Human Biology Nephron Functions

Tubular Processing

• The kidneys play a vital role in regulating body fluid volume and composition.
• Nephrons are the functional units of the kidneys and perform three main processes: filtration, reabsorption, and secretion.
• Tubular processing fine-tunes urine volume and composition to prevent excessive fluid and solute losses.
• Reabsorption is the primary process for most substances in determining final urinary excretion.

Tubular Reabsorption

• Tubular reabsorption is a quantitatively large and highly selective process that allows independent regulation of solute excretion.
• It involves the movement of fluid and solutes from the tubule lumen to the peritubular capillary using both passive and active transport mechanisms.
• Luminal and basal surfaces of tubule epithelial cells feature different transporter proteins, facilitating the establishment of concentration gradients.
• The Na+/K+ ATPase plays a crucial role in reabsorption of many substances by providing a concentration gradient along the nephron.
• Water is passively reabsorbed and closely linked to sodium reabsorption and the permeability of different nephron segments.

Proximal Convoluted Tubule

• The majority of sodium and water reabsorption (approximately 65%) occurs in the proximal convoluted tubule (PCT).
• The PCT has a brush border increasing surface area and mitochondria for energy supply.
• It is also the site of secretion of metabolic acids, bases, and drugs.
• Tubular fluid exiting the PCT is isosmotic due to the freely permeable epithelium to water.
• The PCT is the main site of glucose and amino acid reabsorption.

Glucose and Amino Acids

• Almost all glucose and amino acids are reabsorbed in the PCT via secondary active transport (co-transporters) linked to sodium reabsorption.
• Sodium glucose co-transporters (SGLT2 mainly) on the luminal side move glucose against its concentration gradient.
• Glucose transporters (GLUT) on the basal side allow facilitated diffusion of glucose into the interstitial fluid.
• A similar process occurs for amino acids.

Glucose and Tm

• There is a finite number of SGLT transporters on proximal tubule cells.
• They function well under normal physiological plasma glucose levels.
• When glucose in the filtrate exceeds the transport maximum (Tm), reabsorption cannot keep up, leading to glucose loss in urine.
• Water is retained in the tubule lumen and excreted along with glucose creating an osmotic effect.

Secretion of H+

• Sodium reabsorption is linked to the secondary active transport of hydrogen ions (H+) into the lumen (secretion).
• This is essential for bicarbonate reabsorption in the proximal tubule.
• The Na+/H+ exchanger (NHE) functions as an antiporter.

Loop of Henle

• The loop of Henle is divided into three parts: the thin descending limb, thin ascending limb, and thick ascending limb.
• The thin descending limb is permeable to water and does not actively reabsorb or secrete solutes.
• The thin ascending limb is impermeable to water and also does not actively reabsorb or secrete solutes.
• The thick ascending limb is impermeable to water and actively reabsorbs sodium (approximately 25% of the filtered load) and other solutes.
• This dilution of luminal fluid (hypo-osmotic) occurs as solutes are removed/reabsorbed, but water cannot follow.

Thick Ascending Limb

• Reabsorption of sodium, potassium, and chloride from the tubule lumen is primarily mediated by the sodium, potassium, 2-chloride co-transporter (Na+K+2Cl-).
• The positive charge in the lumen encourages paracellular reabsorption of cations, including calcium (Ca2+) and magnesium (Mg2+).
• As water cannot follow the solutes, the remaining tubular lumen fluid becomes diluted.

Early Distal Tubule

• The early distal tubule is impermeable to water and contributes to the dilution of the filtrate.
• It actively reabsorbs sodium (approximately 5% of the filtered load).
• The early distal tubule contains the macula densa, a structure sensitive to NaCl levels that forms part of the juxtaglomerular apparatus involved in feedback control of glomerular filtration rate (GFR) and blood pressure.

Early Distal Tubule 2

• Sodium-chloride co-transporter on the luminal side further dilutes the tubular lumen fluid.

Late Distal Tubule and Cortical Collecting Tubule

• These segments share similar functional characteristics.
• Water permeability is regulated by antidiuretic hormone (ADH):
  • Water permeable in the presence of ADH.
  • Water impermeable in the absence of ADH.
• Two main cell types exist:
  • Principal cells: involved in sodium reabsorption (through epithelial sodium channels, ENaC) and potassium secretion.
  • Intercalated cells: involved in potassium reabsorption and hydrogen ion secretion.

