Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial

Objective To compare the effects on proteinuria and blood pressure of addition of dietary sodium restriction or angiotensin receptor blockade at maximum dose, or their combination, in patients with non-diabetic nephropathy receiving background treatment with angiotensin converting enzyme (ACE) inhibition at maximum dose

Renoprotective RAAS inhibition does not affect the association between worse renal function and higher plasma aldosterone levels

Abstract Background Aldosterone is elevated in chronic kidney disease (CKD) and may be involved in hypertension. Surprisingly, the determinants of the plasma aldosterone concentration (PAC) and its role in hypertension are not well studied in CKD. Therefore, we studied the determinants of aldosterone and its association with blood pressure in CKD patients. We also studied this during renin-angiotensin-aldosterone system inhibition (RAASi) to establish clinical relevance, as RAASi is the treatment of choice in CKD with albuminuria. Methods We performed a post-hoc analysis on data from a randomized controlled double blind cross-over trial in non-diabetic CKD patients (n = 33, creatinine clearance (CrCl) 85 (75–95) ml/min, proteinuria 3.2 (2.5–4.0) g/day). Patients were treated with losartan 100 mg (ARB), and ARB + hydrochlorothiazide 25 mg (HCT), during both a regular (200 ± 10 mmol Na+/day) and low (89 ± 8 mmol Na+/day) dietary sodium intake, in 6-week study periods. PAC data at the end of each study period were analyzed. The association between PAC and blood pressure was analyzed continuously, and according to PAC above or below the median. Results Lower CrCl was correlated with higher PAC during placebo as well as during ARB (β = −1.213, P = 0.008 and β = −1.090, P = 0.010). Higher PAC was not explained by high renin, illustrated by a comparable association between CrCl and the aldosterone-to-renin ratio. The association between lower CrCl and higher PAC was also found in a second study with single RAASi with ACE inhibition (ACEi; lisinopril 40 mg/day), and dual RAASi (lisinopril 40 mg/day + valsartan 320 mg/day). Higher PAC was associated with a higher systolic blood pressure (P = 0.010) during different study periods. Only during maximal treatment with ARB + HCT + dietary sodium restriction, blood pressure was no longer different in subjects with a PAC above and below the median. Conclusions In CKD patients with a standardized regular sodium intake, worse renal function is associated with a higher aldosterone, untreated and during RAASi with either ARB, ACEi, or both. Furthermore, higher aldosterone is associated with higher blood pressure, which can be treated with the combination of RAASi, HCT and dietary sodium restriction. The first study was performed before it was standard to register trials and the study was not retrospectively registered. The second study was registered in the Netherlands Trial Register on the 5th of May 2006 (NTR675)

Predicting in-hospital mortality using routine parameters in unselected nonsurgical emergency department patients

Background: To assure adequate and efficient treatment in the emergency department (ED) despite increasing patient numbers, early risk stratification might be helpful for directing resource allocation.\ud \ud Objective: To determine whether routine clinical data can predict in-hospital mortality in nonsurgical ED patients and to specifically identify the best predictive parameters.\ud \ud Materials and methods: This retrospective cohort study investigated 34,333 nonsurgical adult patients who attended one of the two participating EDs in Berlin, Germany, within 1 year. Routine clinical data were analysed for their potential to predict in-hospital mortality using logistic regression as well as classification and regression tree (CART) analysis. A validation dataset contained 35,646 patients of the following year.\ud \ud Results: In-hospital mortality was 1.8 % (634/34,333). C-reactive protein (CRP) and red cell distribution width (RDW) were the best predictors of mortality. A model with nine predictors (CRP, RDW, age, potassium, sodium, WBC, platelets, RBC and creatinine) achieved an area under the receiver operating characteristic curve (AUROC) of 0.870 (95 % confidence interval, CI: 0.857–0.883). A three-marker model (CRP, RDW, age) resulted in an AUROC of 0.866 (95 % CI: 0.853–0.878). In the independent validation dataset the AUROC for this three-marker model was 0.837 (95 % CI: 0.825–0.850). CART analysis corroborated the importance of CRP and RDW, and a clinical algorithm for risk stratification was developed (Emergency Processes in Clinical Structures, EPICS score).\ud \ud Conclusion: Two different statistical procedures and independent validation revealed similar results, suggesting a combination of CRP and RDW as a score (EPICS score) for early identification of high-risk patients. This might be particularly helpful in overcrowded situations and where resources are limited. The suggested score should be validated and potentially adapted to diverse ED settings and patient populations in international multicentre trials

