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

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257606
Author(s):  
Tatsuya Suwabe ◽  
Francisco J. Barrera ◽  
Rene Rodriguez-Gutierrez ◽  
Yoshifumi Ubara ◽  
Marie C. Hogan
Keyword(s):  
Growth Rate ◽  
Liver Disease ◽  
Meta Analysis ◽  
Somatostatin Analogs ◽  
Mean Difference ◽  
The Body ◽  
Somatostatin Analog ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Total Liver Volume

Background Uncertainty underlies the effectiveness of somatostatin analogues for slowing the progression of polycystic kidney or liver disease. Methods Eligible studies included randomized controlled trials (RCTs) evaluating somatostatin analog as therapy for patients with polycystic kidney disease (PKD) or polycystic liver disease (PLD) compared to placebo or standard therapy. Two reviewers independently screened studies identified from databases (MEDLINE, EMBASE, Cochrane Database), clinical trial registries, and references from pertinent articles and clinical practice guidelines. Outcome measurements were changes in total liver volume (TLV), total kidney volume (TKV), and estimated glomerular filtration rate (eGFR). Results Of 264 nonduplicate studies screened, 10 RCTs met the inclusion criteria. The body of evidence provided estimates warranting moderate confidence. Meta-analysis of 7 RCTs including a total of 652 patients showed that somatostatin analogs are associated with a lower %TLV growth rate compared to control (mean difference, -6.37%; 95% CI -7.90 to -4.84, p<0.00001), and with a lower %TKV growth rate compared to control (mean difference, -3.66%; 95% CI -5.35 to -1.97, p<0.0001). However, it was not associated with a difference in eGFR decline (mean difference, -0.96 mL/min./1.73m2; 95% CI -2.38 to 0.46, p = 0.19). Conclusions Current body of evidence suggests that somatostatin analogs therapy slows the increase rate of TLV and TKV in patients with PKD or PLD compared to control within a 3-year follow-up period. It does not seem to have an effect on the change in eGFR. Somatostatin analogs therapy can be a promising treatment for ADPKD or ADPLD, and we need to continue to research its effectiveness for ADPKD or ADPLD.

scholarly journals Protective Treatments against Endothelial Glycocalyx Degradation in Surgery: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 (15) ◽  
pp. 6994
Author(s):  
Hasnain Q. R. B. Khan ◽  
Gwendolen C. Reilly
Keyword(s):  
Systematic Review ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Mean Difference ◽  
The Body ◽  
Endothelial Glycocalyx ◽  
Controlled Trials ◽  
Post Operation ◽  
Mean Differences ◽  
Randomised Controlled

The aim was to explore the body of literature focusing on protective treatments against endothelial glycocalyx degradation in surgery. A comprehensive systematic review of relevant articles was conducted across databases. Inclusion criteria: (1) treatments for the protection of the endothelial glycocalyx in surgery; (2) syndecan-1 used as a biomarker for endothelial glycocalyx degradation. Outcomes analysed: (1) mean difference of syndecan-1 (2) correlation between glycocalyx degradation and inflammation; (3) correlation between glycocalyx degradation and extravasation. A meta-analysis was used to present mean differences and 95% confidence intervals. Seven articles with eight randomised controlled trials were included. The greatest change from baseline values in syndecan-1 concentrations was generally from the first timepoint measured post-operatively. Interventions looked to either dampen the inflammatory response or fluid therapy. Methylprednisolone had the highest mean difference in plasma syndecan-1 concentrations. Ulinastatin showed correlations between alleviation of degradation and preserving vascular permeability. In this systematic review of 385 patients, those treated were more likely than those treated with placebo to exhibit less shedding of the endothelial glycocalyx. Methylprednisolone has been shown to specifically target the transient increase of glycocalyx degradation immediately post-operation and has displayed anti-inflammatory effects. We have proposed suggestions for improved uniformity and enhanced confidence for future randomised controlled trials.

scholarly journals Recent Advances in the Management of Autosomal Dominant Polycystic Kidney Disease

2018 ◽  
Vol 13 (11) ◽  
pp. 1765-1776 ◽  
Author(s):  
Fouad T. Chebib ◽  
Vicente E. Torres
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Somatostatin Analogs ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Total Kidney Volume ◽  
Disease Modifying ◽  
Autosomal Dominant Polycystic Kidney ◽  
Disease Stratification

Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic cause of ESKD, is characterized by relentless development of kidney cysts, hypertension, and destruction of the kidney parenchyma. Over the past few years, major advancements in diagnosing, prognosticating, and understanding the pathogenesis and natural course of the disease have been made. Currently, no kidney disease is more suitable for nephron-protective strategies. Early nephrology referral and implementation of these strategies may have a substantial effect. Total kidney volume is a good prognostication marker and allows stratification of patients into slow or rapid progressing disease, with implications for their management. Measurement of total kidney volume, disease stratification, and prognostication are possible using readily available tools. Although some patients require only monitoring and basic optimized kidney protective measures, such as rigorous BP control and various lifestyle and dietary changes, others will benefit from disease-modifying treatments. Vasopressin V2 receptor antagonists, a likely disease-modifying treatment, has been approved in several countries and recently by the US Food and Drug Administration; other therapies, such as somatostatin analogs and other novel agents, are currently in clinical trials. The purpose of this article is to present our views on the optimal management to delay kidney disease progression in ADPKD.

scholarly journals What influences treatment response in animal models of non-alcoholic fatty liver disease? A meta-analysis with meta-regression

2019 ◽  
Author(s):  
Harriet Hunter ◽  
Dana de Gracia Hahn ◽  
Amedine Duret ◽  
Yu Ri Im ◽  
Qinrong Cheah ◽  
...  
Keyword(s):  
Liver Disease ◽  
Animal Models ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Mean Difference ◽  
Hepatic Triglyceride ◽  
Alcoholic Fatty Liver ◽  
Meta Regression ◽  
Alcoholic Fatty Liver Disease

AbstractThe classical drug development pipeline necessitates studies using animal models of human disease to gauge future efficacy in humans, however, there is a comparatively low conversion rate from success in animals to in humans. Non-alcoholic fatty liver disease (NAFLD) is a complex chronic disease without any licensed therapies and hence a major field of animal research. We performed a meta-analysis of 414 interventional rodent studies (6,575 animals) in NAFLD to assess the mean difference in hepatic triglyceride content. 20 of 21 studied drug classes had similar efficacy with a mean difference of −30% hepatic triglyceride. However, when publication bias was accounted for, this reduced to −16% difference. Study characteristics were only able to account for a minority of variability on meta-regression, and we replicated previous findings of high risk of bias across 82% of cohorts. These findings build on previous work in preclinical neuroscience and help to explain the challenge of reproducibility and translation within the field of metabolism.

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

BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e032620 ◽  
Author(s):  
Joshua Griffiths ◽  
Mark T Mills ◽  
Albert CM Ong
Keyword(s):  
Autosomal Dominant ◽  
Data Extraction ◽  
Meta Analysis ◽  
Somatostatin Analogues ◽  
Mean Difference ◽  
Somatostatin Analogue ◽  
Polycystic Kidney ◽  
Polycystic Liver ◽  
Autosomal Dominant Polycystic Kidney ◽  
Long Acting

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.

scholarly journals Age- and height-adjusted total kidney volume growth rate in autosomal dominant polycystic kidney diseases

2018 ◽  
Vol 23 (1) ◽  
pp. 100-111 ◽  
Author(s):  
Eiji Higashihara ◽  
Kouji Yamamoto ◽  
Shinya Kaname ◽  
Takatsugu Okegawa ◽  
Mitsuhiro Tanbo ◽  
...  
Keyword(s):  
Growth Rate ◽  
Autosomal Dominant ◽  
Kidney Diseases ◽  
Volume Growth ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Total Kidney Volume ◽  
Polycystic Kidney Diseases ◽  
Autosomal Dominant Polycystic Kidney

scholarly journals Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver Involvement

2020 ◽  
Vol 15 (9) ◽  
pp. 1267-1278
Author(s):  
Marie C. Hogan ◽  
Julie A. Chamberlin ◽  
Lisa E. Vaughan ◽  
Angela L. Waits ◽  
Carly Banks ◽  
...  
Keyword(s):  
Placebo Group ◽  
Liver Disease ◽  
Liver Volume ◽  
Kidney Volume ◽  
Polycystic Liver Disease ◽  
Total Kidney Volume ◽  
Total Liver Volume ◽  
Total Liver ◽  
Polycystic Liver ◽  
Long Acting

