Effects of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on all-cause mortality, cardiovascular death, and cardiovascular events among peritoneal dialysis patients: A protocol for systematic review.

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.

Understanding and Preventing (N-Nitrosodimethylamine) NDMA Contamination of Medications.

N-nitrosodimethylamine (NDMA) is a hepatotoxic agent and carcinogen contaminant in commonly used medications such as valsartan, losartan, irbesartan, and ranitidine. NDMA can be produced during manufacture, introduced from contaminated ingredients procured elsewhere, or introduced from contaminated solvents and catalysts. The Food and Drug Administration has established a maximum dose of NDMA that is permissible per tablet and guidance for manufacturers. However, many unanswered questions about NDMA contamination need rigorous investigation.

Effects of dual inhibition of renin-angiotensin-aldosterone system on cardiovascular and renal outcomes: balancing the risks and the benefits.

Chronic kidney disease is a worldwide health problem often burdened by severe cardiovascular complications. Hypertension represents one of the most important risk factor in affecting cardiovascular profile of chronic kidney disease patients. Since renin-angiotensin-aldosterone system plays a major role in determining cardiovascular outcome, guidelines recommend the use of renin-angiotensin-aldosteron inhibitors in order to control hypertension.

Renoprotective Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Diabetic Patients with Proteinuria.

BACKGROUND/AIMS: Limited evidence exists on the choice of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in diabetic patients with nephropathy. We aim to assess the renal effectiveness and safety of these drugs among diabetic nephropathy patients. METHODS: This retrospective cohort study was conducted with diabetic nephropathy patients who initiated ACEI or ARB monotherapy. The primary outcome was a composite of end stage of renal disease and renal transplantation, and the secondary outcome was all-cause mortality. The safety endpoint was hyperkalemia. RESULTS: Three thousand seven hundred and thirty-nine ACEI users and 3,316 ARB users were identified. ARBs seemed to be inferior to ACEIs given their poorer renal outcome (HR 1.31; 95% CI, 1.15-1.50) and higher risk of hyperkalemia (HR 1.17; 95% CI, 1.04-1.32). Among the four ACEIs compared, captopril was an inferior treatment choice given its poorer renal outcomes (HR 1.42; 95% CI, 1.05-1.93) and higher mortality rate (HR 1.25; 95% CI, 1.01-1.55). Irbesartan appeared to be a poorer treatment choice among the three ARBs compared, given its inferior renal protective effect (HR 1.35; 95% CI, 1.03-1.78). CONCLUSIONS: Our findings suggest ACEIs as a relatively more renoprotective and safer treatment as compared to ARBs. Captopril and irbesartan may be inferior to the other ACEIs and ARBs respectively.