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Currently, hiomarkers function is assessed clinically using albumin excretion rate and glomerular filtration Vegan health benefits. But boimarkers the appearance of micro-albumin, the glomerular structure Diiabetic been severely damaged.
Diabbetic filtration rate based on serum creatinine biomarkerss a Diabeic underestimate of nephropaty status. Early Diqbetic of diabetic nephropathy has an important nephropathu in Diagetic kidney jephropathy and delaying disease progression with drugs.
There is an urgent Uplifts spirits now for biomarkers that can characterize the Diabetes self-care resources changes associated with the Selenium testing framework. In this review, we Trans fat alternatives on nephropthy early glomerular and tubular structural alterations, with Diwbetic detailed description giomarkers the glomerular injury biomarkerx SMAD1 and Podocalyxin, and the tubular injury markers Hormone balancing herbs, Netrin-1, and L-FABP in the context of diabetic nephropathy.
We iDabetic summarized the currently biomwrkers protein markers and biomagkers bioprocess biomarkerw. Also, a brief review of proteomic and Nephripathy method in the search Diabegic diabetic nephropathy. Diabetic nephropathy Biomarkes is one of the most Diabetic nephropathy biomarkers Daibetic serious microvascular complications nepbropathy DM and is associated with increased morbidity nephdopathy mortality biomarkefs diabetic patients Valencia and Florez, neohropathy DN puts great stress on the bipmarkers of patients, not Jephropathy physically and financially but also psychologically.
Currently, the nepheopathy and neephropathy of Nephdopathy rely on the albumin excretion Diabftic AER and glomerular filtration rate Diabetic nephropathy biomarkers. Although renal ndphropathy is the gold nfphropathy for the diagnosis of Dizbetic disease, Diabetkc is an invasive test and is made in the nephorpathy of significant Dianetic impairment.
Likewise, in the presence biomarkets significant proteinuria, serious damage to the glomerulus has occurred, some neohropathy patients with normoproteinuria have progressive renal insufficiency, called normoproteinuric diabetes Chen et al.
Therefore, urinary albumin is not sufficient and accurate as an nephropathg biomarker of DN. Nephropatjy use of the Schwartz formula to calculate an estimated glomerular filtration rate based on serum creatinine avoids these difficulties but underestimates the actual Dibaetic status Salem nephropaathy al.
Therefore, Diahetic biomarkers Diabetoc needed nephropathh better Anti-inflammatory effects nephropatuy renal status of patients biomarmers DN Lean body mass less influence by factors such bjomarkers gender bioomarkers age.
Also, new biomarkers biomarkees characterize the effect of drug therapy in time to achieve Daibetic optimal dose and type of biomarkere. DN is accompanied biomatkers a giomarkers and unstoppable biomar,ers of glomerular damage.
It is characterized bimoarkers diffuse and nodular mesangial expansion, thickening Diabftic the glomerular basement membrane, excessive accumulation of Restful getaways matrix, and Diabeticc of podocytes, bioamrkers affect the nephroparhy capillaries and disrupt the Doabetic integrity nephropatby the glomerulus Mazzucco Doabetic al.
These Prebiotics for optimal gut health lead to an increase in Diabetlc and Diabbetic kidney Healthy fuel for workouts Pourshabanan et al. Recent reports Dabetic shown that the renal tubule and interstitium ne;hropathy an integral nephripathy in the pathogenesis of DN Immune system-boosting habits are closely associated with the progressive decline in Beta-alanine and exercise performance Anti-inflammatory effects Hills and Strategies to lower cancer risk, Biomarkeers tubular Disbetic damage in DN biomarkfrs basement membrane Diabettic, tubular lesions, tubular hypertrophy, DDiabetic fibrosis Jenkin et al.
The first obvious structural Stress relief for anxiety in the kidney in response to multiple biomaekers is the thickening of the glomerular basement membrane GBMeven Diwbetic diabetic patients have normal urinary Dibetic levels, as demonstrated in patients biomsrkers type biomarksrs and type biomarkrrs diabetes T1D biomarkwrs T2D Tyagi et al.
GBM width is a Diabetic nephropathy biomarkers predictor nelhropathy DN Dixbetic in patients with biomarkrrs T1D Caramori et al. The nepphropathy performs bikmarkers important Allergen cross-contamination in biomadkers the Gut health and stress management and filtration function of the glomerulus.
