Metabolic syndrome and chronic kidney disease: Current status and future directions

Table 1 Criteria in definitions of the metabolic syndrome[2-6]

Definition and its criteria	Values
World Health Organization 1998
Insulin resistance	Type 2 diabetes mellitus or impaired fasting glucose (> 100 mg/dL per 5.6 mmol/L) or impaired glucose tolerance
Plus two of the following:
Abdominal obesity	Waist-to-hip ratio > 0.9 in men or > 0.85 in women or BMI > 30 kg/m2
Triglycerides and/or HDL cholesterol	> 150 mg/dL (1.7 mmol/L) and/or < 35 mg/dL (0.9 mmol/L) in men and < 39 mg/dL (1.0 mmol/L) in women respectively
Blood pressure	≥ 140 mmHg systolic; ≥ 90 mmHg diastolic
Microalbuminuria	Urine albumin ≥ 20 μg/min or albumin-to-creatinine ratio ≥ 30 mg/g
American Heart Association/National Heart, Lung, and Blood Institute (2004)
Any three of the following:
Waist circumference	> 102 cm in men and > 88 cm in women
Triglycerides	≥ 150 mg/dL (1.7 mmol/L)
HDL cholesterol	< 40 mg/dL (1.03 mmol/L) in men and < 50 mg/dL (1.29 mmol/L) in women
Blood pressure	≥ 130 mmHg systolic; ≥ 85 mmHg diastolic
Fasting glucose	≥ 100 mg/dL (5.6 mmol/L)
International Diabetes Federation 2005
Central obesity based on ethnicity	Waist circumference for Europeans > 94 cm in men and 80 cm in women; South Asians, Chinese, and Japanese > 90 cm in men and > 80 cm in women; ethnic South and Central Americans use South Asian data; for sub-Saharan Africans and Eastern Mediterranean and Middle East (Arab) populations use European data.
	Can be assumed if BMI > 30 kg/m2
Plus two of the following:
Triglycerides	≥ 150 mg/dL (1.7 mmol/L)
HDL cholesterol	< 40 mg/dL (1.03 mmol/L) in men and < 50 mg/dL (1.29 mmol/L) in women
Blood pressure	≥ 130 mmHg systolic; ≥ 85 mmHg diastolic; treatment of previously diagnosed hypertension
Fasting glucose	≥ 100 mg/dL (5.6 mmol/L), in which case oral glucose tolerance test is recommended
Harmonized (Consensus) Definition incorporating IDF and AHA/NHLBI definitions (2009)
Any three of the following:
Waist circumference	According to population and country-specific definitions
Triglycerides	≥ 150 mg/dL (1.7 mmol/L)
HDL cholesterol	< 40 mg/dL (1.03 mmol/L) in men and < 50 mg/dL (1.29 mmol/L) in women
Blood pressure	≥ 130 mmHg systolic; ≥ 85 mmHg diastolic
Fasting glucose	≥ 100 mg/dL (5.6 mmol/L) or use of medication

IDF: International Diabetes Federation; AHA/NHLBI: American Heart Association/National Heart, Lung, and Blood Institute.

Table 2 Renal associations of metabolic syndrome

Renal outcome	Ref.
eGFR < 60/mL/min per 1.73 m2	[15,19]
Proteinuria and/or microalbuminuria	[13,22,23,29,30]
Histopathological abnormalities (tubular atrophy, interstitial fibrosis, arterial sclerosis)	[31]
Ultrasound abnormalities (increased intra-renal resistive indices)	[32]

Table 3 Potential mechanisms of chronic kidney disease in metabolic syndrome

Mechanism	Ref.
Oxidative stress	[34,40]
Increased pro-inflammatory cytokines (leptin, interleukin 6, tumor necrosis factor α)	[36]
Increased connective tissue growth and/or fibrosis factors (connective tissue growth factor, transforming growth factor β, type IV collagen)	[35,37-39]
Increased glomerular volume and podocyte hypertrophy	[44]
Triglyceride- and free-fatty acid induced injury	45
Increased ischemia and microvascular injury (angiotensin II)	[46,47]
Hyperuricemia	[48,49]

Table 4 Possible clinical interventions for metabolic syndrome in chronic kidney disease^a,b

Clinical intervention	Ref.
Lifestyle modification: weight reduction, dietary adjustment (calorie and phosphate reduction), increased physical activity, and/or smoking cessation	[91-94]
Weight loss medication (orlistat) or surgery	[95,97]
Lipid-lowering medication (statins, fibrates)	[96,104,105]
Blood pressure-lowering medication (renin-angiotensin system antagonists)	[100]
Blood glucose-lowering medication (metformin, thiazolidinediones)	[102,103]

^aIt is recommended that individual national society guidelines be followed in the management of individual metabolic syndrome components; ^bInterventions are individualized and used in combination.