When cardiac output is reduced by heart failure, the resultant

changes in blood pressure and blood flow to the kidney are sensed

as hypovolemia and lead to renal retention of salt and water.

In some cases despite the expansion of the plasma volume the cardiac output does not improve, so
the kidneys continue to retain fluids. This excessive fluids may leak the vasculature and cause
interstitial edema or pulmonary edema

. Edema associated with heart failure is generally managed with loop diuretics. In some instances,
salt and water retention may become so severe that a combination of thiazides and loop diuretics is
necessary

Reduction of pulmonary vascular congestion with diuretics may actually improve oxygenation and
thereby improve myocardial function.

Kidney Disease and Renal Failure

some renal disorders cause salt wasting, most cause retention of salt and water.

When renal failure is severe (GFR < 5 mL/min), diuretic agents are of little benefit, because
glomerular filtration is insufficient to generate or sustain a natriuretic response. However, a large
number of patients, and even dialysis patients, with milder degrees of renal insufficiency (GFR of 5–
15 mL/min), can be treated with diuretics with some success.

diabetic nephropathy, are frequently associated with development of hyperkalemia at a relatively

early stage of renal failure. This is often due to type IV renal tubular acidosis. In these cases, a
thiazide or loop diuretic will enhance K+ excretion by increasing delivery of salt to the K+ - secreting
collecting tubule.

causes of nephrotic syndrome are associated with primary retention of salt and water by the kidney,
leading to expanded plasma volume and hypertension despite the low plasma oncotic pressure. In
these cases, diuretic therapy may be beneficial in controlling the volume-dependent component of
hypertension

important limitations

 Acetazolamide must Diuretic Agents usually be avoided because it causes NaHCO3 excretion
and can worsen acidosis
 Potassium-sparing diuretics may cause hyperkalemia
 Thiazide diuretics are thought to be ineffective when GFR falls below 30 mL/min
Hepatic Cirrhosis

liver disease is often associated with edema and ascites in conjunction with elevated portal
hydrostatic pressures and reduced plasma oncotic pressures.

when ascites and edema become severe, diuretic therapy can be very useful.

cirrhotic patients are often resistant to loop diuretics because of decreased secretion of the
drug into the tubular fluid and because of high aldosterone levels.

cirrhotic edema is unusually responsive to spironolactone and eplerenone. The combination

of loop diuretics and an aldosterone receptor antagonist may be useful in some patients.

Idiopathic Edema
Idiopathic edema (fluctuating salt retention and edema) is a syndrome found most often in
20- to 30-year-old women.
studies suggest that intermittent diuretic use may actually contribute to the syndrome and
should be ruled out.
While spironolactone has been used for idiopathic edema, it should probably be managed
with moderate salt restriction alone if possible.

HYPERTENSION
he diuretic and mild vasodilator actions of the thiazides are useful in treating virtually all
patients with hypertension
hydrochlorothiazide is the most widely used diuretic for hypertension,
Loop diuretics are usually reserved for patients with mild renal insufficiency (GFR < 30–40
mL/min) or heart failure.
A K+ -sparing diuretic can be added to reduce K+ wasting.
Diuretics enhance the efficacy of many agents, particularly ACE inhibitors. Patients being
treated with powerful vasodilators such as hydralazine or minoxidil usually require
simultaneous diuretics because the vasodilators cause significant salt and water retention.

NEPHROLITHIASIS
Approximately two thirds of kidney stones contain Ca2+ phosphate or Ca2+ oxalate
Although there are many medical conditions that cause hypercalciuria, many patients with
such stones exhibit a defect in proximal tubular Ca2+ reabsorption. This can be treated with
thiazide diuretics, which enhance Ca2+ reabsorption in the DCT and thus reduce the urinary
Ca2+ concentration.
 HYPERCALCEMIA
loop diuretics reduce Ca2+ reabsorption significantly, they can be quite effective in
promoting Ca2+ diuresis. However, loop diuretics alone can cause marked volume
contraction. If this occurs, loop diuretics are ineffective (and potentially counterproductive)
because Ca2+ reabsorption in the proximal tubule would be enhanced. Thus, saline must be
administered simultaneously with loop diuretics if an effective Ca2+ diuresis is to be
maintained. The usual approach is to infuse normal saline and furosemide (80–120 mg)
intravenously.

DIABETES INSIPIDUS

Diabetes insipidus is due to deficient production of ADH (central diabetes insipidus) or inadequate
responsiveness to ADH (nephrogenic diabetes insipidus [NDI]).

Administration of supplementary ADH is effective only in central diabetes insipidus.

Thiazide diuretics can reduce polyuria and polydipsia in nephrogenic diabetes insipidus, which is not
responsive to ADH supplementation.

RENAL & CARDIAC PROTECTION

Aldosterone antagonists have been shown to be cardioprotective in patients with heart disease, they
may exert an additional benefit in lowering albuminuria in patients with diabetes and
microalbuminuria.

Their use has been limited in patients with renal dysfunction because of the increased risk of
inducing hyperkalemia.

Finerenone may produce similar cardiac and renal protection with a lower risk for hyperkalemia.