Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease.

The fluid filling renal cysts in human polycystic kidneys is secreted chiefly by the tubular epithelium lining the cysts via secondary chloride transport. Inhibiting this process by somatostatin therapy should induce shrinking of renal cysts.

In this randomized, cross-over, placebo-controlled trial we compared the risk/benefit profile of 6-month treatment with long-acting somatostatin (octreotide-LAR, 40 mg intramuscularly every 28 days) or placebo in autosomal-dominant polycystic kidney disease (ADPKD) patients with mild-to-moderate renal insufficiency and no evidence of other kidney disease. Volumes of kidney structures were evaluated by a two-slice computed tomography (CT) scanner; while glomerular filtration rate (GFR) was estimated by iohexol plasma clearance.

One patient on somatostatin and one on placebo were prematurely withdrawn because of nonsymptomatic, reversible colelithiasis and asthenia, respectively. In the remaining 12 patients somatostatin was well tolerated. Kidney volume increased by 71 ± 107 mL (P < 0.05) on somatostatin and by 162 ± 114 mL (P < 0.01) on placebo. The percent increase was significantly lower on somatostatin (2.2 ± 3.7% vs. 5.9 ± 5.4%) (P < 0.05). Cystic volume tended to increase less on somatostatin than on placebo (3.0 ± 6.5% vs. 5.6 ± 5.8%). The “parenchymal” volume nonsignificantly increased by 2.5 ± 8.4% on placebo and slightly decreased by 4.4 ± 8.9% on somatostatin. The GFR did not change significantly during both treatment periods.

In ADPKD patients, 6-month somatostatin therapy is safe and may slow renal volume expansion. This may reflect an inhibited growth in particular of smallest cysts beyond the detection threshold of CT scan evaluation. Whether this effect may prove renoprotective in the long term should be tested in additional trials of longer duration.