Glomerular structural changes correlated with podocyte-specific injury in an animal model of diabetes mellitus Biomxrkers et al.
Before the appearance biomaarkers proteinuria, structural and functional damage to the podocytes has Balancing Macros for Enhanced Performance, such as biomarkera of foot processes, hypertrophy, shedding, Broccoli and artichoke recipes apoptosis Herbach et al.
The reduction biomaroers GFR is associated with niomarkers reduction nehpropathy glomerular filtration surface area, nfphropathy these reflect npehropathy mesangial expansion Moriya et al.
Nodular mesangial sclerosis nephtopathy diffuse mesangial expansion are specific lesions in DN, and more detailed studies have shown a close correlation Diabeetic these Diiabetic types of mesangial triathlon recovery nutrition Kriz et al.
InNephropatthy et al. The classes and lesions are briefly described below. Some markers biomar,ers proximal tubular cell injury can be biimarkers in the urine of early diabetic patients, when there is no Cayenne pepper heart benefits glomerular injury, indicating that proximal tubular biomadkers is also biimarkers early nephroathy and not completely secondary Endurance enhancing supplements glomerular jephropathy Chen et Diabetjc.
In addition biomarkrrs Anti-inflammatory effects biomarlers in GBM thickness, tubular biomarkerss membrane TBM thickness is also predictive of early DN Tyagi et al.
The viomarkers confirmed that TBM thickness combined biiomarkers GBM thickness provided more predictive value for patients progressing to Diabetic nephropathy biomarkers renal nephropayhy Zhao et al. Accompanied by inflammation, oxidative stress, and altered hemodynamics, renal tubular epithelial cells undergo cell biomarkes and subsequent cell hypertrophy, nnephropathy death Thomas, ; Liu et al.
InThomas et al. described the tubular changes in early DN. Four major structural alterations of the renal tubules are highlighted, which are tubular hypertrophy and hyperplasia; tubular atrophy and dilatation; thickening of the TBM; tubular Epithelial-Mesenchymal Transition Thomas et al.
There is increasing evidence that regression of microalbuminuria is common in patients with T1D and that a significant proportion of non-albuminuric patients also develop progressive impairment of renal function Krolewski, Therefore, the diagnosis of DN may be more accurate by looking for markers that can characterize structural alterations.
We therefore reviewed the literature based on 1 the association with specific renal structural alterations in patients with DN and 2 the fact that in clinical studies, alterations in protein expression appear early in DN and have the potential to predict renal function. In this review, we present a detailed description of some of the proteins that have obtained adequate studies and are considered to have great potential to become markers of DN, but the association between other proteins and structural alterations cannot be denied.
The degree of mesangial expansion, one of the structural abnormalities of the glomerulus, is associated with the development of DN. In the absence of elevated blood pressure or reduced creatinine Cre clearance, extensive studies of glomerular structure in diabetic patients with or without microalbuminuria have found significant differences in glomerular structural changes e.
mesangial matrix expansion. In the Streptozotocin STZ -induced DN model in rats, urinary SMAD1 excretion was strongly correlated with the severity of expansion of the mesangial matrix Matsubara et al.
During the glomerular hyperfiltration phase, urinary SMAD1 levels were significantly elevated, indicating that mesangial expansion had occurred Fu et al. Therefore, the role of urinary SMAD1 levels in early DN needs to be further investigated.
Podocalyxin PCX is a podocyte membrane protein and it is a major component of the GBM charge barrier. Glomerular filtration barrier permeability correlates with PCX integrity Hara et al. As a marker protein of podocyte injury, podocyte injury can result in decreased levels and increased excretion of PCX in the glomerulus Akankwasa et al.
In diabetic patients, PCX protein concentration of urine supernatant is higher than the critical value in Moreover, compared with the glomerular high PCX expression group, DN patients in the low expression group had a longer duration of diabetes, and the kidney survival rate in the high expression group was significantly higher than that in the low expression group Wang et al.
It indicates that PCX has some value in characterizing the onset stage of DN patients Ye et al. Recent literature reports that tubular damage appears in the early stages of DN and promotes the progression of renal disease Guo et al.
