Use Of Renin-angiotensin System Blockers Research Articles

Real world treatment of hypertension on hemodialyses-data from large Polish database.

The prevalence of hypertension among patients with end stage kidney disease (ESKD) undergoing hemodialysis (HD) ranges from 72-88% depending on applied diagnostic criteria and chosen method of blood pressure measurement. Despite the guidelines recommending the widespread use of renin angiotensin system blockers (RASB) in patients with kidney disease, their utilization in patients on HD may be suboptimal, especially in patients with preserved diuresis. This hesitance often steams from concern is often due to fear of a decrease in eGFR and a subsequent decrease in diuresis. The aim of this study was to compare clinical characteristics, blood pressure, safety, and hemodialysis adequacy indices in hypertensive HD patients on multiple antihypertensive drug regimens, including diuretic treated with RASB (RASB group) or without RASB (no-RASB) with preserved residual diuresis. We sought to examine the real life use of RASB in hemodialysis patients in relation to their clinical characteristics, blood pressure, safety, and hemodialysis adequacy. From a database of 5879 patients receiving hemodialysis (mean age 65.2±14.2 yrs., 60% of males) of the largest provider of HD in the country, we selected the subgroup treated with at least three antihypertensive medications including diuretics. We compared patients treated with RASB to counterparts without RASB (no-RASB). RASB group has similar age and gender proportions as well as BMI and bioimpedance,compared to counterparts. However, dry body mass was significantly lower in the RASB group (78.1±18.3 kg vs. 80.0±18.2 kg, p<0.017). Prevalence of diabetes mellitus was similar in both groups, but RASB-treated patients have cardiovascular diseases more frequently (70.1% vs. 60.8%; p<0.001). Systolic blood pressure and the number of antihypertensive drugs used were significantly higher in RASB patients than in counterparts (146±16 mmHg vs. 144±15 mmHg; p<0.001 and 4.1±0.9 vs. 3.5±0.5; p<0001 respectively). RASB-treated patients have significantly longer dialysis vintage (52.7±44.4 months vs. 40.2±40.9 months; p<0.001) and dialysis time (722±87.1 min./week vs. 713±93.4 min./week;p<0.017) than counterparts. Serum potassium was slightly but significantly higher in RASB (5.3±0.8 mmol/L vs. 5.1±0.7 mmol/L;p<0.01). In the real world setting, RASB can be safely used in HD patients treated with diuretics with preserved residual diuresis. Given that many HD patients present numerous multimorbidities, RASB should not only be considered as an additional hypotensive drug in poorly controlled hypertension but also in other compelling indications in HD patients. The tendency toward hyperkalemia in HD patients could be effectively managed with appropriate diet and HD prescription adjustments.

#1485 Hypertension management of CKD patients referred to Hypertension Excellence centres in 27 countries: on behalf of the ESH Hypertension and Kidney WG

Abstract Background and Aims Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear and may vary across countries. Our aim was to identify unmet needs and heterogeneity of management in this population of patients in Europe and the Middle-East through our network of European Society of Hypertension (ESH) Excellence Centers. Method A survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate pre-existing CKD management quality and data for their management are reported here. Results Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 (75.0%)). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had pre-existing CKD, of whom 10% (5- 30%) were previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine Albumin- Creatinine Ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates for SGLT2 inhibitors (27.5% (20-40%) vs 15% (10-25), p = 0.003), GLP1-RA (10% (10-20%) vs 5% (5-10%), p = 0.003) and mineralocorticoid receptor antagonists (20% (10-30%) vs 15% (10-20%), p = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across centres in Europe countries and in the Middle East. Conclusion Our results indicate deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across centres. This information can be used to build specific programs to improve care in hypertensives with CKD.

Screening and management of hypertensive patients with chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. A pilot survey based on questionnaire.

Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear. A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality. Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries. Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD.

