Loss of immune homeostasis can affect the kidney adversely either directly or indirectly, leading to loss of kidney function. repair, after immune\mediated disease or non\immune mediated injury, result in fibrosis of structures important for renal function, leading eventually to kidney failure. As renal disease often manifests clinically only when substantial damage has already occurred, new diagnostic methods and indeed treatments must be identified to inhibit further progression and promote appropriate tissue repair. Studying cases in which immune homeostasis is usually re\established may reveal new treatment possibilities. Keywords: fibrosis, immune homeostasis, inflammation, kidney disease Introduction The kidneys, as a major filter organ for the blood and the key organ responsible for maintaining total body water balance and circulatory pressure, receive a rich blood supply by which they monitor and change the functional status of multiple organ systems. Besides clearing metabolic waste products, toxins and drugs from our body, the kidneys also clear circulating cytokines and bacterial toxins such as lipopolysaccharide (LPS) and constantly sample blood\borne proteins, contributing to homeostasis of the immune system. The removal of cytokines from the blood can limit inflammation 1, 2, and the clearance of bacterial components reduces would\be immune cell activation by pattern recognition receptors (PRRs) 2, 3. In addition, kidney resident dendritic cells (DCs) appear SELL to be very important in maintaining peripheral tolerance 1. As 85% of the water filtered at the glomerulus is usually reabsorbed immediately by the proximal tubule, cells in the distal nephron downstream experience filtered low molecular weight antigens at concentrations up to 10 occasions higher than SKF 86002 Dihydrochloride in the blood itself. These antigens are taken up readily by a dense network of DCs; for example, via dendrites protruding directly into the tubular lumen, enabling these filtered antigens to be presented to T cells in renal draining lymph nodes more efficiently than possible elsewhere in the body. Through this regular presentation of innocuous antigens in the absence of danger signals, potentially autoreactive T cells recognizing these low molecular weight antigens are inactivated. Thus, the kidneys, in addition to the spleen, assist in maintaining peripheral tolerance to circulating antigens such as hormones and food proteins 1, 4. The kidneys’ important contribution to immune homeostasis becomes especially clear in end stage renal disease (ESRD), where immune function is usually severely compromised. The retention of uraemic toxins and cytokines activates innate immune cells leading to a vicious cycle of further cytokine and reactive oxygen species production, both contributing to tissue damage and increasing cardiovascular risk. Additionally, lymphocyte number and function decrease, leaving the patient functionally immunocompromised and at risk of contamination as well as viral\associated cancers 2, 5. Conversely, the kidneys themselves are also very susceptible to immune\mediated diseases. Loss of immune homeostasis can affect the kidney adversely either directly or indirectly, leading to loss of kidney function. Homeostasis explains the physiological condition of a system under normal conditions. In the immune system, homeostasis therefore refers to its function and maintenance in the uninfected host 6. However, it could be argued that this inflammatory immune response to infections and tissue damage is usually a normal extension of the immune system’s homeostatic function, as long as the immune response resolves. Assuming the latter definition of immune homeostasis, loss of homeostasis includes over\ or under\activity of the immune response, but not the initial reaction to contamination or tissue injury. The following is usually a brief overview of immune\mediated kidney disease which, in accordance with the above definition, will not include congenital kidney diseases or those caused by SKF 86002 Dihydrochloride infections or sterile injury. Direct SKF 86002 Dihydrochloride immune\mediated renal disease Renal diseases associated with loss of immune homeostasis can be grouped according to direct or indirect immune\mediated kidney injury. Direct immune\mediated renal disease involves the immune system targeting SKF 86002 Dihydrochloride specific antigens within the kidney, while in SKF 86002 Dihydrochloride indirect immune\mediated renal disease the kidneys are a bystander victim of processes resulting.