Proteinuria in the Diagnosis & Management of Kidney Disease

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Proteinuriain the Diagnosis Management of
Kidney Disease

• Dr Shamila De Silva
• Consultant Physician
• Senior Lecturer in Medicine
• Faculty of Medicine, Ragama

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Proteinuria

• Marker of renal disease
• Mediates progressive renal dysfunction
• Independent risk factor for CVD

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In this lecture

• Causes of proteinuria
• Evaluating a patient with proteinuria
• Managing proteinuria

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Pathophysiology

• Low molecular weight proteins in plasma filtered
  in to tubules
• Almost completely re-absorbed in PCT
• Normal daily protein excretion lt150 mg
• Of this albumin 10 mg

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Types of Proteinuria

• Functional
• Orthostatic
• Overflow
• Tubular
• Glomerular

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Functional Proteinuria

• Transient
• Sub-nephrotic
• Exercise
• Fever
• Heart failure

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Orthostatic Proteinuria

• Proteinuria only in upright position
• Benign
• Early morning samples normal, but proteinuria in
  samples collected during day

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Overflow Proteinuria

• Increased filtration of LMW protein through a
  normal glomerulus
• Free light chains in Myeloma (Bence-Jones
  proteinuria)
• No albumin dipstick negative

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Tubular Proteinuria

• Injury to tubulo-interstitial compartment
• Loss of normal filtration reabsorption of
  proteins
• Loss of proteins released by tubular epithelial
  cells in response to injury

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Glomerular Proteinuria

• Increased permeability of glomerular capillary
  wall to macromolecules, sp albumin
• Persistent
• May be associated
• with haematuria
• ? GFR

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Classification of Pathological Proteinuria
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Presentation of Renal Disease with Proteinuria

• Asymptomatic
• Symptomatic - Nephrotic
• Nephritic

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Asymptomatic

• Most
• Routine testing
• Screening high risk patients

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High Risk in

• Diabetes
• Hypertension
• CVD IHD, CHF, PVD, CVD
• Structural renal tract disease, calculi or
  prostatic hypertrophy
• Multi-system disease - SLE
• Family h/o Stage 5 CKD or hereditary kidney
  disease

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Nephrotic Syndrome

• Proteinuria gt50 mg/kg/day
• (gt3.5 g/d in 70 kg adult)
• Hypoalbuminaemia
• Oedema
• Hyperlipidaemia

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Clinically..

• Oedema peri-orbital, ankle, sacral, genital
• Pleural effusions, ascites
• Leukonychia
• Xanthelasma
• Frothy urine

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Causes of Nephrotic Syndrome

• Diabetic nephropathy
• Membranous nephropathy
• Minimal change disease
• Focal segmental glomerulosclerosis
• Mesangiocapillary GN
• Renal amyloidosis

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Nephritic Syndrome

• Oedema
• Hypertension
• Proteinuria significant haematuria
• ? GFR

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Clinically..

• ? urine output
• Smoky urine
• Ankle oedema
• Evidence of
• systemic disease /-

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Causes of Nephritic Syndrome

• Post-infectious GN
• IgA Nephropathy
• ANCA-associated vasculitis -
• Wegeners , MPA
• Anti-GBM disease -
• Goodpastures

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Evaluating Proteinuria

• Repeat dipstick
• Urine culture ABST
• Quantify proteinuria
• Measure excretory renal function

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Quantifying Proteinuria

• 24 h urine protein
• Albumin or Protein concentration in spot urine
  sample
• Corrected for hydration state ?
• (1) albumin/creatinine ratio (ACR)
• more sensitive, for detection identification
• (2) protein/creatinine ratio (PCR)
• for quantification monitoring

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Normal Proteinuria

• lt150 mg/day
• Urine PCR lt15 mg/mmol

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Nephrotic-range Proteinuria

• gt3.5 g/d (PCR gt350 mg/mmol)
• Predominantly albumin in glomerular disease

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Non-nephrotic Proteinuria

• 150 mg 3.5 g/d
• PCR 15 350 mg/mmol
• Glomerular disease
• Non-glomerular parenchymal renal disease
• Urinary tract disease

