Proteinuria has been established as a marker of kidney damage in experimental studies and clinicians consider an early reduction in albuminuria as indicative of a favorable response to treatment. Albuminuria is a sensitive marker of kidney disease progression in early stages of CKD and appears to be a cause of CKD progression in some disease. Our initial publication in the general CKD population did not provide sufficient evidence to establish its validity in all settings. Indeed in a subsequently publication in IgA nephropathy, we were able to demonstrate that there is strong association between treatment effects on change in albuminuria and treatment effects on the clinical endpoint. In a subsequent larger meta-analysis in the general CKD population, we were able to provide data that support a role for change in albuminuria as a surrogate endpoint for CKD progression, particularly in patients with higher baseline albuminuria and where there are large treatment effects.

Publications

  1. Inker, L.A., Levey, A.S., Pandya, K., Stoycheff, N., Okparavero, A., Greene, T. and Chronic Kidney Disease Epidemiology Collaboration, 2014. Early change in proteinuria as a surrogate end point for kidney disease progression: an individual patient meta-analysis. American Journal of Kidney Diseases, 64(1), pp.74-85. PMID: 24787763 PMCID: PMC4070618
  2. Inker, LA, Mondal, H, Greene, T, Masaschi, T, Locatelli, F, Schena, FP, Katafuchi, R, Appel, GB, Maes, BD, Li, PK and Praga, M, 2016. Early change in urine protein as a surrogate end point in studies of IgA nephropathy: an individual-patient meta-analysis. American Journal of Kidney Diseases, 68(3), pp.392-401. PMID: 27032886
  3. Heerspink, H.J., Greene, T., Tighiouart, H., Gansevoort, R.T., Coresh, J., Simon, A.L., Chan, T.M., Hou, F.F., Lewis, J.B., Locatelli, F. and Praga, M., 2019. Change in albuminuria as a surrogate endpoint for progression of kidney disease: a meta-analysis of treatment effects in randomised clinical trials. The Lancet Diabetes & Endocrinology7(2), pp.128-139. PMID: 30635226
  4. Coresh, J., Heerspink, H.J., Sang, Y., Matsushita, K., Arnlov, J., Astor, B.C., Black, C., Brunskill, N.J., Carrero, J.J., Feldman, H.I. and Fox, C.S., 2019. Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies. The Lancet Diabetes & Endocrinology7(2), pp.115-127. PMID: 30635225 PMCID: PMC6379893 [Available on 2020-02-01]
  5. Thompson, A., Carroll, K., Inker, L.A., Floege, J., Perkovic, V., Boyer-Suavet, S., Major, R.W., Schimpf, J.I., Barratt, J., Cattran, D.C. and Gillespie, B.S., 2019. Proteinuria reduction as a surrogate end point in trials of IgA nephropathy. Clinical Journal of the American Society of Nephrology14(3), pp.469-481. PMID: 30635299 PMCID: PMC6419287 [Available on 2020-03-07]