The complex effects of adipokines in the patients with kidney disease
Isfahan Kidney Diseases Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
|Date of Submission||14-Dec-2017|
|Date of Decision||12-Mar-2018|
|Date of Acceptance||29-Apr-2018|
|Date of Web Publication||26-Jul-2018|
Dr. Sahar Vahdat
Isfahan Kidney Diseases Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan
Source of Support: None, Conflict of Interest: None
Kidney diseases are categorized as the highest prevalent ones with worldwide noticeable incidence. They cause accelerated cardiovascular diseases and noticeable mortalities. Adipose tissue and its messengers, adipokines, are reported to have the highest relationship with end-stage renal diseases or chronic kidney diseases. Over recent years, with shifting of scientists' mindset from a simple overview of adipose tissue as a fat store to the complex paradigm of this issue as a multipotential secretory organ, the importance of studies on this tissue has emerged.
Keywords: Adipokines, adipose tissue, kidney diseases
|How to cite this article:|
Vahdat S. The complex effects of adipokines in the patients with kidney disease. J Res Med Sci 2018;23:60
| Introduction|| |
Kidney disease is a global health burden with high prevalent as well as high economic cost, of which chronic kidney disease (CKD) is the most famous disorder in the category. It is associated with hypertension, cardiovascular disease (CVD), obesity, and renal dysfunction with five stages, in which stage 3 is the major among the CKD patients. The global prevalence is between 11% and 13%. In the US, the latest report pointed out to 14.8% CKD prevalence with the same, most prevalent stage to the global statement with considerable health cost and medicare. Various factors have been found to have a direct relationship with kidney disease; among them, adipose tissue and adipokines contribute more than other biological elements.,, In recent years, adipokines have become an important part of multipotential secretory organ as well as its role in the biology of a variety of organs in the human body. Understanding the adipobiology of diseases can guide us to get familiar with adipokines that target pharmacology better. There are different adipokines members with various roles in health and diseases. Sometimes, there are controversial ideas about the impact of adipokines in the pathobiology of kidney diseases. Here, the different roles of each important adipokine are discussed.
| Methods|| |
This review was written according to the previous articles with the topic of adipose tissue, adipokines, and their association with Vitamin D. Our keywords were considered as our searching topics and the articles which were published after 2000 were chosen. The literature was collected from PubMed/Medline, EMBASE, Scopus, and Web of Science, and relative information was reviewed meticulously.
| Adiponectin and Kidney Disease|| |
Adiponectin is a 30-kDa protein from adipose tissue, circulating in the plasma with trimer form., Adiponectin is the most available adipose tissue protein which has a suggested anti-atherosclerotic and anti-inflammatory function. The anti-inflammatory feature is due to its effect on vascular walls and suppression the proinflammatory molecules via the help of nuclear factor kappa B (NFκB) signaling pathway. It can also inhibit the subsequent proinflammatory effects by suppressing of tumor necrosis factor (TNF)-α and interleukin (IL)-6 and promoting anti-inflammatory cytokines such as IL-10.
Plasma level of adiponectin and intercellular adhesion molecule (ICAM)-1 can predict albuminuria, and the anti-inflammatory property of adiponectin in kidney injury is probably due to the inhibition of ICAM-1. Increasing ICAM-1 triggers immune cells, especially macrophage, to accumulate in the kidney which is associated with fibrosis, albuminuria, and decline of renal function. Adiponectin can decrease the expression of adhesion molecules in the kidney endothelial cells in response to inflammatory stimuli. Similarly, it has been reported that adiponectin is positively correlated with proteinuria and albuminuria and it is inversely related to body mass index (BMI) and renal function. However, there is an opposite finding that lower level of adiponectin can predict the albuminuria. In addition, in the low level or the absence of enough adiponectin, the level of IL-6 and high-sensitive C-reactive protein (hs-CRP), which is responsible for the renal disorder and atherosclerosis, is increased. The reason is raised by the vasculoprotective actions and anti-inflammatory property of adiponectin in comparison with the presence of IL-6 and hs-CRP in inflammatory states such as obesity. Experimental studies demonstrated that overexpression of adiponectin results in improved proteinuria in early diabetic nephropathy (DN) and endothelial dysfunction, and in adiponectin knockout mice, renal fibrosis and albuminuria are increased, considerably. According to the above statement, it seems that adiponectin has a protective role in the kidney diseases by inhibition of microvascular damage, and lower level of adiponectin in the plasma is in association with the progression of kidney disease. Nevertheless, high adiponectin was reported to be the predictor of CKD progression in male patients.
On the other hand, the following controversial reports have stated the relationship between adiponectin level and the risk of cardiovascular diseases. Some reports have revealed that high level of adiponectin is associated with lower cardiovascular risk factors., In one study, it has been reported that a lower level of adiponectin in the plasma is in association with the past and new CVD events in patient suffering renal failure. Fatal and nonfatal cardiovascular events have also observed to be inversely correlated with lower plasma adiponectin. Some others have suggested that higher plasma adiponectin level is associated with increased cardiovascular risk factors and further renal dysfunction., Rare investigations failed to find any association between plasma adiponectin level and cardiovascular events. However, the controversial reports seem to be due to different inherited and environmental elements.
Furthermore, in nondiabetic end-stage renal disease (ESRD) patients, the mRNA expression of adiponectin is upregulated in the subcutaneous and visceral fat tissue. This overexpression was not observed in diabetic patients. The possible explanation for this difference between two above groups may be because of the association of a low level of adiponectin and diabetes mellitus. In both mentioned groups, the expression of adiponectin receptor type 1 (AdipoR1) is increased in the peripheral blood mononuclear cells (PBMCs) and various tissues., Another important adiponectin receptor, AdipoR2, is also overexpressed only in PBMCs.,
The above statements about the role of adiponectin showed that low-circulating adiponectin is a strong risk factor for CVDs, albuminuria, and also hypertension. Furthermore, in CKD patients, the higher level of adiponectin has been reported to have an adverse correlation with progression of CKD. However, opposite ideas  seem to remain an unsolved question about the exact role of adiponectin in the kidney progression.
| Leptin and Kidney Diseases|| |
Leptin is secreted by adipocytes and demonstrates the body fat. In CKD disease, obesity and hypertension have a central role in renal injury and vascular dysfunction. Leptin is reported to be increased considerably in patients with CKD. In an animal model study of spontaneously hypertensive which is received the high-fat diet, the level of cholesterin and leptin is increased. Moreover, a higher level of leptin and cholesterol leads to vascular dysfunction via upregulated reactive oxygen species (ROS) and nitric oxide (NO) metabolites. The endothelial dysfunction is related to renal injuries and further higher cardiovascular risk.
ESRD patients have a higher level of leptin compared with healthy control. It has been reported that serum leptin concentration is increased in CKD patients which is correlated to the level of CRP. The above-mentioned finding demonstrated the connection between hyperleptinemia and inflammation with CKD pathogenesis. The following findings report that urinary leptin level is lower in these patients due to not degradation of leptin, which remains high in the glomerular filtration rate (GFR). On the other hand, a short-term use of leptin showed no effect on urinary protein excretion. In a long-term treatment with leptin, the animal study demonstrated that urinary protein excretion is increased.
