4). Retransplantation of the liver was necessary in six patients (3%). Quality of life improved in almost all patients. The higher survival rates with liver transplantation alone are higher compared to combined liver and kidney transplantation, and may be due to the more extensive abdominal surgery, as well as renal insufficiency in patients requiring the combined procedure. Daporinad ic50 Combined transplantation using a liver and kidney from the same donor protects the kidney graft from rejection and improves kidney graft survival.43,

44 Combined liver and kidney transplantation should only be performed in patients with advanced renal insufficiency or on dialysis. One of the potential factors in promoting cyst growth is cAMP. Secretin, the major cAMP agonist in cholangiocytes, stimulates the targeting and insertion of several transporters MK-2206 and channels into the apical membrane of cholangiocytes. Biliary epithelia maintain a cAMP-dependent Cl and HCO3 secretion that facilitates fluid secretion.45, 46

Intravenous administration of secretin in ADPKD patients increased fluid secretion in hepatic cysts.47 This suggests that increased cAMP drives fluid secretion in hepatic cysts. Somatostatin analogs are cAMP level inhibitors and decrease fluid secretion and cell proliferation in many cell types, including cholangiocytes,18, 48-51 thereby providing a novel opportunity to modulate cystogenesis. The basic concept is that cyst growth is regulated by a continuous process of secretion and reabsorption. Inhibition of secretion by somatostatin analogs may ultimately result in shrinking of hepatic cysts. The first experiments in humans with massively polycystic livers in the early 1990s failed to demonstrate any decrease in hepatic cyst growth or size following octreotide administration.52

The techniques used to evaluate liver volume were not sensitive enough to detect small but significant differences. In the NADPH-cytochrome-c2 reductase pck (PKHD1, fibrocystin) rat model of autosomal recessive PLD,53 cAMP concentrations in cholangiocytes were 2 times higher than in unaffected rats. In vivo, octreotide lowered cAMP content in cholangiocytes and serum and inhibited hepatic disease progression, leading to reductions in liver weight and cyst volume. This study provided a strong rationale for the potential value of octreotide in the treatment of PLD. A clinical observation in two patients suggested that a 3- to 6-month treatment with somatostatin analogs dramatically decreased liver volume by 15%-38%.54 These developments led to a number of randomized clinical trials that evaluated the effect of long-acting somatostatin analogs in PLD (Fig. 5). The first trial evaluated the effect of lanreotide 120 mg given monthly for 6 months in 54 PLD patients (32 ADPKD; 22 PCLD). The primary endpoint was change in total liver volume assessed by computed tomography (CT). The mean liver volume decreased 2.9% with lanreotide compared to an increase of 1.6% in the placebo group.