Background and objectivesWe assessed safety and efficacy of another somatostatin receptor analog, pasireotide long-acting release, in severe polycystic liver disease and autosomal dominant polycystic kidney disease. Pasireotide long-acting release, with its broader binding profile and higher affinity to known somatostatin receptors, has potential for greater efficacy.Design, setting, participants, & measurementsIndividuals with severe polycystic liver disease were assigned in a 2:1 ratio in a 1-year, double-blind, randomized trial to receive pasireotide long-acting release or placebo. Primary outcome was change in total liver volume; secondary outcomes were change in total kidney volume, eGFR, and quality of life.ResultsOf 48 subjects randomized, 41 completed total liver volume measurements (n=29 pasireotide long-acting release and n=12 placebo). From baseline, there were −99±189 ml/m absolute and −3%±7% change in annualized change in height-adjusted total liver volume (from 2582±1381 to 2479±1317 ml/m) in the pasireotide long-acting release group compared with 136±117 ml/m absolute and 6%±7% increase (from 2387±759 to 2533±770 ml/m) in placebo (P<0.001 for both). Total kidney volumes decreased by −12±34 ml/m and −1%±4% in pasireotide long-acting release compared with 21±21 ml/m and 4%±5% increase in the placebo group (P=0.05 for both). Changes in eGFR were similar between groups. Among the n=48 randomized, adverse events included hyperglycemia (26 of 33 [79%] in pasireotide long-acting release versus four of 15 [27%] in the placebo group; P<0.001), and among the 47 without diabetes at baseline, 19 of 32 (59%) in the pasireotide long-acting release group versus one of 15 (7%) in the placebo group developed diabetes (P=0.001).ConclusionsAnother somatostatin analog, pasireotide long-acting release, slowed progressive increase in both total liver volume/total kidney volume growth rates without affecting GFR decline. Participants experienced higher frequency of adverse events (hyperglycemia and diabetes).Clinical Trial registry name and registration numberPasireotide LAR in Severe Polycystic Liver Disease, NCT01670110PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_08_28_CJN13661119.mp3

scholarly journals The Association of Combined Total Kidney and Liver Volume with Pain and Gastrointestinal Symptoms in Patients with Later Stage Autosomal Dominant Polycystic Kidney Disease

2017 ◽  
Vol 46 (3) ◽  
pp. 239-248 ◽  
Author(s):  
Hedwig M.A. D'Agnolo ◽  
Niek F. Casteleijn ◽  
Tom J.G. Gevers ◽  
Hans de Fijter ◽  
Maartje D.A. van Gastel ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Liver Volume ◽  
Gastrointestinal Symptoms ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Total Liver Volume ◽  
Gi Symptoms ◽  
Autosomal Dominant Polycystic Kidney

Background: There is an ongoing debate if and how kidney and liver volume are associated with pain and gastrointestinal (GI) symptoms in autosomal dominant polycystic kidney disease (ADPKD) patients. Since both kidney and liver volume could interact, we investigated whether combined total kidney and liver volume had stronger associations with ADPKD-related pain and GI symptoms than the volumes of the organs separately. Methods: We used baseline data from the DIPAK-1 study, which included ADPKD patients with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2. MR imaging was performed to measure height-adjusted total kidney volume (hTKV), height-adjusted total liver volume (hTLV) and the combination of both (height-adjusted total kidney liver volume [hTKLV]). Results: Three hundred nine ADPKD patients were included with a mean age of 48 ± 7 years, 53% female, eGFR 50 ± 11 mL/min/1.73 m2 and median hTKV, hTLV and hTKLV of 1,095 (758-1,669), 1,173 (994-1,523) and 2,496 (1,972-3,352) mL/m, respectively. ADPKD-related pain and GI symptoms were present in, respectively, 27.5 and 61.2% of patients. Gender was no effect modifier in the association between kidney and/or liver volume, and symptom burden, indicating that all models could be tested in the overall study population. hTKLV and hTLV were significantly associated with pain and GI symptoms, whereas hTKV was not. Model testing revealed that the associations of pain and GI symptoms with hTKLV were significantly stronger than with hTKV (p = 0.04 and p = 0.04, respectively) but not when compared to hTLV (p = 0.2 and p = 0.5, respectively). Conclusions: This study indicates that combined kidney and liver volume was associated with the presence and severity of pain and GI symptoms in ADPKD, with a more prominent role for hTLV than for hTKV.