With the increased size of adipocyte, the secretion of leptin is increased, which is positively correlated with BMI. Kidney produces a receptor for leptin named ob-Ra. This isoform is not complete and cannot bind to leptin well. Besides, kidneys can produce a lower complete isoform of leptin receptor called ob-Rb. Due to leptin being bound to ob-Ra, which is expressed on mesangial and glomerular endothelial cells, and the exceed leptin not being absorbed, it can stimulate a variety of different cellular system mechanisms such as stimulating of transforming growth factor-beta (TGF-β ) 1, type IV collagen, as well as phosphatidylinositol-3-kinase (PI3K), leading to producing some proinflammatory cytokines and other mediates, which participates in the renal failure and kidney dysfunction. The results of other investigations prove the claim because an increased TGF-β has been observed in renal tubular and mesangial cells in the leptin-treating group, which has an important role in leptin-induced nephropathy.
| Visfatin and Kidney Diseases|| |
Visfatin is predominantly secreted by adipose tissue and enriched in the visceral adipose tissue. It influences the energetic metabolism by participating in the nicotinamide adenine dinucleotide synthesis. An interesting finding of this protein is that it can induce production of both anti-inflammatory and proinflammatory cytokines. The level of circulating visfatin is increased dramatically in CKD patients and is associated with renal function and soluble vascular cell adhesion molecule (VCAM)-1, as a key marker of endothelial damage. In patients, as well as in an animal model of type 2 DN, the level of visfatin is increased. Therefore, visfatin is seemed to be as a proinflammatory adipokine in metabolic syndrome and type 2 diabetes. The other investigations have indicated that administration of visfatin induces secretion of proinflammatory and profibrotic molecules such as type 1 collagen, plasminogen activator inhibitor 1, and TGF-β.,
Yilmaz et al. found that circulating level of visfatin was associated with endothelial dysfunction. Mu et al. reported that higher level of visfatin is associated with endothelial dysfunction, atherosclerosis, and lipid dysregulation in patients contracted with CKD. Axelsson et al. stated that renal function influences circulating level of visfatin; however, they could not find any significant association between markers of insulin resistance with visfatin level in CKD patients. Carrero et al. reported that in CKD patients with poor appetite, visfatin is increased and has an adverse correlation with triglyceride (TG) and fasting serum amino acids. Mahmood et al. found that except for significant positive association between level of visfatin and CKD, there was no difference for visfatin concentration in diabetes and nondiabetes CKD patients. Furthermore, negative correlation with GFR and positive correlation with proteinuria were reported.
| Resistin and Kidney Disease|| |
In 2001, resistin was discovered, and soon after that, it was revealed that it has an association with endothelial damage, inflammation, and insulin resistance. The main source of resistin is visceral adipose tissue-resident macrophage. It has been reported that resistin contributes to the increased risk of atherosclerosis, CVDs, and insulin resistance diseases. Its serum concentration is increased in the CKD and type 2 diabetes patients. Independent association of resistin and GFR in the early stage of hypertension expresses the involvement of this protein in the kidney damage progression. Resistin promotes the expression of adhesion molecules, endothelin, and matrix metalloproteinases and stimulates systemic vascular dysfunction which affects GFR. Furthermore, positive correlation of leukocyte counts, endothelin-1, and CRP with resistin has been revealed.
In the CKD patients, the serum level of resistin is negatively associated with GFR. Likewise, Marouga et al. reported that an increased level of resistin is associated with a decline in the GFR and may participate in the malnutrition–inflammation state. In addition, they found that TNF-α and hs-CRP were the most important independent determinants of serum resistin level. Resistin can induce expression of adhesion molecules such as ICAM-1 and VCAM-1. This induction can be inhibited by adiponectin, ICAM-1, and VCAM-1 through a negative feedback mechanism, as well as other inflammatory markers such as IL-6 and CRP, which is positively correlated with resistin in the patients with CKD. Furthermore, this correlation is seen in patients with renal transplant and animal model with diet-induced obesity.
The molecular experiment has shown that resistin through the NFκB pathway can carry out its effect on the overexpression of inflammatory molecules, including IL-6 and TNF-α. In the ESKD, resistin is reported to increase significantly, which was weakly correlated with inflammation and was not associated with insulin sensitivity and was negatively correlated with adiponectin level. Interestingly, the relationship between resistin level and all-cause death and cardiovascular events depended on adiponectin levels that mean adiponectin can modulate the inflammatory effect caused by resistin and other inflammatory elements.
| Omentin and Kidney Disease|| |
Omentin is a 313 amino acid protein which is mainly expressed in the visceral adipose tissue, which has a link with type 2 diabetes. Except for adipocytes, stromal vascular cells can also produce omentin. There are two kinds of omentin: type 1 and type 2. Omentin-1 is predominantly released in the visceral adipose tissue; however, omentin-2 is abundantly expressed in the intestine. Clinical investigations have demonstrated that administration of metformin in patients with polycystic ovary syndrome increases the serum level of omentin-1 and change in the omentin is negatively associated with hs-CRP. Omentin increases uptake of insulin-induced glucose through activated Akt cellular pathways. The level of omentin is positively correlated with adiponectin. The study on human microvascular endothelial cells cultured with normal serum showed that omentin suppresses NFκB activity, TNF-α, and CRP. The cell culture of human umbilical vein endothelial cells showed that omentin can decrease apoptotic activity and enhance blood flow recovery and differentiation into the vascular-like structure and also capillary density in the ischemic limb of mice.
In the ESRD patients receiving hemodialysis, the plasma level of omentin has been reported to be about 1.7 times higher than that of healthy people. On the other hand, in the CKD patients, the serum level of omentin was reported lower compared with healthy subjects. What's more, it has been reported that in the diabetic CKD patients, the level of omentin is lower than that one in nondiabetic patients. Furthermore, compared to healthy controls, omentin level was lower in stage 2 and 3, but not in stage 4, and an overall decrease in the omentin has been linked with increased inflammation and malnutrition components. In another study conducted on nondiabetic, not dialyzed CKD patients, the serum level of omentin-1 was higher in the patient group compared with healthy population. However, they were failed to find an association between omentin-1 and marker of inflammation (IL-6). In the study into the patients with kidney disorders, the serum level of omentin-1 was significantly lower in the diabetic hemodialysis ones compared with nondiabetic hemodialysis patients. Their hypothesis was based on decrease in omentin-1 linked to atherosclerosis through an effect on the vascular endothelial in inflammatory condition.
Moreover, circulating omentin is introduced as a novel biomarker of endothelial dysfunction. Circulating omentin is correlated with CRP, IL-6, BMI, fat mass percentage, blood pressure (both systolic and diastolic parameters), and independent vasodilation in the normal glucose tolerance subjects and is correlated with systolic blood pressure, BMI, insulin sensitivity, and CRP in the impaired glucose tolerance people. In hemodialysis patients, omentin-1 is introduced as the potential biomarker of subclinical atherosclerosis. In insulin resistance CKD patients, plasma level of omentin-1 was higher compared to healthy controls and was associated with insulin resistance in hemodialysis patients. Nevertheless, the report in the hemodialysis diabetic patients was completely inverse. According to a recent study, the detection of serum omentin level, which was lower in patients with microalbuminuria than in nonmicroalbuminuria and healthy control, can play a pivotal role in early diagnosis and prevention of DN in patients with type 2 diabetes mellitus.
