Renal indications for therapeutic plasma exchange (TPE) continue to expand and nephrologists are well trained to perform this extracorporeal blood purification treatment. In this editorial, I lay out the many reasons nephrologists should consider adding TPE to their clinical practice. All board-eligible nephrologists in the United States have extensive training in the management of blood purification treatments including vascular access, anticoagulation, volume management, and prescription for solute clearance. In fact, the nephrology training program is the only fellowship that requires expertise in any extracorporeal blood purification treatment. In contrast, although most plasma exchange treatments in the United States are managed by hematologists involved with blood-banking procedures, the hematology fellowship does not require training in blood purification. Unfortunately, despite the excellent training provided to all American nephrology fellows, only 40% of U.S. nephrology fellowship programs provide training in plasma exchange.1 Although some previous indications for TPE have not been supported by prospective randomized trials, other, newer indications have been added. Those indications currently in practice can be divided into those that are for “primary” renal diseases and those that are for “secondary” renal diseases (see Table I). A short synopsis follows. For a more detailed description of the role of TPE for these indications, refer to the recent core curriculum on TPE published in the American Journal of Kidney Disease.2 Primary renal disease Goodpasture's disease IgA nephritis/HSP Pauci-immune RPGN Focal segmental glomerulosclerosis (recurrence post-transplant) Transplantation Secondary renal disease APA syndrome Cryoglobulinemia Multiple, myeloma (myeloma kidney) TTP/HUS TPE for Primary Renal Diseases. Goodpasture's syndrome remains the quintessential example of a renal disease treated by TPE. Rapid removal of the anti-glomerular basement membrane antibody has been demonstrated to improve renal function and decrease the likelihood of end-stage renal disease (ESRD).3 TPE is also an excellent management strategy for the associated pulmonary hemorrhage.4 Although not recommended for the chronic form of IgA nephropathy, several small series and case reports have suggested that TPE may help to reverse the occasional IgA nephritis that presents as rapidly progressive glomerulonephritis (RPGN).5 Most recently, a large, prospective, randomized study demonstrated that TPE improved outcome and decreased the tendency to ESRD in patients with advanced ANCA-positive RPGN.6 In the renal transplant population, TPE has become commonplace as a means of reducing proteinuria and maintaining renal function in recipients who have rapid recurrence of their original focal-segmental glomerulosclerosis. 7 TPE has also been used to reduce elevated PRA levels in highly sensitized potential recipients8 and to allow successful transplantation in some cases of donor-recipient ABO incompatibilities.9 Finally, a review of published data on posttransplant recurrence of hemolytic uremic syndrome (HUS) has suggested that TPE can be a useful management strategy.10 TPE for Secondary Renal Diseases. A large randomized study did not find TPE to be of benefit for all cases of diffuse proliferative glomerulonephritis associated with lupus.11 Nonetheless, TPE may still be found to be useful in some particular situations associated with lupus, such as for the removal of the lupus anticoagulant found in the antiphospholipid antibody syndrome, especially in its most aggressive form, catastrophic antiphospholipid antibody syndrome.12,13 Although unsupported by controlled trials, all experts agree that the acute manifestations of cryoglobulinemia respond rapidly to TPE, including associated acute glomerulonephritis.14 A classic Italian study demonstrated that TPE can improve renal outcomes in patients with myeloma kidney.15 Recently, a Canadian trial could not provide proof that TPE was useful in all cases of proteinuric renal failure associated with multiple myeloma.16 However, the results did reveal a greater than 50% reduction in the ultimate need for dialysis in those receiving TPE. Not only have controlled studies supported the use of TPE for thrombotic thrombocytopenic purpura (TTP),17 but its use has become the standard of care for all but the most benign presentations. TPE for Non-Renal Disease. In the United States, the most common indications for TPE are neurologic diseases including myasthenia gravis, Guillain Barré syndrome, and chronic infl ammatory demyelinating polyneuropathy. Considering the capability of TPE to remove large molecular substances that may be pathogenic, almost 100 rational indications for TPE can be considered.18 An exhaustive review of the experimental data supporting the different indications for TPE has recently been published by the American Society for Apheresis.19 A current list of disorders reimbursed by Medicare is found in Table II.20 Many hospitals with limited