FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 334:878-883 April 4, 1996 Number 14 Next

	Full Text PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background 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.

Methods 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.

Results 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.

Conclusions 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.

Source Information

From the Department of Medicine, Medical College of Wisconsin, Milwaukee (V.J.S., R.S., M.S., E.T.M.); the Department of Medicine, Hennepin County Medical Center, Minneapolis (S.K.S.); Arkansas Children's Hospital, Little Rock (E.E.); the Department of Pediatrics, University of Nebraska Medical Center, Omaha (H.L.); Children's Mercy Hospital, Kansas City, Mo. (B.W.); the Departments of Biochemistry and Molecular Biology (S.G.) and Medicine (A.M.C.), University of Kansas Medical Center, Kansas City; and the Department of Medicine, University of California, San Francisco (M.A., F.V.).

Address reprint requests to Dr. Savin at the Nephrology Division, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, 9200 W. Wisconsin Ave., Milwaukee, WI 53226.

Full Text of this Article

This article has been cited by other articles:

• De Smet, E., Rioux, J.-P., Ammann, H., Deziel, C., Querin, S. (2009). FSGS permeability factor-associated nephrotic syndrome: remission after oral galactose therapy. Nephrol Dial Transplant 0: gfp278v1-gfp278 [Abstract] [Full Text]  
• Gutwein, P., Abdel-Bakky, M. S., Schramme, A., Doberstein, K., Kampfer-Kolb, N., Amann, K., Hauser, I. A., Obermuller, N., Bartel, C., Abdel-Aziz, A.-A. H., El Sayed, E. S. M., Pfeilschifter, J. (2009). CXCL16 Is Expressed in Podocytes and Acts as a Scavenger Receptor for Oxidized Low-Density Lipoprotein. Am. J. Pathol. 174: 2061-2072 [Abstract] [Full Text]  
• Le Berre, L., Bruneau, S., Naulet, J., Renaudin, K., Buzelin, F., Usal, C., Smit, H., Condamine, T., Soulillou, J.-P., Dantal, J. (2009). Induction of T Regulatory Cells Attenuates Idiopathic Nephrotic Syndrome. J. Am. Soc. Nephrol. 20: 57-67 [Abstract] [Full Text]  
• Lennon, R., Singh, A., Welsh, G. I., Coward, R. J., Satchell, S., Ni, L., Mathieson, P. W., Bakker, W. W., Saleem, M. A. (2008). Hemopexin Induces Nephrin-Dependent Reorganization of the Actin Cytoskeleton in Podocytes. J. Am. Soc. Nephrol. 19: 2140-2149 [Abstract] [Full Text]  
• Lowik, M., Levtchenko, E., Westra, D., Groenen, P., Steenbergen, E., Weening, J., Lilien, M., Monnens, L., Heuvel, L. v. d. (2008). Bigenic heterozygosity and the development of steroid-resistant focal segmental glomerulosclerosis. Nephrol Dial Transplant 23: 3146-3151 [Abstract] [Full Text]  
• Golgert, W. A., Appel, G. B., Hariharan, S. (2008). Recurrent Glomerulonephritis after Renal Transplantation: An Unsolved Problem. CJASN 3: 800-807 [Abstract] [Full Text]  
• Deegens, J. K. J., Wetzels, J. F. M. (2008). Rituximab for plasma exchange-dependent recurrent focal segmental glomerulosclerosis after renal transplantation. NDT Plus 1: 85-88 [Full Text]  
• Lucke, T., Kanzelmeyer, N., Chobanyan, K., Tsikas, D., Franke, D., Kemper, M. J., Ehrich, J. H.H., Das, A. M. (2008). Elevated asymmetric dimethylarginine (ADMA) and inverse correlation between circulating ADMA and glomerular filtration rate in children with sporadic focal segmental glomerulosclerosis (FSGS). Nephrol Dial Transplant 23: 734-740 [Abstract] [Full Text]  
