SUN-598 - Impact of 8-Year Weight Change on the Risk of Major Adverse Kidney Endpoints and Total Mortality in A Nationwide Cohort of Patients with Diabetes

Introduction
In Colombia, the direct costs of chronic kidney disease (CKD) represent about 4.6% of the total health budget, and most CKD cases are due to diabetes. Excess adiposity in diabetes is associated with poorer glycemic control, impaired plasma lipids, blood pressure, albuminuria and systemic inflammation, all of which favor CKD. However, weight loss in diabetes may also represent unstable diabetes or suboptimal treatment, therefore the relationship between weight change and kidney endpoints in diabetes in not completely known. We assessed the prospective association between weight change over an 8-year period and kidney outcomes among all patients with diagnosed diabetes in Colombia.

Methods
We studied all adults with diagnosed diabetes affiliated to the Colombian Healthcare System between July 1st, 2015 and June 30, 2023. They had to have had a basal estimated glomerular filtration rate (eGFR) >=60 mL/min and not have received any modality of renal replacement therapy. Outcomes were time to end-stage renal disease (ESRD) (eGFR < 15 mL/min, hemodialysis, peritoneal dialysis or renal transplant), advanced chronic kidney disease (aCKD) (eGFR < 30 mL/min, hemodialysis, peritoneal dialysis or renal transplant) and all-cause mortality. The main exposure was weight change divided into eleven 4-Kg brackets, from <-20Kg to >=20Kg. Hazard ratios were obtained relative using Cox proportional hazards models with weight change as a time-dependent covariate and multivariable adjustment for sex, age, race, type of insurance, HbA1c, systolic blood pressure and non-HDL cholesterol.

Results
We studied 2,702,226 patients, 40.3% men, mean age 62.4, mean BMI 28.2%, mean HbA1c 7.29% (56 mmol/mol), self-reported black race 4.2%. All degrees of weight gain greater than 4Kg, or weight loss greater than -4Kg, were significantly associated with an increased risk of ESRD. The HRs for weight gain categories were (all statistically significant): 1.062 for 4 to 8 Kg, 1.094 for 8 to 12 Kg, 1.084 for 12 to 16 Kg, 1.074 for 16 to 20 Kg, and 1.041 for >=20 Kg. The HRs for weight loss categories were also increased (all statistically significant): 1.050 for -4 to -8 Kg, 1.111 for -8 to -12 Kg, 1.159 for -12 to -16 Kg, 1.151 for -16 to -20 Kg, and 1.064 for <=-20 Kg. Very similar results were obtained for the associations of weight change with aCKD and with total mortality. In stratified analyses, results did not differ appreciably by sex or insurance type, but the association between weight gain and ESRD was significantly attenuated among participants of black race.

Conclusions
Weight stability was associated with the lowest risk of major adverse kidney endpoints among patients with diagnosed diabetes. These results are too early to reflect the impact of major weight loss with innovative pharmacological treatments on kidney outcomes in real life conditions. Weight change may be differentially associated with CKD risk in different races.

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