need for plasma exchange treatments may elect not to provide this therapy and have decided to refer the appropriate cases to larger hospitals. Some other medical facilities currently contract with outside mobile apheresis providers who perform TPE with centrifugal equipment; however, costs may sometimes exceed reimbursement. TPE can also be performed by membrane plasma separation, which is similarly safe and effective when compared with the centrifugal method and can be performed by a dialysis nurse using standard hemodialysis machines. In facilities that provide inpatient hemodialysis there is a clear opportunity to utilize this existing capability to provide membrane plasma separation in lieu of contracting for mobile apheresis or referring these cases to other hospitals. When therapeutic plasma exchange is performed with a highly permeable filter and standard dialysis equipment, it is often referred to as membrane plasma separation (MPS). Having undergone considerable investigation and use in both Europe and Japan,21,22 MPS has become increasingly popular in the United States.23-26 There have also been numerous articles detailing the technical and nursing management of the MPS system.27-29 In the prototype MPS circuit, a highly permeable membrane, which is most often in a hollow fiber configuration, is connected to the blood pump and pressure monitoring system of the dialysis machine. With this setup, the dialysis machine is utilized in its “isolated” ultrafiltration mode, which bypasses the dialysate proportioning system. The membrane filter's highly porous wall selectively allows virtually all plasma proteins to pass through unimpeded while cellular blood components pass back to the patient (Figure 1). For added accuracy with volume balance, a peristaltic dual-track plasma pump can be used to draw the plasma into a discard bag as it returns the same volume of albumin or fresh-frozen plasma as the replacement fl uid back to the patient (Figure 2). Of note, considering the impermeability of the membrane to cellular components, this system cannot perform the cellular apheresis procedures (cytapheresis). Simulated cross-section of a single hollow fiber for membrane plasma separation. Schematic representation of a membrane filtration plasma exchange procedure. In the United States, the most commonly used membrane is the Plasmafl o from Asahi Medical (Asahi Kasei Kuraray Medical Co., Ltd., Japan). In general, this filter can be used with most dialysis machines. The membrane's U.S. distributor (Apheresis Technologies) also markets a dual-track plasma pump that is approved for use with the Plasmafl o. This simple and efficient alternative to centrifugationbased TPE systems has been shown to be as safe and effective as centrifugal plasma exchange systems.30 Interestingly, membrane- based plasma exchange is far more popular in Germany and Japan than are centrifugal-based treatments (Table III). The average charges for mobile TPE services acquired through a phone survey of 9 U.S. mobile apheresis providers was approximately $1,100, ranging from $980 to $1,350.31 These charges excluded surcharges or plasma volume replacement fl uid and, in general, exceeded the national average Medicare reimbursement of about $730.32 In contrast, an analysis of the estimated average direct cost of membrane plasma separation provided by the hospital staff in the inpatient dialysis unit is approximately $400 (Table IV).31 Some of the assumptions in this analysis may not be directly applicable to a given hospital, but the analysis does provide a working template for arriving at the specific costs likely to be encountered. From this analysis, it would appear that membrane plasma separation with existing dialysis equipment and staff can be more cost effective than contracted mobile apheresis services, with cost savings of approximately $700 per procedure. A recent cost analysis of 2 commonly used therapies for Guillain Barré syndrome included 5 days of IVIg versus 5 plasma exchange treatments.33 Given the increasing cost of IVIg and, in contrast, the decreasing cost of 5% albumin used as a replacement fl uid for plasma exchange, the estimated expense of a 5-day course of IVIg is $8,800 compared with $3,600 for 5 treatments of plasma exchange. One of the few remaining benefits of IVIg therapy is that it can be performed in almost any medical facility, whereas TPE is less widely available. However, given the wide availability of dialysis in almost all major medical facilities, it would appear that providing TPE with dialysis equipment would offer an excellent option to potentially lower the costs of treating many of the diseases now commonly managed with either IVIg or TPE. In conclusion, nephrologists and their dialysis staff are well trained to manage the TPE procedure. An analysis of the prevailing charges and reimbursements would suggest that providing TPE with dialysis equipment would increase the availability and decrease the cost of this highly effective and potentially lifesaving procedure.