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Published in: Acta Diabetologica 1/2018

01-01-2018 | Original Article

Implication of decreased serum complement 3 in patients with diabetic nephropathy

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

Published in: Acta Diabetologica | Issue 1/2018

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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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Literature
1.
go back to reference Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE (2014) Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103:137–149CrossRefPubMed Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE (2014) Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103:137–149CrossRefPubMed
2.
go back to reference Wang L, Gao P, Zhang M et al (2017) Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013. JAMA 317:2515–2523CrossRefPubMed Wang L, Gao P, Zhang M et al (2017) Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013. JAMA 317:2515–2523CrossRefPubMed
3.
go back to reference Menke A, Casagrande S, Geiss L, Cowie CC (2015) Prevalence of and trends in diabetes among adults in the United States, 1988–2012. JAMA 314:1021–1029CrossRefPubMed Menke A, Casagrande S, Geiss L, Cowie CC (2015) Prevalence of and trends in diabetes among adults in the United States, 1988–2012. JAMA 314:1021–1029CrossRefPubMed
4.
go back to reference O’Shaughnessy MM, Hogan SL, Poulton CJ et al (2017) Temporal and demographic trends in glomerular disease epidemiology in the Southeastern United States, 1986–2015. Clin J Am Soc Nephrol 12:614–623CrossRefPubMed O’Shaughnessy MM, Hogan SL, Poulton CJ et al (2017) Temporal and demographic trends in glomerular disease epidemiology in the Southeastern United States, 1986–2015. Clin J Am Soc Nephrol 12:614–623CrossRefPubMed
5.
go back to reference Doshi SM, Friedman AN (2017) Diagnosis and management of type 2 diabetic kidney disease. Clin J Am Soc Nephrol 12:1366–1373CrossRefPubMed Doshi SM, Friedman AN (2017) Diagnosis and management of type 2 diabetic kidney disease. Clin J Am Soc Nephrol 12:1366–1373CrossRefPubMed
6.
7.
go back to reference Flyvbjerg A (2017) The role of the complement system in diabetic nephropathy. Nat Rev Nephrol 13:311–318CrossRefPubMed Flyvbjerg A (2017) The role of the complement system in diabetic nephropathy. Nat Rev Nephrol 13:311–318CrossRefPubMed
8.
go back to reference Fujita T, Hemmi S, Kajiwara M et al (2013) Complement-mediated chronic inflammation is associated with diabetic microvascular complication. Diabetes Metab Res Rev 29:220–226CrossRefPubMed Fujita T, Hemmi S, Kajiwara M et al (2013) Complement-mediated chronic inflammation is associated with diabetic microvascular complication. Diabetes Metab Res Rev 29:220–226CrossRefPubMed
9.
go back to reference American Diabetes Association (2017) Standards of medical care in diabetes-2017 abridged for primary care providers. Clin Diabetes 35:5–26CrossRefPubMedCentral American Diabetes Association (2017) Standards of medical care in diabetes-2017 abridged for primary care providers. Clin Diabetes 35:5–26CrossRefPubMedCentral
10.
go back to reference Tervaert TW, Mooyaart AL, Amann K et al (2010) Pathologic classification of diabetic nephropathy. J Am Soc Nephrol 21:556–563CrossRefPubMed Tervaert TW, Mooyaart AL, Amann K et al (2010) Pathologic classification of diabetic nephropathy. J Am Soc Nephrol 21:556–563CrossRefPubMed
11.
go back to reference Yang X, Wei RB, Wang Y et al (2017) Decreased serum C3 levels in Immunoglobulin A (IgA) nephropathy with chronic kidney disease: a propensity score matching study. Med Sci Monit 23:673–681CrossRefPubMedPubMedCentral Yang X, Wei RB, Wang Y et al (2017) Decreased serum C3 levels in Immunoglobulin A (IgA) nephropathy with chronic kidney disease: a propensity score matching study. Med Sci Monit 23:673–681CrossRefPubMedPubMedCentral
12.
go back to reference Fujita T, Ohi H, Komatsu K, Endo M, Ohsawa I, Kanmatsuse K (1999) Complement activation accelerates glomerular injury in diabetic rats. Nephron 81:208–214CrossRefPubMed Fujita T, Ohi H, Komatsu K, Endo M, Ohsawa I, Kanmatsuse K (1999) Complement activation accelerates glomerular injury in diabetic rats. Nephron 81:208–214CrossRefPubMed
13.
14.
go back to reference Wehner H, Hohn D, Faix-Schade U, Huber H, Walzer P (1972) Glomerular changes in mice with spontaneous hereditary diabetes. Lab Invest 27:331–340PubMed Wehner H, Hohn D, Faix-Schade U, Huber H, Walzer P (1972) Glomerular changes in mice with spontaneous hereditary diabetes. Lab Invest 27:331–340PubMed
15.
go back to reference Woroniecka KI, Park AS, Mohtat D, Thomas DB, Pullman JM, Susztak K (2011) Transcriptome analysis of human diabetic kidney disease. Diabetes 60:2354–2369CrossRefPubMedPubMedCentral Woroniecka KI, Park AS, Mohtat D, Thomas DB, Pullman JM, Susztak K (2011) Transcriptome analysis of human diabetic kidney disease. Diabetes 60:2354–2369CrossRefPubMedPubMedCentral
17.
