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Background: Use of antihypertensive medications could be associated with an increased risk of kidney cancer. Despite their various mechanisms of action, whether this association differs between different classes of medications remains unclear. Objective: The objective of this study is to compare the risk of kidney cancer between first‐line treatment options of antihypertensive medications in a hypertensive population. Method: In this retrospective cohort study, we used the MarketScan Databases (2007–2021). We included individuals older than 30 years of age with a diagnosis of hypertension who received first‐line medications for hypertension, which included three classes: angiotensin‐converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and dihydropyridine calcium channel blockers (dCCB). We applied a propensity score matching method and created three separate cohorts: (1) ARB versus ACEI, (2) dCCB versus ACEI, and (3) dCCB versus ACEI. For non‐dCCB, we repeated the analyses. The primary outcome was kidney cancer incidence. To assess kidney cancer risk, we applied multivariable conditional Cox proportional hazards models. Results: In the first cohort, ARB use was associated with an increased risk of kidney cancer compared to ACEI use (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.02–1.18). In the second cohort, dCCB use was associated with an increased risk of kidney cancer compared to ACEI use (HR 1.29, 95% CI 1.18–1.40). In the third cohort, dCCB use was associated with a higher risk of kidney cancer compared to ARB use (HR 1.17, 95% CI 1.08–1.28). Null association was shown when comparing non‐dCCB with ACEI or ARB use. Conclusion: Use of dCCB showed a higher risk of kidney cancer compared to ACEI or ARB use in patients with hypertension. [ABSTRACT FROM AUTHOR]

Background: The efficacy of immune checkpoint inhibitors (ICIs) in cancer patients taking anti-hypertensive drugs is still not well established. Objective: To elucidate the effect of anti-hypertensive drugs on the clinical outcome of cancer patients receiving immunotherapy. Design: A retrospective cohort study and meta-analysis. Method: We conducted a real-world retrospective study of cancer patients treated with immunotherapy at two tertiary centers between January 2019 and June 2023, with primary outcomes being overall survival (OS) and progression-free survival (PFS). In addition, we performed a meta-analysis to synthesize currently relevant clinical studies. Results: A retrospective clinical study of 336 patients from 2 centers suggested that the use of anti-hypertensive drugs was related to a preferable OS (hazard ratio (HR) = 0.55, 95% confidence interval (CI): 0.33–0.90) compared to non-users. For PFS, no significant correlation was detected (HR = 0.71, 95% CI: 0.49–1.03). Further analysis revealed that renin–angiotensin system inhibitor (RASi) and calcium channel blocker (CCB) have a synergistic effect with ICIs. In addition, subgroup analysis found that the benefits of RASi or CCB in combination with ICIs are greater in women or patients ⩾65 years of age. There was better disease control in lung cancer patients using RASi, and a significantly longer OS was observed in patients with gastrointestinal tumors taking CCB. Meta-analysis suggested that anti-hypertensive drugs were associated with improved OS, but only the combination of RASi and immunotherapy showed a synergistic effect. No significant correlation with OS was found for other anti-hypertensive drugs, and there was no overall positive effect on PFS. Conclusion: Our study found that use of anti-hypertensive drugs, particularly RASi or CCB, was associated with improved OS in patients undergoing immunotherapy. The synergistic effects of RASi or CCB with ICIs were more pronounced in females or elderly. RASi or CCB exhibited different benefits in various types of tumors. These findings provide valuable insights for treating cancer patients with hypertension. [ABSTRACT FROM AUTHOR]

Background and objective: Collagen biosynthesis is intricately involved in the development and progression of solid tumors. Renin-angiotensin system inhibitors (RASi) impede TGF-β-mediated collagen synthesis in tumors by hindering activation of the angiotensin receptor. Our aim was to investigate a potential association between RASi use and the aggressiveness of prostate cancer (PCa). Methods: We conducted a retrospective multicenter analysis for a cohort of 1250 patients with PCa who underwent radical prostatectomy (RP) between 1990 and 2023 in four European high-volume centers. The study cohort comprised 625 RASi-treated patients and 625 age-matched RASi-naïve patients. Data for various parameters were collected, including age at RP, body mass index (BMI), prostate volume, prostate-specific antigen (PSA), percentage of free PSA, Gleason score (GS) at biopsy and RP, TNM stage, and the rate of biochemical recurrence (BCR). Clinical parameters for patients with and without RASi treatment were documented. Differences between the groups were compared using a Mann-Whitney U test and χ2 tests. Survival analyses were performed using the Kaplan-Meier method. Key findings and limitations: As expected, the RASi group had higher BMI levels than the RASi-naïve group (p

ABSTRACT Background Use of antihypertensive medications could be associated with an increased risk of kidney cancer. Despite their various mechanisms of action, whether this association differs between different classes of medications remains unclear. Objective The objective of this study is to compare the risk of kidney cancer between first‐line treatment options of antihypertensive medications in a hypertensive population. Method In this retrospective cohort study, we used the MarketScan Databases (2007–2021). We included individuals older than 30 years of age with a diagnosis of hypertension who received first‐line medications for hypertension, which included three classes: angiotensin‐converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and dihydropyridine calcium channel blockers (dCCB). We applied a propensity score matching method and created three separate cohorts: (1) ARB versus ACEI, (2) dCCB versus ACEI, and (3) dCCB versus ACEI. For non‐dCCB, we repeated the analyses. The primary outcome was kidney cancer incidence. To assess kidney cancer risk, we applied multivariable conditional Cox proportional hazards models. Results In the first cohort, ARB use was associated with an increased risk of kidney cancer compared to ACEI use (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.02–1.18). In the second cohort, dCCB use was associated with an increased risk of kidney cancer compared to ACEI use (HR 1.29, 95% CI 1.18–1.40). In the third cohort, dCCB use was associated with a higher risk of kidney cancer compared to ARB use (HR 1.17, 95% CI 1.08–1.28). Null association was shown when comparing non‐dCCB with ACEI or ARB use. Conclusion Use of dCCB showed a higher risk of kidney cancer compared to ACEI or ARB use in patients with hypertension.

