Renal dysfunction is an independent predictor for cardiovascular morbidity and mortality. We investigated whether chronic hepatitis C virus (HCV) infection and the related insulin resistance/hyperinsulinemia influence renal function in comparison with a group of healthy subjects and with another group with metabolic syndrome. We enrolled 130 newly diagnosed HCV outpatients matched for age and gender with 130 patients with metabolic syndrome and 130 healthy subjects. Renal function was evaluated by calculation of glomerular filtration rate (e-GFR, mL/min/1.73 m2) using the CKD-EPI equation. The following laboratory parameters were measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, and HOMA to evaluate insulin sensitivity. HCV patients with respect to both healthy subjects and metabolic syndrome patients have a decreased e-GFR: 86.6 ± 16.1 vs 120.2 ± 23.1 mL/min/1.73 m2 (P < 0.0001) and 94.9 ± 22.6 mL/min/1.73 m2 (P = 0.003), respectively. Regarding biochemical variables, HCV patients, in comparison with healthy subjects, have a higher triglyceride level, creatinine, fasting insulin and HOMA (3.4 ± 1.4 vs 2.6 ± 1.3; P < 0.0001). At linear regression analysis, the correlation between e-GFR and HOMA is similar in the metabolic syndrome (r = −0.555, P < 0.0001) and HCV (r = −0.527, P < 0.0001) groups. At multiple regression analysis, HOMA is the major determinant of e-GFR in both groups, accounting for, respectively, 30.8 and 27.8 % of its variation in the metabolic syndrome and HCV. In conclusion, we demonstrate that HCV patients have a significant reduction of e-GFR and that insulin resistance is the major predictor of renal dysfunction.
Chronic C hepatitis Renal function Insulin resistance Cardiovascular risk Metabolic syndrome
This is a preview of subscription content, log in to check access.
Compliance with ethical standards
No relationship with any industry or financial support exists.
Conflict of interest
The authors declare that they have no conflict of interest.
Statement of human and animal rights
This article does not contain any studies with human participants or animals performed by any of the authors.
Written informed consent was obtained from all participants.
Völzke H, Schwahn C, Wolff B et al (2004) Hepatitis B and C virus infection and the risk of atherosclerosis in a general population. Atherosclerosis 174:99–103CrossRefPubMedGoogle Scholar
Targher G, Bertolini L, Padovani R, Rodella S, Arcaro G, Day C (2007) Differences and similarities in early atherosclerosis between patients with non-alcoholic steatohepatitis and chronic hepatitis B and C. J Hepatol 46:1126–1132CrossRefPubMedGoogle Scholar
Mostafa A, Mohamed MK, Saeed M, Hasan A, Fontanet A, Godsland I, Coady E, Esmat G, El-Hoseiny M, Abdul-Hamid M, Hughes A, Chaturvedi N (2010) Hepatitis C infection and clearance: impact on atherosclerosis and cardiometabolic risk factors. Gut 59:1135–1140CrossRefPubMedGoogle Scholar
Perticone M, Miceli S, Maio R, Caroleo B, Sciacqua A, Tassone EJ, Greco L, Staltari O, Sesti G, Perticone F (2014) Chronic HCV infection increases cardiac left ventricular mass index in normotensive patients. J Hepatol 61:755–760CrossRefPubMedGoogle Scholar
Perticone M, Maio R, Tassone EJ, Tripepi G, Di Cello S, Miceli S, Caroleo B, Sciacqua A, Licata A, Sesti G, Perticone F (2015) Insulin-resistance HCV infection-related affects vascular stiffness in normotensives. Atherosclerosis 238:108–112CrossRefPubMedGoogle Scholar
Schillaci G, Verdecchia P, Porcellati C, Cuccurullo O, Cosco C, Perticone F (2000) Continuous relation between left ventricular mass and cardiovascular risk in essential hypertension. Hypertension 35:580–586CrossRefPubMedGoogle Scholar
Willum-Hansen T, Staessen JA, Torp-Pedersen C, Rasmussen S, Thijs L, Ibsen H, Jeppesen J (2006) Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation 113:664–670CrossRefPubMedGoogle Scholar
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351:1296–1305 (Erratum in: (2008) N Engl J Med 18:4)Google Scholar
Fried LF, Shlipak MG, Crump C, Bleyer AJ, Gottdiener JS, Kronmal RA, Kuller LH, Newman AB (2003) Renal insufficiency as predictor of cardiovascular outcomes and mortality in elderly individuals. J Am Coll Cardiol 41:1364–1372CrossRefPubMedGoogle Scholar