• Musante, L., Candiano, G., Petretto, A., Bruschi, M., Dimasi, N., Caridi, G., Pavone, B., Del Boccio, P., Galliano, M., Urbani, A., Scolari, F., Vincenti, F., Ghiggeri, G. M. (2007). Active Focal Segmental Glomerulosclerosis Is Associated with Massive Oxidation of Plasma Albumin. J. Am. Soc. Nephrol. 18: 799-810 [Abstract] [Full Text]  
• He, N., Zahirieh, A., Mei, Y., Lee, B., Senthilnathan, S., Wong, B., Mucha, B., Hildebrandt, F., Cole, D. E., Cattran, D., Pei, Y. (2007). Recessive NPHS2 (Podocin) Mutations Are Rare in Adult-Onset Idiopathic Focal Segmental Glomerulosclerosis. CJASN 2: 31-37 [Abstract] [Full Text]  
• Pardon, A., Audard, V., Caillard, S., Moulin, B., Desvaux, D., Bentaarit, B., Remy, P., Sahali, D., Roudot-Thoraval, F., Lang, P., Grimbert, P. (2006). Risk factors and outcome of focal and segmental glomerulosclerosis recurrence in adult renal transplant recipients. Nephrol Dial Transplant 21: 1053-1059 [Abstract] [Full Text]  
• Herve, C., Dantal, J. (2006). Possible new perspectives for our understanding of nephrotic syndrome recurrence. Nephrol Dial Transplant 21: 10-13 [Full Text]  
• Tumlin, J. A., Miller, D., Near, M., Selvaraj, S., Hennigar, R., Guasch, A. (2006). A Prospective, Open-Label Trial of Sirolimus in the Treatment of Focal Segmental Glomerulosclerosis. CJASN 1: 109-116 [Abstract] [Full Text]  
• Coward, R. J.M., Foster, R. R., Patton, D., Ni, L., Lennon, R., Bates, D. O., Harper, S. J., Mathieson, P. W., Saleem, M. A. (2005). Nephrotic Plasma Alters Slit Diaphragm-Dependent Signaling and Translocates Nephrin, Podocin, and CD2 Associated Protein in Cultured Human Podocytes. J. Am. Soc. Nephrol. 16: 629-637 [Abstract] [Full Text]  
• Nishida, M., Ishida, H., Nakai, N., Morimoto, A., Imashuku, S., Hamaoka, K., Yoshihara, T. (2004). Focal segmental glomerulosclerosis in a girl with myelodysplastic syndrome. Nephrol Dial Transplant 19: 2639-2641 [Full Text]  
• Carraro, M., Zennaro, C., Artero, M., Candiano, G., Ghiggeri, G. M., Musante, L., Sirch, C., Bruschi, M., Faccini, L. (2004). The effect of proteinase inhibitors on glomerular albumin permeability induced in vitro by serum from patients with idiopathic focal segmental glomerulosclerosis. Nephrol Dial Transplant 19: 1969-1975 [Abstract] [Full Text]  
• Ghiggeri, G. M., Carraro, M., Vincenti, F. (2004). Recurrent focal glomerulosclerosis in the era of genetics of podocyte proteins: theory and therapy. Nephrol Dial Transplant 19: 1036-1040 [Full Text]  
• Ruf, R. G., Lichtenberger, A., Karle, S. M., Haas, J. P., Anacleto, F. E., Schultheiss, M., Zalewski, I., Imm, A., Ruf, E.-M., Mucha, B., Bagga, A., Neuhaus, T., Fuchshuber, A., Bakkaloglu, A., Hildebrandt, F., the Arbeitsgemeinschaft fur Padiatrische Nephrolog, (2004). Patients with Mutations in NPHS2 (Podocin) Do Not Respond to Standard Steroid Treatment of Nephrotic Syndrome. J. Am. Soc. Nephrol. 15: 722-732 [Abstract] [Full Text]  
• Sharma, M., Sharma, R., McCarthy, E. T., Savin, V. J. (2004). The Focal Segmental Glomerulosclerosis Permeability Factor: Biochemical Characteristics and Biological Effects. Exp. Biol. Med. 229: 85-98 [Abstract] [Full Text]  
