In the past several decades, apoptosis or programmed death has been the subject of intense investigation in terms of mechanism, sequence of events, biochemistry, and morphology. In contrast to necrosis or accidental cell death, apoptosis is a programmed, active, and highly selective mechanism of cell death, allowing for removal of cells that are redundant or excessively damaged. Apoptosis is initiated by number of different stimuli, including DNA damage, toxins, or extracellular signals. The typical morphological changes of programmed cell death include shrinkage of the cell and the nucleus, condensation and fragmentation of the nuclear chromatin, loss of plasma membrane integrity despite membrane blebbing, and segmentation of the cell into apoptotic bodies that are rapidly ingested by neighboring phagocytic cells. One of the most specific features of apoptosis is the regular fragmentation by an endonuclease of the entire cellular DNA into an oligonucleosome-length unit of 180 pairs. Assays allowing the quantitation of apoptosis include gel electrophoresis of DNA, immunofluresence microscopy, and flow cytometry.In multicellular organisms, apoptosis is an essential component of development and cellular regulation. Abnormal regulation of apoptosis can lead to disorders such as cancer, lymphocytes depletion in AIDS, and degenerative disease. Apoptosis in both excessive and reduced amounts has pathological implications, consequently, control of the apoptotic mechanism may have significant therapeutic implications.Uremia is associated with alterations in host defense mechanisms, which increase the risk of infection and malignancy. The most striking abnormalities occur in cell-mediated immunity and involve primarily T-lymphocytes. These include lymphocytopenia, impaired delayed skin reactivity, and decreased in vitro lymphocyte proliferation. Alterations in humoral immunity affect B-lymphocytes and result in a decrease in immunoglobulin levels and a depressed antibody response to antigens. Dysregulated cytokine synthesis and impaired macrophage Fc receptor function further impair immune function in uremic patients. Finally, PMNLs exhibit impaired chemotaxis, phagocytosis, and an abnormal respiratory burst.Uremic state induces the expression of apoptosis markers Fas-FasL antigens on PMNLs and lymphocytes. And is associated with accelerated apoptosis of leukocytes which in turn contributes in part to cellular malfunction. These effects are amplified once HD starts.Enhanced production of proinflammatory cytokines by dialysate pyrogens, by complement activation, or both, as well as inhibition of anti-inflammatory cytokine secretion, may contribute to the cell-mediated immunosupression seen in patients with ESRD. Further more, multiple alterations of neutrophils occur as a result of uremia per se and bioincompatible dialyzer membranes. The presence of low and high molecular weight inhibitors of neutrophils in the plasma of uremic patients may explain why infections are the most common cause of hospitalization and the second most common cause of death in patients with ESRD. Other middle molecules accumulate, and proteins are modified by oxidative stress, carbonyl stress, or, both, contributes to uremic syndrome.