Aims: This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin-angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD). Methods: Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi. Conclusion: Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm. [ABSTRACT FROM AUTHOR]

Introduction: The clinical benefits of renin–angiotensin system inhibitors (RASi) in patients undergoing hemodialysis remain obscure. Methods: This is a post hoc cohort analysis of the LANDMARK trial investigate whether RASi use was associated with cardiovascular events (CVEs) and all‐cause mortality. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity‐score matching. Results: The risk of CVEs was similar between participants with RASi use at baseline and those without RASi use at baseline and between participants with RASi use during the study period and those without RASi use during the study period. No clinical benefits of RASi use on all‐cause mortality were observed. Serum phosphate levels were significantly associated with the effect of RASi on CVEs. Conclusions: RASi use was not significantly associated with a lower risk of CVEs or all‐cause mortality in hemodialysis patients at risk of vascular calcification. [ABSTRACT FROM AUTHOR]

Introduction: The long-term impact of renin-angiotensin system (RAS) inhibitors for secondary prevention in patients with chronic kidney disease (CKD) and coexisting coronary artery disease remains unclear. Methods: Altogether, 1,160 consecutive patients with CKD (mean age, 70 ± 9 years; 78% men) who underwent their first percutaneous coronary intervention (PCI) between 2000 and 2018 were included and analyzed. Based on their RAS inhibitor use, 674 patients (58%) were allocated to the RAS inhibitor group, and 486 patients (42%) were allocated to the non-RAS inhibitor group. This study evaluated the incidence of 3-point major adverse cardiovascular events (3P-MACE), including cardiovascular death, nonfatal acute coronary syndrome and nonfatal stroke, admission for heart failure (HF), target vessel revascularization (TVR), and all-cause death. Results: During a median follow-up duration of 7.8 years, 280 patients (24.1%) developed 3P-MACE, 134 patients (11.6%) were hospitalized for HF, 171 patients (14.7%) underwent TVR, and 348 patients (30.0%) died of any causes. The cumulative incidence rate of 3P-MACE in the RAS inhibitor group was significantly lower than in the non-RAS inhibitor group (31.7% vs. 39.0%, log-rank test, p = 0.034); however, that of admission for HF in the RAS inhibitor group was significantly higher than in the non-RAS inhibitor group (28.1% vs. 13.3%, log-rank test, p < 0.001). The subgroup of preserved ejection fraction, non-acute myocardial infarction, and non-proteinuria tended to promote the onset of HF rather than cardiovascular prevention by RAS inhibitors. Conclusion: The long-term RAS inhibitor use for patients with CKD after PCI might prevent cardiovascular events but increase the risk of HF.

OBJECTIVE: To systematically evaluate the efficacy and safety of dapagliflozin combined with reninangiotensin system inhibitor (RASI) in the treatment of diabetic nephropathy (DN) based on Meta-analysis method. METHODS: Clinical randomized controlled trials related to dapagliflozin combined with RASI in the treatment of DN from establishment of the database to Jul. 2nd, 2022 were retrieved from CNKI, Wanfang Data, VIP, CBM, Embase, PubMed and the Cochrane Library. Literature screening, data extracting and effect evauation were conducted according to the methods provided in Cochrane system evaluation manual; and Meta-analysis on the enrolled studies was performed by using RevMan 5. 4 software. RESULTS: A total of 25 studies were enrolled, including 3 008 DN patients, 1 460 cases were in the research group (given dapagliflozin combined with RASI) and 1 548 cases were in the control group (treated with RASI alone). Results of Meta-analysis indicated that the improvement of 24 h urine protein quantitation,other renal function indicators and inflammatory factor levels in the research group were better than those in the control group, with statistically significant differences (P < 0. 05). The difference in the incidences of adverse drug reactions between two groups was not statistically significant (P = 0. 10). CONCLUSIONS: The combined treatment of dapagliflozin and RASI can significantly improve the renal function of DN patients, reduce the 24 h urine protein quantitation and inflammatory factors, with good safety. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We aimed to examine whether individuals with initial omission of glucose-lowering drug treatment (GLDT), including those achieving initial remission of type 2 diabetes, may experience a higher risk of major adverse cardiovascular events (MACE) compared with well-controlled individuals on GLDT after a new type 2 diabetes diagnosis in real-world clinical practice. Furthermore, we examined whether a higher risk could be related to lower initiation of statins and renin–angiotensin system inhibitors (RASi). Methods: In this cohort study, we used Danish registers to identify individuals with a first measured HbA1c between 48 and 57 mmol/mol (6.5–7.4%) from 2014 to 2020. Six months later, we divided participants into four groups according to GLDT and achieved HbA1c (<48 vs ≥48 mmol/mol [6.5%]): well-controlled and poorly controlled on GLDT; remission and persistent type 2 diabetes not on GLDT. We reported how much the standardised 5 year risk of MACE could be reduced for each group if initiation of statins and RASi was the same as in the well-controlled group on GLDT. Results: We included 14,221 individuals. Compared with well-controlled participants on GLDT, the 5 year standardised risk of MACE was higher in the three other exposure groups: by 3.3% (95% CI 1.6, 5.1) in the persistent type 2 diabetes group not on GLDT; 2.0% (95% CI 0.4, 3.7) in the remission group not on GLDT; and 3.5% (95% CI 1.3, 5.7) in the poorly controlled group on GLDT. Fewer individuals not on GLDT initiated statins and RASi compared with individuals on GLDT. If initiation of statins and RASi had been the same as in the well-controlled group on GLDT, participants not on GLDT could have reduced their risk of MACE by 2.1% (95% CI 1.2, 2.9) in the persistent type 2 diabetes group and by 1.1% (95% CI 0.4, 1.9) in the remission group. Conclusions/interpretation: Compared with well-controlled individuals on GLDT, individuals not on initial GLDT had a higher 5 year risk of MACE, even among those achieving remission of type 2 diabetes. This may be related to lower use of statins and RASi. [ABSTRACT FROM AUTHOR]

Introduction: This retrospective study was conducted to identify risk factors for developing hand-foot syndrome (HFS) and to determine new strategies for improving quality of life (QoL) in patients undergoing chemotherapy. Methods: Between April 2014 and August 2018, we enrolled 165 cancer patients at our outpatient chemotherapy center who were undergoing capecitabine chemotherapy. Variables related to the development of HFS were extracted from the clinical records of patients for use in regression analysis. HFS severity was assessed at the time of completing capecitabine chemotherapy. The degree of HFS was classified in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Multivariate ordered logistic regression analysis was performed to identify risk factors for the development of HFS. Results: Risk factors for the development of HFS included concomitant use of a renin-angiotensin system (RAS) inhibitor (odds ratio [OR] = 2.85, 95% confidence interval [CI] = 1.20–6.79; p = 0.018), body surface area (BSA) (high) (OR = 12.7, 95% CI = 2.29–70.94; p = 0.004), and albumin (low) (OR = 0.44, 95% CI = 0.20–0.96; p = 0.040). Discussion/Conclusion: Concomitant use of RAS inhibitor, high BSA, and low albumin were identified as risk factors for the development of HFS. The identification of potential risk factors of HFS may assist in the development of strategies that can be used to improve QoL in patients receiving chemotherapy regimens that include capecitabine. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve replacement (TAVR) has become the standard of care for most patients with severe aortic stenosis (AS), but the impact of medical therapy prescribing patterns on post-TAVR patients has not been thoroughly investigated. We analyzed Optum claims data from 9,012 adults who received TAVR for AS (January 2014-December 2018). Pharmacy claims data were used to identify patients who filled ACEI/ARB and/or statin prescriptions during the study's 90-day landmark period post-TAVR. Kaplan-Meier and adjusted Cox Proportional Hazards models were used to evaluate the association of prescribing patterns with mortality during the 3-year follow-up period. Subgroup analyses were performed to examine the impact of 11 potential confounders on the observed associations. A significantly lower adjusted 3-year mortality was observed for patients with post-TAVR prescription for ACEI/ARBs (hazard ratio [HR] = 0.82, 95% confidence interval [CI] 0.74-0.91, P =.0003) and statins (HR = 0.85, 95% CI 0.77-0.94, P =.0018) compared to patients who did not fill prescriptions for these medications post-TAVR. Subgroup analyses revealed that the survival benefit associated with ACEI/ARB prescription was not affected by any of the potential confounding variables, except preoperative ACEI/ARB prescription was associated with significantly lower risk of mortality vs postoperative prescription only. No other subgroup variables had significant interactions associated with survival benefits, including preoperative use of statins. In this large-scale, real-world analysis of patients undergoing TAVR, the prescription of ACEI/ARB and statins was associated with a significantly lower risk of mortality at 3-years, especially in those where the medications were initiated preoperatively. [ABSTRACT FROM AUTHOR]

