Role of serum Cystatin C as a marker of early nephropathy in metabolic syndrome: a case control study

Hemant Goel, Onam Aggarwal, Anuj Kumar, Pramod Lali, Lal Chandra


Background: The metabolic syndrome (MS) has become a significant public health problem and patients with MS are at higher risk for developing renal diseases. Serum Cystatin C suggested as a sensitive endogenous marker than creatinine for slight changes in GFR could be useful marker in MS.

Methods: A total of 200 subjects were included. New International Diabetes Federation (IDF) definition of MS was used as inclusion criteria. Patients excluded were those with hypo/hyperthyroidism, on glucocorticoids, statins and fibrate, malignancy, cirrhosis, active liver disease and conditions affecting abdominal girth. Serum Cystatin C, insulin, creatinine, triglycerides, high density lipoproteins-cholesterol (HDL-C), fasting glucose, Urinary microalbumin and Urinary creatinine were estimated by standard method.

eGFR and HOMA-IR (homeostasis model assessment of insulin resistance) were calculated. The primary outcome assessed was the occurrence of early nephropathy in MS and the secondary outcome included evaluation of early nephropathy by serum Cystatin C and eGFR. Appropriate statistical test was applied by using SPSS Version 21 software.

Results: Fasting insulin levels and insulin resistance were significantly raised in MS cases. eGFR (MDRD) was lower in the MS cases (72.59±8.79mL/min/1.73m2) vs non-MS (130.34±40.75 mL/min/1.73m). Urinary microalbumin levels and serum cystatin C were significantly increased in MS and the cystatin c levels showed significant positive correlation with urinary microalbumin and negative correlation with eGFR.eGFR was found to be lower in the microalbuminuric than normoalbuminuric groups.

Conclusions: Serum Cystatin C levels are higher in MS and can be useful, practical, non-invasive biomarker for evaluation of early renal involvement in MS. 


Cystatin C, Case control study, Early nephropathy, Marker, Metabolic syndrome

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Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American heart association/national heart, lung, and blood institute scientific statement. Circulation. 2005 Oct 25;112(17):2735-52.

McClellan WM, Flanders WD. Risk factors for progressive chronic kidney disease. J Am Soc Nephrol. 2003;14:S65-S70.

Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002;40(2):221-6.

Mussap M, Dalla Vestra M, Fioretto P, Saller A, Varagnolo M, Nosadini R, Plebani M. Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients. Kidney Int. 2002;61:1453-61.

Shlipak MG, Katz R, Sarnak MJ. Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease. Ann Intern Med. 2006;145:237-46.

Coll E, Botey A, Alvarez L. Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment. Am J Kidney Dis. 2000;36(1):29-34.

Randers E, Kristensen JH, Erlandsen EJ, Danielsen H. Serum cystatin C as a marker of the renal function. Scand J Clin Lab Invest. 1998;58:585-92.

Zimmet P. A new IDF worldwide definition of the metabolic syndrome: the rationale and the results. Diabetes Voice. 2005;23:469-80.

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.

Kurella M, Lo JC, Chertow GM. Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults. J Am Soci Nephrol. 2005;16(7):2134-40.

Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287:356-9.

Sawant A, Mankeshwar R, Shah S, Raghavan R, Dhongde G, Raje H, et al. Prevalence of Metabolic Syndrome in Urban India. Cholesterol. 2011;2011:1-7.

Prabhakaran D, Chaturvedi V, Shah P, Manhapra A, Jeemon P, Shah B, et al. Differences in the prevalence of metabolic syndrome in urban and rural India: a problem of urbanization. Chronic Illness. 2007;3(1):8-19.

Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, et al. The metabolic syndrome. Endocrine reviews. 2008;29(7):777-822.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28:412-9.

Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care. 2000;23(1):57-63.

Esteghamati A, Ashraf H, Esteghamati AR, Meysamie A, Khalilzadeh O, Nakhjavani M, et al. Optimal threshold of homeostasis model assessment for insulin resistance in an Iranian population: The implication of metabolic syndrome to detect insulin resistance. Diabetes Res Clin Pract. 2009;84:279-87.

Jeppesen J, Hansen TW, Sussane R. Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease. J Am Coll Cardiol. 2007;49:2112-9.

Chen J, Gu D, Chen CS, Wu X, Hamm LL, Muntner P, et al. Association between the metabolic syndrome and chronic kidney disease in Chinese adults. Nephrol Dial Transplant. 2007;22:1100-6.

Sarnak MJ, Levey AS, Schoolwerth AC. American heart association councils on kidney in cardiovascular disease, high blood pressure research, clinical cardiology, and epidemiology and prevention kidney disease as a risk factor for development of cardiovascular disease: a statement from the American heart association councils on kidney in cardiovascular disease, high blood pressure research, clinical cardiology, and epidemiology and prevention. Circulation. 2003;108(17):2154-69.

Chen J, Gu D, Chen CS. Association between the metabolic syndrome and chronic kidney disease in Chinese adults. Nephrol Dial Transplant. 2007;22(4):1100-6.

Peralta CA, Katz R, Sarnak MJ, Ix J, Fried LF, De Boer I, et al. Cystatin C identifies chronic kidney disease patients at higher risk for complications. J Am Soc Nephrol. 2011;22:147-55.

Palaniappan L, Carnethon M, Fortmann SP. Association between microalbuminuria and the metabolic syndrome: NHANES III. Am J Hypertens. 2003;16:952-8.

Fried LF, Orchard TJ, Kasiske BL. Effect of lipid reduction on the progression of renal disease: a meta-analysis. Kidney Int. 2001;59(1):260-9.

Iseki K, Ikemiya Y, Kinjo K. Body mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int. 2004;65(5):1870-6.

Lane PH, Steffes MW, Mauer SM. Glomerular structure in IDDM women with low glomerular filtration rate and normal urinary albumin excretion. Diabetes. 1992;41:581-6.

Hong CY, Chia KS. Markers of diabetic nephropathy. J Diabetes Complications. 1998;12:43-60.

Tsalamandris C, Allen TJ, Gilbert RE, Sinha A, Panagiotopoulos S, Coo per ME. Progressive decline in renal function in diabetic patients with and without albuminuria. Diabetes. 1994;43:649-55.

Catalano C, Winocour PH, Gillespie S, Gibb I, Alberti KG. Effect of posture and acute glycaemic control on the excretion of retinol-binding protein in normoalbuminuric insulin-dependent diabetic patients. Clin Sci (Lond). 1993;84:461-7.

Uslu S, Efe B, Alataş O, Kebapci N, Colak O, Demirustu C, et al. Serum cystatin C and urinary enzymes as screening markers of renal dysfunction in diabetic patients. J Nephrol. 2005;18:559-67.