Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes

Tomas Vaisar, Blythe Durbin-Johnson, Kathryn Whitlock, Ilona Babenko, Rajnish Mehrotra, David M Rocke, Maryam Afkarian

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2361-2369
Number of pages9
JournalDiabetes Care
Volume41
Issue number11
DOIs
StatePublished - Nov 1 2018

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

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