Nephrology: Kidney Function and Renal Diseases

Introduction to Nephrology

• Nephrology is the study of kidney function and diseases
• Kidney function is essential for maintaining overall health

Kidney Function

• Kidneys act as filters, clearing the body of waste and toxic substances
• They monitor and regulate blood pressure through the juxtaglomerular apparatus
• They produce erythropoietin, which stimulates the production of red blood cells
• They manage water and salt concentrations in the body, responding to antidiuretic hormone and aldosterone
• They convert vitamin D to its active form, increasing calcium levels in the body

Evaluation of Renal Function

• The best test to evaluate renal function is the glomerular filtration rate (GFR)
• GFR measures the volume of plasma cleared of a substance in a unit of time (mL/min)
• An ideal substance to evaluate GFR should be produced endogenously, filtered by the glomerulus, and not reabsorbed or secreted by the renal tubule
• Inulin is the ideal substance, but it is not produced by the body, so serum creatinine is used instead

Serum Creatinine

• Serum creatinine is a waste product that is produced by the body and cleared by the kidneys
• High levels of serum creatinine indicate impaired kidney function
• Normal range of serum creatinine is 0.5-1.0 mg/dL
• Serum creatinine levels are influenced by factors such as aging, diet, and muscle mass

Glomerular Filtration Rate (GFR)

• GFR is the volume of plasma cleared of a substance in a unit of time (mL/min)
• Normal range of GFR is 90-120 mL/min
• GFR is calculated using serum creatinine levels, urinary volume, and creatinine in urine
• GFR is influenced by factors such as aging, diet, and muscle mass

Stages of Kidney Dysfunction

• G1: normal or high GFR (>90 mL/min/1.73m²)
• G2: mildly decreased GFR (60-89 mL/min/1.73m²)
• G3a: mildly to moderately decreased GFR (45-59 mL/min/1.73m²)
• G3b: moderately to severely decreased GFR (30-44 mL/min/1.73m²)
• G4: severely decreased GFR (15-20 mL/min/1.73m²)
• G5: kidney failure (GFR ≤15 mL/min/1.73m²)

Case Study: Antonio

• Antonio is a 70-year-old man with a history of high blood pressure and recent symptoms of nocturia, headaches, and fatigue
• Lab tests reveal high levels of serum creatinine, urea, and potassium, and low levels of sodium and calcium
• Urinalysis shows proteinuria and hemoglobinuria
• Diagnosis is severe renal dysfunction, with a GFR of <15 mL/min

Hyperkalemia

• Hyperkalemia is a medical emergency characterized by high levels of potassium in the blood
• Causes of hyperkalemia include potassium shift outside the cells, drugs interfering with potassium balance, and kidney injury
• Symptoms of hyperkalemia include muscle weakness, paralysis, and cardiac conduction abnormalities
• Treatment of hyperkalemia includes calcium gluconate, insulin, beta2-adrenergic agonists, and sodium bicarbonate

Calcium and Phosphorus

• Calcium and phosphorus are essential for bone health
• Parathyroid hormone (PTH) is the main calcium regulator
• PTH increases calcium reabsorption in the kidneys, favors intestinal calcium and phosphorus reabsorption, and increases bone turnover
• Calcitonin is another hormone involved in calcium regulation, which counteracts the effects of PTH
• Vitamin D is essential for calcium regulation, and its deficiency can lead to hypocalcemia

Hypocalcemia

• Hypocalcemia is a condition characterized by low levels of calcium in the blood
• Symptoms of hypocalcemia include tetany, seizures, hypotension, and psychiatric manifestations
• Causes of hypocalcemia include vitamin D deficiency, reduced gastrointestinal reabsorption, chronic kidney disease, and hypomagnesemia
• Treatment of hypocalcemia includes intravenous and oral calcium, and vitamin D supplements

Hypercalcemia

• Hypercalcemia is a condition characterized by high levels of calcium in the blood
• Symptoms of hypercalcemia include muscle weakness, polyuria, polydipsia, dehydration, nausea, and changes in sensorium
• Causes of hypercalcemia include hyperparathyroidism, vitamin D intoxication, and cancer
• Treatment of hypercalcemia includes hydration, diuretics, and bisphosphonates### Hypercalcemia Treatment
• In medical emergencies, treat the patient first and understand the causes later
• First treatment: intravenous hydration with isotonic saline and glucose (no calcium)
• Next, administer subcutaneous calcitonin to lower serum calcium concentration (not available in Italy)
• Then, give bisphosphonates to the patient
• Consider the onset and duration of action of these drugs
• Isotonic saline takes hours to work, bisphosphonates take a lot of hours
• Loop diuretics can also be used to treat hypercalcemia because they eliminate sodium and calcium
• Glucocorticoids and dialysis may also be useful

Factors that Aggravate Hypercalcemia

• Thiazide diuretics
• Lithium carbonate
• Volume depletion
• Prolonged bed rest or inactivity
• High-calcium diet (>1000 mg/day)
• Calcium supplements
• Vitamin D supplements (>800 IU/day)
• Multivitamins containing calcium

Causes of Hypercalcemia

• Measure parathyroid hormone (PTH) levels after the patient is stabilized
• If PTH is low, the patient may have a tumor (e.g., multiple myeloma) or paraneoplastic syndrome
• If PTH is high, the patient may have primary hyperparathyroidism (e.g., tumor of the parathyroid gland)
• Vitamin D intoxication and granulomatous diseases (e.g., sarcoidosis and TB) can also cause hypercalcemia

Disorders of Water Balance (Dysnatremias)

• Dysnatremias are not disorders of sodium balance, but of water balance
• Sodium concentration is not equal to sodium amount in the body
• Blood volume depends on sodium content (regulated by RAAS and baroreceptors)
• Hypovolemia: sodium depletion → decreased blood volume
• Hypervolemia: sodium increase → increased blood volume

Sodium Concentration

• Not related to sodium amount in the body
• Depends on water balance (regulated by vasopressin and thirst)
• Hyponatremia: water excess → low sodium concentration
• Hypernatremia: water deficit → high sodium concentration

Hyponatremia

• Most common disorder of body fluid and electrolyte balance
• Occurs in 1-2% of hospitalized patients and 30% of ICU patients
• Can lead to various clinical symptoms, from subtle to severe or life-threatening
• Prompt recognition is crucial, as it increases in-hospital mortality by 40%

Symptoms of Hyponatremia

• Expression of central nervous system dysfunction caused by brain cell swelling
• Acute hyponatremia: reversible if properly treated
• Chronic hyponatremia: usually asymptomatic or paucisymptomatic

Causes of Hyponatremia

• Hypovolemic hyponatremia: extrarenal salt loss (e.g., diuretics, nephropathies, mineralocorticoid deficiencies)
• Euvolemic hyponatremia: SIADH (syndrome of inappropriate ADH secretion), hypothyroidism, psychogenic polydipsia, adrenocorticotropic deficiency
• Hypervolemic hyponatremia: heart failure, liver disease, nephrotic syndrome, advanced kidney disease

Treatment of Hyponatremia

• Exclude hyperglycemia and pseudohyponatremia
• Assess severity of symptoms
• If severe, give 150 mL of 3% hypertonic saline over 20 minutes
• if asymptomatic, focus on etiology of the disease
• Avoid rapid correction to prevent osmotic demyelination syndrome### Diabetes Insipidus
• Can be hereditary (x-linked recessive, defect of V2 receptors or aquaporins) or acquired (electrolyte disorders, certain medications, chronic intestinal kidney disease, malnutrition)
• Gestational DI: caused by degradation of ADH, occurs in peripheral circulation

Symptoms of Diabetes Insipidus

• Altered mental status
• Lethargy
• Irritability
• Restlessness
• Muscle twitching
• Hyperreflexia and spasticity
• Seizures (usually in children)
• Coma

Treatment of Hypernatremia

• Determine volume status (sodium balance)
• Calculate water deficit
• Choose a replacement fluid
• Determine the rate of depletion
• Estimate ongoing sensible and insensible losses
• Use the formula: Water deficit = TBW x (Na+s / 140 - 1)
• Replace water deficit with hypotonic solution (e.g. 5% dextrose)
• Monitor and adjust rate of repletion

Key Points of Hypernatremia

• Always reflects a hyperosmolar state
• Always a water problem, sometimes a salt problem
• Requires defect in thirst mechanism or limited access to free water
• Sodium concentration does not provide information about total body salt or volume status
• Calculation of water deficit is useful, but represents only a snapshot
• Use clinical judgment and carefully monitor the patient
• Consider sensible and insensible losses

Approach to Glomerular Diseases

• Simple lab test: serum creatinine
• Accurate test: measurement of glomerular filtration rate (GFR) through inulin clearance
• Other methods: use serum creatinine and GFR to assess renal function
• Urinalysis should be performed in case of altered kidney functionality
• Recognize nephrological syndromes, which can vary from asymptomatic to severe clinical manifestations

Glomerular Diseases

• May present in different clinical forms (nephrological syndromes)
• Variations depend on combinations of serum creatinine, proteinuria, and alterations of urinary sediment
• Recognizing the correct syndrome is crucial for treatment and prognosis

