.

Clinical value of renal biopsy in patients with asymptomatic microscopic haematuria with and without low-grade proteinuria.

Early referral in kidney diseases: an enormous opportunity for prevention. AJKD.

Evaluation of asymptomatic microscopic haematuria. Urol Clin North Am.

Haematuria in children and adolescents with insulin dependent diabetes mellitus. J Diabetes Complications.

Haematuria in Children. A practical approach. Urol Clin North Am.

Haematuria in children. Pediatr Clin North Am.

Haematuria investigation based on a standard protocol: emphasis on the diagnosis of urological malignancy.

Indications for renal biopsy in chronic renal disease. Clinical Medicine.

Microalbuminuria: a marker of cardiovascular risk. AJKD (Editorial).

Microscopic haematuria as a screening marker for urinary tract malignancies.

Presence of diabetes and/or hypertension of more than 3 year’s duration (even if well controlled)

Presence of gross haematuria at any stage (unless already investigated)

Presence of pain or systemic symptoms

Significance of the evaluation of asymptomatic microscopic haematuria in young men.

Smokers (because of association with bladder cancer), occupational exposure to chemicals, history of analgesic abuse or use of herb remedies.

Urinary albumin excretion: a predictor of glomerular findings in adults with microscopic haematuria. QJM.

When— and when not—to order. Postgrad Med.

Microscopic Haematuria

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