This study aimed to assess efficacy of extracorporeal plasma therapy (EPT), including plasmapheresis (PE), immunoadsorption (IA), low-density lipoprotein apheresis (LDL-A), and lymphocytapheresis (LCAP) for adult native kidney patients with primary focal segmental glomerulosclerosis (FSGS).

A literature search was conducted using MEDLINE, EMBASE and Cochrane Databases through August 2022. Studies that reported outcomes of EPT in adult native kidneys with primary FSGS were enrolled.

18 studies with 104 therapy-resistant or refractory primary native FSGS patients were identified. Overall EPT response rate was 56%, with long-term benefit of 46%. Of the 101 non-hemodialysis (HD) patients, 54% achieved remission, with 30% complete remission (CR) and 23% partial remission (PR). Of 31 patients with PE, response rate was 65%; CR and PR rates were 27% and 37% in 30 non-HD patients. Of 61 patients with LDL-A, the response rate was 54%; CR and PR rates were 41% and 3% in 29 non-HD patients. Of 10 patients with IA, response rate was 40%. Of 2 patients with LCAP, 1 achieved CR, and one developed renal failure. All 3 HD patients showed increase in urine output and gradual decrease in urine protein excretion following PE (n = 1) or LDL-A (n = 2). 2 of 3 HD patients ultimately discontinued dialysis.

EPT with immunosuppressive therapy showed benefit in some patients with refractory primary FSGS, and PE appeared to have a higher response rate.

Inflammatory bowel disease (IBD) like Crohn's disease and ulcerative colitis are chronic inflammatory disorders that affect the bowel. The disease is characterized by periods of clinical remission and relapse due to severe intestinal inflammation. Drug therapy of IBD is associated with unpleasant side effects. Further, efficacies of conventional drugs decrease with chronic use and this can represent a major difficulty in the long term management of IBD. However, in active IBD, leukocytes are elevated in the lesion they may be able to be a factor of IBD aggravation. Membrane filters column and leukocyte adsorbing beads have been developed which are direct blood perfusion systems for removing any desired level of leukocytes. Clinical studies with these two new models have shown good effects for active IBD. Clinical data suggest that leukocytapheresis might be an effective adjunct to therapy of IBD, to promote remission, taper conventional drug dosage and potentially should reduce the number of patients who require colectomy. The results may further understandings of the pathophysiology of IBD and this in turn should contribute to a more effective treatment of this disorder.

Scaffolds, growth factors, and cells are three essential components in regenerative medicine. Nonwoven filters, which capture cells, provide a scaffold that localizes and concentrates cells near injured tissues. Further, the cells captured on the filters are expected to serve as a local supply of growth factors. In this study, we investigated the growth factors produced by cells captured on nonwoven filters. Nonwoven filters made of polyethylene terephthalate (PET), biodegradable polylactic acid (PLA), or chitin (1.2-22 μm fiber diameter) were cut out as 13 mm disks and placed into cell-capturing devices. Human mesenchymal stem cells derived from adipose tissues (h-ASCs) and peripheral blood cells (h-PBCs) were captured on the filter and cultured to evaluate growth factor production. The cell-capture rates strongly depended on the fiber diameter and the number of filter disks. Nonwoven filter disks were composed of PET or PLA fibers with fiber diameters of 1.2-1.8 μm captured over 70% of leukocytes or 90% of h-ASCs added. The production of vascular endothelial growth factor (VEGF), transforming growth factor β1, and platelet-derived growth factor AB were significantly enhanced by the h-PBCs captured on PET or PLA filters. h-ASCs on PLA filters showed significantly enhanced production of VEGF. These enhancements varied with the combination of the nonwoven filter and cells. Because of the enhanced growth factor production, the proliferation of human fibroblasts increased in conditioned medium from h-PBCs on PET filters. This device consisting of nonwoven filters and cells should be investigated further for possible use in the regeneration of impaired tissues.

This article is an overview of the immunomodulatory effects of apheresis in renal diseases, especially primary and secondary glomerulonephritis, and the clinical evidence for the efficacy of apheresis therapy. Permeability factor(s) derived from circulating T cells are speculated to have a crucial role in the proteinuria of nephrotic syndrome (NS). Plasma exchange (PE); immunoadsorption plasmapheresis (IAPP), using protein A sepharose cartridges; low-density lipoprotein apheresis; and lymphocytapheresis (LCAP) have been used to remove such factors or pathogenic T cells. Other glomerular diseases induced by specific antibodies such as anti-glomerular basement membrane antibodies, anti-neutrophil cytoplasmic antibodies, and immune-complexes have also been treated with PE, double-filtration plasmapheresis, IAPP, and LCAP. Recommendations, based on the evidence from recent randomized controlled studies, have been established in apheresis therapy for various glomerular diseases.