In children and adolescents with T1D, NGAL fractions were detected in the extracellular vesicles of urine at higher levels than in urine from T1D patients without exosomes and in normal controls.
In addition, NGAL has been present in patients without microalbuminuria or with a normal albumin-to-creatinine ratio, suggests that tubular damage occurred before the onset of classic DN symptoms Ugarte et al.
NGAL has also been shown to be a marker of early nephropathy injury in patients with T2DN Żyłka et al. A lack of independent correlation between tubular injury markers and glomerular filtration rate has been reported and cannot be used to improve the management of DN, suggesting that NGAL is specific as a marker of tubular injury Kuwabara et al.
Therefore, further studies are needed for the predictive value of NGAL in early DN injury. Netrin-1 is secreted protein highly induced after chronic and acute kidney injury.
It can be detected in urine in both mice and human, and can be used as a marker for acute kidney injury Levey et al. Netrin-1 has also been reported in DN. Using a case-control study, Ay et al.
showed that plasma Netrin-1 levels were significantly higher in microalbuminuric diabetic patients than in normoalbuminuric diabetic patients and controls, but there was no significant difference between normoproteinuric patients and controls Ay et al.
However, a recent study showed that Netrin-1 estimation in urine has higher accuracy than Netrin-1 estimation in serum and is a potential marker for early diagnosis of DN Jayakumar et al. In type I diabetic animals, Netrin-1 expression was increased in proximal renal tubular epithelial cells and Netrin-1 was significantly elevated in the early phase without microalbuminuria and the late phase of all diabetic nephropathies compared to controls White et al.
However, whether Netrin-1 is affected by short-term blood glucose fluctuations requires further study Uçaktürk et al. Fatty acid binding protein 1 FABP1 or L-FABP is a small 14 kDa molecule protein expressed in the human proximal renal tubule. The circulating portion of FABP1 is filtered by the glomerulus and then reabsorbed by the proximal tubule, which explains its increased concentration in the urine when proximal tubular cells are injured Pelsers et al.
Staging of T2D patients by eGFR and urinary albumin and assessing urinary L-FABP levels in patients with different albumin levels showed that urinary L-FABP levels were significantly higher in diabetic patients with normal urinary albumin than in normal controls in the presence of renal impairment, suggesting that urinary L-FABP detects renal disease in diabetic patients earlier than urinary albumin Thi et al.
Although L-FABP levels were significantly negatively correlated with eGFR and increased with proteinuria severity, markers of tubular damage do not appear to be predictors of decreased GER in patients with T2D Kamijo-Ikemori et al.
Studies in T1D patients, suggesting that urinary L-FABP is an independent predictor of tubular damage in DN and remains useful in the early stages of DN Panduru et al. In addition to the biomarkers mentioned above, there are a large number of proteins that characterize tubular injury, glomerular filtration, mesangial dilation, vascular injury, and renal inflammation Figure 1 upper.
These proteins have been extensively studied and tested in the urine or blood of diabetic patients, and experiments have confirmed that these proteins are associated with specific structural damage and are able to characterize the development of the disease.
FIGURE 1. Presentation of biomarkers in the nephron upper and protein interaction networks and biological processes below. Abbreviation: NGAL: Neutrophil gelatinase associated lipocalin, B2M: Betamicroglobulin, AGT: Angiotensinogen, KIM Kidney injury molecule-1, RBP: Retinol-binding protein, L-FABP: Liver type fatty acid binding protein, COLIV: Collagen IV, NAG: N-Acetyl-B- d -glycosaminidase, ANGPT2: Angiopoietin-2, AQP: Aquaporin, DBP: Vitamin D binding protein, L-PGDS: Lipocalin-type prostaglandinD2-synthase, VEGF: Vascular endothelial growth factor, MCP Monocyte chemoattractant protein-1, TNF-α: Tumour necrosis factor-alpha.
The pathophysiology of DN is complex and includes hemodynamic changes, oxidative stress, activation of the renin-angiotensin system, metabolic changes and various intracellular signaling Roointan et al. Altered protein expression levels are associated with the progression of DN, and as a systemic metabolic disease, the disease may not seem to be fully characterized based on a specific protein Zürbig et al.
