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Hypertriglyceridemia accompanied by increased serum complement component 3 and proteinuria in non-nephrotic chronic kidney disease

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Abstract

Background

Hypertriglyceridemia (hTG) is a risk factor for progression of chronic kidney disease (CKD); however, it remains unknown whether the adipocytokine complement component 3 (C3) is involved in the association between hTG and CKD.

Methods

The study included 138 patients (54 % male) with non-nephrotic (serum albumin ≥3 g/dl) CKD who had undergone a renal biopsy and did not have hypocomplementemic disease. Renal arteriolopathy was assessed semi-quantitatively. We examined the cross-sectional associations between proteinuria and hTG with or without a higher serum C3 level (hC3), defined as equal or above the median value.

Results

The mean (SD) age of the patients was 42 (±17) years and urine protein was 1.2 (±1.2) g/gCr. Patients with hTG had a significantly higher urine protein than those without hTG. Subgroup analysis showed that the hTG+/hC3+ group had higher grade arteriolopathy and urine protein levels. Multiple logistic regression analysis adjusted for age, sex, and diabetes mellitus showed that hC3+ alone was associated significantly with higher levels of urine protein [odds ratio (OR), 2.98; 95 % confidence interval (CI) 1.19–7.46, p = 0.02]; however, hTG alone showed no such association. hTG+/hC3+ was a significant factor when hTG−/hC3− was used as the reference (adjusted OR 5.32; 95 % CI 1.40–20.17, p = 0.01), with this OR being decreased by adjustment for arteriolopathy.

Conclusions

hTG accompanied by hC3 was associated with proteinuria in non-nephrotic CKD. Arteriolopathy may influence this association. A prospective study is needed to determine the predictive value of this association in CKD progression.

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References

  1. Trevisan R, Dodesini AR, Lepore G. Lipids and renal disease. J Am Soc Nephrol. 2006;17:S145–7.

    Article  CAS  PubMed  Google Scholar 

  2. Thomas G, Sehgal AR, Kashyap SR, Srinivas TR, Kirwan JP, Navaneethan SD. Metabolic syndrome and kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2011;6:2364–73.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Muntner P, Coresh J, Smith JC, Eckfeldt J, Klag MJ. Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study. Kidney Int. 2000;58:293–301.

    Article  CAS  PubMed  Google Scholar 

  4. Verhave JC, Hillege HL, Burgerhof JG, Gansevoort RT, de Zeeuw D, de Jong PE, Group PS. The association between atherosclerotic risk factors and renal function in the general population. Kidney Int. 2005;67:1967–73.

    Article  PubMed  Google Scholar 

  5. Tozawa M, Iseki K, Iseki C, Oshiro S, Ikemiya Y, Takishita S. Triglyceride, but not total cholesterol or low-density lipoprotein cholesterol levels, predict development of proteinuria. Kidney Int. 2005;62:1743–9.

    Article  Google Scholar 

  6. Syrjänen J, Mustonen J, Pasternack A. Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy. Nephrol Dial Transplant. 2000;15:34–42.

    Article  PubMed  Google Scholar 

  7. Michel O, Heudes D, Lamarre I, Masurier C, Lavau M, Bariety J, Chevalier J. Reduction of insulin and triglycerides delays glomerulosclerosis in obese Zucker rats. Kidney Int. 1997;52:1532–42.

    Article  CAS  PubMed  Google Scholar 

  8. Joles JA, van Goor H, van der Horst ML, van Tol A, Weening JJ, Koomans HA. Ovariectomy decreases plasma triglyceride levels and both prevents and alleviates glomerular disease in uninephrectomized female analbuminemic rats. J Am Soc Nephrol. 1996;7:1189–97.

    CAS  PubMed  Google Scholar 

  9. Esterbauer H, Krempler F, Oberkofler H, Patsch W. The complement system: a pathway linking host defence and adipocyte biology. Eur J Clin Invest. 1999;29:653–6.

    Article  CAS  PubMed  Google Scholar 

  10. Walport MJ. Complement. First of two parts. N Engl J Med. 2001;344:1058–66.

    Article  CAS  PubMed  Google Scholar 

  11. Gabrielsson BG, Johansson JM, Lönn M, Jernås M, Olbers T, Peltonen M, Larsson I, Lönn L, Sjöström L, Carlsson B, Carlsson LM. High expression of complement components in omental adipose tissue in obese men. Obes Res. 2003;11:699–708.

    Article  CAS  PubMed  Google Scholar 

  12. Choy LN, Rosen BS, Spiegelman BM. Adipsin and an endogenous pathway of complement from adipose cells. J Biol Chem. 1992;267:12736–41.

    CAS  PubMed  Google Scholar 

  13. Zhang J, Wright W, Bernlohr DA, Cushman SW, Chen X. Alterations of the classic pathway of complement in adipose tissue of obesity and insulin resistance. Am J Physiol Endocrinol Metab. 2007;292:E1433–40.

