Clinical Laboratory Medicine and Kidneys

Introduction to Clinical Laboratory Medicine and Kidneys

• The presentation is on clinical laboratory medicine and the kidneys
• The professor is Nathan Cope, PharmD, BCPS
• The location is South College School of Pharmacy

Learning Objectives

• Describe normal kidney physiology and how it relates to handling substances monitored by laboratory tests
• Understand the utility, usefulness, and limitations of common laboratory tests for renal function
• Estimate creatinine clearance using the Cockcroft-Gault equation given patient demographics and lab values
• Know major components of a urinalysis
• Understand what results from macroscopic, microscopic, and chemical analysis of urine indicate
• Appreciate the pharmacist's role in patient care regarding laboratory tests related to the kidneys

Common Terms and Abbreviations

• Glomerulus: Part of the nephron
• Afferent arteriole: Blood vessel that enters the glomerulus
• Efferent arteriole: Blood vessel that leaves the glomerulus
• Loop of Henle: Part of the nephron
• Distal Convoluted Tubule: Part of the nephron
• Collecting Duct: Part of the nephron
• CKD (chronic kidney disease): A disease of the kidneys
• BMP (basic metabolic panel): Blood test that measures various substances in the blood
• SCr (serum creatinine): Measure of creatinine in the blood
• Creatine: A substance that helps with energy storage in muscles
• CrCl (creatinine clearance): Measure of how well the kidneys remove creatinine from the blood
• Cockcroft-Gault: An equation used to estimate creatinine clearance
• BUN (blood urea nitrogen): Measure of urea in the blood
• Prerenal: Before the kidneys
• Intrarenal: Within the kidneys
• Postrenal: After the kidneys
• MDRD (Modification of Diet in Renal Disease): A method to estimate GFR
• GFR (glomerular filtration rate): A measure of the kidney's function
• Azotemia: Elevated BUN levels
• Erythrocytes: Red Blood Cells
• RBC: Red Blood Cells
• Leukocyte: White Blood Cells
• WBC: White Blood Cells
• Leukocyte esterase: An enzyme produced by white blood cells in the urine
• Casts: Cellular debris formed in the tubules of the kidney.
• Tubular epithelial cells: Cells lining the kidney tubules
• Proteinuria: Protein in the urine
• Nitrite: A product of bacterial activity in the urinary tract.
• Specific gravity: Density of urine
• UTI (urinary tract infection): Bacterial infection in the urinary tract
• Bacteriuria: Bacteria in the urine

Outline

• Review of Kidney Anatomy and Physiology
• Renal Assessment
  • Estimating function
  • Serum Creatinine and Cockcroft-Gault
  • Blood Urea Nitrogen
• Medications and Renal Elimination
• Components of a urinalysis
  • Macroanalysis
  • Microanalysis
  • Chemical analysis

Role of the Kidneys

• Maintain homeostasis
• Excretion/elimination of water, electrolytes, metabolic by-products, and drugs
• Substance activation and synthesis, regulation of blood pressure and metabolism
• Red blood cell production

Renal Anatomy and Physiology

• Nephron: Functional unit of the kidney
• Each kidney contains ~1 million nephrons
• Arterioles: Afferent and efferent
• Glomerulus (Bowman's Capsule): Site of filtration
• Proximal tubule
• Loop of Henle
• Distal convoluted tubule
• Collecting duct
• Glomerular filtration
• Tubular reabsorption
• Tubular secretion

Kidney Injury

• Prerenal: Blood flow to the kidneys is reduced
• Intrarenal (Intrinsic): Injury within the kidney
• Postrenal: Blockage after the kidneys

Assessment of Kidney Function

• Markers of Clearance
  • Exogenous markers (inulin, i-iothalamate, Cr-EDTA)
  • Endogenous markers (serum creatinine, cystatin C)
• Creatinine equations: Cockcroft-Gault equation, GFR-MDRD equation, Cystatin C
• Creatinine and timed urine collection

Muscle and Serum Creatinine

• Creatine and creatine phosphate are energy sources for muscle
• Creatinine is a by-product of muscle metabolism
• Rate of serum creatinine production is constant for a given muscle mass.
• Creatinine clearance is a measure of how well the kidneys filter creatinine; it serves as a surrogate for GFR.
• Cockcroft-Gault Equation is a historical gold standard for drug dosing.