Hematuria

• Macroscopic hematuria: visible blood in urine
• Can be symptomatic or asymptomatic, persistent or intermittent
• Causes: inflammation of urinary bladder, urethra or prostate, urinary infections, kidney stones, polycystic kidney diseases, blood clotting disorders, sickle cell diseases, cancer, trauma
• Glomerular diseases can cause macroscopic hematuria, especially IgA nephropathy
• Asymptomatic urinary abnormalities: diagnosis obtained by urinalysis, proteinuria > 150 mg/day, hematuria, and hyaline or hyaline-granular casts
• Nephrotic syndrome: characterized by proteinuria > 3.5g/day, low serum protein, and low albumin, with edema as the main clinical manifestation

Introduction to Nephrology

• Nephrology is the study of kidney function and diseases
• Kidney function is essential for maintaining overall health

Kidney Function

• Kidneys act as filters, clearing the body of waste and toxic substances
• They monitor and regulate blood pressure through the juxtaglomerular apparatus
• They produce erythropoietin, which stimulates the production of red blood cells
• They manage water and salt concentrations in the body, responding to antidiuretic hormone and aldosterone
• They convert vitamin D to its active form, increasing calcium levels in the body

Evaluation of Renal Function

• The best test to evaluate renal function is the glomerular filtration rate (GFR)
• GFR measures the volume of plasma cleared of a substance in a unit of time (mL/min)
• An ideal substance to evaluate GFR should be produced endogenously, filtered by the glomerulus, and not reabsorbed or secreted by the renal tubule
• Inulin is the ideal substance, but it is not produced by the body, so serum creatinine is used instead

Serum Creatinine

• Serum creatinine is a waste product that is produced by the body and cleared by the kidneys
• High levels of serum creatinine indicate impaired kidney function
• Normal range of serum creatinine is 0.5-1.0 mg/dL
• Serum creatinine levels are influenced by factors such as aging, diet, and muscle mass

Glomerular Filtration Rate (GFR)

• GFR is the volume of plasma cleared of a substance in a unit of time (mL/min)
• Normal range of GFR is 90-120 mL/min
• GFR is calculated using serum creatinine levels, urinary volume, and creatinine in urine
• GFR is influenced by factors such as aging, diet, and muscle mass

Stages of Kidney Dysfunction

• G1: normal or high GFR (>90 mL/min/1.73m²)
• G2: mildly decreased GFR (60-89 mL/min/1.73m²)
• G3a: mildly to moderately decreased GFR (45-59 mL/min/1.73m²)
• G3b: moderately to severely decreased GFR (30-44 mL/min/1.73m²)
• G4: severely decreased GFR (15-20 mL/min/1.73m²)
• G5: kidney failure (GFR ≤15 mL/min/1.73m²)

Case Study: Antonio

• Antonio is a 70-year-old man with a history of high blood pressure and recent symptoms of nocturia, headaches, and fatigue
• Lab tests reveal high levels of serum creatinine, urea, and potassium, and low levels of sodium and calcium
• Urinalysis shows proteinuria and hemoglobinuria
• Diagnosis is severe renal dysfunction, with a GFR of <15 mL/min

Hyperkalemia

• Hyperkalemia is a medical emergency characterized by high levels of potassium in the blood
• Causes of hyperkalemia include potassium shift outside the cells, drugs interfering with potassium balance, and kidney injury
• Symptoms of hyperkalemia include muscle weakness, paralysis, and cardiac conduction abnormalities
• Treatment of hyperkalemia includes calcium gluconate, insulin, beta2-adrenergic agonists, and sodium bicarbonate

Calcium and Phosphorus

• Calcium and phosphorus are essential for bone health
• Parathyroid hormone (PTH) is the main calcium regulator
• PTH increases calcium reabsorption in the kidneys, favors intestinal calcium and phosphorus reabsorption, and increases bone turnover
• Calcitonin is another hormone involved in calcium regulation, which counteracts the effects of PTH
• Vitamin D is essential for calcium regulation, and its deficiency can lead to hypocalcemia

Hypocalcemia

• Hypocalcemia is a condition characterized by low levels of calcium in the blood
• Symptoms of hypocalcemia include tetany, seizures, hypotension, and psychiatric manifestations
• Causes of hypocalcemia include vitamin D deficiency, reduced gastrointestinal reabsorption, chronic kidney disease, and hypomagnesemia
• Treatment of hypocalcemia includes intravenous and oral calcium, and vitamin D supplements

Hypercalcemia

• Hypercalcemia is a condition characterized by high levels of calcium in the blood
• Symptoms of hypercalcemia include muscle weakness, polyuria, polydipsia, dehydration, nausea, and changes in sensorium
• Causes of hypercalcemia include hyperparathyroidism, vitamin D intoxication, and cancer
• Treatment of hypercalcemia includes hydration, diuretics, and bisphosphonates### Hypercalcemia Treatment
• In medical emergencies, treat the patient first and understand the causes later
• First treatment: intravenous hydration with isotonic saline and glucose (no calcium)
• Next, administer subcutaneous calcitonin to lower serum calcium concentration (not available in Italy)
• Then, give bisphosphonates to the patient
• Consider the onset and duration of action of these drugs
• Isotonic saline takes hours to work, bisphosphonates take a lot of hours
• Loop diuretics can also be used to treat hypercalcemia because they eliminate sodium and calcium
• Glucocorticoids and dialysis may also be useful

Factors that Aggravate Hypercalcemia

• Thiazide diuretics
• Lithium carbonate
• Volume depletion
• Prolonged bed rest or inactivity
• High-calcium diet (>1000 mg/day)
• Calcium supplements
• Vitamin D supplements (>800 IU/day)
• Multivitamins containing calcium

Causes of Hypercalcemia

• Measure parathyroid hormone (PTH) levels after the patient is stabilized
• If PTH is low, the patient may have a tumor (e.g., multiple myeloma) or paraneoplastic syndrome
• If PTH is high, the patient may have primary hyperparathyroidism (e.g., tumor of the parathyroid gland)
• Vitamin D intoxication and granulomatous diseases (e.g., sarcoidosis and TB) can also cause hypercalcemia

Disorders of Water Balance (Dysnatremias)

• Dysnatremias are not disorders of sodium balance, but of water balance
• Sodium concentration is not equal to sodium amount in the body
• Blood volume depends on sodium content (regulated by RAAS and baroreceptors)
• Hypovolemia: sodium depletion → decreased blood volume
• Hypervolemia: sodium increase → increased blood volume

Sodium Concentration

• Not related to sodium amount in the body
• Depends on water balance (regulated by vasopressin and thirst)
• Hyponatremia: water excess → low sodium concentration
• Hypernatremia: water deficit → high sodium concentration

Hyponatremia

• Most common disorder of body fluid and electrolyte balance
• Occurs in 1-2% of hospitalized patients and 30% of ICU patients
• Can lead to various clinical symptoms, from subtle to severe or life-threatening
• Prompt recognition is crucial, as it increases in-hospital mortality by 40%

Symptoms of Hyponatremia

• Expression of central nervous system dysfunction caused by brain cell swelling
• Acute hyponatremia: reversible if properly treated
• Chronic hyponatremia: usually asymptomatic or paucisymptomatic

Causes of Hyponatremia

• Hypovolemic hyponatremia: extrarenal salt loss (e.g., diuretics, nephropathies, mineralocorticoid deficiencies)
• Euvolemic hyponatremia: SIADH (syndrome of inappropriate ADH secretion), hypothyroidism, psychogenic polydipsia, adrenocorticotropic deficiency
• Hypervolemic hyponatremia: heart failure, liver disease, nephrotic syndrome, advanced kidney disease

Treatment of Hyponatremia

• Exclude hyperglycemia and pseudohyponatremia
• Assess severity of symptoms
• If severe, give 150 mL of 3% hypertonic saline over 20 minutes
• if asymptomatic, focus on etiology of the disease
• Avoid rapid correction to prevent osmotic demyelination syndrome### Diabetes Insipidus
• Can be hereditary (x-linked recessive, defect of V2 receptors or aquaporins) or acquired (electrolyte disorders, certain medications, chronic intestinal kidney disease, malnutrition)
• Gestational DI: caused by degradation of ADH, occurs in peripheral circulation

Symptoms of Diabetes Insipidus

• Altered mental status
• Lethargy
• Irritability
• Restlessness
• Muscle twitching
• Hyperreflexia and spasticity
• Seizures (usually in children)
• Coma

Treatment of Hypernatremia

• Determine volume status (sodium balance)
• Calculate water deficit
• Choose a replacement fluid
• Determine the rate of depletion
• Estimate ongoing sensible and insensible losses
• Use the formula: Water deficit = TBW x (Na+s / 140 - 1)
• Replace water deficit with hypotonic solution (e.g. 5% dextrose)
• Monitor and adjust rate of repletion

Key Points of Hypernatremia

• Always reflects a hyperosmolar state
• Always a water problem, sometimes a salt problem
• Requires defect in thirst mechanism or limited access to free water
• Sodium concentration does not provide information about total body salt or volume status
• Calculation of water deficit is useful, but represents only a snapshot
• Use clinical judgment and carefully monitor the patient
• Consider sensible and insensible losses