Background and Objective: Collagen biosynthesis is intricately involved in the development and progression of solid tumors. Renin-angiotensin system inhibitors (RASi) impede TGF-β-mediated collagen synthesis in tumors by hindering activation of the angiotensin receptor. Our aim was to investigate a potential association between RASi use and the aggressiveness of prostate cancer (PCa)., Methods: We conducted a retrospective multicenter analysis for a cohort of 1250 patients with PCa who underwent radical prostatectomy (RP) between 1990 and 2023 in four European high-volume centers. The study cohort comprised 625 RASi-treated patients and 625 age-matched RASi-naïve patients. Data for various parameters were collected, including age at RP, body mass index (BMI), prostate volume, prostate-specific antigen (PSA), percentage of free PSA, Gleason score (GS) at biopsy and RP, TNM stage, and the rate of biochemical recurrence (BCR). Clinical parameters for patients with and without RASi treatment were documented. Differences between the groups were compared using a Mann-Whitney U test and χ 2 tests. Survival analyses were performed using the Kaplan-Meier method., Key Findings and Limitations: As expected, the RASi group had higher BMI levels than the RASi-naïve group ( p  < 0.001). However, RASi use was not associated with key markers of PCa aggressiveness such as GS upgrading from biopsy to RP ( p  = 0.089), surgical margin status ( p  = 0.109), and lymph node involvement ( p  = 0.33). Moreover, there were no significant differences between the groups in BCR incidence ( p  = 0.258) or the time to BCR ( p  = 0.683)., Conclusions and Clinical Implications: Our findings indicate that RASi therapy does not have a significant effect on the biological aggressiveness of PCa., Patient Summary: We analyzed data for 1250 patients with prostate cancer and found that the use of a commonly prescribed high blood pressure medication was not associated with a less aggressive form of localized prostate cancer., (© 2024 The Author(s).)

Aim: Older patients with chronic kidney disease (CKD) are more likely to be excluded from clinical trials. This exclusion affects the quality of cardiovascular disease (CVD) prevention in this population., Methods: Baseline data from the Fukuoka Kidney Disease Registry (FKR) cohort, which included 4476 adult patients with CKD stages G1-G5, were cross-sectionally analyzed to compare the use of recommended drugs for preventing CVD in each age group., Results: Different prescribing patterns were observed according to age for the cardiovascular drug classes. Older patients with CKD were less likely to receive renin-angiotensin system (RAS) inhibitors and were more likely to receive calcium channel blockers. The proportion of anticoagulation prescriptions for patients with CKD and atrial fibrillation decreased in the older age group (≥ 75 years). However, the proportion of antiplatelet therapy in patients with ischemic CVD increased linearly with age, even in the very old group aged ≥ 85 years. These findings suggest a severe cardiovascular burden in patients with CKD. Notably, RAS inhibitor use was avoided in the older group despite a severe cardiovascular burden, such as a high prevalence of CVD history and massive albuminuria ＞300 mg/g creatinine. This finding indicates that an older age independently contributed to the non-use of RAS inhibitors, even after adjusting for other covariates., Conclusions: This study suggests that age is a potential barrier to the treatment of patients with CKD and highlights the need to establish individualized treatment strategies for cardiovascular protection in this population.

Abstract Background With the expanded utilization of transcatheter aortic valve implantation (TAVI) to younger and lower surgical risk patients with severe aortic stenosis (AS), optimal medical therapy after TAVI procedure has become the main concern. Renin-angiotensin system inhibitors (RASi) are widely utilized in the area of cardiovascular disease including heart failure and myocardial infarction and revealed the ability to reverse left ventricular (LV) remodeling. Interests have, thus, been drawn in investigating whether the prescription of RASi after the TAVI procedure can prevent or reverse cardiac remodeling and improve long-term clinical outcomes. No recommendation regarding the prescription of RASi after TAVI is proposed yet due to the lack of evidence from randomized controlled trials, especially in the Chinese population. We, therefore, designed this randomized controlled trial to explore the effect of adding fosinopril to standard care in patients who underwent a successful TAVI procedure on the LV remodeling. Methods A total of 200 post-TAVI patients from seven academic hospitals across China will be recruited and randomized with a ratio of 1:1 to receive standard care or standard care plus fosinopril. Follow-up visits will take place at 30 days, 3 months, 6 months, 12 months, and 24 months from randomization to assess the clinical symptoms, any adverse events, cardiac function, and quality of life. Cardiac magnetic resonance will be performed at baseline and repeated at the 24-month follow-up visit to assess LV remodeling. Discussion This study will provide evidence regarding medical therapy for AS patients who underwent TAVI and filling the gap in the Chinese population. Trial registration Chinese Clinical Trial Registry ChiCTR2100042266 . Registered on 17 January 2021

Background: Patients with immunoglobulin A nephropathy who present with focal mesangial proliferation (focal IgAN) can have a relatively good prognosis, and renin–angiotensin system inhibitor (RAS-i) is commonly used as the initial treatment. However, there are some complicated focal IgAN cases with resistance to RAS-i treatment or nephrotic-range proteinuria. Thus, combination therapy including corticosteroids is often used. This study aimed to evaluate the efficacy of combination therapy for complicated focal IgAN cases by comparing to diffuse mesangial proliferation (diffuse IgAN). Methods: We conducted a multicenter retrospective study on 88 children who received 2-year combination therapy. The participants were classified based on pathological severity: focal IgAN (n = 26) and diffuse IgAN (n = 62). Results: In total, 26 patients with focal IgAN and 52 with diffuse IgAN achieved proteinuria disappearance within 2 years (100 vs. 83.9%, P = 0.03). Moreover, the time to proteinuria disappearance was significantly shorter in the focal IgAN group than in the diffuse IgAN group (2.9 vs. 4.2 months, P < 0.01) and all patients with focal IgAN achieved proteinuria disappearance within 8 months. At the last observation (8.6 vs. 10.4 years, P = 0.13), only patients with diffuse IgAN (n = 12) had greater than stage 2 chronic kidney disease. In terms of irreversible adverse events, one patient exhibited cataracts. Conclusion: Combination therapy was significantly effective in patients with complicated focal IgAN. Moreover, the long-term prognosis was good, and the duration of combination therapy for complicated focal IgAN can be decreased to reduce adverse events. [ABSTRACT FROM AUTHOR]

