In patients with type 1 diabetes and new-onset microalbuminuria the development of advanced chronic kidney disease may not require progression to proteinuria

Abstract

Systematic study of the course of renal function decline and progression to proteinuria in patients with type 1 diabetes and new onset microalbuminuria has not been reported. From the 1080 participants with normoalbuminuria enrolled in the 1st Joslin Kidney Study, we identified 109 who developed new onset microalbuminuria in the first four years of observation and followed 79 for a subsequent 12.4±1.4 years to estimate glomerular filtration rate by the four-variable MDRD formula (GFRMDRD) and the course of microalbuminuria. 12–year cumulative risk of advanced chronic kidney disease (CKD)[defined by GFRMDRD<60ml/min/1.73m2] and proteinuria were 23(29%) and 21(27%). However, concordance between these outcomes was weak. Only 12 of the 23 subjects (52%) who developed advanced CKD had progression to proteinuria. Furthermore, this progression generally did not precede but rather accompanied the development of advanced CKD. The remaining 11(48%) subjects who developed advanced CKD experienced only persistent microalbuminuria (8 subjects) or regressed to normoalbuminuria (3 subjects). In conclusion, risk of advanced CKD approaches one-third early after microalbuminuria onset and its development is 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 on the mechanisms initiating and promoting early renal function decline that leads to advanced CKD.