World J Nephrol Urol

World Journal of Nephrology and Urology, ISSN 1927-1239 print, 1927-1247 online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Nephrol Urol and Elmer Press Inc

Journal website http://www.wjnu.org

Review

Volume 6, Number 1-2, June 2017, pages 1-9

Obesity and Kidney Disease: Hidden Consequences of the Epidemic

Figure 2. Obesity-related perihilar focal segmental glomerulosclerosis on a background of glomerulomegaly (periodic acid-Schiff stain, original magnification, × 400). Courtesy of Dr. Patrick D. Walker, MD; Arkana Laboratories, Little Rock, AR.

**Table 1.** Studies Examining the Association of Obesity With Various Measures of CKD
Study	Patients	Exposure	Outcomes	Results	Comments
*Normal weight: BMI 18.5 - 24.9 kg/m²; overweight: BMI 25.0 - 29.9 kg/m²; class I obesity: BMI 30.0 - 34.9 kg/m²; class II obesity: BMI 35.0 - 39.9 kg/m²; class III obesity: BMI ≥ 40 kg/m². BMI: body mass index; CKD: chronic kidney disease; DM: diabetes mellitus; eGFR: estimated glomerular filtration rate; ESRD: end-stage renal disease; HR: hazard ratio; OR: odds ratio; UACR: urine albumin-creatinine ratio.
Prevention of renal and vascular end-stage disease (PREVEND) study [8]	7,676 Dutch individuals without diabetes	Elevated BMI (overweight and obese*), and central fat distribution (waist-hip ratio)	Presence of urine albumin 30 - 300 mg/24 h Elevated and diminished GFR	Obese + central fat: higher risk of albuminuria Obese ± central fat: higher risk of elevated GFR Central fat ± obesity associated with diminished filtration	Cross-sectional analysis
Multinational study of hypertensive outpatients [20]	20,828 patients from 26 countries	BMI and waist circumference	Prevalence of albuminuria by dip stick	Higher waist circumference associated with albuminuria independent of BMI	Cross-sectional analysis
Framingham multi-detector computed tomography (MDCT) cohort [22]	3,099 individuals	Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT)	Prevalence of UACR > 25 mg/g in women and > 17 mg/g in men	VAT associated with albuminuria in men, but not in women	Cross-sectional analysis
CARDIA (coronary artery risk development in young adults) study [11]	2,354 community-dwelling individuals with normal kidney function aged 28 - 40 years	Obesity (BMI > 30 kg/m²) Diet and lifestyle-related factors	Incident microalbuminuria	Obesity (OR: 1.9) and unhealthy diet (OR: 2.0) associated with incident albuminuria	Low number of events
Hypertension detection and follow-up program [10]	5,897 hypertensive adults	Overweight and obese BMI* vs. normal BMI	Incident CKD (1+ or greater proteinuria on urinalysis and/or an eGFR < 60 mL/min/1.73 m²)	Both overweight (OR: 1.21) and obesity (OR: 1.40) associated with incident CKD	Results unchanged after excluding diabetics
Framingham offspring study [9]	2,676 individuals free of CKD stage 3	High vs. normal BMI*	Incident CKD stage 3 Incident proteinuria	Higher BMI not associated with CKD3 after adjustments Higher BMI associated with increased odds of incident proteinuria	Predominantly white, limited geography
Physicians’ health study [13]	11,104 initially healthy men in US	BMI quintiles Increase in BMI over time (vs. stable BMI)	Incident eGFR < 60 mL/min/1.73 m²	Higher baseline BMI and increase in BMI over time both associated with higher risk of incident CKD	Exclusively men
Nation-wide US veterans administration cohort [14]	3,376,187 US veterans with baseline eGFR ≥ 60 mL/min/1.73 m²	BMI categories from < 20 to > 50 kg/m²	Rapid decline in kidney function (negative eGFR slope of > 5 mL/min/1.73 m²)	BMI > 30 kg/m² associated with rapid loss of kidney function	Associations more accentuated in older individuals
Nation-wide population-based study from Sweden [12]	926 Swedes with moderate/advanced CKD compared to 998 controls	BMI ≥ 25 vs. < 25 kg/m²	CKD vs. no CKD	Higher BMI associated with three times higher risk of CKD	Risk strongest in diabetics, but also significantly higher in non-diabetics Cross-sectional analysis
Nation-wide population based study in Israel [17]	1,194,704 adolescent males and females examined for military service	Elevated BMI (overweight and obesity) vs. normal BMI*	Incident ESRD	Overweight (HR: 3.0) and obesity (HR: 6.89) associated with higher risk of ESRD	Associations strongest for diabetic ESRD, but also significantly higher for non-diabetic ESRD
The Nord-Trondelag health study (HUNT-1) [15]	74,986 Norwegian adults	BMI categories*	Incidence of ESRD or renal death	BMI > 30 kg/m² associated with worse outcomes	Associations not present in individuals with BL < 120/80 mm Hg
Community-based screening in Okinawa, Japan [16]	100,753 individuals > 20 years old	BMI quartiles	Incidence of ESRD	Higher BMI associated with increased risk of ESRD in men, but not in women	Average BMI lower in Japan compared to Western countries
Nation-wide US veterans administration cohort [19]	453,946 US veterans with baseline eGFR < 60 mL/min/1.73 m²	BMI categories from < 20 to > 50 kg/m²	Incidence of ESRD Doubling of serum creatinine Slopes of eGFR	Moderate and severe obesity associated with worse renal outcomes	Associations present but weaker in patients with more advanced CKD
Kaiser Permanente Northern California [18]	320,252 adults with and without baseline CKD	Overweight, class I, II and extreme obesity vs. normal BMI*	Incidence of ESRD	Linearly higher risk of ESRD with higher BMI categories	Associations remained present after adjustment for DM, hypertension and baseline CKD
REGARDS (reasons for geographic and racial differences in stroke) study [21]	30,239 individuals	Elevated waist circumference or BMI	Incidence of ESRD	BMI above normal not associated with ESRD after adjustment for waist circumference Higher waist circumference associated with ESRD	Association of waist circumference with ESRD became on-significant after adjustment for comorbidities and baseline eGFR and proteinuria

