Incipient Diabetic Nephropathy Research Articles

Engineering DNA tetrahedron as a sensing surface of lateral flow test strips and ratiometric visual detection of exosomal microRNA-150–5p

We here report that DNA tetrahedral probe-based sensing surfaces are capable of efficiently capturing gold nanoparticles (AuNPs) on lateral flow test strips, and we have developed a ratiometric biosensor for exosomal microRNAs by integrating a tetrahedral probe and a catalytic hairpin assembly (CHA). DNA tetrahedrons were devised with barcodes and labeled with biotin as capture probes on the test and control lines of the strip. The CHA system consists of two hairpin substrates that can form stable duplexes via a programmable assembly reaction triggered by exosomal miRNAs. The duplexes hybridized with barcoded tetrahedra via complementary sequences and bound to streptavidin-modified AuNPs (SA-AuNPs) via biotin. Thus, a red line was observed on the test line owing to the immobilized SA-AuNPs. The remaining SA-AuNPs were captured by using a biotinylated tetrahedron on the control line. Because the barcoded and biotinylated tetrahedra consume SA-AuNPs simultaneously, a stronger signal in the test line results in a weaker signal in the control line, thus forming a ratiometric result. Tetrahedral probes avoid movement along with sample flow on sensing zones like single-stranded probes. The strip can have a detection limit of 58.90 fM with high selectivity due to the use of ratiometric color changing response, CHA signal amplification and tetrahedral capture probes. This system is able to rapidly detect exosomal microRNA-150–5p and may have a potential utility in point-of-care diagnosis of incipient diabetic nephropathy.

Potential Role and Expression Level of Urinary CXCL8 in Different Stages of Incipient Diabetic Nephropathy with Undiminished Creatinine Clearance: A Pilot Study.

Diabetic nephropathy (DN) is one of the most devastating microvascular complications of diabetes, with a high prevalence and poor prognosis. Early intervention is crucial to improve the outcomes of DN. CXCL8 is related to podocyte damage in incipient DN; however, the role and expression level of CXCL8 have never been elucidated, especially in those with undiminished creatinine clearance. Consecutive inpatients with type 2 diabetes were included in this study. Patients were assigned into four groups based on the Mogensen stage, reflecting pathological features through clinical manifestations: non-DN group, hyperfiltration group, microalbuminuria group and overt DN group. Clinical and laboratory data were retrospectively collected and analyzed. Urinary CXCL8 (uCXCL8) was measured using an enzyme-linked immunosorbent assay (ELISA) method and adjusted for urinary creatinine (Cr) from the same urine sample. In total, 88 eligible consecutive inpatients with type 2 diabetes were included in this study. uCXCL8 was differentially expressed in different stages of incipient DN; it decreased in the hyperfiltration phase of incipient DN (1.40±1.01 pg/μmol Cr) and was highly expressed in patients in the microalbuminuria stage (5.01±4.01 pg/μmol Cr). uCXCL8 was positively correlated with age, diabetes course, cystatin C and urinary albuminuria-to-creatinine ratio, but negatively correlated with estimated glomerular filtration rate (P<0.05). uCXCL8 was a risk factor for classic DN after adjusting for age, diabetes course and cystatin C (OR=1.17, 95% CI 0.98-1.4, P=0.045). CXCL8 played an important role in the progression of incipient DN. The unique expression profile of uCXCL8 may provide a reference for understanding the prognosis and mechanisms of incipient DN progression. uCXCL8 was an independent risk factor for the development of classic DN.

Visualizing increased uptake of [18F]FDG and [18F]FTHA in kidneys from obese high-fat diet fed C57BL/6J mice using PET/CT ex vivo.

It is known that high-fat diet (HFD) and/or diabetes may influence substrate preferences and energy demands in the heart preceding diabetic cardiomyopathy. They may also induce structural glomerular changes causing diabetic nephropathy. PET/CT has been utilized to examine uptake of energy substrates, and to study metabolic changes or shifts before onset of metabolic disorders. However, conventional PET/CT scanning of organs with relatively low uptake, such as the kidney, in small animals in vivo may render technical difficulties. To address this issue, we developed a PET/CT ex vivo protocol with radiolabeled glucose and fatty acid analouges, [18F]FDG and [18F]FTHA,to study substrate uptake in mouse kidneys. We also aimed to detect a possible energy substrate shift before onset of diabetic nephropathy. The ex vivo protocol reduced interfering background as well as interindividual variances. We found increased uptake of [18F]FDG and [18F]FTHA in kidneys after HFD, compared to kidneys from young mice on standard chow. Levels of kidney triglycerides also increased on HFD. Lipoprotein lipase (LPL) activity, the enzyme responsible for release of fatty acids from circulating lipoproteins, is normally increased in postprandial mice kidneys. After long-term HFD, we found that LPL activity was suppressed, and could therefore not explain the increased levels of stored triglycerides. Suppressed LPL activity was associated with increased expression of angiopoietin-like protein4, an inhibitor of LPL. HFD did not alter the transcriptional control of some common glucose and fatty acid transporters that may mediate uptake of [18F]FDG and [18F]FTHA. Performing PET/CT ex vivo reduced interfering background and interindividual variances. Obesity and insulin resistance induced by HFD increased the uptake of [18F]FDG and [18F]FTHA and triglyceride accumulation in mouse kidneys. Increased levels of [18F]FDG and [18F]FTHA in obese insulin resistant mice could be used clinically as an indicator of poor metabolic control, and a complementary test for incipient diabetic nephropathy.