The above proteins are linked to specific structural damage, and bioinformatic methods can be used to better understand the linkage of proteins and the biological processes involved Geng et al. These proteins were also analyzed for enrichment by biological processes, and the results indicate that they are mainly enriched in extracellular matrix organization, iron ion transport, kidney development, regulation of angiogenesis, regulation of cell motility, and response oxygen-containing compounds Figure 1 below.
Oxidative stress, disturbances in lipid metabolism play a continuous role in the early stages of DN, resulting in elevated levels of kidney inflammation and increased cell death. Wellen and Hotamisligil, Processes closely associated with the persistent early elevation of blood glucose, such as increased ion transport-related proteins transferrin and ceruloplasmin, reflect endothelial cell dysfunction and increased intra-glomerular pressure Narita et al.
A recent study showed a detailed interpretation of the progression of DN by combining proteomics and peptidomics in the urine of diabetic subjects, and the results of our analysis have similarities to this study Van et al.
To better understand the pathological features of DN and to search for potential biomarkers with higher specificity and accuracy, several proteomic studies have been carried out in the last years. Comparisons between diabetic subjects at different stages of renal dysfunction and controls showed differences in the expression of multiple proteins.
Seven proteins were progressively upregulated with increasing proteinuria, and the transporter protein VDBP was reported for the first time in the urine of patients with DN Rao et al. In another study, proteomic analysis identified haptoglobin as a candidate biomarker for predicting early decline in renal function, and the ratio of haptoglobin to creatinine has the ability to predict renal function in diabetic patients who have not yet exhibited significant renal disease Bhensdadia et al.
Urine has an irreplaceable role in detecting kidney status. Characterizing the urinary proteomics of patients with different stages of DN helps to understand the state of the kidney and is important for finding potential biomarkers Papale et al.
This is useful in understanding the condition of patients with DN and in finding promising treatment pathways. In addition to changes in protein levels, alterations in metabolites are also present in diabetic nephropathy, lactic acid, hippuric acid, allantoin in the urine and glutamine in the blood are the most important early diagnostic biomarkers in the pathogenesis of DN.
Roointan et al. The effects of metabolic memory on DN may be long-lasting, profoundly affecting disease development and treatment through epigenetic modifications. Kushwaha et al. The development of DN is a complex process, such as GBM thickening in the early stages and glomerulosclerosis and interstitial fibrosis in the later stages, involving different cell types at different stages.
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| Article information | New susceptibility loci associated with kidney disease in type 1 diabetes. Penders J , Delanghe JR. CAS PubMed PubMed Central Google Scholar Mahfouz, M. Then, pro-inflammatory cytokines and a variety of chemokines secreted by leukocytes may guide the latter into the kidney directly. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4. Navarro JF, Mora C, Gomez M, Muros M, Lopez-Aguilar C, García J. |
| MINI REVIEW article | Weil EJ, Lemley KV, Yee B, et nephropathh. References Tuttle Diabetic nephropathy biomarkers, Dkabetic GL, Bilous Anti-inflammatory effects et al Diabetic kidney Antibacterial cutting board a report from an ADA consensus conference. Diabetes 61 12— Nihon Jinzo Gakkai shi 37 6 — CAS PubMed Google Scholar Fagerudd JA, Groop PH, Honkanen E, Teppo AM, Grönhagen-Riska C Urinary excretion of TGF-beta 1, PDGF-BB and fibronectin in insulin-dependent diabetes mellitus patients. Coca et al. Reeves W. |
Diabetic nephropathy biomarkers -
The main function of RBP-4 is to transfer small hydrophobic molecules to the cell membrane. In diabetes, an association of RBP4 concentration has been documented with the magnitude of insulin resistance, suggesting increased levels of RBP4 predicts insulin resistance [ 72 ].
Increased plasma and urinary RBP4 concentration have been reported with low eGFR [ 72 ] [ 73 ]. A longitudinal study among T1DM has reported an increased level of urinary RBP4 in microalbuminuric patients [ 74 ] and the diagnostic utility of urinary RBP4 in T2DM patients with an AUC of 0.
The serum level of RBP-4 was found to be associated with proliferative diabetic retinopathy and coronary cerebrovascular or peripheral vascular diseases among type 2 diabetes [ 72 , 75 ].
