Background: The relation between insulin resistance and atherosclerosis is widely recognized, but it remains unknown whether glucose metabolism/insulin resistance is related to renal pathology in humans. Methods: We quantitatively evaluated pathological changes in the glomeruli, tubulointerstitium, and vessels in renal biopsy specimens from 23 patients with non-diabetic chronic kidney disease (CKD), all of whom took a 75-gram oral glucose tolerance test. We correlated the renal pathological changes with fasting plasma glucose (FPG), fasting plasma insulin, 2-hour plasma glucose (2-h PG), 2-hour plasma insulin (2-h PI), homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index. Results: HOMA-IR exceeded 1.73 in 11 patients (47.8%), and 2-h PI exceeded 64.0 µU/ml in 14 (60.9%). FPG significantly correlated with interstitial fibrosis (r = 0.532, p = 0.009). The significance was marginal in the correlation between FPG and tubular atrophy and arterio-arteriolosclerosis. Statistically significant correlation was also found between 2-h PG and arterio-arteriolosclerosis (r = 0.422, p = 0.04) and between HOMA-IR and interstitial fibrosis (r = 0.416, p = 0.04). Conclusion: Although precise mechanisms remain unknown, glucose metabolism/insulin resistance seem to play pathogenic roles in formation and progression of renal pathological changes, especially tubulointerstitial and vascular lesions, in non-diabetic CKD.

Sarnak MJ, Levey AS: Epidemiology of cardiac disease in dialysis patients. Semin Dial 1999;12:69–76.
Ritz E: Renal dysfunction as a novel risk factor: microalbuminuria and cardiovascular risk. Kidney Int 2005;67(suppl 93):S25–S28.
Fort J: Chronic renal failure: a cardiovascular risk factor. Kidney Int 2005;68(suppl 99):S25–S29.
Howard G, O’Leary DH, Zaccaro D, et al: Insulin sensitivity and atherosclerosis. Circulation 1996;93:1809–1817.
Lempiainen P, Mykkanen L, Pyorala K, Laakso M, Kuusisto J: Insulin resistance syndrome predicts coronary heart disease events in elderly nondiabetic men. Circulation 1999;100:123–128.
DeFronzo RA, Alvestrand A, Smith D, Hendler R, Hendler E, Wahren J: Insulin resistance and uremia. J Clin Invest 1981;67:563–568.
Shinohara K, Shoji T, Emoto M, et al: Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease. J Am Soc Nephrol 2002;13:1894–1900.
Dzurik R, Spustova V, Janekova K: The prevalence of insulin resistance in kidney disease patients before the development of renal failure. Nephron 1995;69:281–285.
Becker B, Kronenberg F, Kielstein JT, et al: Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients with kidney disease: the Mild and Moderate Kidney Disease Study. J Am Soc Nephrol 2005;16:1091–1098.
Kobayashi S, Maesato K, Moriya H, Ohtake T, Ikeda T: Insulin resistance in patients with chronic kidney disease. Am J Kidney Dis 2005;45:275–280.
Paolisso G, Barbagallo M, Petrella G, et al: Effects of simvastatin and atorvastatin administration on insulin resistance and respiratory quotient in aged dyslipidemic non- insulin dependent diabetic patients. Atherosclerosis 2000;150:121–127.
Anan F, Takahashi N, Ooie T, Hara M, Yoshimatsu H, Saikawa T: Candesartan, an angiotensin II receptor blocker, improves left ventricular hypertrophy and insulin resistance. Metabolism 2004;53:777–781.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999;130:461–470.
Mosteller RD: Simplified calculation of body-surface area. N Engl J Med 1987;317:1098.
Verbraecken J, Van de Heyning P, De Backer W, Van Gaal L: Body surface area in normal-weight, overweight, and obese adults: a comparison study. Metabolism 2006;55:515–524.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentration in man. Diabetologia 1985;28:412–419.
Ikee R, Kobayashi S, Hemmi N, et al: Involvement of transglutaminase-2 in pathological changes in renal disease. Nephron Clin Pract 2007;105:c139–c146.
Ophascharoesuk V, Pippin JW, Gordon KL, Shankland SJ, Couser WG, Johnson RJ: Role of intrinsic renal cells versus infiltrating cells in glomerular crescent formation. Kidney Int 1998;54:416–425.
Wada T, Hamakawa S, Hori Y, et al: Immunohistochemical localization of latent transforming growth factor-β binding protein in IgA nephropathy. Kidney Int 1997;52(suppl 63):S182–S184.
