Complement C3 and incident hospitalization due to chronic kidney disease: a population-based cohort study

BMC Nephrology - Tập 20 - Trang 1-9 - 2019
Xue Bao1,2, Yan Borné2, Iram Faqir Muhammad2, Christina-Alexandra Schulz2, Margaretha Persson2, Marju Orho-Melander2, Kaijun Niu1, Anders Christensson2, Gunnar Engström2
1Nutritional epidemiology institute and school of public health, Tianjin medical university, Tianjin, China
2Department of Clinical Sciences, Lund University, Malmö, Sweden

Tóm tắt

Circulating C3 has been associated with diabetes and hypertension, which are the leading causes of chronic kidney disease (CKD). C3 activation is considered to contribute to several renal diseases. Here we examined whether elevated C3 concentration is associated with hospitalization due to CKD in the general population, and whether this relationship is mediated by factors such as diabetes and hypertension. Baseline plasma C3 was quantified in 4552 participants, without previous hospital admission due to CKD, from the Malmö Diet and Cancer cohort study. Incidence of first hospitalization due to CKD (main diagnosis) was investigated in relation to C3 levels using Cox proportional hazards regression models after a mean follow-up of 19.2 ± 4.16 years. Traditional risk factors of CKD including diabetes, blood pressure, C-reactive protein and baseline renal function were considered in adjustments and sensitivity analyses. During the follow-up period, 94 subjects were admitted to hospital due to CKD. After multivariate adjustment, the hazard ratios (95% confidence interval) for hospitalization from CKD across quartiles of C3 were 1.00 (reference), 1.68 (0.69, 4.13), 2.71 (1.15, 6.39), and 3.16 (1.36, 7.34) (p for trend = 0.003). Results were generally consistent across different sensitivity analyses. These findings indicate that C3 is associated with incidence of first hospitalization due to CKD in the general population. The observed relationship cannot be entirely attributed to hyperglycemia and hypertension.

