Renal Workshop (proteinuria & haematuria)

Question 1

What is proteinuria?

Answer 1

• Presence of cloudy ‘frothy’ urine (as has protein in
• Normal variant up to 80mg ±20 equates to 0.1 PCI/1+ on dipstick
• Balance between amount of protein filtered by glomerulus and amount reabsorbed by the proximal tubule
• LMW proteins may be filtered but reabsorbed to <0.2 PCI

When patient has a catheter in then reading not that accurate as can be contaminated (e.g. urine sample)

Question 2

Why is proteinuria important marker?

Answer 2

• Marker of intrinsic renal disease ie. damage to the glomerular basement membrane
• Risk factor for progression of renal disease
• Independent risk factor for cardiovascular morbidity and mortality (as hypertension due to INCREASE RAAS system thus, INCREASE Na+)

Question 3

Who is at risk of proteinuria and where should they be tested?

Answer 3

Where → GP practice

Who →

• A GFR less than 60 mL/min/1.73 m²
• Diabetes
• Hypertension
• Cardiovascular disease
  
  • Ischaemic heart disease, chronic heart failure, peripheral vascular disease and cerebral vascular disease
• Structural renal tract disease, multiple renal calculi or prostatic hypertrophy
• Multisystem diseases with potential kidney involvement
• Family history of stage 5 CKD or hereditary kidney disease
• Opportunistic detection of haematuria

Question 4

Draw a nephron & its blood supply (how many nephrons in EACH kidney)

Answer 4

• 1 million nephrons in EACH kidney total → 2 million (as 2 kidneys)

Question 5

Draw a nephron

Answer 5

Question 6

What is the difference between a normal and diseased glomerulus in transport across the glomerulus? (diagram)

Answer 6

Question 7

What is meant by microalbuminuria?

Answer 7

• Refers to albumin above the normal range (>30mg), but below the dipstick threshold of 300mg
• Present in 1/3 of type 1 diabetics
• Level correlates with glucose and hypertension control
• Also correlates with cardiovascular risk as with all cause proteinuria

Question 8

What is the difference between macroalbuminuria and microalbuminuria?

Answer 8

Macroalbuminuria → >70mg albumin in urine

Microalbuminuria → >30mg albumin in urine

Question 9

What are the types of proteinuria?

Answer 9

Transient

• UTI, fever, exercise, pregnancy, orthostatic, extreme cold, seizures, CCF, severe acute illness, factitious

Persistent

• Primary renal disease
  
  • Associated with haematuria
  • Glomerular, tubular, overflow
• Secondary renal disease

Question 10

What are the causes of proteinuria? (& explain them)

Answer 10

1. PRIMARY RENAL DISEASE
   
   1. Glomerular
      
      1. Disease of glomeruli
      2. Mainly albumin
      3. Otherproteins → immunoglobulins, macroglulins (1.5g/24hrs)
   2. Tubular
      
      1. Secretory (secreting proteins)
   3. Overflow
2. PRIMARY GLOMERULAR DISEASE
   
   1. Malignant
   2. Benign
3. SECONDARY RENAL DISEASE
   
   1. DM
   2. Amyloid
   3. Myeloma
   4. Infections → hepatitis/malaria
   5. Connective tissue diseases

Question 11

History & examination clinical evaluation of someone with proteinuria?

Answer 11

History

• Connective tissue diseases
• Vasculitides
• DM
• CCF
• Hypertension
• Uraemic symptoms
• Medications
• FH

Examination

• Nephrotic
• SBE
• CTD
• Rheumatoid disease

Further evaluation

• Ensure not diabetic or suffering from UTI
• Fasting glucose
• Baseline renal function
• M,C and S urine and treat if evidence of bacteriuria

Question 12

What would a protein-creatine ratio to protein excretion graph look like?

Answer 12

Question 13

Why has ACR been recommended in preference to PCR and reagent strip analysis?

Answer 13

• In patients with established disease, there may occasionally be clinical reasons for a specialist subsequently to use PCR instead of ACR to quantify and monitor significant levels of proteinuria (for example, in patients with monoclonal gammopathies)
• Albumin is the predominant protein in the vast majority of proteinuric kidney diseases, including diabetes, hypertension and glomerular diseases
• Albumin measurement offers greater sensitivity, and improved precision, for the detection of lower, but clinically significant, levels of proteinuria compared to PCR

Question 14

What is a clinically significant ACR and what is the equivalent level of proteinuria?

