Top

Published in:

Open Access 01-12-2018 | Educational Review

Combined and sequential liver–kidney transplantation in children

Authors: Ryszard Grenda, Piotr Kaliciński

Published in: Pediatric Nephrology | Issue 12/2018

Abstract

Combined and sequential liver–kidney transplantation (CLKT and SLKT) is a definitive treatment in children with end-stage organ failure. There are two major indications: - terminal insufficiency of both organs, or - need for transplanting new liver as a source of lacking enzyme or specific regulator of the immune system in a patient with renal failure. A third (uncommon) option is secondary end-stage renal failure in liver transplant recipients. These three clinical settings use distinct qualification algorithms. The most common indications include primary hyperoxaluria type 1 (PH1) and autosomal recessive polycystic kidney disease (ARPKD), followed by liver diseases associated with occasional kidney failure. Availability of anti-C5a antibody (eculizumab) has limited the validity of CLKT in genetic atypical hemolytic uremic syndrome (aHUS). The liver coming from the same donor as renal graft (in CLKT) is immunologically protective for the kidney and this provides long-term rejection-free follow-up. No such protection is observed in SLKT, when both organs come from different donors, except uncommon cases of living donation of both organs. Overall long-term outcome in CLKT in terms of graft survival is good and not different from isolated liver or kidney transplantation, however patient survival is inferior due to complexity of this procedure.

Mekahli D, van Stralen KJ, Bonthuis M, Jager KJ, Balat A, Godefroid N, Edvardsson VO, Heaf JG, Jankauskiene A, Kerecuk L, Marinova S, Puteo F, Seeman T, Zurowska A, Pirenne J, Schaefer F, Groothoff JW, ESPN/ERA-EDTA Registry (2016) Kidney versus combined kidney and liver transplantation in young people with autosomal recessive polycystic kidney disease: data from the European Society for Pediatric Nephrology/European renal association-European dialysis and transplant (ESPN/ERA-EDTA) registry. Am J Kidney Dis 68:782–788CrossRef

Kitajima K, Ogawa Y, Miki K, Kai K, Sannomiya A, Iwadoh K, Murakami T, Koyama I, Nakajima I, Fuchinoue S (2017) Long-term renal allograft survival after sequential liver–kidney transplantation from a single living donor. Liver Transpl 23:315–323CrossRef

Riechart S, Koch M, Oh J, Fisch M (2017) Early bilateral nephrectomy in neonatal autosomal recessive polycystic kidney disease: improved prognosis of unnecessary effort? Urologe 56:882–886CrossRef

Harps E, Brinkert F, Ganschow R, Briem-Richter A, van Husen M, Schmidtke S, Herden U, Nashan B, Fischer L, Kemper MJ (2011) Immediate postoperative intensive care treatment of pediatric combined liver–kidney transplantation: outcome and prognostic factors. Transplantation 91:1127–1231CrossRef

Kemper MJ (2005) Concurrent or sequential liver and kidney transplantation in children with primary hyperoxaluria type 1? Pediatr Transplant 9:693–696CrossRef

Büscher R, Büscher AK, Cetiner M, Treckmann JW, Paul A, Vester U, Hoyer PF (2015) Combined liver and kidney transplantation and kidney after liver transplantation in children: indication, postoperative outcome and long-term results. Pediatr Transplant 19:858–865CrossRef

Opelz G, Margreiter R, Dőhler B (2002) Prologation of long-term kidney graft survival by a simultaneous liver transplant: the liver does and the does too. Transplantation 74:1390–1394CrossRef

Rana A, Robles S, Russo M, Halzaun K, Woodland D, Witkowski P, Ratner LE, Hardy MA (2008) The combined organ effect: protection against rejection? Ann Surg 248:871–879CrossRef

Knechtle SJ, Kwun J (2009) Unique aspects of rejection and tolerance in liver transplantation. Semin Liver Dis 29:91–101CrossRef

10.

Key T, Watson C, Clarworthy O’RCM, Goodman RS, Taylor CJ, Butler AJ (2010) The kinetics of donor HLA class I-specific antibody absorption following split liver and kidney transplant. Nephrol Dial Transplant 3:579–581

11.

Créput C, Durrbach A, Menier C, Guettier C, Samuel D, Dausset J, Charpentier B, Carosella ED, Rouas-Freiss N (2003) Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver–kidney transplantation. J Hepatol 39:587–594CrossRef

12.