Principal Cells

• Sodium enters principal cells through ENaC on the luminal side and is transported out of cells by Na+/K+ ATPase to maintain a concentration gradient.
• The number of ENaC channels and the activity of ATPase are under hormonal control by aldosterone.
• Principal cells are an important site of regulation and fine-tuning of sodium reabsorption and potassium secretion.

Medullary Collecting Duct

• The medullary collecting duct is the final site for urine processing.
• Water permeability is regulated by ADH.
• It's surrounded by a medullary interstitium with a high solute concentration.
• It plays a key role in regulating urine concentration.
• Urea permeability allows the medullary interstitium to remain concentrated.

Regulation of Tubular Processes

• Tubular processes are regulated by local feedback, hormonal, and neural mechanisms.
• In contrast to GFR regulation, reabsorption of individual solutes can be adjusted independently, particularly by hormones acting on different parts of the nephron.

Drugs and the Kidney

• Renal impairment can lead to drug accumulation and toxicity
• Nephrotoxic drugs should be avoided in patients with renal impairment
• Drugs can be less effective in patients with impaired renal function
• Medications may need to be modified for elderly patients

Diuretics

• Diuretics promote urine excretion by increasing sodium excretion
• Loop diuretics, Thiazide diuretics, and Potassium sparing diuretics are the main classes
• Potassium sparing diuretics can lead to hyperkalemia
• Loop diuretics and Thiazide diuretics can be combined for improved diuretic effect without K+ loss

Drugs acting on the RAAS

• The Renin-Angiotensin-Aldosterone System (RAAS) plays a crucial role in blood pressure and flow regulation
• Angiotensin Converting Enzyme (ACE) inhibitors, Angiotensin Receptor Blockers (ARBs), and Aldosterone Antagonists are the main classes
• Aldosterone antagonists can be used in conjunction with loop or thiazide diuretics to prevent potassium loss

Potassium sparing diuretics

• Commonly used for conditions associated with edema and hypertension
• Can be used to prevent potassium loss from loop or thiazide diuretics
• Can cause hyperkalaemia

Aldosterone Antagonists

• Bind to the mineralocorticoid receptor (MR) and block aldosterone activation
• Reduce potassium secretion into tubular lumen, leading to potassium retention

### Regulation of GFR via vascular control

• Balance of afferent arteriole (AA) and efferent arteriole (EA) resistances determine GFR
• Dilation of AA or constriction of EA increases GFR
• Constriction of AA or dilation of EA reduces GFR

NSAIDs and GFR

• NSAIDs inhibit prostaglandin production which promotes dilation of the afferent arteriole and increases GFR
• NSAIDs can reduce GFR

ACEi/ARB and GFR

• ACE inhibitors and ARBs prevent angiotensin II action which drives efferent arteriolar constriction
• ACEi and ARBs therefore can also reduce GFR

Drug Metabolism

• The liver is the primary site for drug metabolism.
• Orally administered drugs undergo first-pass metabolism in the liver before entering systemic circulation.
• Drugs can pass through the liver multiple times during systemic circulation, with a fraction metabolized each time.
• Metabolites can be excreted through the kidneys or bile.

Biochemical Pathways of Drug Metabolism in the Liver

• Drug metabolism occurs in two phases:
  • Phase I: Introduces or exposes functional groups (e.g., OH or NH2) to increase polarity and prepare for phase II.
  • Phase II: Conjugation reactions attach large chemical groups to the drug, rendering it inactive and more easily excreted.

Phase I Metabolism

• Involves oxidation, reduction, and hydrolysis.
• Most often decreases drug activity, but can increase activity for pro-drugs.
• Cytochrome P450 enzymes are a critical component of Phase I metabolism.

Cytochrome P450 Enzymes

• A superfamily of enzymes located on the endoplasmic reticulum of hepatocytes.
• Hundreds of isoforms exist with varying protein structure, regulation, and substrate specificity.
• Many are inducible, meaning their activity can be increased by exposure to certain substances.
• These heme-containing enzymes require molecular oxygen, NADPH, and NADPH cytochrome P450 reductase to function.

Major Cytochrome P450 Isoforms

• CYP3A: Metabolizes a large proportion of drugs.
• CYP2D6: Responsible for the metabolism of numerous drugs, including antidepressants and antipsychotics.
• CYP2C9: Involved in the metabolism of many drugs, such as warfarin and NSAIDs.
• CYP1A2: Metabolizes several drugs, including caffeine and some antipsychotics.

