An approach to haematuria

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An approach to haematuria proteinuria in
General Practice
Dr David MAKANJUOLA
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How common is haematuria?

• Children 0.7 - 4
• Young adults (18 - 33 yrs) 5.2
• Older adults (gt 50 yrs) 13 - 18
• Elderly (gt 75 yrs) 13 - males 9 -
  females

various studies detecting asymptomatic haematuria
on dipstick test
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Causes of haematuria

• Glomerular diseases Interstitial diseases
• Medullary diseases Neoplasia
• Infections Calculi
• Obstruction Coagulation defects
• Hypertension A-V malformations
• Endometriosis Foreign body
• Factitious
• Loin pain haematuria syndrome
• Trauma to urinary tract

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From Collar et.al, KI 2001
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Investigation of haematuria

• Urine
• Microscopy - gt 5-10 rbc/hpf (12,500/ml) - 0 -
  few wbcs - Granular (rbc) casts -
  Dysmorphic red cells

• Gram stain Culture Cytology (sensitivity
  50)

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Investigation of haematuria

• Non-invasive imaging
• Plain X-rays (KUB)
• Ultrasound scan
• Intravenous urogram
• Radio-isotope scans

• Invasive procedures
• Cysto-urethroscopy
• Renal biopsy

• Blood
• FBC
• Clotting screen
• Haemoglobin electrophoresis
• Creatinine / GFR
• C3 C4 / ASOT / DNA Abs / ANCA

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Who should be cystoscoped?
Who should undergo renal biopsy?

• Age (? all patients over 50)
• History of cigarette smoking
• Gender
• Macroscopic haematuria
• Positive urine cytology
• Normal red cell morphology

• Abnormal renal function
• Significant proteinuria
• Patient desire for diagnosis and prognosis
• Family history of renal impairment
• Physician preference

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Disorders revealed by renal biopsy
Topham et al 1994

• No abnormality 53
• IgA nephropathy 30
• MPGN 7
• Thin glomerular basement membranes 4

probably an underestimate because electron
microscopy was not performed on all biopsies
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Outcome can be unsatisfactory

• No clear diagnosis or prognosis despite numerous
  investigations
• Renal biopsy not performed
• Doctor uncertain / patient unhappy
• Regular (? indefinite) follow-up in clinic

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Clinical scenario

• 35 year old man has had a medical at work. He
  was noted to have proteinuria on dipstick
  testing, and was advised to consult his General
  Practitioner..

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Proteinuria

• Causes of proteinuria
• Measurement of proteinuria
• Clinical approach and assessment
• Nephrotic syndrome
• Check list

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Renal function - GFR

• Glomerular proteinuria
• Increased filtration of macromolecules across
  glomerular wall
• Glomerulonephritis
• Tubulointerstitial disease
• Tubular proteinuria
• Increased excretion of low molecuar weight
  proteins (b2M Ig light chains RBP)
• Overflow proteinuria
• Overproduction of particular proteins (e.g light
  chains)

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Glomerular Proteinuria Step 1

• Most common cause of persistent proteinuria
• Only form to be detected by urine dipstick
  (albuminuria)

Exclude benign causes, and proteinuria due to
vascular disease

• Benign causes
• Transient proteinuria
• Fever
• Heavy exercise
• Orthostatic proteinuria

• Haemodynamic
• Heart failure
• Hypertension
• Renovascular disease

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Measurement of Urinary Protein

• Urine dipstick
• Detects albumin insensitive to light chains
• Highly specific
• Positive _at_ 300-500mg/day
• Insensitive to microalbuminuria

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Quantifying protein excretion

• Should perform quantitative measure in persistent
  proteinuria
• 24 hour urine collection
• Readily quantified
• Wide understanding
• Cumbersome

• Protein-to-creatinine ratio (PCR)
• Simple
• Validated

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ProteinCreatinine Ratio

• Limitations
• Relies on expected creatinine excretion
• Cf Muscular man vs cachectic old lady
• Racial differences
• High creatinine excretion in blacks
• Can not be used to distinguish orthostatic
  proteinuria
• Wider variation as proteinuria increases
• Caution if patient just exercised

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Clinical Approach to patient with persistent
proteinuria - History

• Systemic Disease
• Diabetes
• Heart Failure
• Systemic inflammatory disease
• Family History
• Polycystic Kidneys
• Reflux nephropathy
• Specific Renal complications / localising
  symptoms
• Macroscopic haematuria
• Loin pain
• Frothy urine

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Examination of the Urinary Sediment

• Look for other evidence of glomerular
  abnormalities
• Red cell casts
• Haematuria
• Glycosuria
• Check whether abnormality is persistent or
  transient

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Clinical Examination

• Blood pressure
• Assessment fluid status
• JVP Pedal oedema cardiac status
• Peripheral Pulses, bruits
• Palpable kidneys?
• Rash, synovitis, vasculitic lesions

