Diuretics and Renal Function

• Diuretics are agents that increase urine output and primarily aim to eliminate excess fluid, reducing extracellular fluid volume to lower blood pressure and rid the body of excess interstitial fluid.

Renal Structure and Function

• Kidneys are paired retroperitoneal organs that weigh 160–175 g each, are 10–12 cm long, and receive 22% of cardiac output, or 1.1 L/min, of blood flow.
• The nephron, consisting of the glomerulus, proximal tubule, loop of Henle, distal tubule, and collecting duct, is the functional unit of the kidney responsible for maintaining homeostasis of internal volume and electrolytes.
• Renal disease may not become apparent until nearly 75% of the approximately 1 million nephrons are compromised.

Glomerular Filtration

• About 20% of total blood flow through the nephron is filtered, equaling approximately 130 mL/min.
• 99% of glomerular filtrate is reabsorbed in the tubules, with only 1% excreted as urine.
• Normal adult urine output is 0.5–1 mL/min or 30–60 mL/hr; output of < 30–60 mL/hr is oliguria, and > 60 mL/hr is polyuria.
• Diuretics increase urine output by interfering with reabsorption in the tubules.

Electrolyte Filtration and Reabsorption

• Na+ is reabsorbed: 70% in the proximal tubules, 20% in loops of Henle, 10% in distal tubules.
  • Inhibition causes less H2O retention
• K+ is mostly reabsorbed in the proximal tubules.
• Cl– and HCO3– are passively reabsorbed in the tubules.
• Aldosterone increases Na and H2O reabsorption in the distal tubule.
• Common electrolytes include Sodium (Na+), Potassium (K+), Chloride (Cl−), Bicarbonate (HCO3−), Hydrogen (H+), Calcium (Ca++), and Magnesium (Mg++).

Acid–Base Balance

• Acid–base balance can be affected by H2O loss and Na+ reabsorption.
  • Na+ is reabsorbed with Cl– to preserve neutrality, or through the exchange of Na+ for H+ or K+.
• Low Cl– or K+ can result in metabolic alkalosis.
• Loss of HCO3– buffer leads to metabolic acidosis.

Diuretic Groups

• The primary therapeutic goal of diuretics: reduce excess cellular fluid volume (ECFV).
• Relevant in respiratory and critical care for treating hypertension and congestive heart failure.
• Major groups include osmotic, carbonic anhydrase inhibitors, thiazides, loop, and potassium-sparing diuretics.

Osmotic Diuretics

• Osmotic diuretics impair the proximal tubule and ascending limb of the loop of Henle from reabsorbing NaCl.
• Osmotic diuretics result in a net K+ loss in urine.
• Examples: Glycerin, isosorbide, mannitol, and urea
  • Mannitol is often selected due to lower toxicity.
• Osmotic diuretics are often used for cerebral edema.

Carbonic Anhydrase Inhibitors

• Carbonic anhydrase inhibitors work within the proximal tubule, decreasing HCO3– and NaCl reabsorption.
• The net result: moderate NaCl increase plus water excretion.
• Carbonic anhydrase inhibitors have weak action and potential for metabolic acidosis.
• Hypokalemia is a common adverse effect.
• Other uses include the treatment of glaucoma, metabolic alkalosis, and altitude sickness.

Loop Diuretics

• Furosemide, bumetanide, and torsemide are loop diuretics.
• Loop diuretics inhibit NaCl reabsorption at the ascending limb of the loop of Henle.
• Loop diuretics are "high-ceiling" diuretics: up to 20% of NaCl and H2O is lost.
• Loop diuretics may cause acute vasodilation within 5 minutes when administered IV
  • Can decrease pulmonary capillary wedge pressure (PCWP), blood pressure, and systemic vascular resistance (SVR).
• Larger doses are required with renal dysfunction.

Thiazide Diuretics

• Thiazide diuretics block NaCl reabsorption at the distal tubule.
• Thiazide diuretics are a first-line treatment for mild hypertension.
• Thiazide diuretics have a narrow therapeutic margin.
• Thiazide diuretics may also decrease peripheral vascular resistance.

Potassium-Sparing Diuretics

• Potassium-sparing diuretics block the exchange of Na+ for K+ and H+.
  • Potassium-sparing diuretics have a weak action.
  • Potassium-sparing diuretics may cause hyperkalemia.
• Spironolactone
  • Spironolactone is a competitive aldosterone antagonist.
  • Spironolactone is common in cirrhosis and ascites.

Potassium-Sparing Diuretics (cont.)

• Triamterene
  • Triamterene blocks Na+ channels in the collecting ducts.
  • Triamterene is short-acting.
  • Triamterene is metabolized by the liver.
• Amiloride
  • Amiloride blocks Na+ channels in the collecting ducts.
  • Amiloride has a moderately long half-life.

Diuretic Combinations

• Diuretic combinations may produce additive or synergistic effects.
• The most common diuretic combination: loop diuretic plus thiazide.

Drug Interactions

• ACE inhibitors and potassium-sparing diuretics can lead to hyperkalemia and cardiac irritability.
• Aminoglycosides and loop diuretics can lead to ototoxicity and nephrotoxicity.
• Digoxin and thiazide and loop diuretics can lead to hypokalemia.
• β blockers and thiazide diuretics can cause hyperglycemia, hyperlipidemia, and hyperuricemia.
• Steroids and thiazide and loop diuretics increase the risk of hypokalemia.
• Carbamazepine or chlorpropamide and thiazide diuretics increase the risk of hyponatremia.

Adverse Effects

• Hypovolemia and acid–base disorders are the most common adverse effects.
  • Hypovolemia: dizziness, extreme thirst, excessive dryness, decreased urine output, dark-colored urine, constipation
  • Acid-base disorders: hypokalemia, hypochloremia
• Other adverse effects: hypokalemia, glucose changes, and ototoxicity.

Special Situations

• Diuretics are not recommended during pregnancy or for breastfeeding women, as they can dehydrate the baby.
• Side effects in children are similar to adults.
  • May require smaller doses
• Furosemide is effective and least toxic in pediatric practice.
  • Loop diuretics may cause nephrocalcinosis

Acute Respiratory Distress Syndrome (ARDS)

• Noncardiogenic pulmonary edema
• Reduction in PCWP is associated with increased survival.

Chronic Lung Disease (CLD) in Preterm Infants

• Lung disease complicated by pulmonary edema
• A single dose of aerosolized furosemide may transiently improve pulmonary mechanics.
• Routine or sustained use is not recommended.