Überfüllung der notaufnahmen: gründe und populationsbezogene einflussfaktoren/Emergency department crowding: reasons and population-based influencing factors

Abstract (German) Hintergrund: Aus Notaufnahmen in Deutschland wird eine zunehmende Überfüllung berichtet, die die Prozesse belastet. Ziel: Ziel der Studie ist es, Gründe für die Überfüllung der Notaufnahmen sowie populationsbezogene Einflussfaktoren zu erfassen und so eine Datengrundlage für evidenzbasierte Forschungs- und Lösungsstrategien zu entwickeln. Methode: Dies ist eine "Mixed-methods"-Studie, die an zwei universitären Notaufnahmen mit soziodemographisch unterschiedlichen Einzugsgebieten durchgeführt wurde (Notaufnahme Nord mit durchschnittlich niedrigem Sozialstatus der Bevölkerung und Notaufnahme Süd mit höherem Sozialstatus). Die Methodik umfasst quantitative deskriptive Analysen eines Sekundärdatensatzes von 34.333 Notfallpatienten und qualitative Fokusgruppeninterviews an beiden beteiligten Einrichtungen. Ergebnisse: Obwohl die Patienten der Notaufnahme Süd deutlich älter waren und häufiger stationär aufgenommen wurden, waren die Morbidität und Krankenhausmortalität der Notaufnahme Nord höher. Die vom Personal genannten Gründe waren an beiden Einrichtungen sehr ähnlich und zeigten insbesondere externe und patientenbezogene Faktoren, die ein erhöhtes Patientenaufkommen sowie einen erschwerten Patientenabfluss bedingen, auf. Es ergaben sich jedoch deutlich unterschiedliche Diskussionsschwerpunkte, die sich anhand der Patientenpopulation nachvollziehen lassen. In beiden Einrichtungen wurde ein erhöhtes Maß an "Sicherheitsmedizin" als Grund für die Überfüllung genannt. Diskussion: Die wahrgenommenen Gründe für die Überfüllung der Notaufnahmen liegen zu einem überwiegenden Teil außerhalb des Einflussbereichs der Notaufnahmen und werden von den Charakteristika ihrer Patientenpopulation mit beeinflusst. Eine Lösung des Problems erfordert daher Maßnahmen, die über Prozessoptimierungen in den Notaufnahmen selbst hinausgehen und im Sozial- bzw. dem Gesundheitssystem eingreifen. Abstract (English) Background: Emergency departments (ED) in Germany report increasing levels of crowding, which have a negative impact on ED processes. Aims: The purpose of this study is to evaluate perceived reasons for ED crowding as well as population-based influencing factors and to develop a database for further research and solution strategies. Methods: This is a mixed methods study conducted at two university EDs with sociodemographically different catchment areas (ED North, population with a lower socioeconomic status, ED South, population with a higher socioeconomic status), comprising a descriptive secondary data analysis of 34,333 ED patients and qualitative focus group interviews with medical staff of these EDs. Results: Although patients were older and more often hospitalized in ED South, morbidity and in-hospital mortality of admitted patients was higher in ED North. Perceived reasons were similar in both institutions with mainly external and patient-related factors causing high patient volumes and a slow outflow of patients. There were marked differences in the key areas of discussion, which can be comprehended on the basis of the patient data. Staff in both EDs reported a perceived high level of "protective medicine" as causing ED crowding. Discussion: Perceived reasons for ED crowding are mainly found outside the influence of the EDs and are affected by their patient population. Solution strategies have to reach beyond process-optimization strategies in the EDs themselves and should intervene at population and social/health care system levels

Concordance of dietary sodium intake and concomitant phosphate load: Implications for sodium interventions

