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Background: The coronavirus disease 2019 (COVID-19) pandemic is driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to an enormous burden on patient morbidity and mortality. The renin–angiotensin–aldosterone system (RAAS) plays a significant role in various pulmonary diseases. Since SARS-CoV-2 utilizes the angiotensin-converting enzyme (ACE)2 receptor to exert its virulence and pathogenicity, the RAAS is of particular importance in COVID 19. Methods: Our preliminary study investigates retrospectively the influence of selected ACE-polymorphisms (I/D location at intron 16 in the B-coding sequence (rs4646994) and A-240T (rs 4291) at the A-promoter) as well as ACE1 and ACE2 serum levels on disease severity and the inflammatory response in inpatients and outpatients with COVID-19. Results: Our study included 96 outpatients and 88 inpatients (65.9% male, mean age 60 years) with COVID-19 from April to December 2020 in four locations in Germany. Of the hospitalized patients, 88.6% participants were moderately ill (n = 78, 64% male, median age 60 years), and 11.4% participants were severely ill or deceased (n = 10, 90% male, median age 71 years). We found no polymorphism-related difference in disease, in age distribution, time to hospitalization and time of hospitalization for the inpatient group. ACE1 serum levels were significantly increased in the DD compared to the II polymorphism and in the TT compared to the AA polymorphism. There was no significant difference in ACE 1 serum levels l between moderately ill and severely ill patients. However, participants requiring oxygen supplementation had significantly elevated ACE1 levels compared to participants not requiring oxygen, with no difference in ACE2 levels whereas females had significantly higher ACE2 levels. Conclusions: Although there were no differences in the distribution of ACE polymorphisms in disease severity, we found increased proinflammatory regulation of the RAAS in patients with oxygen demand and increased serum ACE2 levels in women, indicating a possible enhanced anti-inflammatory immune response. Clinical trial registration: PreBiSeCov: German Clinical Trials Register, DRKS-ID: DRKS00021591, Registered on 27th April 2020. [ABSTRACT FROM AUTHOR]

Background Hyperkalemia (HK) is a frequent condition in patients with chronic kidney disease (CKD) that is associated with high morbidity and mortality. Patiromer has recently been introduced as a potassium binder. Data on patiromer use in patients with CKD in the real-world setting in Europe are lacking. We describe time to discontinuation and changes in serum potassium levels among German CKD stage 3–5 patients starting patiromer. Methods Duration of patiromer use was estimated by Kaplan–Meier curve, starting at patiromer initiation and censoring for death, dialysis, transplant or loss to follow-up. Serum potassium levels and renin–angiotensin–aldosterone system inhibitor (RAASi) use are described at baseline and during follow-up, restricted to patients remaining on patiromer. Results We identified 140 patiromer users within our analysis sample [81% CKD stage 4/5, 83% receiving RAASi, and median K+ 5.7 (5.4, 6.3) mmol/L]. Thirty percent of patiromer users had prior history of polystyrene sulfonate use. Overall, 95% of patiromer users stayed on treatment past 1 month, with 53% continuing for over a year. Mean serum potassium levels decreased after patiromer initiation and remained stable under treatment during follow-up (up to 180 days). Among these patients, 73%–82% used RAASis during the time periods before and after patiromer initiation, with no obvious trend indicating discontinuation. Conclusion Real-world evidence of patiromer use in Germany shows that, in line with what has been observed in clinical trials, patients on patiromer have a reduction in serum potassium when used long-term. Moreover, most patients on patiromer do not discontinue treatment prior to 1 year after initiation. [ABSTRACT FROM AUTHOR]

