Kidney Function Measurement: Renal System MED 204

General

• Measurement of Kidney Function - Renal System Module MED 204, February 2025.
• Lecturer: Prof Triona Ni Chonghaile & Dr. Patrick Walsh

Learning Outcomes

• Define the concept of clearance and calculate clearance values with appropriate units.
• Integrate the concept of clearance to compare renal handling of different substances.
• Recall methods of measuring the glomerular filtration rate (GFR) using clearance.
• Outline the different components of urinalysis.
• Define glucosuria and proteinuria.
• Describe the use of ultrasound for assessing bladder function.

Why Renal Clearance Matters

• It helps assess renal function.
• Patients with kidney disease may exhibit hypertension, edema, hematuria or be asymptomatic.
• It is important to measure GFR (glomerular filtration rate) indirectly via clearance.

Glomerular Filtration Recap

• Plasma from blood entering the glomerulus is filtered into Bowman's capsule.
• Approximately 20% of plasma entering the glomerulus is filtered which equates to ~180 liters/day.
• Filtrate flows through the tubular system reabsorbing substances of value into peritubular plasma.
• Glomerular capillary blood pressure is the primary driving force for glomerular filtration.

Forces Involved in Glomerular Filtration

• Glomerular Capillary Blood Pressure: favors filtration, magnitude ~55 mm Hg.
• Plasma-Colloid Osmotic Pressure: opposes filtration, magnitude ~30 mm Hg.
• Bowman's Capsule Hydrostatic Pressure: opposes filtration, magnitude ~15 mm Hg.
• Net Filtration Pressure: favors filtration, Difference is between favoring and opposing forces = 10 mm Hg, 55 - (30 + 15) = 10.

Renal Assessment and Urine Formation

• Ultrafiltration: Blood is filtered in glomerular capillaries to form the tubular filtrate, GFR = rate of filtration.
• Reabsorption: Most of the filtrate is reabsorbed back into the blood.
• Secretion: Substances are secreted into the filtrate from the blood.

Renal Assessment and Clearance

• The coordination of the three processes determines the substance amount in the urine.
• Renal function is assessed by measuring the excretion rate of a substance in relation to its plasma concentration.
• The clearance of a substance is the measure of this process.

Renal Clearance

• Definition: The milliliters of plasma cleared of a substance in one minute, [mL/min].
• Renal clearance is the volume of blood plasma from which a particular waste product is completely removed in one minute, a substance-specific process.

Clearance Formula

• Formula for Clearance of any substance : Cs = (Us x V)/Ps.
• U = concentration of the substance in urine (mg/mL).
• V = volume of urine excreted per minute (mL/min).
• P = concentration of the substance in plasma (mg/mL).
• The Unit of clearance is mL/min.
  • If [Us] increases then Cs increases.
  • If Volume increases then Cs increases.
  • If [Ps] increases then Cs decreases.

Measurement of Glomerular Filtration Rate (GFR)

• GFR indicates the rate at which plasma is filtered at the glomerular capillaries to form the tubular filtrate.
• GFR is an index of renal function.
• It is measured using clearance.
• A decrease in GFR can be the first sign of renal disease.

GFR Measurement Substance Requirements

• The substance must be freely filtered at the glomerulus.
• It must NOT be reabsorbed from the filtrate.
• It cannot be secreted into the filtrate.
• Substance properties: Not metabolized by tubular cells, does not interfere with kidney function, not toxic, and is easily measured.

Understanding the GFR Measurement Substance

• The substance enters the tubular filtrate via filtration only.
• Then, it flows through the tubules, exiting in urine.

Inulin and Glomerular Filtration Rate (GFR)

• Inulin meets the listed GFR criteria.
• Inulin is the measure of GFR.
• Inulin enters the tubular filtrate through filtration only, then flows through the tubules, exiting in the urine.
• The rate at which it enters the filtrate must equal the rate at which it enters the urine.

GFR of Inulin

• Inulin excretion is proportional to plasma concentration.
• Clearance is independent of plasma concentration.

Inulin Handling in the Nephron

• Pin marks Plasma inulin concentration.
• Uin marks Urine inulin concentration.
• V marks Volume of urine excreted.
• There is no tubular reabsorption of inulin.

