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Old 06-09-2011
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Kidney Why we use a diuretic in nephrogenic DI!

Hi,
Can any one explain me that why we use hydrochlorthiazide (diuretic) in patient of nephrogenic DI.?? because there is already polyuria and we use again diuertic.so what is reason behind to use hydrochlorethiazide..

pls explain it...

thanks in advance...
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Old 06-09-2011
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The concept here is that thiazides initially cause a mild volume contraction, which then signals the proximal tubule to increase Na+ and water reabsorption. So initially there is mild volume loss, but this is then compensated for by increased proximal tubule reabsorption.

This works because thiazides are a mild diuretic. Furosemide would not work because it is a better diuretic, thus the initial volume contraction is greater and the proximal tubule can't keep up. So don't use loop diuretics in nephrogenic DI

Of note is the use of amiloride in Nephrogenic DI caused by lithium toxicity. Normally, lithium is taken up into collecting tubule cells via ENaC channels. Lithium is like Na+ but it actually has a higher affinity for these channels. But it has a lower affinity for the basolateral Na pump, thus lithium is taken up into collecting tubule cells but then is trapped in the cell. Amiloride blocks these ENaC channels (Na channels), so it decreases Lithium uptake into collecting duct cells

Additionally, the mild volume contraction of amiloride leads to a decreased dose required to reach desired plasma concentration, thus increasing it's benefit in lithium toxicity.
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Old 06-09-2011
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The "signal" that I was talking about with volume contraction actually has to do with starling forces.

When there is volume contraction of the ECF (extracellular fluid), the protein concentration in the blood increases. This increases oncotic pressure in the peritubular capillaries and thus Starling forces favor reabsorption of Na+ and thus H20
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Old 06-09-2011
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Also here
Why is HCTZ is a choice of treatment for Nephrogenic DI?
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Pharmacology-, Physiology-, Renal-

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