Estimation of Complement Components (C3 and C4) and hs-CRP Level in Kidney Failure Patients
Keywords:Complement, Inflammatory marker and diabetic, Kidney failure
Several kidney diseases associated with complement activation. Complement activation occurs in progressive chronic kidney disease and may contribute to the chronic inflammation that is characteristically found in the kidney. This study was aimed to detect the level of complement system in kidney failure patients. This study was included (30) patients with renal failure and (15) healthy donors as control group. Serum samples separated from the whole blood of patients and healthy individuals. C3, C4, and high sensitive C- reactive protein (hsCRP) levels were estimated for all samples. The results were analyzed according to patients who were dialysis, non-dialysis, with diabetes, without diabetes, with high blood pressure, and without high blood pressure. The results showed that there was a significant increase (P < 0.05) in C3 level for patients with renal failure (154.12 mg/dl) compared to control group (126.08 mg/dl) while C4 level for renal failure patients (35.38 mg/dl) showed no significant change compared to control group (36.26 mg/dl). However, C3 level of patients under dialysis (152.15 mg/dl), not dialysis (162.01 mg/dl), with diabetic (155.80 mg/dl), and without diabetic (153 mg/dl) recorded significant elevation compared with control group (126.08 mg/dl) but C4 level did not show any significant change for all groups. C3 and C4 concentrations did not record significant alteration (P < 0.05) in patient with hypertension, nonhypertension, and control group. Moreover, seropositivity of CRP for patients with renal failure was ranged from 33.33% to 60% in all patients groups included in this study. hsCRP concentration significantly elevated (P < 0.05) in under dialysis (1.787 mg/L), nondialysis (1.583 mg/L), with diabetic (2.766 mg/L), nondiabetic (1.066 mg/L), with hypertension (1.84 mg/L), and nonhypertension (1.26 mg/L) when compared with control group (0.667 mg/L). The present findings suggest that the increased serum levels of C3, C4, and hs-CRP reflect the of kidney injury. Hence, this reflects the complement system as an important mediator of kidney injury and the role of anti-complement therapy in nephropathy will expand in the future.
Abdul, H. H., I. Sahib and N. Hashim. 2006. Serum immunoglobulins and the complements C3 and C4 levels in the patients with chronic renal failure. Natl. J. Chem. 21: 125-132.
Angeletti, A., J. Reyes-Bahamonde, P. Cravedi and K. Campbell. 2017. Complement in non-antibody-mediated kidney diseases.Front. Med. 4: 1-10.
Bedford, M., C. Farmer, A. Levin, T. Ali and P. Stevens. 2012. Acute kidney injury and CKD: Chicken or egg?
Am. J. Kidney Dis. 59: 485-491.
Burwick, R., R. Fichorova, H. Dawood, H. Yamamoto and B. Feinberg. 2013. Urinary excretion of c5b-9 in severe preeclampsia: Tipping the balance of complement activation in pregnancy. Hypertension. 62: 1040-1045.
Carroll, M. and D. Isenman. 2012. Regulation of humoral immunity by complement. Immunity. 37: 199-207.
Cravedi, P. and P. Heeger. 2014. Complement as a multifaceted modulator of kidney transplant injury. J. Clin. Invest. 124: 2348- 2354.
Eknoyan, G., N. Lameire, R. Barsoum, K. Eckardt, A. Levin, N. Levin, F. Locatelli, A. MacLeod, R. Vanholder, R. Walker and H. Wang. 2004. The burden of kidney disease: Improving global outcomes. Kidney Int. 66(4): 1310-1314.
Engstrom, G., B. Hedblad, G. Berglund, L. Janzon and F. Lindgarde. 2007. Plasma levels of complement C3 is associated with development of hypertension: A longitudinal cohort study. J. Hum. Hypertens. 21: 276-282.
Fearn, A. and N. Sheerin. 2015. Complement activation in progressive renal disease. World J. Nephrol. 4(1): 31-40.
Flyvbjerg, A. 2017. The role of the complement system in diabetic nephropathy. Nat. Rev. Nephrol. 13(5): 311-318.
Geurts, A., D. Mattson, P. Liu, E. Cabacungan, M. Skelton, T. Kurth, C. Yang, B. Endres, J. Klotz, M. Liang and
A. Cowley. 2015. Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats. Hypertension. 65: 447-455.
Inoshita, H., I. Ohsawa, G. Kusaba, M. Ishii, K. Onda, S. Horikoshi, H. Ohi and Y. Tomino. 2010. Complement in patients receiving maintenance hemodialysis: Functional screening and quantitative analysis. BMC Nephrol. 11(34): 1-6.
Johnson, C., A. Levey, J. Coresh, A. Levin, J. Lau and G. Eknoyan. 2004. Clinical practice guidelines for chronic kidney disease in adults: Part 1. Definition, disease stages, evaluation, treatment and risk factors. Am. Fam. Physician. 70(5): 869-876.
Joshua, M. and M. Thurman. 2015. Complement in kidney disease: Core curriculum. Am. J. Kidney Dis. 65(1): 156-168.
Kelly, K., Y. Liu, J. Zhang and J. Dominguez. 2015. Renal C3 complement component: Feed forward to diabetic kidney disease. Am. J. Nephrol. 41(1): 48-56.
