Long-acting somatostatin analogue treatments in autosomal dominant polycystic kidney disease and polycystic liver disease: a systematic review and meta-analysis

Abstract

ObjectivesA number of randomised control trials (RCTs) investigating the effects of long-acting somatostatin analogues in autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD) have been recently reported. We sought to evaluate all available RCTs investigating the efficacy of somatostatin analogues treatment in ADPKD and PLD.Data sourcesElectronic databases; Pubmed, Clincaltrials.gov and Cochrane Central Register of Controlled TrialsEligibility criteria for selecting studiesRCTs and randomised cross-over trials comparing the effects of somatostatin analogue treatment with controls in patients with ADPKD or PLD.Data extraction and synthesisData extraction and bias assessments were performed by two independent reviewers between January and May 2019. Outcomes assessed included estimated glomerular filtration rate (eGFR), total kidney volume (TKV), total liver volume (TLV), progression to end stage renal failure (ESRF) and adverse effects. Data were pooled using a random-effects model and reported as relative risk or mean difference with 95% CIs.ResultsMeta-analysis was performed of six RCTs or randomised cross-over trials and three secondary analyses. A total of 592 patients were included. Compared with controls, somatostatin analogue treatment significantly reduced TLV (mean difference −0.15 L, 95% CI −0.26 to −0.03, p=0.01). There was no significant effect on TKV (mean difference −0.19 L, 95% CI −0.50 to 0.12, p=0.23) or eGFR (mean difference 0.27 mL/min/1.73 m2, 95% CI −2.03 to 2.57, p=0.82). There was no effect on progression to ESRF. Somatostatin analogues were associated with known adverse effects such as gastrointestinal symptoms.ConclusionsThe available RCT data show improvement in TLV with somatostatin analogue treatment. There was no benefit to TKV or eGFR in patients with ADPKD, while being associated with various side effects. Further studies are needed to assess potential benefit in reducing cyst burden in patients with PLD.

Somatostatin analog therapy effectiveness on the progression of polycystic kidney and liver disease: A systematic review and meta-analysis of randomized clinical trials

“…However, the body of evidence has continued to grow and this meta-analysis did not analyzed the effect of these drugs on the total liver volume (TLV). Another previous meta-analysis reported that somatostatin analogs attenuated TLV, but it did not show demonstrated an improvement in TKV and eGFR [22]. This last study used absolute volumes of kidney and liver which may lead to an under-or overestimated effect size due to highly heterogeneous baseline volumes between studies.…”

“…Compared with a previous meta-analysis, we estimated the effect of somatostatin analogues on TLV or TKV using the change in percentage instead of absolute values [22]. We considered this methodology more appropriate because baseline TLV or TKV is highly heterogeneous among studies and therefore the analysis could be over-or under-estimated, and this could lead to inaccurate efficacy estimates.…”

“…Some randomized clinical trials (RCTs) have evaluated the therapeutic effectiveness of somatostatin analogues in these clinical contexts. Moreover, three previous meta-analysis were done to estimate the effectiveness of this therapeutic option [22][23][24]. Two of them reported that somatostatin analogs attenuated the total kidney volume (TKV) increase rate and did not altered estimated glomerular filtration rate (eGFR) [23,24].…”

Cinacalcet may suppress kidney enlargement in hemodialysis patients with autosomal dominant polycystic kidney disease

“…4 ), findings consistent with those in a previous in vivo study 33 . In contrast, CaSR is also expressed in hepatocytes 38 , 39 and a recent meta-analysis revealed that somatostatin analogue treatment improved total liver volume in ADPKD patients 40 . Thus, cinacalcet may also have effects on liver cysts, though additional studies are needed to assess such effects in ADPKD patients.…”

The Lonidamine Derivative H2-Gamendazole Reduces Cyst Formation in Polycystic Kidney Disease

“…Activation of PKA by cAMP also elicits a strong mitogenactivated protein (MAP) kinase response in ADPKD cells, which are primed to be activated by decreased cytosolic calcium caused by PKD mutation (17,19,20). As an understanding of the molecular mechanisms of ADPKD progression has grown in recent years, so has the number of potential therapies (1)(2)(3)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34), including drugs that target cAMP-dependent fluid secretion and target cell growth and proliferation. One such drug is the AVP V2 receptor antagonist, tolvaptan, which has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with ADPKD (17,(35)(36)(37)(38)(39); however, high cost and side effects, including polyuria, nocturia, thirst, and liver complications limit its use in some patients.…”