Purpose: Patients receiving vascular endothelial growth factor–tyrosine kinase inhibitors are at a risk of developing proteinuria. Renin–angiotensin system (RAS) inhibitors exert renoprotective effects and might reduce proteinuria risk in these patients. We investigated the risk factors for and protective effect of RAS inhibitors against proteinuria in patients with renal cell carcinoma (RCC) receiving axitinib. Methods: We retrospectively reviewed the medical records of patients with RCC receiving axitinib at Kobe City Medical Center General Hospital between September 2012 and October 2020. Patients with proteinuria ≥ 2+ at baseline were excluded. The patients were categorized into RAS inhibitor user, non-RAS inhibitor user, and non-user groups. The severity of proteinuria was graded based on the Common Terminology Criteria for Adverse Events, version 5.0. A multivariate Cox proportional hazards model was employed to identify the risk factors for developing grade ≥ 2 proteinuria. Results: Among 42 patients, 28 received antihypertensive drugs at baseline. Among these, 17 and 11 patients were in the RAS inhibitor and non-RAS inhibitor user groups, respectively. Twenty-three patients (54.8%) developed grade ≥ 2 proteinuria. The multivariate analysis revealed that the non-RAS inhibitor user group (P = 0.001) and patients with pre-existing grade 1 proteinuria (P = 0.022) were significantly associated with the development of grade ≥ 2 proteinuria, whereas the RAS inhibitor user group was not significantly associated with it. Conclusion: In patients with RCC receiving axitinib, pre-existing proteinuria and non-RAS inhibitor use were significantly associated with grade ≥ 2 proteinuria development. Our preliminary data should be confirmed by further studies. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting adverse side effect of treatment. CIPN affects the oncological prognosis of patients, as well as their quality of life. To date, no specific pharmacological therapy has demonstrated effectiveness in preventing CIPN. Accumulating preclinical evidence suggests that renin-angiotensin system (RAS) inhibitors may have neuroprotective effects. One hundred and twenty patients were included in this observational study and were followed from the beginning of their neurotoxic chemotherapy schedule until their final assessment, at least one month after its cessation. The National Cancer Institute's common toxicity criteria 4.0 (NCI-CTC 4.0) were used to grade the severity of adverse events. Follow-ups also included electrochemical skin conductance and scales for pain, quality of life and disability. Among patients receiving a platinum-based regimen, the mean grade of sensory neuropathy (NCI-CTC 4.0) was significantly lower in the RAS inhibitor group after the end of their anticancer treatment schedule. Because of the observational design of the study, patients in the RAS inhibitor group cumulated comorbidities at risk of developing CIPN. Randomized controlled trials in platinum-based regimens would be worth conducting in the future to confirm the neuroprotective potential of RAS inhibitors during chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: We previously reported that the concomitant use of enalapril and telmisartan exacerbates the risk of cisplatin (CDDP)-induced acute renal dysfunction compared to other antihypertensive drugs in mice. Thus, in the current study, we investigated the risk of developing chronic kidney disease following repeated concomitant use of CDDP and antihypertensive drugs. Materials and Methods: Male BALB/c mice were divided into 12 groups: (1) Control group (untreated), (2) CDDP group (7 mg/kg, CDDP), (3) AML group (5 mg/kg, amlodipine), (4) ENA group (2.5 mg/kg, enalapril), (5) TEL group (10 mg/kg, telmisartan), (6) LOS group (10 mg/kg, losartan), (7) CDDP+AML group (5 mg/mL, AML), (8) CDDP+ENA group (2.5 mg/kg, ENA), (9) CDDP+LowENA group (1.25 mg/kg, ENA), (10) CDDP+TEL group (10 mg/kg, TEL), (11) CDDP+LowTEL group (5 mg/kg, TEL), and (12) CDDP+LOS group (10 mg/kg, LOS). CDDP was administered intraperitoneally four times every 7 days, and each antihypertensive drug was administered orally from day 3 before CDDP administration until day 24 (six times a week). The degree of renal damage was assessed. The nephrotoxicity of each individual was evaluated by measuring serum creatinine and blood urea nitrogen levels. The degrees of renal fibrosis and epithelial-mesenchymal transition were also examined in kidney tissue sections. Results and Discussion: The results suggest that combinatorial treatment of CDDP and renin-angiotensin system inhibitors, particularly ENA and TEL, may exacerbate CDDP-induced nephrotoxicity. This study clearly demonstrates the need for large-scale clinical studies to construct treatment regimens that do not interfere with the therapeutic intensity of CDDP.

