Immune Dysfunction in Uremia 2020

Abstract

<jats:p>Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failure results in disturbed renal metabolic activities with reduced renin, erythropoietin, and vitamin D production, which adversely affects the immune system. Decreased kidney function also leads to reduced glomerular filtration and the retention of uremic toxins. A large number of uremic toxins with detrimental effects on immune cells have been identified. Besides small water-soluble and protein-bound compounds originating from the intestinal microbiome, several molecules in the middle molecular range, e.g., immunoglobulin light chains, retinol-binding protein, the neuropeptides Met-enkephalin and neuropeptide Y, endothelin-1, and the adipokines leptin and resistin, adversely affect immune cells. Posttranslational modifications such as carbamoylation, advanced glycation products, and oxidative modifications contribute to uremic toxicity. Furthermore, high-density lipoprotein from uremic patients has an altered protein profile and thereby loses its anti-inflammatory properties.</jats:p>

Elevated Monocyte to Lymphocyte Ratio and Increased Mortality among Patients with Chronic Kidney Disease Hospitalized for COVID-19

“…Increased risk of infectious complications and more adverse outcomes have been documented in patients with CKD compared with the general population [ 8 , 9 ], which has been attributed to the presence of severe immune dysfunctions associated with this disease. This includes the emergence of premature immunological aging with loss of thymic function, attrition of telomeres, and epigenetic changes in hematopoietic stem cells, which ultimately results in impaired immune responses [ 10 , 11 ]. Along with their elevated risk of severe infections, patients with CKD often have endothelial dysfunction, enhanced coagulation, and commonly have chronic comorbidities such as diabetes, hypertension, and coronary artery disease, which makes the CKD population especially vulnerable to severe COVID-19 [ 9 , 10 , 11 , 12 ].…”

“…This includes the emergence of premature immunological aging with loss of thymic function, attrition of telomeres, and epigenetic changes in hematopoietic stem cells, which ultimately results in impaired immune responses [ 10 , 11 ]. Along with their elevated risk of severe infections, patients with CKD often have endothelial dysfunction, enhanced coagulation, and commonly have chronic comorbidities such as diabetes, hypertension, and coronary artery disease, which makes the CKD population especially vulnerable to severe COVID-19 [ 9 , 10 , 11 , 12 ]. Indeed, during the current COVID-19 pandemic, several challenges associated with the clinical care of CKD patients have been identified, including, problems with disease monitoring, disruption of the management and application of kidney replacement therapies, delayed or cancellation of kidney transplants, as well as more adverse clinical outcomes [ 13 , 14 , 15 ].…”

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

“…Chronic metabolic acidosis, oxidative stress, the accumulation of uremic toxins, and low-grade inflammation are some of the consequences of end-stage renal disease (ESRD) [ 1 , 2 , 3 ]. They directly affect almost every system, including the immune system, which is the overarching surveillance mechanism to control almost each function [ 4 , 5 ].…”

Coronavirus-associated kidney outcomes in COVID-19, SARS, and MERS: a meta-analysis and systematic review

“…However, the reported prevalence and mortality of AKI for all three coronavirus infection differs between studies. All patients with chronic kidney disease (CKD), including those with end-stage kidney disease (ESKD) or on kidney replacement therapy (KRT), are immunosuppressed making them more susceptible to infection and potentially a more severe course [14][15][16]. The potential increased risk related to preexisting CKD and urgent-start KRT treatment is presently unclear.…”