Dihydropyridine Calcium Channel Blockers and Kidney Outcomes.

Early trials of dihydropyridine calcium channel blockers (DCCBs) suggest a detrimental effect on intraglomerular pressure and an association with albuminuria. We sought to evaluate the associations of DCCB initiation with albuminuria and kidney failure with replacement therapy (KFRT) and to determine whether renin-angiotensin system (RAS) blockade modified these associations. We conducted a target trial emulation study using a new user, active comparator design and electronic health record data from Geisinger Health. We included patients without severe albuminuria or KFRT who were initiated on a DCCB or thiazide (active comparator) between January 1, 2004, and December 31, 2019. Using inverse probability of treatment weighting, we performed doubly robust Cox proportional hazards regression to estimate the association of DCCB initiation with incident severe albuminuria (urine albumin to creatinine ratio > 300 mg/g) and KFRT, overall and stratified by RAS blocker use. There were 11,747and 26,758 eligible patients initiating a DCCB and thiazide, respectively, with a weighted baseline mean age of 60 years, systolic blood pressure of 143 mm Hg, and eGFR of 86 mL/min/1.73 m2, and with a mean follow-up of 8 years. Compared with thiazides, DCCBs were significantly associated with the development of severe albuminuria (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.16-1.43), with attenuation of risk in the presence of RAS blockade (P for interaction < 0.001). The risk of KFRT was increased among patients without RAS blockade (HR, 1.66; 95% CI, 1.19-2.31), but not with RAS blockade (P for interaction = 0.005). DCCBs were associated with increased risk of albuminuria and, in the absence of RAS blockade, KFRT. These findings suggest coupling DCCB therapy with RAS blockade may mitigate adverse kidney outcomes.

Effect of angiotensin-converting enzyme inhibitors versus that of angiotensin receptor blockers on survival in patients undergoing hemodialysis: a nationwide observational cohort study

Background This study aimed to evaluate the patient survival rates based on the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in a large cohort of patients undergoing maintenance hemodialysis (HD). Methods Data from a national HD quality assessment program were used in this retrospective study. The patients were classified into four groups based on the use of renin-angiotensin system blockers (RASBs) as follows: No group, patients without a prescription of any anti-hypertensive drugs including RASBs; Other group, patients with a prescription of anti-hypertensive drugs excluding RASBs; ACEI group, patients with a prescription of an ACEI; and ARB group, patients with a prescription of an ARB. Results The 5-year survival rates in the no, other, ACEI, and ARB groups were 68.6%, 67.8%, 70.6%, and 69.2%, respectively. The ACEI group had the best patient survival trend among the four groups. In multivariable Cox regression analyses, no differences were observed between the ACEI and ARB groups. Among young patients and patients without diabetes or heart disease, the ACEI group had the best patient survival among the four groups. However, among patients with DM or heart disease, the ARB group had the best patient survival. Conclusions Our study found that patients receiving ACEI and ARB had comparable survival. However, patients receiving ARB had better survival in the subgroups of patients with DM or heart disease, and patients receiving ACEI had better survival in the subgroup of young patients or patients without diabetes or heart disease.

The concomitant use of the renin-angiotensin system inhibitors and survival outcomes of patients with pancreatic adenocarcinoma: an analysis from a tertiary center.

