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01-10-2018 | Original Article

Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings

Authors: Jonathan H. Pelletier, Karan R. Kumar, Rachel Engen, Adam Bensimhon, Jennifer D. Varner, Michelle N. Rheault, Tarak Srivastava, Caroline Straatmann, Cynthia Silva, T. Keefe Davis, Scott E. Wenderfer, Keisha Gibson, David Selewski, John Barcia, Patricia Weng, Christoph Licht, Natasha Jawa, Mahmoud Kallash, John W. Foreman, Delbert R. Wigfall, Annabelle N. Chua, Eileen Chambers, Christoph P. Hornik, Eileen D. Brewer, Shashi K. Nagaraj, Larry A. Greenbaum, Rasheed A. Gbadegesin

Published in: Pediatric Nephrology | Issue 10/2018

Abstract

Background and objectives

Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence.

Methods

Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence.

Results

We analyzed 158 patients; 64 (41%) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78% of patients with LSRNS compared to 39% of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76% recurrence rate compared with a 40% recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95% CI 5.6; 1.3–23.7) compared to FSGS predicted disease recurrence.

Conclusions

Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence.

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Fogo AB (2015) Causes and pathogenesis of focal segmental glomerulosclerosis. Nat Rev Nephrol 11(2):76–87CrossRef

Kitiyakara C, Eggers P, Kopp JB (2004) Twenty-one-year trend in ESRD due to focal segmental glomerulosclerosis in the United States. Am J Kidney Dis 44(5):815–825CrossRef

Savin VJ, Sharma R, Sharma M, McCarthy ET, Swan SK, Ellis E, Lovell H, Warady B, Gunwar S, Chonko AM, Artero M, Vincenti F (1996) Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 334(14):878–883CrossRef

McCarthy ET, Sharma M, Savin VJ (2010) Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 5(11):2115–2121CrossRef

Warejko JK, Tan W, Daga A, Schapiro D, Lawson JA, Shril S, Lovric S, Ashraf S, Rao J, Hermle T, Jobst-Schwan T, Widmeier E, Majmundar AJ, Schneider R, Gee HY, Schmidt JM, Vivante A, van der Ven AT, Ityel H, Chen J, Sadowski CE, Kohl S, Pabst WL, Nakayama M, Somers MJG, Rodig NM, Daouk G, Baum M, Stein DR, Ferguson MA, Traum AZ, Soliman NA, Kari JA, El Desoky S, Fathy H, Zenker M, Bakkaloglu SA, Muller D, Noyan A, Ozaltin F, Cadnapaphornchai MA, Hashmi S, Hopcian J, Kopp JB, Benador N, Bockenhauer D, Bogdanovic R, Stajic N, Chernin G, Ettenger R, Fehrenbach H, Kemper M, Munarriz RL, Podracka L, Buscher R, Serdaroglu E, Tasic V, Mane S, Lifton RP, Braun DA, Hildebrandt F (2018) Whole exome sequencing of patients with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 13(1):53–62CrossRef

Sen ES, Dean P, Yarram-Smith L, Bierzynska A, Woodward G, Buxton C, Dennis G, Welsh GI, Williams M, Saleem MA (2017) Clinical genetic testing using a custom-designed steroid-resistant nephrotic syndrome gene panel: analysis and recommendations. J Med Genet 54(12):795–804CrossRef

Sampson MG, Gillies CE, Robertson CC, Crawford B, Vega-Warner V, Otto EA, Kretzler M, Kang HM (2016) Using population genetics to interrogate the monogenic nephrotic syndrome diagnosis in a case cohort. J Am Soc Nephrol 27(7):1970–1983CrossRef

Gbadegesin R, Lavin P, Foreman J, Winn M (2011) Pathogenesis and therapy of focal segmental glomerulosclerosis: an update. Pediatr Nephrol 26(7):1001–1015CrossRef

Cattran DC, Rao P (1998) Long-term outcome in children and adults with classic focal segmental glomerulosclerosis. Am J Kidney Dis 32(1):72–79CrossRef

10.

Mekahli D, Liutkus A, Ranchin B, Yu A, Bessenay L, Girardin E, Van Damme-Lombaerts R, Palcoux JB, Cachat F, Lavocat MP, Bourdat-Michel G, Nobili F, Cochat P (2009) Long-term outcome of idiopathic steroid-resistant nephrotic syndrome: a multicenter study. Pediatr Nephrol 24(8):1525–1532CrossRef

11.

Staeck O, Halleck F, Budde K, Khadzhynov D (2017) Long-term outcomes of kidney transplant recipients with primary idiopathic focal segmental glomerulosclerosis. Transplant Proc 49(10):2256–2259CrossRef

12.

Cormican S, Kennedy C, O'Kelly P, Doyle B, Dorman A, Awan A, Conlon P (2018) Renal transplant outcomes in primary FSGS compared with other recipients and risk factors for recurrence: a national review of the Irish transplant registry. Clin Transpl. https://doi.org/10.1111/ctr.13152 CrossRef

13.

Cleper R, Krause I, Bar Nathan N, Mor M, Dagan A, Weissman I, Frishberg Y, Rachamimov R, Mor E, Davidovits M (2016) Focal segmental glomerulosclerosis in pediatric kidney transplantation: 30 years’ experience. Clin Transpl 30(10):1324–1331CrossRef

14.

Trachtman R, Sran SS, Trachtman H (2015) Recurrent focal segmental glomerulosclerosis after kidney transplantation. Pediatr Nephrol 30(10):1793–1802CrossRef

15.