Table 1. Studies Examining the Association of Obesity With Various Measures of CKD

Study

Patients

Exposure

Outcomes

Results

Comments

*Normal weight: BMI 18.5 - 24.9 kg/m²; overweight: BMI 25.0 - 29.9 kg/m²; class I obesity: BMI 30.0 - 34.9 kg/m²; class II obesity: BMI 35.0 - 39.9 kg/m²; class III obesity: BMI ≥ 40 kg/m². BMI: body mass index; CKD: chronic kidney disease; DM: diabetes mellitus; eGFR: estimated glomerular filtration rate; ESRD: end-stage renal disease; HR: hazard ratio; OR: odds ratio; UACR: urine albumin-creatinine ratio.

Prevention of renal and vascular end-stage disease (PREVEND) study [8]

7,676 Dutch individuals without diabetes

Elevated BMI (overweight and obese*), and central fat distribution (waist-hip ratio)

Presence of urine albumin 30 - 300 mg/24 h
Elevated and diminished GFR

Obese + central fat: higher risk of albuminuria
Obese ± central fat: higher risk of elevated GFR
Central fat ± obesity associated with diminished filtration

Cross-sectional analysis

Multinational study of hypertensive outpatients [20]

20,828 patients from 26 countries

BMI and waist circumference

Prevalence of albuminuria by dip stick

Higher waist circumference associated with albuminuria independent of BMI

Cross-sectional analysis

Framingham multi-detector computed tomography (MDCT) cohort [22]

3,099 individuals

Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT)

Prevalence of UACR > 25 mg/g in women and > 17 mg/g in men

VAT associated with albuminuria in men, but not in women

Cross-sectional analysis

CARDIA (coronary artery risk development in young adults) study [11]

