Anthropometric Measures of Adiposity as Markers of Kidney Dysfunction: A Cross-Sectional Study

It is well established that the obese state not only represents a key variable for defining cardiovascular and metabolic risk but it also contributes to an impaired kidney function [1]. Specifically, excess visceral fat, rather than obesity in general, represents the main link between obesity and kidney function [2]. Obesity may impair renal function directly or indirectly throughout the influence of hormones, development of insulin resistance, low-grade inflammation, adipokines, oxidative stress, protein glycation, sympathetic and endothelial dysfunction, as well as throughout related comorbidities such as type 2 diabetes mellitus, hypertension, dyslipidaemia and accelerated vascular atherosclerosis [3, 4].

Assessment of body mass index (BMI) allows to identify the obese state as a leading cause of increased mortality in various metabolic disorders [5], although BMI does not provide differentiation between fat mass and muscle mass and information on the distribution of fat in specific body areas. These significant limitations cast doubt upon the effectiveness of BMI in practical use, potentially favoring the occurrence of erroneous assessments of adiposity, closely related to individual height. Moreover, the inadequacy in gauging central obesity is of particular concern, given that abdominal fat represents a more accurate indicator of cardiovascular and metabolic risk when compared to overall body fatness [6].

Fat mass and its distribution can be assessed by imaging techniques such as computed tomography and magnetic resonance as well as by ultrasound and dual energy X-ray absorptiometry (DXA). However, the limited availability of expensive devices, high maintenance costs, and requirement of skilled operators may hinder the application of these methods in clinical practice and in research [7]. Given all the above mentioned limitations various body adiposity indices have been proposed throughout the years to assess body shape. Some indicators reflect intra-abdominal fat or “central obesity” such as waist circumference (WC), waist-to-hip ratio (WHR) or weight-adjusted-waist index (WWI). Other markers may better reflect body fat distribution and total fat mass such as ta body shape index (ABSI), waist-to-height ratio (WHtR) and relative fat mass (RFM). Additional others such as the lipid accumulation product (LAP) or the visceral adiposity index (VAI) may be better predictors of visceral fat function associated with cardiovascular risk [8‐13]. The present study was designed to investigate the association between the above mentioned obesity markers, as alternative to BMI, and renal failure.

The results of the present study provide evidence that among different anthropometric markers of adiposity WHR, LAP and VAI represent those more closely associated with renal dysfunction. After correction for various covariates, these variables confirmed their nature as risk factors for renal impairment, showing a greater predictive ability for kidney dysfunction than other anthropometric indices. Interestingly, one of these markers, WHR (and its closely related covariable WHtR) has been shown to represent the best predictor of cardiovascular disease and hypertension development in Asian populations [11, 13]. The present findings expand this information providing evidence that the predictive value of WHR also applies to renal dysfunction as well and that this association can be detected also in a general European population.

The present study was not aimed at investigating the pathophysiological mechanism responsible for the adverse impact of the obese state, particularly of visceral type, on renal function. Several pathways have been identified by previous studies, however [3, 4, 17] Indeed obesity impairs kidney function via the direct effects that adiposity exerts on the kidney, and indirectly due the systemic complications of obesity including diabetes mellitus, vascular atherosclerosis and hypertension [18]. Excess adipose tissue in and around the kidneys may increase the volume of renal sinus fat and peri-renal fat and might result in compression of the thin loop of Henle and vasa recta of the renal medulla, determining alterations in tubular function. Furthermore, the reduction in sodium chloride concentration triggers a macula densa feedback which increases glomerular filtration and maintains sodium balance by activating the renin-angiotensin-aldosterone system. Two additional mechanisms involved in the association between obesity and renal dysfunction are worthy to be mentioned. First, the sympathetic overactivity characterizing the obese state which may represent a factor favoring the progression of the renal disease [19]. An additional factor is represented the adipocytes synthesis of several important adipokines which are implicated not only in insulin resistance but also in inflammation and other physiological processes. All these pathogenetic changes may promote progression of renal dysfunction [20, 21].

There is a consensus that adipose tissue anatomical distribution, and particularly central obesity, is important for determining the impact of obesity on renal dysfunction [22]. BMI does not reflect the fat distribution or even the total adipose tissue level because it is affected by muscle mass [8]. Indeed, many patients with chronic kidney disease in the advanced clinical stages often suffer from chronic caloric consumption, thus, relying only on BMI to evaluate body fat may lead to the so called “obesity paradox” [23, 24]. Likewise, volume overload often detected in kidney disease may also interfere with the ability to assess BMI. WC represents a marker commonly used to reflect abdominal fat accumulation. However it is unable to distinguish subcutaneous adipose and visceral adipose tissue [25]. Evans and coworkers found significant correlations between WHR and estimated GFR decline, increase in urinary albumin‐creatinine ratio and uric acid levels [2]. In another study, Lin and colleagues found in non-diabetic patients with chronic kidney disease that visceral obesity and large proportion of body fat mass was associated with an adverse clinical outcome when compared to normal weight patients and patients with overweight and obesity alone [26].

The present study has some limitations. First, the present study was cross sectional not allowing to determine the ability of the various anthropometric variables to predict 10 year renal disease risk. Second, due the observational nature of this study, the possibility of unmeasured confounding factors, despite adjustment for known prognostic variables, still remains. In addition, because the majority of participants was middle-aged, caution should be made in extrapolating the conclusions of the present study to other age groups. Finally, it is difficult to establish the causality between the WHR, VAI, LAP and renal dysfunction based on this cross-sectional study. Future studies are thus needed to explore the relationships between dynamic chances in these anthropometric markers throughout years and renal disease progression.

In conclusion, WHR, LAP and VAI documented the best positive association with renal dysfunction among other obesity indicators. Anthromorphometric measures that include assessment of central fat deposition such WHR, LAP and VAI are more related to kidney disease than BMI. Relying on BMI alone may underestimate the risk for kidney disease and those anthropomorphic measurements focused on central fat deposition may be more important risk factors for chronic kidney disease than BMI. Future studies are required to investigate in longitudinal studies the ability of these indices in predicting outcomes and identifying high risk subjects for possible intervention.