Oxidation of a Drug by Cytochrome P450

• The process involves both chemical oxidation and reduction steps.
• Cytochrome P450 catalyzes the transfer of one oxygen atom to the drug, while the other atom is reduced to water.

Other Phase I Reactions

• Reductions are less common than oxidations.
• Oxidations that do not involve the CYP450 system occur, such as ethanol metabolism by alcohol dehydrogenase.
• Monoamine oxidase enzymes inactivate biogenic amines like norepinephrine, serotonin, and dopamine.
• Hydrolytic reactions occur in plasma and various tissues, such as the hydrolysis of aspirin to salicylic acid.

Phase II Reactions

• Conjugation reactions involve attaching a large chemical group to the drug molecule.
• Most commonly occurs in the liver, but can also occur in other tissues.
• Common conjugates include glucuronyl, acetyl, methyl, sulphate, and glutathione.
• Conjugating enzymes can be located on the ER or in the cytosol.

Drug Interactions at the Level of Hepatic Metabolism

• Often occur due to interactions at CYP450 enzymes.
• Various factors (drugs, alcohol, food components, environmental contaminants) can alter CYP450 activity.
• CYP450 enzyme induction increases drug metabolism, leading to lower plasma levels and potentially reduced therapeutic efficacy.
• CYP450 enzyme inhibition reduces drug metabolism, leading to higher plasma levels and increased potential for toxicity.

CYP450 Enzyme Induction

• Long-term drug administration can induce CYP450 activity by increasing synthesis or decreasing degradation of the enzyme.
• This results in faster metabolism of the drug and other drugs metabolized by the same enzyme.
• Plasma levels and biological effects of the drugs decrease.

St. John's Wort

• An herbal remedy often used for depression.
• Induces the activity of multiple CYP450 enzymes, leading to increased metabolism and lower plasma levels of various medications (e.g., warfarin, antiepileptic drugs, oral contraceptives).

CYP450 Enzyme Inhibition

• Drugs or other substances can inhibit CYP450 activity.
• This slows down the metabolism of drugs metabolized by the inhibited enzyme.
• Plasma levels and biological effects of the drug increase, raising the risk of toxicity.

Omeprazole

• A proton pump inhibitor.
• A weak inhibitor of many CYP450 enzymes, leading to reduced metabolism of endogenous steroids and co-administered drugs (e.g., warfarin, phenytoin).
• Increased plasma levels of these drugs can lead to toxicity.

Effects of Liver Disease on Drug Action

• Impaired liver function reduces drug-metabolizing capacity.
• Hypoproteinemia reduces drug binding, leading to more unbound and active drug circulating.
• Porto-systemic shunting bypasses the liver, reducing first-pass metabolism.
• Increased bioavailability due to decreased first-pass metabolism.
• Reduced clearance of drugs due to impaired liver function.

Precautions When Prescribing in Liver Disease

• Reduced initial doses of drugs metabolized by the liver.
• Careful monitoring of drug levels and response.
• Consider alternative medications with lower hepatic metabolism.

First-Pass Metabolism

• Orally administered drugs are absorbed into the portal system.
• The liver can metabolize these drugs before they reach systemic circulation.
• This significantly affects bioavailability.

Increased Bioavailability Due to Decreased First-Pass Metabolism

• Liver disease reduces first-pass metabolism due to impaired hepatocyte function and porto-systemic shunting.
• Increased bioavailability leads to higher plasma levels and potential toxicity.
• Initial doses should be reduced for drugs metabolized by the liver in patients with liver disease.

Decreased Protein Binding

• Liver disease can cause hypoproteinemia, reducing drug binding capacity.
• Increased free (unbound) drug levels lead to higher biological effects.

Liver Blood Tests

• Basic liver panel includes:

  • Alanine aminotransferase (ALT)
  • Aspartate aminotransferase (AST)
  • Albumin
  • Alkaline phosphatase
  • Total bilirubin
  • Conjugated bilirubin
  • Gamma-glutamyl transferase (GGT)

• Normal liver blood tests do not always exclude pathology because the liver can compensate for damage.

Total Protein

• Total protein measures the sum of all proteins in the blood sample.
• Albumin is the most abundant protein in blood and is a storage protein.
• Other principal protein measured in a total protein test is Immunoglobulins.

Bilirubin

• Bilirubin is a breakdown product of heme.
• Small amounts of bilirubin are normal in blood due to the turnover of red blood cells.

