Friday, March 12, 2010

CONSULT ROUNDS: Clinical dilemma in Nephrogenic Diabetis Insipidus

In a case with Nephrogenic diabetes insipidus with Stage 4 CKD; both secondary to Lithium
I suppose lithium associated CKD reduces no of AVP2 channels with persisting NDI long after lithium therapy..

I know that Amiloride is the drug of choice for Lithium associated NDI while pt is on lithium therapy..
Once someone is off lithium, can HCTZ should be used instead.
but would it be effective at this GFR??.. probably not..
what do you think
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4 comments:

  1. T-diddyMarch 13, 2010 at 6:49 AM

    T-diddy speaks:

    HCTZ at CKD-4 will not help too much. Thiazides lose potency as the degree of renal dysfunction increases. I will refer you to a paper in NEJM that discusses how diuretics function by class in CKD:
    http://blog.ecu.edu/sites/nephrologyondemand/?p=1709

    T-diddy out.

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  2. Kenar D Jhaveri( kidney 007)March 13, 2010 at 8:08 AM

    Thiazides are used in later stages of CKD just to enhance the effect of the loop diuretics. Remember that these drugs( all diuretics) except aldosterone inhibitors have to be secreted into the luminal side( in your urine), most in the proximal tubule to get to their site of action.
    If their GFR Is low, they have to be at much higher doses to be even secreted to work.
    HCTZ can sometimes work but at doses that we might not use these days( 50mg or 100mg), hence we use metalazone.
    Another excellent resource is
    http://www.nature.com/ki/journal/v39/n2/abs/ki199143a.html

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  3. AmarMarch 13, 2010 at 10:33 PM

    thanks for the great response.. here are my thoughts.

    .. HCTZ has a quiet a different mechanism of action in NDI.. it is not acting as a diuretic. It paradoxically decreases Urine output.. The mechanism is not clear..
    Here's an explanation..
    http://jasn.asnjournals.org/cgi/content/full/15/11/2948
    ..IN a nutshell,Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

    In the refernce you provided T-Diddy( and as suggested by Kenar as well)
    ...HCTZ was recommended at dose of 50 to 100 mg/day at GFR of 20 to 50ml/min..
    I am going to give it a shot to see if it works.. going to watch K closely.. will add aldactone if it drops..

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  4. AnonymousMarch 13, 2010 at 11:49 PM

    Dr. Jhaveri, Thanks for the excellent reference.
    I have 2 questions. (1) Can we use Thiazides at later stages of CKD? How do they enhance the effect of loop diuretics in CKD? ie. the blunting effect of thiazides on loop diuretics-mediated increased distal sodium reabsorption- do we know if this happens during advanced CKD also? (2) Why does Metalazone act in advanced renal failure while other thiazides do not? Thanks.

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