End-stage kidney disease due to Alport syndrome : outcomes in 296 consecutive Australia and New Zealand Dialysis and Transplant Registry cases

Background. Alport syndrome is a rare inheritable renal disease. Clinical outcomes for patients progressing to endstage kidney disease (ESKD) are not well described. Methods. This study aimed to investigate the characteristics and clinical outcomes of patients from Australia and New Zealand commencing renal replacement therapy (RRT) for ESKD due to Alport syndrome between 1965 and 1995 (early cohort) and between 1996 and 2010 (contemporary cohort) compared with propensity score-matched, RRT-treated, nonAlport ESKD controls. Results. A total of 58 422 patients started RRT during this period of which 296 (0.5%) patients had Alport ESKD. In the early cohort, Alport ESKD was associated with superior dialysis patient survival [adjusted hazard ratio (HR): 0.41, 95% confidence interval (CI): 0.20–0.83, P = 0.01], renal allograft survival (HR: 0.74, 95% CI: 0.54–1.01, P = 0.05) and renal transplant patient survival (HR: 0.43, 95% CI: 0.28–0.66, P < 0.001) compared with controls. In the contemporary cohort, no differences were observed between the two groups for dialysis patient survival (HR: 1.42, 95% CI: 0.65–3.11, P = 0.38), renal allograft survival (HR: 1.01, 95% CI: 0.57–1.79, P = 0.98) or renal transplant patient survival (HR: 0.67, 95% CI: 0.26– 1.73, P = 0.41). One Alport patient (0.4%) had post-transplant anti-glomerular basement membrane (anti-GBM) disease. Four female and 41 male Alport patients became parents on RRT with generally good neonatal outcomes. O R IG IN A L A R T IC L E © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. 2277 D ow naded rom http/academ ic.p.com /ndt/article-a/29/12/2277/1851764 by gest on 13 M arch 2019 Conclusion. Alport syndrome patients experienced comparable dialysis and renal transplant outcomes to matched nonAlport ESKD controls in the contemporary cohort due to relatively greater improvements in outcomes for non-Alport ESKD patients over time. Post-transplant anti-GBM disease was rare.

[1]  L. Berardinelli,et al.  Renal transplantation in Alport's syndrome. Personal experience in twelve patients. , 1990, Contributions to nephrology.

[2]  T. Friede,et al.  Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. , 2012, Kidney international.

[3]  A. Renieri,et al.  Autosomal-dominant Alport syndrome: natural history of a disease due to COL4A3 or COL4A4 gene. , 2004, Kidney international.

[4]  M Lunn,et al.  Applying Cox regression to competing risks. , 1995, Biometrics.

[5]  M. Skolnick,et al.  Identification of mutations in the COL4A5 collagen gene in Alport syndrome. , 1990, Science.

[6]  M. Budisavljevic,et al.  Renal transplant in patients with Alport's syndrome. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[7]  M. Van Dyck,et al.  Enalapril in children with Alport syndrome , 2004, Pediatric Nephrology.

[8]  R. Hekmat,et al.  Kidney transplantation in patients with alport syndrome. , 2007, Urology journal.

[9]  D. Colville,et al.  Opinion: Ocular features aid the diagnosis of Alport syndrome , 2009, Nature Reviews Nephrology.

[10]  Alport Ac.  HEREDITARY FAMILIAL CONGENITAL HAEMORRHAGIC NEPHRITIS , 1927 .

[11]  H. Smeets,et al.  X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a "European Community Alport Syndrome Concerted Action" study. , 2003, Journal of the American Society of Nephrology : JASN.

[12]  Marian Knight,et al.  Pregnancy in renal transplant recipients: a UK national cohort study. , 2013, Clinical journal of the American Society of Nephrology : CJASN.

[13]  H. Trivedi,et al.  Outcome of renal transplantation in Alport's syndrome: a single-center experience. , 2012, Transplantation proceedings.

[14]  S. Shahinfar,et al.  Efficacy and safety of losartan in children with Alport syndrome--results from a subgroup analysis of a prospective, randomized, placebo- or amlodipine-controlled trial. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[15]  Ali Ahmed,et al.  Chronic kidney disease associated mortality in diastolic versus systolic heart failure: a propensity matched study. , 2007, The American journal of cardiology.

[16]  R. Martín-Hernández,et al.  Pregnancy in women on chronic dialysis: a review. , 2012, Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia.

[17]  J. Davison,et al.  Pregnancy after transplantation. , 2000, Transplantation reviews.

[18]  Tim Friede,et al.  Safety and Efficacy of the ACE-Inhibitor Ramipril in Alport Syndrome: The Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III EARLY PRO-TECT Alport Trial in Pediatric Patients , 2012, ISRN pediatrics.

[19]  A. Fogo,et al.  Distinct epitopes for anti-glomerular basement membrane alport alloantibodies and goodpasture autoantibodies within the noncollagenous domain of alpha3(IV) collagen: a janus-faced antigen. , 2005, Journal of the American Society of Nephrology : JASN.

[20]  C. Kashtan.  Renal transplantation in patients with Alport syndrome , 2006, Pediatric transplantation.

[21]  J. Grünfeld.  The clinical spectrum of hereditary nephritis. , 1985, Kidney international.

