The acute kidney outreach to prevent deterioration and death – a large pilot study for a cluster randomised trial

Background and objectives: The Acute Kidney Outreach to Reduce Deterioration and Death (AKORDD) trial was a large pilot study for a cluster randomised trial of AKI Outreach. Design, Setting, Participants, and Measurements: An observational Control (Before) phase was conducted in two teaching hospitals (9 miles apart) and their respective catchment areas. In the Intervention (After) phase, a working hours AKI outreach service operated for the intervention hospital/area for 20 weeks, with the other site acting as a control. All AKI alerts in both hospital and community patients were screened for inclusion. Major exclusion criteria were patients who were end of life, or unlikely to benefit from Outreach, or lacking mental capacity, or already referred to the Renal team. The intervention arm included a model of escalation of renal care to AKI patients, depending on AKI stage. The 30-day primary outcome was a combination of death, or deterioration, as shown by any need for dialysis or progression in AKI stage. 1762 adult patients were recruited; 744 at the Intervention site during the After phase. Results: A median of 3.0 non-medication recommendations and 0.5 medication related recommendations per patient were made by the Outreach team, a median of 15.7 hours after the AKI alert. Relatively low rates of the primary outcomes of death within 30 days (11-15%), or requirement for dialysis (0.4 – 3.7%) were seen across all four groups. In an exploratory analysis, at the Intervention hospital during the After phase the was an odds ratio for the combined primary outcome of 0.73 (95% CI 0.42, 1.26, p = 0.26). Conclusions: An AKI outreach service can provide standardised specialist care to those with AKI across a healthcare economy. Trials assessing AKI outreach may benefit from focusing on those patients with "mid-range" prognosis, where nephrological intervention could have the most impact

A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice

Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions

Risk factors associated with the development of active tuberculosis among patients with advanced chronic kidney disease.

OBJECTIVES The risk of developing active TB is greater in those receiving haemodialysis. This study aimed to describe the incidence of active tuberculosis among patients referred for management of kidney disease and dialysis in a high incidence UK city, with the purpose of informing latent TB testing and treatment practice. METHODS Information from the tuberculosis register was cross-referenced with the Department of Renal Medicine patient information system. All patients seen between 1st January 2005 and 1st October 2016 were included in the analyses with the exception of those with prior TB. RESULTS 68 cases of active TB were identified, an incidence of 126/100,000 patient-years (95% CI 97-169). Incidence was lowest in those with CKD 1 or 2 and rose as high as 256/100,000 patient-years (95% CI 183-374) in those receiving renal replacement therapy. 48% of cases were pulmonary and 87% of TB patients gave their ethnicity as either black/black British or Asian/Asian British, significantly more than in the non-TB renal group. Cases occurred steadily over the time period in which patients were in the cohort. CONCLUSION TB incidence was very high among those receiving renal replacement therapy or CKD 4 or 5. Most cases occurred in those of an Asian/Asian British or black/black British background. Testing and treating such patients for latent TB is justified and should include those who have been receiving renal replacement therapy for some years

The Acute Kidney Outreach to Prevent Deterioration and Death trial: a large pilot study for a cluster-randomized trial.

BACKGROUND AND OBJECTIVES The Acute Kidney Outreach to Reduce Deterioration and Death trial was a large pilot study for a cluster-randomized trial of acute kidney injury (AKI) outreach. METHODS An observational control (before) phase was conducted in two teaching hospitals (9 miles apart) and their respective catchment areas. In the intervention (after) phase, a working-hours AKI outreach service operated for the intervention hospital/area for 20 weeks, with the other site acting as a control. All AKI alerts in both hospital and community patients were screened for inclusion. Major exclusion criteria were patients who were at the end of life, unlikely to benefit from outreach, lacking mental capacity or already referred to the renal team. The intervention arm included a model of escalation of renal care to AKI patients, depending on AKI stage. The 30-day primary outcome was a combination of death, or deterioration, as shown by any need for dialysis or progression in AKI stage. A total of 1762 adult patients were recruited; 744 at the intervention site during the after phase. RESULTS A median of 3.0 non-medication recommendations and 0.5 medication-related recommendations per patient were made by the outreach team a median of 15.7 h after the AKI alert. Relatively low rates of the primary outcomes of death within 30 days (11-15%) or requirement for dialysis (0.4-3.7%) were seen across all four groups. In an exploratory analysis, at the intervention hospital during the after phase, there was an odds ratio for the combined primary outcome of 0.73 (95% confidence interval 0.42-1.26; P = 0.26). CONCLUSIONS An AKI outreach service can provide standardized specialist care to those with AKI across a healthcare economy. Trials assessing AKI outreach may benefit from focusing on those patients with 'mid-range' prognosis, where nephrological intervention could have the most impact

