| Abstract|| |
Obesity is accompanied by several disorders. This study investigated the role of chronic renal disease on the linking obesity/hypertension (HTN). It also considered the importance of visceral obesity on renal disease with or without HTN. One hundred and forty seven subjects on mean age 68.9 ± 14.2 years old with visceral obesity were enclosed and they matched for the age, gender, estimated glomerular filtration rate (eGFR), diabetes mellitus, and hypertriglyceridemia to 52 people without visceral obesity as a control group. Visceral obesity was defined by the measurement of waist circumference. Our participants were classified in both eGFR and albuminuria categories according to the Kidney Disease Improving Global Outcomes 2012 criteria. The HTN ratio was equal to 89.1% in the patients’ group. Ratios of 72.1% and 70.1% of our patients and 67.3% and 23.1% of our control group had a low eGFR and albuminuria respectively. The relationship between central obesity and HTN was found to be nonsignificant, but in our subjects without an advanced renal disease (eGFR >60 mL/min/1.73 m2, n= 58) it was found to be significant (χ2 = 5.4, P = 0.02, likelihood ratio = 5.1). Albuminuria was significantly associated with both visceral obesity and visceral obesity with HTN (χ2 =34.7, P =, respectively) and it was supported by a built adjusted model. Chronic renal disease may influence the linki001 and χ2 = 37.7, P = 0.001ng obesity/HTN in elderly participants with obesity in contrast to the general population with obesity but without renal disease. Visceral obesity was significantly associated with albuminuria independently on HTN.
|How to cite this article:|
Raikou VD, Gavriil S. The Role of Chronic Renal Disease on the Linking Obesity/Hypertension. Saudi J Kidney Dis Transpl 2021;32:1637-45
|How to cite this URL:|
Raikou VD, Gavriil S. The Role of Chronic Renal Disease on the Linking Obesity/Hypertension. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Sep 25];32:1637-45. Available from: https://www.sjkdt.org/text.asp?2021/32/6/1637/352424
| Introduction|| |
Obesity, which is defined as excessive fat accumulation, is an increasing problem world-wide. Obesity is associated with a higher risk of cardiovascular disease (CVD), type 2 diabetes mellitus (DM), dyslipidemia, cancer, and chronic kidney disease (CKD). Furthermore, obesity was connected with a shortened life expectancy in the general population. Therefore, prevention and early detection of obesity are extremely important. Obesity is commonly measured by body mass index (BMI) and visceral obesity is characterized by measurements of waist-to-hip ratio (WHR) and/or waist circumference (WC).
CKD also shows an increased prevalence rate, particularly in aging people. Nondialysis elderly patients have become prevalent in nephrology clinics. It is estimated that the number of elderly patients in end-stage renal disease (ESRD) and dialysis has almost doubled in the past 25 years, despite the general notion that elderly people are more likely to die due to other reasons than to reach ESRD. Most studies used glomerular filtration rate (GFR) to identify CKD (GFR <60 mL/min/1.73 m2) and a few of them have combined GFR and albuminuria categories, both of which are required for the diagnosis of CKD.
Moreover, hypertension (HTN) in combination with DM are traditional risk factors and potential leading causes for the development of CKD. Reversely, renal function plays an important role in initiating HTN, particularly during obesity by multiple mechanisms including increased renal tubular sodium reabsorption and activation of the renin-angiotensin-aldosterone system (RAAS). In the meantime, it has been reported that the association between a high BMI and the risk of CKD and its progression was similar among subjects with and without HTN, diabetes, or CVD, despite being overweight increases the risk of advanced CKD in people with these comorbidities.
Nevertheless, the effect of obesity in population with CKD and comorbidities is unclear. Recent study reported that obesity did not confer an increased risk of ESRD in patients with moderate to advanced CKD. On the other hand, it has been recently reported that the age over 75 years is associated with decreased risk for ESRD even adjusting for competing mortality risk factors, although it has been already supported that proteinuria increases ESRD risk.
