Effect of a Long-acting Somatostatin on Disease Progression in Nephropathy Due to Autosomal Dominant Polycystic Kidney Disease: a Long-term Three Year Follow up Study

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common hereditary renal disease, responsible for 8% to 10% of the cases of end stage renal disease (ESRD) in Western countries.

At comparable levels of blood pressure control and proteinuria, patients with ADPKD have faster decline in glomerular filtration rate (GFR) than those with other renal diseases and do not seem to benefit to the same extent of ACE inhibitor therapy. A reasonable explanation for the above findings is that in ADPKD progression is largely dependent on the development and growth of cysts and secondary disruption of normal tissue. Thus, renoprotective interventions in ADPKD - in addition to achieve maximal reduction of arterial blood pressure and proteinuria and to limit the effects of additional potential promoters of disease progression such as dyslipidemia, chronic hyperglycemia or smoking - should also be specifically aimed to correct the dysregulation of epithelial cell growth, secretion, and matrix interactions characteristic of the disease.

The fluid filling renal cysts in human polycystic kidney is formed mainly by a secretion process of the tubular epithelium lining the cysts. Secretion and re-absorption take place at approximately the same rate, with secretion slightly higher, so that the amount of fluid in the cysts increases slowly over time. The same process, via the secondary active chloride transport, is also involved in the secretion of fluid into the lumen of proximal tubules in teleost and elasmobranch fishes. Of interest, this process of chloride transport can be markedly inhibited by somatostatin, as demonstrated in the shark rectal gland.

Recently, somatostatin analogues have become available and used with negligible side effects for long-term treatment of tumors (up to 8-12 months). To evaluate the tolerability and the safety of long-acting somatostatin in ADPKD patients, a prospective cross-over controlled study has been recently performed. This pilot study demonstrated the safety of six month treatment of long-acting somatostatin in patients with ADPKD. Moreover, the percent increase of total kidney volume was significantly lower in patients on somatostatin than in placebo. Preliminary data on late stage ADPKD also suggest that loss of renal function in these patients closely correlates with the increase in kidney volume taken by small cysts (<5 mm3), but not total cyst volume.

Overall, these findings provide the basis for designing a long-term study in ADPKD patients aimed to document the efficacy of the somatostatin treatment in preventing further increase or even reducing the total kidney volume and the renal volume taken up by small cysts, eventually halting kidney disease progression.