Askar M, Schold JD, Eghtesad B, Flechner SM, Kaplan B, Klingman L, Zein NN, Fung J, Srinivas TR (2011) Combined liver–kidney transplants: allosensitization and recipient outcomes. Transplantation 91:1286–1292CrossRef

13.

Grenda R, Jarmużek W, Jankowska I, Rubik J, Kaliciński P (2017) Combined liver–kidney transplantation in children with autosomal recessive polycystic kidney disease (ARPKD) - national center experience. Pediatr Nephrol 32:1672–1673 abstract O73 CrossRef

14.

Simpson N, Cho YW, Cicciarelli JC, Selby RR, Fong TL (2006) Comparison of renal allograft outcomes in combined liver–kidney transplantation versus subsequent kidney transplantation in liver transplant recipients: analysis of UNOS database. Transplantation 82:1298–1303CrossRef

15.

Udagawa T, Kamei K, Ogura M, Tsutsumi A, Noda S, Kasahara M, Fukuda A, Sakamoto S, Shigeta S, Tanaka H, Kuroda T, Matsuoka K, Nakazawa A, Nagai T, Uemura O, Ito S (2012) Sequential liver–kidney transplantation in a boy with congenital hepatic fibrosis and nephronophtysis from living related donor. Pediatr Transplant 16:E275–E280CrossRef

16.

de la Cerda F, Jimenez WA, Gjertson DW, Venick R, Tsai E, Ettenger R (2010) Renal graft outcome after combined liver and kidney transplantation in children: UCLA and UNOS experience. Pediatr Transplant 14:459–464CrossRef

17.

Del Gaudio M, Ravaioli M, Ercolani G, Cescon M, Amaduzzi A, Neri F, Pellegrini S, Feliciangeli G, Lamanna G, Morelli C, D’Arcangelo GL, Comai G, Cucchi M, Stefoni S, Pinna AD (2013) Induction therapy with alemtuzumab (Campath) in combined liver–kidney transplantation: University of Bologna experience. Transplant Proc 45:1969–1970CrossRef

18.

Pinna AD (2013) Induction therapy with alemtuzumab (Campath) in combined liver–kidney transplantation: University of Bologna experience. Transplant Proc 45:1969–1970CrossRef

19.

Sibal A, Malhotra S, Guru FR, Bhatia V, Kapoor A, Seth S, Jerath N, Jasuja S, Rajkumari V, Wadhawan M, Aggarwal DK, Guleria S, Shrivastava RN, Gupta S (2014) Experience of 100 solid organ transplants over a five-yr period from the first successful pediatric multi-organ transplant program in India. Pediatr Transplant 18:740–745CrossRef

20.

Ganschow R, Hoppe B (2015) Review of combined liver and kidney transplantation in children. Pediatr Transplant 19:820–826CrossRef

21.

Brinkert F, Lehnhardt A, Montoya C, Helmke K, Schaefer H, Fischer L, Nashan B, Bergmann C, Ganschow R, Kemper MJ (2013) Combined liver–kidney transplantation for children with autosomal recessive polycystic kidney disease (ARPKD): indication and outcome. Transpl Int 26:640–650CrossRef

22.

Calinescu AM, Wildhaber BE, Poncet A, Toso C, McLin VA (2014) Outcomes of combined liver–kidney transplantation in children: analysis of the scientific registry of transplant recipients. Am J Transplant 14:2861–2868CrossRef

23.

Cochat P, Hulton SA, Acquaviva C, Danpure CJ, Daudon M, De Marchi M, Fargue S, Groothoff J, Harambat J, Hoppe B, Jamieson NV, Kemper MJ, Mandrile G, Marangella M, Picca S, Rumsby G, Salido E, Straub M, van Woerden CS, OxalEurope (2012) Primary hyperoxaluria type 1: indications for screening and guidance for diagnosis and treatment. Nephrol Dial Transplant 27:1729–1736CrossRef

24.

Perera MT, Sharif K, Lloyd C, Foster K, Hulton SA, Mirza DF, McKiernan PJ (2011) Pre-emptive liver transplantation for primary hyperoxaluria (PH-I) arrests long-term renal function deterioration. Nephrol Dial Transplant 26:354–359CrossRef

25.

