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Abstract

Metabolic syndrome (MetS) is a group of conditions characterized by hypertension (HTN), hyperglycaemia or insulin resistance (IR), hyperlipidaemia, and abdominal obesity. MetS is associated with a high incidence of cardiovascular events and mortality and is an independent risk factor for chronic kidney disease (CKD). MetS can cause CKD or accelerate the progression of kidney disease. Recent studies have found that MetS and kidney disease have a cause-and-effect relationship. Patients with CKD, those undergoing kidney transplantation, or kidney donors have a significantly higher risk of developing MetS than normal people. The present study reviewed the possible mechanisms of MetS in patients with CKD, including the disorders of glucose and fat metabolism after kidney injury, IR, HTN and the administration of glucocorticoid and calcineurin inhibitors. In addition, this study reviewed the effect of MetS in patients with CKD on important target organs such as the kidney, heart, brain and blood vessels, and the treatment and prevention of CKD combined with MetS. The study aims to provide strategies for the diagnosis, treatment and prevention of CKD in patients with MetS.

Keywords

chronic kidney disease glucose metabolic disorders metabolic syndrome pathological characteristics therapeutics

Introduction

Metabolic syndrome (MetS) is a group of conditions characterized by metabolic abnormalities. The World Health Organization proposed the diagnostic criteria for MetS in 1998¹; however, the diagnostic criteria and evaluation components for MetS proposed by various countries and related organizations are not uniform.² Nonetheless, the criteria mainly include serum glucose levels, body mass index (BMI), waist circumference (WC), waist–hip ratio, hypertension (HTN), central adiposity, high-density lipoprotein (HDL), cholesterol and triglyceride (TG) levels and impaired glucose tolerance.^3–7 These risk factors independently or cooperatively participate in or aggravate the damage to important target organs such as the heart, brain, blood vessels and kidney.^8–12 MetS can lead to changes in the structure and function of the kidneys in patients with no underlying kidney disease and can result in proteinuria and a decrease in the glomerular filtration rate (GFR). These findings have been confirmed in a large number of clinical studies in different countries.^13–16 Recent studies have found that the prevalence of MetS in patients with kidney disease is significantly higher than that in patients without kidney disease. To date, the mechanism of MetS in patients with chronic kidney disease (CKD) is not completely clear. The present study summarizes the mechanisms of MetS in patients with CKD, the effect of MetS on the kidney, heart, brain, blood vessels and other important target organs and the treatment and prevention of MetS.

Epidemiological characteristics of MetS in patients with CKD

The prevalence of MetS is not the same in patients of different races, sex and ages. It is estimated that the global prevalence of MetS is 20–25%,¹⁶ and the prevalence of CKD in patients with MetS is twice that in patients without MetS.¹⁷ A meta-analysis of 66 studies involving more than 30 countries revealed that MetS increases the risk of CKD by 50%.¹⁸ Recent studies have found that patients with CKD have a higher risk of MetS. Studies from different countries on patients with different CKD stages, dialysis treatment and renal transplantation revealed that the prevalence of MetS in non-dialysis patients with CKD was 42.0–82.1%,^17,19–25 and in CKD stages 3–5 was 39.0–72.3%, 57.0–73.4% and 46.0–72.7%, respectively.^22,23,26 The prevalence of MetS in non-dialysis patients with CKD was different due to various causes, such as chronic interstitial neuropathy (80%), CKD of uncertain aetiology (76.7%), CKD related to vascular causes (76.2%) and diabetic nephropathy (71.3%).^24,26 The prevalence of MetS in patients undergoing dialysis was relatively low (38.6–55.7%),^27,28 which may be related to malnutrition in these patients. Higher age, female sex, being married, higher BMI, larger WC, Type 2 diabetes (T2D) and HTN, shorter haemodialysis (HD) duration, longer interval after placement of arteriovenous fistula, high post-HD creatinine levels, inadequate HD and hyperparathyroidism are risk factors of MetS.²⁷ The probability of MetS in patients undergoing renal transplantation was found to be 34–68%, and the difference was closely related to the types of immunosuppressant drugs received after transplantation.^28,29 Table 1 shows the prevalence of Mets in CKD patients.

Table 1.

The prevalence of Mets in CKD patients.

Author	Years	Country/region	Object	Prevalence (%)	Subgroup	Reference
Pammer	2021	German	CKD	64.30	–	19
Chen	2017	China	CKD	58.40	–	17
Hana’a	2018	Israel	CKD	82.10	–	20
Li	2022	China	Non-dialysis CKD	62.60	–	21
Chang	2021	Taiwan, China	CKD3–5	64.70	CKD3 (63.5%), CKD4 (66.7%), CKD5 (64.8%)	22
Tsai	2018	Taiwan, China	CKD3–5	42.00	CKD3a (39.0%), CKD3b (49.0%), CKD4 (57.0%), CKD5 (46%)	23
Boronat	2016	Spain	Non-diabetes CKD	68.90	Chronic interstitial nephropathy (80%), CKD of uncertain aetiology (76.7%) and CKD related to vascular causes (76.2%)	24
Hung	2022	Taiwan, China	Non-diabetic CKD1–4	50.55	–	25
Kittiskulnam	2018	Thailand	Diabetic CKD	71.30	CKD3a (70.1%), CKD3b (72.3%), CKD4 (73.4%), CKD5 (72.7%)	26
Alswat	2017	Saudi Arabia	HD	38.60	–	27
AlShelleh	2019	Jordan	Transplant patients and dialysis	34.0, 55.7	–	28
Maduram	2010	USA	Paediatric renal transplant recipients	68.00	–	29

CKD, chronic kidney disease; HD, haemodialysis.

The mechanism of MetS in patients with CKD

The kidney is an important organ that maintains the balance of glucose and lipids and has been proven to participate in the pathogenesis of MetS through a variety of mechanisms. Studies have reported that it can cause haemodynamic changes, sympathetic nerve excitation, increased reactive oxygen species (ROS) production, activation of the Renin Angiotensin Aldosterone System (RAAS) system and adipokine abnormalities through insulin resistance (IR), obesity, HTN and hyperlipidaemia.^30–33 IR appears to be the central mechanism of MetS. The risk of MetS in patients with CKD is approximately twice as high as that in non-CKD patients. The increased risk of MetS in patients with CKD can be attributed to a variety of pathophysiological mechanisms. CKD itself can lead to multiple metabolic abnormalities that are characteristic of MetS, including IR, HTN and dyslipidaemia.^34–37 In addition, CKD patients often have decreased physical activity and poor dietary habits, which can further contribute to the development of MetS. Inflammation and oxidative stress, which are common in CKD, can also play a role in the development of MetS by promoting IR and endothelial dysfunction. The pathogenesis of MetS in CKD patients is shown in Figure 1.

Figure 1.

The pathogenesis of MetS in CKD patients.