Creatinine Clearance (CrCl)

• Creatinine clearance is a measure of how well the kidneys remove creatinine from the blood
• Relationship between serum creatinine and creatinine clearance

Ideal Body Weight (IBW)

• Used in calculating appropriate weight for Cockcroft-Gault Equation.

Cockcroft-Gault Equation

• Used to estimate creatinine clearance
• Factors to calculate creatinine clearance include ideal body weight, serum creatinine level, and gender.
• Modifications for adjusted body weight and elderly patients.

In-Class Examples

• Examples given for the calculation of IBW, percentage of IBW and adjusted body weight, if needed using Cockcroft-Gault Equation

Blood Urea Nitrogen (BUN)

• Concentration of urea in the serum
• Urea is renally cleared, but influenced by multiple factors
• Used to monitor renal function, hydration, protein tolerance, and catabolism
• Urea reabsorption parallels water and sodium retention.
• Elevated BUN (azotemia) can be caused by high protein diet, upper gastrointestinal bleed, and certain drugs
• Decreased BUN could indicate malnourishment

BUN and Prerenal Injury

• Ratio of BUN to SCr can help distinguish between different types of kidney injury.
• High BUN:SCr ratio suggests prerenal injury
• Lower BUN:SCr ratio suggests intrarenal injury

Renal Function and the Pharmacist

• Nephrotoxic drugs need careful monitoring
• Dose adjustments are required for drugs eliminated by the kidneys
• Pharmacists need to assess factors beyond just numbers when managing patients with kidney dysfunction

Urinalysis

• Screening tool during hospital/office visits.
• Proper collection is vital for reliable results
• Urinalysis consists of macroscopic, microscopic, and chemical analysis
• Components of a urinalysis including color, turbidity, formed elements (cells, casts), and chemical components measured using chemical analysis.

Urinalysis: Macroscopic

• Includes color and turbidity
• Color changes may indicate certain drugs or diseases
• Turbidity can suggest the presence of precipitates

Examples of Urine Discoloration

• Various drugs and conditions can cause urine discoloration.

Urinalysis: Microscopic (formed elements)

• Includes microorganisms, cells, casts, and crystals in urine samples.
  • Preparation involves using a 12 ml sample, centrifuging it and examining under microscopic magnification.
  • Components examined include:
    • Microorganisms
    • Red blood cells
    • White blood cells
    • Casts (hyaline, cellular, granular, waxy)
    • Crystals (many types)

Cells (Microscopic, continued)

• Microorganisms: contamination
• Red blood cells: hematuria signals problems
• White blood cells: associated with UTIs
• Tubular epithelial cells: inflammation or acute tubular necrosis

Casts (Microscopic)

• Hyaline casts: associated with prerenal azotemia, strenuous exercise, or no specific cause
• Cellular casts: related to various kidney diseases
• Granular and Waxy Casts: advanced kidney conditions

Crystals (Microscopic)

• Various types of crystals are analyzed

Urinalysis: Chemical

• Semiquantitative tests use chemstrips to identify various components in the urinalysis.
• Components assessed here include: Specific gravity, protein, bilirubin, bile, glucose, urobilinogen, blood, ketones

Summary

• Understanding kidney function relates to the appropriate interpretation of clinical tests
• Lab tests and equations help assess kidney function but must be considered together with other clinical factors
• Components of a urinalysis and results can guide appropriate clinical decision making.
• Information regarding renal function is very important in patient care and guiding pharmaceutical care.

Additional Information (FYI only)

• Urinary Sodium

• Interpret in relation to water reabsorption

• Fractional Extraction of Sodium (%FENa)

• Timed Urine Collection

• Reports in ml/min/1.73 m²

• Ucr = urine creatinine

• V = volume of urine

• T = time collected

• BSA = body surface area

• GFR-abbreviated MDRD Equation

• Reports in ml/min/1.73 m²

This quiz focuses on the fundamentals of clinical laboratory medicine as it pertains to kidney function. Participants will explore kidney physiology, laboratory tests for renal function, and the significance of urinalysis. Additionally, the pharmacist's role in interpreting these tests will be highlighted.