In this study, we aimed to investigate the role of the existence of chronic renal disease on the linking between obesity/HTN and to consider the importance of visceral obesity on renal disease with or without HTN as comorbidity.
| Materials and Methods|| |
This is a single-center cross-sectional study, in which 147 participants were enclosed with visceral obesity as the main inclusion criteria. The participants were consecutively collected from the Department of Nephrology outpatient clinic of our Hospital, in which the nondialysis elderly patients are prevalent in accordance to the most Nephrology Clinics worldwide., We also collected 52 people (29 males and 23 females) without visceral obesity as a control group, who should have similar age, gender, classified estimated GFR (eGFR) value, DM and hypertriglyceridemia comparatively with the enrolled in the study participants as inclusion criteria. We noted the number of our participants with HTN (n = 173) and the number of the subjects with HTN in combination to central obesity (n = 131).
We studied 75 males and 72 females on mean age 68.9 ± 14.2 years old. Our exclusion criteria mostly included the uncooperative patients and those who were younger than 18 years of age. Subjects with established dementia or psychiatric symptomatology diagnosed by neuropsychologists had been also excluded from the study.
Detailed individual medical histories and the current pharmaceutical therapy were obtained from the participants. Everybody of the enrolled subjects and control group, who had HTN, was receiving the same antihypertensive medications including calcium channel blockers, beta-blockers, and inhibitors of angiotensin II AT1 receptors. Some participants and control subjects were also using hypoglycemic therapy (n = 41, 27.9% and n = 16, 30.8%, respectively) and hypolipidemic medications (n = 84, 57.1% and n = 31, 59.6%, respectively).
Demographic data including age, gender and lifestyle characteristics regarding current smoking, alcohol drinking, and physical activity were collected using questionnaire. Participants who declared no alcohol consumption during the past month were considered non-drinkers. Physical activity/inactivity was measured based on the World Health Organization (WHO) recommendations for healthy adults.
Anthropometric measurements including height (to the nearest 0.1 cm), body weight (to the nearest 0.1 kg) were recorded by our staff using an anthropometer (Seca, Hamburg, Germany). BMI was calculated by dividing the body weight in kilograms by the square of the height in meters (kg/m2) and categorized based on the WHO classification into underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2). WC measurements made approximately at the midpoint between the lower margin of the last palpable rib and the top of the iliac crest at the end of a normal expiration according to the WHO guidelines and were also recorded by our trained staff.
Overnight fasting plasma glucose, creatinine, triglycerides, high-density lipoprotein cholesterol were recorded from the patient files using the latest results. Biochemical markers were measured using spectrophotometric technique by Chemistry Analyzer (MINDRAY BS-200, Diamond Diagnostics, USA) and were represented as mg/dL.
Spot urine samples from the first-morning void were used for the measurement of albumin and creatinine concentrations by the Chemistry Analyzer.
As hypertensive were defined the subjects, who had a mean systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure (DBP) ≥85 mm Hg and/or those of the participants who were taking antihypertensive therapy due to pre-existed individual history of HTN according to the International Diabetes Federation (IDF) criteria for metabolic syndrome diagnosis.
The presence of chronic renal disease was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria for a duration time more than 3 months. The eGFR was calculated using the CKD Epidemiology Collaboration (CKD-EPI) equation and classified into five categories according to KDIGO 2012 criteria. The enrolled subjects were also classified based on albuminuria, which was defined as urinary albumin-to-creatinine ratio (ACR) ≥30 mg/g according to KDIGO 2012. ACR calculation by using a spot urine sample, such as in this study, is considered an acceptable calculation, as ACR is correlated well with 24-h urinary albumin excretion.
The central/visceral obesity was determined by a WC ≥94 cm in males and ≥80 cm in females using the IDF criteria for metabolic syndrome diagnosis.
| Data analysis|| |
Data were analyzed using SPSS 15.0 Statistical Package for Windows (SPSS Inc, Chicago, Illinois, USA) and expressed as mean ± standard deviation or as median value ± interquartile range for data that showed skewed distribution. Differences between mean values were assessed by using unpaired t-test for two groups and data that showed skewed distributions were compared with Mann-Whitney U- test.