Tài liệu tham khảo

James MT, Hemmelgarn BR, Tonelli M. Early recognition and prevention of chronic kidney disease. Lancet. 2010;375:1296–309. Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382:260–72. Herzog CA, Asinger RW, Berger AK, Charytan DM, Diez J, Hart RG, et al. Cardiovascular disease in chronic kidney disease. A clinical update from kidney disease: improving global outcomes (KDIGO). Kidney Int. 2011;80:572–86. Di Angelantonio E, Chowdhury R, Sarwar N, Aspelund T, Danesh J, Gudnason V. Chronic kidney disease and risk of major cardiovascular disease and non-vascular mortality: prospective population based cohort study. BMJ. 2010;341:c4986. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305. Dunkelberger JR, Song WC. Complement and its role in innate and adaptive immune responses. Cell Res. 2010;20:34–50. McGeer PL, Lee M, McGeer EG. A review of human diseases caused or exacerbated by aberrant complement activation. Neurobiol Aging. 2017;52:12–22. Sahu A, Lambris JD. Structure and biology of complement protein C3, a connecting link between innate and acquired immunity. Immunol Rev. 2001;180:35–48. Wlazlo N, van Greevenbroek MM, Ferreira I, Feskens EJ, van der Kallen CJ, Schalkwijk CG, et al. Complement factor 3 is associated with insulin resistance and with incident type 2 diabetes over a 7-year follow-up period: the CODAM study. Diabetes Care. 2014;37:1900–9. Engström G, Hedblad B, Berglund G, Janzon L, Lindgarde F. Plasma levels of complement C3 is associated with development of hypertension: a longitudinal cohort study. J Hum Hypertens. 2007;21:276–82. Borne Y, Muhammad IF, Lores-Motta L, Hedblad B, Nilsson PM, Melander O, et al. Complement C3 associates with incidence of diabetes, but no evidence of a causal relationship. J Clin Endocrinol Metab. 2017;102:4477–85. Li X, Ding F, Zhang X, Li B, Ding J. The expression profile of complement components in podocytes. Int J Mol Sci. 2016;17:471. Zhou W, Marsh JE, Sacks SH. Intrarenal synthesis of complement. Kidney Int. 2001;59:1227–35. Tang S, Zhou W, Sheerin NS, Vaughan RW, Sacks SH. Contribution of renal secreted complement C3 to the circulating pool in humans. J Immunol. 1999;162:4336–41. Thurman JM. Complement in kidney disease: core curriculum 2015. Am J Kidney Dis. 2015;65:156–68. Berglund G, Elmstahl S, Janzon L, Larsson SA. The Malmo diet and Cancer study. Design and feasibility J Intern Med. 1993;233:45–51. Hedblad B, Nilsson P, Janzon L, Berglund G. Relation between insulin resistance and carotid intima-media thickness and stenosis in non-diabetic subjects. Results from a cross-sectional study in Malmo, Sweden. Diabet Med. 2000;17:299–307. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502. Schulz CA, Persson M, Christensson A, Hindy G, Almgren P, Nilsson PM, et al. Soluble Urokinase-type plasminogen activator receptor (suPAR) and impaired kidney function in the population-based Malmo diet and Cancer study. Kidney Int Rep. 2017;2:239–47. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012;367:20–9. Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450. Qureshi AR, Evans M, Stendahl M, Prutz KG, Elinder CG. The increase in renal replacement therapy (RRT) incidence has come to an end in Sweden-analysis of variations by region over the period 1991-2010. Clin Kidney J. 2013;6:352–7. Kidney Disease. Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and Management of Chronic Kidney Disease. Kidney Int. 2013;3:1–150. Kohl M, Plischke M, Leffondre K, Heinze G. PSHREG: a SAS macro for proportional and nonproportional subdistribution hazards regression. Comput Methods Prog Biomed. 2015;118:218–33. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509. Gabrielsson BG, Johansson JM, Lonn M, Jernas M, Olbers T, Peltonen M, et al. High expression of complement components in omental adipose tissue in obese men. Obes Res. 2003;11:699–708. 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. Kohagura K, Kochi M, Miyagi T, Kinjyo T, Maehara Y, Kinjyo K, et al. Hypertriglyceridemia accompanied by increased serum complement component 3 and proteinuria in non-nephrotic chronic kidney disease. Clin Exp Nephrol. 2014;18:453–60. Tsai S, Clemente-Casares X, Revelo XS, Winer S, Winer DA. Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases? Diabetes. 2015;64:1886–97. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the eighth joint National Committee (JNC 8). JAMA. 2014;311:507–20. Shankar A, Sun L, Klein BE, Lee KE, Muntner P, Nieto FJ, et al. Markers of inflammation predict the long-term risk of developing chronic kidney disease: a population-based cohort study. Kidney Int. 2011;80:1231–8. Remuzzi G, Bertani T. Pathophysiology of progressive nephropathies. N Engl J Med. 1998;339:1448–56. Muscari A, Antonelli S, Bianchi G, Cavrini G, Dapporto S, Ligabue A, et al. Serum C3 is a stronger inflammatory marker of insulin resistance than C-reactive protein, leukocyte count, and erythrocyte sedimentation rate: comparison study in an elderly population. Diabetes Care. 2007;30:2362–8. Ajjan R, Grant PJ, Futers TS, Brown JM, Cymbalista CM, Boothby M, et al. Complement C3 and C-reactive protein levels in patients with stable coronary artery disease. Thromb Haemost. 2005;94:1048–53. 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. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361:1676–87. Pickering MC, D'Agati VD, Nester CM, Smith RJ, Haas M, Appel GB, et al. C3 glomerulopathy: consensus report. Kidney Int. 2013;84:1079–89. Zhang J, Wang Y, Zhang R, Li H, Han Q, Guo R, et al. Implication of decreased serum complement 3 in patients with diabetic nephropathy. Acta Diabetol. 2018;55:31–9.