Chen J, Muntner P, Hamm LL, Jones DW, Batuman V, Fonseca V, Whelton PK, He J (2004) The metabolic Syndrome and chronic renal disease in US adults. Ann Intern Med 140:167–174CrossRefPubMedGoogle Scholar
Kurella M, Lo JC, Chertow GM (2005) Metabolic syndrome and the risk for chronic Kidney disease among nondiabetic adults. J Am Soc Nephrol 16:2134–2140CrossRefPubMedGoogle Scholar
Asrani SK, Buchanan P, Pinsky B, Rey LR, Schnitzler M, Kanwal F (2010) Lack of association between hepatitis C infection and chronic kidney disease. Clin Gastroenterol Hepatol 8:79–84CrossRefPubMedPubMedCentralGoogle Scholar
Moe SM, Pampalone AJ, Ofner S, Rosenman M, Teal E, Hui SL (2008) Association of hepatitis C virus infection with prevalence and development of kidney disease. Am J Kidney Dis 51:885–892CrossRefPubMedPubMedCentralGoogle Scholar
Tsui JI, Vittinghoff E, Shlipak MG, O’Hare AM (2006) Relationship between hepatitis C and chronic kidney disease: results from the Third National Health and Nutrition Examination Survey. J Am Soc Nephrol 17:1168–1174CrossRefPubMedGoogle Scholar
Succurro E, Arturi F, Lugarà M, Grembiale A, Fiorentino TV, Caruso V, Andreozzi F, Sciacqua A, Hribal ML, Perticone F, Sesti G (2010) One-hour postload plasma glucose levels are associated with kidney dysfunction. Clin J Am Soc Nephrol 5:1922–1927CrossRefPubMedPubMedCentralGoogle Scholar
Alberti KG, Eckel RH, Grundy SM et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640–1645CrossRefPubMedGoogle Scholar
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMedGoogle Scholar
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, CKD-EPI (chronic kidney disease epidemiology collaboration) (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentralGoogle Scholar
Satapathy SK, Lingisetty CS, Williams S (2012) Higher prevalence of chronic kidney disease and shorter renal survival in patients with chronic hepatitis C virus infection. Hepatol Int 6:369–378CrossRefPubMedGoogle Scholar
Perticone F, Maio R, Sciacqua A, Perticone M, Laino I, Miceli S, Mazzaferro D, Pascale A, Andreozzi F, Sesti G (2009) Insulin-like growth factor-1 and glomerular filtration rate in hypertensive patients. J Hypertens 27:613–617CrossRefPubMedGoogle Scholar
Sesti G, Sciacqua A, Cardellini M, Marini MA, Maio R, Vatrano M, Succurro E, Lauro R, Federici M, Perticone F (2005) Plasma concentration of IGF-I is independently associated with insulin sensitivity in subjects with different degrees of glucose tolerance. Diabetes Care 28:120–125CrossRefPubMedGoogle Scholar
Thrailkill KM, Quattrin T, Baker L, Kuntze JE, Compton PG, Martha PM Jr (1999) Cotherapy with recombinant human insulin-like growth factor I and insulin improves glycemic control in type 1 diabetes: RhIGF-I in IDDM Study Group. Diabetes Care 22:585–592CrossRefPubMedGoogle Scholar
Sandhu MS, Heald AH, Gibson JM, Cruickshank JK, Dunger DB, Wareham NJ (2002) Circulating concentrations of insulin like growth factor-I and development of glucose intolerance: a prospective observational study. Lancet 359:1740–1745CrossRefPubMedGoogle Scholar
Haylor J, Singh I, el Nahas AM (1991) Nitric oxide synthesis inhibitor prevents vasodilation by insulin-like growth factor I. Kidney Int 39:333–335CrossRefPubMedGoogle Scholar
Vijayan A, Franklin SC, Behrend T, Hammerman MR, Miller SB (1999) Insulin-like growth factor 1 improves renal function in patients with end-stage chronic renal failure. Am J Physiol 276:R929–R934PubMedGoogle Scholar
Shoelson SE, Herrero L, Naaz A (2005) Obesity, inflammation, and insulin resistance. Gastroenterology 128:636–641CrossRefGoogle Scholar
Leoncini G, Ratto E, Viazzi F, Vaccaro V, Parodi D, Parodi A, Falqui V, Tomolillo C, Deferrari G, Pontremoli R (2005) Metabolic syndrome is associated with early signs of organ damage in nondiabetic, hypertensive patients. J Intern Med 257:454–460CrossRefPubMedGoogle Scholar
Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, Moriya K, Koike K (2004) Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 126:840–848CrossRefPubMedGoogle Scholar
Bugianesi E, Salamone F, Negro F (2012) The interaction of metabolic factors with HCV infection: does it matter? J Hepatol 56(suppl 1):S56–S65CrossRefPubMedGoogle Scholar
Biddinger SB, Kahn CR (2006) From mice to men: insights into the insulin resistance syndromes. Ann Rev Physiol 68:123–158CrossRefGoogle Scholar