Khorsandi SE, Samyn M, Hassan A, Vilca-Melendez H, Waller S, Shroff R, Koffman G, Van’t Hoff W, Baker A, Dhawan A, Heaton N (2016) An institutional experience of pre-emptive liver transplantation for pediatric primary hyperoxaluria type 1. Pediatr Transplant 20:523–529CrossRef

26.

Wood K, Holmes R, Knight J (2016) RNA interference in the treatment of renal stone disease; current status and future potentials. Int J Surg 36:713–716CrossRef

27.

Naderi G, Latif A, Tabassomi F, Esfahani ST (2014) Failure of isolated kidney transplantation in a pediatric patient with primary hyperoxaluria type 2. Pediatr Transplant 18:E69–E73CrossRef

28.

Dhondup T, Lorenz EC, Milliner DS, Lieske JC (2017) Combined liver–kidney transplantation for primary Hyperoxaluria type 2: a case report. Am J Transplant. https://doi.org/10.1111/ajt.14418 CrossRef

29.

Hoyer P (2015) Clinical manifestations of autosomal recessive polycystic kidney disease. Curr Opin Pediatr 27:186–192CrossRef

30.

Rawat D, Kelly DA, Milford D, Sharif K, Lloyd C, McKiernan PJ (2013) Phenotypic variation and long-term outcome in children with congenital hepatic fibrosis. J Pediatr Gastoenterol 57:161–166CrossRef

31.

Srinath A, Shneider BL (2012) Congenital hepatic fibrosis and autosomal recessive polycystic kidney disease. J Pediatr Gastroenterol Nutr 54:580–587CrossRef

32.

Gunay-Aygun M, Font-Montgomery E, Lukose L, Tuchman Gerstein M, Piwnica-Worms K, Choyke P, Daryanani KT, Turkbey B, Fischer R, Bernardini I, Sincan M, Zhao X, Sandler NG, Roque A, Douek DC, Graf J, Huizing M, Bryant JC, Mohan P, Gahl WA, Heller T (2013) Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease. Gastroenterology 144:112–121CrossRef

33.

Luoto TT, Pakarinen MP, Jahnukainen T, Jalanko H (2014) Liver disease in autosomal recessive polycystic kidney disease: clinical characteristics and management in relation to renal failure. J Pediatr Gastroenterol Nutr 59:190–196CrossRef

34.

Chapal M, Debout A, Dufay A, Salomon R, Roussey G, Burtey S, Launay EA, Vigneau C, Blancho G, Loirat C, Hourmant M, Fakhouri F (2012) Kidney and liver transplantation in patients with autosomal recessive polycystic kidney disease: a multicentric study. Nephrol Dial Transplant 27:2083–2088CrossRef

35.

Davis ID, Ho M, Hupertz V, Avner ED (2003) Survival of childhood polycystic kidney disease following renal transplantation: the impact of advanced hepatobiliary disease. Pediatr Transplant 7:364–369CrossRef

36.

Khan K, Schwarzenberg SJ, Sharp HL, Matas AJ, Chavers BM (2002) Morbidity from congenital hepatic fibrosis after renal transplantation for autosomal recessive polycystic kidney disease. Am J Transplant 2:360–365CrossRef

37.

Telega G, Cronin D, Avner ED (2013) New approaches to the autosomal recessive polycystic kidney disease patient with dual kidney-liver complications. Pediatr Transplant 17:328–335CrossRef

38.

Boichis H, Passwell J, David R, Miller H (1973) Congenital hepatic fibrosis and nephronophtysis. A family study. Q J Med 42:221–223PubMed

39.

Otto E, Tory K, Attanasio MZhou W, Chaki M, Paruchuri Y, Wise EL, Wolf MT, Utsch B, Becker C, Nürnberg G, Nürnberg P, Nayir A, Saunier S, Antignac C, Hildebrandt F (2009) Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophtysis with liver fibrosis (NPHP1). J Med Genet 46:663–670CrossRef

40.

Duclaux-Loras R, Bacchetta J, Berthiller J, Rivet C, Demède D, Javouhey E, Dubois R, Dijoud F, Lachaux A, Badet L, Boillot O, Cochat P (2016) Pediatric combined liver–kidney transplantation: a single-center experience of 18 cases. Pediatr Nephrol 31:1517–1529CrossRef

41.