Aims: Recently, dipeptidyl peptidase 3 (DPP3) has been discovered as the peptidase responsible for cleavage of angiotensin (1–7) [Ang (1–7)]. Ang (1–7) is part of the angiotensin‐converting enzyme–Ang (1–7)–Mas pathway which is considered to antagonize the renin–angiotensin–aldosterone system (RAAS). Since DPP3 inhibits the counteracting pathway of the RAAS, we hypothesize that DPP3 might be deleterious in the setting of heart failure. However, no data are available on DPP3 in chronic heart failure. We therefore investigated the clinical characteristics and outcome related to elevated DPP3 concentrations in patients with worsening heart failure. Methods and results: Dipeptidyl peptidase 3 was measured in 2156 serum samples of patients with worsening heart failure using luminometric immunoassay (DPP3‐LIA) by 4TEEN4 Pharmaceuticals GmbH, Hennigsdorf, Germany. Predictors of DPP3 levels were selected using multiple linear regression with stepwise backward selection. Median DPP3 concentration was 11.45 ng/mL with a range from 2.8 to 84.9 ng/mL. Patients with higher DPP3 concentrations had higher renin [78.3 (interquartile range, IQR 26.3–227.7) vs. 120.7 IU/mL (IQR 34.74–338.9), P < 0.001, for Q1–3 vs. Q4] and aldosterone [88 (IQR 44–179) vs. 116 IU/mL (IQR 46–241), P < 0.001, for Q1–3 vs. Q4] concentrations. The strongest independent predictors for higher concentration of DPP3 were log‐alanine aminotransferase, log‐total bilirubin, the absence of diabetes, higher osteopontin, fibroblast growth factor‐23 and N‐terminal pro‐B‐type natriuretic peptide concentrations (all P < 0.001). In univariable survival analysis, DPP3 was associated with mortality and the combined endpoint of death or heart failure hospitalization (P < 0.001 for both). After adjustment for confounders, this association was no longer significant. Conclusions: In patients with worsening heart failure, DPP3 is a marker of more severe disease with higher RAAS activity. It may be deleterious in heart failure by counteracting the Mas receptor pathway. Procizumab, a specific antibody against DPP3, might be a potential future treatment option for patients with heart failure. [ABSTRACT FROM AUTHOR]

Background: Hypertension is highly prevalent in older adults and represents a major public health issue since recognition, awareness, treatment and control are insufficient. Analyses of prescription patterns in conjunction with clinical parameters can provide novel insights into the current practice of hypertension management and help to identify barriers to sufficient hypertension control.Methods: A cross-sectional analysis was conducted. Prevalence of hypertension, patterns of antihypertensive therapy, and determinants of blood pressure (BP) control were examined in the Berlin Aging Study II cohort, including 1654 community-dwelling older adults (60-85 years of age).Results: Of the participants, 75.9% had hypertension; 40.6% of these were not prescribed BP medications. Lack of hypertension awareness, younger age, absence of comorbidities, not being on a statin, and not having visited a physician in the past 3 months were associated with lack of treatment. Forty-two percent of treated hypertensive individuals received monotherapy and 58.0% received combination therapy. Renin-angiotensin-aldosterone system (RAAS) inhibitors, and β-blockers were most commonly prescribed, while calcium channel blockers were least prescribed. Only 38.5% of treated hypertensive individuals had their BP controlled to < 140/90 mmHg. Number and choice of BP medications were not predictive of BP control; neither were age, glycated hemoglobin (HbA1c), kidney function, or number of healthcare visits. However, female sex, lower low-density lipoprotein cholesterol (LDL-C) levels and current smoking, amongst others, were positively associated with BP control. There was evidence of significant effect modification by statins in the association of LDL-C and BP.Conclusion: The majority of older adults do not reach BP goals. Antihypertensive prescription patterns do not conform to current guidelines. Using more BP medications was not associated with higher odds of BP control. Lowering LDL-C might be favorable in terms of BP control. [ABSTRACT FROM AUTHOR]

