Clinical Significance of Serum Cystatin C in SLE: A Potential Marker of Disease Damage Beyond Lupus Nephritis
DOI:
https://doi.org/10.22317/jcms.v10i3.1553Keywords:
Cystatin C, systemic lupus erythematosus, lupus nephritis, thyroid dysfunction, SLICC-DIAbstract
Objective: This work aimed to assess the serum level of cystatin C in systemic lupus erythematosus (SLE) patients and to determine the relation to disease characteristics and damage.
Methods: The study included 33 SLE patients presenting to the Internal Medicine and Rheumatology Department and Outpatient clinic, King Abdulaziz University, Saudi Arabia. The medical history, clinical examination, laboratory investigations and medications received by the patients were recorded. The systemic lupus international collaborating clinics damage index (SLICC-DI) was assessed. Serum cystatin C was measured using the immune-nephelometric method.
Results: The mean age of the patients was 35.3±10.7 years; 28 females and 5 males (F:M 5.6:1), disease duration 5.5±3.1 years and their age at onset was 27.9±10.6 years. Serum cystatin C level was significantly higher in patients with lupus nephritis (LN) (2.47±1.57 mg/L vs v mg/L, p=0.003) and diabetes (4.92±0.05 mg/L vs 1.93±1.34 mg/L; p<0.0001) and was lower in those with thyroid dysfunction (1.41±0.75 mg/L vs 2.3±1.59 mg/L, p=0.047). There was a significant correlation between the serum cystatin C level with proteinuria (r=0.57, p=0.011) and with the SLICC-DI (r=0.42,p=0.016). Serum cystatin C could discriminate patients with LN at cut-off value of 0.904 mg/L with area under the curve of 0.765, sensitivity 87% and specificity 50%; p=0.017.
Conclusion: The remarkable association between cystatin C and LN is confirmed and an emerging role is noted in reflecting the extent of disease damage. The likely association with diabetes and thyroid dysfunction should also be taken into consideration when deciding treatment regimens for LN patients.
References
Huang H, Zhang Y, Gui L, Zhang L, Cai M, Sheng Y. Proteomic analyses reveal cystatin c is a promising biomarker for evaluation of systemic lupus erythematosus. Clin Proteomics. 2023;20(1):43.
Gheita TA, Noor RA, Abualfadl E, Abousehly OS, El-Gazzar II, El Shereef RR, et al. Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint. Lupus. 2021;30(9):1526-35.
Soares AA, Eyff TF, Campani RB, Ritter L, Camargo JL, Silveiro SP. Glomerular filtration rate measurement and prediction equations. Clin Chem Lab Med.2009;47:1023–32.
Martínez-Martínez MU, Abud-Mendoza C. Serum cystatin C as a marker of renal function in patients with systemic lupus erythematosus. Reumatol Clin. 2012;8(3):158-9
Brzin J, Popovic T, Turk V, Borchart U, Machleidt W. Human cystatin, a new protein inhibitor of cysteine proteinases. Biochem Biophys Res Commun. 1984;118(1):103-9.
Newman DJ. Cystatin C. Ann Clin Biochem. 2002;39:89-104.
Denamur S, Chazeirat T, Maszota-Zieleniak M, Vivès R, Saidi A, Zhang F et al.. Binding of heparan sulfate to human cystatin C modulates inhibition of cathepsin L: Putative consequences in mucopolysaccharidosis. Carbohydrate Polymers, 2022;293:119734.
Lertnawapan R, Bian A, Rho YH, Raggi P, Oeser A, Solus JF, et al. Cystatin C is associated with inflammation but not atherosclerosis in systemic lupus erythematosus. Lupus. 2012;21(3):279-87.
Madero M, Sarnak MJ, Stevens LA. Serum cystatin C as a marker of glomerular filtration rate. Curr Opin Nephrol Hypertens. 2006;15:610–6.
Kazama JJ, Kutsuwada K, Ataka K, Maruyama H, Gejyo F. Serum cystatin C reliably detects renal dysfunction in patients with various renal diseases. Nephron. 2002;91(1):13-20
Silva MV, Moscoso Solorzano G, Nishida SK, Kirsztajn GM. Are serum cystatin C levels influenced by steroid doses in lupus nephritis patients? J Bras Nefrol. 2011;33(3):306-12
Lamb EJ, Levey AS, Stevens PE. The kidney disease improving global outcomes (KDIGO) guideline update for chronic kidney disease: evolution not revolution. Clin Chem. 2013;59(3):462-5.
Stevens LA, Schmid CH, Greene T, Li L, Beck GJ, Joffe MM, et al. Factors other than glomerular filtration rate affect serum cystatin C levels. Kidney Int. 2009;75:652–60.