Insulin resistance

IR plays a predominant role in MetS.³⁸ Studies have reported an obvious IR, which is linearly related to the estimated GFR (eGFR) in patients with non-diabetic nephropathy, even in the early stage of CKD with normal eGFR. Similarly, patients on continuous ambulatory peritoneal dialysis (CAPD) and those who have undergone kidney transplantation have IR.^39–41 Chronic inflammatory state, mitochondrial damage, accumulation of uremic toxins, renal tubulointerstitial and renal arteriolar lesions, bone mineral metabolism disorder in CKD patients, etc. through oxidative stress, ROS, interleukin-6, monocyte chemotactic protein 1, tumour necrosis factor α and transforming growth factor-β1 IR in CKD patients are caused by the increase of ROS activity, the activation of RAAS system, the increase of proinflammatory factors release and the lack of vitamin D, which cause IR.^42–48 Recent studies have found that the renal–brain peripheral sympathetic reflex may also mediate IR in patients with CKD. Local inflammation and high salt intake after activation of RAAS/ROS may reduce glucose transporter 4 (GLUT4) output, thus triggering IR in patients with CKD.⁴⁹

Lipoprotein abnormalities

Studies have reported that abnormal blood lipids in patients with CKD manifest as high TG and low HDL levels, which were not significantly higher than total cholesterol and low-density lipoprotein (LDL) levels.^50–52 CKD patients generally have IR, hepatic lipoprotein and dialysis with glucose lead to increased synthesis of free fatty acids and very low density lipoprotein (VLDL), resulting in high TG levels.⁵³ In addition, the decreases in the liver lipoprotein lipase and hepatic lipase levels and VLDL receptor expression, as well as the increase in Apolipoprotein CIII (ApoC Ill) and parathyroid hormone levels, decrease the decomposition of VLDL. This leads to the accumulation of a large amount of VLDL in the body, which is an important reason for the increase in TG levels in patients with CKD.^54–57 In recent years, studies have found that the level of irisin is significantly lower in patients with CKD than that in normal people, and the decline is more obvious with the progression of CKD.⁵⁸ However, the level of irisin has been shown to increase in patients undergoing renal replacement therapy.⁵⁹ Studies have also reported decreased serum irisin levels in patients undergoing HD, and it is related to the increased mortality rate in cardiovascular and cerebrovascular diseases.⁶⁰ In conclusion, irisin plays an important role in maintaining the levels of HDL and cholesterol as well as lipid metabolism in patients with CKD.⁶¹

Hypertension

HTN is very common in patients with CKD. Many mechanisms lead to the persistence of HTN in patients with CKD and play an important role in various cardiovascular events. Similarly, HTN promotes the occurrence of MetS in patients with CKD through various mechanisms. The main mechanisms are as follows: (1) In HTN, the increase in aldosterone level leads to the activation of the RAAS that induces IR.^32,37,62 (2) Renal tubulointerstitial injury leads to renal ischaemia, hypoxia, the release of proinflammatory factors and inflammatory reaction, with an increase in Angiotensin II (AngII) production.^63–66 (3) The lower levels of leptin, adiponectin, Klotho and adropin^67–70 in patients with CKD may be involved in the development of MetS. Leptin is closely associated with HTN, which is induced by upregulating the renin–angiotensin system and inflammation.⁷¹ The clearance of leptin is reduced in patients with CKD due to renal dysfunction, and lipid metabolism is disturbed due to hyperinsulinaemia and chronic inflammation, among other factors.^72–74 Adropin is a new polypeptide involved in energy metabolism and stability. Adropin regulates energy metabolism and protects the cardiovascular system by producing nitric oxide and regulating blood pressure.⁷⁵ Studies have reported significantly reduced serum adropin levels in patients with primary HTN, those on maintenance HD and kidney transplant recipients.^70,76,77

Specific treatment for CKD

The specific treatment mode of CKD may lead to an increased risk of MetS. For example, continuous absorption of glucose in the dialysate through the peritoneum leads to abnormal glucose and lipid metabolism.⁷⁸ The rate of increase in fasting blood glucose levels reached 23.4% in patients on CAPD.⁷⁹ However, some studies have shown that new diabetes in patients with peritoneal dialysis is not closely related to the glucose load or peritoneal transport but to IR and obesity.⁸⁰ Immunosuppressive agents are an important cause of CKD, especially MetS, in renal transplant patients. Glucocorticoids mediate the rise in blood glucose levels through the following mechanisms: (1) increasing glucose resistance, (2) reducing insulin secretion and (3) inducing apoptosis of beta cells in the islets of Langerhans.⁸¹ A meta-analysis showed that the incidence of new abnormalities in glucose metabolism in renal transplant patients treated with steroids was significantly higher than in those who did not undergo transplantation.⁸² In addition, an increase in the activity of 11-β-hydroxysteroid dehydrogenase and the production of active glucocorticoids are closely related to MetS.⁸³ The calcineurin inhibitors (CNI) (cyclosporin and tacrolimus) can mediate abnormal glucose and lipid metabolism through the following mechanisms: (1) Direct toxic effect on cells to reduce insulin secretion.⁸⁴ (2) By affecting glucokinase function, cyclosporine causes decreased insulin secretion and apoptosis of islet β cells.⁸⁵ (3) CNI inhibits glucose uptake in peripheral tissues through the endocytosis of GLUT4, leading to increased blood glucose.⁸⁶ (4) CNI can cause hypomagnesaemia, increase cell calcium levels and reduce insulin secretion.⁸⁷ The effect of CNI on the metabolism of patients is dose-dependent.⁸⁴ The mammalian target of rapamycin inhibitor sirolimus can cause apoptosis of pancreatic β-cells and proliferation of the pancreatic duct cells,^88,89 leading to impaired insulin secretion and insulin signal transduction. In addition, long-term use of sirolimus leads to an increase in hepatic gluconeogenesis and IR.⁹⁰ In summary, various immunosuppressants lead to weight gain in patients with CKD by increasing appetite and fat distribution. Moreover, immunosuppressants increase blood pressure via retention of water and sodium, stimulation of the RAAS system, increasing sympathetic activity and direct contraction of blood vessels, among other mechanisms. These drugs lead to abnormal glucose metabolism by directly acting on the β cells in the islets of Langerhans, reducing insulin secretion and sensitivity, inhibiting the expression of the GLUT, reducing the muscle uptake and utilization of glucose and inhibiting glucokinase activity. Furthermore, immunosuppressants reduce the abnormalities in lipid metabolism caused by HDL^91,92 by increasing the activity of lipase, stimulating the liver to synthesize TG and VLDL, reducing the degradation of LDL, reducing the production of HDL-C and reducing the combination of cholesterol efflux and Apolipoprotein A, ultimately leading to MetS. The mechanism of immunosuppressive drugs inducing MetS is shown in Figure 2.

Figure 2.

The mechanism of immunosuppressive drugs inducing MetS.