Urine Zinc-alpha-2-glycoprotein as a Potential Biomarker for Incipient Diabetic Nephropathy: A Pilot Study at a Tertiary Care Hospital

Introduction: Urine albumin-creatinine ratio (UACR) continues to be used as an indicator for detecting diabetic nephropathy (DN); however, damage starts much before that. Currently, no biomarkers are there to indicate incipient damage. As a result, researchers are looking for new biomarkers that could be used to detect DN threats sooner and perhaps hinder the development of end-stage renal disease. The present study intended to know if urine Zinc-alpha-2-glycoprotein (ZAG) levels correlate with glomerular filtration rate (GFR) in the study participants of type 2 diabetes mellitus (T2DM). Materials and Methods: The study included 68 participants with a known history of T2DM. Serum urea and creatinine levels, fasting plasma glucose, serum cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total protein, glycated hemoglobin (HbA1c) and urine ZAG were estimated and UACR along with estimated GFR (eGFR) were calculated for all individuals. The characteristics of the study participants in the microalbuminuric and normoalbuminuric groups were compared. Results: The levels of urine ZAG in the microalbuminuric and normoalbuminuric groups were not observed to be substantially different. The relationship between urine ZAG and diabetes mellitus duration was found to be highly significant in normoalbuminuric patients. Urinary ZAG and correlation with categories of HbA1c % (good &lt;7, 7–9 moderate, &gt;9 poor) among normoalbuminuric individuals were not found to be significant. Conclusion: Despite previous research, we were unable to find a positive relationship between urinary ZAG concentrations and eGFR in this study. Prospective studies with greater sample sizes and follow-up are required to fully comprehend the possible use of ZAG as a biomarker in diabetic nephropathy.

Is there a characteristic pattern of ambulatory blood pressure profile in type 1 diabetic children and adolescents?

To examine the characteristics of ambulatory blood pressure (ABP) including blood pressure variability (BPV) and its association with albuminuria in type 1 diabetic (T1D) children and to identify potential predictors of high-normal albuminuria and microalbuminuria. ABP monitoring was performed in 201 T1D children and adolescents (mean age, 14.7±3.8 years) with T1D duration over 1 year. The level of albuminuria was assessed as the albumin/creatinine ratio (ACR) and patients were further classified as low-normal, high-normal or microalbuminuria. Fifteen T1D children (7.5%) were hypertensive using office blood pressure (BP) and 10 (5%) according to ABP. T1D subjects had elevated 24-hour systolic BP (SBP) and diastolic BP (DBP) (+0.2 and + 0.3 standard deviation score [SDS]) and nighttime SBP and DBP (+0.6 and +0.8 SDS) compared to reference values. Patients with microalbuminuria had significantly higher 24-hour, daytime and nighttime DBP compared to normoalbuminuric subjects. There was a high percentage of nondippers (74.1%). Nighttime diastolic BPV was significantly higher in subjects with high-normal compared to low-normal albuminuria (p=0.01). A weak correlation was found between ACR and daytime DBP SDS (r=0.29, p<0.001 and nighttime DBP SDS (r=0.21, p=0.003). Age and nighttime diastolic BPV were predictors of high-normal albuminuria while nighttime DBP was a strong predictor for microalbuminuria. T1D children have impaired BP regulation although most of them do not fulfill the criteria for sustained hypertension. There is an association between diastolic ABP and diastolic BPV with rising levels of albuminuria pointing to a clear connection between BP and incipient diabetic nephropathy.

Diastolic Pressure and ACR Are Modifiable Risk Factors of Arterial Stiffness in T2DM Without Cardiovascular Disease.

To evaluate early, before the onset of cardiovascular events and of chronic renal insufficiency, the association between chronic kidney disease (CKD)-mineral bone disorder (MBD) biomarkers and vascular stiffness [Cardio Ankle Vascular Index (CAVI)] in the course of type 2 diabetes (T2DM). We evaluated 174 T2DM patients [median age 56 years; male/female (M/F) 100/74] with diabetes duration < 10 years and without decreased estimated glomerular filtration rate (eGFR; ≥60 mL/min/1.73 m2) or macrovascular complications. Thirty-four age-matched healthy subjects [M/F 13/21; age 53.5 (50.0-57.7) years; eGFR 107.5 (97.0-119.7) mL/ min1.73 m2] served as local reference control for CAVI (pathological: ≥8) and the novel CKD-MBD biomarkers. Albumin-to-creatinine ratio (ACR) averaged 8.5 mg/g (5.6-17.2) with 12.6% of the patients showing pathologic values, indicative of incipient diabetic nephropathy. Serum parathyroid hormone, fibroblast growth factor 23, and sclerostin were higher while 1,25-dihydroxyvitamin D and Klotho were lower than a control group. CAVI was normal (<8) in only 54% and correlated positively with age (P < 0.001), hemoglobin 1A1c (P = 0.036), and systolic (P = 0.021) and diastolic blood pressure (DBP) (P = 0.001) and negatively correlated with 25-hydroxyvitamin D (P = 0.046). In multivariate analysis, age, DBP, ACR, and serum Klotho were independent positive predictors of CAVI. In the absence of overt cardiovascular disease and of chronic renal insufficiency, CAVI is frequently pathologic in T2DM. DBP and ACR are modifiable risk factors of vascular stiffness in T2DM, thus warranting optimal assessment.

