Prognosis Of Diabetic Nephropathy Research Articles

Toe-brachial index is more strongly associated with prognosis of diabetic nephropathy than ankle-brachial index in type 2 diabetic patients

Toe-brachial index is more strongly associated with prognosis of diabetic nephropathy than ankle-brachial index in type 2 diabetic patients

PS-B01-5: TISSUE-SPECIFIC REGULATION OF LRG1 EXPRESSION IN MULTIPLE HYPERTENSION MODELS OF MOUSE

Object: Leucine-rich alpha-2-glycoprotein-1 (LRG1), which is firstly isolated from human plasma, has been reported to be related to several diseases as a biomarker or a pathogenic factor. Serum LRG1 is associated with the prognosis of diabetic nephropathy and cardiovascular diseases, and we previously demonstrated that LRG1 especially plays a pivotal role in the initial development of diabetic nephropathy. In addition, a previous study showed that increased plasma LRG1 levels in patients with type 2 diabetes mellitus was associated with increased systolic blood pressure (BP), arterial stiffness estimated by pulse wave velocity, and decreased endothelium-dependent vasodilation estimated by laser doppler flowmetry. However, the relationship between LRG1 and BP have remained substantially unknown. With respect to the function of LRG1, LRG1 is expressed in endothelial cells and promotes pathological angiogenesis by modulating TGF-beta signaling. LRG1 switches TGF-beta signaling from the Smad2/3 pathway to the Smad1/5/8 pathway. In addition, the activation of Smad2/3 signaling enhanced endothelial nitric oxide synthase (eNOS) production and promoted endothelium-dependent vasodilation. Suppressing eNOS activity reduces NO levels and leads to endothelial dysfunction and hypertension. Moreover, LRG1 is increased in response to inflammation and oxidative stress in endothelial cells. However, little is known about the relationship between LRG1 in endothelial cells and eNOS. Based on the previous findings, we hypothesized that LRG1 may inhibit eNOS production by potentially blocking the Smad2/3 pathway, which will promote to form a vicious cycle that progresses vascular endothelial damage and hypertension. As the first step to elucidate this hypothesis, we investigated LRG1 expression in various tissues including vascular endothelium in some hypertension models with endothelial dysfunction. Design and method: Male 10–12 weeks-aged C57/BL mice were divided into control and hypertension with endothelial dysfunction. BP was measured using a tail-cuff method during the experiment, and mice were sacrificed and their organs were collected at the end of the experiment. We examined the expression of LRG1, Smad2/3, Smad1/5/8 and NOS in the vascular endothelium, kidney, heart, adipose tissue by PCR, Western blot and immunohistochemical analyses. Results: We are currently conducting the experiments and will present our findings at this conference. Conclusion: We plan to present the results of tissue-specific regulation of LRG1 expression in some hypertension models of mice at this conference.

Potential Role of N-Cadherin in Diagnosis and Prognosis of Diabetic Nephropathy.

Diabetic nephropathy (DN) is a serious complication of diabetes affecting about half the people with diabetes and the leading cause of end stage renal disease (ESRD). Albuminuria and creatinine levels are currently the classic markers for the diagnosis of DN. However, many shortcomings are arising from the use of these markers mainly because they are not specific to DN and their levels are altered by multiple non-pathological factors. Therefore, the aim of this study is to identify better markers for the accurate and early diagnosis of DN. The study was performed on 159 subjects including 42 control subjects, 50 T2D without DN and 67 T2D subjects with DN. Our data show that circulating N-cadherin levels are significantly higher in the diabetic patients who are diagnosed with DN (842.6 ± 98.6 mg/l) compared to the diabetic patients who do not have DN (470.8 ± 111.5 mg/l) and the non-diabetic control group (412.6 ± 41.8 mg/l). We also report that this increase occurs early during the developmental stages of the disease since N-cadherin levels are significantly elevated in the microalbuminuric patients when compared to the healthy control group. In addition, we show a significant correlation between N-cadherin levels and renal markers including creatinine (in serum and urine), urea and eGFR in all the diabetic patients. In conclusion, our study presents N-cadherin as a novel marker for diabetic nephropathy that can be used as a valuable prognostic and diagnostic tool to slow down or even inhibit ESRD.

