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Implication of decreased serum complement 3 in patients with diabetic nephropathy

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Abstract

Aims

The serum complement 3 (C3) level was reduced in many patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). However, the clinical implications of such change are still less understood. This study was aimed to explore the association between C3 level and the baseline clinicopathological characteristics and the prognosis of T2DM patients with DN.

Methods

A total of 171 T2DM patients with biopsy-proven DN who received follow-up for at least 1 year were recruited. The patients were divided into two groups based on the C3 level: decreased C3 group: < 90 mg/dl (n = 75) and normal C3 group: ≥ 90 mg/dl (n = 96). Renal outcomes were defined by progression to end-stage renal disease (ESRD) or doubling of serum creatinine (D-SCr) level. The influence of serum C3 level on renal outcomes was estimated using Cox regression.

Results

The patients with decreased C3 level had more severe renal insufficiency and glomerular lesions than those in the normal C3 group. During a follow-up period (12–78 months), 51 patients with decreased C3 levels (68.0%) and 36 individuals with normal C3 levels (37.5%) reached the endpoint. The univariate Cox regression indicated that patients in the decreased C3 group had a higher rate of the renal outcomes than patients in the normal C3 group (HR 1.897, 95% CI 1.235–2.913, p = 0.003). But the multivariate COX analysis indicated that the C3 level was not an independent risk factor for progression to ESRD and/or D-SCr (HR 1.389, 95% CI 0.847–2.278, p = 0.193) when adjusting for important clinical variables and pathological findings.

Conclusions

Decreased serum C3 level was significantly associated with more severe renal insufficiency, higher glomerular grading and poor renal outcomes, though it failed to be an independent risk factor in T2DM patients with DN.

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Abbreviations

T2DM:

Type 2 diabetes mellitus

CKD:

Chronic kidney diseases

C3:

Complement 3

NDRD:

Nondiabetic renal diseases

D-SCr:

Doubling of baseline serum creatinine

e-GFR:

Estimated glomerular filtration rate

IFTA:

Interstitial fibrosis and tubular atrophy

HbA1c:

Glycosylated hemoglobin

FSGS:

Focal segmental glomerulosclerosis

MBL:

Mannose-binding lectin

AGEs:

Advanced glycation end products

DN:

Diabetic nephropathy

ESRD:

End-stage renal disease

C4:

Complement 4

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Acknowledgements

This study was supported by Grants 81370823 and 81670662 from the National Natural Science Foundation of China.

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Authors and Affiliations

  1. Division of Nephrology, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, China

    Junlin Zhang, Yiting Wang, Rui Zhang, Hanyu Li, Qianqian Han, Ruikun Guo, Tingli Wang, Li Li & Fang Liu

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  1. Junlin Zhang
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  8. Li Li
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  9. Fang Liu
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Correspondence to Fang Liu.

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The authors have no conflict of interest that is relevant to this article.

Ethical approval

The ethics committee of West China Hospital approved this research. The study protocol was in compliance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Additional informed consent was obtained from all individual participants for whom identifying information is included in this article.

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Zhang, J., Wang, Y., Zhang, R. et al. Implication of decreased serum complement 3 in patients with diabetic nephropathy. Acta Diabetol 55, 31–39 (2018). https://doi.org/10.1007/s00592-017-1060-4

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  • DOI: https://doi.org/10.1007/s00592-017-1060-4

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