Relationship between chronic kidney disease and metabolic syndrome: current perspectives

Figures & data

Table 1 Albuminuria categories in CKD

Category	Albumin/creatinine ratio (mg/g)	Terms
A1	<30	Normal to mildly increased
A2	30–300	Moderately increased
A3	>300	Severely increased

Abbreviation: CKD, chronic kidney disease.

Table 2 GFR categories in CKD

GFR category	GFR (mL/min/1.732 m^2)	Terms
G1	≥90	Normal or high
G2	60–89	Mildly decreased
G3a	45–59	Mildly to moderately decreased
G3b	30–44	Moderately to severely decreased
G4	15–29	Severely decreased
G5	<15	Kidney failure

Abbreviations: CKD, chronic kidney disease; GFR, glomerular filtration rate.

Table 3 Risk of CKD in adults with and without the MetS

Study/author	Patients	Study design	Definition of CKD	Results
Cross-sectional studies of prevalent CKD
Chen et al^Citation21 NHANES III	6,217 US adults	Cross-sectional	eGFR <60 mL/min/1.73 m^2 and/or Microalbuminuria urinary Alb/Cr ratio of 30–300 mg/g	OR for prevalent CKD 2.60 Two components of MetS 2.21 Three components of MetS 3.38 Four components of MetS 4.23 Five components of MetS 5.58 Prevalent microalbumuria 1.89 Three components of MetS 1.62 Four components of MetS 2.45 Five components of MetS 3.19.
Hoehner et al^Citation39 Inter-Tribal Heart Project	934 Native Americans	Cross-sectional	Microalbuminuria Alb/Cr ratio of 30–299 mg/g	OR for prevalent CKD One component of MetS 1.80 Two components of MetS 1.80 Three or more components 2.30.
Palaniappan et al^Citation22 NHANES III	6,217 American adults	Cross-sectional	Microalbuminuria Alb/Cr ratio of 30–299 mg/g	Microalbuminuria was more common in both women and men with MetS. OR 2.2 and 4.1, respectively.
Chen et al^Citation26 Inter-Asia Study	15,160 Chinese adults	Cross-sectional	eGFR <60 mL/min/1.73 m^2	OR for CKD 1.64 One components of MetS 1.51 Two components of MetS 1.50 Three components of MetS 2.13 Four and five components of MetS 2.72.
Tanaka et al^Citation29	6,980 Japanese adults	Cross-sectional; hospital-based survey	eGFR <60 mL/min/1.73 m^2 or proteinuria (+1 dipstick)	OR of prevalent CKD for those with four metabolic syndrome risk factors compared to those with no metabolic syndrome risk factors was 1.77. (The association was significant in participants <60 years only).
Chang et al^Citation30	60,921 Korean adults	Retrospective analysis	eGFR <60 mL/min/1.73 m^2 or proteinuria (+1 dipstick)	Individuals with MetS had a multivariate adjusted OR of 1.680 for CKD compared with those without MetS.
Ryu et al^Citation34	10,685 Korean healthy men	Prospective cohort study; 3.8 years follow-up	eGFR <60 mL/min/1.73 m^2	Increased risk of prevalent CKD in individuals with MetS (HR 1.99, 95% CI 1.46–2.73).
Prospective studies of incident CKD
Kurella et al^Citation23 (ARIC Study)	10,096 US adults	Prospective; 9 years follow-up	eGFR <60 mL/min/1.73 m^2	OR for incident CKD 1.43 Greater risk of CKD in patients with: Two components of MetS than without; OR 1.53 Three components of MetS 1.75 Four components of MetS 1.84 Five components of MetS 2.45.
Yang et al^Citation32	4,248 Chinese adults	Prospective; 5.4 years follow-up	eGFR <60 mL/min/1.73 m^2	Greater risk incident CKD with than without MetS (HR 1.42, 95% CI 1.03–1.73).
Ninomiya et al^Citation33	1,440 adults ≥40 years; no CKD	Prospective; 5 years follow-up	eGFR <60 mL/min/1.73 m^2	Faster decline of eGFR in adults with none to one versus four to five MetS components.
Lucove et al^Citation27 (Strong Heart Study)	1,484 Native Americans	9 years follow-up	eGFR <60 mL/min/1.73 m^2 or Albuminuria urinary Alb/Cr >30 mg/g	MetS was associated with a 30% increased risk of incident CKD. OR for decreased eGFR and albuminuria 1.3 and 1.4, respectively.
Sun et al^Citation28	118,924 Taiwanese	3.7 years follow-up	GFR <60 mL/min/1.73 m^2 or proteinuria (+1 dipstick)	Incidences and HRs on CKD increased with the number of MetS components. The multivariable-adjusted HR for CKD associated with MetS was 1.30 (95% CI 1.24–1.36).
Ryu et al^Citation34	10,685 Korean healthy men	Prospective cohort study 3.8 years follow-up	eGFR <60 mL/min/1.73 m^2	The development of MetS during follow-up was associated with an increased risk of incident CKD (HR 1.75, 95% CI 1.28–1.39).
Thomas et al^Citation35	30,146 adults	Meta-analysis 11 prospective studies	eGFR <60 mL/min/1.73 m^2 and/or Microalbuminuria or proteinuria	Greater CKD risk with than without MetS (OR 1.55, 95% CI 1.34–1.80).