Correlations between categorical variables were defined by Chi-square tests. P values less than 0.05 were considered significant. We built a model using linear regression analysis by enter method for the role of visceral obesity on the development of albuminuria adjusting for covariates including age, gender, BMI, DM, triglycerides, HTN, eGFR value, and WC. Power calculation was per-formed at the end of the study using the Power and Precision statistical package (version 3.0, Biostat, Englewood, NJ, USA) and the sample size was sufficient.
| Results|| |
In Table 1, the differences between the patients with central/visceral obesity and the control group are shown. We observed that the patients with central obesity had significantly higher BMI and albuminuria than the control group. The age, eGFR value, serum triglycerides and serum glucose did not differ between central obesity group of patients and control group according to our inclusion criteria. The systolic and diastolic blood pressure values in central obesity and control groups were also observed similarly. The prevalence rate of HTN in our data was equal to 89.1% (n = 131) for our patients’ group and 80.8% (n = 42) for our control group and all of them were receiving the same antihypertensive therapy. Type 2 DM was in a ratio of 27.9% (n = 41) and 30.8% (n = 16) in the patients group and control group, respectively. A ratio of 72.1% (n = 106) and 67.3% (n = 35) of our patients and control group had a low eGFR respectively. Furthermore, a ratio of 70.1% (n = 103) and 23.1% (n = 12) of patients and control group had albuminuria respectively. The underlying renal disease in both groups included hypertensive nephrosclerosis, diabetic nephropathy, chronic glomerulonephritis, interstitial nephritis, polycystic disease, and other/unknown [Table 1].
|Table 1. The differences between visceral obesity group of patients (n=147) and non-visceral obesity control group (n=52).|
BMI: Body mass index, HDL-C: high-density lipoprotein-cholesterol, ACR: Albumin-to-creatinine ratio in urine sample, eGFR: Estimated glomerular filtration rate, *P <0.05.
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The association between visceral obesity and HTN was found to be non-significant in the total of the studied population. However, in our data without a low eGFR (>60 mL/min/ 1.73 m2) (n = 58, a ratio equal to 29.1% in the total of our participants including the participants with obesity and control group, n = 199) the association between central obesity and HTN was found to be significant (χ2 = 5.4, P = 0.02, likelihood ratio = 5.1, [Figure 1]. In contrast, in our data with a low eGFR (<60 mL/min/1.73 m2) (n = 141, a ratio equal to 70.9% in the total of our data) the relationship between central obesity and HTN was found to be non-significant.
|Figure 1. Bar chart showing the relationship between visceral obesity defined by a high waist circumference and hypertension in patients without a low eGFR (eGFR >60 mL/min/1.73 m2) (n=58) in percentage rate of patients (χ2=5,4, P = 0.02, Likelihood ratio = 5.1).|
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Moreover, Chi-square tests showed significant association between visceral obesity and albuminuria (χ2 = 34.7, P = 0.001, Figure 2). The relationship of albuminuria with both HTN and HTN in combination with obesity was also found significant (χ2 = 8.9, P = 0.003 and χ2 = 37.7, P = 0.001 respectively).
|Figure 2. Bar chart showing the relationship between visceral obesity defined by a high waist circumference and albuminuria (urinary albumin-to-creatinine ratio >30 mg/g) in comparison to normal waist circumference in percentage number of patients (χ2 = 34.7, P = 0.001).|
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The built adjusted linear regression analysis model for albuminuria prediction showed that both the presence of central obesity and the low eGFR value was found to be significant predictors adjusting to the age, gender, BMI, DM, serum triglycerides, and HTN [Table 2].
|Table 2. Visceral obesity as a potential determinant of albuminuria including covariates in our data (n=147).|
Dependent variable: urinary albumin-to-creatinine ratio (ACR, mg/gr).
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| Discussion|| |
According to the WHO, the definition of obesity includes the rate of body fat, which is mainly calculated by a body composition monitor as body fat percentage >25% in men and >35% in women and its accuracy has been validated against of the dual-energy X-ray absorptiometry (DEXA) that is the gold standard reference method., However, because such direct measurement of fat is difficult in clinical practice, BMI, WHR, and/or WC measurements are used as screening tools for obesity.
In this study, we used the WC measurement >94 cm for men and >80 cm for women for the definition of central/visceral obesity and the BMI calculation to classify the normal, overweight, and/or obese participants.
We observed that the patients with central obesity had significantly higher albuminuria than the control group and the unadjusted association between central obesity and albuminuria was found to be extremely significant. The high WC was also found to be a significant risk factor for albuminuria prediction in our adjusted model including potential confounders in agreement with previous reports.,
Visceral adipose tissue has been considered the active organ, which is mainly connected with the pathophysiological mechanisms of obesity-induced kidney disease including elevated insulin resistance. The produced by adipose tissue adipokines promote chronic inflammation and oxidative stress that exacerbate insulin resistance. Insulin resistance and inflammation are associated with multiple abnormalities including endothelial dysfunction, reduced synthase of endothelial nitric oxide, worsening of renal hemodynamic, and injury of podocytes resulting in HTN and albuminuria.