The limited efficacy of chemotherapy in improving survival in pancreatic ductal adenocarcinoma (PDAC) necessitates the exploration of novel strategies to overcome treatment resistance. This study aimed to investigate the impact of combining renin-angiotensin system (RAS) blockers with chemotherapy on survival outcomes in patients with PDAC. Patients with PDAC were enrolled in the retrospective study. We analyzed patients with PDAC (n = 384) at our institution between 2014 and 2021. Survival outcomes, including event-free survival (EFS) and overall survival (OS), were analyzed according to the concomitant use of RAS blockers. Among the 384 patients in the study, 70 (18.2%) concomitantly received angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Patients in the ACEI/ARB group, characterized by older age and more comorbidities, displayed a significantly superior 12-month EFS rate (22.86% versus 13.69%, p = 0.008) compared to the non-ACEI/ARB group, while OS remained similar between the groups. In the multivariate analysis, the use of ACEI/ARB was associated with better 12-month EFS (hazards ratio = 0.71, 95% confidence interval: 0.52-0.96; p = 0.024). Poor performance, advanced disease status, and higher CA19-9 levels were associated with poor survival outcomes. Concomitant use of ACEIs/ARBs in patients with pancreatic cancer resulted in significantly better 12-month EFS. Age, performance status, disease status, and higher CA19-9 levels were independent predictors of survival. The combination strategy might provide better treatment outcomes in patients with PDAC.

Efficacy and safety of finerenone in chronic kidney disease and type 2 diabetes patients: a systematic review and meta-analysis.

The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease. The current guidelines recommend the use of renin-angiotensin system blockers, but recent studies probed into the effects of finerenone to mitigate the risk of cardiorenal events. This meta-analysis was performed to demonstrate the effects of finerenone on cardiorenal events, comprising cardiovascular mortality, heart failure, change in estimated glomerular filtration rate, and serum potassium levels. After screening with our eligibility criteria, 350 articles were identified with an initial literature search on multiple databases, including PubMed, Science Direct, and Cochrane Central. Seven randomized controlled trials with a total of 15462 patients (n=8487 in the finerenone group; n=6975 in the control group) were included. Patients receiving finerenone were at a reduced risk for cardiovascular mortality [HR: 0.84 (0.74, 0.95)], heart failure [OR: 0.79 (0.68, 0.92)], decrease in estimated glomerular filtration rate by 40% [OR: 0.82 (0.74, 0.91)] and by 57% [OR: 0.70 (0.59, 0.82)]; and a higher incidence of moderate hyperkalemia [OR: 2.25 (1.78, 2.84)]. Finerenone, owing to its better mineralocorticoid affinity, and a much lower risk of adverse effects, promises to be a much better alternative than other renin-angiotensin system blockers available for the treatment of chronic kidney disease patients with type 2 diabetes. Further trials should be conducted to provide more definitive evidence to assess the safety and efficacy of finerenone compared to spironolactone and eplerenone.

Effect of components of the renin-angiotensin system, rs2106809 polymorphism of the ACE2 gene, and therapy with RAS blockers on the severity of COVID-19

Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS), providing counter-regulation of its effects and, simultaneously, a receptor for the SARS-CoV-2 entering. It is suggested that factors regulating the balance of the major components of RAS, including ACE2 gene polymorphism, therapy with RAS blockers (ACE inhibitors and angiotensin receptor blockers) - may affect the severity of COVID-19. The aim of the study was to investigate the effect of RAS components, the relationship of ACE2 gene polymorphism rs2106809 and ACEi/ARBs therapy with the COVID-19 severity. The study included patients with COVID-19 hospitalized in Endocrinology research centre (n = 173), who were divided into groups of moderate and severe course. Determination of RAS components was performed by ELISA, identification of polymorphism by PCR. Statistical analysis was performed using nonparametric statistical methods; differences in the distribution of genotype frequencies were assessed using Fisher's exact test χ2. The groups differed significantly in age, blood glucose levels, and inflammatory markers: leukocytes, neutrophils, IL-6, D-dimer, C-reactive protein, ferritin and liver enzymes, which correlated with the severity of the disease. When comparing patients in terms of ACE, ACE2, angiotensin II, ADAM17 there were no statistically significant differences between the groups (p=0.544, p=0.054, p=0.836, p=1.0, respectively), including the distribution by gender (in men: p=0.695, p=0.726, p=0.824, p=0.512; in women: p=0.873, p=0.196, p=0.150, p=0.937). Analysis of the distribution of AA, AG, and GG genotypes of the rs2106809 polymorphism of the ACE2 gene also revealed no differences between patients: χ2 1.35, p=0.071 in men, χ2 5.28, p=0.244 in women. There were no significant differences in the use of RAS blockers between groups with different course severity: χ2 0.208, p=0.648 for ACEi, χ2 1.15, p=0.283 for ARBs. In our study, the influence of activation of RAS components (ACE, ACE2, AT II, ADAM17) and ACE2 gene polymorphism on the severity of COVID-19 course was not confirmed. The severity of COVID-19 course correlated with the level of standard inflammatory markers, indicating the general principles of the infection as a systemic inflammation, regardless of the genetic and functional status of the RAS.