Salivary Glycopatterns as Potential Non-Invasive Biomarkers for Diagnosing and Reflecting Severity and Prognosis of Diabetic Nephropathy.

Discriminating between diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) can help provide more specific treatments. However, there are no ideal biomarkers for their differentiation. Thus, the aim of this study was to identify biomarkers for diagnosing and predicting the progression of DN by investigating different salivary glycopatterns. Lectin microarrays were used to screen different glycopatterns in patients with DN or NDRD. The results were validated by lectin blotting. Logistic regression and artificial neural network analyses were used to construct diagnostic models and were validated in in another cohort. Pearson’s correlation analysis, Cox regression, and Kaplan–Meier survival curves were used to analyse the correlation between lectins, and disease severity and progression. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) and bioinformatics analyses were used to identify corresponding glycoproteins and predict their function. Both the logistic regression model and the artificial neural network model achieved high diagnostic accuracy. The levels of Aleuria aurantia lectin (AAL), Lycopersicon esculentum lectin (LEL), Lens culinaris lectin (LCA), Vicia villosa lectin (VVA), and Narcissus pseudonarcissus lectin (NPA) were significantly correlated with the clinical and pathological parameters related to DN severity. A high level of LCA and a low level of LEL were associated with a higher risk of progression to end-stage renal disease. Glycopatterns in the saliva could be a non-invasive tool for distinguishing between DN and NDRD. The AAL, LEL, LCA, VVA, and NPA levels could reflect the severity of DN, and the LEL and LCA levels could indicate the prognosis of DN.

A modern view on the prognosis of diabetic nephropathy in diabetes mellitus

A modern view on the prognosis of diabetic nephropathy in diabetes mellitus

Integrated bioinformatics analysis reveals novel key biomarkers in diabetic nephropathy.

The underlying molecular mechanisms of diabetic nephropathy have yet not been investigated clearly. In this investigation, we aimed to identify key genes involved in the pathogenesis and prognosis of diabetic nephropathy. We downloaded next-generation sequencing data set GSE142025 from Gene Expression Omnibus database having 28 diabetic nephropathy samples and nine normal control samples. The differentially expressed genes between diabetic nephropathy and normal control samples were analyzed. Biological function analysis of the differentially expressed genes was enriched by Gene Ontology and REACTOME pathways. Then, we established the protein-protein interaction network, modules, miRNA-differentially expressed gene regulatory network and transcription factor-differentially expressed gene regulatory network. Hub genes were validated by using receiver operating characteristic curve analysis. A total of 549 differentially expressed genes were detected including 275 upregulated and 274 downregulated genes. The biological process analysis of functional enrichment showed that these differentially expressed genes were mainly enriched in cell activation, integral component of plasma membrane, lipid binding, and biological oxidations. Analyzing the protein-protein interaction network, miRNA-differentially expressed gene regulatory network and transcription factor-differentially expressed gene regulatory network, we screened hub genes MDFI, LCK, BTK, IRF4, PRKCB, EGR1, JUN, FOS, ALB, and NR4A1 by the Cytoscape software. The receiver operating characteristic curve analysis confirmed that hub genes were of diagnostic value. Taken above, using integrated bioinformatics analysis, we have identified key genes and pathways in diabetic nephropathy, which could improve our understanding of the cause and underlying molecular events, and these key genes and pathways might be therapeutic targets for diabetic nephropathy.

Clinical Acute Kidney Injury and Histologic Acute Tubular-Interstitial Injury and Their Prognosis in Diabetic Nephropathy

