chemistry unit 3 part 1Renal Function & Testing

Course Context and Objectives

• Medical Laboratory Assistant/Technician (MLA/T) Program – Renal Function & Testing module
• Readings tied to:
  • Anderson College A&P Urinary Tract material
  • Linne & Ringsrud’s “Clinical Laboratory Science”, 8th Ed., Ch. 10 (pp. 260–264)
• Learning outcomes
  • Review urinary-system physiology
  • Identify laboratory tests that assess renal function
  • Recall normal reference ranges & critical values
  • Understand special specimen handling requirements

Basic Anatomy & Physiology of the Urinary Tract

• Upper urinary tract
  • Kidneys (cortex, medulla, calyces, pelvis)
  • Ureters
• Lower urinary tract
  • Bladder
  • Internal & external urethral sphincters
  • Urethra
• Nephron = functional unit of the kidney; key vascular components
  • Cortical radiate arteries → afferent arterioles → glomerular capillaries → efferent arterioles → peritubular capillaries → cortical radiate veins

Urine Formation (3 Core Processes)

• Glomerular filtration
  • Water + solutes < protein size forced through capillary endothelium into Bowman’s (glomerular) capsule
• Tubular reabsorption
  • Reclaiming water, glucose, amino acids, required ions back to blood
• Tubular secretion
  • Active removal of H^+, K^+, creatinine, drugs from peritubular blood into filtrate

Epidemiology & Public-Health Impact

• Kidney disease prevalence in Canada: 1/10 citizens
• Diabetes = leading cause of kidney failure (≈36\%)
• >52{,}000 Canadians treated for kidney failure (dialysis or transplant)
• 2019: kidney disease = 10th leading cause of death in Canada
• Chronic kidney disease (CKD) markedly raises cardiovascular-disease risk

Overview of Renal Function Test Menu

• Urea / Urea Nitrogen (BUN)
• Creatinine (serum/urine)
• Creatinine Clearance (CCR)
• Glomerular Filtration Rate – measured or estimated (GFR/eGFR)
• Cystatin C
• Creatine
• Uric Acid

Urea / Urea Nitrogen (BUN)

• Main component of non-protein nitrogen (NPN) fraction in blood
• Equal concentration intra- vs extracellularly; reflects overall NPN shifts
• Biochemistry
  • Protein → amino acids → deamination → ammonia (toxic)
  • Liver enzymes convert ammonia + other amino groups → urea
• Physiology
  • Urea = waste; excreted by kidneys
  • Serum level depends on dietary protein load & renal excretion capacity
• Clinical insights
  • Elevated BUN suggests impaired glomerular filtering
  • Poor sensitivity: doesn’t rise markedly until GFR ↓ by ≥50\%
  • Therefore creatinine is preferred single index
• Specimens & pre-analytical issues
  • Acceptable: serum, lithium/sodium-heparin plasma, urine
  • Gray-top (fluoride) tubes contraindicated – fluoride inhibits urease methods
  • Bacterial degradation → urea loss; refrigerate 4–8\,^{\circ}\text{C} (stable ≤72 h)
  • Urine: keep pH < 4 plus refrigeration to curb bacterial action

Creatinine

• Origin
  • \approx95\% of body creatine phosphate located in skeletal muscle; spontane­ous cyclic dehydration → creatinine
  • Release rate ∝ muscle mass (age/sex/size dependent)
• Advantages over BUN
  • Largely independent of diet, hydration, protein catabolism
  • Freely filtered, minimal tubular secretion, no reabsorption → strong GFR mirror
• Interferents
  • Non-creatinine chromogens in RBCs (proteins, glucose, ascorbic acid, pyruvate) may elevate assays; hence use serum/plasma (not whole blood)
• Specimen notes
  • Serum, heparin plasma, or diluted urine (commonly 1{:}100–1{:}200)
  • Avoid ammonium-heparin when method relies on ammonia measurement
  • Stable refrigerated ≤7 d; avoid hemolysis (falsely ↑ creatinine)
  • Labs routinely auto-report eGFR with serum creatinine
• Quantitative methodology – Jaffe reaction
  • Creatinine + alkaline picrate → orange/red creatinine-picrate complex
  • Rate of colour formation ∝ creatinine concentration
  • Acid-kinetic modification diminishes interference from Jaffe-positive non-creatinine substances (colour from true creatinine is acid-labile)
• Clinical significance
  • Sensitive marker of kidney disease; serum ↑ indicates reduced GFR
  • Basis for creatinine clearance and eGFR calculations

Creatinine Clearance (CCR)

• Definition
  • Volume of plasma cleared of creatinine per minute, normalised to body surface area (BSA).
• Formula \text{CCR} = \frac{U\times V}{P}\times\frac{1.73}{A} where
  • U = urine creatinine \big(\mu\text{mol/L}\big)
  • P = plasma creatinine \big(\mu\text{mol/L}\big)
  • V = urine flow (mL/min)
  • A = patient BSA \big(\text{m}^2\big); 1.73\,\text{m}^2 is reference adult
• Collection protocol
  • 24-h complete urine collection (refrigerated); record volume
  • SST blood draw within 24 h of urine completion
  • Record patient height & weight for BSA calculation
• Interpretation
  • Lower CCR ⇒ impaired glomerular filtration; often indexed to normal ranges corrected for sex & age