Background: Patients with autosomal or X-linked Alport syndrome (AS) with heterozygous mutations in type IV collagen genes have a 1-20 % risk of progressing to end-stage renal disease during their lifetime. We evaluated the long-term renal outcome of patients at risk of progressive disease (chronic kidney disease stages 1-4) with/without nephroprotective therapy. Methods: This was a prospective, non-interventional, observational study which included data from a 4-year follow-up of AS patients with heterozygous mutations whose datasets had been included in an analysis of the 2010 database of the European Alport Registry. Using Kaplan-Meier estimates and logrank tests, we prospectively analyzed the updated datasets of 52 of these patients and 13 new datasets (patients added to the Registry after 2011). The effects of therapy, extrarenal symptoms and inheritance pattern on renal outcome were analyzed. Results: The mean prospective follow-up was 46 ± 10 months, and the mean time on therapy was 8.4 ± 4.4 (median 7; range 2-18) years. The time from the appearance of the first symptom to diagnosis was 8.1 ± 14.2 (range 0-52) years. At the time of starting therapy, 5.4 % of patients had an estimated glomerular filtration rate of <60 ml/min, 67.6 % had proteinuria and 27.0 % had microalbuminuria. Therapeutic strategies included angiotensin-converting enzymer inhibitors (97.1 %), angiotensin receptor antagonists (1 patient), dual therapy (11.8 %) and statins (8.8 %). Among patients included in the prospective dataset, prevented the need for dialysis. Among new patients, no patient at risk for renal failure progressed to the next disease stage after 4 years follow-up; three patients even regressed to a lower stage during therapy. Conclusions: Treatment with blockers of the renin-angiotensin-aldosterone system prevents progressive renal failure in AS patients with heterozygous mutations in the genes causing AS. Considerable numbers of aging AS patients on dialysis may have heterozygous mutations in these genes (present in 1 % of total population) as underlying disease. Hence, greater alertness towards timely diagnosis and therapy has the potential to prevent progressive renal failure in most-if not all-AS patients with heterozygous mutations in the causal genes. [ABSTRACT FROM AUTHOR]

Background: Patient characteristics and blood pressure-related outcomes in randomized clinical trials (RCTs) differ from clinical practice because of stringent selection criteria. The present study aimed to explore the relationship between clinical trials and clinical practice. We analyzed data from patients enrolled in the "Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy" (EARLY) registry comparing blood pressure (BP) effects of the angiotensin receptor blocker (ARB) azilsartan medoxomil (AZL-M) with the angiotensin-converting enzyme (ACE) inhibitor ramipril between patients who met the eligibility criteria of a previous RCT and those who did not.Methods: Patients with primary arterial hypertension were consecutively enrolled from primary care offices in Germany into the EARLY registry in a 7:3 ratio for treatment with AZL-M or an ACE inhibitor, provided that they met the following criteria at baseline: 1) no antihypertensive treatment prior to inclusion or a non-renin-angiotensin system (RAS) based monotherapy; 2) initiation of treatment with either AZL-M or an ACE inhibitor alone. Analyses were performed to evaluate BP effects for patients in the EARLY registry who met the selection criteria of a prior RCT (RCT+) versus those who did not (RCT-).Results: Out of 3,698 patients considered, 1,644 complied with the RCT criteria (RCT+) while 2,054 did not (RCT-). RCT- patients (55.5%) displayed a higher risk profile in terms of age and comorbidities, and a wider spectrum of BP values at baseline, as highlighted by the grades of hypertension and mean BP values. The proportion of patients who achieved target blood pressure control in the RCT+ group was significantly higher for AZL-M versus ramipril (64.1 versus 56.1%; P<0.01), in accordance with the result of the clinical trial. In the RCT- AZL-M group, the proportion of patients who met BP targets was lower (58.1%) than in the RCT+ AZL-M group (64.1%), whereas the proportion of patients with target BP values in the RCT- ramipril and the RCT+ ramipril groups was similar (57.7 versus 56.1%). Thus, in contrast to results for the RCT+ group, in the RCT- group, the target BP attainment rate for AZL-M was not significantly superior to that for ramipril. However, the tolerability profile of AZL-M and ramipril was comparable in both populations. At the 12-month follow-up, death and stroke rates were low (≤0.5%) and adverse events did not differ between the AZL-M and ramipril groups, irrespective of RCT eligibility.Conclusions: These data confirm that the EARLY population comprised a broader spectrum of hypertensive patients than RCTs, and the differences in patient characteristics were accompanied by disparate rates of blood pressure goal attainment. Overall, the validity of the RCT was demonstrated and confirmed in clinical practice with a broader range of patients with various comorbidities. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the adequacy of hypertension management in hypertensive elderly living in long-term-care facilities compared with home-living elderly. Methods: This retrospective, cross-sectional, pharmacoepidemiological study compared data from a community-dwelling population (CD) and from four nursing homes (NH) in Dresden, Germany. Individuals aged ≥65 with the diagnosis of arterial hypertension were included. Demographical, medical, and drug prescription data as well as blood pressure (BP) values were analyzed and compared descriptively after matching the populations by age and gender. Results: Each population comprised 209 patients (mean age 80.4 years [±6], 70.3% women). NH showed a higher number of diseases [7 (5-9) vs. 5 (3-7); p < 0.001]. BP (<140/90 mmHg) was better controlled in NH (61.0% vs. 48.1%; p = 0.015). The median number of BP-lowering drugs was three (2-4; CD) and two (1-3; NH) (range: 0-9). Most frequently used antihypertensives were diuretics and beta-blockers. Among renin-angiotensin system (RAS) blockers, angiotensin-receptor blockers (ARBs) were preferred in CD and angiotensin-converting enzyme (ACE) inhibitors in NH. Drug treatment for secondary prevention of myocardial infarction or stroke [acetylsalicylic acid (ASA) 100, RAS-blocker, beta-blocker, statin] was low among both groups (CD 21.3%; NH 1.6%; p = 0.01). NH received more inappropriate drugs, especially tranquillizers (31.2% vs. 21.0%; p < 0.05) [according to the PRISCUS (Latin for 'old and venerable') list for potentially inappropriate medications in the elderly (PIM)]. Conclusions: NH residents showed better BP control than CD elderly while receiving less antihypertensive drugs. The prescription of antihypertensives was assumed to be more cost effective in NH. Nevertheless, inappropriate drug use is still high (NH > CD), and there is an extended need for professional medication assessment in both groups of elderly. [ABSTRACT FROM AUTHOR]

