Impaired renal function affects clinical outcomes and management of patients with heart failure.

AIMS: Inpatients with heart failure and renal impairment have poor outcomes and variable quality of care. We investigate treatment practice and outcomes in an unselected real-world cohort using historical creatinine measurements. METHODS AND RESULTS: Admissions between 1/4/2013 and 30/4/2015 diagnosed at discharge with heart failure were retrospectively analysed. Stages of chronic kidney disease (CKD) and acute kidney injury (AKI) were calculated from creatinine at discharge and 3-12 months before admission. We identified 1056 admissions of 851 patients (mean age 76 years, 56% Caucasian, 36% with diabetes mellitus, 54% with ischaemic heart disease, and 57% with valvular heart disease). CKD was common; 36%-Stage 3a/b, 11%-Stage 4/5; patients were older, more often diabetic, with higher potassium, lower haemoglobin, and more oedema but similar prevalence of left ventricular systolic dysfunction (LVSD) compared patients with Stages 0-2. AKI was present in 17.0% (10.4%-Stage 1, 3.7%-Stage 2, and 2.9%-Stage 3); these had higher potassium and lower haemoglobin than patients with no AKI. Length of stay was longer in Stage 4/5 CKD [11 days; P = 0.008] and AKI [13 days; P = 0.006]. Mortality was higher with Stage 4/5 CKD (13.8% compared with 7.7% for Stages 0-2 CKD (P = 0.036)] and increased with AKI (5%-no AKI, 20.9%-Stage 1, 35.9%-Stage 2, and 48.4%-Stage 3; P < 0.001). Adjusted for age, diabetes, and LVSD, both AKI and Stage 4/5 CKD were independent predictors of in-hospital mortality. In survivors with LVSD, the discharge prescription of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers decreased with progressive CKD, [84%-no-mild, 59%-moderate, and 36%-severe CKD; P < 0.001]; this was not purely explained by hyperkalaemia. CONCLUSIONS: Inpatients with heart failure and renal impairment, acute and chronic, failed to receive recommended therapy and had poor outcomes

Noninterventional follow-up vs fluid bolus in RESPONSE to oliguria-The RESPONSE trial protocol and statistical analysis plan

Background Oliguria is a frequent trigger for administering a fluid bolus, but the effect of fluid bolus in improving urine output is inadequately demonstrated. Here, we summarize the protocol and detailed statistical analysis plan of the randomized, controlled RESPONSE trial comparing follow-up as the experimental group and a 500 mL crystalloid fluid bolus as the control group for oliguria in critically ill oliguric patients. Methods Our trial is an investigator-initiated, randomized, controlled, pilot trial conducted in three ICUs in two centers. We aim to randomize 1:1 altogether 130 hemodynamically stable oliguric patients either to a 2-hour follow-up without interventions or to receive a crystalloid bolus of 500 mL over 30 minutes. The primary outcome is the change in individual urine output during the 2-hour period compared to 2 hours preceding randomization. Doubling of the urine output is considered clinically significant. Additionally, we record the duration of oliguria, physiological and biochemical variables, adverse events, and the incidences of acute kidney injury and renal replacement therapy. Conclusions Oliguria is a frequent trigger for potentially harmful fluid loading. Therefore, the RESPONSE trial will give information of the potential effect of fluid bolus on oliguria in critically ill patients. Trial registration clinical.trials.gov, NCT02860572.Peer reviewe

Risk of acute kidney injury and survival in patients treated with Metformin:an observational cohort study

Background: Whether metformin precipitates lactic acidosis in patients with chronic kidney disease (CKD) remains under debate. We examined whether metformin use was associated with an increased risk of acute kidney injury (AKI) as a proxy for lactic acidosis and whether survival among those with AKI varied by metformin exposure. Methods: All individuals with type 2 diabetes and available prescribing data between 2004 and 2013 in Tayside, Scotland were included. The electronic health record for diabetes which includes issued prescriptions was linked to laboratory biochemistry, hospital admission, death register and Scottish Renal Registry data. AKI events were defined using the Kidney Disease Improving Global Outcomes criteria with a rise in serum creatinine of at least 26.5 μmol/l or a rise of greater than 150% from baseline for all hospital admissions. Cox Regression Analyses were used to examine whether person-time periods in which current metformin exposure occurred were associated with an increased rate of first AKI compared to unexposed periods. Cox regression was also used to compare 28 day survival rates following first AKI events in those exposed to metformin versus those not exposed. Results: Twenty-five thousand one-hundred fourty-eight patients were included with a total person-time of 126,904 person years. 4944 (19.7%) people had at least one episode of AKI during the study period. There were 32.4 cases of first AKI/1000pyrs in current metformin exposed person-time periods compared to 44.9 cases/1000pyrs in unexposed periods. After adjustment for age, sex, diabetes duration, calendar time, number of diabetes drugs and baseline renal function, current metformin use was not associated with AKI incidence, HR 0.94 (95% CI 0.87, 1.02, p = 0.15). Among those with incident AKI, being on metformin at admission was associated with a higher rate of survival at 28 days (HR 0.81, 95% CI 0.69, 0.94, p = 0.006) even after adjustment for age, sex, pre-admission eGFR, HbA1c and diabetes duration. Conclusions: Contrary to common perceptions, we found no evidence that metformin increases incidence of AKI and was associated with higher 28 day survival following incident AKI

Impact of intravenous fluid composition on outcomes in patients with systemic inflammatory response syndrome

Introduction: Intravenous (IV) fluids may be associated with complications not often attributed to fluid type. Fluids with high chloride concentrations such as 0.9 % saline have been associated with adverse outcomes in surgery and critical care. Understanding the association between fluid type and outcomes in general hospitalized patients may inform selection of fluid type in clinical practice. We sought to determine if the type of IV fluid administered to patients with systemic inflammatory response syndrome (SIRS) is associated with outcome. Methods: This was a propensity-matched cohort study in hospitalized patients receiving at least 500 mL IV crystalloid within 48 hours of SIRS. Patient data was extracted from a large multi-hospital electronic health record database between January 1, 2009, and March 31, 2013. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, readmission, and complications measured by ICD-9 coding and clinical definitions. Outcomes were adjusted for illness severity using the Acute Physiology Score. Of the 91,069 patients meeting inclusion criteria, 89,363 (98 %) received 0.9 % saline whereas 1706 (2 %) received a calcium-free balanced solution as the primary fluid. Results: There were 3116 well-matched patients, 1558 in each cohort. In comparison with the calcium-free balanced cohort, the saline cohort experienced greater in-hospital mortality (3.27 % vs. 1.03 %, P <0.001), length of stay (4.87 vs. 4.38 days, P = 0.016), frequency of readmission at 60 (13.54 vs. 10.91, P = 0.025) and 90 days (16.56 vs. 12.58, P = 0.002) and frequency of cardiac, infectious, and coagulopathy complications (all P <0.002). Outcomes were defined by administrative coding and clinically were internally consistent. Patients in the saline cohort received more chloride and had electrolyte abnormalities requiring replacement more frequently (P <0.001). No differences were found in acute renal failure. Conclusions: In this large electronic health record, the predominant use of 0.9 % saline in patients with SIRS was associated with significantly greater morbidity and mortality compared with predominant use of balanced fluids. The signal is consistent with that reported previously in perioperative and critical care patients. Given the large population of hospitalized patients receiving IV fluids, these differences may confer treatment implications and warrant corroboration via large clinical trials. Trial registration: NCT02083198 clinicaltrials.gov; March 5, 201