1. ¹Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada
2. ²Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts, USA
3. ³Division of Nephrology, Beth Israel-Deaconess Medical Center and Joslin Diabetes Center, Boston, Massachusetts, USA

Correspondence: Bruce A Perkins, Division of Endocrinology and Metabolism, University of Toronto, 200 Elizabeth Street, Room EN-12-217, Toronto, Ontario, Canada M5G 2C4. E-mail: bruce.perkins@uhn.on.ca

Received 11 June 2009; Revised 27 July 2009; Accepted 18 August 2009; Published online 21 October 2009.

Abstract

We sought to study new-onset microalbuminuria, its progression, and the decline of renal function in patients with type 1 diabetes. Using a cohort of 109 patients who developed new-onset microalbuminuria in the first 4 years following enrollment in the 1st Joslin Kidney Study, we simultaneously tracked the change in their renal function and urinary albumin excretion. Of these, 79 patients were followed for an average of 12 years after microalbuminuria onset, wherein their glomerular filtration rate was estimated by the Modification of Diet in Renal Disease Study formula and compared with their microalbuminuria and proteinuria. The concordance between these outcomes was weak. Only 12 of the 23 patients who progressed to advanced (stage 3–5) chronic kidney disease developed proteinuria, which, in general, did not precede but accompanied the progression to advanced chronic kidney disease. The remaining 11 patients who developed advanced disease had persistent microalbuminuria or returned to normal albuminuria. Thus, we found that one-third of patients with type 1 diabetes developed advanced chronic kidney disease relatively soon after the onset of microalbuminuria and this was not conditional on the presence of proteinuria. Contrary to the existing concept of early nephropathy in type 1 diabetes, less emphasis should be placed on the mechanisms of progression to proteinuria and more placed on mechanisms initiating and promoting the early decline of renal function that eventually progresses to advanced chronic kidney disease.