2. Introduction
• Diuretic resistance is defined as failure to achieve the
therapeutically desired reduction in edema even when
a maximal dose of diuretic is employed.
• Less clinically applicable definitions include:
- Persistent congestion despite adequate and
escalating doses of diuretic with >80 mg
Furosemide per day.
- Amount of sodium excreted as a percentage of
filtered load <0.2%
- Failure to excrete at least 90 mmol of sodium within
72 h of a 160 mg oral Furosemide dose given twice
daily.
3. Metrics of Diuretic response
• Weight loss per unit of 40 mg Furosemide (or
equivalent)
• Net fluid loss per milligram of loop diuretic (40
mg of Furosemide or equivalent) during
hospitalization.
• In Diuretic resistance Diuretic Response
4. Causes of Diuretic Resistance
1. Congestive Heart Failure
2. Renal insufficiency
3. Nephrotic syndrome
4. Liver Cirrhosis
5. Use of NSAIDs
5. Causes of Diuretic Resistance contd..
1. Congestive Heart Failure:
Patient with
CHF
1.Gastrointestinal
Edema
2. Renal insufficiency
Reduced rate of drug
absorption
Delayed time to
achieve threshold
dose
Diuretic Resistance
7. Congestive heart failure contd..
Fig: Dose–response curves for diuretics in normal subjects, patients with chronic
kidney disease (CKD), chronic heart failure (CHF) and both renal disease and
heart failure.
8. Causes of Diuretic Resistance contd..
2. Renal Insufficiency:
Fig: Mechanism of action of
Loop diuretics
9. Causes of Diuretic Resistance contd..
2. Renal Insufficiency
Renal insufficiency
1. Low GFR and RBF
2.Low proximal
tubular secretion
Insufficient
intratubular
concentrations of
diuretics
Decreased access of
diuretics to the site
of action
Diuretic Resistance
10. Renal insufficiency contd..
Fig: Dose–response curves for diuretics in normal subjects, patients with chronic
kidney disease (CKD), chronic heart failure (CHF) and both renal disease and
heart failure.
12. Causes of Diuretic resistance contd..
4. Liver Cirrhosis:
Liver cirrhosis
↓
Portal hypertension
↓
Increased hydrostatic pressure and decreased oncotic pressure (due to decreased
production of albumin)
↓
Fluid loss from vessels
↓
Decreased plasma volume
↓
Decreased Renal Blood flow
↓
Increased Renin from Juxtaglomerular apparatus
↓
Increased Aldosterone (secondary hyperaldosteronism)
↓
Increased sodium and water retention
13. Causes of Diuretic resistance contd..
5. Use of NSAIDs:
- NSAIDs may alter renal hemodynamics by
decreasing renal blood flow.
- Prostaglandin inhibition with aspirin or other
NSAIDs has been shown to attenuate diuretic
efficacy.
15. Braking phenomenon
• A physiological response to volume reduction
caused by diuretics.
Volume reduction
1) Increased sodium reabsorption in the proximal
renal tubules
2) Increased renin release
Progressive decline in the extent of natriuresis
17. Post-diuretic Sodium retention
Loop diuretics
Inhibit chloride transport via the Na-K-2Cl
cotransporter in Macula densa cells
Stimulate Renin release
Activation of RAAS system
Increased Na+ reabsorption
18. Renal Adaptation
Distal nephron hypertrophy:
Loop diuretics
Increase the Na+ and Cl- load delivered to the
distal nephron.
Distal tubular hypertrophy and increased local
aldosterone secretion.
20. Combination Diuretic Therapy
• Use of several diuretics acting on a separate
mechanism may be synergistic.
1. LOOP DIURETICS AND THIAZIDES
- Synergistic in normal subjects and in subjects with edema or
renal insufficiency.
- Patients with advanced CKD (chronic Kidney Disease; GFR < 30
mL/min) that are unresponsive to thiazide alone show a marked
natriuresis when a thiazide is added to loop diuretic therapy,
probably by blockade of distal tubular Na+ reabsorption.
21. Combination Diuretics Therapy contd..
2. LOOP DIURETICS OR THIAZIDES AND DISTAL
POTASSIUM-SPARING DIURETICS
-Amiloride or triamterene increases furosemide
natriuresis.