Answer 14

• At normal levels of protein loss, albumin is a minor component (approximately 10–20%) of total urinary protein. On average, when the total protein concentration is 1 g/L, approximately 70% of this will be accounted for by albumin.
• In people without diabetes consider clinically significant proteinuria to be present when the ACR is 30 mg/mmol or more (this is approximately equivalent to PCR 50 mg/mmol or more, or a urinary protein excretion 0.5 g/24 h or more).
• In people with diabetes consider microalbuminuria (ACR more than 2.5 mg/mmol in men and ACR more than 3.5 mg/mmol in women) to be clinically significant.
• Heavy proteinuria should be considered present when the ACR is 70 mg/mmol or more (this is approximately equivalent to PCR 100 mg/mmol or more, or a urinary protein excretion 1 g/24 h or more).
• For the initial detection of proteinuria, if the ACR is 30 mg/mmol or more but less than 70 mg/mmol this should be confirmed by a subsequent early morning sample.

Question 15

How can you quantify proteinuria by a ACR/24hr sample?

Answer 15

• >15 microalbuminuria
• >300 nephrotic range
• Consider further renal consult/investigations…

Question 16

How do you investigate someone with proteinuria?

Answer 16

• URINE DIPSTICK
  
  • First repeat two urine samples by dipstick to confirm persistent proteinuria
  • Do at least one week apart
    
    • NB can be false positive in alkaline urine (pH >8) or in concentrated urine (SG>1.025)
• Bedside
  
  • BP, urine dip, MC&S, PCR/ACR
• Bloods
  
  • U&Es, FBC, HbA1c
  • Specific (if older)– immunoglobulins, myeloma screen, vasculitis screen
• Imaging
  
  • USS
  • CT/MRI
• Special tests
  
  • Renal biopsy

Question 17

What is the management of proteinuria?

Answer 17

• Guided as per underlying disease
• Conservative
  
  • Patient education
  • DM control, BP optimisation, smoking cessation
• Medical
  
  • ACE inhibitors (DECREASE BP)
  • Antihypertensives (DECREASE BP)
  • Immunosuppressants
• Surgical
  
  • Access/fistulae for dialysis
  • Transplant

Question 18

How to check if an individual has haematuria? (& what is AVH)

Answer 18

• Initial test is the urine dipstick
  
  • False positives: Myoglobin/haemoglobin
• Worth repeating on at least two occasions
• The presence of haematuria (VH or NVH) should not be attributed to anti-coagulant or anti-platelet therapy and patients should be evaluated regardless of these medications

AVH = Asymptomatic vascular haematuria

Question 19

What is the assessment of haematuria?

Answer 19

• Often incidental finding
• More than 2 red cells/high powered field
• Significant haematuria is considered to be 1+ or greater
• Trace haematuria should be considered negative
• Can arise from anywhere in urinary tract unlike proteinuria
• Define aetiology
  
  • Age <45>
  • Glomerular/non-glomerular
  • Benign vs malignant

Question 20

Explain the presence of monomorphic red cells in urine

Answer 20

Question 21

Explain red cell casts in urine

Answer 21

Question 22

What is the terminology used to describe haematuria?

Answer 22

Visible haematuria

• Otherwise referred to as macroscopic or gross haematuria
• Urine is coloured pink or red
  
  • (Or on occasion like cola in acute glomerulonephritis)
• Symptoms reported by patient, or seen by health professional

Non-visible haematuria

• Otherwise referred to as microscopic or dipstick positive haematuria
• Symptomatic non-visible haematuria (s-NVH)
  
  • Symptoms such as voiding lower urinary tract symptoms (LUTS): hesitancy, frequency, urgency, dysuria
• Asymptomatic non-visible haematuria (a-NVH)
  
  • Incidental detection in the absence of LUTS or upper urinary tract symptoms

Question 23

What is significant haematuria?

Answer 23

• Any single episode of VH
• Any single episode of s-NVH (in absence of UTI or other transient causes)
• Persistent a-NVH (asymptomatic - NVH) (in absence of UTI or other transient causes)
  
  • Persistence is defined as 2 out of 3 dipsticks positive for NVH

IMPORTANT TO ASK IF IT WAS WITNESSED

Question 24

What are the major causes of haematuria by age and duration?