Omentin seems to play a pleiotropic role in the regulation of metabolism and maintain body to be healthy; however, all in all, it is categorized as a good adipokine with beneficial effect on longer survival rate in patients with various diseases such as diabetes, insulin resistance, cancer, endothelial dysfunction, and atherosclerosis. In other words, despite not fully understanding of omentin functions, an increase in the level of omentin seems to be a marker for leanness, while the decreased level brings about the situation for overweight and obesity along with their comorbidities.
| Apelin and Kidney Disease|| |
Apelin is an adipocytokine produced in the white adipose tissue and expressed in the various organs, including endothelium, heart, and kidney. It is a 36 peptide amino acid from a 77 amino acid precursor that, after some modifications in various organs, has several forms including apelin 36, 19, 17, 15, 13, 12, and 10. Apelin has a special receptor called APJ. It has a potential link with obesity and insulin sensitivity, and it is involved in the pathophysiology of cardiovascular disease in chronic renal failure. In these patients, apelin has been reported to be positively associated with E-selectin and VCAM. However, another study indicated that plasma apelin is not associated with cardiovascular risk in hemodialysis patients.
In kidney allograft recipients, apelin was correlated with coronary artery disease (CAD) and diabetes, and ICAM, adiponectin, and CAD were the predictors of apelin in them; it was significantly decreased. Except for CAD, endothelial damage and inflammation were also predictors of the presence of apelin which indicates the presence of apelin in that it and other adipocytokines may have a direct link with inflammation and disease' exacerbation.
Cellular study of apelin in the DN and measurement of its effect to disease exacerbation indicated that serum apelin level was positively correlated with microalbuminuria. In addition, apelin with its receptor participates in the development of DN. A further step of the study suggested that apelin may regulate glucose metabolism in diabetes. Further, the author reported that apelin may be a pivotal factor for pathological glomerular angiogenesis and facilitates abnormal vessel formation in the diabetic glomeruli, which contributes to the DN development. Apelin induces proliferation of glomerular endothelial cells and has a significant role in the pathological glomerular angiogenesis. Microalbuminuria and overt proteinuria are the common early signs of DN. In this study, the author found that serum apelin was positively correlated with microalbuminuria in type 2 diabetic patients. On the other hand, experiment on the mice with type 1 diabetes reported that apelin retards the progression of DN. It did not affect the blood pressure, glycemia, and body weight, and interestingly short and long treatment with apelin showed that clinical inflammation manifestations were significantly reduced informing that apelin has the protective role in the diabetic kidney. Confirmed reports stated that the level of apelin in the ESRD patients was negatively correlated with hs-CRP and IL-6, and after transplantation for these patients, the mentioned level was significantly increased.
Apelin-13 is one of the most important peptides with paramount biological functions. A study on patients with maintenance hemodialysis without heart failure in the pre- and post-dialysis courses about the association of serum apelin-13 level with asymmetric dimethylarginine (ADMA), as an important factor for the activity of NO synthase (NOS) and production of NO which is contributing to the inflammation, showed that both concentrations were increased and there was a positive correlation which would be affective on the blood pressure. Furthermore, an animal study demonstrated that apelin-13, which regulates the inflammation in DN via regulation of histone acetylation, as an important factor, has a beneficial effect on the treatment approaches. A similar study indicated that apelin-13 may be a therapeutic candidate for treating acute kidney injury (AKI) by inhibiting TGF-β. In agreement with the above-mentioned statements, another study suggested that apelin has potential renoprotective effects and may be an effective agent for retarding CKD progression. In addition, apelin ameliorates vascular calcification by suppressing osteoblastic differentiation of vascular smooth muscle cells via downregulation of sodium-dependent phosphate cotransporter. The complex effects of apelin on the regulation of renal hemodynamics are already determined.
| Other Adipocytokines and Kidney Disease|| |
Vaspin or visceral adipose-derived serine proteinase inhibitor is an adipokine identified in the animal model of type 2 diabetes. It is related to obesity and insulin resistance in human. In patients with type 2 diabetes, the clinical investigations indicate that the level of vaspin is higher than that of normal subjects,, although the similar level in the mentioned groups has also been seen. The clinical evaluation of serum vaspin in hemodialysis patients has revealed the higher concentration compared with healthy subjects. Nonetheless, another result found that mean serum vaspin was not significantly different between hemodialysis patients and healthy population. Furthermore, it has been reported that the serum TG and creatinine of all subjects were independently associated with serum vaspin. Similarly, positive association between vaspin concentrations and serum creatinine was indicted. On the other hand, in type 2 diabetes, microvascular complications were found associated with low vaspin levels. This finding was in parallel with glycemic control by metformin in those patients. It might be due to medications interfering with serum vaspin.
Since vaspin has 50-KDa molecular weight, it cannot be eliminated efficiently in the hemodialysis patients, and furthermore, because other adipokines such as adiponectin or leptin are observed usually higher in ESRD patients, it could be a unique feature in these patients. Moreover, due to the positive correlation of vaspin with BMI and albumin, it could be a representative for nutritional status. An animal study showed that administration of vaspin significantly reduces blood glucose and food intake. Molecular activity evaluation of vaspin shows that it has an inhibitory effect on ADAM as a competitive endothelial NOS (eNOS) inhibitor, which is a potential atherosclerosis risk factor, and therefore, it has an antiatherogenic and antiapoptotic effect on vascular endothelial cells. Due to its important role of vaspin on vascular cells, it acts as a compensatory factor.
Chemerin is a multifunctional protein found throughout the body which has various receptors, including chemokine-like receptor 1 (also known as ChemR23) and C-C chemokine receptor-like 2, and G protein-coupled receptor-1. It is a 16-kDa protein modulating immune responses and affecting lipid and glucose metabolism. Chemerin is one of the most important biomarkers of cardiovascular disease in diabetic CKD patients. In general, it seems that it would be a chemokine to immune cells or an adipokine for adipose tissue. It has a regulatory effect on adipocyte growth and lipid metabolism, and it is predominantly produced in the liver, found in high concentrations in the white adipose tissue. A study on the human showed that chemerin has a positive effect on low-density lipoprotein and has a negative association with high-density lipoprotein cholesterol in obese patients. It has also been stated that chemerin plays a role in the adipogenesis. The mRNA level of chemerin and its receptor was found higher in mature adipocytes. In addition, the intensity of mRNA expression is higher in the high-fat diet condition.
Chemerin has a positive correlation with inflammatory markers, including IL-6, CRP, and TNF-α. In other words, it has proinflammatory functions in various diseases. In an early study on the level of cheremin in the CKD patients, it has been found that mean serum level was about two-fold higher in CKD patients than subjects with GFR >50 ml/min. Moreover, GFR was an independent predictor for circulating cheremin level in both healthy and CKD patients. In type 2 diabetic patients, the level of serum chemerin was found to be higher in macroalbuminuria patients than in microalbuminuria and normoalbuminuria patients. In comparison with healthy people, it has also been found that only macroalbuminuria had a significant difference in terms of serum chemerin level among three above groups. In this study, the authors declared that renal function factors such as creatinine clearance had a significant association with serum chemerin.