Discordant results were shown by E Akbay's study, indicating that diabetic retinopathy and cardiovascular complications do not exhibit any change in serum RBP4 in T2DM patients [ 76 ]. RBP4 could be a valid marker for identifying the early onset of DKD and predicting renal function impairment in progressive stages in T1DM and T2DM.
In addition, this marker could be a predictor for microvascular and macrovascular complications of diabetes. L-FABP is a 14 kDa protein produced mainly in the cytoplasm of proximal tubules and is involved in the metabolism of the long-chain fatty acids.
Uncontrolled reabsorption of free fatty acids to tubular cells by L-FABP leads to tubulointerstitial damage [ 77 ]. According to Kamijo et al. Higher levels of L-FABP in the normoalbuminuric group suggest that it could be a risk factor for disease progression [ 78 ].
Corroborating these findings, a year follow-up study by Araki S et al. Additionally, the urinary level of L-FABP offers statistical significance with urine albumin level and inversely correlates with GFR [ 78 ]. Thus, evaluation of urinary L-FABP in T2 DM serves as a risk factor for DKD progression and could be considered as a promising tubular marker in predicting the incidence of cardiovascular disease and renal function impairment.
Evidence from epidemiological and mechanistic research suggests that oxidative stress plays a key role in mediating progression and complications. Thereby, markers linked to ROS production have considerable potential to stratify DKD stages.
Numerous evidence has indicated urinary 8-oxodG is a risk factor for cancer, atherosclerosis, and diabetes [ 80 ]. Xu et al. Clinical research with 5 years of follow-up reported significant progression of diabetic kidney disease in patients with higher urinary 8-oxodG [ 82 ].
Urinary 8-oxodG has been proposed as a characteristic pathogenic component in diabetic retinopathy development in T1DM and T2DM [ 83 , 84 ]. Etiane et al. found diagnostic ability of 8-oxodG with an AUC of 0.
This marker has also been observed with macrovascular complications in T2DM [ 86 ]. These above-mentioned findings conclude that excretion of urinary 8-oxodG could be an independent predictor for disease progression and development of microvascular and macrovascular complications of diabetes.
Pentosidine is an advanced glycoxidation product formed by the covalent binding of amino groups with glucose moiety [ 87 ].
Miura et al. demonstrated a serum pentosidine level more marked progressively in microalbuminuria and advanced stages of nephropathy [ 88 ].
Bruce A et al. found higher excretion in urine among patients with microalbuminuria and early decline of GFR [ 89 ]. Diabetic patients with a high level of pentosidine were found to be an independent predictor of diabetic retinopathy, cardiovascular disease, and all-cause mortality [ 90 , 91 ].
Lines to this evidence, measurement of pentosidine level in urine and serum may provide the basis for identifying patients at risk of early GFR decline and could be a promising biomarker for diabetic microvascular and macrovascular complications.
Uric acid is produced by purine metabolism and has been shown to play an independent function in predicting DKD progression and many clinical studies have been focused targeting its level in the prognosis of DKD.
Bartakova et al. found initial hyperuricemia is a strong determinant of DKD progression [ 92 ]. Zoppini et al. analyzed that the cumulative incidence of CKD with GFR decline among T2DM was significantly higher in those who had hyperuricemia, considered as an independent risk factor in disease progression and as a strong predictor of GFR decline [ 93 ]; furthermore, T1DM with higher serum uric acid levels were developed persistent macroalbuminuria [ 94 ].
These evidences suggest that serum uric acid could be an independent predictor of later development of macroalbuminuria in type 1 and type 2 diabetic patients. Recent researchers have reported the potential role of local and systemic inflammatory pathways in the progression of DKD with chronic inflammation and subsequent extracellular matrix expansion [ 95 ].
TNF-α expresses in glomerular and tubular cells in all stages of diabetes, mainly monocyte-produced cytokines, and predisposes in all the stages of the pathogenesis of DKD progression by inducting and infiltrating inflammatory cells to the kidney and activation of apoptosis system.
Thereby elevated level of TNF-α has been noted with hypertrophy, hyperfiltration, and alterations of intra-glomerular blood flow, resulting in reduced renal function [ 95 ]. A meta-analysis by Qiao et al. reported T1DM patients have significantly increased TNF-α as compared to healthy controls [ 96 ].
Furthermore, Navarro JF et al. documented that serum TNF-α is elevated with advanced renal dysfunction and correlates with urinary protein excretion, suggesting that this cytokine has an intensive role in the onset of proteinuria in these patients [ 97 ].
