Impact of early life development on later onset chronic kidney disease and hypertension and the role of evolutionary trade-offs

NEW FINDINGS What is the topic of this review? In this report, we summarize the latest clinical evidence linking developmental programming in the kidney to later life blood pressure and kidney disease. What advances does it highlight? Population-level studies now show convincingly that low birth weight, fetal growth restriction and preterm birth are associated with and have a synergistic impact on the risk of kidney disease in later life. A new approach also considers how evolutionary selection pressure might fail to select for long-term robustness of kidney function. ABSTRACT The global burden of kidney disease is high and rising. The risk of kidney disease among individuals is highly variable, in part related to genetic and environmental factors, but also likely to be modulated by developmental programming of the number of nephrons and kidney function in fetal life. The number of nephrons varies widely across the population and is lower among those who were born small or preterm. Population registry evidence clearly shows an association between these birth circumstances and later-life risk of hypertension and kidney disease, not only for chronic kidney disease but also for acquired kidney disease, demonstrating an inherent susceptibility to kidney disease in these individuals. Gestational stressors impact kidney development, a process that is likely to be layered upon the evolutionary history of the kidney and how the organ has developed in response to selection pressure to support reproductive capacity in early adulthood, but not to withstand multiple stresses later in life. Reducing the global burden of kidney disease in future generations will require both individual- and population/environment-level risks to be addressed

Low Nephron Number and Its Clinical Consequences

Epidemiologic studies now strongly support the hypothesis, proposed over two decades ago, that developmental programming of the kidney impacts an individual’s risk for hypertension and renal disease in later life. Low birth weight is the strongest current clinical surrogate marker for an adverse intrauterine environment and, based on animal and human studies, is associated with a low nephron number. Other clinical correlates of low nephron number include female gender, short adult stature, small kidney size, and prematurity. Low nephron number in Caucasian and Australian Aboriginal subjects has been shown to be associated with higher blood pressures, and, conversely, hypertension is less prevalent in individuals with higher nephron numbers. In addition to nephron number, other programmed factors associated with the increased risk of hypertension include salt sensitivity, altered expression of renal sodium transporters, altered vascular reactivity, and sympathetic nervous system overactivity. Glomerular volume is universally found to vary inversely with nephron number, suggesting a degree of compensatory hypertrophy and hyperfunction in the setting of a low nephron number. This adaptation may become overwhelmed in the setting of superimposed renal insults, e.g. diabetes mellitus or rapid catch-up growth, leading to the vicious cycle of on-going hyperfiltration, proteinuria, nephron loss and progressive renal functional decline. Many millions of babies are born with low birth weight every year, and hypertension and renal disease prevalences are increasing around the globe. At present, little can be done clinically to augment nephron number; therefore adequate prenatal care and careful postnatal nutrition are crucial to optimize an individual’s nephron number during development and potentially to stem the tide of the growing cardiovascular and renal disease epidemics worldwide

Preventing CKD in Developed Countries

Chronic kidney disease (CKD) is an important public health concern in developed countries because of both the number of people affected and the high cost of care when prevention strategies are not effectively implemented. Prevention should start at the governance level with the institution of multisectoral polices supporting sustainable development goals and ensuring safe and healthy environments. Primordial prevention of CKD can be achieved through implementation of measures to ensure healthy fetal (kidney) development. Public health strategies to prevent diabetes, hypertension, and obesity as risk factors for CKD are important. These approaches are cost-effective and reduce the overall noncommunicable disease burden. Strategies to prevent nontraditional CKD risk factors, including nephrotoxin exposure, kidney stones, infections, environmental exposures, and acute kidney injury (AKI), need to be tailored to local needs and epidemiology. Early diagnosis and treatment of CKD risk factors such as diabetes, obesity, and hypertension are key for primary prevention of CKD. CKD tends to occur more frequently and to progress more rapidly among indigenous, minority, and socioeconomically disadvantaged populations. Special attention is required to meet the CKD prevention needs of these populations. Effective secondary prevention of CKD relies on screening of individuals at risk to detect and treat CKD early, using established and emerging strategies. Within high-income countries, barriers to accessing effective CKD therapies must be recognized, and public health strategies must be developed to overcome these obstacles, including training and support at the primary care level to identify individuals at risk of CKD, and appropriately implement clinical practice guidelines

When the Earth trembles in the americas: the experience of haiti and chile 2010.

