Week 3 - Clinical Biochemistry of Renal Disease

Overview of Renal Disease

  • The presentation discusses various aspects of clinical biochemistry related to renal diseases including:
    • Structure and functions of the kidney
    • Renal function tests
    • Acute Kidney Injury (AKI)
    • Chronic Kidney Disease (CKD)
    • Electrolyte imbalances
    • Urea & Electrolyte (U&E) profile

Structure of the Kidney

  • Anatomical Structures:
    • Renal hilum: entry/exit point for blood vessels, nerves, and ureters.
    • Major parts include: Cortex, Medulla, Renal Pelvis, Calyces, and Nephrons.
    • Cortical and interlobar blood vessels supply blood throughout the kidney.

Functions of the Kidney

  • Homeostasis Regulation:

    • Volume Regulation: Maintains extracellular fluid and blood pressure.
    • Electrolyte Balance: Regulates levels of
      • Sodium (Na),
      • Potassium (K),
      • Chloride (Cl),
      • Calcium (Ca),
      • Magnesium (Mg),
      • Phosphate (PO4).
    • Acid-Base Balance: Maintains pH through H+ excretion and bicarbonate reabsorption.

  • Excretion of Waste Products:

    • Waste metabolites such as
      • Creatinine,
      • Urea,
      • Uric acid.

  • Endocrine Functions:

    • Vitamin D metabolism (conversion of 25-hydroxy Vitamin D to active form).
    • Production of erythropoietin (stimulates red blood cell production).
    • Production of renin (involved in blood pressure regulation).

The Nephron

  • Functional Unit of the Kidney:
    • Approximately 1 million nephrons per kidney.
    • Composed of two main parts: Glomerulus and Renal Tubule.
    • Glomerulus uses high-pressure filtration to create glomerular filtrate.

Renal Function Tests

  • Evaluates global nephron function and includes:
    • Measurement of Waste Products: Levels of creatinine and urea in plasma.
    • Glomerular Filtration Rate (GFR): Defines blood filtered by glomeruli per unit time (normal: approx. 90-120 mL/min).
    • Protein measurements in urine to assess glomerular integrity.

Creatinine and Urea Measurement

  • Creatinine:

    • Waste product of muscle metabolism, released at a consistent rate.
    • Reference ranges differ by sex:
      • Male: 64-104 µmol/L
      • Female: 49-90 µmol/L
    • Not sensitive for early renal disease detection; GFR can decrease by 50% before creatinine level rises.

  • Urea:

    • End product of protein metabolism, varies with dietary intake and hydration status. Less reliable than creatinine for renal function assessment.

Cystatin C

  • Small protein produced by all nucleated cells, cleared by the kidney; may provide a more accurate GFR measure than creatinine, but is costly.

Measuring/Estimating GFR

  • GFR can be assessed using:

    • Clearance tests (urinary excretion of substances fully filtered without reabsorption).
    • Essentially measures disappearance of substances from the plasma.
    • The most accurate measures require infusion of exogenous markers such as inulin.

  • Creatinine Clearance:

    • Utilizing endogenous creatinine in a timed urine collection (overestimating the GFR).

  • Estimated GFR (eGFR):

    • Calculated from serum creatinine, age, and sex; recommended formula: CKD-EPI.
    • Limitations include inaccuracies in extremes of muscle mass and in certain clinical scenarios (AKI, pregnancy).

Proteinuria and Its Significance

  • Indicates glomerular integrity loss; need for sensitive dipstick tests or measurement of protein/creatinine ratios (PCR or ACR).
  • Clinical significance of proteinuria includes potential nephrotic syndrome and implications for renal impairment.

Acute Kidney Injury (AKI)

  • Definition: Rapid loss of renal function (≤ 7 days), often potentially reversible and commonly occurs alongside existing medical conditions.

  • Causes:

    • Pre-renal: Volume depletion (shock, dehydration).
    • Intrinsic renal: Inflammation (glomerulonephritis), infections (pyelonephritis), or nephrotoxicity (certain drugs).
    • Post-renal: Obstruction (kidney stones, prostatic enlargement).

  • Biochemical Changes: Elevated creatinine and urea levels, electrolyte imbalances, potential for metabolic acidosis.

  • Management: Identify cause, provide supportive care, potential for dialysis.

Chronic Kidney Disease (CKD)

  • Definition: Kidney damage of over 3 months characterized by decreased GFR (
  • Causes: Diabetes, hypertension, glomerular diseases, obstructive uropathy, etc.
  • Management: Control of blood pressure, prevention of progression through various medications, dietary modifications, erythropoiesis stimulation, and nephrology referrals as needed.

Electrolyte Imbalances in CKD

  • As CKD progresses, various imbalances occur:
    • Elevated potassium and phosphate levels.
    • Metabolic acidosis due to decreased acid excretion.
    • Impaired vitamin D synthesis leading to hypocalcaemia.

Summary

  • The kidneys are crucial for fluid/electrolyte balance, blood pressure regulation, waste removal, and endocrine functions.
  • Recognition and timely management of both acute and chronic renal failure are vital for patient outcomes.