#3559 the impact of obesity on clinical outcomes in various levels of co-morbidity of non-dialysis chronic kidney disease patients

Abstract Background and Aims Obesity is a major issue with an estimated prevalence of 1.9 billion adults worldwide. Obesity is an important risk factor for premature death and the development of non-communicable diseases such as diabetes mellitus (DM), heart diseases, and chronic kidney disease (CKD). However, mounting evidence in the literature describes a reverse association whereby obesity may have a protective effect on mortality; this is sometimes referred to as the “obesity paradox”. Several reports question the concept of obesity paradox claiming methodology flaws such as collider stratification bias. In this study, we aimed to examine the effects of obesity on the combined outcomes of all-cause mortality (ACM) and renal replacement therapy (RRT) incidence in a cohort of patients with non-dialysis dependent CKD (NDD-CKD) by correcting for major risk factors to reduce the risk of bias. Method This retrospective study was undertaken on all patients with a documented body mass index (BMI) in the Salford Kidney Study database from October 2002 until December 2016. Patients were grouped according to their BMI into normal weight [BMI 18.5-24.9 kg/m2], overweight [BMI 25–29.9 kg/m2 and obese [BMI> 30 kg/m2]. Patients were also grouped according to their level of co-morbidity into 4 groups: group 1 had CKD only; group 2 had CKD and heart failure (HF); group 3 had CKD and DM; and group 4 had CKD, DM, and HF. Univariate Cox regression as well as three stepwise models of multivariate analysis were performed to study the strength of association between BMI categories and combined outcomes (incidence of RRT and ACM) across the 4 groups of different clusters of co-morbidity. Results A total of 2416 patients were included in the analysis. The median age of the cohort was 67.3 years [IQR 55.9-75.6], 61.8% were male, and 96.4% were of white ethnicity. The median BMI was 28.1 kg/m2 [IQR 24.7-32.6] and the median estimated glomerular filtration rate (eGFR) was 30.7 ml/min/1.73m2 [IQR 20.4-43.5]. At baseline, patients with increasing level of co-morbidity tended to be older with higher prevalence of hypertension (HTN), angina, myocardial infarction (MI), and stroke with lower baseline eGFR. The risk of combined outcomes followed the same trend in the three BMI groups, risk is higher with higher index of co-morbidity (p <0.001). Further analysis of four subgroups of co-morbidity was undertaken. A univariate Cox regression analysis for group 1 [CKD only, n = 1351], and group 2 [CKD and HF, n = 227] showed that patients with obesity had significant lower rates of combined outcomes compared to patients with normal BMI (HR 0.75; 95%CI = 0.63-0.89; p = 0.001 and HR 0.56; 95%CI = 0.38-0.82; p = 0.003 for group 1 and group 2 respectively). In multivariate models, obesity consistently proved to be a strong protective factor against combined outcomes (HR 0.77; 95%CI = 0.65-0.92; p = 0.005 for group 1 and HR 0.53; 95%CI = 0.34-0.83; p = 0.005 for group 2). This was independent of age, gender, HTN, angina, stroke, MI, and prescription of statins and angiotensin converting enzyme inhibitors. For group 3 [CKD and DM, n = 614], and group 4 [CKD, DM, and HF, n = 190], there was no significant difference in the combined outcomes between the different BMI groups when using univariate Cox regression analysis (for patients with obesity: HR 0.78; 95%CI = 0.61-1.01; p = 0.060 and HR 0.70; 95%CI = 0.43-1.16; p = 0.166 for both groups respectively). There was no significant difference in the incidence of RRT in any of the four groups. Conclusion In our largely white NDD-CKD cohort of patients, there was evidence of increasing risk of RRT or ACM as comorbidity increased irrespective of BMI. This is not surprising as ACM would be expected to increase as the burden of disease increases. However, when comparing the effect of BMI within groups, obesity was protective against combined outcomes in group 1 (CKD only) and group 2 (CKD+HF). This ‘protective’ effect was not seen in patients who had concomitant diabetes. These data suggest that diabetes is a potent predictor of outcomes irrespective of BMI, however, in patients without diabetes, obesity may play a protective role.