This article overviews the immunomodulation effects and clinical evidence of apheresis in renal diseases, in particular primary and secondary glomerulonephritis. A considerable permeability factor(s) derived from circulating T cells is speculated to have a crucial role in the proteinuria of nephrotic syndrome (NS). Plasma exchange (PE), immunoadsorption using Protein A sepharose cartridges, low-density lipoprotein apheresis and lymphocyte apheresis (LCAP) were tried to remove such factors or pathogenic T cells. Other glomerular diseases induced by specific antibodies such as antiglomerular basement membrane antibodies, antineutrophil cytoplasmic antibodies and immune-complexes such as lupus nephritis were also treated with PE, double filtration plasma apheresis. IAPP and LCAP. Many reports suggested that apheresis might have beneficial immunomodulation effects for the treatment of glomerular diseases: however, the recommendations based on evidence from small cohorts remain at low-level in most.

We developed a new method of xenogeneic direct hemoperfusion of a bioartificial liver support system consisting of a leukocyte-adsorbent column, an immunoglobulin-adsorbent column, and the substitute unit for hepatic function. By this method, we performed xenogeneic direct hemoperfusion experiment using resected whole swine liver for treatment of a canine liver failure model, and compared the contribution of each adsorbent column both by blood analysis and from the histological point of view.

Canine liver failure model was produced by portocaval shunting and ligating the entire hepatoduodenal ligament. The xenogeneic direct hemoperfusion system was constructed using a roller pump, a leukocyte-adsorbent column, an immunoglobulin-adsorbent column, a combined device of oxygenator and warmer, the resected whole swine liver accommodated in a chamber, and a dissolved oxygen meter through which canine whole blood leaving the external jugular vein circulated in this order.

Xenogeneic direct hemoperfusion was successfully performed for 3 h without hyperacute rejection occurring. Adequate ammonia detoxification and bile juice secretion were exhibited, and no findings of hepatocyte destruction by immunological cells and proteins were detected. Blood data showed that the immunoglobulin adsorbent were more effective than the leukocyte adsorbent in avoiding hyperacute rejection. This result indicates that hyperacute rejection has a closer relation to humoral immune responses, especially regarding removal of complements than to cellular immune responses.

We successfully performed xenogeneic direct hemoperfusion of the whole swine liver without hyperacute rejection using our method.

Cellsorba is a leukocyte removal filter developed by Asahi Medical Co., which adsorbs white blood cells through the perfusion of peripheral blood by means of simple extracorporeal circulation. Leukocytapheresis (LCAP) therapy using the Cellsorba column has been reported to show therapeutic effects for many autoimmune related and inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, neurologic disease, and so on. At present, Cellsorba is listed as a medical device covered by the Japanese national health insurance system for the treatment of active ulcerative colitis (UC) in Japan, and contributes to the improvement of quality of life in many UC patients. This paper reviews the use of Cellsorba and introduces several reports on therapeutic results.

A considerable permeability factor (or factors) derived from circulating T cells has a crucial role in proteinuria of nephrotic syndrome (NS). We attempted to remove pathogenic T cells through lymphocytapheresis (LCAP) in 6 patients with primary NS, 2 patients with minimal change nephrotic syndrome (MCNS), 2 patients with focal segmental glomerulosclerosis (FSGS), 1 patient with membranous nephropathy (MN), and 1 patient with MN and FSGS using Cellsorba (Asahi Medical Co., Osaka, Japan). LCAP was performed 2 times in 2 consecutive weeks and was followed with corticosteroid therapy with or without cyclosporine A in 5 patients. Two patients with MCNS, 1 with FSGS, and 1 with MN and FSGS showed a dramatic decrease of proteinuria (-30% and -94%) in their urine protein/creatinine ratio. Three out of 4 patients had a complete or partial remission (proteinuria <1g/day) within 8 weeks following immunosuppressive therapy. During the LCAP, T cells, especially activated T cells, decreased significantly in the response group. The other 2 patients, 1 with FSGS and 1 with MN, however, had no response to LCAP and following immunosuppressive therapy or low-density lipoprotein apheresis and suffered from end-stage renal failure or death by pneumonia. These results suggested that LCAP might have a beneficial effect on the treatment of NS, especially MCNS and in some patients with FSGS, despite varying responses to LCAP and concomitant immunosuppressive therapy.