Gamma-Glutamyl Transferase (GGT)

• Gamma-glutamyl transferase (GGT) is an enzyme primarily found in the liver.
• Elevated GGT levels indicate liver or bile duct damage.
• GGT levels are also elevated in individuals with chronic alcohol consumption.

Liver Enzymes

• Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) are both aminotransferases found in the liver.
• Elevated levels of both ALT and AST suggest liver damage.
• ALT is generally elevated in acute liver damage.
• Clinicians may use higher AST levels over time to indicate cirrhosis.

Conjugated Bilirubin

• Conjugated bilirubin is a soluble form of bilirubin, produced in the liver.
• The presence of conjugated bilirubin in the blood suggests a blockage of the bile duct or liver dysfunction.
• Conjugated bilirubin is not normally found in the blood.

Epithelial Tissue Specialization in Kidneys

• Epithelial tissue in the kidneys plays a crucial role in filtration, absorption, and secretion.
• Specialised structures like microvilli, cilia, mucoid glands, and keratin contribute to these functions.

Kidney Macrostructure

• The kidney consists of a cortex, medulla, renal pyramids, renal papilla, renal artery, renal vein, renal pelvis, and ureter.
• Minor calyces and major calyces are located within the kidney.

Kidney Microstructure

• The kidney is composed of numerous uriniferous tubules and associated blood vessels.
• The uriniferous tubule is made up of a nephron and a collecting duct.
• Each kidney contains approximately one million nephrons.
• Multiple nephrons drain into a common collecting duct.
• There are slight variations in the definition and naming of different parts of the uriniferous tubule across various sources.

Nephron Structure

• The nephron is the functional unit of the kidney.
• Components of the nephron include the renal corpuscle, proximal convoluted tubule (PT), loop of Henle, and distal convoluted tubule (DT).
• The cortex primarily contains renal corpuscles, PT, and DT, while the medulla mainly contains loops of Henle and collecting ducts.
• Nephrons are categorized as cortical or juxtamedullary based on the location of their renal corpuscle, with cortical nephrons comprising around 80% and juxtamedullary nephrons making up approximately 20%.

Overview of Kidney Microstructure

• The uriniferous tubule encompasses the nephron and collecting duct.
• The nephron consists of the renal corpuscle, proximal tubule, loop of Henle, and distal tubule.
• The renal corpuscle is made up of the glomerulus and Bowman's capsule.
• The glomerulus is a network of capillaries responsible for filtration.
• Bowman's capsule is a double-walled cup that surrounds the glomerulus.
• The parietal layer of Bowman's capsule, composed of simple squamous epithelium, provides containment.
• The visceral layer of Bowman's capsule is made up of modified simple squamous epithelium called podocytes, which play a crucial role in filtration.
• Mesangial cells support the glomerular capillaries.

Blood Supply to the Kidneys

• Blood enters the kidneys through the renal artery.
• The renal artery branches into segmental arteries, which further divide into interlobar arteries.
• Arcuate arteries run along the corticomedullary junction.
• Interlobular arteries branch off from the arcuate arteries and supply afferent arterioles to the renal corpuscles.
• Efferent arterioles arise from the glomerular capillaries.
• Peritubular capillaries surround the renal tubules.
• Vasa recta, low-pressure capillaries, are found in the medulla.
• The blood flow through the kidney involves two capillary beds: the high-pressure glomerular capillaries (filtration) and the low-pressure peritubular capillaries (reabsorption and secretion).

Renal Corpuscle Structure

• The renal corpuscle consists of the glomerulus and Bowman's capsule.
• The glomerular capillaries are fenestrated, allowing for filtration.
• The filtration barrier in the renal corpuscle is composed of three layers: glomerular capillary endothelium, basement membrane, and podocytes with their filtration slits.
• The filtration barrier restricts the passage of substances from the blood based on their size, charge, and shape.

Nephron - Simplified Form

• The nephron consists of the renal corpuscle, proximal convoluted tubule, loop of Henle, and distal convoluted tubule.

Proximal Convoluted Tubule

• Unmodified filtrate produced in Bowman's capsule enters the PCT.
• The PCT is responsible for the reabsorption of the majority of water, sodium, chloride, amino acids, and glucose.
• The PCT also secretes certain drugs and waste molecules.
• The PCT is lined by simple cuboidal cells with microvilli, forming a brush border that increases surface area.