Francis A, Trnka P, McTaggart SJ (2016) Long-term outcome of kidney transplantation in recipients with focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 11(11):2041–2046CrossRef

16.

Vinai M, Waber P, Seikaly MG (2010) Recurrence of focal segmental glomerulosclerosis in renal allograft: an in-depth review. Pediatr Transplant 14(3):314–325CrossRef

17.

Nehus EJ, Goebel JW, Succop PS, Abraham EC (2013) Focal segmental glomerulosclerosis in children: multivariate analysis indicates that donor type does not alter recurrence risk. Transplantation 96(6):550–554CrossRef

18.

Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, Zalewski I, Imm A, Ruf EM, Mucha B, Bagga A, Neuhaus T, Fuchshuber A, Bakkaloglu A, Hildebrandt F, Arbeitsgemeinschaft Fur Padiatrische Nephrologie Study G (2004) Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 15(3):722–732CrossRef

19.

Ding WY, Koziell A, McCarthy HJ, Bierzynska A, Bhagavatula MK, Dudley JA, Inward CD, Coward RJ, Tizard J, Reid C, Antignac C, Boyer O, Saleem MA (2014) Initial steroid sensitivity in children with steroid-resistant nephrotic syndrome predicts post-transplant recurrence. J Am Soc Nephrol 25(6):1342–1348CrossRef

20.

Bierzynska A, McCarthy HJ, Soderquest K, Sen ES, Colby E, Ding WY, Nabhan MM, Kerecuk L, Hegde S, Hughes D, Marks S, Feather S, Jones C, Webb NJ, Ognjanovic M, Christian M, Gilbert RD, Sinha MD, Lord GM, Simpson M, Koziell AB, Welsh GI, Saleem MA (2017) Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management. Kidney Int 91(4):937–947CrossRef

21.

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG (2009) Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42(2):377–381CrossRef

22.

Hart A, Smith JM, Skeans MA, Gustafson SK, Wilk AR, Robinson A, Wainright JL, Haynes CR, Snyder JJ, Kasiske BL, Israni AK (2018) OPTN/SRTR 2016 annual data report: kidney. Am J Transplant 18(Suppl 1):18–113CrossRef

23.

Tejani A, Stablein DH (1992) Recurrence of focal segmental glomerulosclerosis posttransplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study. J Am Soc Nephrol 2(12 Suppl):S258–S263PubMed

24.

Vivarelli M, Massella L, Ruggiero B, Emma F (2017) Minimal change disease. Clin J Am Soc Nephrol 12(2):332–345CrossRef

25.

Ha TS (2017) Genetics of hereditary nephrotic syndrome: a clinical review. Korean J Pediatr 60(3):55–63CrossRef

26.

Cheong HI, Han HW, Park HW, Ha IS, Han KS, Lee HS, Kim SJ, Choi Y (2000) Early recurrent nephrotic syndrome after renal transplantation in children with focal segmental glomerulosclerosis. Nephrol Dial Transplant 15(1):78–81CrossRef

27.

Hoyer JR, Vernier RL, Najarian JS, Raij L, Simmons RL, Michael AF (1972) Recurrence of idiopathic nephrotic syndrome after renal transplantation. Lancet 2(7773):343–348CrossRef

28.

Karp AM, Gbadegesin RA (2017) Genetics of childhood steroid-sensitive nephrotic syndrome. Pediatr Nephrol 32(9):1481–1488 8CrossRef

29.

Adeyemo A, Esezobor C, Solarin A, Abeyagunawardena A, Kari JA, El Desoky S, Greenbaum LA, Kamel M, Kallash M, Silva C, Young A, Hunley TE, de Jesus-Gonzalez N, Srivastava T, Gbadegesin R (2018) HLA-DQA1 and APOL1 as risk loci for childhood-onset steroid-sensitive and steroid-resistant nephrotic syndrome. Am J Kidney Dis 71(3):399–406CrossRef

30.

Gbadegesin RA, Adeyemo A, Webb NJ, Greenbaum LA, Abeyagunawardena A, Thalgahagoda S, Kale A, Gipson D, Srivastava T, Lin JJ, Chand D, Hunley TE, Brophy PD, Bagga A, Sinha A, Rheault MN, Ghali J, Nicholls K, Abraham E, Janjua HS, Omoloja A, Barletta GM, Cai Y, Milford DD, O'Brien C, Awan A, Belostotsky V, Smoyer WE, Homstad A, Hall G, Wu G, Nagaraj S, Wigfall D, Foreman J, Winn MP, Mid-West Pediatric Nephrology C (2015) HLA-DQA1 and PLCG2 are candidate risk loci for childhood-onset steroid-sensitive nephrotic syndrome. J Am Soc Nephrol 26(7):1701–1710CrossRef

Title: Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings
Authors: Jonathan H. Pelletier
Karan R. Kumar
Rachel Engen
Adam Bensimhon
Jennifer D. Varner
Michelle N. Rheault
Tarak Srivastava
Caroline Straatmann
Cynthia Silva
T. Keefe Davis
Scott E. Wenderfer
Keisha Gibson
David Selewski
John Barcia
Patricia Weng
Christoph Licht
Natasha Jawa
Mahmoud Kallash
John W. Foreman
Delbert R. Wigfall
Annabelle N. Chua
Eileen Chambers
Christoph P. Hornik
Eileen D. Brewer
Shashi K. Nagaraj
Larry A. Greenbaum
Rasheed A. Gbadegesin
Publication date: 01-10-2018
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 10/2018
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-018-3994-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings

Abstract

Background and objectives

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and objectives

Methods

Results

Conclusions

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