Respiratory complications and sleep disorders in children with chronic kidney disease: A correlation often underestimated

End-stage renal disease (ESRD) is associated with significantly increased morbidity and mortality resulting from cardiovascular disease (CVD) and infections, accounting for 50% and 20%, respectively, of the total mortality in ESRD patients. It is possible that these two complications are linked to alterations in the immune system in ESRD, as uremia is associated with a state of immune dysfunction characterized by immunodepression that contributes to the high prevalence of infections among these patients, as well as by immunoactivation resulting in inflammation that may contribute to CVD. This review describes disorders of the innate and adaptive immune systems in ESRD, underlining the specific role of ESRD-associated disturbances of Toll-like receptors. Finally, based on the emerging links between the alterations of immune system, CVD, and infections in ESRD patients, it emphasizes the potential role of the immune dysfunction in ESRD as an underlying cause for the high mortality in this patient population and the need for more studies in this area.

Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with systemic inflammation and acquired immunodeficiency, which promote cardiovascular disease, body wasting, and infections as leading causes of death. This phenomenon persists despite dialysis-related triggers of immune deregulation having been largely eliminated. Here we propose a potential immunoregulatory role of the intestinal microbiota in CKD/ESRD. We discuss how the metabolic alterations of uremia favor pathogen overgrowth (dysbiosis) in the gut and an increased translocation of living bacteria and bacterial components. This process has the potential to activate innate immunity and systemic inflammation. Persistent innate immune activation involves the induction of immunoregulatory mediators that suppress innate and adaptive immunity, similar to the concept of 'endotoxin tolerance' or 'immune paralysis' in advanced sepsis or chronic infections. Renal science has largely neglected the gut as a source of triggers for CKD/ESRD-related immune derangements and complications and lags behind on the evolving microbiota research. Interdisciplinary research activities at all levels are needed to unravel the pathogenic role of the intestinal microbiota in kidney disease and to evaluate if therapeutic interventions that manipulate the microbiota, such as pre- or probiotics, have a therapeutic potential to correct CKD/ESRD-related immune deregulation and to prevent the associated complications.