Immune Dysfunction in Uremia 2020.

Area of Science:

• Nephrology
• Immunology
• Cardiology

Background:

• Cardiovascular disease and infections are leading causes of death in chronic kidney disease (CKD) patients.
• These complications are linked to altered immune cell function, including polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells.
• Immune cell dysfunction in CKD can manifest as reduced responses (leading to infections) or pre-activation (leading to inflammation and cardiovascular disease).

Purpose of the Study:

• To review the multifaceted impact of kidney dysfunction on the human immune system.
• To elucidate the mechanisms by which renal failure compromises immune cell function.
• To identify key uremic toxins and modifications contributing to immune dysregulation in CKD.

Main Methods:

• Literature review of studies investigating immune system alterations in CKD.
• Analysis of the effects of reduced renal metabolic activities (renin, erythropoietin, vitamin D) on immune cells.
• Identification and categorization of uremic toxins and their impact on immune cell function.

Main Results:

• Renal failure disrupts immune homeostasis through reduced production of essential hormones and retention of uremic toxins.
• Numerous uremic toxins, including small molecules, protein-bound compounds, and middle molecules (e.g., immunoglobulin light chains, leptin), adversely affect immune cells.
• Posttranslational modifications (carbamoylation, glycation, oxidation) and altered high-density lipoprotein contribute to uremic toxicity and loss of anti-inflammatory properties.

Conclusions:

• Kidney dysfunction profoundly impacts the immune system, predisposing CKD patients to infections and cardiovascular disease.
• Uremic toxins and altered immune cell function are central to CKD-associated morbidity and mortality.
• Understanding these immune dysregulations is crucial for developing targeted therapeutic strategies in CKD management.