Introduction: Histologic acute tubular-interstitial injury (hATI) is often observed in patients with diabetic nephropathy (DN). This study aimed to determine the relationship between hATI and clinical acute kidney injury (cAKI) and evaluate significance of hATI in patients with DN. Methods: Patients with biopsy-proven DN through 2003–2018 in our center were selected. The prevalence of hATI and its correlations with cAKI, tubular injury biomarkers, and serum creatinine were investigated. The renal survival rates and prognostic factors were analyzed by Kaplan-Meier curve and Cox regression model, respectively. Results: Of 1,414 patients with DN, 70.4% were male, with a median age of 50.0 years. The incidences of cAKI and hATI were 8.6% and 57.8%, respectively. The severities of most hATI were mild (91.0%). The incidence of cAKI in those with hATI was only 12.2%. The incidences of cAKI positively correlated with the scores of hATI (Kendall r = 0.273, p < 0.001). The presence of hATI was related to rapid creatinine rise and increased tubular injury biomarkers although without cAKI. After adjusting for significant covariates, multivariate Cox models showed that patients with hATI alone were one and a half times more likely to develop ESRD (hazard ratio [HR]: 1.46; 95% CI, 1.05–2.02) than those without hATI or cAKI, and patients with hATI plus cAKI were 3 times more likely to develop ESRD (HR: 2.96; 95% CI, 1.85–4.72). Conclusion: Our findings indicated that hATI was common in patients with DN where the majorities were mild hATI and without cAKI. hATI was an independent risk factor of DN progression, regardless of episodes of cAKI.

Identifying Potential Diagnostic Genes for Diabetic Nephropathy Based on Hypoxia and Immune Status.

BackgroundThe prognosis of diabetic nephropathy is poor, and early diagnosis of diabetic nephropathy is challenging. Fortunately, searching for DN-specific markers based on machine algorithms can facilitate diagnosis.MethodsxCell model and CIBERSORT algorithm were used to analyze the relationship between immune cells and DN, and WGCNA analysis was used to evaluate the regulatory relationship between hypoxia gene and DN-related immune cells. Lasso regression and ROC regression were used to detect the ability of core genes to diagnose DN, the PPI network of core genes with high diagnostic ability was constructed, and the interaction between core genes was discussed.ResultsThere were 519 differentially expressed genes in renal tubules and 493 differentially expressed genes in glomeruli. Immune and hypoxia responses are involved in the regulation of renal glomerulus and renal tubules. We found that there are 16 hypoxia-related genes involved in the regulation of hypoxia response. Seventeen hypoxia-related genes in renal tubules are involved in regulating hypoxia response on the proteasome signal pathway. Lasso and ROC regression were used to screen anoxic core genes. Further, we found that TGFBR3, APOLD1, CPEB1, and KDR are important in diagnosing DN glomerulopathy, respectively, PSMB8, PSMB9, RHOA, VCAM1, and CDKN1B, which have high specificity for renal tubulopathy in DN.ConclusionHypoxia and immune reactions are involved in the progression of DN. T cells are the central immune response cells. TGFBR3, APOLD1, CPEB1, and KDR have higher diagnostic accuracy in the diagnosis of DN. PSMB8, PSMB9, RHOA, VCAM1, and CDKN1B have higher diagnostic accuracy in DN diagnosis.

Hypoglycemic agents and prognostic outcomes of chronic kidney disease patients with type 2 diabetes

Introduction: Chronic kidney disease (CKD) poses a financial burden on most patients from low/ middle income countries. Glycaemic control with affordable hypoglycemic agents may influence on the prognosis of diabetic nephropathy. Objectives: We aimed to compare the rates of CKD progression and proteinuria in the type 2 diabetic population in response to the use of various hypoglycemic agents. Patients and Methods: A retrospective cross-sectional study of a total of 250 patients of Afro-Caribbean descent at the University hospital of the West Indies between 2018 and 2019 was conducted. The use of hypoglycaemic agents and changes in albuminuria were calculated as odds ratios with a 95% confidence interval (CI). A P value&lt;0.05 was considered statistically significant. Results: Of 250 patients with diabetic nephropathy, the number of rapid CKD progression was highest in patients on insulin (26.3%). In comparison, number of rapid progressions in patients receiving metformin, dipeptidyl peptidase 4 (DPP-4 inhibitors), sulfonylurea and pioglitazone were 19.1%, 22.2%, 21.9% and 20%, respectively. After eliminating confounding factors, comparison within the group analysis on DPP-4 inhibitors (n= 171) demonstrated 62.6% significant improvement in quantitative proteinuria with reduction of mean spot urine albumin creatinine ratio (ACR) from 362.1 ±338.9 mg/g to 303 ±300.1 mg/g (ORs, 0.77; 95% CI 0.41 to 0.97; P = 0.03). Conclusion: Type 2 diabetic patients requiring insulin were found to have progression of CKD than patients on oral hypoglycaemic agents. Among the affordable oral hypoglycaemic agents, DPP-4 inhibitors had an association with reduction in albuminuria.

