Podcast - Non-visible haematuria: and now, what?!

The video version of this podcast can be found here: https://youtu.be/SaizjWg7Fng?si=5067IvQ3Uf9yFVJX 

This episode reviews common abnormal urine tests based on published medical information as well as guidance by NICE and a number of NHS organisations in the UK. Please note that the content on this channel reflects my professional interpretation/summary of the guidance and that I am in no way affiliated with, employed by or funded/sponsored by them. 

My name is Fernando Florido and I am a General Practitioner in the United Kingdom. In this episode, I go through the interpretation and initial management of invisible haematuria, sterile pyuria and proteinuria, always focusing on what is relevant in Primary Care only.

I am not giving medical advice; this video is intended for health care professionals; it is only my summary and my interpretation of the information consulted. You must always use your clinical judgement.   

There is a podcast version of this and other videos that you can access here: 

Primary Care guidelines podcast:  

·      Redcircle: https://redcircle.com/shows/primary-care-guidelines

·      Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK

·      Apple podcasts: https://podcasts.apple.com/gb/podcast/primary-care-guidelines/id1608821148

There is a YouTube version of this and other videos that you can access here: 

• The Practical GP YouTube Channel: 

https://youtube.com/@practicalgp?si=ecJGF5QCuMLQ6hrk 

My summary guide / flowchart can be downloaded here:

·      https://1drv.ms/b/s!AiVFJ_Uoigq0mRCSWQ0Shpin4PS9?e=F5moTm 

The resources consulted can be found here:

Suspected cancer: recognition and referral -NICE guideline [NG12] – urological cancers:

·      https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-site-of-cancer#urological-cancers

Chronic kidney disease: assessment and management - NICE guideline [NG203]:

·      https://www.nice.org.uk/guidance/ng203

Joint consensus statement on the initial assessment of haematuria prepared on behalf of the Renal Association and British Association of Urological Surgeons:

·      https://www.baus.org.uk/_userfiles/pages/files/Publications/haematuria_consensus_guidelines_July_2008.pdf

Assessment and management of non-visible haematuria in primary care BMJ article- BMJ 2009;338:a3021:

·      https://www.bmj.com/content/338/bmj.a3021

·      https://www.bmj.com/bmj/section-pdf/186116?path=/bmj/338/7688/Clinical_Review.full.pdf

North Central London Haematuria clinical pathway PDF:

·      https://gps.northcentrallondon.icb.nhs.uk/pathways/haematuria

Investigating painless haematuria BMJ article - BMJ 2008;337:a260:

·      https://www.bmj.com/content/337/bmj.a260

South East London Urology Adult Primary Care Guidelines:

·      https://www.bing.com/ck/a?!&&p=c2f49d786a34ebffJmltdHM9MTcxMDgwNjQwMCZpZ3VpZD0xZGNjZTJiMC05M2Y4LTYzZTUtMzhkYi1mNmY3OTJjNDYyYzYmaW5zaWQ9NTE4NQ&ptn=3&ver=2&hsh=3&fclid=1dcce2b0-93f8-63e5-38db-f6f792c462c6&u=a1aHR0cHM6Ly9zZWxvbmRvbmNjZy5uaHMudWsvd3AtY29udGVudC91cGxvYWRzL2RsbV91cGxvYWRzLzIwMjMvMTEvSEczMDM3LVNFTC1Vcm9sb2d5LUd1aWRlbGluZXMtRklOQUwtTm92LTIwMjMtMS5wZGY&ntb=1

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Transcript

If you are listening to this podcast on YouTube, for a better experience, switch to the video version. The link is in the top right corner of the video and in the episode description.

Hello and welcome, I’m Fernando, a GP in the UK. Today we are going to go through the interpretation and initial management of non-visible haematuria, always focusing on what is relevant in Primary Care only. 

And for that I will summarise a variety of guidelines and medical publications including NICE guidance and advice provided by a number of NHS bodies in the UK. The links to them are in the episode description and I recommend having a look at them. There you will also be able to find the link to download my summary, which I hope that you will find useful 

Right, so let’s jump into it.

And the reason why this subject generates so many questions is because, when it comes to non-visible haematuria, we are often unsure if and when patients need to be referred and whether they should be referred, to urology, nephrology, or both.

