Association Between Urine Complement Proteins and Kidney Disease, Mortality in T2D

Patients with type 2 diabetes and proteinuric diabetic kidney disease show a strong association between urinary abundance of several complement and complement regulatory proteins and progression to end-stage renal disease and death, according to a study published in Diabetes Care.

As the incidence of diabetes and diabetic kidney disease rises, there is a growing need for new diagnostic and therapeutic tools, particularly to improve early diagnosis. In a cohort of 141 predominantly Mexican-American patients (average age, 57 years) with type 2 diabetes and proteinuric diabetic kidney disease, researchers used urine samples, targeted spectrometry, and time-to-event analyses to determine the association between urine complement proteins and progression to end-stage renal disease or death.

At baseline, the researchers discovered a median estimated glomerular filtration rate of 54 mL/min/1.73 m² and urine protein-to-creatinine ratio of 2.6 g/g. Overall, end-stage renal disease or death occurred in 67 participants, progression to end-stage renal disease occurred in 39 participants over a median of 3.1 years, and 40 people died over a median of 3.6 years.

After adjusting for demographic and clinical covariates, the researchers found that a higher level of urine CD59, an inhibitor of terminal complement complex formation, was significantly associated with lower risk for end-stage renal disease (hazard ratio, 0.50; 95% CI, 0.29-0.87) and death (hazard ratio, 0.56; 95% CI 0.34-0.93). Likewise, higher urine complement components C4 and C8 were associated with lower risk for death (hazard ratio, 0.57; 95% CI, 0.57-0.79 and hazard ratio 0.66; 95% CI, 0.44-0.97, respectively). Conversely, higher urine factor H-related protein 2 was associated with greater risk for death (hazard ratio, 1.61; 95% CI, 1.05-2.48).

The researchers noted certain limitations to their study, such as a modest cohort size, absence of parallel quantification of complement proteins in serum and kidney, and lack of adjudicated causes of death.

With these limitations taken into consideration, the investigators said, “These findings suggest a role for complement pathway activation in diabetic kidney disease progression in people with proteinuria.”

Reference

Vaisar T, Durbin-Johnson B, Whitlock K, et al. Urine complement proteins and the risk of kidney disease progression and mortality in type 2 diabetes [published online August 27, 2018]. Diabetes Care. doi:10.2337/dc18-0699