Rate of Inulin Entry

• Rate of inulin entry into the filtrate: Pin x GFR.
• Rate of inulin entry into the urine: Uin x V.
• Formula: GFR = (Uin x V) / Pin.

Creatinine

• Inulin must be administerd intravenously because it does not naturally occur in the body.
• Inulin is seldomly (not often) used to measure GFR clinically because it is administered intravenously.
• Creatinine, produced in the body, will measure estimated GFR (eGFR) within the clinical setting.

Creatinine

• Creatinine is the main role to facilitate ATP in energy dependent tissues (e.g. muscle and brain).
  • It is Synthesised from arginine in the liver (1g/day) + 1g diet.
  • It is phosphorylated in skeletal muscle and brain.
  • It is an important energy source.
  • • particularly for short bursts of anaerobic energy
• Creatinine is Formed spontaneously from phosphocreatine.
  • Has a consistant synthetic rate (2% of creatine levels/day).
  • Plasma levels depends on muscle bulk and is Removed from the blood by glomerular filtration and tubular secretion.
• If renal filtration is deficient, plasma creatinine levels increase.
• Measurement of creatinine within urine (creatinine clearance) is an indicator of kidney function

Creatinine Details

• Creatinine does not fully meet the criteria for a substance to give a measure of eGFR.
• Small quantities of creatinine secrete into the tubule from the blood.
• The error due to this effect is roughly canceled out via another error that arises in the estimation of plasma creatinine.

Cancellation of Errors in Creatinine Clearance

• Slight secretion results creatinine entering the not only only by filtrate, but also by filtration.
• The "U" in the clearance formula is erroneously high, with the formula: Cs = (Us x V) / Ps.
• The estimation method measures plasma creatinine concentration, resulting in “P” being erroneously high; therefore the errors cancel each other out. As a result, creatinine clearance is commonly used to measure GFR.

Clearance Values

• Inulin clearance ≈ 120 ml/min.
• Creatinine clearance ≈ 120 ml/min.

Clinical Estimation of GFR

• Measuring GFR with creatinine requires creatinine to be in both plasma and urine.
• Mathematical formulas help estimate creatinine from only a measurement of plasma.

Creatinine Account Factors

• Creatinine is derived from the breakdown of creatine in skeletal muscles.
• The quantity entering the plasma increases or decreases depending on skeletal muscle mass.
• Skeletal muscle mass depends on age
• Creatinine release into plasma typically remains constant during the day.

Table Breakdown of Age and eGFR

• Age (years) compared to Average estimated GFR.
  • 20-29 with 116 eGFR
  • 30-39 with 107 eGFR
  • 40-49 with 99 eGFR
  • 50-59 with 93 eGFR
  • 60-69 with 85 eGFR
  • 70+ with 75 eGFR

Estimated GFR (eGFR)

• Measures creatinine clearance
• Takes into account:
  • Gender
  • Age
  • Weight
• Chronic Kidney disease epidemiology collaboration (CDK-EPI 2009) is the current best practice.
• GFR = 141 × min (Scr/K, 1)ɑ × max(Scr/к, 1)-1.209 × 0.993Age × 1.018 [if female]*
• Scr indicates creatinine in mg/dl

Clearance of Other Substances

• Comparing other substance clearances gives information about renal handling, compared to that of inulin.
• Substances with clearance less than inulin are filtered and reabsorbed.
  • This includes glucose, and urea
  • Urine levels are an indication of plasma levels/threshold.

PAH Properties

• Substances with clearances larger than that of inulin are filtered (glomerulus) and secreted (tubular).
• This includes Para-amino-hippuric acid.

Autoregulation of Renal Plasma Flow and Glomerular Filtration Rate

• It is possible to measure renal plasma flow using clearance
• GFR indicated by the blue line
• RPF indicated by the red line

PAH for Renal Flow

• Para-amino-hippuric acid (PAH) is freely filtrable, and nonreabsorbable..
• All PAH that escapes from filtration is secreted during the organic anion secretory pathway in proximal tubule.
• PAH is utterly removed from all plasma that passes throughout the kidneys.
• A Good estimate of effective renal plasma flow (eRPF) is approximately 625 ml/min.