However, multiple factors influence the manifestation of albuminuria in overweight/ obese CKD patients including old age, DM, HTN, antihypertensive medications, and hyperlipidemia. Indeed, these comorbidities are connected to insulin resistance. It has been particularly reported that insulin resistance is associated with hyperlipidemia defined by overproduction of low-density lipoprotein cholesterol and hypertriglyceridemia, which may impair the mitochondrial function and promote kidney cell damage resulting in albuminuria. In this study, old age, DM and hypertriglyceridemia may not be prevalent factors for the demonstration of albuminuria, due to our inclusion criteria for the properly matched control group. Regarding the role of HTN we observed a non-significant association between central obesity and HTN, which is commented below, and the absolute values of blood pressure did not differ in our groups with and/or without visceral obesity. The total of our participants with HTN also received the same anti-hypertensive treatment. Therefore, visceral obesity could be considered as the main risk factor for the manifestation of albuminuria in our data.
Furthermore, we defined the similar eGFR value between patients and control subjects to be another inclusion criteria because eGFR value influences the demonstration of albuminuria. Indeed, our adjusted model showed the low eGFR value to be a significant risk factor for albuminuria prediction in combination with central obesity including confounders. Albuminuria is an early marker of kidney injury and is commonly associated with a low eGFR in CKD.
In the meantime, albuminuria was significantly associated with both HTN and HTN in combination with obesity in our data. These findings are in agreement with those previously reported that obesity is a significant predictor for CKD independently on HTN existence and that the combination between obesity and HTN exacerbates the cardiovascular and kidney disease.
Nevertheless, in this study, we observed that the association between HTN and visceral obesity was found to be non-significant in discordance to previous reports in the general population with obesity. Visceral obesity raises blood pressure by renal vascular dilatation, hyperfiltration, increasing renal tubular sodium reabsorption, impairing pressure natriuresis and causing volume expansion, which is additionally caused by the activation of the sympathetic nervous system and RAAS. Moreover, visceral adiposity results in physical compression of the kidneys medulla, which contributes to the increased sodium reabsorption. Other covariates such as inflammation, oxidative stress, and lipotoxicity also contribute to obesity-mediated HTN. It has been also reported that an abnormality of the natriuretic peptide system has a central role in adipocyte dysmetabolism and HTN.
During the impaired renal function, such as in our data (a ratio of 72.1% had a low eGFR), the above mechanisms connected to the HTN may be altered in comparison to general population with obesity. Indeed, the relationship between obesity and HTN was found to be significant in our participants without an advanced renal disease (eGFR >60 mL/min/ 1.73 m2) controversially to the finding using our patients with a low eGFR (eGFR <60 mL/min/1.73 m2). The glomerulo-tubular and tubulo-glomerular feedback mechanisms, which contribute to the increased sodium reabsorption and the manifestation of HTN in obesity, may be disordered in conditions of impaired renal function (natriuretic nephropathy). Moreover, hyperleptinemia is considered the most probable mechanism by which obesity may increase sympathetic activity and HTN. However, in impaired renal function has been reported acquired leptin receptor resistance, having perhaps, as a result, an inverse impact on the manifestation of HTN in chronic renal disease with obesity. On the other hand, other connected to HTN adipokines in obesity including the protective adiponectin may be altered in chronic renal disease, due to its passive accumulation from reduced renal excretion.
The above quests could be included to the possible mechanisms for what we did not find a strong linking between obesity and HTN in our participants, such as in the general population with obesity. However, more studies need to certify such an observation.
| Conclusion|| |
The linking between obesity and HTN may be confused by the existence of the chronic renal disease in elderly subjects with obesity in contrast to the general population with obesity but without renal disease. Visceral obesity was significantly associated with albuminuria independently of the existence of HTN as comorbidity.
| Compliance with Ethical Standards|| |
The study was approved by the Hospital Institutional Review Board. All procedures were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed oral consent was obtained from all individual participants included in the study.
Conflict of interest: None declared.
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Vaia D. Raikou
Department of Nephrology, Doctors’ Hospital, Athens, Greece.
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]
[Table 1], [Table 2]