Ethnopharmacological Relevance: Triptolide (TP), the primary biologically active ingredient of Tripterygium wilfordii Hook F (TWHF), possesses the potential to solve the shortcomings of TWHF in treating diabetic kidney disease (DKD) in the clinic. Aim of the Study: We conducted a meta-analysis to evaluate the efficacy of TP in treating DKD and offer solid evidence for further clinical applications of TP. Materials and Methods: Eight databases (CNKI, VIP, CBM, WanFang, PubMed, Web of Science, EMBASE, and Cochrane library) were electronically searched for eligible studies until October 17, 2020. We selected animal experimental studies using TP versus renin–angiotensin system inhibitors or nonfunctional liquids to treat DKD by following the inclusion and exclusion criteria. Two researchers independently extracted data from the included studies and assessed the risk of bias with the Systematic Review Centre for Laboratory Animal Experimentation Risk of Bias tool. Fixed-effects meta-analyses, subgroup analyses, and meta-regression were conducted using RevMan 5.3 software. Inplasy registration number: INPLASY2020100042. Results: Twenty-six studies were included. Meta-analysis showed that TP significantly reduced albuminuria (14 studies; standardized mean difference SMD: −1.44 [−1.65, −1.23], I2 = 87%), urine albumin/urine creatinine ratio (UACR) (8 studies; SMD: –5.03 [–5.74, −4.33], I2 = 84%), total proteinuria (4 studies; SMD: –3.12 [–3.75, −2.49], I2 = 0%), serum creatinine (18 studies; SMD: –0.30 [–0.49, −0.12], I2 = 76%), and blood urea nitrogen (12 studies; SMD: –0.40 [–0.60, −0.20], I2 value = 55%) in DKD animals, compared to the vehicle control. However, on comparing TP to the renin–angiotensin system (RAS) inhibitors in DKD treatment, there was no marked difference in ameliorating albuminuria (3 studies; SMD: –0.35 [–0.72, 0.02], I2 = 41%), serum creatinine (3 studies; SMD: –0.07 [–0.62, 0.48], I2 = 10%), and blood urea nitrogen (2 studies; SMD: –0.35 [–0.97, 0.28], I2 = 0%). Of note, TP exhibited higher capacities in reducing UACR (2 studies; SMD: –0.66 [–1.31, −0.01], I2 = 0%) and total proteinuria (2 studies; SMD: –1.18 [–1.86, −2049], I2 = 0%). Meta-regression implicated that the efficacy of TP in reducing DKD albuminuria was associated with applied dosages. In addition, publication bias has not been detected on attenuating albuminuria between TP and RAS inhibitors after the diagnosis of DKD. Systematic Review Registration: https://clinicaltrials.gov/, identifier INPLASY2020100042 [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance: Triptolide (TP), the primary biologically active ingredient of Tripterygium wilfordii Hook F (TWHF), possesses the potential to solve the shortcomings of TWHF in treating diabetic kidney disease (DKD) in the clinic.Aim of the Study: We conducted a meta-analysis to evaluate the efficacy of TP in treating DKD and offer solid evidence for further clinical applications of TP.Materials and Methods: Eight databases (CNKI, VIP, CBM, WanFang, PubMed, Web of Science, EMBASE, and Cochrane library) were electronically searched for eligible studies until October 17, 2020. We selected animal experimental studies using TP versus renin–angiotensin system inhibitors or nonfunctional liquids to treat DKD by following the inclusion and exclusion criteria. Two researchers independently extracted data from the included studies and assessed the risk of bias with the Systematic Review Centre for Laboratory Animal Experimentation Risk of Bias tool. Fixed-effects meta-analyses, subgroup analyses, and meta-regression were conducted using RevMan 5.3 software. Inplasy registration number: INPLASY2020100042.Results: Twenty-six studies were included. Meta-analysis showed that TP significantly reduced albuminuria (14 studies; standardized mean difference SMD: −1.44 [−1.65, −1.23], I2 = 87%), urine albumin/urine creatinine ratio (UACR) (8 studies; SMD: –5.03 [–5.74, −4.33], I2 = 84%), total proteinuria (4 studies; SMD: –3.12 [–3.75, −2.49], I2 = 0%), serum creatinine (18 studies; SMD: –0.30 [–0.49, −0.12], I2 = 76%), and blood urea nitrogen (12 studies; SMD: –0.40 [–0.60, −0.20], I2 value = 55%) in DKD animals, compared to the vehicle control. However, on comparing TP to the renin–angiotensin system (RAS) inhibitors in DKD treatment, there was no marked difference in ameliorating albuminuria (3 studies; SMD: –0.35 [–0.72, 0.02], I2 = 41%), serum creatinine (3 studies; SMD: –0.07 [–0.62, 0.48], I2 = 10%), and blood urea nitrogen (2 studies; SMD: –0.35 [–0.97, 0.28], I2 = 0%). Of note, TP exhibited higher capacities in reducing UACR (2 studies; SMD: –0.66 [–1.31, −0.01], I2 = 0%) and total proteinuria (2 studies; SMD: –1.18 [–1.86, −2049], I2 = 0%). Meta-regression implicated that the efficacy of TP in reducing DKD albuminuria was associated with applied dosages. In addition, publication bias has not been detected on attenuating albuminuria between TP and RAS inhibitors after the diagnosis of DKD.Systematic Review Registration:https://clinicaltrials.gov/, identifier INPLASY2020100042

Introduction The renin-angiotensin system is associated with blood pressure regulation, inflammation, oxidative stress and insulin resistance. It can decrease intracellular oxidative stress. Stimulation with H 2 O 2 leads to increased oxidative stress and activation of the AKT/mTOR pathway. However, the role of renin-angiotensin system inhibitors in oxidative stress-induced endothelial cell dysfunction and H 2 O 2 -induced AKT activation remains unclear. Material and methods Human coronary artery endothelial cells (HCAECs) were used. The cells were treated with H 2 O 2 , captopril, the AKT inhibitor MK-2206, and the AKT activator SC79, either separately, or in combination. p53 and ICAM-1 expression, and p-eNOS, p-Akt and mTOR activation were measured by Western blot. Cell viability was assessed by MTT assay. Levels of reactive oxygen species (ROS) were assayed by flow cytometry. Proliferation was monitored by BrdU labeling, while cell migration and invasion were determined by wound healing and Transwell assays, respectively. Results The renin-angiotensin system inhibitor captopril reversed H 2 O 2 -induced oxidative stress and apoptosis in HCAECs. Co-treatment with captopril and the AKT inhibitor MK-2206 reduced the H 2 O 2 -induced P53 and ICAM-1 protein expression (p < 0.05). The proliferation, migration and invasion of HCAECs were significantly enhanced by co-treatment with captopril and MK-2206 (p < 0.05). Conclusions The study revealed the protective effect of captopril against H 2 O 2 -induced endothelial cell dysfunction through the AKT/mTOR pathway, and its enhancement of cell survival. These findings provide new insights into the protective effects of captopril and novel therapeutic approaches to treatment of cardiovascular disease.

The utilization of antihypertensive drugs plays an important role in blood pressure control among chronic kidney disease (CKD) patients. Limited information was available on how antihypertensive drugs were used among Chinese CKD patients. In the present study, the utilization of antihypertensive drugs among a subgroup of hypertensive participants with a complete record of antihypertensive drug information from the Chinese Cohort Study of Chronic Kidney Disease was analyzed. Among 2213 subjects, 61.7% and 26.5% had their blood pressure controlled to <140/90 mmHg and <130/80 mmHg, respectively. In total, 38.5% were on monotherapy. Of those patients who received combination therapy, 57.8% were treated with a two-drug combination. Renin-angiotensin system inhibitors (RASIs) were the most commonly prescribed drugs (71.2%). Only 10.2% of the patients were prescribed diuretics. After multivariable adjustment, participants taking RASI were more likely to have their blood pressure controlled to <140/90 mmHg (prevalence ratio (PR) 1.153, 95% confidence interval (CI): 1.071-1.240). CKD stage 4 (PR 0.548, 95% CI: 0.434-0.692) was associated with RASIs treatment. Additionally, diabetes (PR 1.498, 95% CI: 1.120-2.004), albumin/creatinine ratio ≥300 mg/g (PR 1.547, 95% CI: 1.020-2.344), and CKD stage 4 (PR 2.022, 95% CI: 1.223-3.343) were associated with diuretic use. The results suggested that combination therapy, diuretics use in general, and utilization of RASIs in advanced CKD stage were insufficient in the current treatment of Chinese hypertensive CKD patients. [ABSTRACT FROM AUTHOR]

