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The effects of angiotensin-converting enzyme inhibitors on peritoneal protein loss and solute transport in peritoneal dialysis patients.

ABSTRACT: OBJECTIVE:The objective of this study was to examine the effects of angiotensin-converting enzyme inhibitors on peritoneal membrane transport, peritoneal protein loss, and proteinuria in peritoneal dialysis patients. METHODS:Fifty-four peritoneal dialysis patients were included in the study. The patients were divided into two groups. Group 1 (n = 34) was treated with angiotensin-converting enzyme inhibitors. Group 2 (n = 20) did not receive any antihypertensive drugs during the entire follow-up. Eleven patients were excluded from the study thereafter. Thus, a total of 30 patients in Group 1 and 13 patients in Group 2 completed the study. We observed the patients for six months. Group 1 patients received maximal doses of angiotensin-converting enzyme inhibitors for six months. Parameters at the beginning of study and at the end of six months were evaluated. RESULTS:At the end of six months, total peritoneal protein loss in 24-hour dialysate effluent was significantly decreased in Group 1, whereas it was increased in Group 2. Compared to the baseline level, peritoneal albumin loss in 24-hour dialysate effluent and 4-hour D/P creatinine were significantly increased in Group 2 but were not significantly changed in Group 1. A covariance analysis between the groups revealed a significant difference only in the decreased amount of total protein loss in 24-hour dialysate. Proteinuria was decreased significantly in Group 1. CONCLUSION:This study suggests that angiotensin-converting enzyme inhibitors reduce peritoneal protein loss and small-solute transport and effectively protect peritoneal membrane transport in peritoneal dialysis patients.

SUBMITTER: Basturk T

PROVIDER: S-EPMC3416891 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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The effects of angiotensin-converting enzyme inhibitors on peritoneal protein loss and solute transport in peritoneal dialysis patients.

Basturk Taner T Unsal Abdulkadir A Koc Yener Y Nezaket Eren E Ahbap Elbis E Sakaci Tamer T Sevinc Mustafa M

Clinics (Sao Paulo, Brazil) 20120801 8

<h4>Objective</h4>The objective of this study was to examine the effects of angiotensin-converting enzyme inhibitors on peritoneal membrane transport, peritoneal protein loss, and proteinuria in peritoneal dialysis patients.<h4>Methods</h4>Fifty-four peritoneal dialysis patients were included in the study. The patients were divided into two groups. Group 1 (n = 34) was treated with angiotensin-converting enzyme inhibitors. Group 2 (n = 20) did not receive any antihypertensive drugs during the en ...[more]

PMID: 22948453

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Project description:BACKGROUND:Based on the International Society for peritoneal dialysis (PD) recommendations, blockade of renin-angiotensin systems with an angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) improves residual kidney function in PD patients. However, the long-term effectiveness of ACEI/ARB use in PD patients has not been fully elucidated. We, therefore, intend to perform a systematic review and meta-analysis to summarize the effects of ACEI/ARB use on long-term mortality, cardiovascular outcomes, and adverse events among PD patients. METHODS:This systematic review will include both randomized controlled trials and non-randomized studies in adult PD patients. We also plan to incorporate data from our cohort study in Thai PD population into this review. We will search PubMed, Medline, EMBASE, Cochrane Library, Web of Science, Scopus, CINAHL, and grey literature from inception to February 29, 2019, with no language restrictions. The process of study screening, selection, data extraction, risk of bias assessment, and grading the strength of evidence will be performed independently by a pair of reviewers. Any discrepancy will be resolved through a team discussion and/or consultation with the third reviewer. The pooled effects estimate and 95% confidence intervals will be estimated using DerSimonian-Laird random-effects models. Heterogeneity will be assessed by the Cochran Q test, I index and tau-squared statistics. The funnel plots along with the Begg and Egger test and trim and fill method will be performed to investigate any evidence of publication bias. Preplanned subgroup analyses and random-effects univariate meta-regressions will be performed to quantify the potential sources of heterogeneity based on studies- and patient-characteristics. RESULTS:This will be the first systematic review and meta-analysis to summarize the long-term effectiveness of renin-angiotensin system inhibitors in PD populations. CONCLUSION:In summary, this systematic review and meta-analysis will summarize the effectiveness of ACEI/ARB on long-term mortality, cardiovascular outcomes, and adverse events among adult PD patients by integrated all available evidences. ETHICS AND DISSEMINATION:Based on the existing published data, an ethical approval is not required. The findings will be disseminated through scientific meetings and publications in peer-reviewed journals.PROSPERO registration number: CRD42019129492.