Metanalysis have demonstrated that there is insufficient trial evidence from high quality studies to answer questions relevant to clinical care and therefore clinical pathways are based on consensus agreement and expert opinions. These have changed over the years and, although the oint Consensus Statement of the Renal Association and British Association of Urological Surgeons has been superseded since they were published in 2008, most of their recommendations remain valid and have been incorporated into Primary Care Pathways with only fairly minor changes. And these pathways are going to be the basis of our review today 

And before we start, let’s clarify some basic concepts:

As we probably know, We should no longer use the terms macroscopic and microscopic haematuria but visible and non-visible haematuria instead. In addition, Non-Visible Haematuria can be sub-divided into:

·      Symptomatic Non-Visible Haematuria, when there are some urinary symptoms and

·      Asymptomatic Non-Visible Haematuria which is just an incidental detection without symptoms. This should really be a rarity because we should only test for haematuria for clinical reasons and not opportunistically.

And why is this? Non-visible haematuria is present in about 2.5% of the general population, although it can be as high as 20%, depending on the study group but the overall incidence of serious conditions is <1.5%. This is why there is consensus that general screening for non-visible haematuria is not warranted.

The next question is, what is better? A dipstick or microscopy?

And the answer is that the test of choice is a urine dipstick or urinalysis. Microscopy, because it misses haemolysed haematuria and because of delays in the processing of the urine samples, has a significant false negative rate. Furthermore, the procedure is more labour intensive, and therefore it is not recommended.

What is a positive result? Scores of 1+ or more are considered positive and both non-haemolysed and haemolysed results are of equal significance. On the other hand, a trace of blood should be regarded as a negative result.

The next question is, what is significant haematuria?

Well, clinically significant haematuria is:

·      Either Any single episode of Visible haematuria.

·      Or Any single episode of symptomatic non visible haematuria, obviously not due to a UTI or another transient cause, or

·      Persistent asymptomatic non-visible haematuria and persistent is defined as 2 out of 3 positive dipsticks.

Transient and spurious causes that need to be excluded before establishing the presence of significant haematuria are, for example:

·      A UTI, and a repeat dipstick test after treatment of the infection will determine whether haematuria is persistent.

·      Exercise induced haematuria such as seen in long distance runners, and in these cases urine testing should be repeated at least three days after such activity

·      Myoglobinuria as seen in rhabdomyolysis when myoglobin is released from necrotic muscle cells and

·      Menstruation leading to urinary contamination and the urine test should be repeated after menstruation has stopped

So, what are the causes of persistent non-visible haematuria?

And, obviously, the main worry is cancer, so, first of all, let us deal with this issue

And according to NICE, non-visible haematuria is only a reason for an urgent cancer referral to exclude bladder cancer if the non-visible haematuria appears in a person aged 60 and over with either dysuria or a raised white cell count on a FBC. 

For all other cases, haematuria only features as a cancer sign if it is visible in the over 45s, like in renal and bladder cancers, or if it is visible and with a raised PSA in the case of prostate cancer.

Other possible non-cancer causes of non-visible haematuria can be urological or nephrological.

Examples of some relatively common urological causes of haematuria can be:

·      Benign prostatic hyperplasia

·      Calculus disease

·      Prostatitis or urethritis and

·      Urethral strictures

The most common nephrological causes are:

·      IgA nephropathy or Berger’s disease

·      Thin basement membrane disease

And finally, we will also bear in mind that haematuria should not be attributed to anti-coagulant therapy and these patients should be fully evaluated regardless of their anticoagulation.

Once a UTI has been excluded, the initial investigations for patients with non-visible haematuria, both symptomatic and asymptomatic are:

·      A blood test for FBC and renal function tests

·      A urine test for ACR

·      a BP check

·      and we will consider an INR if the patient is on anticoagulants and a PSA, a further MSU and an USS if clinically indicated

And then we will consider whether referral is necessary, But, Who should patients be referred to?

Well, a urological cause is more likely in patients with:

·      Visible haematuria

·      Symptomatic non-visible haematuria, whatever their age

·      And asymptomatic non visible haematuria if they are aged 40 or over, although the age threshold will vary depending on the guideline that you look at.

So, in all these cases, initial referral to urology is recommended.

