Relationship between complement and macrophage markers with kidney survival in patients with diabetic nephropathy.

Background: Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease (ESKD) worldwide. Macrophages and the complement system have interrelated roles in DN. We aimed to determine associations between macrophage and complement markers with the progression of DN.

Methods: This retrospective cohort study included patients diagnosed with sole DN by kidney biopsy. Using immunohistochemistry, CD68⁺ and CD163⁺ cells and complement markers were counted in glomerular and tubulointerstitial areas. The primary outcome was evolution to ESKD and/or doubling serum creatinine (SCr).

Results: Forty-six patients were included. The median SCr at baseline was 2.7 (1.41-3.1) mg/dL. During the median follow-up of 32 months (range 6-54), 50% of patients reached the primary outcome. Most of the clinical and histological findings were comparable between progressors and non-progressors, while progressors had a higher median number of glomerular CD68+ cells and a higher percentage of glomerulosclerosis. After adjustments for age, sex, and SCr, the median glomerular CD68+ cell number was the sole independent predictor of progression. Glomerular C4d was associated with nephrotic-range proteinuria but not with the progression of kidney failure.

Conclusions: Glomerular CD68+ cell count may serve as a promising predictor of kidney disease progression among patients with DN. Glomerular C4d was associated with nephrotic-range proteinuria but not with the progression of kidney failure.