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

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

Renal Diseases and Kidney Function

• Normally, renal diseases are bilateral, affecting both kidneys.
• A healthy individual has 2 million nephrons, 120 ml/min of creatinine clearance, and 1mg/dl of serum creatinine.
• If serum creatinine increases from 1 to 2 mg/dl, the creatinine clearance is reduced to 70 ml/min, indicating a significant loss of nephrons.

Calculating Creatinine Clearance

• To calculate creatinine clearance, you need:
  • Serum creatinine of the patient
  • Urinary volume (ml) over 24 hours
  • Creatinine in urine
  • Weight of the patient
  • Sex of the patient
• The formula is: urinary creatinine (mg/ml) x urinary volume (ml) / serum creatinine (mg/dl)

Glomerular Filtration Rate (GFR)

• Normal range of GFR is 90-120 ml/min
• Serum creatinine levels differ between males (0.6-1.2 mg/dl) and females (0.5-1.1 mg/dl)
• Factors that can influence GFR include:
  • Aging
  • Diet
  • Muscle mass

Kidney Function and Muscle Mass

• A single healthy kidney is able to sustain normal renal function
• Muscle mass affects serum creatinine levels, with reduced muscle mass leading to lower creatinine levels and normal GFR, and abundant muscle mass leading to higher creatinine levels and normal GFR

Evaluating Renal Function

• Serum creatinine and urinalysis should be performed to evaluate renal function
• If both tests are normal, kidney functionality is likely normal
• If both tests are altered, it's likely a kidney dysfunction
• If only one test is altered, further tests are needed

Glomerular Diseases

• Glomerular diseases can present in different clinical forms, known as nephrological syndromes
• These syndromes can vary from asymptomatic forms to mild/severe clinical manifestations with acute renal dysfunction
• Recognizing the correct nephrological syndrome is important for treatment and complication management

Evaluation of Kidney Dysfunction

• GFR (Glomerular Filtration Rate) is used to evaluate the stage of kidney dysfunction
• 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)

Hyperkalemia and Kidney Function

• Hyperkalemia is unusual in healthy individuals
• Two mechanisms may be associated with the development of hyperkalemia:
  • Increased release from cells (e.g., metabolic acidosis, insulin deficiency, use of beta blockers, exercise)
  • Reduced urinary potassium excretion (e.g., reduced aldosterone secretion, reduced response to aldosterone, oliguria, acute and chronic kidney disease, selective impairment in potassium secretion)

Clinical Case: Antonio

• Antonio's symptoms: nocturia, frequent urination at night, headaches, tiredness, lack of appetite, nausea, pale, edema in the lower limbs, and high blood pressure
• Lab test results:
  • Low sodium (133 mmol/L)
  • High potassium (5.8 mmol/L)
  • Low bicarbonate (16 mmol/L)
  • Anemia (Hb 9.6 g/dl)
  • High urea (190 mg/dl)
  • High serum creatinine (8.2 mg/dl)
  • High uric acid (9.1 mg/dl)
  • Low calcium (7.8 mg/dl)
  • High phosphorus (6.5 mg/dl)
  • Urinalysis: pH 6, protein 3+, Hb 1+ (altered, presence of proteinuria and hemoglobin)
• Clinical features indicate severe renal dysfunction

Acute Renal Dysfunction and Kidney Disease

• Acute renal dysfunction can be classified into three types: pre-renal, renal, and post-renal AKI
• Renal AKI can include tubulointerstitial diseases and glomerulonephritis
• Glomerulonephritis can progress to end-stage kidney disease if not treated
• 15% of cases of end-stage renal disease are due to untreated glomerulonephritis

Evaluating Renal Functionality

• GFR (Glomerular Filtration Rate) evaluation can be done with serum creatinine, but it's not always accurate due to muscle mass variation.
• Elderly people have lower creatinine levels, and patients with Rheumatoid Arthritis may have normal creatinine levels but low GFR.

Urinalysis

• Urinalysis should be performed in case of altered kidney functionality.
• If both serum creatinine and urinalysis are normal, kidney functionality is likely normal.
• If only one is altered, further tests are needed.

Glomerular Diseases

• Glomerular diseases present in different clinical forms called nephrological syndromes.
• These syndromes vary from asymptomatic forms to mild/severe clinical manifestations with acute renal dysfunction.
• Recognizing the correct nephrological syndrome is crucial due to different complications and treatments.

Clinical Case

• Antonio, a 70-year-old man, experiences frequent urination at night, headaches, and fatigue, indicating possible renal dysfunction.
• His lab test results show low sodium, high potassium, low bicarbonate, anemia, high urea, high serum creatinine, and proteinuria.
• These results indicate severe renal dysfunction.

Renal Function Tests

• Urea and serum creatinine are very important for evaluating kidney function.
• Uric acid is also associated with kidney function, but can be altered for other reasons.

Acute Kidney Injury (AKI)

• AKI can be classified into pre-renal, renal, and post-renal AKI.
• Renal AKI can further be classified into tubulointerstitial diseases and glomerulonephritis.

Glomerulonephritis

• Untreated glomerulonephritis can progress to end-stage kidney disease.
• 15% of end-stage renal disease cases are due to untreated glomerulonephritis.

Hematuria

• Macroscopic hematuria can be classified based on color, ranging from bright red to coke-like.
• The color of hematuria is an important factor to consider in diagnosis.
• Hematuria can be symptomatic or asymptomatic, persistent or intermittent.