Madureira Silva MV, Moscoso-Solorzano GT, Nishida SK, Mastroianni-Kirsztajn G. Serum Beta 2-microglobulin/cystatin C index: a useful biomarker in lupus nephritis? Nephron Extra. 2012;2(1):169-76.
Al Musaimi O, Abu-Nawwas AH, Al Shaer D, Khaleel NY, Fawzi M. Influence of age, gender, smoking, diabetes, thyroid and cardiac dysfunctions on cystatin C biomarker. Semergen. 2019;45(1):44-51.
Fatemi A, Rahami Z, Smiley A. Role of Cystatin C in predicting disease activity and flare-up in systemic lupus erythematosus: A longitudinal follow-up study. Int J Prev Med. 2021;12:63.
Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-86.
Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E, Gordon C, et al. The reliability of the systemic lupus international collaborating clinics/American college of rheumatology damage index in patients with systemic lupus erythematosus. Arthritis Rheum. 1997;40(5):809-13.
Gheita TA, Abd El Baky AM, Assal HS, Farid TM, Rasheed IA, Thabet EH. Serum cystatin C, urinary neutrophil gelatinase-associated lipocalin and N-acetyl-beta-D-glucosaminidase in juvenile and adult patients with systemic lupus erythematosus: Correlation with clinical manifestations, disease activity and damage. Saudi J Kidney Dis Transpl. 2015;26(3):497-506
Peixoto L, Aguiar P, de Bragança R, Martins JR, Acabado AJ, Ducla-Sores JL. Cystatin C: A promising marker of renal function in patients with systemic lupus erythematosus? Acta Med Port. 2015;28(3):333-41.
Chew C, Pemberton PW, Husain AA, Haque S, Bruce IN. Serum cystatin C is independently associated with renal impairment and high sensitivity C-reactive protein in systemic lupus erythematosus. Clin Exp Rheumatol. 2013;31(2):251-5.
Xu B, Zhang YM, Yang YW, Liu YS, Feng JF. Diagnostic performance of serum cystatin C and complement component 1q in lupus nephritis. Arthritis Res Ther. 2019;21(1):267.
Caravaca F. Cystatin C: yes, but. Nefrologia. 2006;26:421–5
Garcia-Garcia P, Castejon R, Tutor-Ureta P, Silvestre RA, Mellor-Pita S, Jimenez-Ortiz C, Yebra-Bango M. Serum cystatin C is associated with kidney function but not with cardiovascular risk factors or subclinical atherosclerosis in patients with systemic lupus erythematosus. Clin Rheumatol. 2017;36(12):2709-2717.
Xiong K, Zhang S, Zhong P, Zhu Z, Chen Y, Huang W, et al. Serum cystatin C for risk stratification of prediabetes and diabetes populations. Diabetes Metab Syndr. 2023;17(11):102882.
González KA, Stickel AM, Kaur SS, Ramos AR, González HM, Tarraf W. Serum Cystatin-C is linked to increased prevalence of diabetes and higher risk of mortality in diverse middle-aged and older adults. PLoS One. 2022;17(9):e0270289.
Wei W, Li S, Liu J, Liu Y, Chen K, Chen S, et al. Prognostic value of creatinine-to-cystatin c ratio in patients with type 2 diabetes mellitus: a cohort study. Diabetol Metab Syndr. 2022;14(1):176.
Luo Y, Wang Q, Li H, Lin W, Yao J, Zhang J, et al. Serum cystatin C is associated with peripheral artery stiffness in patients with type 2 diabetes mellitus combined with chronic kidney disease. Clin Biochem. 2023;118:110593.
Tapper M, McGrowder DA, Dilworth L, Soyibo A. Cystatin C, vitamin D and thyroid function test profile in chronic kidney disease patients. Diseases. 2021;9(1):5.
Zhang D, Gao L, Ye H, Chi R, Wang L, Hu L, et al. Impact of thyroid function on cystatin C in detecting acute kidney injury: a prospective, observational study. BMC Nephrol. 2019;20(1):41.
Fricker M, Wiesli P, Brändle M, Schwegler B, Schmid C. Impact of thyroid dysfunction on serum cystatin C. Kidney Int. 2003;63(5):1944-7
El-Metwally, E.M., El-Hussiny, M.AB., Abd-Elgawad, M.S. et al. Level of cystatin C in functional thyroid disorders and its relation to GFR. Comp Clin Pathol 2017;26:1141–7
Gao D, Shao J, Jin W, Xia X, Qu Y. Correlations of serum cystatin C and hs-CRP with vascular endothelial cell injury in patients with systemic lupus erythematosus. Panminerva Med. 2018;60(4):151-5.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Journal of Contemporary Medical Sciences
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