Approach to Glomerular Diseases

• Simple lab test: serum creatinine
• Accurate test: measurement of glomerular filtration rate (GFR) through inulin clearance
• Other methods: use serum creatinine and GFR to assess renal function
• Urinalysis should be performed in case of altered kidney functionality
• Recognize nephrological syndromes, which can vary from asymptomatic to severe clinical manifestations

Glomerular Diseases

• May present in different clinical forms (nephrological syndromes)
• Variations depend on combinations of serum creatinine, proteinuria, and alterations of urinary sediment
• Recognizing the correct syndrome is crucial for treatment and prognosis

Hematuria

• Macroscopic hematuria: visible blood in urine
• Can be symptomatic or asymptomatic, persistent or intermittent
• Causes: inflammation of urinary bladder, urethra or prostate, urinary infections, kidney stones, polycystic kidney diseases, blood clotting disorders, sickle cell diseases, cancer, trauma
• Glomerular diseases can cause macroscopic hematuria, especially IgA nephropathy
• Asymptomatic urinary abnormalities: diagnosis obtained by urinalysis, proteinuria > 150 mg/day, hematuria, and hyaline or hyaline-granular casts
• Nephrotic syndrome: characterized by proteinuria > 3.5g/day, low serum protein, and low albumin, with edema as the main clinical manifestation

Introduction to Nephrology

• Nephrology is the study of kidney function and diseases
• Kidney function is essential for maintaining overall health

Kidney Function

• Kidneys act as filters, clearing the body of waste and toxic substances
• They monitor and regulate blood pressure through the juxtaglomerular apparatus
• They produce erythropoietin, which stimulates the production of red blood cells
• They manage water and salt concentrations in the body, responding to antidiuretic hormone and aldosterone
• They convert vitamin D to its active form, increasing calcium levels in the body

Evaluation of Renal Function

• The best test to evaluate renal function is the glomerular filtration rate (GFR)
• GFR measures the volume of plasma cleared of a substance in a unit of time (mL/min)
• An ideal substance to evaluate GFR should be produced endogenously, filtered by the glomerulus, and not reabsorbed or secreted by the renal tubule
• Inulin is the ideal substance, but it is not produced by the body, so serum creatinine is used instead

Serum Creatinine

• Serum creatinine is a waste product that is produced by the body and cleared by the kidneys
• High levels of serum creatinine indicate impaired kidney function
• Normal range of serum creatinine is 0.5-1.0 mg/dL
• Serum creatinine levels are influenced by factors such as aging, diet, and muscle mass

Glomerular Filtration Rate (GFR)

• GFR is the volume of plasma cleared of a substance in a unit of time (mL/min)
• Normal range of GFR is 90-120 mL/min
• GFR is calculated using serum creatinine levels, urinary volume, and creatinine in urine
• GFR is influenced by factors such as aging, diet, and muscle mass

Stages of Kidney Dysfunction

• G1: normal or high GFR (>90 mL/min/1.73m²)
• G2: mildly decreased GFR (60-89 mL/min/1.73m²)
• G3a: mildly to moderately decreased GFR (45-59 mL/min/1.73m²)
• G3b: moderately to severely decreased GFR (30-44 mL/min/1.73m²)
• G4: severely decreased GFR (15-20 mL/min/1.73m²)
• G5: kidney failure (GFR ≤15 mL/min/1.73m²)

Case Study: Antonio

• Antonio is a 70-year-old man with a history of high blood pressure and recent symptoms of nocturia, headaches, and fatigue
• Lab tests reveal high levels of serum creatinine, urea, and potassium, and low levels of sodium and calcium
• Urinalysis shows proteinuria and hemoglobinuria
• Diagnosis is severe renal dysfunction, with a GFR of <15 mL/min

Hyperkalemia

• Hyperkalemia is a medical emergency characterized by high levels of potassium in the blood
• Causes of hyperkalemia include potassium shift outside the cells, drugs interfering with potassium balance, and kidney injury
• Symptoms of hyperkalemia include muscle weakness, paralysis, and cardiac conduction abnormalities
• Treatment of hyperkalemia includes calcium gluconate, insulin, beta2-adrenergic agonists, and sodium bicarbonate

Calcium and Phosphorus

• Calcium and phosphorus are essential for bone health
• Parathyroid hormone (PTH) is the main calcium regulator
• PTH increases calcium reabsorption in the kidneys, favors intestinal calcium and phosphorus reabsorption, and increases bone turnover
• Calcitonin is another hormone involved in calcium regulation, which counteracts the effects of PTH
• Vitamin D is essential for calcium regulation, and its deficiency can lead to hypocalcemia

Hypocalcemia

• Hypocalcemia is a condition characterized by low levels of calcium in the blood
• Symptoms of hypocalcemia include tetany, seizures, hypotension, and psychiatric manifestations
• Causes of hypocalcemia include vitamin D deficiency, reduced gastrointestinal reabsorption, chronic kidney disease, and hypomagnesemia
• Treatment of hypocalcemia includes intravenous and oral calcium, and vitamin D supplements

Hypercalcemia

• Hypercalcemia is a condition characterized by high levels of calcium in the blood
• Symptoms of hypercalcemia include muscle weakness, polyuria, polydipsia, dehydration, nausea, and changes in sensorium
• Causes of hypercalcemia include hyperparathyroidism, vitamin D intoxication, and cancer
• Treatment of hypercalcemia includes hydration, diuretics, and bisphosphonates### Hypercalcemia Treatment
• In medical emergencies, treat the patient first and understand the causes later
• First treatment: intravenous hydration with isotonic saline and glucose (no calcium)
• Next, administer subcutaneous calcitonin to lower serum calcium concentration (not available in Italy)
• Then, give bisphosphonates to the patient
• Consider the onset and duration of action of these drugs
• Isotonic saline takes hours to work, bisphosphonates take a lot of hours
• Loop diuretics can also be used to treat hypercalcemia because they eliminate sodium and calcium
• Glucocorticoids and dialysis may also be useful

Factors that Aggravate Hypercalcemia

• Thiazide diuretics
• Lithium carbonate
• Volume depletion
• Prolonged bed rest or inactivity
• High-calcium diet (>1000 mg/day)
• Calcium supplements
• Vitamin D supplements (>800 IU/day)
• Multivitamins containing calcium

Causes of Hypercalcemia

• Measure parathyroid hormone (PTH) levels after the patient is stabilized
• If PTH is low, the patient may have a tumor (e.g., multiple myeloma) or paraneoplastic syndrome
• If PTH is high, the patient may have primary hyperparathyroidism (e.g., tumor of the parathyroid gland)
• Vitamin D intoxication and granulomatous diseases (e.g., sarcoidosis and TB) can also cause hypercalcemia

Disorders of Water Balance (Dysnatremias)

• Dysnatremias are not disorders of sodium balance, but of water balance
• Sodium concentration is not equal to sodium amount in the body
• Blood volume depends on sodium content (regulated by RAAS and baroreceptors)
• Hypovolemia: sodium depletion → decreased blood volume
• Hypervolemia: sodium increase → increased blood volume

Sodium Concentration

• Not related to sodium amount in the body
• Depends on water balance (regulated by vasopressin and thirst)
• Hyponatremia: water excess → low sodium concentration
• Hypernatremia: water deficit → high sodium concentration

Hyponatremia

• Most common disorder of body fluid and electrolyte balance
• Occurs in 1-2% of hospitalized patients and 30% of ICU patients
• Can lead to various clinical symptoms, from subtle to severe or life-threatening
• Prompt recognition is crucial, as it increases in-hospital mortality by 40%

Symptoms of Hyponatremia

• Expression of central nervous system dysfunction caused by brain cell swelling
• Acute hyponatremia: reversible if properly treated
• Chronic hyponatremia: usually asymptomatic or paucisymptomatic

Causes of Hyponatremia

• Hypovolemic hyponatremia: extrarenal salt loss (e.g., diuretics, nephropathies, mineralocorticoid deficiencies)
• Euvolemic hyponatremia: SIADH (syndrome of inappropriate ADH secretion), hypothyroidism, psychogenic polydipsia, adrenocorticotropic deficiency
• Hypervolemic hyponatremia: heart failure, liver disease, nephrotic syndrome, advanced kidney disease

Treatment of Hyponatremia

• Exclude hyperglycemia and pseudohyponatremia
• Assess severity of symptoms
• If severe, give 150 mL of 3% hypertonic saline over 20 minutes
• if asymptomatic, focus on etiology of the disease
• Avoid rapid correction to prevent osmotic demyelination syndrome### Diabetes Insipidus
• Can be hereditary (x-linked recessive, defect of V2 receptors or aquaporins) or acquired (electrolyte disorders, certain medications, chronic intestinal kidney disease, malnutrition)
• Gestational DI: caused by degradation of ADH, occurs in peripheral circulation

Symptoms of Diabetes Insipidus

• Altered mental status
• Lethargy
• Irritability
• Restlessness
• Muscle twitching
• Hyperreflexia and spasticity
• Seizures (usually in children)
• Coma

Treatment of Hypernatremia

• Determine volume status (sodium balance)
• Calculate water deficit
• Choose a replacement fluid
• Determine the rate of depletion
• Estimate ongoing sensible and insensible losses
• Use the formula: Water deficit = TBW x (Na+s / 140 - 1)
• Replace water deficit with hypotonic solution (e.g. 5% dextrose)
• Monitor and adjust rate of repletion

