*1.1. Epidemiology*

In adults within a large, community-based population, in an integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not been supported with dialysis or undergone kidney transplantation, an independent, ranked association between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization was reported. As GFR decreased from 59 to 45 (mL/min/1.73 m2), the risk of death increased to 1.8 reaching gradually the highest values of almost 6 times more in the end stage renal disease patients [1]. Similar results for the association of CKD progression with cardiovascular disease and death was also reported in metanalysis studies [2,3]. The unadjusted prevalence of stage 3 and 4 CKD in USA increased from the late 1990s to the early 2000s with a rise in the prevalence of diabetes, hypertension, and obesity. However, the overall prevalence has stabilized since 2003 to 2004 and 6.9% of the population has CKD in 2011 to 2012. Reasons for the recent

**Citation:** Kotsis, V.; Martinez, F.; Trakatelli, C.; Redon, J. Impact of Obesity in Kidney Diseases. *Nutrients* **2021**, *13*, 4482. https://doi.org/ 10.3390/nu13124482

Academic Editors: Fernando Fernandez-Aranda, Janet Treasure and Empar Lurbe

Received: 4 November 2021 Accepted: 10 December 2021 Published: 15 December 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

stabilization of overall CKD prevalence despite continued aging of the U.S. population and the increased prevalence of obesity include better control of hypertension, successful glycemic control with the newer drugs, and expanded use of medications blocking the renin–angiotensin system in patients with proteinuria [4]. In the UK, the prevalence of eGFR < 60 mL/min/1–73 m<sup>2</sup> was 7.7%, 7.0% and 7.3% in 2003, 2009/2010, and 2016, respectively initially decreased in 2010 but again increased in 2016 [5]. At the same time in the UK the prevalence of diabetes and obesity increased during 2003–2016, while prevalence of hypertension and smoking fell.

Beyond the impact of diabetes and hypertension on the increased risk of CKD in the obese patients, the direct role of obesity in kidney injury has been demonstrated in animal models and epidemiological studies in humans. BMI has been reported as an independently significant factor for the development of CKD in most studies [6–10] with an odds ratio from the lowest to the highest BMI of 1.273 for developing ESKD, after adjustment for age, sex, systolic blood pressure, and proteinuria [6], but obesity risk appeared largely mediated by diabetes and hypertension in other studies [8] or not to be associated with ESKD [11]. A recent metanalysis of studies from a general population with normal baseline renal function reported that obesity increased the relative risk of developing low eGFR by 1.28 and albuminuria by 1.51 [12]. Table 1 collected studies of CKD risk in adults with metabolic syndrome.


**Table 1.** Risk of CKD in adults with metabolic syndrome (·MS).

Nondiabetic participants with normal baseline kidney function and metabolic syndrome according to the National Cholesterol Education Program who were included in the Atherosclerosis Risk in Communities study had an adjusted risk of developing CKD of

1.43 compared with participants with no features of the metabolic syndrome [19]. Central fat distribution indices, i.e., waist to hip circumference or visceral fat, are better related with the risk of ESKD compared to BMI [26–28]. Meta analyses reported that metabolic syndrome components such as obesity, impaired fasting glucose, elevated blood pressure, and hypertriglyceridemia were associated with significant increases in proteinuria and albuminuria risk [25].

Metabolically healthy obesity (MHO) is an obesity phenotype that obesity is not associated with metabolic complications such as insulin resistance, inflammation, hypertension, or T2D. Compared with metabolically healthy non-obesity phenotype, the odds ratios for incident CKD for MHO were similar to the comparison group, but significantly increased for metabolically abnormal non-obese and obesity phenotype respectively after adjustment for confounders [29–31]. However, other studies reported that MHO may have an intermediate future risk to develop ESKD.