[22]  A. Nocera,et al.  Alport syndrome: HLA association and kidney graft outcome. , 2004, European journal of immunogenetics.

[23]  H. Smeets,et al.  X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. , 2000, Journal of the American Society of Nephrology : JASN.

[24]  Jie Ding,et al.  Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. , 2013, Journal of the American Society of Nephrology : JASN.

[25]  C. Antignac.  Molecular genetics of basement membranes: the paradigm of Alport syndrome. , 1995, Kidney international. Supplement.

[26]  H. Smeets,et al.  Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. , 1994, Nature genetics.

[27]  U. Helmchen,et al.  Kidney transplantation in Alport's syndrome: long-term outcome and allograft anti-GBM nephritis. , 1992, Clinical nephrology.

[28]  R. Pijnenborg,et al.  Risk of Obstetrical Complications in Organ Transplant Recipient Pregnancies , 2013, Transplantation.

[29]  T. Watnick,et al.  Aortic abnormalities in males with Alport syndrome. , 2010, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[30]  M. Bobrow,et al.  GENETICS OF CLASSIC ALPORT'S SYNDROME , 1988, The Lancet.

[31]  J. Alexander,et al.  Alport's syndrome: risk of glomerulonephritis induced by anti-glomerular-basement-membrane antibody after renal transplantation. , 1988, Nephron.

[32]  G. Mazzucco,et al.  COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome. , 2002, Kidney international.

[33]  Y. Sado,et al.  J Am Soc Nephrol 15: 1466–1474, 2004 Mouse Model of X-Linked Alport Syndrome , 2022 .

[34]  H. Smeets,et al.  The clinical spectrum of type IV collagen mutations. , 1997, Human mutation.

[35]  R. Elias,et al.  Obstetric outcome in pregnant women on long-term dialysis: a case series. , 2010, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[36]  M. Bobrow,et al.  Localization of the gene for classic Alport syndrome. , 1989, Genomics.

[37]  J. Feingold,et al.  Estimating prevalence in single-gene kidney diseases progressing to renal failure. , 2000, Kidney international.

[38]  J. Oliveira,et al.  X-inactivation modifies disease severity in female carriers of murine X-linked Alport syndrome , 2010 .

[39]  D. Colville,et al.  Retinal abnormalities characteristic of inherited renal disease. , 2011, Journal of the American Society of Nephrology : JASN.

[40]  H. Karakayalı,et al.  Acute rejection rates and survival of renal transplant recipients with Alport's Syndrome. , 2008, Transplantation proceedings.

[41]  F. Dekker,et al.  Outcomes of male patients with Alport syndrome undergoing renal replacement therapy. , 2012, Clinical journal of the American Society of Nephrology : CJASN.

[42]  J. Squifflet,et al.  OUTCOME OF THIRTY PATIENTS WITH ALPORT'S SYNDROME AFTER RENAL TRANSPLANTATION , 1991, Transplantation.

[43]  W. R. Richardson,et al.  The pathogenesis of Alport syndrome involves type IV collagen molecules containing the alpha 3(IV) chain: evidence from anti-GBM nephritis after renal transplantation. , 1992, Kidney international.

[44]  N. Gretz,et al.  Alport's syndrome as a cause of renal failure in Europe , 1987, Pediatric Nephrology.

[45]  C. Wilson,et al.  Absence of nephritogenic GBM antigen(s) in some patients with hereditary nephritis. , 1982, Kidney international.

[46]  R. Kalluri,et al.  COL4A5 gene deletion and production of post-transplant anti-alpha 3(IV) collagen alloantibodies in Alport syndrome. , 1994, Kidney international.

[47]  S. Constantinescu,et al.  Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. , 2003, Clinical transplants.

[48]  Jie Ding,et al.  Clinical practice recommendations for the treatment of Alport syndrome: a statement of the Alport Syndrome Research Collaborative , 2012, Pediatric Nephrology.

[49]  K. Tryggvason,et al.  COL4A5 deletions in three patients with Alport syndrome and posttransplant antiglomerular basement membrane nephritis. , 1994, Journal of the American Society of Nephrology : JASN.

[50]  C. Antignac,et al.  A large tandem duplication within the COL4A5 gene is responsible for the high prevalence of Alport syndrome in French Polynesia. , 2004, Kidney international.

[51]  R. Torra,et al.  Incidence of renal failure and nephroprotection by RAAS inhibition in heterozygous carriers of X-chromosomal and autosomal recessive Alport mutations. , 2012, Kidney international.

[52]  J. Savige.  Hereditary abnormalities of renal basement membranes , 1991, Pathology.

[53]  C. Atkin,et al.  X-linked inheritance of Alport syndrome: family P revisited. , 1983, American journal of human genetics.

[54]  H. Smeets,et al.  A COL4A3 gene mutation and post-transplant anti-alpha 3(IV) collagen alloantibodies in Alport syndrome. , 1995, Kidney international.

[55]  A. Chompret,et al.  Genetic heterogeneity of Alport syndrome. , 1985, Kidney international.

[56]  C. Kashtan.  Alport Syndrome and Thin Basement Membrane Nephropathy , 2015 .