PracticeUpdate Diabetes March 2019

EDITOR’S PICKS 18

Adiposity and Risk of Decline in Glomerular Filtration Rate British Medical Journal Take-home message • It has been well-established that obesity is associated with increased prevalence of hypertension and type 2 diabetes. Kidney disease may also be associated with obesity, and, if so, it would become an essential part of screening for obese patients. This research paper used a global, collaborative meta-analysis of more than five million individuals in 63 cohorts from the Chronic Kidney Disease Prognosis Consortium (CKD-PC) to determine the relation between measures of adiposity and the risk of GFR decline and death. The primary outcome in this study was GFR decline, which was defined as a 40% eGFR decline, an eGFR <10 mL/min/1.73 m 2 , or end-stage renal disease (ESRD). The results of the meta-analysis showed that, over a mean follow-up of 8 years, 246, 607 (5.6%) individuals in the general popu- lation cohorts had GFR decline. When adjusted for age, gender, race, and current smoking, the hazard ratios for GFR decline with different body mass indices (BMI) compared with a “normal” BMI of 25 were 1.18 for BMI 30, 1.69 for BMI 35, and 2.02 for BMI 40. • The major conclusion of this meta-analysis was that elevated BMI, waist circumfer- ence, and waist-to-height ratio are independent risk factors for GFR decline and death. While the associations were not as profound when the final analysis was done to adjust for comorbidities, this still represents a major finding in medicine. It can be another point of discussion with patients about the benefits of losing weight to achieve a BMI closer to 25. It also presents another possible screening test to add to the list when caring for obese patients. Jason Sloane MD Abstract

RESULTS Over a mean follow-up of eight years, 246607 (5.6%) individuals in the general pop- ulation cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782329 (14.7%) died. Adjusting for age, sex, race, and cur- rent smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% con- fidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results

PARTICIPANTS Adults in 39 general population cohorts (n=5459014), of which 21 (n=594496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84417); and 18 cohorts with chronic kidney disease (n=91 607). MAIN OUTCOME MEASURES GFR decline (esti- mated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/ min/1.73 m 2 ) and all cause mortality.

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 col- lected between 1970 and 2017.

COMMENT By F. Perry Wilson MD, MSCE T his meta-analysis combined individual-level data from 63 separate cohort studies spanning 40 countries between 1970 and 2017 to create the largest-ever analysis of the effect of body mass index (BMI) on loss of kidney function. The outcome was defined by a 40% decrease in estimated glomerular filtration rate (eGFR), a reduction to eGFR below 10mL/min/1.73m 2 , or the provision of dialysis – a composite that represents substantial progression of kidney disease or the development of new kidney disease. The primary findings were that the risk of kidney function loss increases roughly linearly with higher BMI, starting at a BMI of 25. There were few data to suggest that there was substantial risk variation at BMI values less than 25. Interestingly, the relationship between waist circumference and waist:height ratio was similarly associated with kidney function decline, but did not exhibit the threshold effect seen in BMI. This argues that these measures of central adiposity may be

more salient than BMI in terms of predicting kidney function decline. Finally, cohorts with substantial comorbidity (established in patients with preexisting chronic kidney disease or cardiovas- cular disease) demonstrated a somewhat u-shaped relationship, with increased risk of kidney function decline among those at high (>30) and low (<20) BMIs. This finding may be due to the fact that weight loss may herald further worsening of these chronic conditions. Providers can use these findings to encourage weight loss in patients with BMI >25, adding kidney disease to the mul- tiple other risks overweight and obesity can confer.

Dr. Wilson is Interim Director of the Program of Applied Translational Research, and Assistant Professor of Medicine (Nephrology) at Yale School of Medicine in New Haven, Connecticut.

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