Effect of MetS on target organs in patients with CKD

CKD and MetS are associated with a high incidence of cardiovascular events and mortality.^93–95 When two types of diseases exist simultaneously in patients, large-sample studies must be conducted to verify whether they will aggravate target organ damage. The animal study discovered that obesity lasting for just 2 months can induce albuminuria, potentially because of elevated inflammation or oxidative stress.⁹⁶ MetS can lead to proteinuria and a decline in renal function.⁹⁷ A Korean study on patients with CKD and MetS found that obesity and metabolic abnormalities (1.41 and 1.38 times, respectively) were significantly related to adverse renal outcomes [eGFR reduction >50% or progression to end-stage renal disease (ESRD)] after 3.1 years of follow-up. Patients with obesity and metabolic abnormalities had a 1.53 times increased risk of CKD progression.⁹⁸ A study conducted in China reported a significantly increased risk of CKD progression in patients with MetS (Odds Ratio (OR) = 1.4).³⁰ Similarly, a study conducted in Taiwan found that the renal survival time of patients with stage 3–5 CKD and MetS was significantly lower than that of patients without complications.²³ Similar results were reported by studies conducted in the United States on patients with stage 3–4 CKD. Furthermore, the risk of ESRD in patients with MetS increased 1.33 times. HTN, abnormal glucose and lipid metabolism were closely related to the increased risk of ESRD (OR values 1.83, 1.67 and 1.07, respectively).⁹⁹ The GFR of children with MetS decreased faster each year than those without the syndrome (65 versus 88 mL/min/1.73 m²).²⁹ The GFR of patients with MetS was lower 1.5 years after transplantation; however, there was no difference compared with patients without MetS 5 years after transplantation.¹⁰⁰ A German study found that the risk ratios of all-cause death and cardiovascular events in patients with CKD and MetS were 1.26 and 1.48, respectively. The risk ratio of all-cause death and cardiovascular events caused by abnormal glucose metabolism was the highest. The study found that the risk ratio increased to 1.50–2.50 with an increase in the components of MetS.¹⁹ A study conducted on patients with stage 3–5 CKD found that central obesity and all-cause mortality showed a U-shaped curve.¹⁰¹ Left ventricular hypertrophy in children with MetS who underwent kidney transplantation was found to be independently related to MS with elevated LDL cholesterol.¹⁰² Another study reported that the incidence of left ventricular hypertrophy and left ventricular eccentric hypertrophy was 2.6–3.0 times higher than that in patients without MetS.¹⁰³ Similarly, MetS has been reported to cause significant thickening of the carotid intima-media in African American renal transplant recipients.¹⁰⁴ These findings demonstrate that patients with MetS who have CKD and those who have undergone kidney transplantation have poor renal prognoses and experience cardiovascular complications.

Treatment of CKD combined with MetS

The chief goal of the treatment of CKD combined with MetS is to control each component of MetS. For obese patients, lifestyle interventions, such as diet restriction and aerobic exercise are conducive to weight control and an improvement in renal prognosis to achieve the standard weight.^105–107 A randomized controlled study reported that after an average follow-up of 1 year of patients following a Mediterranean diet,¹⁰⁸ the decline rate of eGFR was significantly lower (0.66 versus 1.25 ml/min/1.73 m²) and the incidence of eGFR <60 mL/min/1.73 m² was significantly lower than that of the control group.¹⁰⁹ Among morbidly obese patients, bariatric surgery is the best method for long-term weight loss.¹¹⁰ A study conducted 1 year after bariatric surgery on 30 obese patients with CKD revealed that proteinuria decreased by 63.7%, and the GFR after surgery was significantly higher than that before surgery (94 versus 79 ml/min).¹¹¹ Alex et al.¹¹² reported the same findings and concluded that the renal protective effect of weight loss surgery was significantly greater than the damage caused by the surgery to the kidney. In adolescents with a history of kidney disease, a study reported that urinary microalbuminuria/creatine decreased by 17 mg/g and eGFR increased by 26 ml/min/1.73 m² 3 years after weight loss surgery. The renal function and albuminuria of patients with no history of nephrosis before surgery remained stable.¹¹³ The findings show that surgery can effectively reduce the weight of all patients and delay or reverse the progression of kidney disease.

Pharmacological and non-pharmacological treatments should be combined for controlling blood pressure in patients with CKD and MetS. The Dietary Approaches to Stop Hypertension diet has been recommended,¹¹⁴ which comprises more fruits and vegetables, and the minimum sodium intake (1200 mg/day) is conducive to controlling HTN and reducing the risk of kidney disease progression.^115–117 The renin–angiotensin system in patients with MetS is closely related to IR.¹¹⁸ Blocking RAAS has a positive effect on the control of HTN and an effect on glucose metabolism. Therefore, RAAS inhibitors are the preferred antihypertensive agents for the treatment of patients with MetS.^119,120 The study found that irbesartan and telmisartan could significantly improve IR and increase the level of adiponectin, in addition to demonstrating a good antihypertensive effect.^121,122 RAAS inhibitors combined with high-intensity interval training (HIIT) can significantly reduce mean arterial pressure.¹¹⁹ β-blockers and thiazide diuretics are not recommended for blood pressure control in MetS, and calcium channel blockers can be used under special circumstances; however, they do not offer any other benefits. Therefore, these agents are not recommended for patients with MetS.⁶³ Recent studies have shown that reserpine can effectively treat MetS by inhibiting soluble epoxide hydrolase.¹²³

Statins have been listed as the first choice for treating hyperlipidaemia in patients with MetS as these agents inhibit the inflammatory reaction, improve endothelial dysfunction, stabilize atherosclerotic plaques, inhibit platelet aggregation and have antioxidant properties. In addition, statins can reduce proteinuria in patients with MetS and delay the progression of kidney disease.¹²⁴ Among the seven commonly used statins, rosuvastatin can not only reduce TG and LDL levels but also induce a significant increase in HDL levels,¹²⁵ which is a good choice for patients with CKD and elevated TG and decreased HDL levels as the main lipid metabolism abnormalities. However, some studies have found that high-dose atorvastatin has a significant effect on lipoprotein and apolipoprotein levels in women with MetS but has no significant effect on reducing inflammation, thrombosis or platelet aggregation.¹²⁶ Atorvastatin combined with silymarin was found to enhance the anti-lipid, anti-oxidation and anti-inflammatory effects in a rat model.¹²⁷ A study reported improved efficacy of statins combined with HIIT in MetS.¹²⁸ However, rosuvastatin should be used with caution in patients undergoing renal replacement therapy and patients with CKD having eGFR <30 ml/min/1.73 m². Ezetimibe, cholestyramine and other drugs can be used to control blood lipids in patients with MetS who cannot tolerate statins.^129,130 A study found that the combination of niacin and cholestyramine has a positive effect on blood lipid and weight control in patients with MetS.¹³¹ Most of the drugs for diabetes can be used for patients with abnormal glucose tolerance in MetS. Presently, metformin, pioglitazone, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors have been studied for the treatment of MetS, and reduced the hazard ratio for a composite renal and cardiovascular death endpoint in patients with CKD attributed to various causes, with or without type 2 diabetes.¹³² GLP-1RAs are the latest group of antidiabetic drugs. A large number of studies have shown that GLP-1RAs have multiple effects, with outstanding advantages in controlling blood glucose, lowering lipid levels and blood pressure, helping in weight loss, preventing atherosclerosis and inhibition of Ang II actions.^133–139 Linagliptin affects Insulin receptor substrate1/serine/threonine protein kinase B (IRS1/Akt) signalling and prevents high glucose-induced apoptosis in podocytes.¹⁴⁰ Among incretin-based therapeutic agents, tirzepatide was associated with a significantly reduced risk of diabetic kidney disease.¹⁴¹ Imeglimin, as the first member of a new class of oral antidiabetic drugs, exhibits unique mechanisms that can potentially benefit patients with diabetes. By reducing ROS production and increasing mitochondrial DNA synthesis, imeglimin has the potential to mitigate the occurrence of diabetic nephropathy.¹⁴² Thiazolidinedione, an insulin sensitizer, can improve insulin sensitivity and IR in patients with MetS, improve HDL levels and reduce TG levels.^143–145 Metformin plays an important role in improving insulin sensitivity and is safe for adolescents and children.¹⁴⁶ In cases of CKD combined with MetS, drugs for blood glucose control should be selected according to the patient’s renal function. For example, it is recommended to select linagliptin, repaglinide and rosiglitazone for patients with stage 5 CKD.