Other Substances Clearance

• Other substances can be classified into the following cases:
  • Case 1: Normal Clearance - Freely filtered, not absorbed, not secreted. Like Inulin, normal GFR of is 125 ml/min.
  • Case 2: Freely filtered, fully reabsorbed, not secreted. Clearance of Renal is approximately 0 ml/min. Like glucose and amino acids.
  • Case 3: Renal plasma flow = renal clearance, such as with para aminohippuric acid (PAH), is freely filtered, not absorbed, and fully secreted. With approximately 625 ml/min.
  • Case 4: Freely filtered, a lower than GFR value, is renal clearance than is slightly reabsorbed, not secreted. With something like urea at approximately 65 ml/min.

GFR and Renal Disease

• It is critical to be aware of GFR in estimating an extent and course of kidney illnesses.
• Falls in GFR generally point out kidney problems.
• It is safe to say that constant reduces in GFR will signal a sickness progressing, increases normally signal recovery.

Kidney Injury Causes

• Alterations in blood, from sources such as hemorrhage, heart attacks, and hypotension.
• Damage to the liver from toxins, inflammations such as from glomerulonephritis, and from tubular necrosis.
• Abnormalities within the Tract, especially in the Urethral and Prostate that commonly include obstructions from enlargement/stones.
• Urea and electrolyte (U+E) measurements assess acute kidney injury and measure Sodium, Potassium, Chloride, Bicarbonate, Urea, and Creatinine

Estimates of GFR and Disease

• The relationship between concentration and clearance estimates GFR.
• In cases such as kidney illnesses, GFR falls which is often mirrored by raising plasma

Urine

• Urine consists of sterile, clear and amber in colour. pH values range from ~5.0- 6.0
• Approx. 93-97% water
• A person usually passes at least 1.2 Liters a day

Urine Composition

• Consists of water, inorganic, and organic substances:
  • For Water, approximately 95 g/100 ml of urine.
  • For Urea, approximately 2 g/100 ml of urine.
  • For Sodium, approximately 0.6 g/100 ml of urine.
  • For Chloride, approximately 0.6 g/100 ml of urine.
  • For Sulfate, approximately 0.18 g/100 ml of urine.
  • For Potassium, approximately 0.15 g/100 ml of urine.
  • For Phosphate, approximately 0.12 g/100 ml of urine.
  • For Creatinine, approximately 0.1 g/100 ml of urine.
  • For ammonia, approximately 0.05 g/100 ml of urine.
  • For Uric Acid, approximately 0.03 g/100 ml of urine.
  • For Calcium, approximately 0.015 g/100 ml of urine.
  • For Magnesium, approximately 0.01 g/100 ml of urine.
• Significant deviations in volume or composition result from diet, drugs, or renal disorders.

Urinalysis

• An analysis of urine with physical, chemical, and microscopic methods to test for diseases/drug presence.
• First started in 4000BC.
  • Hippocrates, the “father of medicine” exclaimed that, “no organ system of the human body provides as much info as its urine excretion.”
• Includes checking of appearance, concentration, and overall content.
• Diagnosing certain conditions like Liver/kidney Disorders, UTIs, cancer, or diabetes.

Visual Examination

• Indicates both hydration state and content.
  • Color-ranges from pale yellow to dark amber.
    • Can signify dehydration, medications, diseases, or even diet.
  • Clarity-Ranging from clear, cloudy, or turbid.
    • Can indicate mucus, sperm, inflammation, or even bacteria

Urinalysis – Chemical Analysis

• Utilizes test strips and pads containing chemicals.
• Change of colors gives an insight into substance amount present.
• Dipsticks tests for:
  • Bilirubin
  • Glucose
  • Haemoglobin
  • Ketones
  • Nitrite
  • pH
  • Urobilinogen
  • Protein
  • Esterases
• Chemical examinations accompany follow microscope examinations.

Relationship Between Plasma Glucose and Excretion Levels

• Glucosuria: Presence of glucose in the urine due to glomerular filtration exceeding the renal tubule's reabsorption capacity.