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Cause of Proteinuria Related to Quantity
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Microalbuminuria

• Albumin excretion 30 300 mg/d
• ACR - 2.5 30 mg/mmol for men
• 3.5 30 mg/mmol for women
• Not detected by dipsticks
• Early DM nephropathy
• Indicator of CVD risk in at-risk populations

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Cardiovascular survival (Kaplan-Meier) according
to microalbuminuria status in a population-based
cohort aged 50 to 70 yr.
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Measuring Excretory Renal Function

• Plasma Creatinine
• Calculate eGFR
• Categorize according to CKD stage

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Classification of CKD NKF-KDOQI 2000

• Stage Description GFR
• Normal GFR other evidence of CKD gt90
• Mild Impairment 60-89
• Moderate Impairment 30-59
• Severe Impairment 15-29
• Established Renal Failure (ERF) lt15
• persistent microalbuminuria
• persistent proteinuria
• persistent haematuria
• structural abnormalities of kidneys
• biopsy-proven chronic GN

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When to Refer for Specialist Renal Assessment

• ACR gt70
• unless due to diabetes and already treated
• ACR gt30 with haematuria
• Stage 4 or 5 CKD
• with or without diabetes
• irrespective of level of proteinuria
• Rapidly declining eGFR
• 5 ml/min in 1 year or 10 ml/min within 5 years
• irrespective of level of proteinuria

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Management - Aims

• Identify underlying cause
• ? treat where possible
• Minimise risk of renal function deterioration
• ? control HPT, ? proteinuria
• Minimise risk of CVD
• Prepare patients with progressive renal disease
  for RRT

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General Management

• Exercise
• Healthy weight
• Stop smoking

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BP Control in Non-diabetics

• Aim lt140/90
• ACR gt30 ? ACEI (ARB if intolerant)
• ACR gt70 ? ACEI ARB is better
• ACR gt70 but NOT hypertensive ? ACEI ARB is
  reno-protective

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BP Control in Diabetics

• ACR gt2.5 (men) gt3.5 (women) ?
• ACEI or ARB (even if not hypertensive)
• Increase ACEI/ARB to maximum tolerated dose
  before adding second agent
• DM CKD or ACR 70 mg/mmol ?
• Aim to keep BP lt130/80

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• Limit dietary sodium to 50-70 mmol/d
• Check S.K eGFR 1-2 weeks after commencing or
  increasing dose of ACEI or ARB
• If K gt6 mmol/l or
• eGFR ? by gt25 from baseline
• (s.creatinine ? by gt30)
• ? stop ACEI/ARB

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CVD Risk Management

• Major cause of mortality in patients with
  proteinuric renal disease
• Statins for primary secondary prevention
• Low dose Aspirin for secondary prevention
• Avoid multiple antiplatelet drugs in CKD ? high
  bleeding risk

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In Summary

• Proteinuria is a powerful risk factor for
  development of progressive renal dysfunction and
  CVD
• Measurement of urine albumin to creatinine ratio
  (or protein to creatinine ratio) on a spot
  urine sample has made 24-hour urine collections
  for proteinuria quantification unnecessary
• Screening for proteinuria should be undertaken in
  patients with risk factors for development of CKD

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• Early identification of patients with proteinuria
  offers the best chance of preventing progressive
  renal dysfunction
• BP control, blockade of RAAM CVD risk factor
  management are the key therapeutic goals in
  proteinuric patients

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References

• Topham P. Proteinuric renal disease. Clinical
  Medicine 20099(3)284-7
• Early identification and management of chronic
  kidney disease in adults in primary and secondary
  care. Clinical guideline CG73. London NICE,
  2008. www.nice.org.uk/Guidance/CG73
• Wolf G, Ritz E. Combination therapy with ACE
  inhibitors and angiotensin II receptor blockers
  to halt progression of
• chronic renal disease pathophysiology and
  indications. Review. Kidney International
  200567799812.

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Acknowledgements

• Colleagues at the Department of Medicine, Ragama,
  sp Prof Janaka De Silva
• Mentors throughout my career, sp Dr Sivakumaran
  Prof Ken Farrington
• My husband

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