In ESRD patients who prepared for transplantation, the level of serum chemerin was evaluated, which was decreased significantly after 3 months of transplantation, compared with the time before the operation. Serum creatinine was also reduced and GFR was improved. Another study confirmed that serum chemerin was normal after renal transplantation. During hemodialysis procedure, the serum level of chemerin remained higher than in healthy subjects or kidney transplantation. The only reasonable explanation for higher chemerin level in patients with kidney diseases  is related to renal dysfunction, and according to the studies on genetic expression of chemerin in CKD compared to healthy control, which was not significantly different, as well as its level in the adipose tissue which was not related to overproduction, possible causes of elevated circulating chemerin do not seem to be related to genetic factors, and elevated circulating chemerin levels that depend on renal function are not genetically determined. On the other hand, due to the considerable complications of the high level of chemerin in CKD patients, this issue should be targeted at the next clinical studies.
Progranulin is a cysteine-rich secreted protein with 68–88-kDa molecular weight. It expresses in a variety of cells such as immune cells, epithelial cells, adipocytes, and neurons. It has wound repair and tissue remodeling properties, as well as early embryogenesis and growth factor-like features, which regulates cell division, survival, and migration by regulation of ERK and PI3K signaling pathways. Association of progranulin with the alteration of adipocytes which results in progression to obesity has been survived. It consequently leads to insulin resistance and initiation of type 2 diabetes mellitus.
A clinical study on the kidney showed that progranulin serum level depends on the renal function. In various stages of CKD (1–5), it has been reported that serum progranulin is significantly different, being highest in the ESKD. It has also been found that GFR is an independent predictor factor for circulating serum progranulin. Moreover, it seems that progranulin is involved in the proinflammatory state among patients with renal disease. Therefore, similar to the previous statements of chemerin, renal filtration is the most pivotal efficient factor, eliminating the progranulin. In diabetic kidney disease, progranulin has also been found to have a crucial role in the pathophysiology renal decline and it can be used as an early prognostic factor for diabetic kidney disease. Moreover, it is introduced as a marker for diabetic microangiopathy and its severity. Nevertheless, progranulin plays a protective role with anti-inflammatory properties in the kidney of patients with renal ischemia–reperfusion injury.
Interleukin-1, interleukin-6, tumor necrosis facor-alpha, and C-reactive protein
IL-1 is divided into two important subtypes of IL-1α and IL-1β. Both are involved in the inflammatory responses in different parts of the animal and human bodies. Lots of studies have been carried out to indicate the exact role of IL-1 in the kidney function. In an animal model of AKI, necroinflammation commonly occurs. Mutant mice are protected against renal necroinflammation., In CKD models, IL-1 plays an inflammatory role in the exacerbation of CKD. It appears that IL-1 contributes to leukocyte adhesion and vascular leakage, which leads to a systemic endothelial dysfunction. Intrarenal inflammasome, as well as renal parenchymal cell necrosis by IL-1 and other inflammatory factors, results in renal dysfunction.
IL-6 is a pleiotropic cytokine with various functions. In IgA nephropathy, immune complex and complement component stimulate mesangial cells to release IL-6 which causes proliferation and recruitment of inflammatory factors and immune cell, involved in the necrosis of renal cells. In DN, proteinuria is observed due to elevated proinflammatory cytokines such as IL-6., Hyperglycemia can trigger tubules, podocytes, mesangial cells, and interstitial tissues, which participate in the systemic inflammatory process in DN., Furthermore, both type 1 and type 2 diabetes are positively correlated with increased IL-6 level.,In vitro studies on the IL-6 showed that IL-6 induces insulin resistance., IL-6 has also a direct relationship with AKI. Clinical findings demonstrated that IL-6 signaling and transcription are increased in ischemic AKIs. In CKDs, IL-6 is observed to remain high. Meantime, infiltrated IL-6 is due to a reduced clearance and renal dysfunction which contributes to the accumulation of IL-6. This issue consequently results in inflammatory responses and an increase in the IL-6 production.,
TNF-α is a proinflammatory cytokine and necessary part of tissue damage. It comes from macrophages infiltrating adipose tissue and kidney. TNF-α, as well as IL-6, mediates chronic and acute inflammation in a variety of disorders such as patients with kidney disease  and cardiovascular disease. Limitation of TNF-α in an animal model with renal failure leads to a reduction of renal inflammation and fibrosis. TNF-α is associated with the prevalence and severity of CKD. This relationship is reported in various clinical and epidemiological studies., Besides, TNF-α receptor-2 is positively associated with developing risk of CKD. One of the main reasons for this observation comes from a lack of proper clearance in the renal and elevated inflammatory cytokines, leading to progression of renal dysfunction. In addition, in kidney, TNF-α contributes to angiotensin II-dependent hypertension, independent of blood pressure. Deficiency in TNF-α in thw kidney increases renal eNOS expression, resulting in increased bioavailability of NO. With the various roles of TNF-α in the inflammatory kidney diseases, a more precise study with better framework should be done to understand the pathophysiology of TNF-α in kidney disorders.
CRP is an acute-phase reactant. Although it does not belong to adipokines due to its noticeable role in kidney pathogenesis, it provides beneficial information about inflammation status of the disease. It has been reported that CRP is not significantly increased in CKD patients. The confirmed results approve this finding. However, other reports stated that CRP can be a predictor of mortalities in hemodialysis patients. In chronic dialysis patients, CRP is found to be a risk factor of death. Another investigation found that CRP predicts all-cause and CVD mortality in hemodialysis patients. In CKD patients with type 2 diabetes, CRP is positively associated with severity and progression of the disease. Furthermore, CRP is found to have a significant association with eGFR, while others declined any relative association.,,
| Conclusion|| |
Kidney diseases have become one of the fast-growing diseases with many interrelated comorbidities. Recent epidemiological data have proven the necessity of especial global monitoring for both diagnosis and prediction of diseases through the evaluation of above-mentioned factors. Despite emerging strategies and constant investigation, still, we face many problems in the treatment. If we are not able to reverse or at least stop the disease progression, is it time to change our mind and monitor other elements such as adipokine due to their beneficial and detrimental ramifications?
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hill NR, Fatoba ST, Oke JL, Hirst JA, O'Callaghan CA, Lasserson DS, et al.
Global prevalence of chronic kidney disease – A systematic review and meta-analysis. PLoS One 2016;11:e0158765.
Saran R, Robinson B, Abbott KC, Agodoa LY, Albertus P, Ayanian J, et al.
US renal data system 2016 annual data report: Epidemiology of kidney disease in the United States. Am J Kidney Dis 2017;69:A7-8.
Axelsson J. Fat Mass, Adipokines and Clinical Complications of Chronic Kidney Disease. Karolinska Institute, Stockholm, Sweden: Institutionen för Klinisk Vetenskap/Department of Clinical Sciences; 2006.
Izadi V, Azadbakht L. Specific dietary patterns and concentrations of adiponectin. J Res Med Sci 2015;20:178-84.
Pourmoghaddas Z, Sadeghi M, Hekmatnia A, Sanei H, Tavakoli B, Roohafza H, et al
. Different measurements of the obesity, adiponectin and coronary heart disease: A single-center study from Isfahan. J Res Med Sci 2012;17:S218-22.
Chaldakov GN, Stankulov IS, Hristova M, Ghenev PI. Adipobiology of disease: Adipokines and adipokine-targeted pharmacology. Curr Pharm Des 2003;9:1023-31.
Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci 2015;36:461-70.
Rüster C, Wolf G. Adipokines promote chronic kidney disease. Nephrol Dial Transplant 2013;28 Suppl 4:iv8-14.
Miyamoto S, Sharma K. Adipokines protecting CKD. Nephrol Dial Transplant 2013;28 Suppl 4:iv15-22.
Jia T, Carrero JJ, Lindholm B, Stenvinkel P. The complex role of adiponectin in chronic kidney disease. Biochimie 2012;94:2150-6.
Lenghel AR, Kacso IM, Bondor CI, Rusu C, Rahaian R, Gherman Caprioara M, et al.
Intercellular adhesion molecule, plasma adiponectin and albuminuria in type 2 diabetic patients. Diabetes Res Clin Pract 2012;95:55-61.
Guebre-Egziabher F, Bernhard J, Funahashi T, Hadj-Aissa A, Fouque D. Adiponectin in chronic kidney disease is related more to metabolic disturbances than to decline in renal function. Nephrol Dial Transplant 2005;20:129-34.
Kacso IM, Bondor CI, Kacso G. Plasma adiponectin is related to the progression of kidney disease in type 2 diabetes patients. Scand J Clin Lab Invest 2012;72:333-9.
Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, et al.
Association between adiponectin and mediators of inflammation in obese women. Diabetes 2003;52:942-7.
Nakamaki S, Satoh H, Kudoh A, Hayashi Y, Hirai H, Watanabe T, et al.
Adiponectin reduces proteinuria in streptozotocin-induced diabetic wistar rats. Exp Biol Med (Maywood) 2011;236:614-20.
Sharma K. The link between obesity and albuminuria: Adiponectin and podocyte dysfunction. Kidney Int 2009;76:145-8.
Koshimura J, Fujita H, Narita T, Shimotomai T, Hosoba M, Yoshioka N, et al.
Urinary adiponectin excretion is increased in patients with overt diabetic nephropathy. Biochem Biophys Res Commun 2004;316:165-9.
Kollerits B, Fliser D, Heid IM, Ritz E, Kronenberg F; MMKD Study Group, et al.
Gender-specific association of adiponectin as a predictor of progression of chronic kidney disease: The mild to moderate kidney disease study. Kidney Int 2007;71:1279-86.
Abdallah E, Waked E, Nabil M, El-Bendary O. Adiponectin and cardiovascular outcomes among hemodialysis patients. Kidney Blood Press Res 2012;35:247-53.
Hayashi M, Shibata R, Takahashi H, Ishii H, Aoyama T, Kasuga H, et al.
Association of adiponectin with carotid arteriosclerosis in predialysis chronic kidney disease. Am J Nephrol 2011;34:249-55.
Becker B, Kronenberg F, Kielstein JT, Haller H, Morath C, Ritz E, et al.
Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients with kidney disease: The mild and moderate kidney disease study. J Am Soc Nephrol 2005;16:1091-8.
Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, et al.
Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 2002;13:134-41.
Kishida K, Funahashi T, Shimomura I. Adiponectin as a routine clinical biomarker. Best Pract Res Clin Endocrinol Metab 2014;28:119-30.
Ambarkar M, Pemmaraju SV, Gouroju S, Manohar SM, Bitla AR, Yajamanam N, et al.
Adipokines and their relation to endothelial dysfunction in patients with chronic kidney disease. J Clin Diagn Res 2016;10:BC04-8.
Tsai YC, Lee CT, Huang TL, Cheng BC, Kuo CC, Su Y, et al.
Inflammatory marker but not adipokine predicts mortality among long-term hemodialysis patients. Mediators Inflamm 2007;2007:19891.
Martinez Cantarin MP, Waldman SA, Doria C, Frank AM, Maley WR, Ramirez CB, et al.
The adipose tissue production of adiponectin is increased in end-stage renal disease. Kidney Int 2013;83:487-94.
Shen YY, Charlesworth JA, Kelly JJ, Peake PW. The effect of renal transplantation on adiponectin and its isoforms and receptors. Metabolism 2007;56:1201-8.
Knight SF, Quigley JE, Yuan J, Roy SS, Elmarakby A, Imig JD, et al.
Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet. Hypertension 2008;51:352-9.
Bełtowski J, Jamroz-Wiśniewska A, Wójcicka G, Lowicka E, Wojtak A. Renal antioxidant enzymes and glutathione redox status in leptin-induced hypertension. Mol Cell Biochem 2008;319:163-74.
Naini AE, Vahdat S, Hedaiati ZP, Shahzeidi S, Pezeshki AH, Nasri H, et al.
The effect of Vitamin D administration on serum leptin and adiponectin levels in end-stage renal disease patients on hemodialysis with Vitamin D deficiency: A placebo-controlled double-blind clinical trial. J Res Med Sci 2016;21:1.
Mak RH, Cheung W, Cone RD, Marks DL. Leptin and inflammation-associated cachexia in chronic kidney disease. Kidney Int 2006;69:794-7.
Tesauro M, Mascali A, Franzese O, Cipriani S, Cardillo C, Di Daniele N, et al.
Chronic kidney disease, obesity, and hypertension: The role of leptin and adiponectin. Int J Hypertens 2012;2012:943605.
Wolf G, Hamann A, Han DC, Helmchen U, Thaiss F, Ziyadeh FN, et al.
Leptin stimulates proliferation and TGF-beta expression in renal glomerular endothelial cells: Potential role in glomerulosclerosis [seecomments]. Kidney Int 1999;56:860-72.
Gunduz Z, Dursun N, Akgun H, Ozturk F, Okur H, Koc N, et al.
Renal effects of long-term leptin infusion and preventive role of losartan treatment in rats. Regul Pept 2005;132:59-66.
Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, et al.
Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 2007;178:1748-58.
Kang YS, Song HK, Lee MH, Ko GJ, Han JY, Han SY, et al.
Visfatin is upregulated in type-2 diabetic rats and targets renal cells. Kidney Int 2010;78:170-81.
Song HK, Lee MH, Kim BK, Park YG, Ko GJ, Kang YS, et al.
Visfatin: A new player in mesangial cell physiology and diabetic nephropathy. Am J Physiol Renal Physiol 2008;295:F1485-94.
Yilmaz MI, Saglam M, Carrero JJ, Qureshi AR, Caglar K, Eyileten T, et al.
Serum visfatin concentration and endothelial dysfunction in chronic kidney disease. Nephrol Dial Transplant 2008;23:959-65.
Mu J, Feng B, Ye Z, Yuan F, Zeng W, Luo Z, et al.
Visfatin is related to lipid dysregulation, endothelial dysfunction and atherosclerosis in patients with chronic kidney disease. J Nephrol 2011;24:177-84.
Axelsson J, Witasp A, Carrero JJ, Qureshi AR, Suliman ME, Heimbürger O, et al.
Circulating levels of visfatin/pre-B-cell colony-enhancing factor 1 in relation to genotype, GFR, body composition, and survival in patients with CKD. Am J Kidney Dis 2007;49:237-44.
Carrero JJ, Witasp A, Stenvinkel P, Qureshi AR, Heimbürger O, Bárány P, et al.
Visfatin is increased in chronic kidney disease patients with poor appetite and correlates negatively with fasting serum amino acids and triglyceride levels. Nephrol Dial Transplant 2010;25:901-6.