Glucocorticoids for the treatment of IgA nephropathy: pros and cons. Research data and own experience

IgA nephropathy is the most common pattern of primary glomerular diseases worldwide and remains a leading cause of chronic kidney disease and kidney failure. The incidence of IgA nephropathy is 2.5 per 100,000 population per year. Presentation ranges from isolated haematuria to significant proteinuria, acute kidney injury and even chronic kidney disease. The 10-year risk of progression to end stage kidney disease or halving of GFR is 26 %. The basis of management of IgA nephropathy is goal-directed supportive care in the form of rigorous blood pressure control, use of renin-angiotensin system blockers in the maximum tolerated dose, and a focus on life-style modification that includes smoking cessation, weight management, and restriction of sodium intake. Ho­wever, supportive therapy does not always achieve its goals and cannot affect the autoimmune pathogenesis of the disease, while the role of immunosuppressants and systemic glucocorticoids remains controversial. This review presents an analysis of clinical trials and our own experience regarding the role of steroids and supportive therapy in the treatment of IgA nephropathy.

Lost in translation: assessing the nomenclature change for diabetic kidney disease in Japan.

Recently in Japan, the term "tonyobyo sei jinzobyo", the Japanese translation of "diabetic kidney disease", has been increasingly used in place of the term "tonyobyo sei jinsho", the Japanese translation of "diabetic nephropathy". Many international diabetes and nephrology guidelines have defined diabetic kidney disease as a condition caused by diabetes, typically presenting with albuminuria, similar to or identical to current and historical definitions for diabetic nephropathy. However, recent guidelines from the Japanese Society of Nephrology propose a broader disease concept for the term diabetic kidney disease, including patients without albuminuria. A rationale for proposing a broader disease concept for diabetic kidney disease may have come from changes in the kidney phenotype of patients with diabetes observed in recent years. Epidemiological studies have shown that an increasing proportion of patients with diabetes have reduced kidney function, while the prevalence of those with albuminuria appears to have decreased. However, these studies also suggested that the more advanced age of patients presenting with diabetes and increased use of renin-angiotensin system blockers may have contributed to this change in disease phenotype. We believe the principal rationale for the nomenclature change from diabetic nephropathy to diabetic kidney disease was to create a more easily understood, lay-language term for English speakers, rather than to create a term to encompass a broader population of diabetes with chronic kidney disease (CKD). Further discussion and international consensus are needed for the definition of diabetic kidney disease, to avoid ambiguity or possible confusion.

Survival Benefit of Renin-Angiotensin System Blockers in Critically Ill Cancer Patients: A Retrospective Study.

