1. An approach to haematuria & proteinuria in General Practice
Dr David MAKANJUOLA

2. How common is haematuria?
Children %
Young adults ( yrs) 5.2%
Older adults (> 50 yrs) %
Elderly (> 75 yrs) 13% - males % - females
various studies detecting asymptomatic haematuria on dipstick test 13

3. 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 14

4. From Collar et.al, KI 2001

5. Investigation of haematuria
Urine
Microscopy - > 5-10 rbc/hpf (12,500/ml) few wbc’s Granular (rbc) casts Dysmorphic red cells
Gram stain Culture Cytology *(sensitivity 50%) 17

6. 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 18

7. 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

8. Disorders revealed by renal biopsy
Topham et al 1994
No abnormality %
IgA nephropathy %
MPGN %
Thin glomerular basement membranes 4%*
*probably an underestimate because electron microscopy
was not performed on all biopsies

9. 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 10

10. 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…..

11. Proteinuria Causes of proteinuria Measurement of proteinuria
Clinical approach and assessment
Nephrotic syndrome
Check list

12. Renal function - GFR Glomerular proteinuria Tubular 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)

13. 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

14. Measurement of Urinary Protein
Urine dipstick
Detects albumin; insensitive to light chains
Highly specific
mg/day
Insensitive to microalbuminuria

15. 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

16. Protein:Creatinine 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

17. 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

18. Examination of the Urinary Sediment
Look for other evidence of glomerular abnormalities
Red cell casts
Haematuria
Glycosuria
Check whether abnormality is persistent or transient

19. Clinical Examination Blood pressure Assessment fluid status
JVP; Pedal oedema; cardiac status
Peripheral Pulses, bruits
Palpable kidneys?
Rash, synovitis, vasculitic lesions

20. Evaluation of Proteinuria – General Practice

21. Evaluation of Persistent Proteinuria – General Practice

22. Prognosis Depends upon degree of proteinuria 20 year follow up:
Hypertension in 50%
Renal Insufficiency in 40%

23. 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?

24. 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

25. 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 < 1-2g/day.
Unexplained rising creatinine
Suspicion of active glomerulonephritis

26. Nephrotic Syndrome Oedema Hypoalbuminaemia
Heavy proteinuria (>3g/day)

27. Nephrotic syndrome – Clinical caseAM
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.

28. Minimal Change Disease

29. 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
Hodgkin’s disease

30. 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

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

32. FSGS Most common idiopathic nephrotic syndrome in adults (33%)
Increasing incidence
More common in blacks
Treatment very difficult

33. Membranous Nephropathy

34. 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

35. 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

36. Amyloidosis More common in elderly Two main types of renal amyloid
Normal
More common in elderly
Two main types of renal amyloid
AL amyloid
AA amyloid

37. Diabetic Nephropathy
Leading cause of renal disease in dialysis patients in UK
Increasing incidence
Importance of considering other causes
ACE-I; AIIRB

38. 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

39. Proteinuria – Less nephrological concern
Transient proteinuria
Orthostatic proteinuria
Stable low level proteinuria, especially in elderly
Low level proteinuria with other vascular disease
Diabetic microalbuminuria

40. 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

41. Proteinuria – Who to Refer?
Persistent proteinuria (esp > 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…..

42. QUESTIONS