Project description:ImportanceThe renin-angiotensin system has been implicated in mood disorders. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are among the most commonly used medications, yet their effects on mental health outcomes, particularly suicide, are poorly understood. This study examined the association between suicide and exposure to ACEIs and ARBs. Because of differences in their mode of action, it was speculated that ARBs would be associated with a higher risk of suicide than ACEIs.ObjectiveTo examine the association between suicide and exposure to ARBs compared with ACEIs.Design, setting, and participantsThis population-based nested case-control study of individuals aged 66 years and older used administrative claims databases in Ontario, Canada, from January 1, 1995, to December 31, 2015. Data analysis was performed from January to April 2019. Cases were individuals who died by suicide within 100 days of receiving an ACEI or ARB. The date of death served as the index date. For each case, 4 controls were identified and matched by age (within 1 year), sex, and presence of hypertension and diabetes. All individuals received an ACEI or ARB within 100 days before the index date.ExposuresUse of an ACEI or ARB.Main outcomes and measuresConditional logistic regression was used to estimate odds ratios for the association between suicide and exposure to ARBs compared with ACEIs.ResultsNine hundred sixty-four cases were matched to 3856 controls. The median (interquartile range) age of cases and controls was 76 (70-82) years. Most cases (768 [79.7%]) and controls (3068 [79.6%]) were men. Among cases, 260 (26.0%) were exposed to ARBs, and 704 (18.4%) were exposed to ACEIs. Among controls, 741 (74.0%) were exposed to ARBs, and 3115 (81.6%) were exposed to ACEIs. Compared with ACEI exposure, ARB exposure was associated with higher risk of death by suicide (adjusted odds ratio, 1.63; 95% CI, 1.33-2.00). The findings were consistent in a sensitivity analysis excluding individuals with a history of self-harm (odds ratio, 1.60; 95% CI, 1.29-1.98).Conclusions and relevanceThe use of ARBs may be associated with an increased risk of suicide compared with ACEIs. Preferential use of ACEIs over ARBs should be considered whenever possible, particularly in patients with severe mental health illness.

Project description:The angiotensin-converting enzyme (ACE) is a two-domain dipeptidylcarboxypeptidase, which has a direct involvement in the control of blood pressure by performing the hydrolysis of angiotensin I to produce angiotensin II. At the same time, ACE hydrolyzes other substrates such as the vasodilator peptide bradykinin and the anti-inflammatory peptide N-acetyl-SDKP. In this sense, ACE inhibitors are bioactive substances with potential use as medicinal products for treatment or prevention of hypertension, heart failures, myocardial infarction, and other important diseases. This review examined the most recent literature reporting ACE inhibitors with the help of molecular modeling. The examples exposed here demonstrate that molecular modeling methods, including docking, molecular dynamics (MD) simulations, quantitative structure-activity relationship (QSAR), etc, are essential for a complete structural picture of the mode of action of ACE inhibitors, where molecular docking has a key role. Examples show that too many works identified ACE inhibitory activities of natural peptides and peptides obtained from hydrolysates. In addition, other works report non-peptide compounds extracted from natural sources and synthetic compounds. In all these cases, molecular docking was used to provide explanation of the chemical interactions between inhibitors and the ACE binding sites. For docking applications, most of the examples exposed here do not consider that: (i) ACE has two domains (nACE and cACE) with available X-ray structures, which are relevant for the design of selective inhibitors, and (ii) nACE and cACE binding sites have large dimensions, which leads to non-reliable solutions during docking calculations. In support of the solution of these problems, the structural information found in Protein Data Bank (PDB) was used to perform an interaction fingerprints (IFPs) analysis applied on both nACE and cACE domains. This analysis provides plots that identify the chemical interactions between ligands and both ACE binding sites, which can be used to guide docking experiments in the search of selective natural components or novel drugs. In addition, the use of hydrogen bond constraints in the S2 and S2' subsites of nACE and cACE are suggested to guarantee that docking solutions are reliable.

Project description:BackgroundThe role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reducing risk of cardiovascular events (CVEs) and preserving kidney function in patients with chronic kidney disease is well-documented. However, the efficacy and safety of these agents in dialysis patients is still a controversial issue.MethodsWe systematically searched MEDLINE, Embase, Cochrane Library and Wanfang for randomized trials. The relative risk (RR) reductions were calculated with a random-effects model. Major cardiovascular events, changes in GFR and drug-related adverse events were analyzed.ResultsEleven trials included 1856 participants who were receiving dialysis therapy. Compared with placebo or other active agents groups, ARB therapy reduced the risk of heart failure events by 33% (RR 0.67, 95% CI 0.47 to 0.93) with similar decrement in blood pressure in dialysis patients. Indirect comparison suggested that fewer cardiovascular events happened during treatment with ARB (0.77, 0.63 to 0.94). The results indicated no significant differences between the two treatment regimens with regard to frequency of myocardial infarction (1.0, 0.45 to 2.22), stroke (1.16, 0.69 to 1.96), cardiovascular death (0.89, 0.64 to 1.26) and all-cause mortality (0.94, 0.75 to 1.17). Five studies reported the renoprotective effect and revealed that ACEI/ARB therapy significantly slowed the rate of decline in both residual renal function (MD 0.93 mL/min/1.73 m2, 0.38 to 1.47 mL/min/1.73 m2) and urine volume (MD 167 ml, 95% CI 21 ml to 357 ml). No difference in drug-related adverse events was observed in both treatment groups.ConclusionsThis study demonstrates that ACE-Is/ARBs therapy decreases the loss of residual renal function, mainly for patients with peritoneal dialysis. Overall, ACE-Is and ARBs do not reduce cardiovascular events in dialysis patients, however, treatment with ARB seems to reduce cardiovascular events including heart failure. ACE-Is and ARBs do not induce an extra risk of side effects.

Dataset Information

The effects of angiotensin-converting enzyme inhibitors on peritoneal protein loss and solute transport in peritoneal dialysis patients.

Publications

The effects of angiotensin-converting enzyme inhibitors on peritoneal protein loss and solute transport in peritoneal dialysis patients.

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