Renal outcomes of agalsidase beta treatment for Fabry disease

Role of proteinuria and timing of treatment initiation

David G. Warnock, Alberto Ortiz, Michael Mauer, Gabor E. Linthorst, João P. Oliveira, Andreas L. Serra, L. Máródi, Renzo Mignani, Bojan Vujkovac, Dana Beitner-Johnson, Roberta Lemay, Alexander Cole, Einar Svarstad, Stephen Waldek, Dominique P. Germain, Christoph Wanner

Research output: Contribution to journalArticle

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Abstract

Background. The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta. Methods. Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression. Results. Men within the first quartile had a mean eGFR slope of -0.1 mL/min/1.73m2/year, whereas men with the most rapid renal disease progression (Quartile 4) had a 1*mean eGFR slope of -6.7 mL/min/1.73m2/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr)-1 g/g (odds ratio 112 95% confidence interval (95% CI) 4-3109 P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19 95% CI 2-184 P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope -4.4 mL/min/1.73m2/year). Conclusions. Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy particularly if proteinuria is-1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes.

Original languageEnglish
Pages (from-to)1042-1049
Number of pages8
JournalNephrology Dialysis Transplantation
Volume27
Issue number3
DOIs
Publication statusPublished - May 2012

Fingerprint

Fabry Disease
Proteinuria
Kidney
Disease Progression
Glomerular Filtration Rate
Therapeutics
Creatinine
Odds Ratio
Confidence Intervals
Enzyme Replacement Therapy
agalsidase beta
Proteins
Registries
Logistic Models
Regression Analysis

Keywords

  • Alpha galactosidase
  • Enzyme replacement therapy
  • Fabry disease
  • Genetic renal disease
  • Proteinuria

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Warnock, D. G., Ortiz, A., Mauer, M., Linthorst, G. E., Oliveira, J. P., Serra, A. L., ... Wanner, C. (2012). Renal outcomes of agalsidase beta treatment for Fabry disease: Role of proteinuria and timing of treatment initiation. Nephrology Dialysis Transplantation, 27(3), 1042-1049. https://doi.org/10.1093/ndt/gfr4200

Renal outcomes of agalsidase beta treatment for Fabry disease : Role of proteinuria and timing of treatment initiation. / Warnock, David G.; Ortiz, Alberto; Mauer, Michael; Linthorst, Gabor E.; Oliveira, João P.; Serra, Andreas L.; Máródi, L.; Mignani, Renzo; Vujkovac, Bojan; Beitner-Johnson, Dana; Lemay, Roberta; Cole, Alexander; Svarstad, Einar; Waldek, Stephen; Germain, Dominique P.; Wanner, Christoph.

In: Nephrology Dialysis Transplantation, Vol. 27, No. 3, 05.2012, p. 1042-1049.

Research output: Contribution to journalArticle

Warnock, DG, Ortiz, A, Mauer, M, Linthorst, GE, Oliveira, JP, Serra, AL, Máródi, L, Mignani, R, Vujkovac, B, Beitner-Johnson, D, Lemay, R, Cole, A, Svarstad, E, Waldek, S, Germain, DP & Wanner, C 2012, 'Renal outcomes of agalsidase beta treatment for Fabry disease: Role of proteinuria and timing of treatment initiation', Nephrology Dialysis Transplantation, vol. 27, no. 3, pp. 1042-1049. https://doi.org/10.1093/ndt/gfr4200
Warnock, David G. ; Ortiz, Alberto ; Mauer, Michael ; Linthorst, Gabor E. ; Oliveira, João P. ; Serra, Andreas L. ; Máródi, L. ; Mignani, Renzo ; Vujkovac, Bojan ; Beitner-Johnson, Dana ; Lemay, Roberta ; Cole, Alexander ; Svarstad, Einar ; Waldek, Stephen ; Germain, Dominique P. ; Wanner, Christoph. / Renal outcomes of agalsidase beta treatment for Fabry disease : Role of proteinuria and timing of treatment initiation. In: Nephrology Dialysis Transplantation. 2012 ; Vol. 27, No. 3. pp. 1042-1049.
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