Chronic Kidney Disease as a Systemic Inflammatory Syndrome: Update on Mechanisms Involved and Potential Treatment

Abstract

Chronic kidney disease (CKD) is characterized by manifestations and symptoms involving systemic organs and apparatus, associated with elevated cardiovascular morbidity and mortality, bone disease, and other tissue involvement. Arterial hypertension (AH), diabetes mellitus (DM), and dyslipidemia, with glomerular or congenital diseases, are the traditional risk factors recognized as the main causes of progressive kidney dysfunction evolving into uremia. Acute kidney injury (AKI) has recently been considered an additional risk factor for the worsening of CKD or the development of CKD de novo. Evidence underlies the role of systemic inflammation as a linking factor between AKI and CKD, recognizing the role of inflammation in AKI evolution to CKD. Moreover, abnormal increases in oxidative stress (OS) and inflammatory status in CKD seem to exert an important pathogenetic role, with significant involvement in the clinical management of this condition. With our revision, we want to focus on and update the inflammatory mechanisms responsible for the pathologic conditions associated with CKD, with particular attention on the development of AKI and AKI-CKD de novo, the alteration of calcium-phosphorus metabolism with bone disease and CKD-MBD syndrome, the status of malnutrition and malnutrition–inflammation complex syndrome (MICS) and protein-energy wasting (PEW), uremic sarcopenia, the status of OS, and the different inflammatory pathways, highlighting a new approach to CKD. The depth comprehension of the mechanisms underlying the development of inflammation in CKD may present new possible therapeutic approaches in CKD and hopefully improve the management of correlated morbidities and provide a reduction in associated mortality.

Follistatin-Like-1 (FSTL1) Is a Fibroblast-Derived Growth Factor That Contributes to Progression of Chronic Kidney Disease

“…There is still a limited understanding of the mechanism(s) responsible for the progression of CKD [17]. Here, we present an experimental design and microarray-based approach to identify new genes that may play a role in the progression of tubule-interstitial (TI) injury.…”

The Signaling Pathway of TNF Receptors: Linking Animal Models of Renal Disease to Human CKD

“…TNF-α is primarily produced by activated immune cells, and its increase in the circulation can be detected within minutes after the pro-inflammatory stimuli [ 32 ]; TNF-α can also be expressed by activated endothelial cells [ 33 ], fibroblasts [ 34 ], adipose tissue [ 35 ], cardiac myocytes [ 36 ], and neurons [ 37 ]. Abnormally elevated production, and/or sustained higher values of TNF-α, have been associated with autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases [ 38 , 39 ], and chronic inflammatory disease states, such as sepsis, CKD, obesity, and diabetes [ 35 , 40 , 41 ].…”

Neuroimmunoendocrine Link Between Chronic Kidney Disease and Olfactory Deficits

“…CKD is characterized by a low-grade systemic inflammatory status that plays a key role in the progression of the disease and the increased morbidity and mortality ( Mihai et al, 2018 ), which are also affected by malnutrition and chronic inflammation ( Tinti et al, 2021 ). As illustrated in Figure 1 , CKD is associated with the dysregulation of synthesis, release, and degradation of soluble molecules of the immune system, the disruption of cytokines and inflammatory mediators, and decreased adrenal clearance accounting for high levels of circulating cytokines ( Rossaint et al, 2016 ).…”

“…The PRL receptor is also expressed in immune system cells, including lymphocytes, macrophages, and thymic epithelial cells ( Bouchard et al, 1999 ), where the ligand acts as an immunomodulatory cytokine ( Leite De Moraes et al, 1995 ). Hyperprolactinemia is associated with autoimmune diseases such as lupus and multiple sclerosis ( Borba et al, 2018 ) and possibly contributes to the inflammatory mechanisms associated with CKD ( Tinti et al, 2021 ).…”