    Article  CAS  PubMed  Google Scholar 

  14. Onat A, Yazici M, Can G, Sniderman A. Evidence for a complex risk profile in obese postmenopausal Turkish women with hypertriglyceridaemia and elevated apolipoprotein B. Clin Sci (Lond). 2004;107:97–104.

    Article  CAS  Google Scholar 

  15. Hernández-Mijares A, Jarabo-Bueno MM, López-Ruiz A, Solá-Izquierdo E, Morillas-Ariño C, Martínez-Triguero ML. Levels of C3 in patients with severe, morbid and extreme obesity: its relationship to insulin resistance and different cardiovascular risk factors. Int J Obes (Lond). 2007;31:927–32.

    Article  Google Scholar 

  16. Engström G, Hedblad B, Janzon L, Lindgärde F. Weight gain in relation to plasma levels of complement factor 3: results from a population-based cohort study. Diabetologia. 2005;48:2525–31.

    Article  PubMed  Google Scholar 

  17. Ohsawa I, Inoshita H, Ishii M, Kusaba G, Sato N, Mano S, Onda K, Gohda T, Horikoshi S, Ohi H, Tomino Y. Metabolic impact on serum levels of complement component 3 in Japanese patients. J Clin Lab Anal. 2010;24:113–8.

    Article  CAS  PubMed  Google Scholar 

  18. Wlazlo N, van Greevenbroek MM, Ferreira I, Jansen EJ, Feskens EJ, van der Kallen CJ, Schalkwijk CG, Bravenboer B, Stehouwer CD. Low-grade inflammation and insulin resistance independently explain substantial parts of the association between body fat and serum C3: the CODAM study. Metabolism. 2012;61:1787–96.

    Article  CAS  PubMed  Google Scholar 

  19. van Greevenbroek MM, Ghosh S, van der Kallen CJ, Brouwers MC, Schalkwijk CG, Stehouwer CD. Up-regulation of the complement system in subcutaneous adipocytes from nonobese, hypertriglyceridemic subjects is associated with adipocyte insulin resistance. J Clin Endocrinol Metab. 2012;97:4742–52.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Kojima C, Takei T, Ogawa T, Nitta K. Serum complement C3 predicts renal arteriolosclerosis in non-diabetic chronic kidney disease. J Atheroscler Thromb. 2012;19:854–61.

    Article  CAS  PubMed  Google Scholar 

  21. Oksjoki R, Kovanen PT, Pentikäinen MO. Role of complement activation in atherosclerosis. Curr Opin Lipidol. 2003;14:477–82.

    Article  CAS  PubMed  Google Scholar 

  22. Yasojima K, Schwab C, McGeer EG, McGeer PL. Generation of C-reactive protein and complement components in atherosclerotic plaques. Am J Pathol. 2001;158:1039–51.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Bhakdi S, Torzewski M, Klouche M, Hemmes M. Complement and atherogenesis: binding of CRP to degraded, nonoxidized LDL enhances complement activation. Arterioscler Thromb Vasc Biol. 1999;19:2348–54.

    Article  CAS  PubMed  Google Scholar 

  24. Praga M, Borstein B, Andres A, Arenas J, Oliet A, Montoyo C, Ruilope LM, Rodico JL. Nephrotic proteinuria without hypoalbuminemia: clinical characteristics and response to angiotensin-converting enzyme inhibition. Am J Kidney Dis. 1991;17:330–8.

    Article  CAS  PubMed  Google Scholar 

  25. Praga M, Morales E, Herrero JC, Pérez Campos A, Domínguez-Gil B, Alegre R, Vara J, Martínez MA. Absence of hypoalbuminemia despite massive proteinuria in focal segmental glomerulosclerosis secondary to hyperfiltration. Am J Kidney Dis. 1999;33:52–8.

    Article  CAS  PubMed  Google Scholar 

  26. Kohagura K, Kochi M, Miyagi T, Kinjyo T, Maehara Y, Nagahama K, Sakima A, Iseki K, Ohya Y. An association between uric acid levels and renal arteriolopathy in chronic kidney disease: a biopsy-based study. Hypertens Res. 2013;36:43–9.

    Article  CAS  PubMed  Google Scholar 

  27. Massy ZA, Nguyen Khoa T, Lacour B, Descamps-Latscha B, Man NK, Jungers P. Dyslipidaemia and the progression of renal disease in chronic renal failure patients. Nephrol Dial Transplant. 1999;14:2392–7.

    Article  CAS  PubMed  Google Scholar 

  28. Volp AC, Barbosa KB, Bressan J. Triacylglycerols and body fat mass are possible independent predictors of C3 in apparently healthy young Brazilian adults. Nutrition. 2012;28:544–50.

    Article  CAS  PubMed  Google Scholar 

  29. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, Collaborators Developing the Japanese Equation for Estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.

    Article  CAS  PubMed  Google Scholar 

  30. Engström G, Hedblad B, Eriksson KF, Janzon L, Lindgärde F. Complement C3 is a risk factor for the development of diabetes: a population-based cohort study. Diabetes. 2005;54:570–5.

