Top

Published in:

Open Access 01-12-2015 | Research

Excellent long-term outcome of renal transplantation in cystinosis patients

Authors: Camille Cohen, Marina Charbit, Bernadette Chadefaux-Vekemans, Magali Giral, Valérie Garrigue, Michèle Kessler, Corinne Antoine, Renaud Snanoudj, Patrick Niaudet, Henri Kreis, Christophe Legendre, Aude Servais

Published in: Orphanet Journal of Rare Diseases | Issue 1/2015

Abstract

Background

Cystinosis is a rare lysosomal disorder leading to end stage renal disease in more than 90 % of patients before 20 years of age. Data about safety and efficiency of renal transplantation in patients with cystinosis is scarce. We evaluated long-term outcomes of renal transplantation in adult patients with cystinosis.

Methods

Data of renal transplantation (n = 31) in 30 adult patients with cystinosis in 5 French university transplant centers between 1980 and 2013 were retrospectively analyzed. A control cohort of 93 patients was matched for age, graft date, living/deceased donor status and transplant center.

Results

Median age at transplantation was 20.4 years (7–36.5). At transplantation, all patients with cystinosis had corneal cystine deposits, 3 had diabetes and 7 had hypothyroidism. Graft survival was better in patients with cystinosis than in control patients (p = 0.013). Multivariate analysis confirmed that cystinosis was an independent protective factor for graft survival (Hazard Ratio (HR) 0.11; CI95 [0.02-0.61]). Specific complications of cystinosis occurred during follow up: diabetes mellitus (n = 4), hypothyroidism (n = 1), liver involvement (n = 1), neurologic involvement (n = 2). Proportion of post-transplant diabetes mellitus (PTDM) was not statistically different in cystinosis group compared to control group: 4 (13.0 %) compared to 5 (5.0 %), respectively (p = 0.25), with no differences regarding calcineurin inhibitors and steroids treatments during follow-up.

Conclusions

Renal transplantation appears to be safe with excellent long-term outcomes in patients with cystinosis. These patients may receive standard immunosuppressive regimens with steroids and calcineurin inhibitors.

Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med. 2002;347:111–21.PubMedCrossRef

Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet. 1998;18:319–24.PubMedCrossRef

Anikster Y, Lucero C, Touchman JW, Huizing M, McDowell G, Shotelersuk V, et al. Identification and detection of the common 65-kb deletion breakpoint in the nephropathic cystinosis gene (CTNS). Mol Genet Metab. 1999;66:111–6.PubMedCrossRef

Forestier L, Jean G, Attard M, Cherqui S, Lewis C, van’t Hoff W, et al. Molecular characterization of CTNS deletions in nephropathic cystinosis: development of a PCR-based detection assay. Am J Hum Genet. 1999;65:353–9.PubMedCentralPubMedCrossRef

Gahl WA, Bashan N, Tietze F, Bernardini I, Schulman JD. Cystine transport is defective in isolated leukocyte lysosomes from patients with cystinosis. Science. 1982;217:1263–5.PubMedCrossRef

Sansanwal P, Yen B, Gahl WA, Ma Y, Ying L, Wong L-JC, et al. Mitochondrial autophagy promotes cellular injury in nephropathic cystinosis. J Am Soc Nephrol. 2010;21:272–83.PubMedCentralPubMedCrossRef

Prencipe G, Caiello I, Cherqui S, Whisenant T, Petrini S, Emma F, et al. Inflammasome activation by cystine crystals: implications for the pathogenesis of cystinosis. J Am Soc Nephrol. 2014;25:1163–9.PubMedCentralPubMedCrossRef

Brodin-Sartorius A, Tête M-J, Niaudet P, Antignac C, Guest G, Ottolenghi C, et al. Cysteamine therapy delays the progression of nephropathic cystinosis in late adolescents and adults. Kidney Int. 2012;81:179–89.PubMedCrossRef

Gahl WA, Balog JZ, Kleta R. Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy. Ann Intern Med. 2007;147:242–50.PubMedCrossRef

10.

Chabli A, Aupetit J, Raehm M, Ricquier D, Chadefaux-Vekemans B. Measurement of cystine in granulocytes using liquid chromatography-tandem mass spectrometry. Clin Biochem. 2007;40:692–8.PubMedCrossRef

11.

Dharnidharka VR, Fiorina P, Harmon WE. Kidney transplantation in children. N Engl J Med. 2014;371:549–58.PubMedCrossRef

12.

Horslen S, Barr ML, Christensen LL, Ettenger R, Magee JC. Pediatric transplantation in the United States, 1996–2005. Am J Transplant. 2007;7(5 Pt 2):1339–58.PubMedCrossRef

13.

Ehrich JH, Brodehl J, Byrd DI, Hossfeld S, Hoyer PF, Leipert KP, et al. Renal transplantation in 22 children with nephropathic cystinosis. Pediatr Nephrol. 1991;5:708–14.PubMedCrossRef

14.

