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LABORATORY INVESTIGATION LABORATORY INVESTIGATION ON ON
RENAL DISORDERSRENAL DISORDERS
Rahajoe Imam SantosaRahajoe Imam SantosaConsultant Clinical Pathologist
CLINICAL LABORATORY UPDATE III - 2008CLINICAL LABORATORY UPDATE III - 2008
RENAL FUNCTION TEST
Renal FunctionRenal DiordersRenal Function TestGFRLaboratory AspectSummary
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RENAL FUNCTIONS
• Filtration• Re-absorption • Secretion• Excretion• Regulation• Metabolic• Endocrine
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CAUSES OF RENAL FAILURE
PRERENAL : • Cardiogenic and hypovolemic shock
RENAL : • ACE-inhibitors and NSAID´s impair renal autoregulation• Fulminant hypertension
• Renal artery stenosis and embolism
• Vasculitis in glomerular capillaries
• Renal vein thrombosis
•Toxic tubular damage (organic solvents, myoglobin, aminoglycosides, and X-ray contrast)
RENAL DISORDERS
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POSTRENAL : (Obstructions of the lumen, the wall and by pressure)
• Lumen: Tumors, calculus and blood clots within the lumen of the renal pelvis, ureter, and bladder
• Wall: Strictures of the ureter, the ureterovesical region, urethra, and pinhole meatus
• Congenital disorders such as megaureter, bladder neck obstruction, and urethral valve
• Neuromuscular dysfunction in the urinary tract
• Pressure: Compression by tumours, aortic aneurysm, retroperitoneal fibrosis or gland enlargement, retrocaval ureter, prostate hypertrophy, phymosis, and diverticulitis
RENAL DISORDERS
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• Older age• Family history of CKD• Decreased renal mass• Ethnicity• Diabetes Mellitus (DM)• Hypertension• Autoimmune Diseases• Infections (systemic, urinary tract)• Nephrolithiasis• Obstruction to the urinary tract• Drug toxicity
RISK FACTORS
RENAL DISORDERS
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• Blood Urea Nitrogen (BUN)• Creatinine• Creatinine Clearance• Glomerular Filtration Rate (GFR)
• Cockroft-Gault equation• MDRD (Modification of Diet in Renal
Disease) equation• Urinalysis• Uric acid
RENAL FUNCTION TEST
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RENAL FUNCTION TEST
• Fractional Excretion of Sodium (FENa)• Fractional Excretion of Urea (FEUrea)• Electrolytes (Na, K, Cl, Ca, P, Mg)• Urine concentrating ability• Urine/plasma osmolality• Urinary Anion Gap {(Na++ K+) – Cl-}• Tubular function tests• Associated tests (hormones, CBC, etc)
• Urea is a relatively nontoxic substance made by the liver to dispose of ammonia resulting from protein metabolism• The real urea concentration is BUN x 2.14• Normal BUN range is 8-25 mg/dL• BUN is a sensitive indicator of renal diseases
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BUN (BLOOD UREA NITROGEN)
RENAL FUNCTION TEST
RENAL FUNCTION TEST
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• The breakdown product of creatine phosphate released from skeletal muscle at a steady rate• Amount produced relates to muscle mass (1-2%/day of muscle creatine converted to creatinine)• Freely filtered by the glomerulus and some tubular excretion• Generally a more sensitive and specific test for renal function than the BUN• Normal range is 0.6-1.3 mg/dL
CREATININE
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CREATININE v/s GFR
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RENAL FUNCTION TEST
CLEARANCE
• A timed urine sample and serum sample used to approximate the glomerular filtration rate• It is not an exact measure of the GFR because some is not filtered and some is secreted into the proximal tubule• In health these cancel each other out, when the GFR drops below 30mL/min the tubular secretion exceeds the amount filtered and can give a false elevation
• Incomplete urine collection• Assess adequacy of collection from steady state creatinine
• Adult ages < 50 years (lean body weight)• Male 20-35 mg/kg and females 15-20 mg/kg has a daily creatinine excretion
• Adult ages 50-90 years (lean body weight)• progressive 50% decline in creatinine excretion
RENAL FUNCTION TEST
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ERRONEOUS VALUES IN CLEARANCE
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◦Appearance◦Specific gravity◦Osmolality◦pH◦Glucose◦Protein◦Urinary sediments
RENAL FUNCTION TEST
URINALYSIS
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FeNa= Amount of Na excreted Amount of Na filtered
FeNa= UNa x Urine volume PNa x GFR
FeNa = UNa x V PNa x[(UCr x V) /PCr]
FeNa % = UNa x PCr X 100 PNa x UCr
FRACTIONAL EXCRETION OF FILTERED SODIUM (FENa)
RENAL FUNCTION TEST
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Measures urine concentrating ability Depends on the quantity of particles, not size or
