Age-related changes in GFR

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GFR Fundamentals - The Kidney's Sieve

  • Glomerular Filtration Rate (GFR): Volume of fluid filtered from glomeruli into Bowman's space per minute. Normal: ~100-125 mL/min.
  • Filtration Barrier: A sieve with 3 layers creating size and charge selectivity.
    • Fenestrated capillary endothelium: Blocks cells.
    • Glomerular Basement Membrane (GBM): Contains heparan sulfate for a negative charge barrier.
    • Podocyte foot processes: Form filtration slits.

Glomerular filtration barrier components and structure

  • Filtration Fraction (FF): The proportion of renal plasma flow (RPF) that is filtered across the glomerulus. $FF = GFR / RPF$. Normal ≈ 20%.

⭐ The GBM's negative charge is crucial for repelling albumin. Loss of this charge (e.g., minimal change disease) causes selective proteinuria.

The Aging Filter - Senescence & Sclerosis

  • Physiological Decline: GFR naturally ↓ with age, starting from 30-40 years.

    • Rate of decline: Approx. 1 mL/min/1.73m² per year.
    • By age 80, GFR can be 50-60 mL/min, impacting drug dosage calculations.
  • Structural Changes (Nephrosclerosis):

    • Glomerulosclerosis: Scarring of glomeruli.
    • Arteriolosclerosis: Hyaline thickening of afferent & efferent arterioles.
    • Tubulointerstitial Fibrosis: Scarring of tubules and surrounding tissue.
    • Result: ↓ number of functional nephrons & ↓ renal blood flow.

Age-related changes in renal collagen and CD31 expression

Clinical Pearl: Serum creatinine may remain in the normal range in the elderly despite a significant ↓ in GFR. This is due to age-related ↓ muscle mass (sarcopenia), leading to reduced creatinine production. Always estimate GFR (e.g., using CKD-EPI) rather than relying on serum creatinine alone for renal function assessment.

Clinical Consequences - Geriatric Dosing Dilemmas

  • Physiological Decline: GFR naturally ↓ with age, roughly 1 mL/min/year after age 40. This decline significantly impacts drug pharmacokinetics.
  • Masked Dysfunction: Elderly patients often have ↓ muscle mass, leading to lower creatinine production.
    • A normal serum creatinine level can mask underlying renal impairment, creating a false sense of security.
  • Dosing Challenges: Failure to adjust drug doses for age-related ↓ GFR is a major cause of adverse drug events.
    • Increased risk of toxicity from drugs cleared by the kidneys.
    • Common culprits: Aminoglycosides, Vancomycin, Digoxin, DOACs, Metformin.

Clinical Pearl: Always estimate GFR or creatinine clearance (CrCl) using formulas like the Cockcroft-Gault or MDRD equation in geriatric patients before prescribing renally excreted drugs. Do not rely on serum creatinine alone.

High-Yield Points - ⚡ Biggest Takeaways

  • Glomerular Filtration Rate (GFR) begins a progressive decline after age 30-40, decreasing by about 1 mL/min/year.
  • This decline is primarily due to the loss of functional nephrons (glomerulosclerosis) and reduced renal blood flow.
  • Despite a significant drop in GFR, serum creatinine often remains within the normal range.
  • This discrepancy occurs because of age-related muscle atrophy, leading to lower creatinine production.
  • Crucially, this necessitates dose adjustments for renally-cleared drugs in elderly patients.

Practice Questions: Age-related changes in GFR

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Which factor most strongly influences protein filtration at the glomerulus?

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Flashcards: Age-related changes in GFR

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In addition to inulin, _____ clearance may also be used to estimate GFR

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In addition to inulin, _____ clearance may also be used to estimate GFR

creatinine

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