https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)61692-4.pdf

Maternal and child undernutrition: consequences for adult health and human capital.

Acute kidney injury

The "fetal" or "early" origins of adult disease hypothesis was originally put forward by David Barker and colleagues and stated that environmental factors, particularly nutrition, act in early life to program the risks for adverse health outcomes in adult life. This hypothesis has been supported by a worldwide series of epidemiological studies that have provided evidence for the association between the perturbation of the early nutritional environment and the major risk factors (hypertension, insulin resistance, and obesity) for cardiovascular disease, diabetes, and the metabolic syndrome in adult life. It is also clear from experimental studies that a range of molecular, cellular, metabolic, neuroendocrine, and physiological adaptations to changes in the early nutritional environment result in a permanent alteration of the developmental pattern of cellular proliferation and differentiation in key tissue and organ systems that result in pathological consequences in adult life. This review focuses on those experimental studies that have investigated the critical windows during which perturbations of the intrauterine environment have major effects, the nature of the epigenetic, structural, and functional adaptive responses which result in a permanent programming of cardiovascular and metabolic function, and the role of the interaction between the pre- and postnatal environment in determining final health outcomes.

https://www.physiology.org/doi/pdf/10.1152/physrev.00053.2003

Developmental Origins of the Metabolic Syndrome: Prediction, Plasticity, and Programming

Many plants and animals are capable of developing in a variety of ways, forming characteristics that are well adapted to the environments in which they are likely to live. In adverse circumstances, for example, small size and slow metabolism can facilitate survival, whereas larger size and more rapid metabolism have advantages for reproductive success when resources are more abundant. Often these characteristics are induced in early life or are even set by cues to which their parents or grandparents were exposed. Individuals developmentally adapted to one environment may, however, be at risk when exposed to another when they are older. The biological evidence may be relevant to the understanding of human development and susceptibility to disease. As the nutritional state of many human mothers has improved around the world, the characteristics of their offspring--such as body size and metabolism--have also changed. Responsiveness to their mothers' condition before birth may generally prepare individuals so that they are best suited to the environment forecast by cues available in early life. Paradoxically, however, rapid improvements in nutrition and other environmental conditions may have damaging effects on the health of those people whose parents and grandparents lived in impoverished conditions. A fuller understanding of patterns of human plasticity in response to early nutrition and other environmental factors will have implications for the administration of public health.

Developmental plasticity and human health.

1 Many human fetuses have to adapt to a limited supply of nutrients In doing so they permanently change their structure and metabolism 2 These 'programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension 3 This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area

In utero programming of chronic disease

The hyperfiltration theory: a paradigm shift in nephrology.

Background: The success rate of transplanted organs from brain-dead cadaver donors is consistently inferior to that of living sources. As cadaver and living unrelated donors are equally genetically disparate with a given recipient, the difference must lie within the donor himself and/or the effects of organ preservation and storage. We have hypothesized that irreversible central nervous system injury may up-regulate proinflammatory mediators and cell surface molecules in peripheral organs to be engrafted, making them more prone to host inflammatory and immunological responses. Methods. Rats undergoing surgically induced acutely increased intracranial pressure (explosive brain death) were followed for 6 hr. Their peripheral tissues were examined by reverse transcriptase polymerase chain reaction and immunohistology, serum factors were assessed by enzyme-linked immunosorbent assay, and the influence of inflammatory molecules in the blood stream was determined by cross-circulation experiments with normal animals. Results. mRNA expression of both lymphocyte- and macrophage-associated products increased dramatically in all tissues. Similar factors in serum were coincidentally increased; these were shown to be active in vivo by cross-circulation with normal animals. The organs of all control groups, including animals with important ischemic injury and with hemorrhagic shock, were negative. Up-regulation of MHC class I and II antigens and the co-stimulatory molecule B7 suggests increased immunogenicity of the peripheral organs. These changes could be inhibited by: (i) administration of a recombinant soluble P-selectin glycoprotein ligand-Ig, a P- and E-selectin antagonist; and (ii) a fusion protein, cytotoxic T lymphocyte antigen 4-Ig, which blocks B7-mediated T-cell co-stimulation. Conclusions. Activation of peripheral organs following explosive brain death may be caused by various interrelated events, including the effects of massive acute central injury, hypotension, and circulating factors. Almost complete suppression of these changes could be produced by biological agents. Such interventions, if reproducible in humans, could improve the quality of organs from marginal donors, broadening the criteria for donor acceptance.

Effects of explosive brain death on cytokine activation of peripheral organs in the rat.

https://www.jbc.org/content/274/9/5830.full.pdf

Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells.

https://www.ajkd.org/article/0272-6386(95)90161-2/pdf

Fewer nephrons at birth: A missing link in the etiology of essential hypertension?

Background. Initial ischemia/reperfusion injury occurring secondary to organ retrieval, storage, and transplantation has been associated with late renal allograft deterioration and failure. In addition, there is an apparent synergy, reported in several clinical series, between the initial injuries of ischemia/reperfusion and acute rejection; the long-term results of graft survival are significantly deceased after both events in combination as compared with either alone or if no such episodes occur. Methods. In the present study, we examined patterns of proteinuria, cellular infiltration, cytokine expression, and glomerulosclerosis over time in Lewis and Fischer 344 rats after 45 min of warm ischemia of a single kidney and with or without contralateral nephrectomy. Both early (4 hr to 7 days) and late (2-52 weeks) events were studied serially in the affected kidneys morphologically, by immunohistology and by reverse transcriptase polymerase chain reaction. Results. Intercellular adhesion molecule 1, endothelin, and major histocompatibility complex class II expression were up-regulated within 2 to 5 days after injury; T cells and macrophages increased transiently. Proteinuria developed after approximately 8 weeks only in animals bearing a single injured kidney, and not in those with a retained native organ. Progressive morphological changes occurred after 16 weeks, including glomerulosclerosis, arterial obliteration, and interstitial fibrosis. After a period of relative quiescence, expression of intercellular adhesion molecule 1 again increased in relation to progressive macrophage infiltration and their associated products, particularly, interleukin 1, tumor necrosis factor-α, transforming growth factor-β, and inducible nitric oxide synthase. Monocyte chemotactic protein 1 was intensely up-regulated by 24 weeks, coincident with a dramatic rise in this infiltrating population. These changes remained virtually at baseline in animals with a retained native kidney. Conclusions. These data imply that chronic injury after significant initial ischemia and reperfusion occurs when there is already a 50% renal mass reduction, but not when two kidneys remain in place. Permanent nephron loss resulting from such an insult could account for this phenomenon. Early ischemia and reperfusion, if severe enough in a single kidney, may be an important antigen-independent risk factor for later renal deterioration and failure. In the context of a renal allograft, it may contribute to chronic rejection.

Harald S. Mackenzie

Papers

The hyperfiltration theory: a paradigm shift in nephrology.

Effects of explosive brain death on cytokine activation of peripheral organs in the rat.

Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells.

Fewer nephrons at birth: A missing link in the etiology of essential hypertension?

Cellular and molecular predictors of chronic renal dysfunction after initial ischemia/reperfusion injury of a single kidney.