2,354 community-dwelling individuals with normal kidney function aged 28 - 40 years

Obesity (BMI > 30 kg/m²)
Diet and lifestyle-related factors

Incident microalbuminuria

Obesity (OR: 1.9) and unhealthy diet (OR: 2.0) associated with incident albuminuria

Low number of events

Hypertension detection and follow-up program [10]

5,897 hypertensive adults

Overweight and obese BMI* vs. normal BMI

Incident CKD (1+ or greater proteinuria on urinalysis and/or an eGFR < 60 mL/min/1.73 m²)

Both overweight (OR: 1.21) and obesity (OR: 1.40) associated with incident CKD

Results unchanged after excluding diabetics

Framingham offspring study [9]

2,676 individuals free of CKD stage 3

High vs. normal BMI*

Incident CKD stage 3
Incident proteinuria

Higher BMI not associated with CKD3 after adjustments
Higher BMI associated with increased odds of incident proteinuria

Predominantly white, limited geography

Physicians’ health study [13]

11,104 initially healthy men in US

BMI quintiles
Increase in BMI over time (vs. stable BMI)

Incident eGFR < 60 mL/min/1.73 m²

Higher baseline BMI and increase in BMI over time both associated with higher risk of incident CKD

Exclusively men

Nation-wide US veterans administration cohort [14]

3,376,187 US veterans with baseline eGFR ≥ 60 mL/min/1.73 m²

BMI categories from < 20 to > 50 kg/m²

Rapid decline in kidney function (negative eGFR slope of > 5 mL/min/1.73 m²)

BMI > 30 kg/m² associated with rapid loss of kidney function

Associations more accentuated in older individuals

Nation-wide population-based study from Sweden [12]

926 Swedes with moderate/advanced CKD compared to 998 controls

BMI ≥ 25 vs. < 25 kg/m²

CKD vs. no CKD

Higher BMI associated with three times higher risk of CKD

Risk strongest in diabetics, but also significantly higher in non-diabetics
Cross-sectional analysis

Nation-wide population based study in Israel [17]

1,194,704 adolescent males and females examined for military service

Elevated BMI (overweight and obesity) vs. normal BMI*

Incident ESRD

Overweight (HR: 3.0) and obesity (HR: 6.89) associated with higher risk of ESRD

Associations strongest for diabetic ESRD, but also significantly higher for non-diabetic ESRD

The Nord-Trondelag health study (HUNT-1) [15]

74,986 Norwegian adults

BMI categories*

Incidence of ESRD or renal death

BMI > 30 kg/m² associated with worse outcomes

Associations not present in individuals with BL < 120/80 mm Hg

Community-based screening in Okinawa, Japan [16]

100,753 individuals > 20 years old

BMI quartiles

Incidence of ESRD

Higher BMI associated with increased risk of ESRD in men, but not in women

Average BMI lower in Japan compared to Western countries

Nation-wide US veterans administration cohort [19]

453,946 US veterans with baseline eGFR < 60 mL/min/1.73 m²

BMI categories from < 20 to > 50 kg/m²

Incidence of ESRD
Doubling of serum creatinine
Slopes of eGFR

Moderate and severe obesity associated with worse renal outcomes

Associations present but weaker in patients with more advanced CKD

Kaiser Permanente Northern California [18]

320,252 adults with and without baseline CKD

Overweight, class I, II and extreme obesity vs. normal BMI*

Incidence of ESRD

Linearly higher risk of ESRD with higher BMI categories

Associations remained present after adjustment for DM, hypertension and baseline CKD

REGARDS (reasons for geographic and racial differences in stroke) study [21]

30,239 individuals

Elevated waist circumference or BMI

Incidence of ESRD

BMI above normal not associated with ESRD after adjustment for waist circumference
Higher waist circumference associated with ESRD

Association of waist circumference with ESRD became on-significant after adjustment for comorbidities and baseline eGFR and proteinuria