Mahmood N, Junejo AM, Jamal Q, Awan R. Association of visfatin with chronic kidney disease in a cohort of patients with and without diabetes. J Pak Med Assoc 2010;60:922-6.
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al.
The hormone resistin links obesity to diabetes. Nature 2001;409:307-12.
Dimitriadis K, Tsioufis C, Selima M, Tsiachris D, Miliou A, Kasiakogias A, et al.
Independent association of circulating resistin with glomerular filtration rate in the early stages of essential hypertension. J Hum Hypertens 2009;23:668-73.
Hu WL, Qiao SB, Li JJ. Decreased C-reactive protein-induced resistin production in human monocytes by simvastatin. Cytokine 2007;40:201-6.
Axelsson J, Bergsten A, Qureshi AR, Heimbürger O, Bárány P, Lönnqvist F, et al.
Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance. Kidney Int 2006;69:596-604.
Marouga A, Dalamaga M, Kastania AN, Antonakos G, Thrasyvoulides A, Kontelia G, et al.
Correlates of serum resistin in elderly, non-diabetic patients with chronic kidney disease. Clin Lab 2013;59:1121-8.
Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A. Resistin, an adipokine with potent proinflammatory properties. J Immunol 2005;174:5789-95.
Therrien FJ, Agharazii M, Lebel M, Larivière R. Neutralization of tumor necrosis factor-alpha reduces renal fibrosis and hypertension in rats with renal failure. Am J Nephrol 2012;36:151-61.
Spoto B, Mattace-Raso F, Sijbrands E, Pizzini P, Cutrupi S, D'Arrigo G, et al.
Resistin and all-cause and cardiovascular mortality: Effect modification by adiponectin in end-stage kidney disease patients. Nephrol Dial Transplant 2013;28 Suppl 4:iv181-7.
Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC, et al.
Identification of omentin as a novel depot-specific adipokine in human adipose tissue: Possible role in modulating insulin action. Am J Physiol Endocrinol Metab 2006;290:E1253-61.
de Souza Batista CM, Yang RZ, Lee MJ, Glynn NM, Yu DZ, Pray J, et al.
Omentin plasma levels and gene expression are decreased in obesity. Diabetes 2007;56:1655-61.
Tan BK, Adya R, Farhatullah S, Chen J, Lehnert H, Randeva HS, et al.
Metformin treatment may increase omentin-1 levels in women with polycystic ovary syndrome. Diabetes 2010;59:3023-31.
Maruyama S, Shibata R, Kikuchi R, Izumiya Y, Rokutanda T, Araki S, et al.
Fat-derived factor omentin stimulates endothelial cell function and ischemia-induced revascularization via endothelial nitric oxide synthase-dependent mechanism. J Biol Chem 2012;287:408-17.
Alcelik A, Tosun M, Ozlu MF, Eroglu M, Aktas G, Kemahli E, et al.
Serum levels of omentin in end-stage renal disease patients. Kidney Blood Press Res 2012;35:511-6.
Tekce H, Tekce BK, Aktas G, Alcelik A, Sengul E. Serum omentin-1 levels in diabetic and nondiabetic patients with chronic kidney disease. Exp Clin Endocrinol Diabetes 2014;122:451-6.
Sengul E, Duygulu G, Dindar S, Bunul F. Serum omentin-1, inflammation and carotid atherosclerosis in patients with non-diabetic chronic kidney disease. Ren Fail 2013;35:1089-93.
Kocijancic M, Vujicic B, Racki S, Zaputovic L, Dvornik S. Serum omentin-1 level in diabetic patients on haemodialysis: A pilot study. Biochem Med 2014;24:S65-6.
Moreno-Navarrete JM, Ortega F, Castro A, Sabater M, Ricart W, Fernández-Real JM, et al.
Circulating omentin as a novel biomarker of endothelial dysfunction. Obesity (Silver Spring) 2011;19:1552-9.
Kocijancic M, Cubranic Z, Vujicic B, Racki S, Dvornik S, Zaputovic L, et al.
Soluble intracellular adhesion molecule-1 and omentin-1 as potential biomarkers of subclinical atherosclerosis in hemodialysis patients. Int Urol Nephrol 2016;48:1145-54.
Qasema A, Faragea S, Elmesallamya FA, Elsaidb HH. Association of plasma omentin-1 level with insulin resistance in chronic kidney disease patients. Endocrinology 2015;1:72-6.
Kocijancic M, Vujicic B, Racki S, Cubranic Z, Zaputovic L, Dvornik S, et al.
Serum omentin-1 levels as a possible risk factor of mortality in patients with diabetes on haemodialysis. Diabetes Res Clin Pract 2015;110:44-50.
Al-Kirwi IN, AL-Fahdawi SS. Evaluations of omentin as a predictor for type 2 diabetic nephropathy. Int J Sci Eng Res 2016;10:804-8.
Jaikanth C, Gurumurthy P, Cherian KM, Indhumathi T. Emergence of omentin as a pleiotropic adipocytokine. Exp Clin Endocrinol Diabetes 2013;121:377-83.
Halabis M, Dziedzic M, Warchulinska J, Kaznowska-Bystryk I, Solski J. Omentin-a new adipokine with many roles to play. Curr Issues Pharm Med Sci 2015;28:176-80.
Malyszko J, Malyszko JS, Pawlak K, Mysliwiec M. Visfatin and apelin, new adipocytokines, and their relation to endothelial function in patients with chronic renal failure. Adv Med Sci 2008;53:32-6.
Kleinz MJ, Davenport AP. Emerging roles of apelin in biology and medicine. Pharmacol Ther 2005;107:198-211.
Boucher J, Masri B, Daviaud D, Gesta S, Guigné C, Mazzucotelli A, et al.
Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology 2005;146:1764-71.
Małyszko J, Małyszko JS, Koźminski P, Myśliwiec M. Apelin and cardiac function in hemodialyzed patients: Possible relations? Am J Nephrol 2006;26:121-6.
Leal VO, Lobo JC, Stockler-Pinto MB, Farage NE, Calixto A, Geloneze B, et al.
Apelin: A peptide involved in cardiovascular risk in hemodialysis patients? Ren Fail 2012;34:577-81.
Malyszko J, Malyszko JS, Pawlak K, Wolczynski S, Mysliwiec M. Apelin, a novel adipocytokine, in relation to endothelial function and inflammation in kidney allograft recipients. Transplant Proc 2008;40:3466-9.
Zhang BH, Wang W, Wang H, Yin J, Zeng XJ. Promoting effects of the adipokine, apelin, on diabetic nephropathy. PLoS One 2013;8:e60457.
Day RT, Cavaglieri RC, Feliers D. Apelin retards the progression of diabetic nephropathy. Am J Physiol Renal Physiol 2013;304:F788-800.
El-Shehaby AM, El-Khatib MM, Battah AA, Roshdy AR. Apelin: A potential link between inflammation and cardiovascular disease in end stage renal disease patients. Scand J Clin Lab Invest 2010;70:421-7.
Zhang DL, Liao H, Wei YY, Zhang Y, Zhang QD, Wang ZG, et al.
Elevation of serum apelin-13 is positively correlated with ADMA in patients on maintenance hemodialysis. Clin Nephrol 2009;71:405-12.