Increasing evidence argues for the promotion of tumorigenesis through activation of the renin-angiotensin system pathway. Accordingly, a benefit of renin-angiotensin system blockers (RABs) treatments has been suggested in patients with solid cancers in terms of survival. We aimed to evaluate in-ICU survival and one-year survival in cancer patients admitted to the ICU with respect to the use of RABs. We conducted a retrospective observational single-center study in a 24-bed medical ICU. We included all solid cancer patients (age ≥ 18 years) requiring unplanned ICU admission. From 2007 to 2020, 1845 patients with solid malignancies were admitted (median age 67 years (59-75), males 61.7%). The most frequent primary tumor sites were the gastrointestinal tract (26.8%), the lung (24.7%), the urological tract (20.1%), and gynecologic and breast cancers (13.9%). RABs were used in 414 patients, distributed into 220 (53.1%) with angiotensin-receptor blockers (ARBs) and 194 (46.9%) with angiotensin-converting enzyme inhibitors (ACEis). After multivariate adjustment, ARBs use (OR = 0.62, 95%CI (0.40-0.92), p = 0.03) and ACEis use (OR = 0.52, 95%CI (0.32-0.82), p = 0.006) were both associated with improved in-ICU survival. Treatment with ARBs was independently associated with decreased one-year mortality (OR = 0.6, 95%CI (0.4-0.9), p = 0.02), whereas treatment with ACEis was not. In conclusion, this study argues for a beneficial impact of RABs use on the prognosis of critically ill cancer patients.

CLINICAL AND DEMOGRAPHIC DETERMINANTS OF PULSE WAVE VELOCITY TRAJECTORIES IN HYPERTENSIVE PATIENTS: A RETROSPECTIVE STUDY

Objective: Arterial stiffness (AS) is a strong predictor of cardiovascular disease and all-cause mortality. Its behaviour over time, assessed through repeated measurements, is still largely unexplored. The aim of this study was to assess the clinical and demographic determinants of trajectories of carotid-femoral pulse wave velocity (cf-PWV) in a cohort of French hypertensive adults. Design and method: From a population of 7806 patients referred to HEGP Pharmacology Unit (Paris, France) from 1981 to 2022, we selected those who had at least 3 cf-PWV recordings over time. Those with missing treatment information or rare vascular diseases were excluded. Cluster of trajectories analysis was performed and multinomial regression was used to detect differences in baseline characteristics between the identified clusters. Results: 564 patients were included in the analysis (median follow-up was 4.2 [3.2-6.4] years). Four clusters of stiffness trajectories were identified: low-stable (A, n = 199), medium-stable (B, n = 184), high-increasing (C, n = 127), and high-low-high (D, n = 54) clusters (Figure 1). Mean BP (MBP) and cf-PWV at baseline were progressively higher in the medium-stable, high-increasing, and high-low-high clusters compared to the stable one (MBP was 96 ± 12, 99 ± 12 and 101 ± 15 mmHg in clusters B, C, and D vs 92 ± 12 mmHg in cluster A; cf-PWV was 9.7 ± 1.2, 11.6 ± 1.6 and 15.3 ± 2.7 m/s in clusters B, C, and D vs 7.7 ± 1.0 m/s in cluster A; all p &lt; 0.001). On multinomial regression analysis, older age, higher MBP, and diabetes were associated to increased probability of belonging to either C or D clusters when compared to the stable one. Anti-hypertensive treatment with blockers of renin-angiotensin system (RAS) was associated with a decreased probability of belonging to the C or D clusters (Table 1). Conclusions: This real-life data obtained by repeated cf-PWV assessments on a large time span shows that patients who will experience PWV worsening over time are characterized by older age, higher MBP and diabetes at baseline. The use of RAS blockers has a protective effect on PWV trajectories.

Association of Renin-Angiotensin System Blockers with Survival in Patients on Maintenance Hemodialysis.