Objective: To analyze perioperative blood pressure in patients undergoing transurethral resection of bladder tumor with photodynamic diagnosis. Methods: A total of 109 consecutive patients who underwent photodynamic diagnosis‐assisted transurethral resection of bladder tumor at Kanazawa University, Kanazawa, Ishikawa, Japan, were included in this study and considered as the photodynamic diagnosis group. Clinical data were collected, and perioperative systolic bladder pressure and vasopressor usage were analyzed. In contrast, consecutive patients who previously underwent conventional transurethral resection of bladder tumor (without the use of oral 5‐aminolevulinic acid) were used as the control group. Results: The systolic blood pressure before anesthesia, lowest systolic blood pressure from the anesthesia induction to the start of operation and lowest systolic blood pressure during operation were significantly lower in the photodynamic diagnosis group. The rate of vasopressor use was significantly higher in the photodynamic diagnosis group. On multivariate analysis, we found that general anesthesia and regular use of renin–angiotensin system inhibitor were associated with an increased risk of hypotension (lowest systolic blood pressure from the anesthesia induction to the start of operation <80 mmHg). Conclusions: Oral intake of 5‐aminolevulinic acid can obviously cause a drop in intraoperative blood pressure in patients undergoing transurethral resection of bladder tumor. Therefore, urologists and anesthesiologists should consider withdrawal of renin–angiotensin system inhibitors and monitor the blood pressure during photodynamic diagnosis‐assisted transurethral resection of bladder tumor. [ABSTRACT FROM AUTHOR]

Purpose Renin‐angiotensin system (RAS) inhibitors carry a risk of normotensive ischemic acute kidney injury in dehydration and concurrent nonsteroidal anti‐inflammatory drug (NSAID) use. Although the estimated number of patients with chronic kidney disease (CKD) is 20 000, Fujieda, Japan, has only three nephrologists. On 25 March 2016, we reorganized the CKD network to include pharmacists and distributed a CKD manual. We assessed effects of pharmacist participation in the CKD network and CKD manual distribution on patient hospitalizations because of drug‐related kidney injury. Methods: Changes in the prevalence of RAS inhibitor–related estimated glomerular filtration rate (eGFR) declines of greater than or equal to 30% and hyperkalemia of greater than or equal to 6.0 mEq/L in 129 hospitalized CKD patients, drug prescriptions of 14 150 hospitalized patients, and annual medical checkup data in 36 042 citizens were investigated before and after pharmacist participation. Results: After pharmacist participation, patient hospitalizations due to RAS inhibitor–related eGFR declines decreased (71.4% to 38.1%, P = .03) and hyperkalemia declined (38.1% to 9.5%, P = .03). Pharmacist participation influenced the decrease in RAS inhibitor–related eGFR declines (P = .03). NSAID prescriptions decreased (13.4% to 11.8%, P = .003) and acetaminophen prescriptions increased (6.6% to 8.0%, P = .002) among 14 150 hospitalized patients, whereas RAS inhibitor prescriptions decreased (43.2% to 39.4%, P = .002) among 6930 hospitalized patients with eGFR less than 60 mL/min/1.73 m2. A significant number of citizens shifted from CKD stage G3a‐3b to G1‐2. Conclusions: Pharmacist participation in the CKD network and CKD manual distribution decreased both hospitalizations due to RAS inhibitor–related kidney injury and citizens with CKD stage G3a‐3b. [ABSTRACT FROM AUTHOR]

Although guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) should be treated with renin-angiotensin system (RAS) inhibitors, the long-term efficacy of RAS inhibitors in HFrEF patients with moderate-to-severe chronic kidney disease (CKD) remains unclear. The present study included consecutive patients hospitalized for acute heart failure across five Japanese teaching hospitals. The impact of RAS inhibitors on 2-year all-cause mortality was evaluated in patients with an ejection fraction ≤40% and CKD, defined as an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2, at discharge. Its severity was subclassified from 3B to 5 according to eGFR. Overall, 553 patients (age, 76 ± 11 years; 68% male) were included. RAS inhibitors were prescribed more frequently in 227 patients with stage 3B (71.2%) than in 107 patients with stage 4 or 5 CKD (45.7%). All-cause mortality was recorded in 119 patients (23.4%) (55 [18.5%] patients with stage 3B; 64 [30.3%] patients with stage 4 or 5 CKD), within the median follow-up period of 609 (220–983) days. After many-to-one propensity score matching (87 pairs in stage 3; 60 pairs in stage 4 or 5 CKD), those with RAS inhibitors had reduced mortality rate in stage 3B (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.19–0.83) but not in stage 4 or 5 CKD (HR, 1.08; 95% CI, 0.57–2.03). In HFrEF patients with CKD, RAS inhibitors are associated with reduction in mortality in stage 3B CKD, but the association is less clear in stage 4 or 5 CKD. • Long-term mortality remains high in heart failure patients with reduced EF and CKD. • RAS inhibitors are associated with lower mortality in stage 3B CKD patients. • A relation between the agents and prognosis is unclear in stage 4 or 5 CKD patients. [ABSTRACT FROM AUTHOR]

Introduction: The renin-angiotensin system is associated with blood pressure regulation, inflammation, oxidative stress and insulin resistance. It can decrease intracellular oxidative stress. Stimulation with H2O2 leads to increased oxidative stress and activation of the AKT/mTOR pathway. However, the role of renin-angiotensin system inhibitors in oxidative stress-induced endothelial cell dysfunction and H2O2-induced AKT activation remains unclear.Material and Methods: Human coronary artery endothelial cells (HCAECs) were used. The cells were treated with H2O2, captopril, the AKT inhibitor MK-2206, and the AKT activator SC79, either separately, or in combination. p53 and ICAM-1 expression, and p-eNOS, p-Akt and mTOR activation were measured by Western blot. Cell viability was assessed by MTT assay. Levels of reactive oxygen species (ROS) were assayed by flow cytometry. Proliferation was monitored by BrdU labeling, while cell migration and invasion were determined by wound healing and Transwell assays, respectively.Results: The renin-angiotensin system inhibitor captopril reversed H2O2-induced oxidative stress and apoptosis in HCAECs. Co-treatment with captopril and the AKT inhibitor MK-2206 reduced the H2O2-induced P53 and ICAM-1 protein expression (p < 0.05). The proliferation, migration and invasion of HCAECs were significantly enhanced by co-treatment with captopril and MK-2206 (p < 0.05).Conclusions: The study revealed the protective effect of captopril against H2O2-induced endothelial cell dysfunction through the AKT/mTOR pathway, and its enhancement of cell survival. These findings provide new insights into the protective effects of captopril and novel therapeutic approaches to treatment of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Renin-angiotensin system inhibitor and calcium channel blocker (CCB) are widely used in controlling blood pressure (BP) in patients with chronic kidney disease (CKD). We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and CCB (i.e., ACEI/ARB + CCB) with ACEI/ARB monotherapy in patients with hypertension and CKD. Methods: Publications were identified from PubMed, Embase, Medline, and Cochrane databases. Only randomized controlled trials (RCTs) of BP lowering treatment for patients with hypertension and CKD were considered. The outcomes of end-stage renal disease (ESRD), cardiovascular events, BP, urinary protein measures, estimated glomerular filtration rate (GFR), and adverse events were extracted. Results: Based on seven RCTs with 628 patients, ACEI/ARB + CCB did not show additional benefit for the incidence of ESRD (risk ratio [RR] = 0.84; 95% confidence interval [CI]: 0.52–1.33) and cardiovascular events (RR = 0.58; 95% CI: 0.21–1.63) significantly, compared with ACEI/ARB monotherapy. There were no significant differences in change from baseline to the end points in diastolic BP (weighted mean difference [WMD] = −1.28 mmHg; 95% CI: −3.18 to −0.62), proteinuria (standard mean difference = −0.55; 95% CI: −1.41 to −0.30), GFR (WMD = −0.32 ml/min; 95% CI: −1.53 to −0.89), and occurrence of adverse events (RR = 1.05; 95% CI: 0.72–1.53). However, ACEI/ARB + CCB showed a greater reduction in systolic BP (WMD = −4.46 mmHg; 95% CI: −6.95 to −1.97), compared with ACEI/ARB monotherapy. Conclusion: ACEI/ARB + CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.

