Case 3 – Alan Hays Consultation 1 Doctor : You have not seen 38 yr old Alan Hays, a roofer, before, as he is a new patient. The nurse picked up microscopic haematuria at his new patient medical and asked him to come in to discuss this with you.

Case 3 – Alan Hays Consultation 1 Patient : You are Alan Hays, aged 38, a roofer. You moved house recently, and joined the practice, at your new pt medical the nurse found blood in your urine, and asked you to book in with the doctor. You are fit and well, completely asymptomatic. You live with your 35 yr old girlfriend, Donna. You have taken up running with a couple of mates to try to get fitter. You smoke 10/day and drink 15 pints beer per wk.

Microscopic/ Invisible haematuria Visible haematuria (VH) = macroscopic haematuria/ gross haematuria Invisible haematuria (IH) = microscopic haematuria or ‘dipstick positive haematuria’ Significant haematuria is defined as: any single episode of VH any single episode of symptomatic NVH (in absence of UTI or other transient causes). persistent asymptomatic -IH (in absence of UTI or other transient causes) : defined as 2 out of 3 dipsticks positive (≥1+, not trace) for IH

Microscopic/ Invisible Haematuria – what it isn’t Transient microscopic haematuria: UTI Exercise related (repeat ≥ 3d after exercise) Spurious microscopic haematuria: Menstrual contamination Sexual intercourse Foods (esp. beetroot, blackberries and rhubarb) Rhabdomyolysis Drugs (doxorubicin, chloroquine, rifampicin) Chronic lead or mercury poisoning.

Case 3 – Alan Hays Consultation 2 Doctor: Alan has come back to see you to discuss a second urine test, which shows 1 + blood only. He has just been on holiday for a week to Tenerife, where he had a good rest. He feels great, but is a bit anxious now about his test result.

Case 3 – Alan Hays Consultation 2 – patient: You were asked to bring in a further urine sample 1 wk later, and the receptionist called to ask you to book in with the doctor again to discuss the result. If asked to be examined your BP is 122/73

How risky is it? 2 – 13% of the population may have IH but < 1.5% of these have significant pathology. Urine dipstick testing is highly sensitive (97%) and moderately specific (75%) for the detection of haematuria Visible haematuria is associated with cancer in 8-25% of cases, IH assoc with cancer in only 2.6% < 0.5% of people aged under 50 years investigated for asymptomatic invisible haematuria have cancer Data suggest that invisible haematuria detected on dipstick screening has a sensitivity of < 3% and a positive predictive value of 0.2% for cancer Invisible haematuria =20 times more likely to develop end stage renal failure than those without: but the absolute risk is low: 34 v 2/100 000 person years!

Testing Presence of haematuria (VH or IH) should not be attributed to anti-coagulant or anti-platelet therapy and patients should be evaluated regardless of these medications. Population screening is considered justified in Japan but no other country has a national programme Regard two out of three positive dipstick tests as confirmation 1+ or more NOT trace

Assessment SYMPTOMS: Also ascertain Examine visible haematuria, loin pain, Dysuria Pelvic pain Also ascertain Risk factors for urinary tract cancer (smoking; exposure to chemicals used in leather, dye, and rubber manufacturing; cyclophosphamide treatment). A family history (Alports, Polycystic kidneys) Examine Blood pressure Abdominally

UTI Exclude UTI and/or other transient cause If UTI then treat and test again after proof of clearance – 2 out of 3 positive means IH Remember recurrent UTI can be a sx of bladder cancer or in men 35-50 with sx. chronic prostatitis Check urine for blood again in a week or more

Tests Plasma creatinine/eGFR. Measure Proteinuria: Send urine for albumin:creatinine ratio (ACR) on a random sample (according to local practice). Sickle cell disease/ trait (Urothelial cancers are detected by cystoscopy rather than imaging, imaging alone can provide false reassurance and should not be undertaken) (N.B. 24 hour urine collections for protein are rarely required. An approximation to the 24 hour urine protein or albumin excretion (in mg) is obtained by multiplying the ratio (in mg/mmol) x10.)

Management 1 3 possible routes: Urology Referral Nephrology referral So if after all the above there is no UTI, 2 out of 3 positive dipstick test, normal clinical examination and normal/ stable eGFR then: 3 possible routes: Urology Referral Nephrology referral Continued Observation

Cystoscopy and imaging of upper renal tract – CT  USS X Urological referral All patients with a-IH aged ≥ 35-40 yrs or even younger if smokers/ other risk factors for bladder cancer NICE says urgent if >60 yrs (Asymptomatic visible haematuria (any age)).* (Sustained symptomatic IH (any age)). Cystoscopy and imaging of upper renal tract – CT  USS X There is no high quality evidence that asymptomatic IH for urinary tract cancer improves outcome compared with investigating visible haematuria only. IH becomes VH in 3 months of bladder cancer recurrences * N.B. Some patients <40 yrs with cola-coloured urine and an inter-current (usually upper respiratory tract) infection will have an acute glomerulonephritis, and a nephrology referral may be considered more appropriate if clinically suspected.

Nephrological referral 1)Any Age: eGFR < 30 mL/min/1.73m (CKD 4 and5) A sustained > or = 25% ↘ in eGFR and a change in category or a sustained ↘of ≥15 mL/min/1.73m2 2) Under 40: Urinary ACRof ≥30 mg/mmol (2 measurements) BP > 140/90 eGFR < 60 Visible haematuria coinciding with intercurrent (usually upper respiratory tract) infection Concern about rare or genetic causes of haematuria

Nephrology referral risks and benefits: Benefits of interventions to slow progression of kidney disease (BP control, Salt restriction, RAS blockade to reduce proteinuria) do not vary with renal histology Most conditions diagnosed by renal biopsy in patients with a-IH (IgA and thin BM nephropathy) are not amenable to disease specific treatment; even membranous nephropathy treatment only benefits those with proteinuria or a progressive reduction in renal function

Nephrology referral Kidney biopsy provides a tissue diagnosis but carries important risks, including life threatening bleeding NB Hypertension is a common unrelated comorbidity in older patients

Observation in Primary Care Most patients with IH wont meet the referral criteria Monitoring for as long as the haematuria persists Consider USS of renal tract if not referring and >CKD3 Most are likely to have glomerular haematuria (IgA disease and thin basement membrane nephropathy) Annual assessment of blood pressure Dipstick test of urine for IH estimated glomerular filtration rate urinary ACR The 1% risk of missed urological cancer in patients already investigated once for asymptomatic invisible haematuria does not justify repeat urological testing

https://www.nice.org.uk/guidance/cg182/resources http://www.bmj.com/content/349/bmj.g6768