Acute Kidney Injury: Global Health Alert

Acute kidney injury (AKI) is increasingly prevalent in developing and developed countries and is associated with severe morbidity and mortality. Most etiologies of AKI can be prevented by interventions at the individual, community, regional and in-hospital levels. Effective measures must include community-wide efforts to increase an awareness of the devastating effects of AKI and provide guidance on preventive strategies, as well as early recognition and management. Efforts should be focused on minimizing causes of AKI, increasing awareness of the importance of serial measurements of serum creatinine in high risk patients, and documenting urine volume in acutely ill people to achieve early diagnosis; there is as yet no definitive role for alternative biomarkers. Protocols need to be developed to systematically manage prerenal conditions and specific infections. More accurate data about the true incidence and clinical impact of AKI will help to raise the importance of the disease in the community, increase awareness of AKI by governments, the public, general and family physicians and other health care professionals to help prevent the disease. Prevention is the key to avoid the heavy burden of mortality and morbidity associated with AKI

Clinical and patient-reported outcomes of Chinese patients undergoing haemodialysis in hospital or in the community: A 1-year longitudinal study

Aim: Little is known about the effect of haemodialysis (HD) setting on outcomes of patients with end stage renal disease (ESRD). The study aimed at comparing clinical outcomes and patient-reported outcomes (PRO) of patients on community-based (CBHD) and hospital- based haemodialysis (HBHD). Methods: A prospective cohort of Chinese ESRD patients receiving HBHD (n=89) or CBHD (n=117) in Hong Kong were followed up for 12 months. Subjects were assessed on clinical outcomes of dialysis adequacy (Kt/V) and blood haemoglobin and PRO of health-related quality of life (SF-12v2), general health condition (Global Rating Scale (GRS)) and confidence to cope with their illness (Patient Enablement Instrument (PEI)). Differences between groups were analysed by independent t-tests for the SF-12v2, GRS and PEI scores. Chi-square tests were used to analyse the difference in proportion of patients reaching the targets of Kt/V and blood haemoglobin and with GRS>0 and PEI>0. Multiple linear and logistic regressions were performed to assess the adjusted difference-in-difference estimation. Results: The mean PEI and GRS scores of CBHD patients at 12 months were significantly higher than those of HBHD patients. CBHD patients had significantly greater improvement in self-efficacy and were more likely to be enabled after 12 months than the HBHD patients. Conclusion: The study showed similar clinical outcomes and PRO between CBHD and HBHD but CBHD was more effective than HBHD in promoting patient enablement over a 12-month period. The results suggest added value for patients receiving CBHD and support the transfer of HD care from the hospital to the community.published_or_final_versio

Pregnancy in Chronic Kidney Disease: Need for Higher Awareness. A Pragmatic Review Focused on What Could Be Improved in the Different CKD Stages and Phases

Pregnancy is possible in all phases of chronic kidney disease (CKD), but its management may be difficult and the outcomes are not the same as in the overall population. The prevalence of CKD in pregnancy is estimated at about 3%, as high as that of pre-eclampsia (PE), a better-acknowledged risk for adverse pregnancy outcomes. When CKD is known, pregnancy should be considered as high risk and followed accordingly; furthermore, since CKD is often asymptomatic, pregnant women should be screened for the presence of CKD, allowing better management of pregnancy, and timely treatment after pregnancy. The differential diagnosis between CKD and PE is sometimes difficult, but making it may be important for pregnancy management. Pregnancy is possible, even if at high risk for complications, including preterm delivery and intrauterine growth restriction, superimposed PE, and pregnancy-induced hypertension. Results in all phases are strictly dependent upon the socio-sanitary system and the availability of renal and obstetric care and, especially for preterm children, of intensive care units. Women on dialysis should be aware of the possibility of conceiving and having a successful pregnancy, and intensive dialysis (up to daily, long-hours dialysis) is the clinical choice allowing the best results. Such a choice may, however, need adaptation where access to dialysis is limited or distances are prohibitive. After kidney transplantation, pregnancies should be followed up with great attention, to minimize the risks for mother, child, and for the graft. A research agenda supporting international comparisons is highly needed to ameliorate or provide knowledge on specific kidney diseases and to develop context-adapted treatment strategies to improve pregnancy outcomes in CKD women

Acute Kidney Injury in Pregnancy: The Need for Higher Awareness. A Pragmatic Review Focused on What Could Be Improved in the Prevention and Care of Pregnancy-Related AKI, in the Year Dedicated to Women and Kidney Diseases

Pregnancy-related acute kidney injury (pAKI), preeclampsia (PE), and the hypertensive disorders of pregnancy are closely related conditions, which are, in turn, frequently linked to pre-existing and often non-diagnosed chronic kidney disease (CKD). The current literature and research mainly underline the effects of pregnancy complications on the offspring; this review strongly emphasizes the maternal health as well. These conditions not only negatively affect pregnancy outcomes, but have a relevant effect on the future health of affected mothers and their children. Therefore, dedicated diagnostic and follow-up programs are needed, for optimizing materno-foetal health and reducing the impact of pregnancy-related problems in the mothers and in the new generations. This narrative review, performed on the occasion of the 2018 World Kidney Day dedicated to women's health, focuses on three aspects of the problem. Firstly, the risk of AKI in the hypertensive disorders of pregnancy (the risk is the highest in developing countries; however PE is the main cause of pregnancy related AKI worldwide). Secondly, the effect of AKI and the hypertensive disorders of pregnancy on the development of CKD in the mother and offspring: long-term risks are increased; the entity and the trajectories are still unknown. Thirdly, the role of CKD in the pathogenesis of AKI and the hypertensive disorders of pregnancy: CKD is a major risk factor and the most important element in the differential diagnosis; pregnancy is a precious occasion for early diagnosis of CKD. Higher awareness on the importance of AKI in pregnancy is needed to improve short and long term outcomes in mothers and children

Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression

Background Acute changes in GFR can occur after initiation of interventions targeting progression of CKD. These acute changes complicate the interpretation of long-term treatment effects. Methods To assess the magnitude and consistency of acute effects in randomized clinical trials and explore factors that might affect them, we performed a meta-analysis of 53 randomized clinical trials for CKD progression, enrolling 56,413 participants with at least one estimated GFR measurement by 6 months after randomization. We defined acute treatment effects as the mean difference in GFR slope from baseline to 3 months between randomized groups. We performed univariable and multivariable metaregression to assess the effect of intervention type, disease state, baseline GFR, and albuminuria on the magnitude of acute effects. Results The mean acute effect across all studies was 20.21 ml/min per 1.73 m2 (95% confidence interval, 20.63 to 0.22) over 3 months, with substantial heterogeneity across interventions (95% coverage interval across studies, 22.50 to 12.08 ml/min per 1.73 m2). We observed negative average acute effects in renin angiotensin system blockade, BP lowering, and sodium-glucose cotransporter 2 inhibitor trials, and positive acute effects in trials of immunosuppressive agents. Larger negative acute effects were observed in trials with a higher mean baseline GFR. Conclusion The magnitude and consistency of acute GFR effects vary across different interventions, and are larger at higher baseline GFR. Understanding the nature and magnitude of acute effects can help inform the optimal design of randomized clinical trials evaluating disease progression in CKD

A meta-analysis of GFR slope as a surrogate endpoint for kidney failure

Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min−1 per 1.73 m2 or kidney failure with replacement therapy). We used a Bayesian mixed-effects meta-regression model to relate treatment effects on GFR slope with those on the clinical endpoint across all studies and by disease groups (diabetes, glomerular diseases, CKD or cardiovascular diseases). Treatment effects on the clinical endpoint were strongly associated with treatment effects on total slope (median coefficient of determination (R2) = 0.97 (95% Bayesian credible interval (BCI) 0.82–1.00)) and moderately associated with those on chronic slope (R2 = 0.55 (95% BCI 0.25–0.77)). There was no evidence of heterogeneity across disease. Our results support the use of total slope as a primary endpoint for clinical trials of CKD progression

Comparative functional analysis of aquaporins/glyceroporins in mammals and anurans

Maintenance of fluid homeostasis is critical to establishing and maintaining normal physiology. The landmark discovery of membrane water channels (aquaporins; AQPs) ushered in a new area in osmoregulatory biology that has drawn from and contributed to diverse branches of biology, from molecular biology and genomics to systems biology and evolution, and from microbial and plant biology to animal and translational physiology. As a result, the study of AQPs provides a unique and integrated backdrop for exploring the relationships between genes and genome systems, the regulation of gene expression, and the physiologic consequences of genetic variation. The wide species distribution of AQP family members and the evolutionary conservation of the family indicate that the control of membrane water flux is a critical biological process. AQP function and regulation is proving to be central to many of the pathways involved in individual physiologic systems in both mammals and anurans. In mammals, AQPs are essential to normal secretory and absorptive functions of the eye, lung, salivary gland, sweat glands, gastrointestinal tract, and kidney. In urinary, respiratory, and gastrointestinal systems, AQPs are required for proper urine concentration, fluid reabsorption, and glandular secretions. In anurans, AQPs are important in mediating physiologic responses to changes in the external environment, including those that occur during metamorphosis and adaptation from an aquatic to terrestrial environment and thermal acclimation in anticipation of freezing. Therefore, an understanding of AQP function and regulation is an important aspect of an integrated approach to basic biological research

De novo Assembly of a 40 Mb Eukaryotic Genome from Short Sequence Reads: Sordaria macrospora, a Model Organism for Fungal Morphogenesis

Filamentous fungi are of great importance in ecology, agriculture, medicine, and biotechnology. Thus, it is not surprising that genomes for more than 100 filamentous fungi have been sequenced, most of them by Sanger sequencing. While next-generation sequencing techniques have revolutionized genome resequencing, e.g. for strain comparisons, genetic mapping, or transcriptome and ChIP analyses, de novo assembly of eukaryotic genomes still presents significant hurdles, because of their large size and stretches of repetitive sequences. Filamentous fungi contain few repetitive regions in their 30–90 Mb genomes and thus are suitable candidates to test de novo genome assembly from short sequence reads. Here, we present a high-quality draft sequence of the Sordaria macrospora genome that was obtained by a combination of Illumina/Solexa and Roche/454 sequencing. Paired-end Solexa sequencing of genomic DNA to 85-fold coverage and an additional 10-fold coverage by single-end 454 sequencing resulted in ∼4 Gb of DNA sequence. Reads were assembled to a 40 Mb draft version (N50 of 117 kb) with the Velvet assembler. Comparative analysis with Neurospora genomes increased the N50 to 498 kb. The S. macrospora genome contains even fewer repeat regions than its closest sequenced relative, Neurospora crassa. Comparison with genomes of other fungi showed that S. macrospora, a model organism for morphogenesis and meiosis, harbors duplications of several genes involved in self/nonself-recognition. Furthermore, S. macrospora contains more polyketide biosynthesis genes than N. crassa. Phylogenetic analyses suggest that some of these genes may have been acquired by horizontal gene transfer from a distantly related ascomycete group. Our study shows that, for typical filamentous fungi, de novo assembly of genomes from short sequence reads alone is feasible, that a mixture of Solexa and 454 sequencing substantially improves the assembly, and that the resulting data can be used for comparative studies to address basic questions of fungal biology