Hypertension and chronic kidney disease (CKD) are closely interlinked pathophysiologic states, such that sustained hypertension can lead to worsening kidney function and progressive decline in kidney function can conversely lead to worsening blood pressure (BP) control. The pathophysiology of hypertension in CKD is complex and is a sequela of multiple factors, including reduced nephron mass, increased sodium retention and extracellular volume expansion, sympathetic nervous system overactivity, activation of hormones including the renin-angiotensin-aldosterone system, and endothelial dysfunction. Currently, the treatment target for patients with CKD is a clinic systolic BP < 130 mm Hg. The main approaches to the management of hypertension in CKD include dietary salt restriction, initiation of treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic therapy. Uncontrolled hypertension can lead to significant cardiovascular morbidity and mortality and accelerate progression to end-stage kidney disease. Although intensive BP control has not been shown in clinical trials to slow the progression of CKD, intensive BP control reduces the risk for adverse cardiovascular outcomes and mortality in the CKD population. Complete author and article information provided at the end of the article.

Malformations of cortical development (MCD) result from abnormal neuronal positioning during corticogenesis. MCD are believed to be the morphological and perhaps physiological bases of several neurological diseases, spanning from mental retardation to autism and epilepsy. In view of the fact that during development, an appropriate blood supply is necessary to drive organogenesis in other organs, we hypothesized that vasculogenesis plays an important role in brain development and that E15 exposure in rats to the angiogenesis inhibitor thalidomide would cause postnatal MCD. Our results demonstrate that thalidomide inhibits angiogenesis in vitro at concentrations that result in significant morphological alterations in cortical and hippocampal regions of rats prenatally exposed to this vasculotoxin. Abnormal neuronal development was associated with vascular malformations and a leaky blood-brain barrier. Protein extravasation and uptake of fluorescent albumin by neurons, but not glia, was commonly associated with abnormal cortical development. Neuronal hyperexcitability was also a hallmark of these abnormal cortical regions. Our results suggest that prenatal vasculogenesis is required to support normal neuronal migration and maturation. Altering this process leads to failure of normal cerebrovascular development and may have a profound implication for CNS maturation.Keywords cortical dysplasia; angiogenesis; brain development; vasculogenesis; blood-brain barrier; endothelium Malformations of cortical development (MCD) result from abnormal neuronal positioning during corticogenesis. Genetic/epigenetically-induced MCD represent one of the most common etiologic factors associated with CNS pathologies, i.e. neurological deficits, autism, developmental delay, and epilepsy (Taylor et al., 1971;Robain, 1996). While the exact mechanisms underlying MCD are unknown, it is clear that single genes may be responsible for distinct MCD including lissencephaly, subcortical band heterotopias, NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2014 January 23. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript periventricular nodular heterotopia, and tuberous sclerosis (Gardiner, 1999;Steinlein, 2004). Although the exact pathogenesis of MCD remains unknown, environmental factors also appear to be involved (Montenegro et al., 2002;Montenegro, 2003;Bassanini and Battaglia, 2006).Animal models of CNS disorders have provided a crucial step toward both the understanding of mechanisms involved and discovery of therapeutic factors. In the case of MCD, the animal model that most realistically recapitulates the morphology of human cortical dysplasia is based on prenatal exposure to methylazoxymethanol acetate (MAM; Battaglia et al., 2003a). A prenatal exposure to this putative anti-proliferative and cytotoxic agent (Cattaneo et al., 1995) induces cerebral heterotopias that share striking similarities with those observed in humans (Colacitti et al., 1999;Battaglia et al., 2003a)...

Introduction After dialysis-requiring acute kidney injury (AKI-D), recovery of sufficient kidney function to discontinue dialysis is an important clinical and patient-oriented outcome. Predicting the probability of recovery in individual patients is a common dilemma. Methods This cohort study examined all adult members of Kaiser Permanente Northern California who experienced AKI-D between January 2009 and September 2015 and had predicted inpatient mortality of <20%. Candidate predictors included demographic characteristics, comorbidities, laboratory values, and medication use. We used logistic regression and classification and regression tree (CART) approaches to develop and cross-validate prediction models for recovery. Results Among 2214 patients with AKI-D, mean age was 67.1 years, 40.8% were women, and 54.0% were white; 40.9% of patients recovered. Patients who recovered were younger, had higher baseline estimated glomerular filtration rates (eGFR) and preadmission hemoglobin levels, and were less likely to have prior heart failure or chronic liver disease. Stepwise logistic regression applied to bootstrapped samples identified baseline eGFR, preadmission hemoglobin level, chronic liver disease, and age as the predictors most commonly associated with coming off dialysis within 90 days. Our final logistic regression model including these predictors had a correlation coefficient between observed and predicted probabilities of 0.97, with a c-index of 0.64. An alternate CART approach did not outperform the logistic regression model (c-index 0.61). Conclusion We developed and cross-validated a parsimonious prediction model for recovery after AKI-D with excellent calibration using routinely available clinical data. However, the model’s modest discrimination limits its clinical utility. Further research is needed to develop better prediction tools.