An approach to haematuria & proteinuria in General Practice

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

2. How common is haematuria? Children 0.7 - 4% Young adults (18 - 33 yrs) 5.2% Older adults (> 50 yrs) 13 - 18% Elderly (> 75 yrs) 13% - males 9% - females various studies detecting asymptomatic haematuria on dipstick test

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

4. From Collar et.al, KI 2001

5. Investigation of haematuria Urine • Microscopy - > 5-10 rbc/hpf (12,500/ml) - 0 - few wbc’s - Granular (rbc) casts - Dysmorphic red cells • Gram stain Culture Cytology *(sensitivity 50%)

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

7. Who should undergo renal biopsy? Who should be cystoscoped? • 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 No abnormality 53% IgA nephropathy 30% MPGN 7% Thin glomerular basement membranes 4%* Topham et al 1994 *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. 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 • 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 ‘Benign’ causes: • Transient proteinuria • Fever • Heavy exercise • Orthostatic proteinuria • Most common cause of persistent proteinuria • Only form to be detected by urine dipstick (albuminuria) Exclude benign causes, and proteinuria due to vascular disease……… Haemodynamic • Heart failure • Hypertension • Renovascular disease

14. Measurement of Urinary Protein • Urine dipstick • Detects albumin; insensitive to light chains • Highly specific • Positive @ 300-500mg/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 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.

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

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. Normal Amyloidosis • 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