Background and aims: Both a high dietary sodium and high phosphate load are associated with an increased cardiovascular risk in patients with chronic kidney disease (CKD), and possibly also in non-CKD populations. Sodium and phosphate are abundantly present in processed food. We hypothesized that (modulation of) dietary sodium is accompanied by changes in phosphate load across populations with normal and impaired renal function. Methods and Results: We first investigated the association between sodium and phosphate load in 24-h urine samples from healthy controls (n = 252), patients with type 2 diabetes mellitus (DM, n = 255) and renal transplant recipients (RTR, n = 705). Secondly, we assessed the effect of sodium restriction on phosphate excretion in a nondiabetic CKD cohort (ND-CKD: n = 43) and a diabetic CKD cohort (D-CKD: n = 39). Sodium excretion correlated with phosphate excretion in healthy controls (R = 0.386, P <0.001), DM (R = 0.490, P <0.001), and RTR (R = 0.519, P <0.001). This correlation was also present during regular sodium intake in the intervention studies (ND-CKD: R = 0.491, P <0.001; D-CKD: R = 0.729, P <0.001). In multivariable regression analysis, sodium excretion remained significantly correlated with phosphate excretion after adjustment for age, gender, BMI, and eGFR in all observational cohorts. In ND-CKD and D-CKD moderate sodium restriction reduced phosphate excretion (31 +/- 10 to 28 +/- 10 mmol/d; P = 0.04 and 26 +/- 11 to 23 +/- 9 mmol/d; P = 0.02 respectively). Conclusions: Dietary exposure to sodium and phosphate are correlated across the spectrum of renal function impairment. The concomitant reduction in phosphate intake accompanying sodium restriction underlines the off-target effects on other nutritional components, which may contribute to the beneficial cardiovascular effects of sodium restriction. (C) 2016 Published by Elsevier B.V. on behalf of The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University

Renoprotective RAAS inhibition does not affect the association between worse renal function and higher plasma aldosterone levels

Aldosterone is elevated in chronic kidney disease (CKD) and may be involved in hypertension. Surprisingly, the determinants of the plasma aldosterone concentration (PAC) and its role in hypertension are not well studied in CKD. Therefore, we studied the determinants of aldosterone and its association with blood pressure in CKD patients. We also studied this during renin-angiotensin-aldosterone system inhibition (RAASi) to establish clinical relevance, as RAASi is the treatment of choice in CKD with albuminuria. We performed a post-hoc analysis on data from a randomized controlled double blind cross-over trial in non-diabetic CKD patients (n = 33, creatinine clearance (CrCl) 85 (75-95) ml/min, proteinuria 3.2 (2.5-4.0) g/day). Patients were treated with losartan 100 mg (ARB), and ARB + hydrochlorothiazide 25 mg (HCT), during both a regular (200 ± 10 mmol Na+/day) and low (89 ± 8 mmol Na+/day) dietary sodium intake, in 6-week study periods. PAC data at the end of each study period were analyzed. The association between PAC and blood pressure was analyzed continuously, and according to PAC above or below the median. Lower CrCl was correlated with higher PAC during placebo as well as during ARB (β = -1.213, P = 0.008 and β = -1.090, P = 0.010). Higher PAC was not explained by high renin, illustrated by a comparable association between CrCl and the aldosterone-to-renin ratio. The association between lower CrCl and higher PAC was also found in a second study with single RAASi with ACE inhibition (ACEi; lisinopril 40 mg/day), and dual RAASi (lisinopril 40 mg/day + valsartan 320 mg/day). Higher PAC was associated with a higher systolic blood pressure (P = 0.010) during different study periods. Only during maximal treatment with ARB + HCT + dietary sodium restriction, blood pressure was no longer different in subjects with a PAC above and below the median. In CKD patients with a standardized regular sodium intake, worse renal function is associated with a higher aldosterone, untreated and during RAASi with either ARB, ACEi, or both. Furthermore, higher aldosterone is associated with higher blood pressure, which can be treated with the combination of RAASi, HCT and dietary sodium restriction. The first study was performed before it was standard to register trials and the study was not retrospectively registered. The second study was registered in the Netherlands Trial Register on the 5th of May 2006 (NTR675