Zsengellér ZK, Aljinovic N, Teot LA, Korson M, Rodig N, Sloan JL, Venditti CP, Berry GT, Rosen S (2014) Methylmalonic acidemia: a megamitochondrial disorder affecting the kidney. Pediatr Nephrol 29:2139–2146CrossRef

42.

Sloan JL, Manoli I, Venditti CP (2015) Liver or combined liver–kidney transplantation for patients with isolated methylmalonic acidemia: who and when? J Pediatr 166:1346–1350CrossRef

43.

Spada M, Calvo PL, Brunati A, Peruzzi L, Dell’Olio D, Romagnoli R, Porta F (2015) Liver transplantation in severe methylmalonic acidemia: The sooner, the better. J Pediatr 167:1173CrossRef

44.

Niemi A, Kim I, Krueger C, Cowan TM, Baugh N, Farrell R, Bonham CA, Concepcion W, Esquivel CO, Enns GM (2015) Treatment of methylmalonic acidemia by liver or combined liver–kidney transplantation. J Pediatr 166:1455–1461CrossRef

45.

Spada M, Calvo PL, Brunati A, Peruzzi L, Dell’Olio D, Romagnoli R, Porta F (2015) Early liver transplantation for neonatal-onset methylmalonic acidemia. Pediatrics 136:e252–e256CrossRef

46.

Crowther DC, Belorgey D, Miranda E, Kinghorn KJ, Sharp LK, Lomas DA (2004) Practical genetics: alpha-1-antitrypsin deficiency and the serpinopathies. Eur J Hum Genet 12:167–172CrossRef

47.

Lhotta K (2002) Beyond hepatorenal syndrome: glomerulonephritis in patients with liver disease. Semin Nephrol 22:302–308PubMed

48.

Loreno M, Boccagni P, Rigotti P, Naccarato R, Burra P (2002) Combined liver–kidney transplantation in a 15-year-old boy with alpha1-antitrypsin deficiency. J Hepatol 36:565–568CrossRef

49.

Elzouki AN, Lindgren S, Nilsson S, Veress B, Eriksson S (1997) Severe alpha1-antitrypsin deficiency (PiZ homozygosity) with membranoproliferative glomerulonephritis and nephrotic syndrome, reversible after orthotopic liver transplantation. J Hepatol 26:1403–1407CrossRef

50.

Belingheri M, Ghio L, Sala A, Menni F, Trespidi L, Ferraresso M, Berardinelli L, Rossi G, Edefonti A, Parini R (2007) Combined liver–kidney transplantation in glycogen storage disease Ia: a case beyond the guidelines. Liver Transpl 13:762–764CrossRef

51.

Panaro F, Andorno E, Basile G, Morelli N, Bottino G, Fontana I, Bertocchi M, DiDomenico S, Miggino M, Saltalamacchia L, Ghinolfi D, Bonifazio L, Jarzembowski TM, Valente U (2004) Simultaneous liver–kidney transplantation for glycogen storage disease type IA (von Gierke’s disease). Transplant Proc 36:1483–1484CrossRef

52.

Jalanko H, Peltonen S, Koskinen A, Puntila J, Isoniemi H, Holmberg C, Pinomäki A, Armstrong E, Koivusalo A, Tukiainen E, Mäkisalo H, Saland J, Remuzzi G, de Cordoba S, Lassila R, Meri S, Jokiranta TS (2008) Successful liver–kidney transplantation in two children with aHUS caused by a mutation in complement factor H. Am J Transplant 8:216–221PubMed

53.

Saland JM, Ruggenenti P, Remuzzi G, Consensus Study Group (2009) Liver–kidney transplantation to cure atypical hemolytic uremic syndrome. J Am Soc Nephrol 20:940–949CrossRef

54.

Saland J (2014) Liver–kidney transplantation to cure atypical HUSL: still an option post eculizumab? Pediatr Nephrol 29:329–332CrossRef

55.

Zuber J, Le Quintrec M, Krid S, Bertoye C, Gueutin V, Lahoche A, Heyne N, Ardissino G, Chatelet V, Noël LH, Hourmant M, Niaudet P, Frémeaux-Bacchi V, Rondeau E, Legendre C, Loirat C, French Study Group for Atypical HUS (2012) Eculizumab for atypical hemolytic uremic syndrome recurrence in renal transplantation. Am J Transplant 12:3337–3354CrossRef

56.

Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A, Coppo R, Emma F, Johnson S, Karpman D, Landau D, Langman CB, Lapeyraque AL, Licht C, Nester C, Pecoraro C, Riedl M, van de Kar NC, Van de Walle J, Vivarelli M, Frémeaux-Bacchi V (2016) HUS international. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol 31:15–39CrossRef

57.

Coppo R, Bonaudo R, Peruzzi L, Amore A, Brunati A, Romagnoli R, Salizzoni M, Galbusera M, Gotti E, Daina E, Noris M, Remuzzi G (2016) Liver transplantation or aHUS; still needed in the eculizumab era? Pediatr Nephrol 31:759–768CrossRef

58.

Nadim MK, Sung RS, Davis CL, Andreoni KA, Biggins SW, Danovitch GM, Feng S, Friedewald JJ, Hong JC, Kellum JA, Kim WR, Lake JR, Melton LB, Pomfret EA, Saab S, Genyk YS (2012) Simultaneous liver–kidney transplantation summit: current state and future directions. Am J Transplant 12:2901–2908CrossRef

59.

Fong TL, Khemichian S, Shah T, Hutchinson IV, Cho YW (2012) Combined liver–kidney transplantation is preferable to liver transplant alone for cirrhotic patients with renal failure. Transplantation 94:411–416CrossRef

60.

Sharma P, Shu X, Schaubel DE, Sung RS, Magee JC (2016) Propensity score-based survival benefit of simultaneous liver–kidney transplant over liver transplant alone for recipients with pretransplant renal dysfunction. Liver Transpl 22:71–79CrossRef

61.

Matloff R, Arnon R (2015) The kidney in pediatric liver disease. Curr Gastroenterol Rep 17:1–9CrossRef

62.

Brinkert F, Kemper MJ, Briem-Richter A, van Husen M, Treszl A, Ganschow R (2011) High prevalence of renal dysfunction in children after liver transplantation: non-invasive diagnosis using a cystatin C-based equation. Nephrol Dial Transplant 26:1407–1412CrossRef

63.

Harambat J, Ranchin B, Dubourg L, Liutkus A, Hadj-Haïssa A, Rivet C, Boillot O, Lachaux A, Cochat P (2008) Renal function in pediatric liver transplantation: a long-term follow-up study. Transplantation 86:1028–1034CrossRef

64.

Filler G, Melk A, Marks SD (2016) Practice recommendations for the monitoring of renal function in pediatric non-renal organ transplant recipients. Pediatr Transplant 20:352–363CrossRef

65.

Glover TE, Watson CJ, Gibbs P, Bradley JA, Ntzani EE, Kosmoliaptsis V (2016) Conversion from calcineurin to mammalian target of rapamycin inhibitors in liver transplantation: a meta-analysis of randomized controlled trials. Transplantation 100:621–629CrossRef

66.

Ganschow R, Ericzon BG, Dhawan A, Sharif K, Martzloff ED, Rauer B, Ng J, Lopez P (2017) Everolimus and reduced calcineurin inhibitor therapy in pediatric liver transplant recipients: results from a multicenter, prospective study. Pediatr Transplant. https://doi.org/10.1111/petr.13024 CrossRef

67.

Hamdani G, Zhang B, Liu C, Goebel J, Zhang Y, Neuhus E (2017) Outcomes of pediatric kidney transplantation on recipients of a non-renal solid organ transplant. Am J Transplant 17:1928–1934CrossRef

Title: Combined and sequential liver–kidney transplantation in children
Authors: Ryszard Grenda
Piotr Kaliciński
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 12/2018
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-017-3880-4

At a glance: The STEP trials

Springer Medicine

Combined and sequential liver–kidney transplantation in children

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 12/2018

Diagnosis and management of bladder bowel dysfunction in children with urinary tract infections: a position statement from the International Children’s Continence Society

Outcome of membranoproliferative glomerulonephritis and C3-glomerulopathy in children and adolescents

Treatment strategies for children with steroid-dependent nephrotic syndrome: in need of controlled studies

Disruptive technological advances in vascular access for dialysis: an overview

Interdialytic weight gain and vasculopathy in children on hemodialysis: a single center study

Does idiopathic hypercalciuria affect bone metabolism during childhood? A prospective case-control study