charge Mainly due to ADH Normal range : urine : 300-900mOsm/L plasma : 285+10 mOsm/L Prior to collection, fluid intake restricted, first
void submitted for evaluation Measuring using osmometer (the fact of
freezing point depression)
OSMOLALITY OF URINE
RENAL FUNCTION TEST
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Proximal Tubular Function◦ Phosphate re-absorption◦ Aminoaciduria◦ Glucosuria◦ Fractional HCO3
- excretion
Distal Tubular Function◦ Acidification (Ammonium chloride load)◦ Concentration (Water deprivation test)
TESTS OF TUBULAR FUNCTION
RENAL FUNCTION TEST
GLOMERULAR FILTRATION RATE
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GFR >45 ml/min symptom less except for underlying pathology and hypertension
GFR <45 ml/min tiredness, diminished well being
GFR <30 ml/min anaemia, metabolic abnormalities e.g. acidosis, Ca/PO4 homeostasis
GFR <15 ml/min nausea, vomiting and gastritis
GFR <10 ml/min cardiovascular and neurological symptoms
GFR <5 ml/min End Stage Renal Disease
RENAL DISORDERS
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the best estimate of the number of functioning nephrons or functional renal mass
an excellent measure of renal filtering capacity
fundamental to the glomerular pathology management of drug therapy (through
glomerular clearance) monitoring of the progression to ESRD to
facilitate timely management decisions monitoring of the adequacy of renal
replacement therapy
CLINICAL USE
GLOMERULAR FILTRATION RATE
NKF, Am J Kid Dis, 39,2(Suppl1), 2002
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COMPOUNDS USED TO MEASURE GFR
Should not be metabolized, or alter GFR Should be freely filtered in the glomeruli, but
neither reabsorbed nor secreted Inulin (a polysaccharide) is ideal Creatinine is most popular
◦ There is some exchange of creatinine in the tubules, as a result, creatinine clearance overestimates GFR by about 10%
Urea can be used, but about 40% is (passively) reabsorbed
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• COCKCROFT-GAULT FORMULA• Calculated Creatinine Clearance/GFR
(140–age) x wt (kg) 72 X serum creatinine(mg/dl)
For females, subtract 15% (or multiply by 0.85)
*Applicable only when patient is in a steady state, not edematous, not obese and normal muscle mass and activity
ESTIMATED GFR (eGFR)
GLOMERULAR FILTRATION RATE
ESTIMATED GFR (eGFR)
• May be less accurate in certain populations• Normal or near normal renal function• Children• >70 years of age• Ethnic groups• Pregnant women• Unusual muscle mass• Morbid obesity
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GLOMERULAR FILTRATION RATE
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Cysteine proteinase inhibitor C (MW:13000) Small size, freely filtered by glomerulus Constant production rate by all nucleated cells No known extra-renal excretion routes Correlation of 1/[cystatin C] (r = 0.81) with Cr-EDTA clearance is better than 1/[Plasma Creatinine] (r = 0.51) Not influenced by muscle mass, diet or
subjects sex
CYSTATIN-C
Newman et al , Kidney Int 1995;47:312-318
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• specific and sensitive parameter for glomerular filtration rate
• independent from urine collection, only one serum sample
• no interference by various drugs or other factors
• fast, accurate and simple method for assessment of glomerular filtration rate
CYSTATIN-C
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• Urea
• 24 hr Clearance Creatinine
• Creatinine
• Cystatin C (?)
• CCr calculated from Cr (Cockcroft-Gault)
• GFR calculated from Creatinine
• 3 hr CCr with Cimetidine
• Direct GFR measurement
51Cr-EDTA , Inulin and Iohexol clearance
Inaccurate
Accurate
RENAL FUNCTION TESTS
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• Biological variable• fasting state• postural change• seasonal variations• diet habit, etc.
• Analytical variable• pre-analytical factors• analytical factors• post-analytical factors
FACTORS AFFECTING LAB. RESULTS
LABORATORY ASPECT
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• Imprecission CV (coefficient of variation)
Inaccuracy Bias (from target value)
Total laboratory error TE = % bias + 1.96 CV Goal is <10%
(bias ≤ 4% and CV ≤ 3%)
CLINICAL LABORATORY PERFORMANCE
LABORATORY ASPECT
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Interferences :• Glucose• Uric acid• Ketones• Ascorbic acid• Cephalosporins
Influenced by :• Muscle mass• Weight• Height• Sex• Age• Food intake
LABORATORY ASPECTCREATININE (JAFFE METHOD)
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Fuller’s Earth (aluminum silicate, Lloyd’s reagent)◦ adsorbs creatinine to eliminate protein
interference Acid blanking
◦ after color development; dissociates Janovsky complex
Pre-oxidation◦ addition of ferricyanide oxidizes bilirubin
Kinetic methods o Creatinase, Creatininase, Creatinine
deaminase (iminohydrolase)
MODIFICATIONS OF THE JAFFE METHOD
LABORATORY ASPECT