The response of the nephrological community to the Haiti and Chile earthquakes which occurred in the first months of 2010 is described. In Haiti, renal support was organized by the Renal Disaster Relief Task Force (RDRTF) of the International Society of Nephrology (ISN) in close collaboration with Médecins Sans Frontières (MSF), and covered both patients with acute kidney injury (AKI) and patients with chronic kidney disease (CKD). The majority of AKI patients (19/27) suffered from crush syndrome and recovered their kidney function. The remaining 8 patients with AKI showed acute-to-chronic renal failure with very low recovery rates. The intervention of the RDRTF-ISN involved 25 volunteers of 9 nationalities, lasted exactly 2 months, and was characterized by major organizational difficulties and problems to create awareness among other rescue teams regarding the availability of dialysis possibilities. Part of the Haitian patients with AKI reached the Dominican Republic (DR) and received their therapy there. The nephrological community in the DR was able to cope with this extra patient load. In both Haiti and the DR, dialysis treatment was able to be prevented in at least 40 patients by screening and adequate fluid administration. Since laboratory facilities were destroyed in Port-au-Prince and were thus lacking during the first weeks of the intervention, the use from the very beginning on of a point-of-care device (i-STAT®) was very efficient for the detection of aberrant kidney function and electrolyte parameters. In Chile, nephrological problems were essentially related to difficulties delivering dialysis treatment to CKD patients, due to the damage to several units. This necessitated the reallocation of patients and the adaptation of their schedules. The problems could be handled by the local nephrologists. These observations illustrate that local and international preparedness might be life-saving if renal problems occur in earthquake circumstances

К анализу производственных затрат при столбовой системе отработки тонких пологих пластов угля комплексами нового поколения

У статті проаналізовано основні виробничі витрати при стовбовій системі відпрацювання тонких положистих пластів вугілля комплексами нового покоління. Розглянуто залежність собівартості видобутку вугілля при різних параметрах відпрацювання тонких положистих пластів вугілля.The article discusses the basic production spending for system development Pole thin flat layers of coal complexes of new generation. We consider the dependence of the cost of coal at different parameters development thin shallow coal seams

Compulsivity Reveals a Novel Dissociation between Action and Confidence

Confidence and actions are normally tightly interwoven—if I am sure that it is going to rain, I will take an umbrella—therefore, it is difficult to understand their interplay. Stimulated by the ego-dystonic nature of obsessive-compulsive disorder (OCD), where compulsive actions are recognized as disproportionate, we hypothesized that action and confidence might be independently updated during learning. Participants completed a predictive-inference task designed to identify how action and confidence evolve in response to surprising changes in the environment. While OCD patients (like controls) correctly updated their confidence according to changes in the environment, their actions (unlike those of controls) mostly disregarded this knowledge. Therefore, OCD patients develop an accurate, internal model of the environment but fail to use it to guide behavior. Results demonstrated a novel dissociation between confidence and action, suggesting a cognitive architecture whereby confidence estimates can accurately track the statistic of the environment independently from performance.B.D.M. was supported by Wellcome Trust and Royal Society (Sir Henry Dale Fellowship 102612/A/13/Z). T.W.R. was supported by Wellcome Trust (Senior Investigator Award 104631/Z/14/Z). M.M.V. is supported by a Pinsent Darwin Scholarship in Mental Pathology and an Angharad Dodds John Bursary in Mental Health and Neuropsychiatry

Outcomes of acute kidney injury in children and adults in sub-Saharan Africa: a systematic review

Background Access to diagnosis and dialysis for acute kidney injury can be life-saving, but can be prohibitively expensive in low-income settings. The burden of acute kidney injury in sub-Saharan Africa is presumably high but remains unknown. We did a systematic review to assess outcomes of acute kidney injury in sub-Saharan Africa and identify barriers to care. Methods We searched PubMed, African Journals Online, WHO Global Health Library, and Web of Science for articles published between Jan 1, 1990, and Nov 30, 2014. We scored studies, and all were of medium-to-low quality. We made a pragmatic decision to include all studies to best refl ect reality, and did a descriptive analysis of extracted data. This study is registered with PROSPERO, number CRD42015015690. Findings We identifi ed 3881 records, of which 41 met inclusion criteria, including 1403 adult patients and 1937 paediatric patients. Acute kidney injury in sub-Saharan Africa is severe, with 1042 (66%) of 1572 children and 178 (70%) 253 of adults needing dialysis in studies reporting dialysis need. Only 666 (64%) of 1042 children (across 11 studies) and 58 (33%) of 178 adults (across four studies) received dialysis when needed. Overall mortality was 34% in children and 32% in adults, but rose to 73% in children and 86% in adults when dialysis was needed but not received. Major barriers to access to care were out-of-pocket costs, erratic hospital resources, late presentation, and female sex. Interpretation Patients in these studies are those with resources to access care. In view of overall study quality, data interpretation should be cautious, but high mortality and poor access to dialysis are concerning. The global scarcity of resources among patients and health centres highlights the need for a health-system-wide approach to prevention and management of acute kidney injury in sub-Saharan Africa