Discussion

The prevalence of MetS in patients with CKD is significantly higher than that in patients without CKD due to renal tubulointerstitial injury, accumulation of uremic toxins, abnormal bone mineral metabolism and the use of specific drugs. Presently, the treatments for MetS in patients with CKD aim to manage the components of MetS reach the standard components of MetS. In the future, studies should focus on the specific mechanisms of MetS in patients with CKD for effective intervention. The interventions can include selecting immunosuppressants, such as mycophenolate mofetil that have less effect on glucose and lipid metabolism, correcting acidosis, eliminating asymmetric dimethylarginine in the serum and supplementing active vitamin D to reduce IR.^147–149 In addition, considering the effect of CKD, appropriate drugs and dosage should be selected based on the level of renal function. Finally, the chief issue in MetS is IR. IR leads to increased levels of inflammatory mediators in the body, increased ROS production and the activation of the RAAS system, among other changes. Some new treatment options that need to be explored for MetS in patients with CKD, such as fasting to change the intestinal flora,¹⁵⁰ garlic,¹⁵¹ Azadirachta indica,¹⁵² cardamom,¹⁵³ ginkgo leaf,¹⁵⁴ Scutellaria baicalensis, onion, turmeric and their active ingredients,^155–158 have been explored. These treatments are expected to improve the inflammatory status, reduce ROS production and RAAS activation and become a new therapeutic target for MetS.

Conclusion

In conclusion, the incidence of MetS is significantly higher among patients with kidney disease compared to those without, primarily due to disturbances in glucose and fat metabolism, IR, HTN and the utilization of glucocorticoids and CNIs following kidney injury. The implementation of blood pressure control, statins and novel blood glucose-regulating drugs can mitigate the occurrence of MetS in kidney disease patients, thereby reducing kidney damage. However, there are also some limitations in this manuscript, such as some new therapeutic strategies, and new therapeutic schemes of traditional Chinese medicine require is warranted through large-scale studies.

Footnotes

Appendix

Acknowledgements

None.

Declarations

ORCID iD

Jurong Yang

References

Alberti

Eckel

Grundy

, et al. Harmonizing the MetS: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640–1645.

Lin

Tan

Pan

, et al. MetS-related kidney injury: a review and update. Front Endocrinol (Lausanne) 2022; 13: 904001.

Saklayen

MG.

The global epidemic of the metabolic syndrome. Curr Hypertens Rep 2018; 2: 12.

Stone

Bilek

Rosenbaum

Recent National Cholesterol Education Program Adult Treatment Panel III update: adjustments and options. Am J Cardiol 2005; 96: 53E–59E.

Moy

Bulgiba

The modified NCEP ATP III criteria maybe better than the IDF criteria in diagnosing MetS among Malays in Kuala Lumpur. BMC Public Health 2010; 10: 678.

Ford

ES.

Prevalence of the MetS defined by the International Diabetes Federation among adults in the US. Diabetes Care 2005; 28: 2745–2749.

Chinese Diabetes Society. Clinical guidelines for prevention and treatment of type 2 diabetes mellitus in the elderly in China (2022 edition). Zhonghua Nei Ke Za Zhi 2022; 61: 12–50.

Silveira Rossi

Barbalho

Reverete

Araujo

, et al. MetS and cardiovascular diseases: going beyond traditional risk factors. Diabetes Metab Res Rev 2022; 38: e3502.

Tirandi

Carbone

Montecucco

, et al. The role of MetS in sudden cardiac death risk: recent evidence and future directions. Eur J Clin Invest 2022; 52: e13693.

10.

Zhang

Liu

Zhang

, et al. Association of MetS and its components with risk of stroke recurrence and mortality: a meta-analysis. Neurology 2021; 97: e695–e705.

11.

Zhao

Yang

Maimaitiaili

, et al. Cardiac, macro-, and micro-circulatory abnormalities in association with individual MetS component: the Northern Shanghai Study. Front Cardiovasc Med 2021; 8: 690521.

12.

Nilsson

Laurent

Cunha

, et al. Characteristics of healthy vascular ageing in pooled population-based cohort studies: the global Metabolic syndrome and Artery REsearch Consortium. J Hypertens 2018; 36: 2340–2349.

13.

Ciardullo

Ballabeni

Trevisan

, et al. Metabolic syndrome, and not obesity, is associated with chronic kidney disease. Am J Nephrol 2021; 52: 666–672.

14.

Qin

Chen

, et al. Association between MetS and incident CKD among Chinese: a nation-wide cohort study and updated meta-analysis. Diabetes Metab Res Rev 2021; 37: e3437.

15.

Stenvinkel

Shiels

PG.

Metabolic syndrome in combination with chronic kidney disease – it’s a gut feeling. J Intern Med 2021; 290: 1108–1111.

16.

Moustakim

Mziwira

El Ayachi

, et al. Association of metabolic syndrome and chronic kidney disease in Moroccan adult population. Metab Syndr Relat Disord 2021; 19: 460–468.

17.

Chen

Kong

Jia

, et al. Association between MetS and CKD in a Chinese urban population. Clin Chim Acta 2017; 470: 103–108.

18.

Shahab

Mahsa

Behnam

, et al. MetS and its components are associated with increased CKD risk: evidence from a meta-analysis on 11 109 003 participants from 66 studies. Int J Clin Pract 2018; 23: e13201.

19.

Pammer

Lamina

Schultheiss

, et al. Association of the MetS with mortality and major adverse cardiac events: a large CKD cohort. J Intern Med 2021; 290: 1219–1232.