Key Points of Hypernatremia

• Always reflects a hyperosmolar state
• Always a water problem, sometimes a salt problem
• Requires defect in thirst mechanism or limited access to free water
• Sodium concentration does not provide information about total body salt or volume status
• Calculation of water deficit is useful, but represents only a snapshot
• Use clinical judgment and carefully monitor the patient
• Consider sensible and insensible losses

Approach to Glomerular Diseases

• Simple lab test: serum creatinine
• Accurate test: measurement of glomerular filtration rate (GFR) through inulin clearance
• Other methods: use serum creatinine and GFR to assess renal function
• Urinalysis should be performed in case of altered kidney functionality
• Recognize nephrological syndromes, which can vary from asymptomatic to severe clinical manifestations

Glomerular Diseases

• May present in different clinical forms (nephrological syndromes)
• Variations depend on combinations of serum creatinine, proteinuria, and alterations of urinary sediment
• Recognizing the correct syndrome is crucial for treatment and prognosis

Hematuria

• Macroscopic hematuria: visible blood in urine
• Can be symptomatic or asymptomatic, persistent or intermittent
• Causes: inflammation of urinary bladder, urethra or prostate, urinary infections, kidney stones, polycystic kidney diseases, blood clotting disorders, sickle cell diseases, cancer, trauma
• Glomerular diseases can cause macroscopic hematuria, especially IgA nephropathy
• Asymptomatic urinary abnormalities: diagnosis obtained by urinalysis, proteinuria > 150 mg/day, hematuria, and hyaline or hyaline-granular casts
• Nephrotic syndrome: characterized by proteinuria > 3.5g/day, low serum protein, and low albumin, with edema as the main clinical manifestation

Introduction to Nephrology

• Nephrology is the study of kidney function and diseases
• Kidney function is essential for maintaining overall health

Kidney Function

• Kidneys act as filters, clearing the body of waste and toxic substances
• They monitor and regulate blood pressure through the juxtaglomerular apparatus
• They produce erythropoietin, which stimulates the production of red blood cells
• They manage water and salt concentrations in the body, responding to antidiuretic hormone and aldosterone
• They convert vitamin D to its active form, increasing calcium levels in the body

Evaluation of Renal Function

• The best test to evaluate renal function is the glomerular filtration rate (GFR)
• GFR measures the volume of plasma cleared of a substance in a unit of time (mL/min)
• An ideal substance to evaluate GFR should be produced endogenously, filtered by the glomerulus, and not reabsorbed or secreted by the renal tubule
• Inulin is the ideal substance, but it is not produced by the body, so serum creatinine is used instead

Serum Creatinine

• Serum creatinine is a waste product that is produced by the body and cleared by the kidneys
• High levels of serum creatinine indicate impaired kidney function
• Normal range of serum creatinine is 0.5-1.0 mg/dL
• Serum creatinine levels are influenced by factors such as aging, diet, and muscle mass

Glomerular Filtration Rate (GFR)

• GFR is the volume of plasma cleared of a substance in a unit of time (mL/min)
• Normal range of GFR is 90-120 mL/min
• GFR is calculated using serum creatinine levels, urinary volume, and creatinine in urine
• GFR is influenced by factors such as aging, diet, and muscle mass

Stages of Kidney Dysfunction

• G1: normal or high GFR (>90 mL/min/1.73m²)
• G2: mildly decreased GFR (60-89 mL/min/1.73m²)
• G3a: mildly to moderately decreased GFR (45-59 mL/min/1.73m²)
• G3b: moderately to severely decreased GFR (30-44 mL/min/1.73m²)
• G4: severely decreased GFR (15-20 mL/min/1.73m²)
• G5: kidney failure (GFR ≤15 mL/min/1.73m²)

Case Study: Antonio

• Antonio is a 70-year-old man with a history of high blood pressure and recent symptoms of nocturia, headaches, and fatigue
• Lab tests reveal high levels of serum creatinine, urea, and potassium, and low levels of sodium and calcium
• Urinalysis shows proteinuria and hemoglobinuria
• Diagnosis is severe renal dysfunction, with a GFR of <15 mL/min

Hyperkalemia

• Hyperkalemia is a medical emergency characterized by high levels of potassium in the blood
• Causes of hyperkalemia include potassium shift outside the cells, drugs interfering with potassium balance, and kidney injury
• Symptoms of hyperkalemia include muscle weakness, paralysis, and cardiac conduction abnormalities
• Treatment of hyperkalemia includes calcium gluconate, insulin, beta2-adrenergic agonists, and sodium bicarbonate

Calcium and Phosphorus

• Calcium and phosphorus are essential for bone health
• Parathyroid hormone (PTH) is the main calcium regulator
• PTH increases calcium reabsorption in the kidneys, favors intestinal calcium and phosphorus reabsorption, and increases bone turnover
• Calcitonin is another hormone involved in calcium regulation, which counteracts the effects of PTH
• Vitamin D is essential for calcium regulation, and its deficiency can lead to hypocalcemia

Hypocalcemia

• Hypocalcemia is a condition characterized by low levels of calcium in the blood
• Symptoms of hypocalcemia include tetany, seizures, hypotension, and psychiatric manifestations
• Causes of hypocalcemia include vitamin D deficiency, reduced gastrointestinal reabsorption, chronic kidney disease, and hypomagnesemia
• Treatment of hypocalcemia includes intravenous and oral calcium, and vitamin D supplements

Hypercalcemia

• Hypercalcemia is a condition characterized by high levels of calcium in the blood
• Symptoms of hypercalcemia include muscle weakness, polyuria, polydipsia, dehydration, nausea, and changes in sensorium
• Causes of hypercalcemia include hyperparathyroidism, vitamin D intoxication, and cancer
• Treatment of hypercalcemia includes hydration, diuretics, and bisphosphonates### Hypercalcemia Treatment
• In medical emergencies, treat the patient first and understand the causes later
• First treatment: intravenous hydration with isotonic saline and glucose (no calcium)
• Next, administer subcutaneous calcitonin to lower serum calcium concentration (not available in Italy)
• Then, give bisphosphonates to the patient
• Consider the onset and duration of action of these drugs
• Isotonic saline takes hours to work, bisphosphonates take a lot of hours
• Loop diuretics can also be used to treat hypercalcemia because they eliminate sodium and calcium
• Glucocorticoids and dialysis may also be useful

Factors that Aggravate Hypercalcemia

• Thiazide diuretics
• Lithium carbonate
• Volume depletion
• Prolonged bed rest or inactivity
• High-calcium diet (>1000 mg/day)
• Calcium supplements
• Vitamin D supplements (>800 IU/day)
• Multivitamins containing calcium

Causes of Hypercalcemia

• Measure parathyroid hormone (PTH) levels after the patient is stabilized
• If PTH is low, the patient may have a tumor (e.g., multiple myeloma) or paraneoplastic syndrome
• If PTH is high, the patient may have primary hyperparathyroidism (e.g., tumor of the parathyroid gland)
• Vitamin D intoxication and granulomatous diseases (e.g., sarcoidosis and TB) can also cause hypercalcemia

Disorders of Water Balance (Dysnatremias)

• Dysnatremias are not disorders of sodium balance, but of water balance
• Sodium concentration is not equal to sodium amount in the body
• Blood volume depends on sodium content (regulated by RAAS and baroreceptors)
• Hypovolemia: sodium depletion → decreased blood volume
• Hypervolemia: sodium increase → increased blood volume

Sodium Concentration

• Not related to sodium amount in the body
• Depends on water balance (regulated by vasopressin and thirst)
• Hyponatremia: water excess → low sodium concentration
• Hypernatremia: water deficit → high sodium concentration

Hyponatremia

• Most common disorder of body fluid and electrolyte balance
• Occurs in 1-2% of hospitalized patients and 30% of ICU patients
• Can lead to various clinical symptoms, from subtle to severe or life-threatening
• Prompt recognition is crucial, as it increases in-hospital mortality by 40%

Symptoms of Hyponatremia

• Expression of central nervous system dysfunction caused by brain cell swelling
• Acute hyponatremia: reversible if properly treated
• Chronic hyponatremia: usually asymptomatic or paucisymptomatic

Causes of Hyponatremia

• Hypovolemic hyponatremia: extrarenal salt loss (e.g., diuretics, nephropathies, mineralocorticoid deficiencies)
• Euvolemic hyponatremia: SIADH (syndrome of inappropriate ADH secretion), hypothyroidism, psychogenic polydipsia, adrenocorticotropic deficiency
• Hypervolemic hyponatremia: heart failure, liver disease, nephrotic syndrome, advanced kidney disease

Treatment of Hyponatremia

• Exclude hyperglycemia and pseudohyponatremia
• Assess severity of symptoms
• If severe, give 150 mL of 3% hypertonic saline over 20 minutes
• if asymptomatic, focus on etiology of the disease
• Avoid rapid correction to prevent osmotic demyelination syndrome### Diabetes Insipidus
• Can be hereditary (x-linked recessive, defect of V2 receptors or aquaporins) or acquired (electrolyte disorders, certain medications, chronic intestinal kidney disease, malnutrition)
• Gestational DI: caused by degradation of ADH, occurs in peripheral circulation

