Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Background Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). Findings Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9–16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32–0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity

Anestesia por infusão contínua de propofol em cães pré-medicados com acepromazina e fentanil Anesthesia by continuous infusion of propofol in dogs premedicated with acepromazine and fentanyl

O propofol (2,6 diisopropilfenol) é um agente hipnótico de ultra curta duração que produz sedação e hipnose similar aos barbitúricos, sendo desprovido de ação analgésica. Quimicamente, é o único agente anestésico venoso que pode ser usado tanto na indução como na manutenção anestésica. O presente trabalho objetivou avaliar freqüência cardíaca, respiratória, oximetria, pressão arterial média, volume minuto e volume corrente em cães pré-medicados com acepromazina e fentanil e anestesiados por infusão contínua de propofol. Dez cães foram submetidos à medicação pré-anestésica com acepromazina (0,1mg.kg-1) e fentanil (0,01mg.kg-1), indução (3,16mg.kg-1) e manutenção anestésica com propofol em infusão contínua por noventa minutos, na velocidade de 0,4mg.kg-1.min-1. Os parâmetros foram mensurados imediatamente após a indução, 10, 20, 30, 60 e 90 minutos após; final da infusão e 30 minutos após o seu término. Os parâmetros foram analisados por análise de variância para valores repetidos e as médias foram analisadas pelo teste de Tuckey em nível de 5%. O protocolo utilizado não produziu variações estatisticamente significativas em nenhum dos parâmetros analisados. Um animal apresentou apnéia durante a indução. Embasado nesses resultados, verifica-se que o presente protocolo é seguro e eficaz para a realização de anestesia venosa em caninos.<br>Propofol (2,6 diisopropylphenol) is an ultra short duration hypnotic agent that produces sedation and hypnosis similar to barbituric agent, but lacks analgesic action. This is a chemically unique anesthetic agent that can be used for induction and anesthetic maintenance. The objective of this research was to evaluate the cardiac and respiratory rate, oximetry, mean arterial blood pressure and tidal volume and minute volume in dogs premedicated with acepromazine and fentanyl and anesthetized by continuous infusion by propofol. Ten dogs were submitted to anesthesia by continuous propofol infusion during ninety minutes. Using acepromazine (0.1mg.kg-1) and fentanyl (0.01mg.kg-1) as pre anesthetic drugs, anesthesia was induced using propofol (3.16mg.kg-1) and maintained by continuous infusion of propofol in a rate of 0.4mg.kg-1 .min-1. The parameters were measured immediately after induction, at 10, 20, 30, 60 and 90 minutes following induction; by the end of infusion and 30 minutes after the end of infusion. The parameters were analyzed by analysis of variance for repeated measures and the means were analyzed by the Tuckey test to 5% of significance. The protocol used had no statistical effect on the parameters analyzed. One animal showed apnea during the induction phase. The results obtained in this experiment suggest that this protocol might be safely and efficiently used for routine intravenous anesthesia in dogs

Testing a global standard for quantifying species recovery and assessing conservation impact.

Recognizing the imperative to evaluate species recovery and conservation impact, in 2012 the International Union for Conservation of Nature (IUCN) called for development of a "Green List of Species" (now the IUCN Green Status of Species). A draft Green Status framework for assessing species' progress toward recovery, published in 2018, proposed 2 separate but interlinked components: a standardized method (i.e., measurement against benchmarks of species' viability, functionality, and preimpact distribution) to determine current species recovery status (herein species recovery score) and application of that method to estimate past and potential future impacts of conservation based on 4 metrics (conservation legacy, conservation dependence, conservation gain, and recovery potential). We tested the framework with 181 species representing diverse taxa, life histories, biomes, and IUCN Red List categories (extinction risk). Based on the observed distribution of species' recovery scores, we propose the following species recovery categories: fully recovered, slightly depleted, moderately depleted, largely depleted, critically depleted, extinct in the wild, and indeterminate. Fifty-nine percent of tested species were considered largely or critically depleted. Although there was a negative relationship between extinction risk and species recovery score, variation was considerable. Some species in lower risk categories were assessed as farther from recovery than those at higher risk. This emphasizes that species recovery is conceptually different from extinction risk and reinforces the utility of the IUCN Green Status of Species to more fully understand species conservation status. Although extinction risk did not predict conservation legacy, conservation dependence, or conservation gain, it was positively correlated with recovery potential. Only 1.7% of tested species were categorized as zero across all 4 of these conservation impact metrics, indicating that conservation has, or will, play a role in improving or maintaining species status for the vast majority of these species. Based on our results, we devised an updated assessment framework that introduces the option of using a dynamic baseline to assess future impacts of conservation over the short term to avoid misleading results which were generated in a small number of cases, and redefines short term as 10 years to better align with conservation planning. These changes are reflected in the IUCN Green Status of Species Standard