20.

Hana’a

Arnona

Rachel

The MetS and its components are differentially associated with chronic diseases in a high-risk population of 350 000 adults: a cross-sectional study. Diabetes Metab Res Rev 2019; 35: e3121.

21.

Wang

, et al. Optimal Obesity- and lipid-related indices for predicting MetS in CKD patients with and without type 2 diabetes mellitus in China. Nutrients 2022; 14:1334.

22.

Chang

F-C

Lee

M-C

Chiang

C-K

, et al. Angiopoietin-2 is associated with MetS in CKD. J Formos Med Assoc 2021; 120: 2113–2119.

23.

Tsai

M-H

Hsu

C-Y

Lin

M-Y

, et al. Incidence, prevalence, and duration of CKD in Taiwan: results from a community-based screening program of 106,094 individuals. Nephron 2018; 140: 175–184.

24.

Boronat

Bosch

Lorenzo

, et al. Prevalence and determinants of the MetS among subjects with advanced nondiabetes-related CKD in Gran Canaria, Spain. Ren Fail 2016; 38: 198–203.

25.

Hung

C-C

Zhen

Y-Y

Niu

S-W

, et al. Predictive value of HbA1c and MetS for renal outcome in non-diabetic CKD stage 1–4 patients. Biomedicines 2022; 10: 1858.

26.

Kittiskulnam

Thokanit

Katavetin

, et al. The magnitude of obesity and MetS among diabetic CKD population: a nationwide study. PLoS One 2018; 13: e0196332.

27.

Alswat

Althobaiti

Alsaadi

, et al. Prevalence of MetS among the end-stage renal disease patients on hemodialysis. J Clin Med Res 2017; 9: 687–694.

28.

AlShelleh

AlAwwa

Oweis

, et al. Prevalence of MetS in dialysis and transplant patients. Diabetes Metab Syndr Obes 2019; 12: 575–579.

29.

Maduram

John

Hidalgo

, et al. MetS in pediatric renal transplant recipients: comparing early discontinuation of steroids vs. Steroid group. Pediatr Transplant 2010; 14: 351–357.

30.

Liu

Wang

, et al. Both insulin resistance and MetS accelerate the progression of CKD among Chinese adults: results from a 3-year follow-up study. Int Urol Nephrol 2018; 50: 2239–2244.

31.

Min

Kim

Jeong

, et al. Independent association of serum aldosterone level with MetS and insulin resistance in Korean adults. Korean Circ J 2018; 48: 198–208.

32.

Sharma

Liao

Zheng

, et al. New pandemic: obesity and associated nephropathy. Front Med (Lausanne) 2021; 8: 673556.

33.

Vatier

Jéru

Fellahi

, et al. Leptin, adiponectin, lipodystrophic and severe insulin resistance syndromes. Ann Biol Clin (Paris) 2020; 78: 261–264.

34.

da Silva

do Carmo

, et al. Role of hyperinsulinemia and insulin resistance in hypertension: MetS revisited. Can J Cardiol 2020; 36: 671–682.

35.

Zhu

Scherer

PE.

Immunologic and endocrine functions of adipose tissue: implications for kidney disease. Nat Rev Nephrol 2018; 14: 105–120.

36.

Markova

Miklankova

Hüttl

, et al. The effect of lipotoxicity on renal dysfunction in a nonobese rat model of MetS: a urinary proteomic approach. J Diabetes Res 2019; 2019: 8712979.

37.

Martin-Taboada

Vila-Bedmar

Medina-Gómez

From obesity to CKD: how can adipose tissue affect renal function?

Nephron 2021; 145: 609–613.

38.

Liao

M-T

Sung

C-C

Hung

K-C

, et al. Insulin resistance in patients with CKD. J Biomed Biotechnol 2012; 2012: 691369.

39.

Nallamothu

Nimmanapalli

Sachan

, et al. Insulin resistance in nondiabetic CKD patients. Saudi J Kidney Dis Transpl 2021; 32: 1300–1309.

40.

Spoto

Pisano

Zoccali

Insulin resistance in CKD: a systematic review. Am J Physiol Renal Physiol 2016; 311: F1087–F1108.

41.

Srivastava

Singh

Usha , et al. Insulin resistance in predialytic, nondiabetic, CKD patients: a hospital-based study in Eastern Uttar Pradesh, India. Saudi J Kidney Dis Transpl 2017; 28: 36–43.

42.

Szeto

Liu

Soong

, et al. Protection of mitochondria prevents high-fat diet-induced glomerulopathy and proximal tubular injury. Kidney Int 2016; 90: 997–1011.

43.

Thomas

Zhang

Mitch

WE.

Molecular mechanisms of insulin resistance in CKD. Kidney Int 2015; 88: 1233–1239.

44.

Alipoor

Hosseinzadeh

Hosseinzadeh-Attar

MJ.

Adipokines in critical illness: a review of the evidence and knowledge gaps. Biomed Pharmacother 2018; 108: 1739–1750.

45.

Nakashima

Kato

Ohkido

, et al. Role and treatment of insulin resistance in patients with CKD: a review. Nutrients 2021; 13: 4349.

46.

Miyamoto

Miyazaki

Honda

, et al. Retention of acetylcarnitine in CKD causes insulin resistance in skeletal muscle. J Clin Biochem Nutr 2016; 59: 199–206.

47.

Fayed

El Nokeety

Heikal

, et al. Fibroblast growth factor-23 is a strong predictor of insulin resistance among CKD patients. Ren Fail 2018; 40: 226–230.

48.

Lee

C-L

Liu

W-J

Tsai

S-F.

Development and validation of an insulin resistance model for a population with CKD using a machine learning approach. Nutrients 2022; 14: 2832.

49.

Cao

Shi

, et al. A renal–cerebral–peripheral sympathetic reflex mediates insulin resistance in CKD. EBioMedicine 2018; 37: 281–293.

50.

Barbagallo

Cefalù

Giammanco

, et al. Lipoprotein abnormalities in CKD and renal transplantation. Life (Basel) 2021; 11: 315.

51.

Strazzella

Ossoli

Calabresi

High-density lipoproteins and the kidney. Cells 2021; 10: 764.

52.

Kosugi

Eriguchi

Yoshida

, et al. Association between CKD and new-onset dyslipidemia: The Japan Specific Health Checkups (J-SHC) study. Atherosclerosis 2021; 332: 24–32.

53.

Keane

Tomassini

Neff

DR.

Lipid abnormalities in patients with CKD: implications for the pathophysiology of atherosclerosis. J Atheroscler Thromb 2013; 20: 123–133.

54.

Kashyap

Pegu

Paul

Study of lipid abnormalities in non diabetic CKD patients with special reference to hemodialysis. J Assoc Physicians India 2020; 68: 77.

55.

Reaven

GM.