Symptoms of Diabetes Insipidus

• Altered mental status
• Lethargy
• Irritability
• Restlessness
• Muscle twitching
• Hyperreflexia and spasticity
• Seizures (usually in children)
• Coma

Treatment of Hypernatremia

• Determine volume status (sodium balance)
• Calculate water deficit
• Choose a replacement fluid
• Determine the rate of depletion
• Estimate ongoing sensible and insensible losses
• Use the formula: Water deficit = TBW x (Na+s / 140 - 1)
• Replace water deficit with hypotonic solution (e.g. 5% dextrose)
• Monitor and adjust rate of repletion

Key Points of Hypernatremia

• Always reflects a hyperosmolar state
• Always a water problem, sometimes a salt problem
• Requires defect in thirst mechanism or limited access to free water
• Sodium concentration does not provide information about total body salt or volume status
• Calculation of water deficit is useful, but represents only a snapshot
• Use clinical judgment and carefully monitor the patient
• Consider sensible and insensible losses

Approach to Glomerular Diseases

• Simple lab test: serum creatinine
• Accurate test: measurement of glomerular filtration rate (GFR) through inulin clearance
• Other methods: use serum creatinine and GFR to assess renal function
• Urinalysis should be performed in case of altered kidney functionality
• Recognize nephrological syndromes, which can vary from asymptomatic to severe clinical manifestations

Glomerular Diseases

• May present in different clinical forms (nephrological syndromes)
• Variations depend on combinations of serum creatinine, proteinuria, and alterations of urinary sediment
• Recognizing the correct syndrome is crucial for treatment and prognosis

Hematuria

• Macroscopic hematuria: visible blood in urine
• Can be symptomatic or asymptomatic, persistent or intermittent
• Causes: inflammation of urinary bladder, urethra or prostate, urinary infections, kidney stones, polycystic kidney diseases, blood clotting disorders, sickle cell diseases, cancer, trauma
• Glomerular diseases can cause macroscopic hematuria, especially IgA nephropathy
• Asymptomatic urinary abnormalities: diagnosis obtained by urinalysis, proteinuria > 150 mg/day, hematuria, and hyaline or hyaline-granular casts
• Nephrotic syndrome: characterized by proteinuria > 3.5g/day, low serum protein, and low albumin, with edema as the main clinical manifestation

Introduction to Nephrology

• Nephrology is the study of kidney function and diseases
• Kidney function is essential for maintaining overall health

Kidney Function

• Kidneys act as filters, clearing the body of waste and toxic substances
• They monitor and regulate blood pressure through the juxtaglomerular apparatus
• They produce erythropoietin, which stimulates the production of red blood cells
• They manage water and salt concentrations in the body, responding to antidiuretic hormone and aldosterone
• They convert vitamin D to its active form, increasing calcium levels in the body

Evaluation of Renal Function

• The best test to evaluate renal function is the glomerular filtration rate (GFR)
• GFR measures the volume of plasma cleared of a substance in a unit of time (mL/min)
• An ideal substance to evaluate GFR should be produced endogenously, filtered by the glomerulus, and not reabsorbed or secreted by the renal tubule
• Inulin is the ideal substance, but it is not produced by the body, so serum creatinine is used instead

Serum Creatinine

• Serum creatinine is a waste product that is produced by the body and cleared by the kidneys
• High levels of serum creatinine indicate impaired kidney function
• Normal range of serum creatinine is 0.5-1.0 mg/dL
• Serum creatinine levels are influenced by factors such as aging, diet, and muscle mass

Glomerular Filtration Rate (GFR)

• GFR is the volume of plasma cleared of a substance in a unit of time (mL/min)
• Normal range of GFR is 90-120 mL/min
• GFR is calculated using serum creatinine levels, urinary volume, and creatinine in urine
• GFR is influenced by factors such as aging, diet, and muscle mass

Stages of Kidney Dysfunction

• G1: normal or high GFR (>90 mL/min/1.73m²)
• G2: mildly decreased GFR (60-89 mL/min/1.73m²)
• G3a: mildly to moderately decreased GFR (45-59 mL/min/1.73m²)
• G3b: moderately to severely decreased GFR (30-44 mL/min/1.73m²)
• G4: severely decreased GFR (15-20 mL/min/1.73m²)
• G5: kidney failure (GFR ≤15 mL/min/1.73m²)

Case Study: Antonio

• Antonio is a 70-year-old man with a history of high blood pressure and recent symptoms of nocturia, headaches, and fatigue
• Lab tests reveal high levels of serum creatinine, urea, and potassium, and low levels of sodium and calcium
• Urinalysis shows proteinuria and hemoglobinuria
• Diagnosis is severe renal dysfunction, with a GFR of <15 mL/min

Hyperkalemia

• Hyperkalemia is a medical emergency characterized by high levels of potassium in the blood
• Causes of hyperkalemia include potassium shift outside the cells, drugs interfering with potassium balance, and kidney injury
• Symptoms of hyperkalemia include muscle weakness, paralysis, and cardiac conduction abnormalities
• Treatment of hyperkalemia includes calcium gluconate, insulin, beta2-adrenergic agonists, and sodium bicarbonate

Calcium and Phosphorus

• Calcium and phosphorus are essential for bone health
• Parathyroid hormone (PTH) is the main calcium regulator
• PTH increases calcium reabsorption in the kidneys, favors intestinal calcium and phosphorus reabsorption, and increases bone turnover
• Calcitonin is another hormone involved in calcium regulation, which counteracts the effects of PTH
• Vitamin D is essential for calcium regulation, and its deficiency can lead to hypocalcemia

Hypocalcemia

• Hypocalcemia is a condition characterized by low levels of calcium in the blood
• Symptoms of hypocalcemia include tetany, seizures, hypotension, and psychiatric manifestations
• Causes of hypocalcemia include vitamin D deficiency, reduced gastrointestinal reabsorption, chronic kidney disease, and hypomagnesemia
• Treatment of hypocalcemia includes intravenous and oral calcium, and vitamin D supplements

Hypercalcemia

• Hypercalcemia is a condition characterized by high levels of calcium in the blood
• Symptoms of hypercalcemia include muscle weakness, polyuria, polydipsia, dehydration, nausea, and changes in sensorium
• Causes of hypercalcemia include hyperparathyroidism, vitamin D intoxication, and cancer
• Treatment of hypercalcemia includes hydration, diuretics, and bisphosphonates### Hypercalcemia Treatment
• In medical emergencies, treat the patient first and understand the causes later
• First treatment: intravenous hydration with isotonic saline and glucose (no calcium)
• Next, administer subcutaneous calcitonin to lower serum calcium concentration (not available in Italy)
• Then, give bisphosphonates to the patient
• Consider the onset and duration of action of these drugs
• Isotonic saline takes hours to work, bisphosphonates take a lot of hours
• Loop diuretics can also be used to treat hypercalcemia because they eliminate sodium and calcium
• Glucocorticoids and dialysis may also be useful

Factors that Aggravate Hypercalcemia

• Thiazide diuretics
• Lithium carbonate
• Volume depletion
• Prolonged bed rest or inactivity
• High-calcium diet (>1000 mg/day)
• Calcium supplements
• Vitamin D supplements (>800 IU/day)
• Multivitamins containing calcium

Causes of Hypercalcemia

• Measure parathyroid hormone (PTH) levels after the patient is stabilized
• If PTH is low, the patient may have a tumor (e.g., multiple myeloma) or paraneoplastic syndrome
• If PTH is high, the patient may have primary hyperparathyroidism (e.g., tumor of the parathyroid gland)
• Vitamin D intoxication and granulomatous diseases (e.g., sarcoidosis and TB) can also cause hypercalcemia

Disorders of Water Balance (Dysnatremias)

• Dysnatremias are not disorders of sodium balance, but of water balance
• Sodium concentration is not equal to sodium amount in the body
• Blood volume depends on sodium content (regulated by RAAS and baroreceptors)
• Hypovolemia: sodium depletion → decreased blood volume
• Hypervolemia: sodium increase → increased blood volume

Sodium Concentration

• Not related to sodium amount in the body
• Depends on water balance (regulated by vasopressin and thirst)
• Hyponatremia: water excess → low sodium concentration
• Hypernatremia: water deficit → high sodium concentration

Hyponatremia

• Most common disorder of body fluid and electrolyte balance
• Occurs in 1-2% of hospitalized patients and 30% of ICU patients
• Can lead to various clinical symptoms, from subtle to severe or life-threatening
• Prompt recognition is crucial, as it increases in-hospital mortality by 40%

Symptoms of Hyponatremia

• Expression of central nervous system dysfunction caused by brain cell swelling
• Acute hyponatremia: reversible if properly treated
• Chronic hyponatremia: usually asymptomatic or paucisymptomatic

Causes of Hyponatremia

• Hypovolemic hyponatremia: extrarenal salt loss (e.g., diuretics, nephropathies, mineralocorticoid deficiencies)
• Euvolemic hyponatremia: SIADH (syndrome of inappropriate ADH secretion), hypothyroidism, psychogenic polydipsia, adrenocorticotropic deficiency
• Hypervolemic hyponatremia: heart failure, liver disease, nephrotic syndrome, advanced kidney disease