The renin-angiotensin-aldosterone system plays a key role in the regulation of human blood pressure. The aldosterone-to-renin ratio (ARR) is widely accepted for screening the primary hyperaldosteronism (PAL). Various cutoffs for positive PAL screening have been defined in patient cohorts from endocrinological referral centers and primary care. However, the distribution of the ARR in the general population is largely unknown. We aim to provide reference ranges for plasma aldosterone concentration (PAC), plasma renin concentration (PRC), and the ARR for the general population of north-east Germany. A cohort of 3?300 subjects participated in the first follow-up of the longitudinal, population-based Study of Health in Pomerania (SHIP). PAC and PRC were measured by radioimmunometric procedures. The reference interval was defined as the central 95% range between the 2.5 thand 97.5 thpercentiles. A reference population comprising 1?347 healthy subjects was selected. Sex and age-specific (25-54 and 55-74 years) reference ranges are presented. The upper reference limit for the ARR was 14.2 and 20.3 in younger, and 22.4 and 25.5 in older men and women, respectively. Time of blood sampling had no influence on the ARR, while beta blockers, and agents acting on the renin-angiotensin system were associated with higher and lower ARR, respectively. Our upper reference limit for the ARR is clearly lower than previously reported values from studies of hypertensive patients in primary care or hypertension referral centers. We confirm that PAC and PRC are associated with various factors, including sex, age, intake of estrogen, and various antihypertensive medications. [ABSTRACT FROM AUTHOR]

Franz Volhard and his students' tortuous road to renovascular hypertension. Harry Goldblatt's name is irrevocably linked to the phenomenon that renal artery constriction increases blood pressure via renin release, even in the absence of significantly decreased renal function. However, "getting there was more than half the fun." A lively competition took place earlier in this century elucidating the role of the kidney in hypertension, in which Franz Volhard and his disciples played a major role. I have reviewed the extensive German literature of the time, and observed that Franz Volhard and his young associates made major contributions investigating decreases in renal perfusion and resultant increases in blood pressure. Hessel, Hartwich, and Volhard made seminal observations in this regard that even preceded those of Goldblatt. A sojourn into this past history gives a revealing insight into our cumulative-albeit still incomplete-knowledge of the kidney, renin-angiotensin system, and blood pressure regulation. Franz Volhard was a colorful figure whose contributions extended far beyond classifying renal diseases. [ABSTRACT FROM AUTHOR]