Compensatory hyperinsulinemia and the development of an atherogenic lipoprotein profile: the price paid to maintain glucose homeostasis in insulin-resistant individuals. Endocrinol Metab Clin North Am 2005; 1: 49–62.

56.

Samouilidou

Karpouza

Kostopoulos

, et al. Lipid abnormalities and oxidized LDL in CKD patients on hemodialysis and peritoneal dialysis. Ren Fail 2012; 34: 160–164.

57.

Tournis

Makris

Cavalier

, et al. Cardiovascular risk in patients with primary hyperparathyroidism. Curr Pharm Des 2020; 26: 5628–5636.

58.

Shad

Akbari

Qujeq

, et al. Measurement of serum irisin in the different stages of CKD. Caspian J Intern Med 2019; 10: 314–319.

59.

Gan

Chen

, et al. Circulating irisin level in CKD patients: a systematic review and meta-analysis. Int Urol Nephrol 2022; 54: 1295–1302.

60.

Dong

Deng

, et al. Lower serum irisin levels are associated with the increasing mortality of cardiovascular and cerebrovascular diseases in hemodialysis patients. Ann Palliat Med 2021; 10: 6052–6061.

61.

Wen

M-S

Wang

C-Y

Lin

S-L

, et al. Decrease in irisin in patients with CKD. PLoS One 2013; 8: e64025.

62.

Mende

Einhorn

Fatty kidney disease: a new renal and endocrine clinical entity? Describing the role of the kidney in obesity, METS, and type 2 diabetes. Endocr Pract 2019; 25: 854–858.

63.

Katsimardou

Imprialos

Stavropoulos

, et al. Hypertension in MetS: novel insights. Curr Hypertens Rev 2020; 16: 12–18.

64.

Correia-Costa

Morato

Sousa

, et al. Urinary fibrogenic cytokines ET-1 and TGF-β1 are associated with urinary angiotensinogen levels in obese children. Pediatr Nephrol 2016; 31: 455–464.

65.

Aihara

K-I

Ikeda

Yagi

, et al. Transforming growth factor-β1 as a common target molecule for development of cardiovascular diseases, renal insufficiency and MetS. Cardiol Res Pract 2010; 2011: 175381.

66.

Cabandugama

Gardner

Sowers

. The renin angiotensin aldosterone system in obesity and hypertension: roles in the cardiorenal MetS. Med Clin North Am 2017; 101: 129–137.

67.

J-W

Chi

P-J

Lin

Y-L

, et al. Serum leptin levels are positively associated with aortic stiffness in patients with CKD stage 3–5. Adipocyte 2020; 9: 206–211.

68.

Coimbra

Rocha

Valente

, et al. New insights into adiponectin and leptin roles in CKD. Biomedicines 2022; 10: 2642.

69.

Kim

Lee

Chae

D-W

, et al. Serum klotho is inversely associated with MetS in CKD: results from the KNOW-CKD study. BMC Nephrol 2019; 20: 119.

70.

Maciorkowska

Musiałowska

Małyszko

Adropin and irisin in arterial hypertension, diabetes mellitus and CKD. Adv Clin Exp Med 2019; 28: 1571–1575.

71.

Xue

Zhang

, et al. Leptin mediates high-fat diet sensitization of angiotensin II-elicited hypertension by upregulating the brain renin–angiotensin system and inflammation. Hypertension 2016; 67: 970–976.

72.

Korczynska

Czumaj

Chmielewski

, et al. The causes and potential injurious effects of elevated serum leptin levels in CKD patients. Int J Mol Sci 2021; 22: 4685.

73.

Nasrallah

Ziyadeh

FN.

Overview of the physiology and pathophysiology of leptin with special emphasis on its role in the kidney. Semin Nephrol 2013; 33: 54–65.

74.

Mao

Fang

Liu

, et al. Leptin and CKDs. J Recept Signal Transduct Res 2018; 38: 89–94.

75.

Esmaili

Hemmati

Karamian

Physiological role of adiponectin in different tissues: a review. Arch Physiol Biochem 2020; 126: 67–73.

76.

Boric-Skaro

Mizdrak

Luketin

, et al. Serum adropin levels in patients on hemodialysis. Life (Basel) 2021; 11: 337.

77.

Cecerska-Heryć

Adamiak

Serwin

, et al. Comparative analysis of adropin concentration changes in response to kidney transplantation. Eur J Intern Med 2021; 84: 112–114.

78.

Kadiroğlu

Ustündag

Kayabaşi

, et al. A comparative study of the effect of icodextrin based peritoneal dialysis and hemodialysis on lipid metabolism. Indian J Nephrol 2013; 23: 358–361.

79.

Szeto

C-C

Chow

K-M

Kwan

BC-H

, et al. New-onset hyperglycemia in nondiabetic Chinese patients started on peritoneal dialysis. Am J Kidney Dis 2007; 49: 524–532.

80.

Bernardo

Oliveira

Santos

, et al. Insulin resistance in nondiabetic peritoneal dialysis patients: associations with body composition, peritoneal transport, and peritoneal glucose absorption. Clin J Am Soc Nephrol 2015; 12: 2205–2212.

81.

Penfornis

Kury-Paulin

Immunosuppressive drug-induced diabetes. Diabetes Metab 2006; 32: 539–546.

82.

Culliford

Phagura

Sharif

Autosomal dominant polycystic kidney disease is a risk factor for posttransplantation diabetes mellitus: an updated systematic review and meta-analysis. Transplant Direct 2020; 6: e553.

83.

Legeza

Marcolongo

Gamberucci

, et al. Fructose, glucocorticoids and adipose tissue: implications for the MetS. Nutrients 2017; 9: 426.

84.

Marchetti

Navalesi

The metabolic effects of cyclosporin and tacrolimus. J Endocrinol Invest 2000; 23: 482–490.

85.

Bamgbola

Metabolic consequences of modern immunosuppressive agents in solid organ transplantation. Ther Adv Endocrinol Metab 2016; 7: 110–127.

86.

Pereira

Palming

Rizell

, et al. Cyclosporine A and tacrolimus reduce the amount of GLUT4 at the cell surface in human adipocytes: increased endocytosis as a potential mechanism for the diabetogenic effects of immunosuppressive agents. J Clin Endocrinol Metab 2014; 99: E1885–E1894.

87.

Rodríguez-Morán

Guerrero-Romero

Insulin secretion is decreased in non-diabetic individuals with hypomagnesaemia. Diabetes Metab Res Rev 2011; 27: 590–596.

88.

Zahr

Molano

Pileggi

, et al. Rapamycin impairs in vivo proliferation of islet beta-cells. Transplantation 2007; 84: 1576–1583.

89.

Bell

Cao

Moibi

, et al. Rapamycin has a deleterious effect on MIN-6 cells and rat and human islets. Diabetes 2003; 52: 2731–2739.

90.

Ahmed

Biddle

Augustine

, et al. Post-transplantation diabetes mellitus. Diabetes Ther 2020; 11: 779–801.

91.