Abbreviations: Alb, albumin; ARIC; Atherosclerosis Risk in Communities; CI, confidence interval; CKD, chronic kidney disease; Cr, creatine; eGFR, estimated glomerular filtration rate; HR, hazard ratio; MetS, metabolic syndrome; NHANES, National Health and Nutrition Examination Survey; OR, odds ratio.

Table 4 Studies that evaluated the association between insulin resistance and CKD

Study/author	Patients	Study design	Definition of CKD	Results
Cross-sectional studies of prevalent CKD
Hoehner et al^Citation39	934 Native Americans	Cross-sectional	Microalbuminuria Alb/Cr ratio of 30–299 mg/g	OR for CKD Two components of MetS, 1.8 Three or more components, 2.3.
Chen et al^Citation41	6,453 US adults without diabetes	Cross-sectional	eGFR<60 mL/min/1.73 m^2	OR of CKD Serum insulin 4.03 (CI 1.81–8.95; P=0.001) C-peptide 11.4 (CI 4.07–32.1; P<0.001) HbA1c 2.67 (CI 1.31–5.46; P=0.002) HOMA-insulin resistance 2.65 (CI 1.25–5.62; P=0.008).
Prospective studies of incident CKD
Niskanen et al^Citation40	144 middle-aged adults	Prospective observational 10 years follow-up	Microalbuminuria: urinary albumin excretion of 30–300 mg/24 hour Macroalbuminuria: >300 mg/24 hour	The development of both micro and macroalbuminuria was strongly associated with hyperglycemia and fasting insulin levels (trend P<0.001).
Nerpin et al^Citation42	1,070 elderly men	Prospective 7 years follow-up	Cystatin C-based eGFR <50 mL/min/1.73 m^2	Higher insulin sensitivity at baseline was associated with lower risk of impaired renal function; OR for 1-unit higher of insulin sensitivity 0.58 ([95% CI 0.40–0.84]; P<0.004).
Li et al^Citation43	2,696 Chinese adults	Prospective 7 years follow-up	Decline in renal function defined as drop in eGFR by 25% or >5 mL/min/1.73 m^2/year	Insulin resistance was NOT associated with decline in renal function OR 0.97 (0.79–1.19).

Abbreviations: Alb, albumin; CI, confidence interval; CKD, chronic kidney disease; Cr, creatine; eGFR, estimated glomerular filtration rate; HbA_1c, hemoglobin A_1c; HOMA, hemostasis model assessment; MetS, metabolic syndrome; OR, odds ratio.

Table 5 Summary of potential interventions in MetS and CKD

Intervention	Effect(s)
Physical activity	Improves glucose and lipids metabolism Reduces inflammation Improves endothelial function
Weight loss	Decreases proteinuria Increases GFR in obese patients Delays progression to ESRD in CKD patients
Blood pressure control <140/90 mmHg	Decreases the risk of CKD progression Reduces risk of cardiovascular events
Sibutramine	Decreased Cystatin C but not creatinine in clinical trials of obese women with polycystic ovaries Increases blood pressure
Orlistat	No effect on renal function in clinical trials
Metformin	Improves insulin sensitivity Improves endothelial function
RAAS inhibitors	Decrease proteinuria Decrease inflammation Lowers markers of oxidative stress Increase adiponectin
HMG-CoA reductase inhibitors	Preserve renal function and decrease proteinuria in CKD patients

Abbreviations: CKD, chronic kidney disease; CoA, coenzyme A; ESRD, end stage renal disease; GFR, glomerular filtration rate; HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA; MetS, metabolic syndrome; RAAS, renin-angiotensin-aldosterone system.

