Immune Dysfunction in Uremia

Dear Colleagues,

Cardiovascular disease as a consequence of inflammation and infections is the main cause for the increased occurrence of morbidity and mortality among patients with chronic kidney disease (CKD). Both complications are directly or indirectly linked to a compromised immune defense, innate as well as adaptive. The specific coordinated roles of neutrophils, monocytes/macrophages, lymphocytes, and antigen-presenting cells in maintaining an efficient immune response are affected. Furthermore, a state of genomic instability with declining kidney function may lead to the genomic damage and dysfunction of immune cells.
Kidney dysfunction leads to impaired glomerular filtration, resulting in the retention of toxic solutes affecting all organs of the body, inducing both primary activation of the immune system and lack of responsiveness when confronted with infection or other foreign stimuli. In CKD, proteins may become irreversibly changed by posttranslational modifications, resulting in an altered effect on the immune response. Uremic toxins may also be generated or introduced into the body via the intestine. Acute renal failure has a severe impact on the immune system as well, both on the molecular (e.g., complement, cytokines, and lymphocytes) and the cellular level (e.g., neutrophils, macrophages, lymphocytes).
Kidney replacement therapies per se may adversely affect the immune system. Critical evaluation and systematic design of preventive and therapeutic interventions for patients with kidney disease will help to develop novel therapeutic strategies to improve immune response. Kidney transplantation may reverse uremia-related defects but also induce immune dysfunction by immunosuppressive therapy. In addition to impaired glomerular filtration, disturbed metabolic activities of the kidney per se may be involved in manifestations of the uremic syndrome. Several substances that are produced by the kidneys, such as erythropoietin, calcitriol, and renin, affect the immune system.
The focus of this Special Issue of Toxins will be on the interrelated factors interfering with the immune response in patients with kidney dysfunction.

Prof. Dr. R. Vanholder
Prof. Dr. Gerald Cohen
Guest Editors

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