Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data

BACKGROUND: Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. METHODS: UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. RESULTS: Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. CONCLUSIONS: UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD

Haplodiploid androgenetic breeding in oat: genotypic variation in anther size and microspore development stage Melhoramento por haplodiploidização androgenética: variação genotípica no tamanho das anteras e no estágio de desenvolvimento dos micrósporos em aveia

Oat (Avena spp.) is poorly responsive to the haplodiploidization process, which leads to the production of homozygous lines in one step, increasing breeding efficiency. Androgenetic haploids in small grain cereal crops are obtained from microspores cultured at the mononucleate stage, which can be identified by the size of anthers. In order to identify the appropriate anther size for in vitro culture, microspore cytological analyses were made in Avena sativa cultivars UPF 7, UPF 18, UFRGS 14, Stout and Avena sterilis CAV 3361, cultivated in growth chamber under controlled light and temperature conditions. Variation was observed within and among genotypes for anther size at each microspore developmental stage and according to the position of spikelets in the panicle. Architecture variation in panicle shape and non-linear microsporogenesis maturation increased the challenge of identifying potentially androgenetic oat anthers. Cytological screening before culture is critical in identifying microspores at the right stage for oat androgenesis.<br>A aveia (Avena spp.) tem sido pouco responsiva à haplodiploidização, um processo que aumenta a eficiência da seleção no melhoramento por gerar, em uma etapa, linhas puras homozigóticas. A fase mononucleada do micrósporo é critica para o sucesso da androgênese in vitro nos cereais de inverno e, em geral, pode ser inferida pelo tamanho da antera. Foram medidas anteras e analisados citológicamente micrósporos das cultivares de Avena sativa UPF 7, UPF 18, UFRGS 14, Stout e da linhagem CAV 3361 de Avena sterilis, cultivadas em câmaras de crescimento sob temperaturas dia-noite variando de 16ºC a 9ºC e 12 horas de intensidade luminosa de 300 mol m-2 s-1. O tamanho das anteras em cada fase de desenvolvimento dos micrósporos variou significativamente entre genótipos e de acordo com a região de inserção das espiguetas na panícula. A variação na arquitetura da panícula e a maturação não linear das espiguetas aumentam as dificuldades para a identificação das anteras potencialmente androgenéticas e podem explicar, em parte, os baixos resultados da androgênese na aveia. Os dados mostram a necessidade de uma análise citológica prévia para auxiliar a determinar a fase ideal de desenvolvimento dos micrósporos potencialmente responsivos à cultura de anteras, para o uso da androgenese na aveia