Objective

We examined the association of urine complement proteins with progression to end-stage renal disease (ESRD) or death in people with type 2 diabetes and proteinuric diabetic kidney disease (DKD).

Research design and methods

Using targeted mass spectrometry, we quantified urinary abundance of 12 complement proteins in a predominantly Mexican American cohort with type 2 diabetes and proteinuric DKD (n = 141). The association of urine complement proteins with progression to ESRD or death was evaluated using time-to-event analyses.

Results

At baseline, median estimated glomerular filtration rate (eGFR) was 54 mL/min/1.73 m² and urine protein-to-creatinine ratio 2.6 g/g. Sixty-seven participants developed ESRD or died, of whom 39 progressed to ESRD over a median of 3.1 years and 40 died over a median 3.6 years. Higher urine CD59, an inhibitor of terminal complement complex formation, was associated with a lower risk of ESRD (hazard ratio [HR] [95% CI per doubling] 0.50 [0.29-0.87]) and death (HR [95% CI] 0.56 [0.34-0.93]), after adjustment for demographic and clinical covariates, including baseline eGFR and proteinuria. Higher urine complement components 4 and 8 were associated with lower risk of death (HR [95% CI] 0.57 [0.41-0.79] and 0.66 [0.44-0.97], respectively); higher urine factor H-related protein 2, a positive regulator of the alternative complement pathway, was associated with greater risk of death (HR [95% CI] 1.61 [1.05-2.48]) in fully adjusted models.

Conclusions

In a largely Mexican American cohort with type 2 diabetes and proteinuric DKD, urine abundance of several complement and complement regulatory proteins was strongly associated with progression to ESRD and death.

In the article cited above, the authors miscategorized CD59 as a transmembrane protein when it is in fact a glycosylphosphatidylinositol-anchored surface protein. The sentence on page 2367 in the last paragraph of the first column was corrected to read: CD59, a major regulator of the complement activity, is a glycosylphosphatidylinositol- anchored membrane protein that binds to the C5-8 complex and inhibits assembly of C9 monomers into the terminal complement complex, thus protecting cells from complement-mediated injury (33). The error does not change the results or conclusions of the article. The online version of the article has been corrected to reflect these changes.