Table 6 Clinical summary

1. CKD is associated with MetS and its individual components in cross sectional studies.

2. Incident CKD is associated with MetS and vice versa, which suggests a bidirectional relationship.

3. An improved understanding of the pathogenesis of this relationship is needed to design clinical trials aiming toward therapeutic interventions.

Abbreviations: CKD, chronic kidney disease; MetS, metabolic syndrome.

Chen J Muntner P Hamm LL The metabolic syndrome and chronic kidney disease in US adults Ann Intern Med 2004 140 3 167 174 14757614

 PubMed Web of Science ®Google Scholar

Hoehner CM Greenlund KJ Rith-Najarian S Casper ML McClellan WM Association of the insulin resistance syndrome and microalbuminuria among nondiabetic native Americans. The Inter-Tribal Heart Project J Am Soc Nephrol 2002 13 6 1626 1634 12039992

 PubMed Web of Science ®Google Scholar

Palaniappan L Carnethon M Fortmann SP Association between microalbuminuria and the metabolic syndrome: NHANES III Am J Hypertens 2003 16 11 Pt 1 952 958 14573334

 PubMed Web of Science ®Google Scholar

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 1106 17272313

 PubMed Web of Science ®Google Scholar

Tanaka H Shiohira Y Uezu Y Higa A Iseki K Metabolic syndrome and chronic kidney disease in Okinawa, Japan Kidney Int 2006 69 2 369 374 16408128

 PubMed Web of Science ®Google Scholar

Chang IH Han JH Myung SC Association between metabolic syndrome and chronic kidney disease in the Korean population Nephrology (Carlton) 2009 14 3 321 326 19444966

 PubMed Web of Science ®Google Scholar

Ryu S Chang Y Woo HY Time-dependent association between metabolic syndrome and risk of CKD in Korean men without hypertension or diabetes Am J Kidney Dis 2009 53 1 59 69 18838200

 PubMed Web of Science ®Google Scholar

Kurella M Lo JC Chertow GM Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults J Am Soc Nephrol 2005 16 7 2134 2140 15901764

 PubMed Web of Science ®Google Scholar

Yang T Chu CH Hsu CH Impact of metabolic syndrome on the incidence of chronic kidney disease: a Chinese cohort study Nephrology (Carlton) 2012 17 6 532 538 22487238

 PubMed Web of Science ®Google Scholar

Ninomiya T Kiyohara Y Kubo M Metabolic syndrome and CKD in a general Japanese population: the Hisayama Study Am J Kidney Dis 2006 48 3 383 391 16931211

 PubMed Web of Science ®Google Scholar

Lucove J Vupputuri S Heiss G North K Russell M Metabolic syndrome and the development of CKD in American Indians: the Strong Heart Study Am J Kidney Dis 2008 51 1 21 28 18155529

 PubMed Web of Science ®Google Scholar

Sun F Tao Q Zhan S Metabolic syndrome and the development of chronic kidney disease among 118 924 non-diabetic Taiwanese in a retrospective cohort Nephrology (Carlton) 2010 15 1 84 92 20377775

 PubMed Web of Science ®Google Scholar

Thomas G Sehgal AR Kashyap SR Srinivas TR Kirwan JP Navaneethan SD Metabolic syndrome and kidney disease: a systematic review and meta-analysis Clin J Am Soc Nephrol 2011 6 10 2364 2373 21852664

 PubMed Web of Science ®Google Scholar

Chen J Muntner P Hamm LL Insulin resistance and risk of chronic kidney disease in nondiabetic US adults J Am Soc Nephrol 2003 14 2 469 477 12538749

 PubMed Web of Science ®Google Scholar

Niskanen LK Penttilã I Parviainen M Uusitupa MI Evolution, risk factors, and prognostic implications of albuminuria in NIDDM Diabetes Care 1996 19 5 486 493 8732714

 PubMed Web of Science ®Google Scholar

Nerpin E Risérus U Ingelsson E Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort Diabetes Care 2008 31 8 1550 1555 18509205

 PubMed Web of Science ®Google Scholar

Li Y Xie D Qin X Metabolic syndrome, but not insulin resistance, is associated with an increased risk of renal function decline Clin Nutr Epub 4 16 2014

 Web of Science ®Google Scholar