Malekzadeh MH, Neustein HB, Schneider JA, Pennisi AJ, Ettenger RB, Uittenbogaart CH, et al. Cadaver renal transplantation in children with cystinosis. Am J Med. 1977;63:525–33.PubMedCrossRef

15.

Van Stralen KJ, Emma F, Jager KJ, Verrina E, Schaefer F, Laube GF, et al. Improvement in the renal prognosis in nephropathic cystinosis. Clin J Am Soc Nephrol. 2011;6:2485–91.PubMedCentralPubMedCrossRef

16.

Ladrière M: The western europe cohort of kidney transplanted recipients - the DIVAT network. Clin Transpl. 2010;460-461

17.

Metzger RA, Delmonico FL, Feng S, Port FK, Wynn JJ, Merion RM. Expanded criteria donors for kidney transplantation. Am J Transplant. 2003;3 Suppl 4:114–25.PubMedCrossRef

18.

Sis B, Mengel M, Haas M, Colvin RB, Halloran PF, Racusen LC, et al. Banff’09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant. 2010;10:464–71.PubMedCrossRef

19.

Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461–70.PubMedCrossRef

20.

Kleta R, Bernardini I, Ueda M, Varade WS, Phornphutkul C, Krasnewich D, et al. Long-term follow-up of well-treated nephropathic cystinosis patients. J Pediatr. 2004;145:555–60.PubMedCrossRef

21.

Kashtan CE, McEnery PT, Tejani A, Stablein DM. Renal allograft survival according to primary diagnosis: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol. 1995;9:679–84.PubMedCrossRef

22.

Spicer RA, Clayton PA, McTaggart SJ, Zhang GY, Alexander SI: Patient and Graft Survival Following Kidney Transplantation in Recipients With Cystinosis: A Cohort Study. Am J Kidney Dis. 2015;65(1):172-3.

23.

Broyer M, Tete MJ, Gubler MC. Late symptoms in infantile cystinosis. Pediatr Nephrol. 1987;1:519–24.PubMedCrossRef

24.

Dobbels F, Ruppar T, De Geest S, Decorte A, Van Damme-Lombaerts R, Fine RN. Adherence to the immunosuppressive regimen in pediatric kidney transplant recipients: a systematic review. Pediatr Transplant. 2010;14:603–13.PubMedCrossRef

25.

Wühl E, van Stralen KJ, Wanner C, Ariceta G, Heaf JG, Bjerre AK, et al. Renal replacement therapy for rare diseases affecting the kidney: an analysis of the ERA-EDTA Registry. Nephrol Dial Transplant. 2014;29(4):1–8.CrossRef

26.

Spear GS, Gubler MC, Habib R, Broyer M. Renal allografts in cystinosis and mesangial demography. Clin Nephrol. 1989;32:256–61.PubMed

27.

Cochat P, Fargue S, Mestrallet G, Jungraithmayr T, Koch-Nogueira P, Ranchin B, et al. Disease recurrence in paediatric renal transplantation. Pediatr Nephrol. 2009;24:2097–108.PubMedCentralPubMedCrossRef

28.

Filler G, Amendt P, von Bredow MA, Rohde W, Ehrich JH. Slowly deteriorating insulin secretion and C-peptide production characterizes diabetes mellitus in infantile cystinosis. Eur J Pediatr. 1998;157:738–42.PubMedCrossRef

29.

Robert JJ, Tête MJ, Guest G, Gagnadoux MF, Niaudet P, Broyer M. Diabetes mellitus in patients with infantile cystinosis after renal transplantation. Pediatr Nephrol. 1999;13:524–9.PubMedCrossRef

30.

Nesterova G, Gahl WA. Cystinosis: the evolution of a treatable disease. Pediatr Nephrol. 2013;28:51–9.PubMedCentralPubMedCrossRef

31.

Emma F, Nesterova G, Langman C, Labbé A, Cherqui S, Goodyer P, et al. Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant. 2014;29(4):87–94.CrossRef

Title: Excellent long-term outcome of renal transplantation in cystinosis patients
Authors: Camille Cohen
Marina Charbit
Bernadette Chadefaux-Vekemans
Magali Giral
Valérie Garrigue
Michèle Kessler
Corinne Antoine
Renaud Snanoudj
Patrick Niaudet
Henri Kreis
Christophe Legendre
Aude Servais
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2015
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-015-0307-9

At a glance: The STEP trials

Springer Medicine

Excellent long-term outcome of renal transplantation in cystinosis patients

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2015

A hypomorphic BMPR1B mutation causes du Pan acromesomelic dysplasia

A proposed definition of rare diseases for China: from the perspective of return on investment in new orphan drugs

Glycogen storage disease type Ia (GSDIa) but not Glycogen storage disease type Ib (GSDIb) is associated to an increased risk of metabolic syndrome: possible role of microsomal glucose 6-phosphate accumulation

Progressive hemifacial atrophy: a review

Clinical characteristics and prognostic factors of adult hemophagocytic syndrome patients: a retrospective study of increasing awareness of a disease from a single-center in China

Naproxcinod shows significant advantages over naproxen in the mdx model of Duchenne Muscular Dystrophy