Chen H, Li J, Jiao L, Petersen RB, Li J, Peng A, et al.
Apelin inhibits the development of diabetic nephropathy by regulating histone acetylation in akita mouse. J Physiol 2014;592:505-21.
Chen H, Wan D, Wang L, Peng A, Xiao H, Petersen RB, et al.
Apelin protects against acute renal injury by inhibiting TGF-β1. Biochim Biophys Acta 2015;1852:1278-87.
Wang LY, Diao ZL, Zhang DL, Zheng JF, Zhang QD, Ding JX, et al.
The regulatory peptide apelin: A novel inhibitor of renal interstitial fibrosis. Amino Acids 2014;46:2693-704.
Han X, Wang LY, Diao ZL, Liu WH. Apelin: A novel inhibitor of vascular calcification in chronic kidney disease. Atherosclerosis 2016;244:1-8.
Hus-Citharel A, Bouby N, Frugière A, Bodineau L, Gasc JM, Llorens-Cortes C, et al.
Effect of apelin on glomerular hemodynamic function in the rat kidney. Kidney Int 2008;74:486-94.
Hida K, Wada J, Eguchi J, Zhang H, Baba M, Seida A, et al.
Visceral adipose tissue-derived serine protease inhibitor: A unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci U S A 2005;102:10610-5.
El-Mesallamy HO, Kassem DH, El-Demerdash E, Amin AI. Vaspin and visfatin/nampt are interesting interrelated adipokines playing a role in the pathogenesis of type 2 diabetes mellitus. Metabolism 2011;60:63-70.
Ye Y, Hou XH, Pan XP, Lu JX, Jia WP. Serum vaspin level in relation to postprandial plasma glucose concentration in subjects with diabetes. Chin Med J (Engl) 2009;122:2530-3.
Youn BS, Klöting N, Kratzsch J, Lee N, Park JW, Song ES, et al.
Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes 2008;57:372-7.
Inoue J, Wada J, Teshigawara S, Hida K, Nakatsuka A, Takatori Y, et al.
The serum vaspin levels are reduced in Japanese chronic hemodialysis patients. BMC Nephrol 2012;13:163.
Seeger J, Ziegelmeier M, Bachmann A, Lössner U, Kratzsch J, Blüher M, et al.
Serum levels of the adipokine vaspin in relation to metabolic and renal parameters. J Clin Endocrinol Metab 2008;93:247-51.
Gulcelik NE, Karakaya J, Gedik A, Usman A, Gurlek A. Serum vaspin levels in type 2 diabetic women in relation to microvascular complications. Eur J Endocrinol 2009;160:65-70.
Klöting N, Kovacs P, Kern M, Heiker JT, Fasshauer M, Schön MR, et al.
Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects. Diabetologia 2011;54:1819-23.
Jung CH, Lee WJ, Hwang JY, Lee MJ, Seol SM, Kim YM, et al.
Vaspin increases nitric oxide bioavailability through the reduction of asymmetric dimethylarginine in vascular endothelial cells. PLoS One 2012;7:e52346.
Ferland DJ, Watts SW. Chemerin: A comprehensive review elucidating the need for cardiovascular research. Pharmacol Res 2015;99:351-61.
Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, Collier G, et al.
Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 2007;148:4687-94.
Salama FE, Anass QA, Abdelrahman AA, Saeed EB. Chemerin: A biomarker for cardiovascular disease in diabetic chronic kidney disease patients. Saudi J Kidney Dis Transpl 2016;27:977-84.
Lőrincz H, Katkó M, Harangi M, Somodi S, Gaál K, Fülöp P, et al.
Strong correlations between circulating chemerin levels and lipoprotein subfractions in nondiabetic obese and nonobese subjects. Clin Endocrinol (Oxf) 2014;81:370-7.
Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, Parlee SD, et al.
Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 2007;282:28175-88.
Roh SG, Song SH, Choi KC, Katoh K, Wittamer V, Parmentier M, et al.
Chemerin – A new adipokine that modulates adipogenesis via its own receptor. Biochem Biophys Res Commun 2007;362:1013-8.
Lehrke M, Becker A, Greif M, Stark R, Laubender RP, von Ziegler F, et al.
Chemerin is associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis. Eur J Endocrinol 2009;161:339-44.
Teta D. Adipokines as uremic toxins. J Ren Nutr 2012;22:81-5.
Pfau D, Bachmann A, Lössner U, Kratzsch J, Blüher M, Stumvoll M, et al.
Serum levels of the adipokine chemerin in relation to renal function. Diabetes Care 2010;33:171-3.
Hu W, Feng P. Elevated serum chemerin concentrations are associated with renal dysfunction in type 2 diabetic patients. Diabetes Res Clin Pract 2011;91:159-63.
Rutkowski P, Sledzinski T, Zielinska H, Lizakowski S, Goyke E, Szrok-Wojtkiewicz S, et al.
Decrease of serum chemerin concentration in patients with end stage renal disease after successful kidney transplantation. Regul Pept 2012;173:55-9.
Blaszak J, Szolkiewicz M, Sucajtys-Szulc E, Konarzewski M, Lizakowski S, Swierczynski J, et al.
High serum chemerin level in CKD patients is related to kidney function, but not to its adipose tissue overproduction. Ren Fail 2015;37:1033-8.
Rabo SA, Mohamed NA, Tawfik NA, Hamed MM. Serum chemerin level in chronic kidney disease. Egypt J Intern Med 2016;28:99.
Leiherer A, Muendlein A, Kinz E, Vonbank A, Rein P, Fraunberger P, et al.
High plasma chemerin is associated with renal dysfunction and predictive for cardiovascular events – Insights from phenotype and genotype characterization. Vascul Pharmacol 2016;77:60-8.
Bonomini M, Pandolfi A. Chemerin in renal dysfunction and cardiovascular disease. Vascul Pharmacol 2016;77:28-34.
He Z, Bateman A. Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med (Berl) 2003;81:600-12.
Nguyen AD, Nguyen TA, Martens LH, Mitic LL, Farese RV Jr. Progranulin: At the interface of neurodegenerative and metabolic diseases. Trends Endocrinol Metab 2013;24:597-606.
Bateman A, Bennett HP. The granulin gene family: From cancer to dementia. Bioessays 2009;31:1245-54.
Daniel R, Daniels E, He Z, Bateman A. Progranulin (acrogranin/PC cell-derived growth factor/granulin-epithelin precursor) is expressed in the placenta, epidermis, microvasculature, and brain during murine development. Dev Dyn 2003;227:593-9.
Nicoletto BB, Canani LH. The role of progranulin in diabetes and kidney disease. Diabetol Metab Syndr 2015;7:117.
Richter J, Focke D, Ebert T, Kovacs P, Bachmann A, Lössner U, et al.
Serum levels of the adipokine progranulin depend on renal function. Diabetes Care 2013;36:410-4.
Schlatzer D, Maahs DM, Chance MR, Dazard JE, Li X, Hazlett F, et al.
Novel urinary protein biomarkers predicting the development of microalbuminuria and renal function decline in type 1 diabetes. Diabetes Care 2012;35:549-55.
Xu L, Zhou B, Li H, Liu J, Du J, Zang W, et al.
Serum levels of progranulin are closely associated with microvascular complication in type 2 diabetes. Dis Markers 2015;2015:357279.
