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Introduction to Renal function and Renal Disease
Farid Nakhoul M.D.
Director
Ambulatory Nephrology unit
Rambam-Health Care Campus
Faculty of Medicine Haifa
Tel: 04-8542841 Fax: 048542946
Email:[email protected]
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Introduction
• Anatomy
• Physiology
• GFR
• Proteinuria
• ARF VS CRF
• Research
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Tryggvason, K. et al. N Engl J Med 2006;354:1387-1401
Glomerular Filtration System
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Structure of the Glomerulus(1)
• One of the central function of the kidney is to excrete low molecular weight water-soluble plasma waste products into the urine. Whereas macromolecules the size of albumin and larger are retained. The filtration of plasma occurs in specialized filtration units called Glomeruli.
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Structure of the Glomerulus(2)
The glomerular filtration barrier consists of the three layers of the capillary wall:
1. The innermost fenestrated vascular endothelium.
2. The GBM: the GBM is regarded as a primary size and charge-selective molecular sieve of the glomerulus . The GBM contains type IV collagen, laminin, nidogen, and proteoglycans as its main components.
3. Podocyte cell layer facing the urinary space.
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Tryggvason, K. et al. N Engl J Med 2006;354:1387-1401
Components of the Slit-Diaphragm Protein Complex That Form a Porous Slit-Diaphragm Filter
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Screening for Kidney DiseaseUrine Examination
• Urine Protein
• Urine Albumin
• Urine Sediment-Microscopy: Casts !
• Hematuria: Microscopic or Macroscopic, Dysmorphic blood cells
• Leukocyturia
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Proteinuria
Proteinuria is the halmark of glomerular disease
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Urinary Protein Excretion Measurment
• Negative
• Trace-between 15-30 mg/dl
• 1+ - between 30-100mg/dl
• 2+ - between 100-300 mg/dl
• 3+ - between 300- 1000mg/dl
• 4+ > 1000mg/dl
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Protein-to-Creatinine Ratio
Measurment of protein excretion in the urine can be performed by several different techniques. Previously, protein excretion was measured on a 24 hr urine collection (which remains the gold standard), with the normal value being less than 150 mg/day (10 mg albumin/day). Currently, the preferred methods is the total protein-to-creatinine ratio (mg/mg) or total albumin-to-creatinine ratio on a random urine specimen.
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Urinary Protein/creatinine Ratio
• Creatinine excretion is 1mg/min>>1440mg/day (20-25 mg/kg)
• Women , Children, Elderly persons !!!• Early morning urine sample• 150-250 mg/day protein or Max. 30 mg
Albumin per day or 20-25 mg/dl protein.• Protein to Creatinine ratio greater than 3.0 or
3.5 or less than 0.2 mg/mg indicate protein excretion rates of greater than 3.0 or 3.5 gram/day or less than 0.2 gram/day respectively.
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Stevens, L. A. et al. N Engl J Med 2006;354:2473-2483
Normal Values for GFR in Men and Women
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Assessment of Kidney Function
• Plasma Creatinine
• BUN
• Uric Acid, Calcium-Phosphore,Albumin,Hb
• Plasma Creatinine/BUN Ratio
• CCT (GFR): Measured , Calculated
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Stevens, L. A. et al. N Engl J Med 2006;354:2473-2483
Factors Affecting Creatinine Generation
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Measuring GFR
• Exogenous substances– Inulin, Cr-EDTA, Iothalamate– Time consuming, expensive, radioactivity
• Endogenous substances– Creatinine (cystatin-C)– Over 40 GFR estimation equations based on serum
creatinine
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Cockcroft and Gault
• Developed in 1976 from 249 people (96% male)– Subsequently validated in at least 58 studies
• A measure of creatinine clearance• Estimate urine creatinine based on age, weight and
sex of patient.• False elevation of serum creatinine assays (in 1976)
gave lower results, serendipitously approximating the GFR
• Newer (better) creatinine assays give falsely elevated GFR estimates (approx 15%)
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MDRD
• 1990s: Modification of Diet in Renal Disease study.
• Can progression of renal disease be slowed by dietary modification?
• Multiple ancillary studies to validate tools
• Devised and published the MDRD formulae for GFR estimation
• Used Beckman-Coulter CX3 assay at Cleveland Clinic Laboratory
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MDRD - Opportunity
• MDRD formula adopted by the NKDEP
• National Kidney Disease Education Program
• Aim to highlight moderate to severe renal disease more simply than can be done from serum creatinine alone.
• Renal disease is bad for patients and health systems
• Earlier detection (pre-symptomatic) allows better chance for intervention
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MDRD - Levy 1999
> +/- 30% scatter using results from one instrument
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Stevens, L. A. et al. N Engl J Med 2006;354:2473-2483
Relationship of Serum Creatinine Level to Measured GFR in the Modification of Diet in Renal Disease Study
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Stevens, L. A. et al. N Engl J Med 2006;354:2473-2483
Relation of Estimated GFR to Measured GFR in the Participants in the Modification of Diet in Renal Disease (MDRD) Study
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Glomerular Disease
• Nephrotic Syndrome Sediment: Protein
• Nephritic Syndrome Sediment: Casts
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Proteinuria
• Asymptomatic Non-nephrotic Proteinuria (<3.5 gr Protein/day).
• Nephrotic Syndrome: Pathognomonic of glomerular disease.
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Nephrotic SyndromeDefinition
• Urinary protein level exceeding 3.5 gr per 1.73m2 of body-surface area/day.
• Hypoalbuminemia.
• Sodium retention (Edema-State).
• Hyperlipoproteinemia.
• Hypercoagulability/Infections/Anemia
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Renal Imaging:CT Scan\
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Renal Imaging
• CT-Scan of abdomen with and without Contrast.
• Ultrasound( Parenchyma, Cortex/Medulla)
• Doppler of renal arteries
• Isotopes(DTPA, DMSA)
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Introduction
Diagnosis
Kidney Needle Biopsy (KNB)
(Closed, Laparoscopic)
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Stevens, L. A. et al. N Engl J Med 2006;354:2473-2483
Normal Values for GFR in Men and Women