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01-01-2007 | Original Article

Cyclosporin therapy in patients with Alport syndrome

Authors: Marina Charbit, Marie-Claire Gubler, Michèle Dechaux, Marie-France Gagnadoux, Jean-Pierre Grünfeld, Patrick Niaudet

Published in: Pediatric Nephrology | Issue 1/2007

Abstract

Alport syndrome (AS) is a hereditary disorder of type IV collagen characterized by the association of progressive hematuric nephritis and sensorineural hearing loss. An increase in proteinuria is linked with progressive renal failure. Preliminary data have shown that cyclosporin therapy reduces proteinuria, thereby suggesting that it may also slow the progression of AS nephropathy. We treated nine AS patients manifesting proteinuria >1 g/m²/day and a glomerular filtration rate (GFR) >50 ml/min/1.73 m² with cyclosporin for at least 6 months. At the end of this 6-month period, mean proteinuria had decreased from 2±1.06 to 0.65±0.73 g/day, and mean albuminemia had increased from 29±5.2 to 35±6.5 g/l. Mean inulin clearance had decreased from 102±29 to 74±16.3 ml/min/1.73 m². Cyclosporin treatment was stopped in four patients because of inefficacy or adverse effects and continued in the remaining five patients for an additional 14–42 months. At the end of this second treatment period, control renal biopsies revealed significant lesions of cyclosporin nephrotoxicity in three patients. Based on these results we conclude that while cyclosporin therapy can decrease proteinuria in most patients with AS, it may be associated with nephrotoxicity, thereby precluding its long-term use.

Kashtan CE (1998) Alport syndrome and thin glomerular basement membrane disease. J Am Soc Nephrol 9:1736–1750PubMed

Barker DF, Hostikka SL, Zhou J, Chow LT, Oliphant AR, Gerken SC, Gregory MC, Skolnick MH, Atkin CL, Tryggvason K (1990) Identification of mutations in the COL4A5 collagen gene in Alport syndrome. Science 248:1224–1227CrossRef

Heiskari N, Zhang X, Zhou J, Leinonen A, Barker D, Gregory M, Atkin CL, Netzer KO, Weber M, Reeders S, Gronhagen-Riska C, Neumann HP, Trembath R, Tryggvason K (1996) Identification of 17 mutations in ten exons in the COL4A5 collagen gene, but no mutations found in four exons in COL4A6: A study of 250 patients with hematuria and suspected of having Alport syndrome. J Am Soc Nephrol 7:702–709PubMed

Antignac C, Knebelmann B, Druout L, Gros F, Deschenes G, Hors-Cayla MC, Zhou J, Tryggvason K, Grunfeld JP, Broyer M, Gubler MC (1994) Deletions in the COL4A5 collagen gene in X-linked Alport syndrome. Characterization of the pathological transcripts in nonrenal cells: Correlation with disease expression. J Clin Invest 93:1195–1207CrossRef

Rumpelt HJ (1980) Hereditary nephropathy (Alport syndrome): correlation of clinical data with glomerular basement membrane alterations. Clin Nephrol 13:203–207PubMed

Mochizuki T, Lemmink HH, Mariyama M, Antignac C, Gubler MC, Pirson Y, Verellen-Dumoulin C, Chan B, Schroder CH, Smeets HJ (1994) Identification of mutations in the a3(IV) and a4(IV) collagen genes in autosomal recessive Alport syndrome. Nat Genet 8:77–81CrossRef

Pescucci C, Mari F, Longo I, Vogiatzi P, Caselli R, Scala E, Abaterusso C, Gusmano R, Seri M, Miglietti N, Bresin E, Renieri A (2004) Autosomal-dominant Alport syndrome: Natural history of a disease due to COL4A3 or COL4A4 gene. Kidney Int 65:1598–1603CrossRef

van der Loop FT, Heidet L, Timmer ED, van den Bosch BJ, Leinonen A, Antignac C, Jefferson JA, Maxwell AP, Monnens LA, Schroder CH, Smeets HJ (2000) Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation. Kidney Int 58:1870–1875CrossRef

Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Verellen C, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Krejcova S, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2000) X-linked Alport syndrome: Natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol 11:649–657

10.