Treatment of Hyponatremia

• Exclude hyperglycemia and pseudohyponatremia
• Assess severity of symptoms
• If severe, give 150 mL of 3% hypertonic saline over 20 minutes
• if asymptomatic, focus on etiology of the disease
• Avoid rapid correction to prevent osmotic demyelination syndrome### Diabetes Insipidus
• Can be hereditary (x-linked recessive, defect of V2 receptors or aquaporins) or acquired (electrolyte disorders, certain medications, chronic intestinal kidney disease, malnutrition)
• Gestational DI: caused by degradation of ADH, occurs in peripheral circulation

Symptoms of Diabetes Insipidus

• Altered mental status
• Lethargy
• Irritability
• Restlessness
• Muscle twitching
• Hyperreflexia and spasticity
• Seizures (usually in children)
• Coma

Treatment of Hypernatremia

• Determine volume status (sodium balance)
• Calculate water deficit
• Choose a replacement fluid
• Determine the rate of depletion
• Estimate ongoing sensible and insensible losses
• Use the formula: Water deficit = TBW x (Na+s / 140 - 1)
• Replace water deficit with hypotonic solution (e.g. 5% dextrose)
• Monitor and adjust rate of repletion

Key Points of Hypernatremia

• Always reflects a hyperosmolar state
• Always a water problem, sometimes a salt problem
• Requires defect in thirst mechanism or limited access to free water
• Sodium concentration does not provide information about total body salt or volume status
• Calculation of water deficit is useful, but represents only a snapshot
• Use clinical judgment and carefully monitor the patient
• Consider sensible and insensible losses

Approach to Glomerular Diseases

• Simple lab test: serum creatinine
• Accurate test: measurement of glomerular filtration rate (GFR) through inulin clearance
• Other methods: use serum creatinine and GFR to assess renal function
• Urinalysis should be performed in case of altered kidney functionality
• Recognize nephrological syndromes, which can vary from asymptomatic to severe clinical manifestations

Glomerular Diseases

• May present in different clinical forms (nephrological syndromes)
• Variations depend on combinations of serum creatinine, proteinuria, and alterations of urinary sediment
• Recognizing the correct syndrome is crucial for treatment and prognosis

Hematuria

• Macroscopic hematuria: visible blood in urine
• Can be symptomatic or asymptomatic, persistent or intermittent
• Causes: inflammation of urinary bladder, urethra or prostate, urinary infections, kidney stones, polycystic kidney diseases, blood clotting disorders, sickle cell diseases, cancer, trauma
• Glomerular diseases can cause macroscopic hematuria, especially IgA nephropathy
• Asymptomatic urinary abnormalities: diagnosis obtained by urinalysis, proteinuria > 150 mg/day, hematuria, and hyaline or hyaline-granular casts
• Nephrotic syndrome: characterized by proteinuria > 3.5g/day, low serum protein, and low albumin, with edema as the main clinical manifestation

Introduction to Nephrology

• Nephrology is the study of kidney function and diseases
• Kidney function is essential for maintaining overall health

Kidney Function

• Kidneys act as filters, clearing the body of waste and toxic substances
• They monitor and regulate blood pressure through the juxtaglomerular apparatus
• They produce erythropoietin, which stimulates the production of red blood cells
• They manage water and salt concentrations in the body, responding to antidiuretic hormone and aldosterone
• They convert vitamin D to its active form, increasing calcium levels in the body

Evaluation of Renal Function

• The best test to evaluate renal function is the glomerular filtration rate (GFR)
• GFR measures the volume of plasma cleared of a substance in a unit of time (mL/min)
• An ideal substance to evaluate GFR should be produced endogenously, filtered by the glomerulus, and not reabsorbed or secreted by the renal tubule
• Inulin is the ideal substance, but it is not produced by the body, so serum creatinine is used instead

Serum Creatinine

• Serum creatinine is a waste product that is produced by the body and cleared by the kidneys
• High levels of serum creatinine indicate impaired kidney function
• Normal range of serum creatinine is 0.5-1.0 mg/dL
• Serum creatinine levels are influenced by factors such as aging, diet, and muscle mass

Glomerular Filtration Rate (GFR)

• GFR is the volume of plasma cleared of a substance in a unit of time (mL/min)
• Normal range of GFR is 90-120 mL/min
• GFR is calculated using serum creatinine levels, urinary volume, and creatinine in urine
• GFR is influenced by factors such as aging, diet, and muscle mass

Stages of Kidney Dysfunction

• G1: normal or high GFR (>90 mL/min/1.73m²)
• G2: mildly decreased GFR (60-89 mL/min/1.73m²)
• G3a: mildly to moderately decreased GFR (45-59 mL/min/1.73m²)
• G3b: moderately to severely decreased GFR (30-44 mL/min/1.73m²)
• G4: severely decreased GFR (15-20 mL/min/1.73m²)
• G5: kidney failure (GFR ≤15 mL/min/1.73m²)

Case Study: Antonio

• Antonio is a 70-year-old man with a history of high blood pressure and recent symptoms of nocturia, headaches, and fatigue
• Lab tests reveal high levels of serum creatinine, urea, and potassium, and low levels of sodium and calcium
• Urinalysis shows proteinuria and hemoglobinuria
• Diagnosis is severe renal dysfunction, with a GFR of <15 mL/min

Hyperkalemia

• Hyperkalemia is a medical emergency characterized by high levels of potassium in the blood
• Causes of hyperkalemia include potassium shift outside the cells, drugs interfering with potassium balance, and kidney injury
• Symptoms of hyperkalemia include muscle weakness, paralysis, and cardiac conduction abnormalities
• Treatment of hyperkalemia includes calcium gluconate, insulin, beta2-adrenergic agonists, and sodium bicarbonate

Calcium and Phosphorus

• Calcium and phosphorus are essential for bone health
• Parathyroid hormone (PTH) is the main calcium regulator
• PTH increases calcium reabsorption in the kidneys, favors intestinal calcium and phosphorus reabsorption, and increases bone turnover
• Calcitonin is another hormone involved in calcium regulation, which counteracts the effects of PTH
• Vitamin D is essential for calcium regulation, and its deficiency can lead to hypocalcemia

Hypocalcemia

• Hypocalcemia is a condition characterized by low levels of calcium in the blood
• Symptoms of hypocalcemia include tetany, seizures, hypotension, and psychiatric manifestations
• Causes of hypocalcemia include vitamin D deficiency, reduced gastrointestinal reabsorption, chronic kidney disease, and hypomagnesemia
• Treatment of hypocalcemia includes intravenous and oral calcium, and vitamin D supplements

Hypercalcemia

• Hypercalcemia is a condition characterized by high levels of calcium in the blood
• Symptoms of hypercalcemia include muscle weakness, polyuria, polydipsia, dehydration, nausea, and changes in sensorium
• Causes of hypercalcemia include hyperparathyroidism, vitamin D intoxication, and cancer
• Treatment of hypercalcemia includes hydration, diuretics, and bisphosphonates### Hypercalcemia Treatment
• In medical emergencies, treat the patient first and understand the causes later
• First treatment: intravenous hydration with isotonic saline and glucose (no calcium)
• Next, administer subcutaneous calcitonin to lower serum calcium concentration (not available in Italy)
• Then, give bisphosphonates to the patient
• Consider the onset and duration of action of these drugs
• Isotonic saline takes hours to work, bisphosphonates take a lot of hours
• Loop diuretics can also be used to treat hypercalcemia because they eliminate sodium and calcium
• Glucocorticoids and dialysis may also be useful

Factors that Aggravate Hypercalcemia

• Thiazide diuretics
• Lithium carbonate
• Volume depletion
• Prolonged bed rest or inactivity
• High-calcium diet (>1000 mg/day)
• Calcium supplements
• Vitamin D supplements (>800 IU/day)
• Multivitamins containing calcium

Causes of Hypercalcemia

• Measure parathyroid hormone (PTH) levels after the patient is stabilized
• If PTH is low, the patient may have a tumor (e.g., multiple myeloma) or paraneoplastic syndrome
• If PTH is high, the patient may have primary hyperparathyroidism (e.g., tumor of the parathyroid gland)
• Vitamin D intoxication and granulomatous diseases (e.g., sarcoidosis and TB) can also cause hypercalcemia

Disorders of Water Balance (Dysnatremias)

• Dysnatremias are not disorders of sodium balance, but of water balance
• Sodium concentration is not equal to sodium amount in the body
• Blood volume depends on sodium content (regulated by RAAS and baroreceptors)
• Hypovolemia: sodium depletion → decreased blood volume
• Hypervolemia: sodium increase → increased blood volume

Sodium Concentration

• Not related to sodium amount in the body
• Depends on water balance (regulated by vasopressin and thirst)
• Hyponatremia: water excess → low sodium concentration
• Hypernatremia: water deficit → high sodium concentration

Hyponatremia

• Most common disorder of body fluid and electrolyte balance
• Occurs in 1-2% of hospitalized patients and 30% of ICU patients
• Can lead to various clinical symptoms, from subtle to severe or life-threatening
• Prompt recognition is crucial, as it increases in-hospital mortality by 40%