• Floege, J. (2003). Recurrent glomerulonephritis following renal transplantation: an update. Nephrol Dial Transplant 18: 1260-1265 [Full Text]  
• Caridi, G., Bertelli, R., Di Duca, M., Dagnino, M., Emma, F., Onetti Muda, A., Scolari, F., Miglietti, N., Mazzucco, G., Murer, L., Carrea, A., Massella, L., Rizzoni, G., Perfumo, F., Ghiggeri, G. M. (2003). Broadening the Spectrum of Diseases Related to Podocin Mutations. J. Am. Soc. Nephrol. 14: 1278-1286 [Abstract] [Full Text]  
• Carraro, M., Zennaro, C., Candiano, G., Musante, L., Bruschi, M., Ghiggeri, G. M., Artero, M., Faccini, L. (2003). Nephrotic urine prevents increased rat glomerular albumin permeability induced by serum from the same patient with idiopathic nephrotic syndrome. Nephrol Dial Transplant 18: 689-693 [Abstract] [Full Text]  
• Cattran, D., Neogi, T., Sharma, R., McCarthy, E. T., Savin, V. J. (2003). Serial Estimates of Serum Permeability Activity and Clinical Correlates in Patients with Native Kidney Focal Segmental Glomerulosclerosis. J. Am. Soc. Nephrol. 14: 448-453 [Abstract] [Full Text]  
• Glassock, R. J. (2003). Circulating Permeability Factors in the Nephrotic Syndrome: A Fresh Look at an Old Problem. J. Am. Soc. Nephrol. 14: 541-543 [Full Text]  
• Nachman, P. H., Martin, J. (2002). Developments in the Immunotherapy of Glomerular Disease. Journal of Pharmacy Practice 15: 472-489 [Abstract]  
• Mundel, P., Shankland, S. J. (2002). Podocyte Biology and Response to Injury. J. Am. Soc. Nephrol. 13: 3005-3015 [Full Text]  
• Carraro, M., Caridi, G., Bruschi, M., Artero, M., Bertelli, R., Zennaro, C., Musante, L., Candiano, G., Perfumo, F., Ghiggeri, G. M. (2002). Serum Glomerular Permeability Activity in Patients with Podocin Mutations (NPHS2) and Steroid-ResistantNephrotic Syndrome. J. Am. Soc. Nephrol. 13: 1946-1952 [Abstract] [Full Text]  
• Huber, T. B., Reinhardt, H. C., Exner, M., Burger, J. A., Kerjaschki, D., Saleem, M. A., Pavenstadt, H. (2002). Expression of Functional CCR and CXCR Chemokine Receptors in Podocytes. J. Immunol. 168: 6244-6252 [Abstract] [Full Text]  
• Reiser, J., von Gersdorff, G., Simons, M., Schwarz, K., Faul, C., Giardino, L., Heider, T., Loos, M., Mundel, P. (2002). Novel concepts in understanding and management of glomerular proteinuria. Nephrol Dial Transplant 17: 951-955 [Full Text]  
• Frishberg, Y., Rinat, C., Megged, O., Shapira, E., Feinstein, S., Raas-Rothschild, A. (2002). Mutations in NPHS2 Encoding Podocin Are a Prevalent Cause of Steroid-Resistant Nephrotic Syndrome among Israeli-Arab Children. J. Am. Soc. Nephrol. 13: 400-405 [Abstract] [Full Text]  
• Bussemaker, E., Passauer, J., Franz, T., Gross, P. (2001). Tryptophan immunoadsorption strongly reduces proteinuria in recurrent nephrotic syndrome. Nephrol Dial Transplant 16: 1270-1272 [Full Text]  
• MARKOWITZ, G. S., APPEL, G. B., FINE, P. L., FENVES, A. Z., LOON, N. R., JAGANNATH, S., KUHN, J. A., DRATCH, A. D., D'AGATI, V. D. (2001). Collapsing Focal Segmental Glomerulosclerosis Following Treatment with High-Dose Pamidronate. J. Am. Soc. Nephrol. 12: 1164-1172 [Abstract] [Full Text]  
• Ghiggeri, G. M., Artero, M., Carraro, M., Perfumo, F. (2001). Permeability plasma factors in nephrotic syndrome: more than one factor, more than one inhibitor. Nephrol Dial Transplant 16: 882-885 [Full Text]  