Glomerular Filtration Rate (GFR) & eGFR

• Physiology
  • Glomeruli = microscopic “sieve” that allows water & small solutes through while retaining cells/proteins
• Importance
  • Primary indicator of early kidney disease; influences staging & management of CKD
• Ideal tracer characteristics (for measured clearance)
  • Inert, freely filtered, non-protein-bound, neither reabsorbed nor secreted, not metabolised
• Historical “gold standard”
  • Inulin clearance; rarely used today due to cost/inconvenience
  • Radiolabelled isotopes (e.g., iothalamate) alternative but similar drawbacks
• Estimation (eGFR)
  • No direct universal method; modern practice = formula-based estimate using serum creatinine, age, sex (± race in older equations)
  • eGFR automatically calculated; NOT an orderable test
  • Thresholds
    • \text{eGFR}\ge 90\,\text{mL/min/1.73 m}^2 → normal
    • 60–89 → possible early CKD
    • 15–59 → kidney disease (moderate-severe, stage 3–4)
    • <15 → kidney failure (stage 5)
  • Caveats: extremes of age, muscle mass (amputees, cachectic, obese) reduce accuracy
• Prognostic integration
  • Combine GFR category with albuminuria level to stage and predict CKD outcome (Kidney Disease: Improving Global Outcomes – KDIGO table)

Cystatin C

• Low-molecular-weight cysteine protease inhibitor; produced at constant rate by all nucleated cells → less muscle-mass bias than creatinine
• GFR is inversely proportional to cystatin C level
• Analytical methods: particle-enhanced turbidimetric or nephelometric immunoassay (rapid, precise)
• Pre-analytical
  • Overnight fast required; red-top serum → aliquot → refrigerated transport
  • Not universally available in all labs

Creatine & Creatine Kinase (CK)

• Creatine
  • Synthesised mainly in liver; transported to muscle as high-energy phosphate reservoir driving ATP regeneration
  • Converts to creatine phosphate (via CK) → eventually loses PO4^{3-} & H2O → creatinine (renal excretion)
  • Supplementation may enhance short-burst athletic performance; testing seldom ordered clinically
• Creatine Kinase (CK)
  • Enzyme catalysing creatine ↔ creatine phosphate interconversion
  • High serum CK indicates muscle injury (e.g., trauma, muscular dystrophy) or strenuous exercise
  • Formerly key marker for myocardial infarction; replaced by cardiac Troponin due to better specificity
• Distinction
  • Creatinine = waste metabolite; CK = catalytic enzyme; both relate to muscle physiology but represent different biochemical entities

Uric Acid

• Final catabolic product of purine nucleosides
• Elevations seen in
  • Gout (monosodium urate crystal arthritis)
  • Increased nucleic-acid turnover (e.g., chemotherapy, hemolysis)
  • Renal disease (reduced excretion)
• Pathophysiology
  • Plasma urate filtered freely; proximal tubular reabsorption + distal secretion modulate excretion
  • Progressive CKD → retention & rising serum uric acid
• Sex influence: normal plasma levels higher in males vs females

Reference Ranges & Critical Values (Chemistry Panel)

• Creatinine
  • Male 50!–!120\,\mu\text{mol/L}
  • Female 40!–!100\,\mu\text{mol/L}
• Urea 2.5!–!8.5\,\text{mmol/L}
• CK
  • Male 0!–!180\,\text{U/L}
  • Female 0!–!150\,\text{U/L}
• Uric Acid
  • Male 200!–!500\,\mu\text{mol/L}
  • Female 150!–!450\,\mu\text{mol/L}
• eGFR interpretive strata already listed above
• (No specific critical highs/lows provided for all analytes in transcript)

Specimen Handling – Cross-Test Summary

• Temperature control 4–8\,^{\circ}\text{C} prevents bacterial/metabolic degradation (urea, creatinine)
• pH acidification (<4) further stabilises urine urea collections
• Timed urine collections (24 h) essential for CCR; label start/stop times accurately
• Avoid hemolysis (releases chromogens → spurious creatinine values)
• Tube selection critical (avoid fluoride for urease assays; avoid ammonium-heparin if assay measures ammonia)

Real-World & Practical Implications

• Early laboratory detection (creatinine, eGFR, cystatin C) enables CKD staging, slowing progression via lifestyle or pharmacologic intervention
• Laboratory professionals must respect patient preparation instructions (fasting, collection timing) to ensure analytic validity
• Ethical duty: safeguard copyrighted educational materials; limit use to Anderson College learning environments
• Public-health messaging: modifiable kidney-health factors (BP control, diabetes management, weight, smoking cessation, medication adherence, family history awareness)

Everyday Kidney-Health Tips (Patient-Education Snapshot)

• Regular medical check-ups & lab work
• Manage diabetes & hypertension
• Maintain healthy weight & balanced diet; limit alcohol
• Stay physically active; cease smoking
• Know family renal-disease history
• Adhere to prescriptions; avoid nephrotoxins when possible

Key Take-Home Connections

• Creatinine and eGFR together = frontline assessment of renal function; BUN provides adjunct but less specific data
• CCR offers more precise filtration assessment but requires cumbersome timed urine; largely supplanted by eGFR except in special cases (e.g., extremes of muscle mass)
• Cystatin C gaining ground as creatinine-independent GFR marker, especially where muscle mass is atypical
• Associated analytes (CK, uric acid) provide insight into systemic or comorbid conditions (muscle pathology, gout, tumour lysis)
• Proper specimen handling & understanding assay limitations are fundamental for accurate interpretation