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

Figures

Figure 1.
Figure 1. Putative mechanisms of action whereby obesity causes chronic kidney disease.
Figure 2.
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

Table 1. Studies Examining the Association of Obesity With Various Measures of CKD
 
StudyPatientsExposureOutcomesResultsComments
*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 diabetesElevated 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 countriesBMI and waist circumferencePrevalence of albuminuria by dip stickHigher waist circumference associated with albuminuria independent of BMICross-sectional analysis
Framingham multi-detector computed tomography (MDCT) cohort [22]3,099 individualsVisceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT)Prevalence of UACR > 25 mg/g in women and > 17 mg/g in menVAT associated with albuminuria in men, but not in womenCross-sectional analysis
CARDIA (coronary artery risk development in young adults) study [11]2,354 community-dwelling individuals with normal kidney function aged 28 - 40 yearsObesity (BMI > 30 kg/m2)
Diet and lifestyle-related factors
Incident microalbuminuriaObesity (OR: 1.9) and unhealthy diet (OR: 2.0) associated with incident albuminuriaLow number of events
Hypertension detection and follow-up program [10]5,897 hypertensive adultsOverweight and obese BMI* vs. normal BMIIncident 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 CKDResults unchanged after excluding diabetics
Framingham offspring study [9]2,676 individuals free of CKD stage 3High 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 USBMI quintiles
Increase in BMI over time (vs. stable BMI)
Incident eGFR < 60 mL/min/1.73 m2Higher baseline BMI and increase in BMI over time both associated with higher risk of incident CKDExclusively men
Nation-wide US veterans administration cohort [14]3,376,187 US veterans with baseline eGFR ≥ 60 mL/min/1.73 m2BMI categories from < 20 to > 50 kg/m2Rapid decline in kidney function (negative eGFR slope of > 5 mL/min/1.73 m2)BMI > 30 kg/m2 associated with rapid loss of kidney functionAssociations more accentuated in older individuals
Nation-wide population-based study from Sweden [12]926 Swedes with moderate/advanced CKD compared to 998 controlsBMI ≥ 25 vs. < 25 kg/m2CKD vs. no CKDHigher BMI associated with three times higher risk of CKDRisk 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 serviceElevated BMI (overweight and obesity) vs. normal BMI*Incident ESRDOverweight (HR: 3.0) and obesity (HR: 6.89) associated with higher risk of ESRDAssociations strongest for diabetic ESRD, but also significantly higher for non-diabetic ESRD
The Nord-Trondelag health study (HUNT-1) [15]74,986 Norwegian adultsBMI categories*Incidence of ESRD or renal deathBMI > 30 kg/m2 associated with worse outcomesAssociations not present in individuals with BL < 120/80 mm Hg
Community-based screening in Okinawa, Japan [16]100,753 individuals > 20 years oldBMI quartilesIncidence of ESRDHigher BMI associated with increased risk of ESRD in men, but not in womenAverage 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 m2BMI categories from < 20 to > 50 kg/m2Incidence of ESRD
Doubling of serum creatinine
Slopes of eGFR
Moderate and severe obesity associated with worse renal outcomesAssociations present but weaker in patients with more advanced CKD
Kaiser Permanente Northern California [18]320,252 adults with and without baseline CKDOverweight, class I, II and extreme obesity vs. normal BMI*Incidence of ESRDLinearly higher risk of ESRD with higher BMI categoriesAssociations remained present after adjustment for DM, hypertension and baseline CKD
REGARDS (reasons for geographic and racial differences in stroke) study [21]30,239 individualsElevated waist circumference or BMIIncidence of ESRDBMI 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