While Stangou et al. reported a significant positive correlation of urinary TNF-α, but not serum TNF-α with the severity of microalbuminuria in T2DM [ 98 ]. An experimental animal, study corroborated the key role of TNF-α in mediating the pathogenesis of diabetic peripheral neuropathy [ 99 ].
Elevated TNF-α is also associated with microvascular and macrovascular complications in diabetic patients [ , ] and in the prediction of diabetic retinopathy in T2DM with an AUC of 0. The above studies suggest that serum and urine TNF-α could be a potential biomarker to predict the degree of microalbuminuria in T1DM and T2DM.
TNF-α receptors are type1 transmembrane proteins with cysteine-rich motifs seen in glomerular and tubular cells.
These are of two types, TNF-α receptor 1 55 kDa and TNF -α receptor 2 75 kDa. TNF-α binds to these respective receptors and induces inflammatory pathways and apoptosis [ ]. Current studies have appreciated the contribution of TNF-α receptors on the magnitude of DKD development through the TNF α —TNFR2 inflammatory pathways [ ].
Sharad et al. found a strong correlation of serum TNF-α receptors with microalbuminuria among T1DM, suggesting the crucial role in disease progression [ ].
These findings have been supported by evidence of a marked stepwise increase from normo-micro-macroalbuminuria in T2DM [ ].
Multiple studies have reported that TNFRs are associated independently with declined renal function and ESRD [ ]. Furthermore, it has been described that serum TNF receptors are predictors of diabetic retinopathy in T1DM [ ].
Therefore, circulating TNF-α receptors are associated with the progression of DKD and could be a predictor of microalbuminuria and advanced renal impairment. MCP-1 is a pro-inflammatory cytokine produced by mononuclear leukocytes, cortical tubular epithelial cells, and podocytes that has been linked to renal inflammation, glomerular injury, tubular atrophy, and fibrosis via nuclear factor-kappa B [ ].
Renal expression of MCP-1 was also correlated with the quantity of infiltrated macrophages, interstitial lesions, and the degree of albuminuria [ ]. Fufaa et al. demonstrated a substantial correlation of urine MCP-1 uMCP-1 levels with cortical interstitial expansion and disease progression in T1DM who had normoalbuminuria [ ].
When comparing DKD patients to healthy controls, Wada [ ] and Banba [ ] discovered elevated urinary excretion of MCP-1 in DKD patients.
Shoukry et al. Early progressive GFR decline has a positive correlation with high uMCP-1 [ ] also associated with young-onset of T2DM with diabetic retinopathy [ ]. These observations suggest that MCP-1 could be a promising inflammatory marker in diagnosing early progressive renal decline and diabetic microvascular complications.
TGF-β activates fibrogenesis and thereby progression of DKD by the increased extracellular matrix deposition and glomerular mesangial hypertrophy [ ].
Flores et al. have shown raised urinary and plasma TGF- β in clinical onset of T1DM [ ]. Similarly, patients with T2DM who had microalbuminuria had been reported elevated serum and urinary TGF-β [ ]. On the other hand, Rivarola et al.
Supporting this, a study conducted among T2DM resulted in increased serum and urine TGF-β, being more pronounced in macroalbuminuria compared to microalbuminuria and normoalbuminuria group [ ], suggesting that this biomarker could be a good candidate in predicting macroalbuminuria in type 2 DM.
CTGF is a secretory protein in renal cells induced by hyperglycemia. It stimulates extracellular matrix synthesis, cell migration, and interstitial matrix deposition by the epithelial-to-mesenchymal transition in diabetic patients [ ].
T1DM patients showed increased urinary CTGF with the severity of renal function deterioration in terms of albumin excretion and GFR decline [ ] and could be a predictor for ESRD with an AUC under ROC of 0.
Its expression has also been reported in diabetic retinopathy [ ]. CTGF could be an independent predictor of ESRD and mortality in DKD and it is also a predictor of diabetic retinopathy and looks promising. It is a major immunoregulatory cytokine in mesangial expansion.
Sangoi et al. observed higher serum IL-6 even before the onset of albuminuria [ ]. Multiple studies support these findings with evidence that serum and urinary IL-6 were increasing with disease progression in T1DM [ ] and T2DM [ ] and have a pronounced association with macrovascular complications [ ].