CLINICAL AND PROGNOSTIC VALUE OF PROTEOLYSIS FACTORS IN CHILDREN WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

2019 ◽  
Vol 23 (2) ◽  
pp. 91-99
Author(s):  
Z. R. Bashirova
Keyword(s):  
Urinary Excretion ◽  
Renal Damage ◽  
Autosomal Dominant ◽  
Inverse Correlation ◽  
The Body ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Total Kidney Volume ◽  
Correlation Relationship ◽  
Autosomal Dominant Polycystic Kidney

BACKGROUND. One of the perspectives of modern Nephrology is the study of the mechanisms of nephrosclerosis in ADPKD. Matrix metalloproteinase system (MMP/TIMP)— enzymes that play a key role in the processes of proteolysis in the kidney. THE AIM: to determine the expression of the urine MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I, to establish their relationship with the volume of the kidney corrected to the surface of the body and the functional state of the kidneys, an additional criterion of progression. PATIENTS AND METHODS. The study included 34 children with ADPKD. The level of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I were determined in urine by ELISA. RESULTS. eGFR in children with total kidney volume greater than 97‰ was significantly lower than in children with normal total kidney volume. In the group of children with a total volume of the kidneys more than 97 percentile,a statistically significant increase in the level of TIMP-1 and TIMP-2 and PAI-I in the urine, and a statistically significant low level of urinary excretion of MMP-3 and MMP-9, compared with the group of children with ADPKD with normal total volume of the kidneys. In the group of children with ADPKD and total kidney volume of more than 97 percentiles of an inverse correlation relationship between the level of eGFR and TIMP-2 and PAI-I, as well as a direct correlation relationship between the total volume of kidney and the urinary excretion of TIMP-1. CONCLUSION. MMP and its inhibitors play an important role in renal damage in children with ADPKD. These proteolysis factors are promising to use as an indicator of the severity of the accumulation of extracellular matrix, that is, monitoring the process of fibrosis, and used as a predictor of progression.

scholarly journals Place of Cabergoline in Acromegaly: A Meta-Analysis

2011 ◽  
Vol 96 (5) ◽  
pp. 1327-1335 ◽  
Author(s):  
Laure Sandret ◽  
Patrick Maison ◽  
Philippe Chanson
Keyword(s):  
Treatment Duration ◽  
Meta Analysis ◽  
Single Agent ◽  
Somatostatin Analogs ◽  
Somatostatin Analog ◽  
Individual Data ◽  
Duration Of Treatment ◽  
Single Agent Therapy ◽  
Accurate Picture ◽  
Igf I

Context: Cabergoline is widely considered to be poorly effective in acromegaly. Objective: The aim of this study was to obtain a more accurate picture of the efficacy of cabergoline in acromegaly, both alone and in combination with somatostatin analogs. Design: We systematically reviewed all trials of cabergoline therapy for acromegaly published up to 2009 in four databases (PubMed, Pascal, Embase, and Google Scholar). We identified 15 studies (11 prospective) with a total of 237 patients; none were randomized or placebo-controlled. A meta-analysis was conducted on individual data (n = 227). Results: Cabergoline was used alone in nine studies. Fifty-one (34%) of the 149 patients achieved normal IGF-I levels. In multivariate analysis, the decline in IGF-I was related to the baseline IGF-I concentration (β = 1.16; P &lt;0.001), treatment duration (β = 0.28; P &lt; 0.001), and baseline prolactin concentration (β = −0.18; P = 0.01), and with a trend toward a relation with the cabergoline dose (β = 0.38; P =0.07). In five studies, cabergoline was added to ongoing somatostatin analog treatment that had failed to normalize IGF-I. Forty patients (52%) achieved normal IGF-I levels. The change in IGF-I was significantly related to the baseline IGF-I level (β = 0.74; P &lt; 0.001) but not to the dose of cabergoline, the duration of treatment, or the baseline prolactin concentration. Conclusion: This meta-analysis suggests that cabergoline single-agent therapy normalizes IGF-I levels in one third of patients with acromegaly. When a somatostatin analog fails to control acromegaly, cabergoline adjunction normalizes IGF-I in about 50% of cases. This effect may occur even in patients with normoprolactinemia.

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