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Evaluation of Proteinuria General Practice
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Evaluation of Persistent Proteinuria General
Practice
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Prognosis

• Depends upon degree of proteinuria
• 20 year follow up
• Hypertension in 50
• Renal Insufficiency in 40

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Assessment of proteinuria in the Nephrology clinic
Questions to address
What is the cause? What impact on future renal
function? What impact on general vascular
system? Does patient require kidney biopsy or
further investigation? What follow up does
patient require, in what setting, and how
frequently?
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Investigations in Nephrology Clinic

• Quantify proteinuria
• Urine Microscopy
• Immune serological investigations
• ANA Autoantibodies complement (ANCA)
• Rheumatoid factor (cryoglobulins)
• Ig and protein electrophoresis
• Hepatitis serology, (HIV)
• CRP
• Consider Renal Biopsy

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Renal Biopsy - Indications

• Before performing biopsy, need to ask
• Will it be safe?
• Will it give diagnostic information?
• Will it give prognostic information?
• Will it help guide further therapy?
• Nephrotic range proteinuria
• Most nephrologists would not perform a biopsy
  with isolated proteinuria lt 1-2g/day.
• Unexplained rising creatinine
• Suspicion of active glomerulonephritis

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Nephrotic Syndrome

• Oedema
• Hypoalbuminaemia
• Heavy proteinuria (gt3g/day)

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Nephrotic syndrome Clinical case

• AM
• 23 year old man from Egham.
• Presented at age 3 with nephrotic syndrome, never
  biopsied. Numerous relapses (15). Normal
  serological investigations.
• Rarely off steroids
• Cushingoid
• Relapse 2003 whilst on 5mg prednisolone.
• Attends clinic with mother, Oedema, low JVP
• Creatinine 88mmol/l Alb 18g/dl, 24 hr protein 5g.

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Minimal Change Disease
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Minimal Change Disease

• 90 childhood nephrotic syndrome
• Common in young adults
• 15 total adult cases
• Steroid responsive (80)
• steroid sensitive
• 2nd line therapy

• Associations
• NSAIDs
• Paraneoplastic
• Hodgkins disease

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Clinical Case -2

• SH
• 76 lady
• Rapid onset oedema and dyspnoea
• Gross oedema Proteinuria 13g/day
• Urinalysis Prot 4, blood trace
• Creatinine 176mmol/l, Alb 22g /dl

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FSGS
Collapsing
Mild
Moderate
Associations Idiopathic Morbid obesity Heroin
abuse HIV infection NSAID (Minimal change disease)
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FSGS

• Most common idiopathic nephrotic syndrome in
  adults (33)
• Increasing incidence
• More common in blacks
• Treatment very difficult

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Membranous Nephropathy
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Membranous nephropathy

• 2nd most common cause of nephrotic syndrome in
  adults (30)
• Usually idiopathic
• Associated with
• Autoimmune diseases
• Hepatitis B
• Carcinoma
• Drugs (eg penicillamine, captopril, NSAID)

• Outcome very variable
• 1/3 spontaneous remission
• 1/3 partial remission or very slow progression
• 1/3 progressive renal impairment
• Higher incidence of thromboembolism
• Therapy very difficult

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Clinical case - 4

• JH
• 76 year old lady noted to have impaired renal
  function by GP.
• Mild oedema, raised JVP
• 24 hr protein 3.2g
• Cr 188mmol/l Alb 27g/dl
• IgG paraprotein

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Amyloidosis

• More common in elderly
• Two main types of renal amyloid
• AL amyloid
• AA amyloid

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Diabetic Nephropathy

• Leading cause of renal disease in dialysis
  patients in UK
• Increasing incidence
• Importance of considering other causes
• ACE-I AIIRB

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Persistent Proteinuria - Checklist

• Is it persistent?
• Are there other associated urinary abnormalities
• Is it a manifestation of systemic disease (eg DM,
  CCF, IHD) or underlying renal disease?
• Quantify protein excretion
• Check Blood pressure
• Check baseline biochemistry

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Proteinuria Less nephrological concern

• Transient proteinuria
• Orthostatic proteinuria
• Stable low level proteinuria, especially in
  elderly
• Low level proteinuria with other vascular disease
• Diabetic microalbuminuria

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Proteinuria follow up

• Remember
• Higher vascular risk
• Increased hypertension
• Increased risk of subsequent renal dysfunction
• Annual dipstick
• Annual BP
• Annual GFR
• Annual quantification of proteinuria

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Proteinuria Who to Refer?

• Persistent proteinuria (esp gt 1g/day)
• Associated haematuria
• Associated impaired renal function, especially if
  declining
• Associated hypertension
• High levels of proteinuria or increasing
  proteinuria
• Family history of renal disease
• Concerned..

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QUESTIONS