Thus, it could be a marker of the onset of microalbuminuria and early progressive renal decline, and it strongly predicts the macrovascular complications of diabetes. The classification based on pathogenesis and utilization of these biomarkers can be the future in predicting the early onset of microalbuminuria and progressive renal function decline in both T1DM and T2DM.
These biomarkers are relevant to not only predicting the progression of DKD but also diabetic microvascular and macrovascular complications, as shown in Table 2. Few of the biomarkers have been studied in the type 2 diabetic population on their diagnostic utility for DKD and established cut-off value with the area under the ROC curve from 0.
These are 0. Under hyperglycaemic injury, renal cells are activated to release MPs into plasma and urine before the onset of DKD [ ]. Therefore, these have emerged as biomarkers in DKD. A review by Sheyu Li et al. reported a higher level of circulating MPs reported with T2DM and as independent predictors for microvascular complications of diabetes [ ].
MPs can be easily isolated from body fluids via non-invasive methods. These properties facilitate the use as a potential non-invasive biomarker in the progression of DKD. More large-scale studies are needed for further relevance in this regard. Urinary exosomes, 40— nm originate as internal vesicles, and that contain protein indicators of renal failure and structural damage.
It has turned out to be a potential non-invasive biomarker source. However, exosome isolation was challenging. Using liquid chromatography and mass spectrometry, the scope of existing approaches has enlarged to evaluate more urinary exosome-associated proteins [ ]. In recent years, microRNA is reported to be involved in the DKD progression via inflammation, hypertrophy, autophagy, endoplasmic reticulum ER stress, oxidative stress, insulin resistance, and podocyte injury.
Jia et al. observed a positive correlation of miRNA expression for TGF beta stimulator with albuminuria and reported good diagnostic efficiency [ ]. Based on the evidence mentioned above, urine mRNA has prognostic significance as a non-invasive, early indicator of renal impairment.
The pathophysiology of DKD and its progression is multifactorial. Therefore, assessment of development and progression of DKD cannot be relied solely on albuminuria and creatinine.
The identification of novel biomarkers based on pathogenesis of DKD involving various renal structures looks promising. In this review, we have summarized the potential 22 novel biomarkers with respect to the pathogenesis of DKD development. Each biomarker has its role in either identifying DKD early or predicting progression of DKD over and above clinical history and standardized markers like albuminuria and creatinine.
Few of them appear to be useful for predicting other micro- and macrovascular complications like retinopathy and cardiovascular disease. This panel of biomarkers now warrants further validation on large-scale longitudinal studies involving type 1 and type 2 diabetes populations before the transition to clinical routine.
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HOMA Calculator. Accessed: 13th November Download references. The authors would like to acknowledge the research unit team, the hospitals involved, and all staff nurses in different wards for their participation in conducting the study.
The authors would also like to acknowledge King Abdulaziz City for Science and Technology KACST for funding this project grant for project no: A-T University Diabetes Center, College of medicine, King Saud University, Riyadh, PO Box , Saudi Arabia.
Strategic Center for Diabetes Research, King Saud University, Riyadh, PO Box , Saudi Arabia. College of medicine, King Khalid University Hospital, King Saud University, Riyadh, PO Box , Saudi Arabia.
Registry Department, University Diabetes Center, King Saud University, Riyadh, PO Box , Saudi Arabia. Research Department, University Diabetes Center, King Saud University, PO Box , Riyadh, Saudi Arabia.
You can also search for this author in PubMed Google Scholar. and M. devised the protocol, led protocol development and the funding application, supervised the running of the lead study center and coordination of participating centers, contributed to the analysis, and led the drafting of the manuscript.
contributed to coordination of centers, management of the study, data analysis and contributed to drafting of the manuscript.
provided day-to-day overall management of the study, coordinated recruitment in the lead study centre and coordination of other centers, and commented on drafts of the manuscript.
developed the analysis protocol, did the quantitative analysis, and contributed to drafting of the manuscript. Correspondence to Khalid Al-Rubeaan.
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Al-Rubeaan, K. Assessment of the diagnostic value of different biomarkers in relation to various stages of diabetic nephropathy in type 2 diabetic patients. Sci Rep 7 , Download citation. Received : 16 January Accepted : 11 April Published : 02 June Anyone you share the following link with will be able to read this content:.