Additional studies are needed to confirm whether the use of renin-angiotensin system blockers (RASBs) induces survival benefits in patients on hemodialysis (HD). This study aimed to evaluate patient survival with the use of RASBs in a large sample of maintenance HD patients. This study used data from the national HD quality assessment program and claim data from South Korea (n = 54,903). A patient using RASBs was defined as someone who had received more than one prescription during the 6 months of each HD quality assessment period. The patients were divided into three groups as follows: Group 1, no prescription for anti-hypertensive drugs; Group 2, prescription for anti-hypertensive drugs other than RASBs; and Group 3, prescription for RASBs. The five-year survival rates in Groups 1, 2, and 3 were 72.1%, 64.5%, and 66.6%, respectively (p < 0.001 for Group 1 vs. Group 2 or 3; p = 0.001 for Group 2 vs. Group 3). Group 1 had the highest patient survival rates among the three groups, and Group 3 had higher patient survival rates compared to Group 2. Group 3 had higher patient survival rates than Group 2; however, the difference in patient survival rates between Group 2 and Group 3 was relatively small. Multivariate Cox regression analyses showed similar trends as those of univariate analyses. The highest survival rates from our study were those of patients who had not used anti-hypertensive drugs. Between patients treated with RASBs and those with other anti-hypertensive drugs, patient survival rates were higher in patients treated with RASBs.

Factors associated with the progression of mesangial lesions in IgA nephropathy: A comparative analysis of renal re-biopsies.

IgA nephropathy (IgAN) is the most common primary glomerular disease, and is the leading cause of chronic renal failure. Because mesangial lesions are the main pathological changes seen in IgAN, we investigated factors associated with the progression of mesangial lesions in IgAN. We enrolled participants with IgAN who underwent repeat renal biopsies. Based on the progression of mesangial proliferative lesions, the participants were divided into progressive and stable groups. The progression group included participants with a ratio of mesangial cell proliferation score ≥ 1.1 (i.e., proliferation of > 10%) in the second biopsy specimen compared to the first biopsy specimen. The stable group included participants who did not fulfill the aforementioned criteria. We recorded the laboratory parameters, expression of renin-angiotensin system (RAS) receptors (angiotensin II type 1 receptor [AT1R], angiotensin II type 2 receptor [AT2R], Mas receptor [MasR], and the Mas-related G protein-coupled receptor, member D [MrgD]) and mesangial matrix proteins (collagen [Col] IV, fibronectin [FN] and laminin) at the first and second renal biopsies, and the use of immunosuppressive therapy and/or RAS blockers after the first biopsy. We enrolled 24 patients with IgAN who underwent repeat renal biopsies. Half of patients showed progression of mesangial lesions on repeat renal biopsy after a median of 4.3 (1-6) years. The progression group had significantly higher expression levels of AT1R and mesangial matrix proteins (Col IV and FN), and significantly lower expression of AT2R and MasR, compared to the stable group. Multivariate analysis showed that the use of RAS blockers (hazard ratio [HR], 0.27; 95% CI, 0.08-0.97; p < 0.05) and the level of proteinuria (HR, 1.8; 95% CI, 1.04-3.12; p < 0.05) were associated with progression of mesangial lesions. Additionally, the progression group exhibited a more rapid decline of renal function compared to the stable group (0.38 and 0.012 ml/min/1.73 m2/month, respectively; p = 0.004). Continuous activation of the intrarenal RAS and massive proteinuria correlate with histological progression of mesangial lesions in IgAN patients, which may further accelerate the deterioration of renal function.

Cardiorenal benefits of mineralocorticoid antagonists in CKD and type2 diabetes : Lessons from the FIGARO-DKD trial.

Diabetic kidney disease (DKD) develops in almost half of all patients with diabetes and is the most common cause of chronic kidney disease (CKD) worldwide. Despite the high risk of chronic renal failure in these patients, only few therapeutic strategies are available. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with DKD was established years ago and remains the hallmark of therapy. The past 2years have seen adramatic change in our therapeutic arsenal for CKD. Sodium-glucose co-transporter‑2 inhibitors (SGLT2s) have been successfully introduced for the treatment of CKD. Afurther addition is anovel compound antagonizing the activation of the mineralocorticoid receptor: finerenone. Finerenone reduces albuminuria and surrogate markers of cardiovascular disease in patients who are already on optimal therapy. In the past, treatment with other mineralocorticoid receptor antagonists was hampered by asignificantly increased risk of hyperkalemia. Finerenone had amuch smaller effect on hyperkalemia. Together with areduced effect on blood pressure and no signs of gynecomastia, this therapeutic strategy had amore specific anti-inflammatory effect and a smaller effect on the volume/electrolyte axis. In the FIDELIO-DKD study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of DKD and the incidence of cardiovascular events, with arelatively safe adverse event profile. In this article, we summarize the available evidence on the cardioprotective and nephroprotective effects of finerenone and analyze the molecular mechanisms involved. In addition, we discuss the potential future role of mineralocorticoid receptor inhibition in the treatment of patients with diabetic CKD.