Urinary sediment microRNAs can be used as potential noninvasive biomarkers for diagnosis, reflecting the severity and prognosis of diabetic nephropathy

BackgroundPatients with both diabetes mellitus (DM) and kidney disease could have diabetic nephropathy (DN) or non-diabetic renal disease (NDRD). IgA nephropathy (IgAN) and membranous nephropathy (MN) are the major types of NDRD. No ideal noninvasive diagnostic model exists for differentiating them. Our study sought to construct diagnostic models for these diseases and to identify noninvasive biomarkers that can reflect the severity and prognosis of DN.MethodsThe diagnostic models were constructed using logistic regression analysis and were validated in an external cohort by receiver operating characteristic curve analysis method. The associations between these microRNAs and disease severity and prognosis were explored using Pearson correlation analysis, Cox regression, Kaplan–Meier survival curves, and log-rank tests.ResultsOur diagnostic models showed that miR-95-3p, miR-185-5p, miR-1246, and miR-631 could serve as simple and noninvasive tools to distinguish patients with DM, DN, DM with IgAN, and DM with MN. The areas under the curve of the diagnostic models for the four diseases were 0.995, 0.863, 0.859, and 0.792, respectively. The miR-95-3p level was positively correlated with the estimated glomerular filtration rate (p < 0.001) but was negatively correlated with serum creatinine (p < 0.01), classes of glomerular lesions (p < 0.05), and scores of interstitial and vascular lesions (p < 0.05). However, the miR-631 level was positively correlated with proteinuria (p < 0.001). A low miR-95-3p level and a high miR-631 level increased the risk of progression to end-stage renal disease (p = 0.002, p = 0.011).ConclusionsThese four microRNAs could be noninvasive tools for distinguishing patients with DN and NDRD. The levels of miR-95-3p and miR-631 could reflect the severity and prognosis of DN.

Diabetic Nephropathy: A Comprehensive Review for Health Care Professionals

The prevalence of Chronic Kidney Disease (CKD) continues to escalate at an alarming rate and diabetes has become the most common single cause of End-Stage Renal Disease (ESRD) in the world. This is because diabetes, particularly type 2, is increasing in prevalence, and the patients are living longer now. Diabetes is the major cause of end-stage renal disease in the developed world, accounting for 40% to 50% of cases. Diabetic nephropathy contributes significantly to the economic burden of diabetes. In UK, the cost of diabetic complications in 2011/2012 was estimated at £14 billion, by 2035/2036 this is expected to rise to £22 billion. Worldwide, healthcare costs for diabetic patients are much higher than non- diabetic patients. Also, among diabetic patients the cost of health care is much higher in those with complications (Micro &lt; Macro&lt;Micro + Macrovascular complications) than in those without complications, therefore identifying and controlling diabetes and its complications is essential in reducing the burden of the disease. In this review we shall explore the pathophysiology, risk factors, staging, screening, management and prognosis of Diabetic Nephropathy in explicit details to make it easily understandable for the Health Care Professionals. Keywords: Diabetic Nephropathy, Diabetes, Health Care Professionals

Prediction Value of Serum NGAL in the Diagnosis and Prognosis of Experimental Acute and Chronic Kidney Injuries.

Sensitive and accurate serum biomarkers for monitoring acute and chronic kidney disease progression are more convenient and can better evaluate drug efficiency in pharmacological research. Neutrophil Gelatinase-associated Lipocalin (NGAL) is considered a hopeful early biomarker of acute kidney injury (AKI), but its utility in early prediction and prognosis of diabetic nephropathy (DN) and immune-mediated glomerulonephritis is still not clear. Moreover, detailed prognosis studies of NGAL in AKI are lacking, and most studies use a urine source. In the current study, through two experimental AKI and two chronic kidney injury animal models, serum NGAL (sNGAL) prediction values on diagnosis and prognosis of kidney injuries in animal disease models have been investigated thoroughly. Four experimental kidney disease models include cisplatin-induced and lipopolysaccharide (LPS)-induced AKI, streptozocin-induced diabetic nephropathy (DN), and cationized-bovine serum albumin (c-BSA)-induced membranous nephropathy (MN), respectively. The sNGAL concentration was measured at different stages of kidney injury (KI) in each experimental model, and receiver operating characteristic (ROC) analyses were performed to investigate the diagnosis efficiency of sNGAL for KI. Western blot and immunohistochemistry were used to measure the protein levels in the kidneys, and pathological analysis was used as the gold standard to confirm KI. Results suggest that sNGAL can predict early diagnosis of cisplatin-induced AKI accurately but is less powerful in later stages compared to blood urea nitrogen (BUN) and serum creatinine (Scr). sNGAL is sensitive but lacks specificity to evaluate early kidney injury for LPS-induced AKI under low-dosage LPS challenge. sNGAL is not an efficient biomarker for early diagnosis of STZ-induced DN, but sNGAL is an efficient predictor for the early diagnosis and prognosis of immune-mediated MN. In conclusion, application of sNGAL as a kidney injury biomarker to determine the diagnosis and prognosis in pharmacological studies is dependent on experimental animal models.