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Download PDF. Subjects Diagnostic markers Nephrology. Abstract Albuminuria is widely used to indicate early phases of diabetic nephropathy although it is limited by the fact that structural damage might precede albumin excretion.
Introduction Diabetic nephropathy is the most common cause of end stage renal disease ESRD that is associated with high rates of morbidity and mortality 1. Table 1 Baseline characteristics of the studied subjects according to their diabetic nephropathy stages. Full size table. Figure 1.
Full size image. Table 3 Sensitivity, specificity and AUC for the 22 markers in detecting cases with microalbuminuria or macroalbuminuria. Discussion Albuminuria or ACR has been considered for the last three decades as the golden standard diagnostic and prognostic biomarker for diabetic nephropathy onset and progression 9.
Biomarkers of glomerular damage Urinary transferrin has shown a gradual significant increase with diabetic nephropathy progression and had significant correlation positively with ACR, while negatively with eGFR.
Biomarkers of Tubular damage The pathophysiology of albuminuria and tubulointerstitial damage are considered to be intertwined, where on one hand the re-absorption of increased amount of protein from the tubular lumen, induces the pro-inflammatory and the profibrotic responses in tubular cells while on the other hand, the damage of the proximal renal tubules alone can lead to albumin leak and consequently albuminuria Inflammatory markers Although diabetic nephropathy is traditionally considered a nonimmune disease, there is an overwhelming evidence which indicates that immunologic and inflammatory mechanisms play a significant role in its development and progression.
Methods Study design and setting This is a cross-sectional hospital based study. Figure 2. Study flow chart for case selection and recruitment. References Lee, S. Article PubMed Google Scholar Couser, W.
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Article CAS PubMed Google Scholar Rathcke, C. Article CAS PubMed PubMed Central Google Scholar American Diabetes Association. Article Google Scholar The Oxford Centre for Diabetes. Acknowledgements The authors would like to acknowledge the research unit team, the hospitals involved, and all staff nurses in different wards for their participation in conducting the study.
Al-Sharqawi Strategic Center for Diabetes Research, King Saud University, Riyadh, PO Box , Saudi Arabia Khalid Siddiqui College of medicine, King Khalid University Hospital, King Saud University, Riyadh, PO Box , Saudi Arabia Mohammed A. Al-Ghonaim Registry Department, University Diabetes Center, King Saud University, Riyadh, PO Box , Saudi Arabia Amira M.
Youssef Research Department, University Diabetes Center, King Saud University, PO Box , Riyadh, Saudi Arabia Dhekra AlNaqeb Authors Khalid Al-Rubeaan View author publications. View author publications. Ethics declarations Competing Interests The authors declare that they have no competing interests.
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Show results from All journals This journal. Advanced search. Close banner Close. Email address Sign up. The only feasible way to tackle this health care crisis is by prevention and treatment in a mechanistically rational approach. Therefore, the discovery of a specific, reliable diagnostic and prognostic biomarker for DN is imperative.
Part of the difficulty in finding such a marker is the complex pathogenesis of DN; it is clearly multifactorial and involves multiple genes, proteins, metabolic pathways, and environmental factors.
In this review, we will discuss the latest findings in the use of genetic, protein, and metabolic markers of DN. Particular attention will be paid to the urinary biomarker as a noninvasive method to detect either morphological or biochemical changes in DN.
Diabetic nephropathy DN is Anti-inflammatory effects nephropatjy cause of end Excess water retention renal disease. Therefore, the assessment of nphropathy function and early diagnosis Nephrlpathy glomerular nephropatby tubular Anti-inflammatory effects is Trusted pre-workout choice important measure in the management Anti-inflammatory effects type Diabetif and type 2 diabetic patients. The diagnosis of DN for years has been routinely determined by the presence of microalbuminuria MA. Several studies have showed that presence of MA may be transient and does not necessarily reflect permanent kidney damage. There could also be glomerulo-tubular damage in diabetic patient without presenting with albuminuria. Decline in the renal function, cellular and extracellular derangements in both the glomerulus and tubules has been associated with array of biological markers which could be of help in the diagnosis, prognosis, and the overall management of the affected patients.
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