Chlorthalidone and Advanced Chronic Kidney Disease.

Chlorthalidone and Advanced Chronic Kidney Disease.

ANTIHYPERTENSIVE TREATMENT INITIATION IN FRANCE: WHAT DID GENERAL PRACTITIONERS PRESCRIBE IN 2021?

Objective: Hypertension (HT) is the leading reason for visits to general practitioners (GPs). The diagnosis of HT and the decision to initiate drug treatment form an integral part of their natural field of practice. The recent national and international guidelines have made proposals that are specifically dedicated to this sequence of care. The objective of this study is to analyse the prescribing behaviours of GPs when initiating treatment for patients newly diagnosed with hypertension. Design and method: Data from the IQVIA Longitudinal Patient Database (LPD) France were used. LPD France is a permanent observatory to which a nationally representative panel of physicians – including GPs (n = 1200) – contribute anonymised electronic medical records (EMR). This analysis included all antihypertensive drug prescriptions made by the GPs from July 2020 to June 2021, which were then extrapolated to the entire population of mainland France. Initiation was defined by the establishment of an antihypertensive treatment for a patient already registered with the GP and who was receiving antihypertensive treatment for the first time in 24 months. Results: Over the 12-month period analysed, 869 283 patients had received an initial antihypertensive drug prescription following consultation with a GP. Monotherapy was prescribed in 71.5% of cases (versus 67.3% the previous year) and dual therapy in 21.5% of cases (versus 23.2% the previous year). Fixed-dose combinations accounted for 62% of the dual therapies. The therapeu tic classes of the prescribed monotherapies were distributed as follows: Conclusions: These findings reveal prescriptions that appeared to be consistent with the latest guidelines in which the first-line use of renin-angiotensin system blockers and calcium channel blockers is preferred. It is also interesting to note that treatment initiation with dual therapies was much less common, with a use rate of fixed-dose combinations slightly higher than that of the free-dose combinations. *IQVIA EMR LPD Médecins Généralistes / Cardiologues Libéraux’. EMR = Electronic Medical Records, LPD = Longitudinal Patient Data

Effect of preoperative renin-angiotensin system blockade on vasoplegia after cardiac surgery: A systematic review with meta-analysis.

BACKGROUNDVasoplegia is a common complication of cardiac surgery but its causal relationship with preoperative use of renin angiotensin system (RAS) blockers [angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARB)] is still debated.AIMTo update and summarize data on the effect of preoperative use of RAS blockers on incident vasoplegia.METHODSAll published studies from MEDLINE, EMBASE, and Web of Science providing relevant data through January 13, 2021 were identified. A random-effects meta-analysis method was used to pool estimates, and post-cardiac surgery shock was differentiated from vasoplegia.RESULTSTen studies reporting on a pooled population of 15672 patients (none looking at ARBs exclusively) were included in the meta-analysis. All were case-control studies. Use of ACEIs was associated with an increased risk of vasoplegia [pooled adjusted odds ratio (Aor) of 2.06, 95%CI: 1.45-2.93] and increased inotropic/vasopressor support requirement (pooled aOR 1.19, 95%CI: 1.10-1.29). Post-cardiac surgery shock was increased in the presence of left ventricular dysfunction (pooled aOR 2.32, 95%CI: 1.60-3.36; I2 49%) but not increased by the use of beta blockers (pooled aOR 0.78, 95%CI: 0.36-1.69; I2 77%). Two randomized control trials (RCTs), not eligible for the meta-analysis, did not show an association between continuation of RAS blockers and vasoplegia. CONCLUSIONPreoperative continuation of ACEIs is associated with an increased need for inotropic support postoperatively and with an increased risk of vasoplegia in observational studies but not in RCTs. The absence of a consensus definition of vasoplegia should lead to the use of perioperative cardiovascular monitoring when designing RCTs to better understand this discrepancy.