Bhat

Usmani

Azhie

, et al. Metabolic consequences of solid organ transplantation. Endocr Rev 2021; 42: 171–197.

92.

LaGuardia

Zhang

Obesity and MetS in kidney transplantation. Curr Hypertens Rep 2013; 15: 215–223.

93.

Düsing

Zietzer

Goody

, et al. Vascular pathologies in CKD: pathophysiological mechanisms and novel therapeutic approaches. J Mol Med (Berl) 2021; 99: 335–348.

94.

Lim

Sidor

Tonial

, et al. Uremic toxins in the progression of CKD and cardiovascular disease: mechanisms and therapeutic targets. Toxins (Basel) 2021; 13: 142.

95.

Mok

Ballew

Matsushita

CKD measures for cardiovascular risk prediction. Atherosclerosis 2021; 335: 110–118.

96.

Mima

Yasuzawa

King

, et al. Obesity-associated glomerular inflammation increases albuminuria without renal histological changes. FEBS Open Bio 2018; 8: 664–670.

97.

Kawamoto

Akase

Ninomiya

, et al. MetS is a predictor of decreased renal function among community-dwelling middle-aged and elderly Japanese. Int Urol Nephrol 2019; 51: 2285–2294.

98.

Yun

H-R

Kim

Park

, et al. Obesity, metabolic abnormality, and progression of CKD. Am J Kidney Dis 2018; 72: 400–410.

99.

Navaneethan

Schold

Kirwan

, et al. MetS, ESRD, and death in CKD. Clin J Am Soc Nephrol 2013; 8: 945–952.

100.

Tainio

Qvist

Hölttä

, et al. Metabolic risk factors and long-term graft function after paediatric renal transplantation. Transpl Int 2014; 27: 583–592.

101.

Shen

F-C

Chiu

Y-W

Kuo

M-C

, et al. U-shaped association between waist-to-hip ratio and all-cause mortality in stage 3–5 CKD patients with body mass index paradox. J Pers Med 2021; 11: 1355.

102.

Sgambat

Clauss

Lei

, et al. Effects of obesity and MetS on cardiovascular outcomes in pediatric kidney transplant recipients: a longitudinal study. Pediatr Nephrol 2018; 33: 1419–1428.

103.

Wilson

Greenbaum

Barletta

, et al. High prevalence of the MetS and associated left ventricular hypertrophy in pediatric renal transplant recipients. Pediatr Transplant 2010; 1: 52–60.

104.

Sgambat

Clauss

Lei

, et al. Increased carotid intima-media thickness in African American pediatric kidney transplant recipients. Pediatr Transplant 2018; 22: e13163.

105.

Straznicky

Grima

Lambert

, et al. Exercise augments weight loss induced improvement in renal function in obese MetS individuals. J Hypertens 2011; 29: 553–564.

106.

Navaneethan

Yehnert

Moustarah

, et al. Weight loss interventions in CKD: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2009; 4: 1565–1574.

107.

C-P

Sheu

WH-H

Lee

I-T

, et al. Weight loss reduces serum monocyte chemoattractant protein-1 concentrations in association with improvements in renal injury in obese men with MetS. Clin Chem Lab Med 2015; 53: 623–629.

108.

Estruch

Ros

Salas-Salvadó

, et al. Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018; 378: e34.

109.

Díaz-López

Becerra-Tomás

Ruiz

, et al. Effect of an intensive weight-loss lifestyle intervention on kidney function: a randomized controlled trial. Am J Nephrol 2021; 52: 45–58.

110.

Chauhan

Vaid

Gupta

, et al. Metabolic, renal, and nutritional consequences of bariatric surgery: implications for the clinician. South Med J 2010; 103: 775–783; quiz 784–785.

111.

Morales

Porrini

Martin-Taboada

, et al. Renoprotective role of bariatric surgery in patients with established CKD. Clin Kidney J 2020; 14: 2037–2046.

112.

Chang

Chen

Still

, et al. Bariatric surgery is associated with improvement in kidney outcomes. Kidney Int 2016; 90: 164–171.

113.

Nehus

Khoury

Inge

, et al. Kidney outcomes three years after bariatric surgery in severely obese adolescents. Kidney Int 2017; 91: 451–458.

114.

Sacks

Obarzanek

Windhauser

, et al. Rationale and design of the dietary approaches to stop hypertension trial (DASH). A multicenter controlled-feeding study of dietary patterns to lower blood pressure. Ann Epidemiol 1995; 5: 108–118.

115.

Lee

Hyun

, et al. DASH dietary pattern and CKD in elderly Korean adults. Eur J Clin Nutr 2017; 71: 755–761.

116.

Song

Lobene

Wang

, et al. The DASH diet and cardiometabolic health and CKD: a narrative review of the evidence in East Asian countries. Nutrients 2021; 13: 984.

117.

Coresh

Anderson

CAM

, et al. Adherence to healthy dietary patterns and risk of CKD progression and all-cause mortality: findings from the CRIC (Chronic Renal Insufficiency Cohort) study. Am J Kidney Dis 2021; 77: 235–244.

118.

Henriksen

Prasannarong

The role of the renin–angiotensin system in the development of insulin resistance in skeletal muscle. Mol Cell Endocrinol 2013; 378: 15–22.

119.

Ramirez-Jimenez

Morales-Palomo

Moreno-Cabañas

, et al. Effects of antihypertensive medication and high-intensity interval training in hypertensive MetS individuals. Scand J Med Sci Sports 2021; 31: 1411–1419.

120.

Masajtis-Zagajewska

Majer

Nowicki

Losartan and eprosartan induce a similar effect on the acute rise in serum uric acid concentration after an oral fructose load in patients with MetS. J Renin Angiotensin Aldosterone Syst 2021; 2021: 2214978.

121.

Takagi

Niwa

Mizuno

, et al. Telmisartan as a metabolic sartan: the first meta-analysis of randomized controlled trials in MetS. J Am Soc Hypertens 2013; 7: 229–235.

122.

Wang

Qiao

Han

D-W

, et al. Telmisartan improves insulin resistance: a meta-analysis. Am J Ther 2018; 25: e642–e651.

123.

Verma

Paliwal

Sharma

Therapeutic potential of reserpine in MetS: an evidence based study. Pharmacol Res 2022; 186: 106531.

124.

Sadowitz

Maier

Gahtan

Basic science review: statin therapy – Part I: the pleiotropic effects of statins in cardiovascular disease. Vasc Endovascular Surg 2010; 44: 241–251.

125.

Stalenhoef

AFH

Ballantyne

Sarti

, et al. A comparative study with rosuvastatin in subjects with MetS: results of the COMETS study. Eur Heart J 2005; 26:2664–2672.

126.

Velarde

Choudhary

Bravo-Jaimes

, et al. Effect of atorvastatin on lipogenic, inflammatory and thrombogenic markers in women with the MetS. Nutr Metab Cardiovasc Dis 2021; 31: 634–640.