• Prasad, G. V. R., Sweet, J. M., Cardella, C. J. (2001). First recurrence of focal segmental glomerulosclerosis in a third renal allograft. Nephrol Dial Transplant 16: 407-409 [Full Text]  
• Kemper, M. J., Wolf, G., Muller-Wiefel, D. E. (2001). Transmission of Glomerular Permeability Factor from a Mother to Her Child. NEJM 344: 386-387 [Full Text]  
• CHADBAN, S. J. (2001). Glomerulonephritis Recurrence in the Renal Graft. J. Am. Soc. Nephrol. 12: 394-402 [Full Text]  
• SCHWARZ, A. (2001). New Aspects of the Treatment of Nephrotic Syndrome. J. Am. Soc. Nephrol. 12: S44-S47 [Abstract] [Full Text]  
• CANDIANO, G., MUSANTE, L., CARRARO, M., FACCINI, L., CAMPANACCI, L., ZENNARO, C., ARTERO, M., GINEVRI, F., PERFUMO, F., GUSMANO, R., GHIGGERI, G. M. (2001). Apolipoproteins Prevent Glomerular Albumin Permeability Induced In Vitro by Serum from Patients with Focal Segmental Glomerulosclerosis. J. Am. Soc. Nephrol. 12: 143-150 [Abstract] [Full Text]  
• Cheong, H. I., Han, H. W., Park, H. W., Ha, I. S., Han, K. S., Lee, H. S., Kim, S. J., Choi, Y. (2000). Early recurrent nephrotic syndrome after renal transplantation in children with focal segmental glomerulosclerosis. Nephrol Dial Transplant 15: 78-81 [Abstract] [Full Text]  
• Andresdottir, M. B., Ajubi, N., Croockewit, S., Assmann, K. J. M., Hibrands, L. B., Wetzels, J. F. M. (1999). Recurrent focal glomerulosclerosis: natural course and treatment with plasma exchange. Nephrol Dial Transplant 14: 2650-2656 [Abstract] [Full Text]  
• DENAMUR, E., BOCQUET, N., MOUGENOT, B., DA SILVA, F., MARTINAT, L., LOIRAT, C., ELION, J., BENSMAN, A., RONCO, P. M. (1999). Mother-to-Child Transmitted WT1 Splice-Site Mutation Is Responsible for Distinct Glomerular Diseases. J. Am. Soc. Nephrol. 10: 2219-2223 [Abstract] [Full Text]  
• ESNAULT, V. L. M., BESNIER, D., TESTA, A., COVILLE, P., SIMON, P., SUBRA, J.-F., AUDRAIN, M. A. P. (1999). Effect of Protein A Immunoadsorption in Nephrotic Syndrome of Various Etiologies. J. Am. Soc. Nephrol. 10: 2014-2017 [Abstract] [Full Text]  
• CHEUNG, P. K., STULP, B., IMMENSCHUH, S., BORGHUIS, T., BALLER, J. F. W., BAKKER, W. W. (1999). Is 100KF an Isoform of Hemopexin? Immunochemical Characterization of the Vasoactive Plasma Factor 100KF. J. Am. Soc. Nephrol. 10: 1700-1708 [Abstract] [Full Text]  
• Binder, C. J., Weiher, H., Exner, M., Kerjaschki, D. (1999). Glomerular Overproduction of Oxygen Radicals in Mpv17 Gene-Inactivated Mice Causes Podocyte Foot Process Flattening and Proteinuria : A Model of Steroid-Resistant Nephrosis Sensitive to RadicalScavenger Therapy. Am. J. Pathol. 154: 1067-1075 [Abstract] [Full Text]  
• SHARMA, M., SHARMA, R., MCCARTHY, E. T., SAVIN, V. J. (1999). "The FSGS Factor": Enrichment and in Vivo Effectof Activity from Focal Segmental Glomerulosclerosis Plasma. J. Am. Soc. Nephrol. 10: 552-561 [Abstract] [Full Text]  
• Butani, L., Polinsky, M., Kaiser, B., Baluarte, H. (1999). Predictive value of race in post-transplantation recurrence of focal segmental glomerulosclerosis in children. Nephrol Dial Transplant 14: 166-168 [Abstract]  
• Orth, S. R., Ritz, E. (1998). The Nephrotic Syndrome. NEJM 338: 1202-1211 [Full Text]  
• Lesavre, P., Grunfeld, J.-P. (1996). Idiopathic Focal Segmental Glomerulosclerosis -- New Lessons from Kidney Transplantation. NEJM 334: 914-915 [Full Text]