Blood pressure control in chronic kidney disease according to underlying renal disease: the Fukushima CKD cohort.

Inadequate blood pressure control is one of the important causes of chronic kidney disease (CKD), but only a limited number of reports have examined blood pressure control in Japanese patients with pre-dialysis CKD. Differences in blood pressure control due to underlying renal disease in pre-dialysis patients with CKD were investigated in the present study using the baseline data of the Fukushima CKD cohort study. The study involved 1351 CKD patients, classified by underlying disease of primary renal disease, hypertensive nephropathy, diabetic nephropathy, other nephropathies, or unknown. Target blood pressure of CKD patients was defined as < 130/80mmHg in patients under 75years old with diabetes and/or proteinuria, and < 140/90mmHg in other patients. The achievement rate of target systolic blood pressure was lower in the diabetic and hypertensive nephropathy groups than in the primary renal disease group (33.3%, 46.0% vs. 68.1%, p < 0.001). However, the number of antihypertensive medications increased in the diabetic and hypertensive nephropathy groups compared to the primary renal disease group (2.16, 2.04 vs. 1.55, p < 0.001). Inadequate blood pressure control was independently related to the underlying renal disease, with a significant difference between diabetic nephropathy and primary renal disease (odds ratio 3.19; 95% confidence interval, 2.16-4.69; p < 0.001). This study showed that blood pressure control differs by the underlying renal disease. Blood pressure control was poor especially in diabetic nephropathy despite multidrug combination antihypertensive treatment. It is necessary to verify whether strict blood pressure control improves patients' prognosis in diabetic nephropathy.

Serum Bilirubin Levels Can be Used as a Potential Biomarker in the Progression of Diabetic Nephropathy in Rats

AbstractBackground: Diabetes mellitus is a widespread syndrome and a major cause of morbidity and mortality all over the world. Diabetic nephropathy is a progressive and irreversible renal affection that may end by renal failure in sever conditions. Bilirubin is the end product of heme catabolism. It has been recognized as a strong antioxidant. Many studies relate bilirubin to diabetes.Aim of Study: The present investigation aimed to study the changes in serum billirubin level in diabetic nephropathy and to know whether there is a correlation between its level and the stages of nephropathy in diabetic rats.Material and Methods: Sixty male albino rats were used and divided into the following groups; non-diabetic control group, diabetic nephropathy group and insulin-treated diabetic nephropathy group. By the end of the experimental period, 24 hours urine samples were collected to measure urine volume & urinary creatinine concentration and calculation of creatinine clearance. Then systolic blood pressure (SBP) was measured using rat tail sphygmomanometer technique. Fasting blood samples were collected for estimation of glycemic state, liver function tests and renal function tests. Finally both kidneys were fixed in 10% formalin solution for histopathology by using H&E & periodic acid schiffe (PAS).Results: Our data showed that streptozotocin injection significantly elevated glycemic state, aspartate transaminase (AST), alanine transaminase (ALT), serum urea, serum creat-inin, SBP and significantly decreased seum albumin, creatinin clearance, total and direct bilirubin. Alkaline phosphatase (ALP) and serum albumin showed insignificant change. Histopathological examination of the same group showed slight thickening of the basement membrane, arterioles, few inflammatory cells and hydropic changes in renal tubules. Insulin treatment significantly decreased glycemic state, AST, ALT, serum urea, serum creatinin, SBP and significantly elevated seum albumin, creatinin clearance, total and direct bilirubin. Histopathological examination of the same group showed some healthy glomeruli but still hydropic changes in renal tubules.Conclusion: Regular monitoring of bilirubin in diabetic patients is essential marker for progression and prognosis of diabetic nephropathy and effect of treatment.