Does community-wide chronic kidney disease management improve patient outcomes?

BACKGROUND The number of patients starting renal replacement therapy (RRT) is increasing in England, as it is worldwide. Improvements in the management of chronic kidney disease (CKD) across communities to alter this trend are a public health priority. We have prospectively studied changes in the incidence and modality of treatment for end-stage renal disease following the introduction of a CKD management programme in the West Midlands region of England. METHODS Nephrology service to approximately 700 000 adult population of mixed ethnicity in urban and suburban areas, many with social deprivation. The programme was introduced in stages between 2003 and 2006 and comprised primary care education and financial incentives, personal clinical reports written directly to patients following every consultation, routine laboratory estimated glomerular filtration rate (eGFR) reporting, eGFR graph surveillance to identify and monitor patients at risk, multidisciplinary pre-RRT care and conservative care. Prevalent patients: 10 552 with CKD and 8509 without CKD with diabetes. Outcomes: access to nephrology care, trends in RRT incidence and starting modality, place of death without RRT. Incident count was adjusted for changes in the local adult population recorded in national censuses. RESULTS Ninety-one per cent of patients aged ≥75 years with incident CKD stage 5 were known to a nephrologist. The population-adjusted incident RRT rate peaked in 2005 and then declined; the proportion starting with transplant, peritoneal dialysis or haemodialysis by arterio-venous fistula increased to 63% by 2012 (P = 0.001 versus 2005). Fifty-two per cent of patients receiving planned conservative care without dialysis died out of hospital. CONCLUSIONS Following the introduction of a community-wide systematic CKD management programme, the population-adjusted incidence of RRT reduced, modality of initiation of RRT improved and a majority of patients receiving planned conservative care without dialysis died out of hospital

Earlier intervention for acute kidney injury: evaluation of an outreach service and a long-term follow-up.

BACKGROUND There have been few studies of earlier systematic intervention to reduce the impact of acute kidney injury (AKI). In 2009, we piloted an AKI outreach service with a before and after study, and we report on the study and its longer-term follow-up. METHODS AKI patients were identified using a laboratory delta check for creatinine of 75%. In the 4-week before phase patients received standard care. In a consecutive 7-week after phase an outreach team of nephrology doctors and nurses reviewed all alerts twice daily, 5 days a week. The primary clinical team caring for the patient was called to be given advice on AKI care. RESULTS There were 157 and 251 patients in the before and after groups, respectively, who were comparable in their characteristics. The mean age was 70 years in both groups and ∼ 80% of each group were admitted to the hospital. In the after group, the Outreach telephone call was successful in 88%, at a median of 14 h. Substantial numbers of recommendations were made, largely related to fluid balance, investigations and medication use. Survival showed an immediate non-significant improvement in the after group, but converged at about 4 years. CONCLUSION Outreach shows potential to improve outcomes in AKI. In order to achieve this it seems likely that at least a five-day per week service will be needed to assist good renal and general medical care for this vulnerable group

Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape

Witte et al show that previously acquired substitutions in the SARS-CoV-2 spike protein enable the acquisition of new antibody escape substitutions. New and old substitutions interact to enable escape from broadly neutralizing antibodies