Obesity Related Glomerulopathy: weighing in the effect of Body Surface Area

Importance Obesity-related glomerulopathy (ORG), part of the cardio-renal spectrum, has an early reversible stage of hyperfiltration. Early identification in the obese adolescent population provides an opportunity to reverse the damage. Objective Age-appropriate formulae for estimated glomerular filtration rate (eGFR), are standardized to ideal body surface area (BSA) and provide assessment of renal function in mL/min/1.73 m 2 units, may underestimate prevalence of early ORG. We investigated whether adjusting eGFR to actual BSA more readily identifies early ORG. Design Cross sectional cohort study. Data were collected between 2011-2015 and analysis was performed between January-November 2020. Setting Electronic health records clinical data base from 12 academic health centers and community health centers in the New York metropolitan area. Participants 22,417 women and girls ages 12-21 years for whom data of body measurements and renal function were available. Main Outcome and measures The hypothesis was generated using previously collected health record data. eGFR was calculated in two ways: BSA-standardized eGFR according to KDIGO recommended formula; and Absolute eGFR adjusted to individual BSA. Hyperfiltration was defined above a threshold of 135mL/min/1.73 m 2 or 135 mL/min, respectively. The prevalence of hyperfiltration according to each formula was assessed in parallel to 24-hour urine creatinine. Results 22,417 female adolescents mean age 17 with high prevalence of underrepresented populations (32.6% African American, 12.8% Caucasians and 40.4% Hispanic) were evaluated. Serum creatinine values and hyperfiltration rates according to BSA-standardized eGFR were similar,13.4-15.3%, across Body Mass Index (BMI) groups. Prevalence of hyperfiltration determined by Absolute eGFR differed across groups: Underweight – 2.3%; Normal 6.1%; Overweight – 17.4%; Obese – 31.4%. This trend paralleled the rise in 24-hour urine creatinine across BMI groups. Conclusions and relevance Absolute eGFR more readily identifies early ORG compared to currently used formulae, which are adjusted to an archaic value of a BSA, not representative of current population BMI measures. The high proportion of underrepresented populations in this study accounts for the higher-than-expected obesity rates and should raise awareness for missed opportunities for screening, early diagnosis, and intervention particularly in young Black adults. Key points Question Do the currently recommended formulae estimating GFR reliably predict hyperfiltration due to Obesity Related Glomerulopathy (ORG)? Findings Renal function in relation to BMI was evaluated in a cohort of 22,417 adolescents from the New York metropolitan. Serum creatinine values and BSA-standardized eGFR (mL/min/1.73m 2 ) were similar across BMI groups, and as a result, hyperfiltration rates were also similar. However, Absolute eGFR (mL/min) adjusted to individual BSA, created a positive trend across BMI groups similar to urine creatinine. Meaning Absolute eGFR better reflects the prevalence of hyperfiltration due to Obesity Related Glomerulopathy providing an opportunity for early intervention and damage reversal.