Loop of Henle

• The loop of Henle, a hairpin-shaped structure, has three main segments: descending limb, thin ascending limb, and thick ascending limb.
• The descending limb is permeable to water and allows for water reabsorption.
• The ascending limb is impermeable to water but actively reabsorbs sodium and other solutes.
• The loop of Henle plays an important role in establishing a hyperosmolar medullary interstitium, which is crucial for urine concentration.

Distal Convoluted Tubule

• Divided into early and late segments, the DCT actively reabsorbs sodium and secretes potassium and hydrogen ions.
• The DCT is lined by simple cuboidal cells.
• Water permeability varies in the DCT depending on the specific segment and the presence of antidiuretic hormone (ADH).
• The early DCT loops back to the vascular pole of its own renal corpuscle, forming part of the juxtaglomerular apparatus.

Juxtaglomerular Apparatus

• The JGA consists of three components: the macula densa, extraglomerular mesangial cells (Lacis cells), and granular or juxtaglomerular cells.
• The macula densa, specialized cells in the early DCT, monitors changes in filtrate composition (e.g., sodium concentration).
• The granular cells in the afferent arteriole produce renin, a key enzyme in the renin-angiotensin-aldosterone system.
• The JGA plays a crucial role in regulating glomerular filtration rate through tubuloglomerular feedback and blood pressure control.

Collecting Duct

• The collecting duct is the final site of urine processing.
• Water permeability in the collecting duct is regulated by ADH.
• The collecting duct is surrounded by a medullary interstitium with a high solute concentration, further aiding in urine concentration.
• It plays a critical role in regulating urine concentration.
• The collecting duct is lined by simple columnar cells.

Body Fluid Compartments

• Approximately 60% of body weight is comprised of water.
• Water distribution varies with age, sex, and body fat.
• Body fluids are distributed in various compartments separated by semipermeable membranes.
• Intracellular fluid (ICF) constitutes approximately 28 liters and represents the fluid within cells.
• Extracellular fluid (ECF) consists of interstitial fluid, found between cells, and plasma, the non-cellular component of blood.

Body Fluid Composition

• The capillary membrane is permeable to water and electrolytes but not most plasma proteins.
• Interstitial fluid and plasma have similar compositions except for proteins, which remain in plasma.
• The cell membrane is permeable to water but not most electrolytes.
• The major cation in ECF is sodium, while the main anion is chloride.
• Potassium is the primary cation in ICF, and phosphate is the primary anion.
• Osmotic equilibrium is maintained between different fluid compartments.

Glomerular Filtration

• Nephron is the functional unit of the kidney
• Three main processes performed by the nephron are:
  • Filtration
  • Reabsorption
  • Secretion
• Urinary excretion rate is the sum of filtration, secretion, and reabsorption
• Filtration is the first step in the process of urine formation. It is essential for clearing waste products.
• Kidneys receive approximately 20% of cardiac output, which translates to around 1 litre/min of renal blood flow.
• Renal plasma flow is approximately 600 ml / min
• 20% of renal plasma flow passes through the filtration barrier to form filtrate
• Filtration fraction: ~120 mL/min
• Glomerular filtration rate (GFR) is the volume of filtrate formed by all the nephrons in both kidneys per unit time.
• Three main structures compose the glomerular filtration barrier:
  • Glomerular capillary endothelium (fenestrated)
  • Basement membrane (negative charge)
  • Epithelial cells (podocytes)
• The filtration barrier limits the passage of substances based on their:
  • Size
  • Charge
  • Shape
• Blood cells and most plasma proteins are excluded from the filtrate
• Glomerular capillary filtration coefficient (Kf) reflects the:
  • Surface area available for filtration
  • Hydraulic conductivity of the filtration barrier
• Net filtration pressure (NFP) is the sum of the hydrostatic and colloid osmotic pressures acting across the filtration barrier.
• NFP equation: PG – PB – πG + πB.
• Typical value for NFP is 10 mmHg
• GFR is determined by the glomerular filtration barrier and net filtration pressure
• Autoregulation of GFR ensures that GFR stays relatively constant across a range of systemic blood pressures, preventing large changes in renal excretion of water and solutes.
• Two mechanisms of autoregulation:
  • Myogenic response
  • Tubuloglomerular feedback
• Myogenic response is the inherent ability of smooth muscle in afferent arterioles to respond to changes in vessel circumference.
• Tubuloglomerular feedback (TGF) links changes in [NaCl] in the tubule lumen to control afferent arteriole resistance. It utilizes the juxtaglomerular apparatus (JGA).
• The JGA is composed of:
  • Macula densa cells
  • Lacis cells
  • Granular cells