Diabetológia és szervátültetés

Diabetes increases the risk of different kidney diseases. The most important is diabetic nephropathy, however, ischemic kidney disease, chronic pyleonephritis and papilla necrosis may also develop. The prognosis of diabetic nephropathy has improved recently, however, it is still the primary cause of dialysis and transplantation. Cardiovascular diseases predict mostly mortality in diabetic patients, however, cerebrovascular insults and peripheral obstructive arterial diseases necessitating lower limb amputations are also important. Diabetic retinopathy is almost always present with diabetic nephropathy. Diabetic neuropathy may also develop, furthermore vascular complications often combine. All these urge complex workup, follow-up and early treatment. If transplantation is indicated, preemptive operation should be preferred, and living donation shows the best outcomes. Different forms of carbohydrate disorder may occur after transplantation: new-onset diabetes or diabetes known before transplantation may progress. Renal transplantation with pancreas transplantation may be indicated in type 1 diabetes with end-stage diabetic nephropathy, most often simultaneously. This may result in normoglycemia and insulin-independence and the progression of other complications may also halt. Transplant associated hyperglycemia occurs in most of the patients early, however, it is often transitory. Despite stabilization of the patient and of the immunosuppressive therapy, about one third of the patients may develop posttransplant diabetes. Insulin secretion disorder is the primary cause, but insulin resistance is also needed. Insulin administration may help, however, other antidiabetics can also be useful. Carbohydrate metabolism should be checked in both cadaveric and living donors. The authors make an attempt to summarize the above conditions with Hungarian relevance as well. Orv Hetil. 2018; 159(46): 1930-1939.

Analysis, Nutrition, and Health Benefits of Tryptophan.

Tryptophan is an essential plant-derived amino acid that is needed for the in vivo biosynthesis of proteins. After consumption, it is metabolically transformed to bioactive metabolites, including serotonin, melatonin, kynurenine, and the vitamin niacin (nicotinamide). This brief integrated overview surveys and interprets our current knowledge of the reported multiple analytical methods for free and protein-bound tryptophan in pure proteins, protein-containing foods, and in human fluids and tissues, the nutritional significance of l-tryptophan and its isomer d-tryptophan in fortified infant foods and corn tortillas as well the possible function of tryptophan in the diagnosis and mitigation of multiple human diseases. Analytical methods include the use of acid ninhydrin, near-infrared reflectance spectroscopy, colorimetry, basic hydrolysis; acid hydrolysis of S-pyridylethylated proteins, and high-performance liquid and gas chromatography-mass spectrometry. Also covered are the nutritional values of tryptophan-fortified infant formulas and corn-based tortillas, safety of tryptophan for human consumption and the analysis of maize (corn), rice, and soybean plants that have been successfully genetically engineered to produce increasing tryptophan. Dietary tryptophan and its metabolites seem to have the potential to contribute to the therapy of autism, cardiovascular disease, cognitive function, chronic kidney disease, depression, inflammatory bowel disease, multiple sclerosis, sleep, social function, and microbial infections. Tryptophan can also facilitate the diagnosis of certain conditions such as human cataracts, colon neoplasms, renal cell carcinoma, and the prognosis of diabetic nephropathy. The described findings are not only of fundamental scientific interest but also have practical implications for agriculture, food processing, food safety, nutrition, and animal and human health. The collated information and suggested research need will hopefully facilitate and guide further studies needed to optimize the use of free and protein-bound tryptophan and metabolites to help improve animal and human nutrition and health.

Evaluate Role of Transforming Growth Factor-β1 for the Prognosis of Diabetic Nephropathy in Pakistani Patients

Evaluate Role of Transforming Growth Factor-β1 for the Prognosis of Diabetic Nephropathy in Pakistani Patients

Potential Role of Serum and Urinary Biomarkers in Diagnosis and Prognosis of Diabetic Nephropathy.