127.

Marková

Malínská

Hüttl

, et al. The combination of atorvastatin with silymarin enhances hypolipidemic, antioxidant and anti-inflammatory effects in a rat model of MetS. Physiol Res 2021; 70: 33–43.

128.

Morales-Palomo

Ramirez-Jimenez

Ortega

, et al. Exercise training adaptations in MetS individuals on chronic statin treatment. J Clin Endocrinol Metab 2020; 105: dgz304.

129.

Catapano

Graham

De Backer

, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2016; 37: 2999–3058.

130.

Robidoux

Dyslipidemia management update. Curr Opin Pharmacol 2017; 33: 47–55.

131.

Richard

Ganesh

George

, et al. The effect of gemfibrozil, niacin and cholestyramine combination therapy on MetS in the Armed Forces Regression Study. Am J Med Sci 2011; 341: 378–382.

132.

Mima

Sodium–glucose cotransporter 2 inhibitors in patients with non-diabetic chronic kidney disease. Adv Ther 2021; 38: 2201–2212.

133.

Liang

, et al. Hepatic adenylate cyclase 3 is upregulated by Liraglutide and subsequently plays a protective role in insulin resistance and obesity. Nutr Diabetes 2016; 1: e191.

134.

Færch

Torekov

Vistisen

, et al. GLP-1 response to oral glucose is reduced in prediabetes, screen-detected type 2 diabetes, and obesity and influenced by sex: the ADDITION-PRO study. Diabetes 2015; 64: 2513–2525.

135.

Acosta

Camilleri

Burton

, et al. Exenatide in obesity with accelerated gastric emptying: a randomized, pharmacodynamics study. Physiol Rep 2015; 3: e12610.

136.

Hiramatsu

Ozeki

Asai

, et al. Liraglutide improves glycemic and blood pressure control and ameliorates progression of left ventricular hypertrophy in patients with type 2 diabetes mellitus on peritoneal dialysis. Ther Apher Dial 2015; 19: 598–605.

137.

Keith

William

David

, et al. Effects of the once-weekly glucagon-like peptide-1 receptor agonist dulaglutide on ambulatory blood pressure and heart rate in patients with type 2 diabetes mellitus. Hypertension 2014; 4: 731–737.

138.

Danne

Biester

Kapitzke

, et al. Liraglutide in an adolescent population with obesity: a randomized, double-blind, placebo-controlled 5-week trial to assess safety, tolerability, and pharmacokinetics of liraglutide in adolescents aged 12–17 years. J Pediatr 2017; 181: 146–153.e3.

139.

Mima

Hiraoka-Yamomoto

, et al. Protective effects of GLP-1 on glomerular endothelium and its inhibition by PKCβ activation in diabetes. Diabetes 2012; 61: 2967–2979.

140.

Mima

Yasuzawa

Nakamura

, et al. Linagliptin affects IRS1/Akt signaling and prevents high glucose-induced apoptosis in podocytes. Sci Rep 2020; 10: 5775.

141.

Mima

Gotoda

Lee

, et al. Effects of incretin-based therapeutic agents including tirzepatide on renal outcomes in patients with type 2 diabetes: a systemic review and meta-analysis. Metabol Open 2023; 17: 100236.

142.

Mima

Mitochondria-targeted drugs for diabetic kidney disease. Heliyon 2022; 8: e08878.

143.

Colca

Scherer

PE.

The MetS, thiazolidinediones, and implications for intersection of chronic and inflammatory disease. Mol Metab 2022; 55: 101409.

144.

Gurka

Mack

Chi

, et al. Use of MetS severity to assess treatment with vitamin E and pioglitazone for non-alcoholic steatohepatitis. J Gastroenterol Hepatol 2021; 36: 249–256.

145.

Marusyn

OV.

The relationship between obesity, glycemia and leptin level of type 2 diabetes mellitus patients with MetS. Wiad Lek 2018; 71: 1165–1168.

146.

Hahr

Molitch

ME.

Management of diabetes mellitus in patients with CKD: core curriculum 2022. Am J Kidney Dis 2022; 79: 728–736.

147.

Tagi

Samvelyan

Chiarelli

MetS in children. Minerva Pediatr 2020; 72: 312–325.

148.

Bellasi

Micco

Santoro

, et al. Correction of metabolic acidosis improves insulin resistance in CKD. BMC Nephrol 2016; 17: 158.

149.

Tahar

Zerdoumi

Saidani

, et al. Effects of oral vitamin D₃ supplementation in stage 3 CKD subjects: insulin resistance syndrome and hormonal disturb interactions. Ann Biol Clin (Paris) 2018; 76: 313–325.

150.

Wang

Sun

, et al. Effects of active vitamin D on insulin resistance and islet β-cell function in non-diabetic CKD patients: a randomized controlled study. Int Urol Nephrol 2022; 54: 1725–1732.

151.

Wilkinson

Manoogian

ENC

Zadourian

, et al. Ten-hour time-restricted eating reduces weight, blood pressure, and atherogenic lipids in patients with MetS. Cell Metab 2020; 31: 92–104.e5.

152.

Pérez-Rubio

Méndez-Del Villar

Cortez-Navarrete

The role of garlic in metabolic diseases: a review. J Med Food 2022; 25: 683–694.

153.

Yarmohammadi

Mehri

Najafi

, et al. The protective effect of Azadirachta indica (neem) against MetS: a review. Iran J Basic Med Sci 2021; 24: 280–292.

154.

Yahyazadeh

Rahbardar

Razavi

, et al. The effect of Elettaria cardamomum (cardamom) on the MetS: narrative review. Iran J Basic Med Sci 2021; 24: 1462–1469.

155.

Eisvand

Razavi

Hosseinzadeh

The effects of Ginkgo biloba on MetS: a review. Phytother Res 2020; 34: 1798–1811.

156.

Rahimi

Askari

Hosseinzadeh

Promising influences of Scutellaria baicalensis and its two active constituents, baicalin, and baicalein, against MetS: a review. Phytother Res 2021; 35: 3558–3574.

157.

Galavi

Hosseinzadeh

Razavi

BM.

The effects of Allium cepa L. (onion) and its active constituents on MetS: a review. Iran J Basic Med Sci 2021; 24: 3–16.

158.

Vafaeipour

Razavi

Hosseinzadeh

Effects of turmeric (Curcuma longa) and its constituent (curcumin) on the MetS: an updated review. J Integr Med 2022; 20: 193–203.

Chronic kidney disease combined with metabolic syndrome is a non-negligible risk factor

Abstract

Keywords

Introduction

Epidemiological characteristics of MetS in patients with CKD

The mechanism of MetS in patients with CKD

Insulin resistance

Lipoprotein abnormalities

Hypertension

Specific treatment for CKD

Effect of MetS on target organs in patients with CKD

Treatment of CKD combined with MetS

Discussion

Conclusion

Footnotes

Appendix

Acknowledgements

Declarations

ORCID iD

References