An approach to haematuria & proteinuria

in General Practice

Dr David MAKANJUOLA

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

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

From Collar et.al, KI 2001

Investigation of haematuriaUrine • Microscopy - > 5-10 rbc/hpf (12,500/ml)

- 0 - few wbc’s - Granular (rbc) casts - Dysmorphic red cells

• Gram stain Culture Cytology *(sensitivity 50%)

Investigation of haematuria

Blood• FBC

• Clotting screen

• Haemoglobin electrophoresis

• Creatinine / GFR

• C3 & C4 / ASOT / DNA Abs / ANCA

Non-invasive imaging

• Plain X-rays (KUB)

• Ultrasound scan

• Intravenous urogram

• + Radio-isotope scans

Invasive procedures

• Cysto-urethroscopy

• 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

Who should undergo renal biopsy?

• Abnormal renal function• Significant proteinuria• Patient desire for diagnosis

and prognosis• Family history of renal

impairment• Physician preference

Disorders revealed by renal biopsy

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

Topham et al 1994

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

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…..

Proteinuria

• Causes of proteinuria

• Measurement of proteinuria

• Clinical approach and assessment

• Nephrotic syndrome

• Check list

Renal function - GFR• Glomerular proteinuria

– Increased filtration of macromolecules across glomerular wall

• Glomerulonephritis• Tubulointerstitial disease

• Tubular proteinuria– Increased excretion of low

molecuar weight proteins (2M; Ig light chains; RBP)

• Overflow proteinuria– Overproduction of particular

proteins (e.g light chains)

Glomerular Proteinuria – Step 1

‘Benign’ causes:– Transient proteinuria

• Fever• Heavy exercise

– Orthostatic proteinuria

Exclude benign causes, and proteinuria due to vascular disease………

Haemodynamic• Heart failure• Hypertension• Renovascular disease

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

Measurement of Urinary Protein

• Urine dipstick

• Detects albumin; insensitive to light chains

• Highly specific

• Positive @ 300-500mg/day

• Insensitive to microalbuminuria

Quantifying protein excretion

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

• Should perform quantitative measure in persistent proteinuria

24 hour urine collection– Readily quantified– Wide understanding– Cumbersome

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

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

Examination of the Urinary Sediment

• Look for other evidence of glomerular abnormalities

• Red cell casts

• Haematuria

• Glycosuria

• Check whether abnormality is persistent or transient

Clinical Examination

• Blood pressure

• Assessment fluid status• JVP; Pedal oedema; cardiac status

• Peripheral Pulses, bruits

• Palpable kidneys?

• Rash, synovitis, vasculitic lesions

Evaluation of Proteinuria – General PracticeHistory, Physical

Examination, urinalysis

Repeat visit for qualitative proteinuria test

Positive

Measure U&E, Albumin, Quantify urine protein excretion

Negative

Transient Proteinuria; Reassure Patient

Evaluation of Persistent Proteinuria – General Practice

U&ELFT

Quantify proteinuria

Abnormal Renal Function,Proteinuria > 1g /day

Age >30

Normal Renal FunctionProteinuria <1g/day

Age <30

Renal USSBiochemical profileNephrology referral

Split Urine test

Overnight urine protein <50mg Overnight urine protein >50mg

Orthostatic proteinuriaReassure Nephrology Referral

Prognosis

• Depends upon degree of proteinuria

• 20 year follow up:– Hypertension in 50%– Renal Insufficiency in 40%

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?

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

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

Nephrotic Syndrome

• Oedema

• Hypoalbuminaemia

• Heavy proteinuria (>3g/day)

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 88mol/l; Alb 18g/dl, 24 hr protein 5g.

Minimal Change Disease

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

Clinical Case -2

• SH

• 76 lady

• Rapid onset oedema and dyspnoea

• Gross oedema; Proteinuria 13g/day

• Urinalysis Prot 4+, blood –trace

• Creatinine 176mol/l, Alb 22g /dl

FSGS

Mild ModerateCollapsing

Normal

AssociationsIdiopathicMorbid obesityHeroin abuseHIV infectionNSAID(Minimal change disease)

FSGS

• Most common idiopathic nephrotic syndrome in adults (33%)

• Increasing incidence

• More common in blacks

• Treatment very difficult

Membranous Nephropathy

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

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 188mol/l; Alb 27g/dl

• IgG paraprotein

Amyloidosis

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

– AL amyloid– AA amyloid

Normal

Diabetic Nephropathy

• Leading cause of renal disease in dialysis patients in UK

• Increasing incidence

• Importance of considering other causes

• ACE-I; AIIRB

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

Proteinuria – Less nephrological concern

• Transient proteinuria

• Orthostatic proteinuria

• Stable low level proteinuria, especially in elderly

• Low level proteinuria with other vascular disease

• Diabetic microalbuminuria

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

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…..

QUESTIONS