Answer 24

Question 25

Explain the types of **microscopic haematuria**

Answer 25

***_Glomerular_*** * Associated with acanthrocytes/anisocytosis * Associated with *proteinuria* and *red cell casts* * *IgA*/thin membrane disease/hereditary nephritis (Alport’s) ***_Non-glomerular_*** * Papillary necrosis * Nutcracker phenomenon → RARE, with *abdominal pain*, *link with psychiatric distress (left renal vein is being compressed due to vertebrae)* * AVMs * Neoplasms – bladder, urethral, prostate * Hyperuricosuria * Hypercalciuria * Tropical – SCD, malaria, schistosomiasis * Nephrocalcinosis * Cystic diseases – PKD, medullary sponge kidney

Question 26

What are the **2** types of *haematuria & the causes?*

Answer 26

***_Benign_*** * Drugs * UTIs * High INR/VWD * Menstrual contamination * Mild trauma * Sexual intercourse * Vigorous exercise * Fictitious ***_Malignant_*** * Renal cell carcinoma * Bladder cancer * Herbal weight loss preparations * Cyclophosphamide * Smoking * Dyes, rubber and leather manufacturers

Question 27

When test & what tests for *prostate cancer*?

Answer 27

* Consider *prostate-specific antigen* (PSA) test & *PR* exam * When to test someone: * Any UTI symptoms*e.g. nocturia, polyuria, hesitency* * *Erectile dysfunction* * *Visible haematuria* *REFER down cancer pathway if their PSA levels are high*

Question 28

When test & what tests for bladder *cancer*?

Answer 28

* Go down cancer pathway if they are *45 and over* and have: * _unexplained_ visible *haematuria _without_ UTI* * *Persistent* visible *haematuria with treated UTI* * *Aged 60 and over and have:* * *_Non-visible_* haematuria & either *dysuria OR raiseed*

Question 29

When test & what tests for renal *cancer*?

Answer 29

Refer cancer pathway if: * Aged 45 and over and have: * _Unexplained_ visible *haematuria* _without_ UTI * *VISIBLE* haematuria that *persists*/*recurs* after successful treatment of UTI

Question 30

Who should be referred to **urology**?

Answer 30

* All patients with **visible haematuria** (any age) * Some patients *\<40 yrs* with cola-coloured urine and an intercurrent (usually upper respiratory tract) infection will have an acute glomerulonephritis, and a nephrology referral may be considered more appropriate if clinically suspected * All patients with **symptomatic non-visible haematuria** (any age) * All patients with **asymptomatic non-visible haematuria ≥45 years** (usually through screening)

Question 31

Who should be referred to **renal**?

Answer 31

1. Evidence of **declining GFR** (usually only 1ml/min lost every year but, here accelerated loss of GFR) 1. By \>10ml/min at any stage within the previous 5 years, or by \>5ml/min within the last 1 year 2. Stage **4 or 5 CKD** (eGFR \<30ml/min) 3. Significant **proteinuria** (ACR ≥30mg/mmol or PCR ≥50mg/mmol) 4. Isolated **haematuria** 1. Ie. in the absence of significant proteinuria with hypertension in those aged \<45 5. Visible haematuria coinciding with intercurrent (usually upper respiratory tract) **infection**

Question 32

What should you *monitor* **long-term** with patients with haematuria of undetermined aetiology?

Answer 32

* Voiding LUTS * Visible haematuria * Significant or increasing proteinuria * Progressive renal impairment (falling eGFR) * Hypertension * Noting that the development of hypertension in older people may have no relation to the haematuria and therefore not increase the likelihood of underlying glomerular disease ***_Further management_*** * If creatinine abnormal in presence of confirmed haematuria and PCR of \>0.3 then refer to renal * If glomerular source ruled out, need to image upper tract with: * USS * CT → better than IVU in studies * ***Renal biopsy*** with isolated haematuria in the absence of proteinuria not backed by evidence * Study 75 people – 36% thin membrane disease, 23% IgA – what would it change in management? * If upper tract imaging unhelpful needs lower tract *imaging* with: * ***Cystoscopy*** (which is usually more fruitful in males) * *CT/cytology*