Diuretic Resistance in  ARF

I have treated a number of edematous patients with diuretics, with little effect,
what is the cause of this “diuretic resistance”?

Diuretic resistance does indeed exist.  There are three broad types: acute tolerance, chronic tolerance, and disease-induced refractory edema.

Acute tolerance ("braking phenomenon") manifests as tachyphylaxis (i.e., a decreased saliuretic response with repeated doses of diuretic agent); it is probably due to extracellular fluid contraction induced by diuresis because it can easily be counteracted by fluid repletion. The patient is dry there is no point using diuretics.

Chronic tolerance describes gradual tachyphylaxis encountered with long-term administration of loop diuretics. It is due to compensatory hypertrophy of the distal tubule because mTAL blockade allows increased concentrations of sodium to reach this segment.Concomitant administration of thiazide diuretics, which block sodium reabsorption at the distal tubule, restores diuresis.

Generalized edema refractory to diuretic therapy is encountered in acute and chronic renal insufficiency, congestive heart failure, hepatic cirrhosis, and the nephrotic syndrome. In these disease states, diuretic resistance occurs because of decreased diuretic or sodium delivery to the luminal border of the mTAL (altered pharmacokinetics) or because of decreased natriuretic response to a given concentration of drug in the urine (altered pharmacodynamics). In uremia, endogenous organic acids compete with loop diuretics for active transport sites at the proximal tubule, and less diuretic reaches the mTAL

Please note: these tutorials are for personal study purposes only.  They are not currently peer reviewed, and no responsibility will be taken for mistakes or inaccuracies. Reproduction of information is forbidden. All material is copyrighted by the GasWorks Group.