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

Alternatives to immediate release tacrolimus in solid organ transplant recipients: When the gold standard is in short supply

Given the current climate of drug shortages in the United States, this review summarizes available comparative literature on the use of alternative immunosuppressive agents in adult solid organ transplant recipients including kidney, pancreas, liver, lung, and heart, when immediate‐release tacrolimus (IR‐TAC) is not available. Alternative options explored include extended‐release tacrolimus (ER‐TAC) formulations, cyclosporine, belatacept, mammalian target of rapamycin inhibitors, and novel uses of induction therapy for maintenance immunosuppression. Of available alternatives, only ER‐TAC formulations are of non‐inferior efficacy compared to IR‐TAC when used de novo or after conversion in stable kidney transplant recipients (KTRs). All other alternatives were associated with higher rates of biopsy‐proven rejection, but improved tolerance from classic adverse effects of IR‐TAC including nephrotoxicity and development of diabetes. While most alternative therapies are approved in KTRs, access via third‐party payors is an obstacle in non‐KTRs. In the setting of IR‐TAC shortage, alternate therapeutic options may be plausible depending on the organ population and individual patient situation to ensure appropriate, effective immunosuppression for each patient.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156148/2/ctr13903.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156148/1/ctr13903_am.pd

Vitamin D, and Kidney Disease

Mineral metabolism abnormalities, such as low 1,25-dihydroxyvitamin D (1,25(OH)2D) and elevated parathyroid hormone (PTH), are common at even higher glomerular filtration rate than previously described. Levels of 25-hydroxyvitamin D (25(OH)D) show an inverse correlation with those of intact PTH and phosphorus. Studies of the general population found much higher all-cause and cardiovascular (CV) mortality for patients with lower levels of vitamin D; this finding suggests that low 25(OH)D level is a risk factor and predictive of CV events in patients without chronic kidney disease (CKD). 25(OH)D/1,25(OH)2D becomes deficient with progression of CKD. Additionally, studies of dialysis patients have found an association of vitamin D deficiency with increased mortality. Restoration of the physiology of vitamin D receptor activation should be essential therapy for CKD patients

Cardiovascular risk factors and incident albuminuria in screen-detected type 2 diabetes.

BACKGROUND: It is unclear whether cardiovascular risk factor modification influences the development of renal disease in people with type 2 diabetes identified through screening. We determined predictors of albuminuria five years after a diagnosis of screen-detected diabetes within the ADDITION-Europe study, a pragmatic cardiovascular outcome trial of multifactorial cardiovascular risk management. METHODS: In 1,826 participants with newly diagnosed, screen-detected diabetes without albumiuria, we explored associations between risk of new albuminuria (≥2.5 mg mmol(-1) males and ≥3.5 mg mmol(-1) females) and: 1) baseline cardio-metabolic risk factors and 2) changes from baseline to one year in systolic blood pressure (∆SBP) and glycated haemoglobin (∆HbA1c ) using logistic regression. RESULTS: Albuminuria developed in 268 (15%) participants; baseline body mass index and active smoking were independently associated with new onset albuminuria in the five years after detection of diabetes. In a model adjusted for age, gender, and baseline HbA1c and blood pressure, a 1% decrease in HbA1c and 5 mmHg decrease in SBP during the first year were independently associated with lower risks of albuminuria (Odds Ratio (OR), 95% confidence interval: 0.76, 0.62 to 0.91 and 0.94, 0.88 to 1.01, respectively). Further adjustment did not materially change these estimates. There was no interaction between ΔSBP and ΔHBA1c in relation to albuminuria risk, suggesting likely additive effects on renal microvascular disease. CONCLUSIONS: Baseline measurements and changes in HbA1c and SBP a year after diagnosis of diabetes through screening independently associate with new onset albuminuria four years later. Established multifactorial treatment for diabetes applies to cases identified through screening.Individual centres in Denmark, the Netherlands and the United Kingdom were responsible for funding. ADDITION-Denmark has been given unrestricted grants from Novo Nordisk AS, Novo Nordisk Scandinavia AB, Novo Nordisk U.K., AstraZeneca Denmark, Pfizer Denmark, GlaxoSmithKline Pharma Denmark, Servier Denmark A/S, and HemoCue Denmark A/S. Part of the grant from Novo Nordisk was transferred to the other centers. ADDITIONNetherlands was supported by unrestricted grants from Novo Nordisk, GlaxoSmithKline, and Merck. ADDITION-Cambridge was supported by the Wellcome Trust (grant reference no: G061895) and the Medical Research Council (grant reference no: G0001164), the National Institute for Health Research (NIHR) Health Technology Assessment Programme (grantcare.diabetesjournals.org Sandbæk and Associates 2021 reference no: 08/116/300), and National Health Service research and development support funding (including the Primary Care Research and DiabetesResearch Networks), and the NIHR under its Programme Grants for Applied Research scheme (RP-PG-0606-1259). ADDITION-Leicester was supported by the Department of Health and Support for Sciences, the NIHR Health Technology Assessment Programme (grant reference no: 08/116/300), National Health Service research and development support funding (including the Primary Care Research and Diabetes Research Networks Leicestershire, Northamptonshire and Rutland Collaborative for Leadership in Applied Health Research and Care) and the NIHR Leicester Loughborough Lifestyle Biomedical Research Unit. ADDITION-Netherlands was supported by the Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht and by unrestricted grants from Novo Nordisk and Glaxo Smith Kline