Outcomes in adults and children with end-stage kidney disease requiring dialysis in sub-Saharan Africa: a systematic review

Background The burden of end-stage kidney disease (ESKD) in sub-Saharan Africa is unknown but is probably high. Access to dialysis for ESKD is limited by insufficient infrastructure and catastrophic out-of-pocket costs. Most patients remain undiagnosed, untreated, and die. We did a systematic literature review to assess outcomes of patients who reach dialysis and the quality of dialysis received. Methods We searched PubMed, African Journals Online, WHO Global Health Library, and Web of Science for articles in English or French from sub-Saharan Africa reporting dialysis outcomes in patients with ESKD published between Jan 1, 1990, and Dec 22, 2015. No studies were excluded to best represent the current situation in sub-Saharan Africa. Outcomes of interest included access to dialysis, mortality, duration of dialysis, and markers of dialysis quality in patients with ESKD. Data were analysed descriptively and reported using narrative synthesis. Findings Studies were all of medium to low quality. We identified 4339 studies, 68 of which met inclusion criteria, comprising 24 456 adults and 809 children. In the pooled analysis, 390 (96%) of 406 adults and 133 (95%) of 140 children who could not access dialysis died or were presumed to have died. Among those dialysed, 2747 (88%) of 3122 adults in incident ESKD cohorts, 496 (16%) of 3197 adults in prevalent ESKD cohorts, and 107 (36%) of 294 children with ESKD died or were presumed to have died. 2508 (84%) of 2990 adults in incident ESKD cohorts discontinued dialysis compared with 64 (5%) of 1364 adults in prevalent ESKD cohorts. 41 (1%) of 4483 adults in incident ESKD cohorts, 2280 (19%) of 12 125 adults in prevalent ESKD cohorts, and 71 (19%) of 381 children with ESKD received transplants. 16 studies reported on management of anaemia, 17 on dialysis frequency, eight on dialysis accuracy, and 22 on vascular access for dialysis Interpretation Most patients with ESKD starting dialysis in sub-Saharan Africa discontinue treatment and die. Further work is needed to develop equitable and sustainable strategies to manage individuals with ESKD in sub-Saharan Africa

Challenges to the right to health in sub-Saharan Africa: reflections on inequities in access to dialysis for patients with end-stage kidney failure

Realization of the individual’s right to health in settings such as sub-Saharan Africa, where health care adequate resources are lacking, is challenging. This paper demonstrates this challenge by illustrating the example of dialysis, which is an expensive but life-saving treatment for people with kidney failure. Dialysis resources, if available in sub-Saharan Africa, are generally limited but in high demand, and clinicians at the bedside are faced with deciding who lives and who dies. When resource limitations exist, transparent and objective priority setting regarding access to such expensive care is required to improve equity across all health needs in a population. This process however, which weighs individual and population health needs, denies some the right to health by limiting access to health care.This paper unpacks what it means to recognize the right to health in sub-Saharan Africa, acknowledging the current resource availability and scarcity, and the larger socio-economic context. We argue, the first order of the right to health, which should always be realized, includes protection of health, i.e. prevention of disease through public health and health-in-all policy approaches. The second order right to health care would include provision of universal health coverage to all, such that risk factors and diseases can be effectively and equitably detected and treated early, to prevent disease progression or development of complications, and ultimately reduce the demand for expensive care. The third order right to health care would include equitable access to expensive care. In this paper, we argue that recognition of the inequities in realization of the right to health between individuals with “expensive” needs versus those with more affordable needs, countries must determine if, how, and when they will begin to provide such expensive care, so as to minimize these inequities as rapidly as possible. Such a process requires good governance, multi-stakeholder engagement, transparency, communication and a commitment to progress. We conclude the paper by emphasizing that striving towards the progressive realization of the right to health for all people living in SSA is key to achieving equity in access to quality health care and equitable opportunities for each individual to maximize their own state of health