Obesity-Related Kidney Disease: Current Understanding and Future Perspectives

Abstract

Obesity is a serious chronic disease and an independent risk factor for the new onset and progression of chronic kidney disease (CKD). CKD prevalence is expected to increase, at least partly due to the continuous rise in the prevalence of obesity. The concept of obesity-related kidney disease (OKD) has been introduced to describe the still incompletely understood interplay between obesity, CKD, and other cardiometabolic conditions, including risk factors for OKD and cardiovascular disease, such as diabetes and hypertension. Current therapeutics target obesity and CKD individually. Non-pharmacological interventions play a major part, but the efficacy and clinical applicability of lifestyle changes and metabolic surgery remain debatable, because the strategies do not benefit everyone, and it remains questionable whether lifestyle changes can be sustained in the long term. Pharmacological interventions, such as sodium-glucose co-transporter 2 inhibitors and the non-steroidal mineralocorticoid receptor antagonist finerenone, provide kidney protection but have limited or no impact on body weight. Medicines based on glucagon-like peptide-1 (GLP-1) induce clinically relevant weight loss and may also offer kidney benefits. An urgent medical need remains for investigations to better understand the intertwined pathophysiologies in OKD, paving the way for the best possible therapeutic strategies in this increasingly prevalent disease complex.

Keywords: chronic kidney disease; fatty kidney disease; obesity; obesity-related kidney disease; overweight.

Figure 1

Pathophysiological associations and therapeutic options in obesity-related kidney disease. Figure 1 shows the known or suspected obesity-related risk factors (yellow box) directly or indirectly implicated in the development of chronic kidney disease (CKD). CKD is traditionally categorized according to the presence and degree of albuminuria and glomerular filtration capacity (eGFR), and by a range of different kinds of kidney-specific damage, as well as resulting or exacerbating cardiovascular disease (red box). The green box shows approved or suggested/potential pharmaceutical or non-pharmaceutical interventions that may address obesity-related risk factors in CKD. Dashed and solid lines indicate potential and well-established associations/effects, respectively. Details are available in the text. Made with BioRender.com.