Zhou M, Tang W, Fu Y, Xu X, Wang Z, Lu Y, et al.
Progranulin protects against renal ischemia/reperfusion injury in mice. Kidney Int 2015;87:918-29.
Mulay SR, Kulkarni OP, Rupanagudi KV, Migliorini A, Darisipudi MN, Vilaysane A, et al.
Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1β secretion. J Clin Invest 2013;123:236-46.
Komada T, Usui F, Kawashima A, Kimura H, Karasawa T, Inoue Y, et al.
Role of NLRP3 inflammasomes for rhabdomyolysis-induced acute kidney injury. Sci Rep 2015;5:10901.
Anders HJ. Of inflammasomes and alarmins: IL-1β and IL-1α in kidney disease. J Am Soc Nephrol 2016;27:2564-75.
Dalla Vestra M, Mussap M, Gallina P, Bruseghin M, Cernigoi AM, Saller A, et al.
Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. J Am Soc Nephrol 2005;16 Suppl 1:S78-82.
Navarro JF, Milena FJ, Mora C, León C, García J. Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: Effect of angiotensin-converting enzyme inhibition and pentoxifylline administration. Am J Nephrol 2006;26:562-70.
Kaur H, Chien A, Jialal I. Hyperglycemia induces toll like receptor 4 expression and activity in mouse mesangial cells: Relevance to diabetic nephropathy. Am J Physiol Renal Physiol 2012;303:F1145-50.
Pfäfflin A, Brodbeck K, Heilig CW, Häring HU, Schleicher ED, Weigert C, et al.
Increased glucose uptake and metabolism in mesangial cells overexpressing glucose transporter 1 increases interleukin-6 and vascular endothelial growth factor production: Role of AP-1 and HIF-1alpha. Cell Physiol Biochem 2006;18:199-210.
Gurr W, Yavari R, Wen L, Shaw M, Mora C, Christa L, et al.
Areg family protein is overexpressed in islets from a patient with new-onset type 1 diabetes and acts as T-cell autoantigen in NOD mice. Diabetes 2002;51:339-46.
Andriankaja OM, Barros SP, Moss K, Panagakos FS, DeVizio W, Beck J, et al.
Levels of serum interleukin (IL)-6 and gingival crevicular fluid of IL-1beta and prostaglandin E(2) among non-smoking subjects with gingivitis and type 2 diabetes. J Periodontol 2009;80:307-16.
Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem 2003;278:45777-84.
Lagathu C, Bastard JP, Auclair M, Maachi M, Capeau J, Caron M, et al.
Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: Prevention by rosiglitazone. Biochem Biophys Res Commun 2003;311:372-9.
Grigoryev DN, Liu M, Hassoun HT, Cheadle C, Barnes KC, Rabb H, et al.
The local and systemic inflammatory transcriptome after acute kidney injury. J Am Soc Nephrol 2008;19:547-58.
Pecoits-Filho R, Heimbürger O, Bárány P, Suliman M, Fehrman-Ekholm I, Lindholm B, et al.
Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis 2003;41:1212-8.
Takahashi T, Kubota M, Nakamura T, Ebihara I, Koide H. Interleukin-6 gene expression in peripheral blood mononuclear cells from patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Ren Fail 2000;22:345-54.
Caglar K, Peng Y, Pupim LB, Flakoll PJ, Levenhagen D, Hakim RM, et al.
Inflammatory signals associated with hemodialysis. Kidney Int 2002;62:1408-16.
Barreto DV, Barreto FC, Liabeuf S, Temmar M, Lemke HD, Tribouilloy C, et al.
Plasma interleukin-6 is independently associated with mortality in both hemodialysis and pre-dialysis patients with chronic kidney disease. Kidney Int 2010;77:550-6.
Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E, et al.
Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 2000;101:2149-53.
Matoba K, Kawanami D, Ishizawa S, Kanazawa Y, Yokota T, Utsunomiya K, et al.
Rho-kinase mediates TNF-α-induced MCP-1 expression via p38 MAPK signaling pathway in mesangial cells. Biochem Biophys Res Commun 2010;402:725-30.
Lee BT, Ahmed FA, Hamm LL, Teran FJ, Chen CS, Liu Y, et al.
Association of C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 with chronic kidney disease. BMC Nephrol 2015;16:77.
Gupta J, Mitra N, Kanetsky PA, Devaney J, Wing MR, Reilly M, et al.
Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC. Clin J Am Soc Nephrol 2012;7:1938-46.
Upadhyay A, Larson MG, Guo CY, Vasan RS, Lipinska I, O'Donnell CJ, et al.
Inflammation, kidney function and albuminuria in the framingham offspring cohort. Nephrol Dial Transplant 2011;26:920-6.
Shankar A, Sun L, Klein BE, Lee KE, Muntner P, Nieto FJ, et al.
Markers of inflammation predict the long-term risk of developing chronic kidney disease: A population-based cohort study. Kidney Int 2011;80:1231-8.
Bemelmans MH, Gouma DJ, Buurman WA. Influence of nephrectomy on tumor necrosis factor clearance in a murine model. J Immunol 1993;150:2007-17.
Zhang J, Patel MB, Griffiths R, Mao A, Song YS, Karlovich NS, et al.
Tumor necrosis factor-α produced in the kidney contributes to angiotensin II-dependent hypertension. Hypertension 2014;64:1275-81.
Ernandez T, Mayadas TN. Immunoregulatory role of TNFalpha in inflammatory kidney diseases. Kidney Int 2009;76:262-76.
Bergstrom J, Lindholm B, Qureshi A. C-reactive protein as predictor for serum albumin and mortality in hemodialysis. J Am Soc Nephrol 1995;6:573-7.
Iseki K, Tozawa M, Yoshi S, Fukiyama K. Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients. Nephrol Dial Transplant 1999;14:1956-60.
Yeun JY, Levine RA, Mantadilok V, Kaysen GA. C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2000;35:469-76.
Yeo ES, Hwang JY, Park JE, Choi YJ, Huh KB, Kim WY, et al.
Tumor necrosis factor (TNF-alpha) and C-reactive protein (CRP) are positively associated with the risk of chronic kidney disease in patients with type 2 diabetes. Yonsei Med J 2010;51:519-25.
Sarnak MJ, Poindexter A, Wang SR, Beck GJ, Kusek JW, Marcovina SM, et al.
Serum C-reactive protein and leptin as predictors of kidney disease progression in the modification of diet in renal disease study. Kidney Int 2002;62:2208-15.
|This article has been cited by|
||Immunostaining characteristics of irisin in benign and malignant renal cancers
| ||T. Kuloglu,G. Artas,M. Yardim,i. Sahin,Y. Aydin,N. Beyoglu,I. H. Özercan,M. H. Yalcin,K. Ugur,S. Aydin |
| ||Biotechnic & Histochemistry. 2019; : 1 |
|[Pubmed] | [DOI]|
||Adiponectin inhibits proliferation of vascular endothelial cells induced by Ox-LDL by promoting dephosphorylation of Caveolin-1 and depolymerization of eNOS and up-regulating release of NO
| ||Yan Lu,Xiaoying Gao,Ruihua Wang,Jing Sun,Beibei Guo,Ruipeng Wei,Yongping Jia |
| ||International Immunopharmacology. 2019; 73: 424 |
|[Pubmed] | [DOI]|