Factors that Determine GFR

• The volume of filtrate formed by all the nephrons in both kidneys per unit time.
• It is determined by:
  • Glomerular capillary filtration coefficient (Kf)
  • Net filtration pressure (NFP)
• Kf reflects the surface area available for filtration and the hydraulic conductivity of the filtration barrier.
• NFP is the sum of the hydrostatic and colloid osmotic pressures acting across the filtration barrier.
• Most physiological regulation of GFR occurs due to changes in glomerular hydrostatic pressure (PG).
• PG depends on these three factors:
  • Arterial pressure
  • Afferent arteriole resistance
  • Efferent arteriole resistance
• Afferent arteriole dilation and/or efferent arteriole constriction increases GFR
• Afferent arteriole constriction and/or efferent arteriole dilation reduces GFR

Factors that Influence GFR

• Angiotensin II preferentially constricts the efferent arteriole, thus increasing PG and GFR
• Prostaglandins and atrial natriuretic peptide (ANP) dilate the afferent arteriole, increasing PG and GFR
• Noradrenaline (sympathetic nervous system), adenosine, and endothelin tend to vasoconstrict the afferent arteriole, reducing PG and GFR.

Indicators of Renal Decline

• Proteinuria / Albuminuria: Indicate damage to kidneys
• Haematuria: Indicate damage to kidneys
• Estimated GFR / GFR: Indicate kidney function
• Serum Creatinine / Urea: Indicate kidney function
• Calcium / Phosphate: Indicate homeostasis and kidney function, but not quantitive
• Electrolytes / pH: Indicate kidney function, but not quantitive
• Fluid balance / Urine volume: Indicate kidney function, but not quantitive
• Haemoglobin: Indicate kidney function, but not quantitive

Measuring Renal Function

• Glomerular Filtration Rate (GFR): Volume of filtrate formed by nephrons in both kidneys per unit time
• GFR: Directly related to nephron function and declines in all forms of progressive kidney diseases
• GFR: Accepted as best overall index of kidney function in health and disease
• GFR: Does not tell you cause or location of kidney problem
• GFR: Linked to body surface area, typical young male GFR = 120 ml/min/1.73m2
• GFR: Linked to age, sex, and body size, declines with increasing age
• GFR: Difficult to measure directly

Routine Measures of GFR

• Rationale: If something normally filtered by the kidney builds up in the blood, it indicates decreased GFR and therefore decreased renal function
• Measurement using exogenous markers: More accurate, but can be time-consuming and expensive (e.g. inulin infusion)
• Measurement via endogenous markers: More cost-effective and routinely used in clinical practice
• Three tests routinely used to assess renal function:
  • Serum urea
  • Serum creatinine
  • Estimated GFR (eGFR)
• All tests: Use a single serum measurement, making them convenient for routine assessment and monitoring of renal function

Serum Creatinine

• Serum creatinine: More accurately reflects GFR than urea
• Creatinine: Formed from breakdown of creatine, a skeletal muscle component
• Creatinine: Produced at a more steady rate for a given individual
• Serum creatinine: Still relatively inaccurate as a point measure of GFR, but useful for monitoring trends
• Inaccuracies with serum creatinine: Result from the way its production varies between individuals and relates to muscle mass
• Factors affecting muscle mass: Age, sex, amputation, malnutrition, muscle wasting
• Diet: Also affects creatinine levels (vegetarian diet vs. meat rich diet)

Estimated GFR (eGFR)

• eGFR: Uses equations to calculate (estimate) the GFR based on a single serum measurement
• eGFR calculations: Incorporate simple clinical information along with a single serum measurement
• Most eGFR calculations: Use serum creatinine, age, sex, and CKD-EPI equation (recommended by NICE)
• Normal eGFR: >90 ml/min/1.73m2
• Newer tests available: Use serum cystatin C (eGFRcystatinC)

Limitations of eGFR

• eGFR: Does not include a measure of body size
• eGFR: May be influenced by factors that alter muscle mass (e.g. amputation, malnutrition)
• Limitations on eGFR use: Children, acute kidney injury, drug calculations
• eGFR: More accurate than serum creatinine alone
• eGFR: Useful in monitoring renal function and detecting early decline

Test your knowledge on the critical functions of the nephron, including filtration, reabsorption, and secretion. This quiz will help you understand how the kidneys process and manage fluid and waste. Explore the daily rates of filtration and excretion as you match terms with their descriptions.