Purpose of review:Diabetic nephropathy (DN) is a progressive kidney disease caused by alterations in kidney architecture and function, and constitutes one of the leading causes of end-stage renal disease (ESRD). The purpose of this review is to summarize the state of the art of the DN-biomarker field with a focus on the new strategies that enhance the sensitivity of biomarkers to predict patients who will develop DN or are at risk of progressing to ESRD.Objective:In this review, we provide a description of the pathophysiology of DN and propose a panel of novel putative biomarkers associated with DN pathophysiology that have been increasingly investigated for diagnosis, to predict disease progression or to provide efficient personal treatment.Methods:We performed a review of the literature with PubMed and Google Scholar to collect baseline data about the pathophysiology of DN and biomarkers associated. We focused our research on new and emerging biomarkers of DN.Key findings:In this review, we summarized the critical signaling pathways and biological processes involved in DN and highlighted the pathogenic mediators of this disease. We next proposed a large review of the major advances that have been made in identifying new biomarkers which are more sensitive and reliable compared with currently used biomarkers. This includes information about emergent biomarkers such as functional noncoding RNAs, microRNAs, long noncoding RNAs, exosomes, and microparticles.Limitations:Despite intensive strategies and constant investigation, no current single treatment has been able to reverse or at least mitigate the progression of DN, or reduce the morbidity and mortality associated with this disease. Major difficulties probably come from the renal disease being heterogeneous among the patients.Implications:Expanding the proteomics screening, including oxidative stress and inflammatory markers, along with metabolomics approaches may further improve the prognostic value and help in identifying the patients with diabetes who are at high risk of developing kidney diseases.

Effects of overexpressing FoxO1 on apoptosis in glomeruli of diabetic mice and in podocytes cultured in high glucose medium

Podocyte apoptosis induced by high levels of glucose is a key event in the development and prognosis of diabetic nephropathy (DN). Forkhead transcription factor O1 (FoxO1) has been defined as a critical mediator of oxidative stress in animal models of diabetes and is involved in mitophagy. To test the role of FoxO1 in regulating podocyte apoptosis both in vivo and in vitro, we generated FoxO1 overexpression models. High-glucose (HG) induced podocyte apoptosis with decreased mitophagy. These changes were accompanied by mitochondrial dysfunction and more severe podocyte loss in mouse kidney. FoxO1 overexpression prevented the apoptosis induced by HG. Reduction of cell apoptosis and renal damage depended upon the expression of PTEN-induced putative kinase 1 (PINK1). These findings suggest that specific overexpression of renal FoxO1 decreases podocyte apoptosis, which may be explained in part by its regulation of PINK1, and that targeting FoxO1 may represent a novel therapeutic approach for DN.

Kidney injury molecule-1 (Kim-1): an early biomarker for nephropathy in type II diabetic patients

Renal damage is a serious major microvascular diabetic complication implicated in the death of diabetic patients, which would necessitate the need for new biomarkers to detect early stage of diabetic nephropathy (DN). Kidney injury molecule-1 (Kim-1), a type I transmembrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. So, the present study was conducted to estimate and evaluate Kim-1 as a biomarker for DN. This cross-sectional study was carried out on 60 male and female type II diabetic patients (whose serum creatinine level was less than 2 mg/dL). Diabetic patients were classified as microalbuminuric with nephropathy (urinary albumin was 30–300 mg/dL) and normoalbuminuric without nephropathy (urinary albumin was <30 mg/dL). Twenty matched apparently healthy subjects were included as control group. Patients and controls were assessed for fasting blood glucose, glycosylated hemoglobin (HbA1c), serum creatinine, blood urea nitrogen (BUN), microalbuminuria, and urinary Kim-1. Urinary Kim-1 levels were elevated significantly tenfold in type II diabetic microalbuminuric patients as compared to the control group and normoalbuminuric diabetic patient. Urinary Kim-1 levels were positively correlated with microalbuminuria, serum creatinine, BUN, duration of diabetes, and BMI. Higher urinary Kim-1 level in T2D particularly in those with nephropathy and its correlation with urinary microalbumin, serum creatinine, blood urea, and BUN may reflect the role of Kim-1 as a biomarker for diagnosis and prognosis of diabetic nephropathy among T2D patients taking into account other risk factors.