Symptoms of Hyponatremia

• Expression of central nervous system dysfunction caused by brain cell swelling
• Acute hyponatremia: reversible if properly treated
• Chronic hyponatremia: usually asymptomatic or paucisymptomatic

Causes of Hyponatremia

• Hypovolemic hyponatremia: extrarenal salt loss (e.g., diuretics, nephropathies, mineralocorticoid deficiencies)
• Euvolemic hyponatremia: SIADH (syndrome of inappropriate ADH secretion), hypothyroidism, psychogenic polydipsia, adrenocorticotropic deficiency
• Hypervolemic hyponatremia: heart failure, liver disease, nephrotic syndrome, advanced kidney disease

Treatment of Hyponatremia

• Exclude hyperglycemia and pseudohyponatremia
• Assess severity of symptoms
• If severe, give 150 mL of 3% hypertonic saline over 20 minutes
• if asymptomatic, focus on etiology of the disease
• Avoid rapid correction to prevent osmotic demyelination syndrome### Diabetes Insipidus
• Can be hereditary (x-linked recessive, defect of V2 receptors or aquaporins) or acquired (electrolyte disorders, certain medications, chronic intestinal kidney disease, malnutrition)
• Gestational DI: caused by degradation of ADH, occurs in peripheral circulation

Symptoms of Diabetes Insipidus

• Altered mental status
• Lethargy
• Irritability
• Restlessness
• Muscle twitching
• Hyperreflexia and spasticity
• Seizures (usually in children)
• Coma

Treatment of Hypernatremia

• Determine volume status (sodium balance)
• Calculate water deficit
• Choose a replacement fluid
• Determine the rate of depletion
• Estimate ongoing sensible and insensible losses
• Use the formula: Water deficit = TBW x (Na+s / 140 - 1)
• Replace water deficit with hypotonic solution (e.g. 5% dextrose)
• Monitor and adjust rate of repletion

Key Points of Hypernatremia

• Always reflects a hyperosmolar state
• Always a water problem, sometimes a salt problem
• Requires defect in thirst mechanism or limited access to free water
• Sodium concentration does not provide information about total body salt or volume status
• Calculation of water deficit is useful, but represents only a snapshot
• Use clinical judgment and carefully monitor the patient
• Consider sensible and insensible losses

Approach to Glomerular Diseases

• Simple lab test: serum creatinine
• Accurate test: measurement of glomerular filtration rate (GFR) through inulin clearance
• Other methods: use serum creatinine and GFR to assess renal function
• Urinalysis should be performed in case of altered kidney functionality
• Recognize nephrological syndromes, which can vary from asymptomatic to severe clinical manifestations

Glomerular Diseases

• May present in different clinical forms (nephrological syndromes)
• Variations depend on combinations of serum creatinine, proteinuria, and alterations of urinary sediment
• Recognizing the correct syndrome is crucial for treatment and prognosis

Hematuria

• Macroscopic hematuria: visible blood in urine
• Can be symptomatic or asymptomatic, persistent or intermittent
• Causes: inflammation of urinary bladder, urethra or prostate, urinary infections, kidney stones, polycystic kidney diseases, blood clotting disorders, sickle cell diseases, cancer, trauma
• Glomerular diseases can cause macroscopic hematuria, especially IgA nephropathy
• Asymptomatic urinary abnormalities: diagnosis obtained by urinalysis, proteinuria > 150 mg/day, hematuria, and hyaline or hyaline-granular casts
• Nephrotic syndrome: characterized by proteinuria > 3.5g/day, low serum protein, and low albumin, with edema as the main clinical manifestation

Introduction to Nephrology

• Nephrology is the study of kidney function and diseases
• Kidney function is essential for maintaining overall health

Kidney Function

• Kidneys act as filters, clearing the body of waste and toxic substances
• They monitor and regulate blood pressure through the juxtaglomerular apparatus
• They produce erythropoietin, which stimulates the production of red blood cells
• They manage water and salt concentrations in the body, responding to antidiuretic hormone and aldosterone
• They convert vitamin D to its active form, increasing calcium levels in the body

Evaluation of Renal Function

• The best test to evaluate renal function is the glomerular filtration rate (GFR)
• GFR measures the volume of plasma cleared of a substance in a unit of time (mL/min)
• An ideal substance to evaluate GFR should be produced endogenously, filtered by the glomerulus, and not reabsorbed or secreted by the renal tubule
• Inulin is the ideal substance, but it is not produced by the body, so serum creatinine is used instead

Serum Creatinine

• Serum creatinine is a waste product that is produced by the body and cleared by the kidneys
• High levels of serum creatinine indicate impaired kidney function
• Normal range of serum creatinine is 0.5-1.0 mg/dL
• Serum creatinine levels are influenced by factors such as aging, diet, and muscle mass

Glomerular Filtration Rate (GFR)

• GFR is the volume of plasma cleared of a substance in a unit of time (mL/min)
• Normal range of GFR is 90-120 mL/min
• GFR is calculated using serum creatinine levels, urinary volume, and creatinine in urine
• GFR is influenced by factors such as aging, diet, and muscle mass

Stages of Kidney Dysfunction

• G1: normal or high GFR (>90 mL/min/1.73m²)
• G2: mildly decreased GFR (60-89 mL/min/1.73m²)
• G3a: mildly to moderately decreased GFR (45-59 mL/min/1.73m²)
• G3b: moderately to severely decreased GFR (30-44 mL/min/1.73m²)
• G4: severely decreased GFR (15-20 mL/min/1.73m²)
• G5: kidney failure (GFR ≤15 mL/min/1.73m²)

Case Study: Antonio

• Antonio is a 70-year-old man with a history of high blood pressure and recent symptoms of nocturia, headaches, and fatigue
• Lab tests reveal high levels of serum creatinine, urea, and potassium, and low levels of sodium and calcium
• Urinalysis shows proteinuria and hemoglobinuria
• Diagnosis is severe renal dysfunction, with a GFR of <15 mL/min

Hyperkalemia

• Hyperkalemia is a medical emergency characterized by high levels of potassium in the blood
• Causes of hyperkalemia include potassium shift outside the cells, drugs interfering with potassium balance, and kidney injury
• Symptoms of hyperkalemia include muscle weakness, paralysis, and cardiac conduction abnormalities
• Treatment of hyperkalemia includes calcium gluconate, insulin, beta2-adrenergic agonists, and sodium bicarbonate

Calcium and Phosphorus

• Calcium and phosphorus are essential for bone health
• Parathyroid hormone (PTH) is the main calcium regulator
• PTH increases calcium reabsorption in the kidneys, favors intestinal calcium and phosphorus reabsorption, and increases bone turnover
• Calcitonin is another hormone involved in calcium regulation, which counteracts the effects of PTH
• Vitamin D is essential for calcium regulation, and its deficiency can lead to hypocalcemia

Hypocalcemia

• Hypocalcemia is a condition characterized by low levels of calcium in the blood
• Symptoms of hypocalcemia include tetany, seizures, hypotension, and psychiatric manifestations
• Causes of hypocalcemia include vitamin D deficiency, reduced gastrointestinal reabsorption, chronic kidney disease, and hypomagnesemia
• Treatment of hypocalcemia includes intravenous and oral calcium, and vitamin D supplements

Hypercalcemia

• Hypercalcemia is a condition characterized by high levels of calcium in the blood
• Symptoms of hypercalcemia include muscle weakness, polyuria, polydipsia, dehydration, nausea, and changes in sensorium
• Causes of hypercalcemia include hyperparathyroidism, vitamin D intoxication, and cancer
• Treatment of hypercalcemia includes hydration, diuretics, and bisphosphonates### Hypercalcemia Treatment
• In medical emergencies, treat the patient first and understand the causes later
• First treatment: intravenous hydration with isotonic saline and glucose (no calcium)
• Next, administer subcutaneous calcitonin to lower serum calcium concentration (not available in Italy)
• Then, give bisphosphonates to the patient
• Consider the onset and duration of action of these drugs
• Isotonic saline takes hours to work, bisphosphonates take a lot of hours
• Loop diuretics can also be used to treat hypercalcemia because they eliminate sodium and calcium
• Glucocorticoids and dialysis may also be useful

Factors that Aggravate Hypercalcemia

• Thiazide diuretics
• Lithium carbonate
• Volume depletion
• Prolonged bed rest or inactivity
• High-calcium diet (>1000 mg/day)
• Calcium supplements
• Vitamin D supplements (>800 IU/day)
• Multivitamins containing calcium

Causes of Hypercalcemia

• Measure parathyroid hormone (PTH) levels after the patient is stabilized
• If PTH is low, the patient may have a tumor (e.g., multiple myeloma) or paraneoplastic syndrome
• If PTH is high, the patient may have primary hyperparathyroidism (e.g., tumor of the parathyroid gland)
• Vitamin D intoxication and granulomatous diseases (e.g., sarcoidosis and TB) can also cause hypercalcemia

Disorders of Water Balance (Dysnatremias)