Introduction: The long-term impact of renin-angiotensin system (RAS) inhibitors for secondary prevention in patients with chronic kidney disease (CKD) and coexisting coronary artery disease remains unclear., Methods: Altogether, 1,160 consecutive patients with CKD (mean age, 70 ± 9 years; 78% men) who underwent their first percutaneous coronary intervention (PCI) between 2000 and 2018 were included and analyzed. Based on their RAS inhibitor use, 674 patients (58%) were allocated to the RAS inhibitor group, and 486 patients (42%) were allocated to the non-RAS inhibitor group. This study evaluated the incidence of 3-point major adverse cardiovascular events (3P-MACE), including cardiovascular death, nonfatal acute coronary syndrome and nonfatal stroke, admission for heart failure (HF), target vessel revascularization (TVR), and all-cause death., Results: During a median follow-up duration of 7.8 years, 280 patients (24.1%) developed 3P-MACE, 134 patients (11.6%) were hospitalized for HF, 171 patients (14.7%) underwent TVR, and 348 patients (30.0%) died of any causes. The cumulative incidence rate of 3P-MACE in the RAS inhibitor group was significantly lower than in the non-RAS inhibitor group (31.7% vs. 39.0%, log-rank test, p = 0.034); however, that of admission for HF in the RAS inhibitor group was significantly higher than in the non-RAS inhibitor group (28.1% vs. 13.3%, log-rank test, p < 0.001). The subgroup of preserved ejection fraction, non-acute myocardial infarction, and non-proteinuria tended to promote the onset of HF rather than cardiovascular prevention by RAS inhibitors., Conclusion: The long-term RAS inhibitor use for patients with CKD after PCI might prevent cardiovascular events but increase the risk of HF., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Aims In heart failure with reduced ejection fraction (HFrEF), renin–angiotensin system inhibitors (RASi) improve morbidity and mortality. However, patients aged >80 years constituted a small minority in trials. We assessed the association between RASi use and mortality/morbidity in HFrEF patients aged >80 years. Methods and results We included patients with ejection fraction <40% and age >80 years from the Swedish Heart Failure Registry. Propensity scores for RASi use were calculated from 37 variables. Cox regression models for RASi vs. non-RASi with all-cause mortality and all-cause mortality/heart failure (HF) hospitalization as outcomes were fitted in a 1:1 propensity-score-matched cohort. To assess consistency, the same analyses were performed in a 'positive control' cohort aged ≤80 years. Of 6710 patients [median age (interquartile range) 85 (82–87) years; 38% women], 5384 (80%) received RASi. Propensity-score matching yielded 2416 patients, [age 86 (83–91) years]. RASi use was associated with hazard ratio (HR) (95% confidence interval) 0.78 (0.72–0.86) for all-cause mortality and 0.86 (0.79–0.94) for all-cause mortality/HF hospitalization. In positive control patients aged ≤80 years (17 842 patients in the overall cohort, 2126 after matching), HR for all-cause mortality was 0.81 (0.71–0.91), whereas it was 0.85 (0.76–0.94) for all-cause mortality/HF hospitalization. Conclusion In HFrEF patients with age >80 years, RASi were relatively underused compared with in younger patients, despite similar association with reduced morbidity and mortality and no apparent association with risk of syncope-related hospitalization. These results may be interpreted as hypothesis generating for randomized clinical trials on RASi in this elderly HFrEF subpopulation. View large Download slide View large Download slide [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to investigate the effect of renin-angiotensin system inhibitors (RASIs) on bevacizumab (BV)-induced proteinuria in non-small cell lung cancer (NSCLC) patients.Materials and Methods: We retrospectively reviewed the medical records of NSCLC patients receiving BV between 2008 and 2014 at 11 hospitals. The patients were categorized into three groups according to their antihypertensive drug use: RASI user, non-RASI user, and non-user groups. The primary outcome was a proteinuria event of any grade during the first 6 cycles of BV treatment.Results: A total of 211 patients were included, 89 of whom received antihypertensive drugs. Of these 89 patients, 49 were in the RASI user group, and 40 were in the non-RASI user group. The non-user group comprised 122 patients. The occurrence of proteinuria in the RASI user group was significantly lower than that in the non-RASI user group (P = 0.037) but was not significantly lower than that in the non-user group (P = 0.287). Patients using RASIs had a lower rate of proteinuria than those who did not use RASIs according to multivariate analysis (odds ratio 0.32; 95% confidence interval 0.12-0.86; P = 0.024).Conclusion: Our study suggests that RASI administration reduces the risk of proteinuria in patients receiving BV. [ABSTRACT FROM AUTHOR]

Aims: We examined whether the use of a renin-angiotensin-aldosterone system (RAS) inhibitor plays a role in protecting against left atrial appendage thrombus (LAAT) in patients with hypertension complicated by atrial fibrillation (AF). Methods: Two observational studies were conducted on patients with diagnoses of hypertension and AF, who were categorized into RAS inhibitor user or nonuser groups. Demographic characteristics, clinical characteristics, echocardiographic parameters and hemostatic markers were examined and the occurrence of LAAT during follow-up were recorded. Results: In the first study (n = 131), LA peak systolic strain and LAA emptying flow velocity (LAA eV) were significantly increased in patients on RAS inhibitors compared with the nonuser group (p < 0.05). Lower D-dimer and fibrinogen levels were observed in patients on RAS inhibitors (p < 0.05). In the second study (n = 99), 25.9% (n = 11) of patients on RAS inhibitors developed LAAT, compared with 46.7% (n = 21) in the nonuser group (p < 0.05). After controlling for risk factors related to LAAT, use of RAS inhibitors remained associated with a significantly lower risk of developing LAAT (HR, 0.406; 95% CI, 0.191–0.862; p = 0.019). Conclusions: RAS inhibitors use was associated with a significant reduction in the risk of LAAT in patients with hypertension and AF. [ABSTRACT FROM AUTHOR]