Khan, T. and K. Khan. 2015. Acute kidney injury and chronic kidney disease. Vet. Pathol. 52(3): 441-444.
Kościelska-Kasprzak, K., D. Bartoszek, M. Myszka, M. Żabińska and M. Klinger. 2014. The complement cascade and renal disease. Arch. Immunol. Ther. Exp. 62: 47-57.
Kumar, S. and B. Shobharani. 2015. Comparative study of hscrp in chronic kidney disease. IOSR J. Pharm. 5(7): 8-12.
Lameire, N., W. Van Biesen and R. Vanholder. 2005. Acute renal failure. Lancet. 365: 417-430.
Liu, Y., C. Liu, A. Yang, J. Cowley and M. Liang. 2014. Base-resolution maps of 5-methylcytosine and 5hydroxymethylcytosine in Dahl S rats: Effect of salt and genomic sequence. Hypertension. 63: 827-838.
Morita, Y., H. Ikeguchi, J. Nakamura, N. Hotta, Y. Yuzawa and S. Matsuo. 2000. Complement activation products in the urine from proteinuric patients. J. Am. Soc. Nephrol. 11: 700-707.
Mustafa, N. 2018. Evaluation of complement components (C3 and C4) in diabetic retinopathy patients. Res. J. Pharm. Technol. 11(9): 3773-3776.
Nilsson, B., O. Hamad, H. Ahlstrom, J. Kullberg, L. Johansson, L. Lindhagen, A. Haenni, K. Ekdahl and L. Lind. 2014. C3 and C4 are strongly related to adipose tissue variables and cardiovascular risk factors. Eur. J. Clin. Invest. 44: 587-596.
Onda, K., I. Ohsawa, H. Ohi, M. Tamano, S. Mano, M. Wakabayashi, A. Toki, S. Horikoshi, T. Fujita and Y. Tomino. 2011. Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function. BMC Nephrol. 12: 64.
Ortega, O., I. Rodrigus and P. Gallar. 2002. Significance of high C-reactive protein levels in pre dialysis patients. Nephrol. Dial. Transplant. 17: 1105-1109.
Østergaard, J., T. Hansen, S. Thiel and A. Flyvbjerg. 2005. Complement activation and diabetic vascular complications. Clin. Chim. Acta. 361: 10-19.
Pan, M., J. Zhang, Z. Li, L. Jin, Y. Zheng, Z. Zhou, S. Zhen and G. Lu. 2017. Increased C4 and decreased C3 levels are associated with a poor prognosis in patients with immunoglobulin a nephropathy: A retrospective study. BMC Nephrol. 18(231): 1-7.
Panichi, V., M. Migliori, S. De Pietro, D. Taccola, A. Bianchi, M. Norpoth, M. Metelli, L. Giovannini, C. Tetta and R. Palla. 2001. C reactive protein in patients with chronic renal diseases. Ren. Fail. 23(3-4): 551-562.
Pechman, K., D. Basile, H. Lund and D. Mattson. 2008. Immune suppression blocks sodium-sensitive hypertension following recovery from ischemic acute renal failure. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294: 1234-1239.
Poppelaars, F., B. Faria, M. da Costa, C. Franssen, W. van Son, S. Berger, M. Daha and M. Seelen. 2018. The complement system in dialysis: A forgotten story? Front. Immunol. 9: 71.
Razeghi, E., S. Parkhideh, F. Ahmadi and P. Khashayar. 2008. Serum CRP levels in pre-dialysis patients. Ren. Fail. 30: 193-198.
Regal, J., C. Laule, L. McCutcheon, K. Root, H. Lund, S. Hashmat and D. Mattson. 2018. The complement system in hypertension and renal damage in the Dahl SS rat. Physiol. Rep. 6(6): 1-6.
Stenvinkel, P., O. Heimbürger, F. Paultre, U. Diczfalusy, T. Wang, L. Berglund and T. Jogestrand. 1999. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 55(5): 1899-1911.
Tang, Z. and N. Sheerin. 2009. Complement activation and progression of chronic kidney disease. Hong Kong J. Nephrol. 11(2): 41-46.
Ueda, Y., K. Nagasawa, H. Tsukamoto, T. Horiuchi, S. Yoshizawa, T. Tsuru, I. Furugo and Y. Niho. 1995. Urinary C4 excretion in systemic lupus erythematosus. Clin. Chim. Acta. 243: 11-23.
Wada, T. and M. Nangaku. 2013. Novel roles of complement in renal diseases and their therapeutic consequences. Kidney Int. 84(3): 441-450.
Zipfel, P., S. Heinen, M. Józsi and C. Skerka. 2006. Complement and diseases: Defective alternative pathway control results in kidney and eye diseases. Mol. Immunol. 43(1-2): 97-106.
Zwirner, J., M. Burg, M. Schulze, R. Brunkhorst, O. Götze, K. Koch and J. Floege. 1997. Activated complement C3: A potentially novel predictor of progressive IgA nephropathy. Kidney Int. 51(4): 1257-1264.
How to Cite
Authors who publish with this journal agree to the following terms:
1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License [CC BY-NC-ND 4.0] that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).