Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium

Abstract

Objective: To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality.

Design: Individual participant data meta-analysis.

Setting: Cohorts from 40 countries with data collected between 1970 and 2017.

Participants: Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607).

Main outcome measures: GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m²) and all cause mortality.

Results: Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index.

Conclusions: Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.

Fig 1

Association between body mass index and risk of decline in glomerular filtration rate in general population cohorts, as shown by meta-analysed hazard ratios and 95% confidence intervals related to body mass index. Association is modelled by linear splines with knots at body mass indices 20, 25, 30, and 35. Circles indicate points with significant differences in risk from the reference point at body mass index 25

Fig 2

Association between body mass index and risk of decline in glomerular filtration rate in general population cohorts, as shown by hazard ratios in individual studies at body mass index 35 versus 25, sorted by average follow-up time (shortest to longest). Study acronyms/abbreviations are listed in eAppendix 2 in the supplementary materials

Fig 3

Body mass index interactions with risk of decline in glomerular filtration rate in general population cohorts, by estimated GFR (eGFR) category, sex, diabetes status, and Asian ethnicity. Meta-analysed hazard ratios and 95% confidence intervals are related to body mass index, modelled by linear splines with knots at body mass indices of 20, 25, 30, and 35 (reference is body mass index 25 in each category)

Fig 4

Association of body mass index with risk of decline in glomerular filtration rate in high cardiovascular risk cohorts, as shown by meta-analysed hazard ratios and 95% confidence intervals related to body mass index, modelled by linear splines with knots at body mass indices 20, 25, 30, and 35. Circles indicate points with significant differences in risk from the reference point at body mass index 25

Fig 5

Association of body mass index with risk of decline in glomerular filtration rate in high cardiovascular risk cohorts, as shown by hazard ratios in individual studies at body mass index 35 versus 25, sorted by average follow-up time (shortest to longest). Study acronyms/abbreviations are listed in eAppendix 2 in the supplementary materials

Fig 6

Association of body mass index with risk of decline in glomerular filtration rate in cohorts with chronic kidney disease, as shown by meta-analysed hazard ratios and 95% confidence interval related to body mass index, modelled by linear splines with knots at body mass indices 20, 25, 30, and 35. Circles indicate points with significant differences in risk from the reference point at body mass index 25

Fig 7

Association of body mass index with risk of decline in glomerular filtration rate in cohorts with chronic kidney disease, as shown by hazard ratios in individual studies at body mass index 35 v 25, sorted by average follow-up time (shortest to longest). Study acronyms/abbreviations are listed in eAppendix 2 in the supplementary materials

Fig 8

Association of waist circumference and waist-to-height ratio with risk of decline in glomerular filtration rate in general population cohorts, as shown by meta-analysed hazard ratios and 95% confidence intervals. Circles indicate points with significant differences in risk from the reference point (sex specific reference point for waist circumference (92 cm for men (M), 78 cm for women (F)); common reference point 0.5 cm/m for waist-to-height ratio)