Valli V, Baumal R, Thorner P, Jacobs R, Marrano P, Davies C, Qizilbash B, Clarke H (1991) Dietary modification reduces splitting of glomerular basement membranes and delays death due to renal failure in canine X-linked hereditary nephritis. Lab Invest 65:67–73PubMed

11.

Grodecki K-M, Gains M-J, Baumal R, Osmond DH, Cotter B, Valli VE, Jacobs RM (1997) Treatment of X-linked hereditary nephritis in Samoyed dogs with angiotensin converting enzyme(ACE) inhibitor. J Comp Pathol 117:209–225CrossRef

12.

Gross O, Beirowski B, Koepke ML, Kuck J, Reiner M, Addicks K, Smyth N, Schulze-Lohoff E, Weber M (2003) Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in COL4A3-knockout mice with Alport syndrome. Kidney Int 63:438–446CrossRef

13.

Proesmans W, Knockaert H, Trouet D (2000) Enalapril in pediatric patients with Alport syndrome: 2 years experience. Eur J Pediatr 159:430–433CrossRef

14.

Proesmans W, Van Dyck M (2004) Enalapril in children with Alport syndrome. Pediatric Nephrol 19:271–275CrossRef

15.

Callis L, Vila A, Nieto J, Fortuny G (1992) Effects of cyclosporin A on proteinuria in patients with Alport’s syndrome. Pediatr Nephrol 6:140–144CrossRef

16.

Callis L, Vila A, Carrera M, Nieto J (1999) Long-term effects of cyclosporin A in Alport’s syndrome. Kidney Int 55:1051–1056CrossRef

17.

Chen D, Jefferson B, Harvey SJ, Zheng K, Gartley CJ, Jacobs RM, Thorner PS (2003) Cyclosporin A slows the progressive renal disease of Alport syndrome (X-linked hereditary nephritis): results from a canine model. J Am Soc Nephrol 14:690–698CrossRef

18.

Gubler MC, Antignac C, Deschênes G, Knebelmann B, Hors-Cayla MC, Grünfeld JP, Broyer M, Habib R (1992) Genetic, clinical and morphologic heterogeneity in Alport syndrome. Adv Nephrol Necker Hosp 22:14–34

19.

Iijima K, Hamahira K, Tanaka R, Kobayashi A, Nozu K, Nakamura H, Yoshikawa N (2002) Risk factors for cyclosporin-induced tubulointerstitial lesions in children with minimal change nephritic syndrome. Kidney Int 61:1801–1805CrossRef

20.

Kano K, Kyo K, Yamada Y, Ito S, Ando T, Arisaka O (1999) Comparison between pre-and posttreatment clinical and renal biopsies in children receiving low dose cyclosporin-A for 2 years for steroid-dependant nephritic syndrome. Clin Nephrol 55:424–425

21.

Habib R, Niaudet P (1994) Comparison between pre- and posttreatment renal biopsies in children receiving cyclosporin for idiopathic nephrosis. Clin Nephrol 42:141–146PubMed

22.

Gregory MJ, Smoyer WE, Sedman A, Kershaw DB, Valentini RP, Johnson K, Bunchman TE (1996) Long-term cyclosporin therapy for pediatric nephritic syndrome: a clinical and histological analysis. J Am Soc Nephrol 7:543–549

23.

Schmitt F, Martinez F, Brillet G, Nguyen-Khoa T, Brouard R, Sissmann J, Lacour B, Grunfeld JP (1998) Acute renal effects of AT1-receptor blockade after exogenous angiotensin II infusion in healthy subjects. J Cardiovasc Pharmacol 31:314–321CrossRef

24.

Oberbauer R, Haas M, Mayer G (1996) Proteinuria as consequence of altered glomerular permselectivity-clinical implications. Clin Nephrol 46:357–361PubMed

Title: Cyclosporin therapy in patients with Alport syndrome
Authors: Marina Charbit
Marie-Claire Gubler
Michèle Dechaux
Marie-France Gagnadoux
Jean-Pierre Grünfeld
Patrick Niaudet
Publication date: 01-01-2007
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 1/2007
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-006-0227-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cyclosporin therapy in patients with Alport syndrome

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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