• Dysnatremias are not disorders of sodium balance, but of water balance
• Sodium concentration is not equal to sodium amount in the body
• Blood volume depends on sodium content (regulated by RAAS and baroreceptors)
• Hypovolemia: sodium depletion → decreased blood volume
• Hypervolemia: sodium increase → increased blood volume

Sodium Concentration

• Not related to sodium amount in the body
• Depends on water balance (regulated by vasopressin and thirst)
• Hyponatremia: water excess → low sodium concentration
• Hypernatremia: water deficit → high sodium concentration

Hyponatremia

• Most common disorder of body fluid and electrolyte balance
• Occurs in 1-2% of hospitalized patients and 30% of ICU patients
• Can lead to various clinical symptoms, from subtle to severe or life-threatening
• Prompt recognition is crucial, as it increases in-hospital mortality by 40%

Symptoms of Hyponatremia

• Expression of central nervous system dysfunction caused by brain cell swelling
• Acute hyponatremia: reversible if properly treated
• Chronic hyponatremia: usually asymptomatic or paucisymptomatic

Causes of Hyponatremia

• Hypovolemic hyponatremia: extrarenal salt loss (e.g., diuretics, nephropathies, mineralocorticoid deficiencies)
• Euvolemic hyponatremia: SIADH (syndrome of inappropriate ADH secretion), hypothyroidism, psychogenic polydipsia, adrenocorticotropic deficiency
• Hypervolemic hyponatremia: heart failure, liver disease, nephrotic syndrome, advanced kidney disease

Treatment of Hyponatremia

• Exclude hyperglycemia and pseudohyponatremia
• Assess severity of symptoms
• If severe, give 150 mL of 3% hypertonic saline over 20 minutes
• if asymptomatic, focus on etiology of the disease
• Avoid rapid correction to prevent osmotic demyelination syndrome### Diabetes Insipidus
• Can be hereditary (x-linked recessive, defect of V2 receptors or aquaporins) or acquired (electrolyte disorders, certain medications, chronic intestinal kidney disease, malnutrition)
• Gestational DI: caused by degradation of ADH, occurs in peripheral circulation

Symptoms of Diabetes Insipidus

• Altered mental status
• Lethargy
• Irritability
• Restlessness
• Muscle twitching
• Hyperreflexia and spasticity
• Seizures (usually in children)
• Coma

Treatment of Hypernatremia

• Determine volume status (sodium balance)
• Calculate water deficit
• Choose a replacement fluid
• Determine the rate of depletion
• Estimate ongoing sensible and insensible losses
• Use the formula: Water deficit = TBW x (Na+s / 140 - 1)
• Replace water deficit with hypotonic solution (e.g. 5% dextrose)
• Monitor and adjust rate of repletion

Key Points of Hypernatremia

• Always reflects a hyperosmolar state
• Always a water problem, sometimes a salt problem
• Requires defect in thirst mechanism or limited access to free water
• Sodium concentration does not provide information about total body salt or volume status
• Calculation of water deficit is useful, but represents only a snapshot
• Use clinical judgment and carefully monitor the patient
• Consider sensible and insensible losses

Approach to Glomerular Diseases

• Simple lab test: serum creatinine
• Accurate test: measurement of glomerular filtration rate (GFR) through inulin clearance
• Other methods: use serum creatinine and GFR to assess renal function
• Urinalysis should be performed in case of altered kidney functionality
• Recognize nephrological syndromes, which can vary from asymptomatic to severe clinical manifestations

Glomerular Diseases

• May present in different clinical forms (nephrological syndromes)
• Variations depend on combinations of serum creatinine, proteinuria, and alterations of urinary sediment
• Recognizing the correct syndrome is crucial for treatment and prognosis

Hematuria

• Macroscopic hematuria: visible blood in urine
• Can be symptomatic or asymptomatic, persistent or intermittent
• Causes: inflammation of urinary bladder, urethra or prostate, urinary infections, kidney stones, polycystic kidney diseases, blood clotting disorders, sickle cell diseases, cancer, trauma
• Glomerular diseases can cause macroscopic hematuria, especially IgA nephropathy
• Asymptomatic urinary abnormalities: diagnosis obtained by urinalysis, proteinuria > 150 mg/day, hematuria, and hyaline or hyaline-granular casts
• Nephrotic syndrome: characterized by proteinuria > 3.5g/day, low serum protein, and low albumin, with edema as the main clinical manifestation

Introduction to Nephrology

• Nephrology is the study of kidney function and diseases
• Kidney function is essential for maintaining overall health

Kidney Function

• Kidneys act as filters, clearing the body of waste and toxic substances
• They monitor and regulate blood pressure through the juxtaglomerular apparatus
• They produce erythropoietin, which stimulates the production of red blood cells
• They manage water and salt concentrations in the body, responding to antidiuretic hormone and aldosterone
• They convert vitamin D to its active form, increasing calcium levels in the body

Evaluation of Renal Function

• The best test to evaluate renal function is the glomerular filtration rate (GFR)
• GFR measures the volume of plasma cleared of a substance in a unit of time (mL/min)
• An ideal substance to evaluate GFR should be produced endogenously, filtered by the glomerulus, and not reabsorbed or secreted by the renal tubule
• Inulin is the ideal substance, but it is not produced by the body, so serum creatinine is used instead

Serum Creatinine

• Serum creatinine is a waste product that is produced by the body and cleared by the kidneys
• High levels of serum creatinine indicate impaired kidney function
• Normal range of serum creatinine is 0.5-1.0 mg/dL
• Serum creatinine levels are influenced by factors such as aging, diet, and muscle mass

Glomerular Filtration Rate (GFR)

• GFR is the volume of plasma cleared of a substance in a unit of time (mL/min)
• Normal range of GFR is 90-120 mL/min
• GFR is calculated using serum creatinine levels, urinary volume, and creatinine in urine
• GFR is influenced by factors such as aging, diet, and muscle mass

Stages of Kidney Dysfunction

• G1: normal or high GFR (>90 mL/min/1.73m²)
• G2: mildly decreased GFR (60-89 mL/min/1.73m²)
• G3a: mildly to moderately decreased GFR (45-59 mL/min/1.73m²)
• G3b: moderately to severely decreased GFR (30-44 mL/min/1.73m²)
• G4: severely decreased GFR (15-20 mL/min/1.73m²)
• G5: kidney failure (GFR ≤15 mL/min/1.73m²)

Case Study: Antonio

• Antonio is a 70-year-old man with a history of high blood pressure and recent symptoms of nocturia, headaches, and fatigue
• Lab tests reveal high levels of serum creatinine, urea, and potassium, and low levels of sodium and calcium
• Urinalysis shows proteinuria and hemoglobinuria
• Diagnosis is severe renal dysfunction, with a GFR of <15 mL/min

Hyperkalemia

• Hyperkalemia is a medical emergency characterized by high levels of potassium in the blood
• Causes of hyperkalemia include potassium shift outside the cells, drugs interfering with potassium balance, and kidney injury
• Symptoms of hyperkalemia include muscle weakness, paralysis, and cardiac conduction abnormalities
• Treatment of hyperkalemia includes calcium gluconate, insulin, beta2-adrenergic agonists, and sodium bicarbonate

Calcium and Phosphorus

• Calcium and phosphorus are essential for bone health
• Parathyroid hormone (PTH) is the main calcium regulator
• PTH increases calcium reabsorption in the kidneys, favors intestinal calcium and phosphorus reabsorption, and increases bone turnover
• Calcitonin is another hormone involved in calcium regulation, which counteracts the effects of PTH
• Vitamin D is essential for calcium regulation, and its deficiency can lead to hypocalcemia

Hypocalcemia

• Hypocalcemia is a condition characterized by low levels of calcium in the blood
• Symptoms of hypocalcemia include tetany, seizures, hypotension, and psychiatric manifestations
• Causes of hypocalcemia include vitamin D deficiency, reduced gastrointestinal reabsorption, chronic kidney disease, and hypomagnesemia
• Treatment of hypocalcemia includes intravenous and oral calcium, and vitamin D supplements

Hypercalcemia

• Hypercalcemia is a condition characterized by high levels of calcium in the blood
• Symptoms of hypercalcemia include muscle weakness, polyuria, polydipsia, dehydration, nausea, and changes in sensorium
• Causes of hypercalcemia include hyperparathyroidism, vitamin D intoxication, and cancer
• Treatment of hypercalcemia includes hydration, diuretics, and bisphosphonates### Hypercalcemia Treatment
• In medical emergencies, treat the patient first and understand the causes later
• First treatment: intravenous hydration with isotonic saline and glucose (no calcium)
• Next, administer subcutaneous calcitonin to lower serum calcium concentration (not available in Italy)
• Then, give bisphosphonates to the patient
• Consider the onset and duration of action of these drugs
• Isotonic saline takes hours to work, bisphosphonates take a lot of hours
• Loop diuretics can also be used to treat hypercalcemia because they eliminate sodium and calcium
• Glucocorticoids and dialysis may also be useful

Factors that Aggravate Hypercalcemia

• Thiazide diuretics
• Lithium carbonate
• Volume depletion
• Prolonged bed rest or inactivity
• High-calcium diet (>1000 mg/day)
• Calcium supplements
• Vitamin D supplements (>800 IU/day)
• Multivitamins containing calcium