    Article  PubMed  Google Scholar 

  31. Cianflone K, Lu H, Smith J, Yu W, Wang H. Adiponectin, acylation stimulating protein and complement C3 are altered in obesity in very young children. Clin Endocrinol (Oxf). 2005;62:567–72.

    Article  CAS  Google Scholar 

  32. Cianflone K, Maslowska M, Sniderman AD. Acylation stimulating protein (ASP), an adipocyte autocrine: new directions. Semin Cell Dev Biol. 1999;10:31–41.

    Article  CAS  PubMed  Google Scholar 

  33. Nagahama K, Iseki K, Inoue T, Touma T, Ikemiya Y, Takishita S. Hyperuricemia and cardiovascular risk factor clustering in a screened cohort in Okinawa, Japan. Hypertens Res. 2004;27:227–33.

    Article  PubMed  Google Scholar 

  34. Hill GS, Heudes D, Bariéty J. Morphometric study of arterioles and glomeruli in the aging kidney suggests focal loss of autoregulation. Kidney Int. 2003;63:1027–36.

    Article  PubMed  Google Scholar 

  35. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world—a growing challenge. N Engl J Med. 2007;356:213–5.

    Article  CAS  PubMed  Google Scholar 

  36. Iseki K, Ikemiya Y, Kinjo K, Inoue T, Iseki C, Takishita S. Body mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int. 2004;65:1870–6.

    Article  PubMed  Google Scholar 

  37. van Oostrom AJ, Alipour A, Plokker TW, Sniderman AD, Cabezas MC. The metabolic syndrome in relation to complement component 3 and postprandial lipemia in patients from an outpatient lipid clinic and healthy volunteers. Atherosclerosis. 2007;190:167–73.

    Article  PubMed  Google Scholar 

  38. Engström G, Hedblad B, Janzon L, Lindgärde F. Complement C3 and C4 in plasma and incidence of myocardial infarction and stroke: a population-based cohort study. Eur J Cardiovasc Prev Rehabil. 2007;14:392–7.

    Article  PubMed  Google Scholar 

  39. Muscari A, Massarelli G, Bastagli L, Poggiopollini G, Tomassetti V, Drago G, Martignani C, Pacilli P, Boni P, Puddu P. Relationship of serum C3 to fasting insulin, risk factors and previous ischaemic events in middle-aged men. Eur Heart J. 2000;21:1081–90.

    Article  CAS  PubMed  Google Scholar 

  40. Muscari A, Bozzoli C, Puddu GM, Sangiorgi Z, Dormi A, Rovinetti C, Descovich GC, Puddu P. Association of serum C3 levels with the risk of myocardial infarction. Am J Med. 1995;98:357–64.

    Article  CAS  PubMed  Google Scholar 

  41. Levey AS, de Jong PE, Coresh J, El Nahas M, Astor BC, Matsushita K, Gansevoort RT, Kasiske BL, Eckardt KU. The definition, classification, and prognosis of chronic kidney disease: a KDIGO controversies conference report. Kidney Int. 2011;80:17–28.

    Article  PubMed  Google Scholar 

  42. Iseki K, Ikemiya Y, Iseki C, Takishita S. Proteinuria and the risk of developing end-stage renal disease. Kidney Int. 2003;63:1468–74.

    Article  PubMed  Google Scholar 

  43. Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol. 1998;81:7B–12B.

    Article  CAS  PubMed  Google Scholar 

  44. Hernández-Mijares A, Bañuls C, Bellod L, Jover A, Solá E, Morillas C, Víctor VM, Rocha M. Effect of weight loss on C3 and C4 components of complement in obese patients. Eur J Clin Invest. 2012;42:503–9.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank the following doctors who gave invaluable advice and support—A. Miyagi, A. Hirano, J. Ishikawa, M. Miyazato, K. Tokashiki, N. Tomiyama, S. Chinen, M Yamazato and A. Ishida. We are also grateful to S. Hatoma and M. Ohta for technical assistance.

Conflict of interest

The authors have declared that no conflict of interest exists.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Nephrology and Neurology, University of the Ryukyus School of Medicine, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan

    Kentaro Kohagura, Masako Kochi, Tsuyoshi Miyagi, Takanori Kinjyo, Yuichi Maehara, Kojiro Kinjyo, Kazufumi Nagahama, Atsushi Sakima & Yusuke Ohya

  2. Dialysis Unit, University of the Ryukyus School of Medicine, Okinawa, Japan

    Kunitoshi Iseki

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  1. Kentaro Kohagura
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  2. Masako Kochi
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Correspondence to Kentaro Kohagura.

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Kohagura, K., Kochi, M., Miyagi, T. et al. Hypertriglyceridemia accompanied by increased serum complement component 3 and proteinuria in non-nephrotic chronic kidney disease. Clin Exp Nephrol 18, 453–460 (2014). https://doi.org/10.1007/s10157-013-0825-5

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  • DOI: https://doi.org/10.1007/s10157-013-0825-5

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