Cytapheresis therapy has recently been investigated as a treatment for several diseases, especially autoimmune related diseases such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. The removal of leukocyte components has been performed by the centrifugal method; however, using fiber technology or column technology, leukocyte components can be removed simply, and these technologies are more effective than the centrifugal method in removing numbers of cells. Each of 3 types of leukocytapheresis methods removes a different kind of cell in its therapeutic principle. Thus, if we understand what kind of cells should be removed, we can choose the best method for removing leukocytes. For this reason, the authors propose an international standard for unifying names. The therapy that makes use of a centrifuge to selectively remove about 40% of neutrophils and more than 60% of lymphocytes may be called a lymphocyte removal therapy, lymphocytapheresis (LCA). Using cellulose acetate beads in a G-1 granulocyte removal column, granulocytes and monocytes are removed but not lymphocytes, so we suggest calling this granulocytapheresis (GCAP). In addition, using a leukocyte removal filter, the Cellsorba leukocyte removal filter, 99% of both granulocytes and monocytes and about 70% of lymphocytes are removed. We propose calling this leukocytapheresis (LCAP). In the near future, we hope that we will be able to select one of these methods for cytapheresis for each disease pathogenesis or cellular immune abnormality. Presently, a lot of research is on-going to analyze how cytapheresis is effective for the immune related diseases. The mechanism of cytapheresis will be clarified by investigators. We strongly believe that cytapheresis therapies offer good news to those patients suffering from incurable diseases as well as their physicians.

48 healthy donors underwent peripheral blood stem cell (PBSC) apheresis for allogeneic transplantation beginning on day 4 of G-CSF (2 x 5 microg/kg) mobilization. In one to four (median two) large-volume mononuclear cell aphereses, a median of 55.9 x 10(9) of lymphocytes (range 21.0-109.2 x 10[9]) were collected, an amount comparable to lymphocyte numbers removed by therapeutic lymphaphereses in autoimmune diseases. Mean peripheral lymphocyte counts decreased from premobilization values of 2.31 x 10(9)/l to 1.31 x 10(9)/l at a median of 34 d (1 month) and 1.53 x 10(9)/l at a median of 327 d (11 months). The decrease in peripheral lymphocyte counts was significantly correlated with the number of lymphocytes removed and the number of aphereses. Neutrophil and platelet counts returned to normal values after 1 month whereas monocyte counts and haemoglobin concentrations were significantly decreased at 1 month but not at 11 months.

This article is the fourth of a 4 part series describing the currently available apheresis devices and technologies. The sections include the following: Part 1, Membrane Plasma Separator (published in Vol. 1, No. 1); Part 2, Membrane Plasma Fractionator (published in Vol. 1, No. 2); Part 3, Adsorbent (published in Vol. 1, No. 3); and Part 4, Leukocyte Filter.

Significant advances have been made in the capabilities to remove white blood cells (WBCs) from blood by both centrifugal and filtration techniques. New techniques have applications for both donor products (and their effects upon the recipients) and for selected disease therapeutics. The immunomodulatory effects of donor WBCs may be therapeutic, e.g., granulocytes harvested by apheresis may be used for the treatment of sepsis, or mononuclear cells collected by apheresis for peripheral blood progenitor (stem) cell transplantation or graft versus leukemia effect. In contrast, WBCs are removed from many transfusable components to decrease the immune effects in recipients. This has been accomplished primarily by the use of leukoreduction filters although newer adaptations of centrifugal equipment allow for the reduction of WBCs to target range of <1 x 10(6) WBCs/product. Therapeutic WBC removal by centrifuge has been used for treatment of the effects due to elevated levels of WBCs or platelets. More specific cellular immunotherapy has included lymphocytapheresis for the treatment of autoimmune diseases such as systemic lupus erythematosis (SLE). Various mononuclear cell fractions collected by apheresis have been used for lymphokine activated killer cells (LAK) and tumor infiltrating lymphocytes (TIL) cell therapy or autologous stem cell transplantation. The development of WBC adsorbent filters for therapeutic use has evolved as nonspecific filter materials have been demonstrated to show selective WBC removal, and filter columns permit therapeutic reductions in WBCs using online filtration therapy. Specific adsorption techniques, e.g., CD-34 selection, are in use in vitro and indicate directions for further developments in cellular immunotherapy.