Definitive evidence of whether renin angiotensin system (RAS) inhibition is beneficial on cardiovascular events (CVE) among patients undergoing hemodialysis (HD) is lacking. The objective of this study was to investigate the association of RAS inhibitor usage with CVEs in patients enrolled in the Dialysis Outcomes Practice Pattern Study in Japan (J-DOPPS). Association of RAS inhibitor prescription with outcomes including all-cause death, death caused by CVE, and hospitalization due to cardiac failure was investigated by using a multivariable Cox proportional hazards model. Of the 3848 patients enrolled, 1784 (45%) patients were treated by RAS inhibitors. After adjusting for potential cofounders by Cox proportional hazards models, we found a statistically insignificant but positive association of RAS inhibitor usage with death caused by CVE (HR: 1.46, 95%CI: 0.96-2.23, P = 0.08). Similar results were observed in the association of RAS inhibitor with all-cause death, hospitalization due to cardiac failure, and hospitalization due to CV disease (HR for all-cause death: 1.24, 95%CI: 0.84-1.48, P = 0.28, HR for hospitalization due to cardiac failure: 1.24, 95%CI: 0.84-1.81, P = 0.28, and HR for hospitalization due to CV disease: 1.20, 95%CI: 0.95-1.51, P = 0.13). Sensitivity analyses using propensity scores gave similar results. RAS inhibition did not show favorable association with CVEs suggesting that RAS inhibition alone was insufficient to reduce the risk of CV complications in patients undergoing HD. Some strategies in addition to RAS inhibition may be needed to protect against CVEs in this population. [ABSTRACT FROM AUTHOR]

Although renin-angiotensin system (RAS) inhibitors reduce the risk of cardiovascular diseases and end-stage kidney disease (ESKD) in chronic kidney disease (CKD) patients, they are often discontinued in clinical practice due to drug-related adverse events. However, limited evidence is available about the clinical impact of RAS inhibitor discontinuation in CKD patients. A comprehensive search of publications investigating the effect of discontinuing RAS inhibitors on clinical outcomes in CKD patients in PubMed, the Cochrane Library, and Web of Science was conducted (inception to November 7, 2022), and potentially relevant studies were searched by hand (through November 30, 2022). Two reviewers independently extracted data according to the PRISMA and MOOSE guidelines and assessed the quality of each study with risk-of-bias tools, RoB2 and ROBINS-I. The pooled hazard ratio (HR) for each outcome was integrated with a random-effect model. A total of 1 randomized clinical trial and 6 observational studies involving 248,963 patients were included in the systematic review. The meta-analysis of observational studies showed that discontinuation of RAS inhibitors was associated with a higher risk of all-cause mortality (HR, 1.41 [95% CI, 1.23-1.62]; I 2  = 97%), ESKD (1.32 [95% CI, 1.10-1.57]; I 2  = 94%) and MACE (1.20 [95% CI 1.15-1.25]; I 2  = 38%), but not with hyperkalemia (0.79 [95% CI 0.55-1.15]; I 2  = 90%). Overall risk of bias was moderate-to-serious, and quality of evidence (GRADE system) was low-to-very low. The present study suggests that CKD patients would benefit from continuing RAS inhibitors., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Inhibition of the renin-angiotensin system (RAS) has been used to treat diabetic nephropathy. However, RAS inhibition increases the risk of renal complications. In this study, we evaluated the effect of combining RAS inhibitor treatment with beraprost sodium (BPS), a prostaglandin I2 analog, in diabetic nephropathy with arteriosclerosis obliterans. Methods: This study was a prospective, randomized, open-label study. Twenty-six Japanese patients (age >30 years) with diabetic nephropathy and arteriosclerosis obliterans were randomly assigned to the BPS group (n=13), which received the combination of an RAS inhibitor and BPS (120 µg/day) therapy, or the control group (n=13), which received only an RAS inhibitor. Patients were followed up for 1 year. The primary endpoint was the effect of BPS on renal function. Results: In the control group, serum creatinine (1.64±0.87 to 2.34±1.53 mg/dL, p<0.001), 1/creatinine (0.82±0.47 to 0.65±0.47, p=0.003) cystatin C (1.77±0.61 to 2.18±0.86 mg/L, p<0.001), and the estimated glomerular filtration rate (43.9±26.1 to 34.0±24.6 mL/min/1.73 m², p=0.004) were significantly worsened 48 weeks after the start of treatment. Conversely, in the BPS group, serum creatinine (1.71±0.75 to 1.66± 0.81 mg/dL, p=0.850), 1/creatinine (0.66±0.19 to 0.71±0.25, p=0.577), cystatin C (1.79±0.55 to 1.80±0.57 mg/L, p=0.999), and the estimated glomerular filtration rate (35.8±10.8 to 38.7±14.4 mL/min/1.73 m², p= 0.613) were unchanged. Conclusions: Combination treatment with BPS and an RAS inhibitor prevented the progression of diabetic nephropathy. These observations should be confirmed in large-scale studies with long-term followup. [ABSTRACT FROM AUTHOR]

Background/Aims: The purpose of our study was to elucidate the relationship between asymmetric dimethylarginine (ADMA) and intrarenal lesions and to determine the effect of renin-angiotensin system inhibitors (RAS-Is) on serum ADMA levels, nitric oxide (NO) synthesis and oxidative stress in normotensive patients with chronic kidney disease (CKD). Methods: This study included 23 normotensive patients with chronic glomerulonephritis and normal or mildly impaired renal function who underwent renal biopsy. We evaluated the relationship between serum ADMA levels and intrarenal lesions, and examined renal function, urinary protein excretion, ADMA levels, NO synthesis, oxidative stress and blood pressure (BP) before and 3 months after starting the treatment with RAS-Is. Results: Serum ADMA levels were correlated only with arterial intimal fibroplastic thickness. Despite comparable renal function and BP, serum ADMA levels and excretion of urinary protein excretion significantly decreased, and urinary NO metabolite excretion significantly increased after starting the treatment with RAS-Is. Oxidative stress markers also tended to be reduced by the treatment. Conclusion: These findings suggest that RAS-Is improve the NO system and decrease oxidative stress in normotensive patients with CKD. In addition, ADMA may be associated with intrarenal lesions and can be a useful marker for the effects of treatment in the early stages of CKD. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]