go back to reference Barbu A, Hamad OA, Lind L, Ekdahl KN, Nilsson B (2015) The role of complement factor C3 in lipid metabolism. Mol Immunol 67:101–107CrossRefPubMed Barbu A, Hamad OA, Lind L, Ekdahl KN, Nilsson B (2015) The role of complement factor C3 in lipid metabolism. Mol Immunol 67:101–107CrossRefPubMed
19.
go back to reference Schalkwijk CG, Poland DC, van Dijk W et al (1999) Plasma concentration of C-reactive protein is increased in type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation. Diabetologia 42:351–357CrossRefPubMed Schalkwijk CG, Poland DC, van Dijk W et al (1999) Plasma concentration of C-reactive protein is increased in type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation. Diabetologia 42:351–357CrossRefPubMed
20.
go back to reference Flyvbjerg A (2010) Diabetic angiopathy, the complement system and the tumor necrosis factor superfamily. Nat Rev Endocrinol 6:94–101CrossRefPubMed Flyvbjerg A (2010) Diabetic angiopathy, the complement system and the tumor necrosis factor superfamily. Nat Rev Endocrinol 6:94–101CrossRefPubMed
21.
go back to reference Wada J, Makino H (2013) Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci 124:139–152CrossRefPubMed Wada J, Makino H (2013) Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci 124:139–152CrossRefPubMed
22.
go back to reference Vlassara H, Uribarri J, Cai W et al (2012) Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease. Clin J Am Soc Nephrol 7:934–942CrossRefPubMedPubMedCentral Vlassara H, Uribarri J, Cai W et al (2012) Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease. Clin J Am Soc Nephrol 7:934–942CrossRefPubMedPubMedCentral
23.
go back to reference Moorhead JF, Chan MK, El-Nahas M, Varghese Z (1982) Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet 2:1309–1311CrossRefPubMed Moorhead JF, Chan MK, El-Nahas M, Varghese Z (1982) Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet 2:1309–1311CrossRefPubMed
24.
go back to reference Chiarelli F, Verrotti A, La Penna G, Morgese G (1988) Low serum C4 concentrations in type-1 diabetes mellitus. Eur J Pediatr 147:197–198CrossRefPubMed Chiarelli F, Verrotti A, La Penna G, Morgese G (1988) Low serum C4 concentrations in type-1 diabetes mellitus. Eur J Pediatr 147:197–198CrossRefPubMed
25.
go back to reference Barnett AH, Mijovic C, Fletcher J et al (1984) Low plasma C4 concentrations: association with microangiopathy in insulin dependent diabetes. Br Med J (Clin Res Ed) 289:943–945CrossRef Barnett AH, Mijovic C, Fletcher J et al (1984) Low plasma C4 concentrations: association with microangiopathy in insulin dependent diabetes. Br Med J (Clin Res Ed) 289:943–945CrossRef
26.
go back to reference Cooper ME, Duff R, Buchanan R, McPherson J, Jerums G (1986) Low serum C4 concentrations and microangiopathy in type I and type II diabetes. Br Med J (Clin Res Ed) 292:801CrossRef Cooper ME, Duff R, Buchanan R, McPherson J, Jerums G (1986) Low serum C4 concentrations and microangiopathy in type I and type II diabetes. Br Med J (Clin Res Ed) 292:801CrossRef
27.
go back to reference Fortpied J, Vertommen D, Van Schaftingen E (2010) Binding of mannose-binding lectin to fructosamines: a potential link between hyperglycaemia and complement activation in diabetes. Diabetes Metab Res Rev 26:254–260CrossRefPubMed Fortpied J, Vertommen D, Van Schaftingen E (2010) Binding of mannose-binding lectin to fructosamines: a potential link between hyperglycaemia and complement activation in diabetes. Diabetes Metab Res Rev 26:254–260CrossRefPubMed
28.
go back to reference Qin X, Goldfine A, Krumrei N et al (2004) Glycation inactivation of the complement regulatory protein CD59: a possible role in the pathogenesis of the vascular complications of human diabetes. Diabetes 53:2653–2661CrossRefPubMed Qin X, Goldfine A, Krumrei N et al (2004) Glycation inactivation of the complement regulatory protein CD59: a possible role in the pathogenesis of the vascular complications of human diabetes. Diabetes 53:2653–2661CrossRefPubMed
29.
go back to reference Li L, Chen L, Zang J et al (2015) C3a and C5a receptor antagonists ameliorate endothelial-myofibroblast transition via the Wnt/beta-catenin signaling pathway in diabetic kidney disease. Metabolism 64:597–610CrossRefPubMed Li L, Chen L, Zang J et al (2015) C3a and C5a receptor antagonists ameliorate endothelial-myofibroblast transition via the Wnt/beta-catenin signaling pathway in diabetic kidney disease. Metabolism 64:597–610CrossRefPubMed
30.
go back to reference Mizuno M, Blanchin S, Gasque P, Nishikawa K, Matsuo S (2007) High levels of complement C3a receptor in the glomeruli in lupus nephritis. Am J Kidney Dis 49:598–606CrossRefPubMed Mizuno M, Blanchin S, Gasque P, Nishikawa K, Matsuo S (2007) High levels of complement C3a receptor in the glomeruli in lupus nephritis. Am J Kidney Dis 49:598–606CrossRefPubMed
Metadata
Title
Implication of decreased serum complement 3 in patients with diabetic nephropathy
Authors
Junlin Zhang
Yiting Wang
Rui Zhang
Hanyu Li
Qianqian Han
Ruikun Guo
Tingli Wang
Li Li
Fang Liu
Publication date
01-01-2018
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 1/2018
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-017-1060-4

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