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

Impact of acute versus repetitive moderate intensity endurance exercise on kidney injury markers.

Exercise may lead to kidney injury through several mechanisms. Urinary Kidney Injury Molecule-1 (uKIM1) and Neutrophil Gelatinase-Associated Lipocalin (uNGAL) are known biomarkers for acute kidney injury, but their response to repetitive exercise remains unknown. We examined the effects of a single versus repetitive bouts of exercise on markers for kidney injury in a middle-aged population. Sixty subjects (aged 29-78 years, 50% male) were included and walked 30, 40 or 50 km for three consecutive days. At baseline and after exercise day 1 and 3, a urine sample was collected to determine uNGAL and uKIM1. Furthermore, urinary cystatin C, creatinine, and osmolality were used to correct for dehydration-related changes in urinary concentration. Baseline uNGAL was 9.2 (5.2-14.7) ng/mL and increased to 20.7 (11.0-37.2) ng/mL and 14.2(8.0-26.3) ng/mL after day 1 and day 3, respectively, (P ≤ 0.001). Baseline uKIM1 concentration was 2.6 (1.4-6.0) ng/mL and increased to 5.2 (2.4-9.1) ng/mL (P = 0.002) after day 1, whereas uKIM1 was not different from baseline at day 3 (2.9 [1.4-6.4] ng/mL (P = 0.52)). Furthermore, both uNGAL and uKIM1 levels were higher after day 1 compared to day 3 (P < 0.01). When corrected for urinary cystatin C, creatinine, and osmolality, uNGAL demonstrated a similar response compared to the uncorrected data, whereas differences in uKIM1 between baseline, day 1 and day 3 (Ptime = 0.63) were no longer observed for cystatin C and creatinine corrected data. A single bout of prolonged exercise significantly increased uNGAL concentration, whereas no changes in uKIM1 were found. Repetitive bouts of exercise show that there is no cumulative effect of kidney injury markers

Economic evaluations of interventions to manage hyperphosphataemia in adult haemodialysis patients: A systematic review

© 2015 Asian Pacific Society of Nephrology. Managing hyperphosphataemia in haemodialysis patients is resource-intensive. A search for cost-effective interventions in this field is needed to inform decisions on the allocation of healthcare resources. NHSEED, MEDLINE, EMBASE and CINAHL were searched for full economic evaluations of hyperphosphataemia-managing interventions in adult haemodialysis patients, published between 2004 and 2014, in English, French, Dutch or German. Incremental cost-effectiveness ratios of the interventions were up-rated to 2013US$using Purchasing Power Parity conversion rates and Consumer Price Indices. The quality of included studies was assessed using the Extended Consensus on Health Economic Criteria List. Twelve out of the 1681 retrieved records fulfilled the inclusion criteria. They reported only on one aspect of hyperphosphataemia management, which is the use of phosphate binders (calcium-based and calcium-free, in first-line and sequential use). No economic evaluations of other phosphorus-lowering interventions were found. The included articles derived from five countries and most of them were funded by pharmaceutical companies. The incremental cost-effectiveness ratios of phosphate binders ranged between US$11 461 and US$157 760 per quality-adjusted life-year gained. Calcium-based binders (especially calcium acetate) appear to be the optimal cost-effective first- and second-line therapy in prevalent patients, while the calcium-free binder, lanthanum carbonate, might provide good value for money, as second-line therapy, in incident patients. The studies\u27 overall quality was suboptimal. Drawing firm conclusions was not possible due to the quality heterogeneity and inconsistent results. Future high-quality economic evaluations are needed to confirm the findings of this review and to address other interventions to manage hyperphosphataemia in this population