Katafuchi R, Kiyoshi Y, Oh Y, et al: Glomerular score as a prognosticator in IgA nephropathy: its usefulness and limitation. Clin Nephrol 1998;49:1–8.
Nieuwhof C, Kruytzer M, Frederiks P, van Breda Vriesman PJ: Chronicity index and mesangial IgG deposition are risk factors for hypertension and renal failure in early IgA nephropathy. Am J Kidney Dis 1998;31:962–970.
Furuhashi M, Nakata T, Ura N, Shimamoto K: Insulin sensitivity and lipid metabolism in human CD36 deficiency. Diabetes Care 2003;26:471–474.
Fujiwara T, Saitoh S, Takagi S, et al: Development and progression of atherosclerotic disease in relation to insulin resistance and hyperinsulinemia. Hypertens Res 2005;28:665–670.
Kobayashi S, Maejima S, Ikeda T, Nagase M: Impact of dialysis therapy on insulin resistance in end-stage renal disease: comparison of hemodialysis and continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 2000;15:65–70.
Kaartinen K, Syrjanen J, Porsti I, et al: Insulin resistance and the progression of IgA nephropathy. Nephrol Dial Transplant 2007;22:778–783.
Chen HM, Liu ZH, Zeng CH, Li SJ, Wang QW, Li LS: Podocyte lesions in patients with obesity-related glomerulopathy. Am J Kidney Dis 2006;48:772–779.
Kang DH, Kanellis J, Hugo C, et al: Role of the microvascular endothelium in progressive renal disease. J Am Soc Nephrol 2002;13:806–816.
Nangaku M: Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. Intern Med 2004;43:9–17.
Kreisberg JI, Ayo SH: The glomerular mesangium in diabetes mellitus. Kidney Int 1993;43:109–113.
Lorenzi M, Cagliero E, Toledo S: Glucose toxicity for human endothelial cells in culture. Delayed replication, disturbed cell cycle, and accelerated death. Diabetes 1985;34:621–627.
Jones SC, Saunders HJ, Pollock CA: High glucose increases growth and collagen synthesis in cultured human tubulointerstitial cells. Diabet Med 1999;16:932–938.
Sarafidis PA, Ruilope LM: Insulin resistance, hyperinsulinemia, and renal injury: mechanisms and implications. Am J Nephrol 2006;26:232–244.
Ikee R, Kobayashi S, Saigusa T, et al: Impact of hypertension and hypertension-related vascular lesions in IgA nephropathy. Hypertens Res 2006;29:15–22.
The DECODE Study Group: Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Lancet 1999;354:617–621.
Singleton JR, Smith AG, Russell JW, Feldman EL: Microvascular complications of impaired glucose tolerance. Diabetes 2003;52:2867–2873.
Reaven GM, Lithell H, Landsberg L: Hypertension and associated metabolic abnormalities: the role of insulin resistance and the sympathoadrenal system. N Engl J Med 1996;334:374–381.
Wu J, Chen X, Xie Y, et al: Characteristics and risk factors of intrarenal arterial lesions in patients with IgA nephropathy. Nephrol Dial Transplant 2005;20:719–727.
Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS: Prevalence of chronic kidney disease and decreased kidney function in the adult US population: third national health and nutrition examination survey. Am J Kidney Dis 2003;41:1–12.
Hemmelgarn BR, Zhang J, Manns BJ, et al: Progression of kidney dysfunction in the community-dwelling elderly. Kidney Int 2006;69:2155–2161.
Stern SE, Williams K, Ferrannini E, DeFronzo RA, Bogardus C, Stern MP: Identification of individuals with insulin resistance using routine clinical measurements. Diabetes 2005;54:333–339.
Harris MI, Goldstein DE, Flegal KM, Little RR, Cowie CC, Wiedmeyer HM, et al: Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults. Diabetes Care 1998;21:518–524.
Basu R, Breda E, Oberg AL, Powell CC, Man CD, Basu A, et al: Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance. Diabetes 2003;52:1738–1748.
Lindeman RD: Renal physiology and pathophysiology of aging. Contrib Nephrol. Basel, Karger, 1993, vol 105, pp 1–12.
Kaplan C, Pasternack B, Shah H, Gallo G: Age-related incidence of sclerotic glomeruli in human kidneys. Am J Pathol 1975;80:227–234.
Langenfeld MR, Forst T, Hohberg C, et al: Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study. Circulation 2005;111:2525–2531.
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