Soluble tumor necrosis factor receptor 2 is associated with progressive diabetic kidney disease in patients with type 2 diabetes mellitus.

Chronic low-grade inflammation is considered one of the major mechanisms for the progression of diabetic kidney disease. We investigated the prognostic value of circulating soluble tumor necrosis factor receptor 2 (sTNFR2) for early nephropathy in patients with type 2 diabetes. A total of 364 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 were followed up for a median of 4 years. Renal outcomes were defined as a composite of either or both a >30% decline in the eGFR and/or albuminuria stage progression determined with consecutive tests. Seventy-three patients developed renal composite events. Serum concentrations of sTNFR2 were strongly associated with the risk of renal function decline and progressive changes in albuminuria. Through a receiver operating characteristic curve analysis, a serum sTNFR2 level of 1.608 ng/mL was adopted as the discriminator value for predicting renal outcomes (area under the curve 0.63, 95% confidence interval 0.57-0.70, p < 0.001), yielding a sensitivity of 75.3% and a specificity of 51.2%. The association of sTNFR2 levels ≥1.608 ng/mL to renal outcomes was significant after adjusting for relevant variables (hazard ratio 2.27, 95% confidence interval 1.23-4.20, p = 0.009) and remained consistent across subgroups stratified by age, sex, systolic blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system blockers. Higher circulating levels of sTNFR2 are independently associated with an eGFR decline and progressive albuminuria in patients with type 2 diabetes.

Сравнение эффективности лосартана и комбинации валсартана / сакубитрила у лиц с хронической сердечной недостаточностью с низкой фракцией выброса левого желудочка в сочетании с сахарным диабетом 2 типа

The purpose — to compare the efficacy and safety of the use of two regimens for the use of renin-angiotensin system blockers — valsartan / sacubitril (V/C) and losartan in patients with diabetes mellitus (DM) type 2 in combination with chronic heart failure (HF) and low ejection fraction (EF) of the left ventricle (LV). Material and methods. We observed 46 patients with type 2 diabetes. All these patients had previously suffered from myocardial infarction and had clinical manifestations of chronic HF class II-III with LV EF &lt; 40%. All patients were recommended lifestyle changes, they received adequate hypoglycemic and organ-protective therapy. Two groups were distinguished: group A (16 patients, taking V/C at an initial dose of 100 mg/day, followed by titration to 400 mg/day) and group B (30 patients, taking losartan at an initial dose of 50 mg/day, with titration up to 150 mg/day). In the course of treatment and after 11 months, clinical and laboratory studies were performed, in dynamics, echocardiography with tissue Doppler, ultrasound of the brachiocephalic arteries, and a test with reactive hyperemia were performed. Results. During treatment in group A, compared with group B, a more significant positive dynamics of clinical manifestations and the following studied parameters were noted: HOMA-IR and ΔHOMA-B indices, glycated hemoglobin levels, chronic HF class, LV EF, left atrial volume index, ratio of early diastolic velocity of transmitral blood flow to early diastolic velocity of the mitral valve ring, carotid intima-media complex thickness, and indexbrachial arteries resistivity; all changes are significant. Conclusions. Combined neurohumoral blockade using V/S compared with losartan in patients with DM type 2 and chronic HF with low LV EF helped to have more positive changes in clinical-laboratory and instrumental indicators.