NON-PROTEIN NITROGENOUS BIOMARKERS Flashcards
Ref: eGFR
<60 mL/ min/ 1.73 m2
Ref: Creatinine Clearance
1.30 - 2.30 mL/ sec/ 1.73 m2
Ref: ACR (albumin: creatinine ratio)
<3 mg/mmol
Ref: Ammonia (plasma)
<35 μmol/L
Critical: Ammonia (plasma)
> 199 μmol/L
Ref: Creatinine
Female: 40-100 μmol/L
Male: 50-120 μmol/L
Ref: Urea
2.5 - 8.0 mmol/L
Ref: Uric Acid (urate)
Female: 150 - 400 mol/L
Male: 200 - 500 mol/L
What is RAAS ?
Renin-Angiotensin-Aldosterone System ?
- responds to low blood pressure/ low [Na] = REABSORBS sodium and water
- kidney releases renin
- liver releases angiotensinogen
- renin converts angiotensinogen to angiotensin I
- angiotensin I converted to angiotensin II by ACE in lungs
- angiotensin II acts on adrenal gland to release aldosterone
- aldosterone promotes KIDNEY REABSORPTION OF SODIUM AND WATER
ACE = angiotensin-converting-enzymes
How and where is ammonia produced ?
- in the liver by deamination of proteins
- in the intestine by bacteria and endogenous enzymes
- in renal tubular cells (from glutamine etc.)
Clinical Significance of increased ammonia
- liver and kidney disease
- Reye’s Syndrome (CNS disorder)
Specimen type for Ammonia
- lithium heparin or EDTA
- immediately on ice (4°C)
Interferences for Ammonia Testing
- HEMOLYSIS; RBCs contain ammonia = increased
- smoking and ethanol = increased
- prolonged venous occlusion and fist clenching = increased
- AMMONIUM HEPARIN = increased
- delayed handling = increased
What is urea ?
Produced in the liver from ammonia
- freely filtered but 50% is reabsorbed in PCT
Clinical Significance of Increased Urea
- increased protein deamination/ intake
- increased protein catabolism from tissue breakdown and gastrointestinal bleeds
- congestive heart failure
Clinical Significance of Decreased Urea
- severe liver disease
- low protein intake
T or F: Urea is a good indicator of renal function
FALSE; urea is NOT a good indicator of renal function
Interferences in two-step urease reaction
- HEMOLYSIS; RBCs contain ammonia = increased
- AMMONIUM HEPARIN (forest green top) = increased
- endogenous ammonia = increased
- SODIUM FLOURIDE anticoagulant inhibits urease (gray top) = decreased
What is uric acid ?
Formed from oxidation of purine bases
- freely filtered, some reabsorbed by PCT
Clinical Significance of Increased Uric Acid
Hyperuricemia:
- chronic renal failure; decreased excretion
- chemotherapy
- thiazide diuretics
- hypertension
Clinical Significance of Decreased Uric Acid
Hypouricemia = Fanconi’s Syndrome (loss of uric acid in PCT), decreased liver enzymes required for depurination
Interferences in two-step uric acid (uricase) reaction
- SODIUM FLOURIDE anticoagulant (gray top) = increased
- salicylates = increased
- bilirubin = decreased
- ascorbic acid/ vit C = decreased
- hemolysis = decreased
What is creatinine ?
- formed from creatine in skeletal muscle
- freely filtered
- dependant on muscle mass (higher in males)
- little change in response to diet
Clinical Significance of Increased vs Decreased Creatinine
- used to estimate glomerular filtration rate
Increased = decreased GFR
Decreased = muscular dystrophy; inadequate conversion of creatine
What does creatinine clearance test for ?
Glomerular function
Sample Requirements for Creatinine Clearance
- blood sample drawn within 72 hours of urine collection
- 24 hour urine collection must be refrigerated
Creatinine Clearance Formula
C (mL/s) = (UV/P) x (1.73/SA)
where,
U = urine creatinine concentration (μmol/L)
V = volume of urine (mL/ sec OR mL/ min)
P = plasma creatinine concentration (μmol/L)
SA = of patient, calculated using height and weight
How many seconds in 24 hours ?
24 hours = 86,400 seconds
Why does the creatinine clearance test overestimates GFR ?
~10% of creatinine in urine is due to tubular secretion
Creatinine clearance is __ in renal disease.
Creatinine clearance is DECREASED in renal disease.
Why is eGFR useful ?
estimates GFR WITHOUT a 24 URINE COLLECTION
In what cases is eGFR not applicable ?
- acute kidney injury
- abnormal muscle mass
- medication ie. salicylates, furosemide
Albuminuria is a marker for __.
Abuminuria is a marker for CHRONIC KIDNEY DISEASE.
Proteinuria due to low MW globulins is a marker for __.
Proteinuria due to low MW globulins is a marker for TUBULAR DAMAGE.
What is ACR used for ?
Albumin:Creatinine Ratio is used to overcome diurnal variation of albumin/ hydration
How many positive ACR results are required to diagnose chronic kidney disease (CKD) ? What is used to monitor CKD ?
- 2 or more positive ACR results to diagnose
- ACR is also used for monitoring
What small peptide is a good indicator of GFR ? Why ?
β-microglobulin:
- freely filtered by glomerulus
- unaffected by muscle mass and diet
- increased in renal failure and malignancies
Causes of pre-renal Acute Kidney Injury (AKI)
- decreased circulating blood supply (hypovolemia)
- cardiac failure
- burns, hemorrhage, vomiting, diarrhea, sepsis
Causes of renal Acute Kidney Injury (AKI) ?
- vascular, glomerular, interstitial damage
- myoglobinuria
- heavy metal poisoning
Causes of post-renal Acute Kidney Injury (AKI) ?
- obstruction of flow of urine after kidney
- prostatic enlargement, renal stones, fibrosis, neoplasms
What does isosthenuria indicate in CKD ?
- SG is the SAME as protein-free plasma
- kidney’s lack of concentrating ability
What is the primary cause of CKD ?
Diabetes mellitus > hypertension > glomerular nephritis
Creatinine is measured by the __ reaction.
Creatinine is measured by the JAFFE KINETIC reaction.
Interferences in the Jaffe Kinetic reaction
- ketones, ascorbate, cephalosporin, glucose, proteins = increased
- bilirubin and HEMOGLOBIN = decreased
NOTE: jaffe kinetic reaction is used to measure creatinine
