Hyperuricemia is a common problem among renal transplant recipients. Its prevalence is clearly attributable to cyclosporine (CsA) use, although individual patients may have other risk factors as well. CsA lowers the urinary clearance of uric acid. The specific mechanism for this is unknown, but may involve alteration in tubular transport. Hyperuricemia may add on to several other factors in contributing to progressive deterioration of graft function and ultimately graft loss. The therapy of hyperuricemia may be particularly challenging in transplant patients.

Background Tolvaptan and octreotide-long-acting release (LAR) have renoprotective effects in autosomal dominant polycystic kidney disease (ADPKD) that are partially mediated by amelioration of compensatory glomerular hyperfiltration. We compared the effects of tolvaptan and octreotide-LAR combination therapy versus those of tolvaptan monotherapy in patients with ADPKD.Methods This pilot, randomized, placebo-controlled, cross-over trial primarily compared the effects of 1-and 4-week treatments with octreotide-LAR (two 20-mg i.m. injections) or placebo (two i.m. 0.9% saline solution injections) added-on tolvaptan (up to 90 and 30 mg/d) on GFR (iohexol plasma clearance) in 19 consenting patients with ADPKD referred to a clinical research center in Italy. Analyses were intention-to-treat. The local ethical committee approved the study.Results At 4 weeks, GFR significantly decreased by a median (interquartile range) of 3 (21 to 5) ml/min per 1.73 m 2 with tolvaptan and placebo (P50.01) and by 7 (3-14) ml/min per 1.73 m 2 with tolvaptan and octreotide-LAR (P50.03). GFR changes during the two treatment periods differed by 2 (25 to 14) ml/min per 1.73 m 2 (P50.28). At 1 week, GFR significantly decreased by 3 (0-7) ml/min per 1.73 m 2 with tolvaptan and placebo (P50.006) and by 10 (26 to 16) ml/min per 1.73 m 2 with tolvaptan and octreotide-LAR add-on therapy (P,0.001). GFR changes during the two treatment periods significantly differed by 3 (0-12) ml/min per 1.73 m 2 (P50.012). Total kidney volume nonsignificantly changed by 4 (248 to 23) ml with tolvaptan and placebo (P50.74), whereas it decreased significantly by 41 (25-77) ml with tolvaptan and octreotide-LAR (P50.001). Changes during the two treatment periods differed by 36 (0-65) ml (P50.01). Octreotide-LAR also attenuated (P50.02) the aquaretic effect of tolvaptan. Treatments were well tolerated.Conclusions In patients with ADPKD, octreotide-LAR added-on tolvaptan reduced GFR more effectively than octreotide-LAR and placebo. Octreotide-LAR also reduced total and cystic kidney volumes and attenuated the acquaretic effect of tolvaptan.