Younger patients, generally under 40 or 45 years of age with asymptomatic non-visible haematuria are more likely to have a renal cause. Nephrology referral is not always necessary unless performing a renal biopsy is going to be justified. So, the risk factors that should definitely trigger a nephrology referral with a view to renal biopsy are:

·      Proteinuria with an ACR ≥30 mg/mmol or a PCR ≥50 mg/mmol

·      An eGFR <60 ml/min

·      Or Hypertension, i.e. BP >140/90

There are a few Primary Care guidelines governing non-visible haematuria and I have reviewed the South-East London haematuria guideline as well as the North and Central London haematuria pathway. They both cover this area very clearly and you can find the links to them in the episode description. These pathways cover both visible and non-visible haematuria but, here I have only summarised non- visible haematuria section of the pathway. I have combined them creating a streamlined pathway so that it is clear from a Primary perspective. You can also find a link to download this summary in the episode description.

So, let’s have a look at it:

Right, so we start with checking the urine dipstick. And we find that there is non-visible haematuria. Then we ask ourselves, has the patient got symptoms? and if they do, we will ask ourselves, do we suspect a UTI? And if the answer is yes, we will treat it and recheck the urine dipstick after the antibiotics. If there is no UTI, we will then investigate with a blood test for a full blood count and renal function tests, a urine test for ACR and we will check the blood pressure.  We will also consider an INR if the patient is on anticoagulants and a PSA, a repeat MSU and an ultrasound scan. if clinically indicated. And after that, we will ask ourselves, is the patient over 60, with dysuria or a raised white blood cell count on a full blood count? And if the answer is yes, then they would meet the cancer referral criteria so we would make an urgent Cancer referral to urology. If the answer is no, this is where some of the guidance varies. Some guidelines will say that we can just monitor these patients in primary care, but others will recommend referral. So, on this occasion, I have taken the conservative approach and recommend that we should refer the patient or at the very least, seek specialist advice. And then we will look at the patient’s age, and again, the age threshold can also vary depending on the guideline that you consult. But generally, if the patient is over 45, we will do a routine urology referral because urological causes would be more common in this age group And conversely, if the patient is under 45, it would be a routine nephrology referral and we will make this referral, especially if the investigations show abnormalities like, for example, an eGFR below 60, an ACR of 30 or more, a PCR of 50 or more or if the blood pressure is higher than 140/90.

Now, if we go back up to the beginning and we find that the patient has non-visible haematuria but does not have any symptoms. Then we will need to repeat the test to confirm it and we will do so for up to 3 occasions. We will then ask ourselves if at least two out of three dipstick tests have come back positive. And, if the answer is yes, then we will investigate and rejoin the pathway that we have just explored. If the answer is no, as precaution we will check for proteinuria and we will check the patient’s ACR. If the ACR is normal then we can reassure the patient and stop here. But if the ACR is high, then we will investigate the patient with the standard investigations already mentioned and, following a conservative approach, we would consider seeking specialist advice or refer the patient.

If you have any doubts, here at the bottom you have the links to the original pathways that I have consulted to create this one.  

Finally, Patients with persistent non visible haematuria not meeting criteria for referral, or who have been referred and have had normal investigations, will need long term monitoring, usually in Primary Care, due to the uncertainty of the underlying diagnosis. Patients should be monitored for the development of:

·      Symptoms

·      Visible haematuria

·      Significant or increasing proteinuria

·      Progressive renal impairment with a falling eGFR and

·      Hypertension

So, the NICE guideline on CKD says that annual follow-up of these patients should continue for as long as the non-visible haematuria persists and it should include:

·      repeat dipstick testing for haematuria

·      Review of symptoms

·      A blood test to check renal function and eGFR

·      A urine test for ACR and

·      A Blood pressure check

Referral or re-referral to urology will be needed if the patient develops at any stage either:

·      Visible haematuria or

·      Symptomatic non-visible haematuria

And nephrology referral will be needed if there is:

·      Deteriorating renal function (that is, a drop in eGFR >5 ml/min within previous year or >10 ml/min within past five years)

·      CKD stage 4 or 5 (that is, when the eGFR is <30 ml/min)

·      Or if there is Proteinuria with ACR ≥30 mg/mmol or PCR ≥50 mg/mmol

We have come to the end of this episode. Remember that this is not medical advice and it is only my summary and my interpretation of the guidelines. You must always use your clinical judgement.

Thank you for listening and goodbye.