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      High cut-off haemodialysis induces remission of recurrent idiopathic focal segmental glomerulosclerosis after renal transplantation but is no alternative to plasmapheresis

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          Abstract

          A 26-year-old male experienced a recurrence of idiopathic focal segmental glomerulosclerosis (iFSGS) after his second renal transplant. Reduction of proteinuria was rapidly induced by plasmapheresis (PP) and the patient has remained in remission with a once-weekly PP regimen, which has now been continued for >3½ years. We were also able to induce remission of iFSGS in this patient by treatment with high cut-off haemodialysis using the Theralite™ dialyser. This observation lends support for the pathophysiological role of an as yet unknown, circulating glomerular filtration barrier permeability factor with an estimated weight of between 30 and 50 kDa.

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          Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis.

          V Savin, R. Sharma, M. Sharma … (1996)
          Heavy proteinuria and progressive renal injury recur after transplantation in up to 40 percent of patients with renal failure caused by idiopathic focal segmental glomerulosclerosis. A circulating factor may be responsible for this recurrence. To determine whether patients with focal segmental glomerulosclerosis have a circulating factor capable of causing glomerular injury, we tested serum samples from 100 patients with the disorder in an in vitro assay of glomerular permeability to albumin. Of the 56 patients who had undergone renal transplantation, 33 had recurrences. Sixty-four patients, many of whom had undergone transplantation, were being treated with dialysis. Thirty-one patients with other renal diseases and nine normal subjects were also studied. The 33 patients with recurrent focal segmental glomerulosclerosis after transplantation had a higher mean (+/-SE) value for permeability to albumin (0.47+/-0.06) than the normal subjects (0.06+/-0.07) or the patients who did not have recurrences (0.14+/-0.06). After plasmapheresis in six patients with recurrences, the permeability was reduced (from 0.79+/-0.06 to 0.10+/-0.05, P = 0.008), and proteinuria was significantly decreased. Patients with corticosteroid-sensitive nephrotic syndrome or with membranous nephropathy after transplantation had low levels of serum activity. The circulating factor bound to protein A and hydrophobic-interaction columns and had an apparent molecular mass of about 50 kd. A circulating factor found in some patients with focal segmental glomerulosclerosis is associated with recurrent disease after renal transplantation and may be responsible for initiating the renal injury.
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            Treatment of acute renal failure secondary to multiple myeloma with chemotherapy and extended high cut-off hemodialysis.

            Stephen Harding, Mark Cook, J Chappel … (2009)
            Extended hemodialysis using a high cut-off dialyzer (HCO-HD) removes large quantities of free light chains in patients with multiple myeloma. However, the clinical utility of this method is uncertain. This study assessed the combination of chemotherapy and HCO-HD on serum free light chain concentrations and renal recovery in patients with myeloma kidney (cast nephropathy) and dialysis-dependent acute renal failure. An open-label study of the relationship between free light chain levels and clinical outcomes in 19 patients treated with standard chemotherapy regimens and HCO-HD. There were sustained early reductions in serum free light chain concentrations (median 85% [range 50 to 97]) in 13 patients. These 13 patients became dialysis independent at a median of 27 d (range 13 to 120). Six patients had chemotherapy interrupted because of early infections and did not achieve sustained early free light chain reductions; one of these patients recovered renal function (at 105 d) the remaining 5 patients did not recover renal function. Patients who recovered renal function had a significantly improved survival (P < 0.012). In dialysis-dependent acute renal failure secondary to myeloma kidney, patients who received uninterrupted chemotherapy and extended HCO-HD had sustained reductions in serum free light chain concentrations and recovered independent renal function.
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              Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies.

              Steven Reid, Helena Chandler, Daniel G. Mead … (2007)
              Of patients with newly diagnosed multiple myeloma, approximately 10% have dialysis-dependent acute renal failure, with cast nephropathy, caused by monoclonal free light chains (FLC). Of these, 80 to 90% require long-term renal replacement therapy. Early treatment by plasma exchange reduces serum FLC concentrations, but randomized, controlled trials have shown no evidence of renal recovery. This outcome can be explained by the low efficiency of the procedure. A model of FLC production, distribution, and metabolism in patients with myeloma indicated that plasma exchange might remove only 25% of the total amount during a 3-wk period. For increasing FLC removal, extended hemodialysis with a protein-leaking dialyzer was used. In vitro studies indicated that the Gambro HCO 1100 dialyzer was the most efficient of seven tested. Model calculations suggested that it might remove 90% of FLC during 3 wk. This dialyzer then was evaluated in eight patients with myeloma and renal failure. Serum FLC reduced by 35 to 70% within 2 hr, but reduction rates slowed as extravascular re-equilibration occurred. FLC concentrations rebounded on successive days unless chemotherapy was effective. Five additional patients with acute renal failure that was caused by cast nephropathy then were treated aggressively, and three became dialysis independent. A total of 1.7 kg of FLC was removed from one patient during 6 wk. Extended hemodialysis with the Gambro HCO 1100 dialyzer allowed continuous, safe removal of FLC in large amounts. Proof of clinical value now will require larger studies.
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                Author and article information

                Journal
                Journal ID (nlm-ta): NDT Plus
                Journal ID (hwp): ndtplus
                Journal ID (publisher-id): ndtplus
                Title: NDT Plus
                Publisher: Oxford University Press
                ISSN (Print): 1753-0784
                ISSN (Electronic): 1753-0792
                Publication date (Print): October 2011
                Publication date (Electronic): 26 July 2011
                Publication date PMC-release: 26 July 2011
                Volume: 4
                Issue: 5
                Pages: 321-323
                Affiliations
                Division of Nephrology and Renal Transplantation, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
                Author notes
                Correspondence and offprint requests to: Dennis A. Hesselink; E-mail: d.a.hesselink@ 123456erasmusmc.nl
                Article
                DOI: 10.1093/ndtplus/sfr084
                PMC ID: 3182260
                PubMed ID: 21969845
                SO-VID: 9bc85751-d830-4e83-bf0b-0b2952a9e433
                Copyright © © The Author 2011. Published by Oxford University Press [on behalf of ERA-EDTA].
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 23 March 2011
                Date accepted : 17 June 2011
                Categories
                Subject: II. Clinical Reports
                Subject: Case Reports

                ScienceOpen disciplines: Nephrology
                Keywords: proteinuria,focal segmental glomerulosclerosis,plasmapheresis,transplantation
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: proteinuria, focal segmental glomerulosclerosis, plasmapheresis, transplantation

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