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Does octreotide hold promise for treatment of polycystic kidney disease?

Posted Jan 05 2014 12:00am
One of the most frustrating things in clinical nephrology is to give a diagnosis of polycystic kidney disease (PKD) to a young patient, and follow that up by saying that they could progress to end stage renal disease requiring dialysis, and “there is not much I can offer to change that”.

Autosomal dominant PKD is the most prevalent monogenic disorder, and the average rate of GFR decline could be as much as 4.4 to 5.9 ml/min . Recently, the well-publicized TEMPO trial has shown a potential clinical application for tolvaptan in stemming the progression of PKD by slowing the growth of the total kidney volume and eGFR decline over a 3-year period.

Another agent that is being studied for a few years for a potential role in inhibiting cyst growth in PKD is octreotide, a long acting somatostatin analogue. This is an agent we in the nephrology universe have been using for some time for the treatment of hepatorenal syndrome. A randomized placebo controlled trial had first reported in 2005 that a 6-month treatment with somatostatin could slow cyst growth. Although we know that decline in kidney function in PKD follows cyst growth, the study stopped short of saying that slowing the cyst growth in this case would translate in to clinically meaningful renoprotection. A similar effect on liver volume has been reported as well.

A few months ago, we saw the results of the ALADIN trial published in the Lancet. This study had a longer follow-up period than the previous studies, and indicated a significantly lower kidney volume in patients treated with octreotide at 1-year follow-up, but not at 3-years.

Given the data we have so far, it appears that octreotide could have a potential role in the treatment of PKD. For some reason, it appears that octreotide slows growth in kidney volume over one year, but the effects become insignificant over the long term. Obviously, more comprehensive studies looking at long-term hard outcome data are needed. Another interesting thing would be to compare the data for octreotide vs. tolvaptan. Although both these agents have shown promise so far (in addition to other contenders like mTOR inhibitors), a major concern is cost. All other things being equal, octreotide could me a cheaper alternative than tolvaptan for what essentially could be a lifelong treatment. At my time of writing this, a ten-day course of 15 mg tolvaptan pills was priced at $3440.00, while a 100 mcg octreotide injection was priced at $11.93!

I can’t wait for the day when we will be able to offer our patients something more definitive for treatment of PKD, rather than the current bandaid regimen of ACE inhibitors, increased water intake, hand-holding, etc.

Posted by Veeraish Chauhan
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