Complement Deposition on Renal Histopathology of Patients with Diabetic Nephropathy

Aims: As the potential role of the complement system in diabetic nephropathy (DN) is increasingly reported, this study aimed to investigate C1q and C3c deposition as seen on renal histopathology, as well as its association with clinical and pathological parameters, in DN patients.

Methods: Renal biopsy specimens from 161 DN patients were investigated using direct immunofluorescence, light, and electron microscopy. For direct immunofluorescence, staining for C1q and C3c on fresh-frozen renal tissue was performed immediately after biopsy. Complement deposition was defined as the presence of C1q or C3c of at least 1 + on a 0-4 + Scale. The association between complement deposition and clinicopathological data was also analyzed.

Results: On direct immunofluorescence microscopy, C1q and C3c were detected in specimens from 44/161 (27.3%) and 89/161 (55.3%) patients, respectively. Regarding clinical data, patients with C1q deposition had a significantly higher level of urinary protein (7.25 ± 4.20 g/24 h vs. 4.97 ± 3.76 g/24 h; P < 0.01) and significantly lower estimated glomerular filtration rate (eGFR; 34.16 ± 25.21 mL/min/1.73 m vs. 51.17 ± 31.56 mL/min/1.73 m, respectively; P < 0.01), whereas patients with vs. without C3c deposition had a significantly lower eGFR (40.09 ± 27.97 mL/min/1.73 m vs. 54.48 ± 32.49 mL/min/1.73 m, respectively; P < 0.01). On renal histopathology, patients with C1q deposition had significantly higher Scores for interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation and vascular lesions (P < 0.01, P < 0.05 and P < 0.05, respectively), whereas patients with C3c deposition had significantly higher IFTA Scores and proportions of global sclerosis (P < 0.01 and P < 0.01, respectively).

Conclusion: Complement deposition of C1q and C3c on renal histopathology is associated with more severe kidney damage in patients with DN.