A study of association of proteinuria with hba1c in diabetes mellitus

Diabetic nephropathy occurs in as many as 30% of insulin dependent diabetes mellitus patients and 25% of noninsulin-dependent diabetes mellitus patients. Diabetic nephropathy is a dreaded disease with progressive and continuous. Deterioration in glomerular function resulting in irreversible renal failure. Diabetic nephropathy is an important cause of morbidity and mortality and is now among the most common cause of end-stage renal disease. However, there is an early phase of diabetic renal disease called incipient diabetic nephropathy. This study is intended to study the association of Proteinuria with HbA1C in Diabetes Mellitus.

ITRAQ plasma proteomics analysis for candidate biomarkers of type 2 incipient diabetic nephropathy

BackgroundDiabetic nephropathy is the most frequent cause of end-stage renal disease worldwide. Identification of biomarkers for diabetic nephropathy for early diagnosis may be the key to avoiding damage from this condition.MethodsProteomic iTRAQ technology was first used to identify differentially expressed plasma proteins in type 2 incipient diabetic nephropathy (IDN) using a Q-Exactive mass spectrometer.ResultsCompared with controls, 57 proteins (32 upregulated and 25 downregulated proteins) were identified. Furthermore, the gelsolin, collectin-11, PTPRJ, and AKAP-7 proteins were confirmed by Western blots as candidate biomarkers for type 2 IDN through ROC analysis.ConclusionsThese findings offer a theoretical basis for the early treatment of diabetic nephropathy.

Serum uromodulin and Roux-en-Y gastric bypass: improvement of a marker reflecting nephron mass

BackgroundEarly diagnosis of kidney disease in obese patients and in such patients with type 2 diabetes (T2D) can significantly improve treatment outcome. Serum uromodulin (sUMOD) may be a sensitive parameter for early detection of nephropathy. ObjectivesTo analyze sUMOD and traditional markers of kidney function in a cohort study of patients with and without obesity or T2D undergoing metabolic surgery compared with blood donors. SettingUniversity of Heidelberg, Germany. MethodsPatients with obesity (body mass index >35 kg/m2) without T2D (n = 10) and T2D (n = 10) and patients with nonsevere obesity (body mass index, 25–35 kg/m2) and insulin-dependent T2D (n = 16) undergoing Roux-en-Y gastric bypass (RYGB) were enrolled. The control group consisted of 190 blood donors. sUMOD was compared with established renal markers. ResultsUsing sUMOD, impaired kidney function at baseline was present in both groups with T2D and in none of the patients with obesity without T2D. This impairment was not detectable through traditional markers. Significant improvement of sUMOD was shown in patients with obesity and T2D 12 months postoperatively (from 130.0 ± 77.5 to 239.5 ± 179.0 ng/mL; P = .004) and in patients with nonsevere obesity and T2D 6 months after RYGB (from 140.6 ± 78.0 to 298.7 ± 154.0 ng/mL; P = .017). In patients with obesity without T2D, sUMOD remained stable (P = .375). ConclusionssUMOD may serve as a tissue-specific biomarker in incipient diabetic nephropathy. Improvement of sUMOD after RYGB seems to profoundly restore the structural integrity of nephrons in these patients at risk for diabetic nephropathy.

Obese and hypertensive elderly patient, with incipient diabetic nephropathy and previous cardiovascular event, long-term treated with secretagogues

We report the case of a 75-year old patient affected by type 2 diabetes for about 20 years, treated for a prolonged period with insulin secretagogues. He is also affected by arterial hypertension, obesity and incipient diabetic nephropathy and had suffered a cardiovascular event. He was referred to us by his GP to verify his high values of glycated hemoglobin (HbA1c) and for an excessive weight increase (Diabetology)

Osteopontin as a marker of vasculopathy in pediatric patients with type 1 diabetes mellitus: Relation to vascular structure.

Type 1 diabetes mellitus (T1DM) is associated with serious micro-vascular and macro-vascular complications. Osteopontin (OPN) has emerged as a strong predictor of incipient diabetic nephropathy and a first-ever cardiovascular event in adults with T1DM. OPN is linked to coronary atherosclerosis in type 2 diabetes. The aim of the study was to test the hypothesis that OPN could be a potential marker for micro-vascular complications in children and adolescents with T1DM and we assessed its relation to carotid and aortic intima media thickness (CIMT and AIMT) as non-invasive index for subclinical atherosclerosis. Eighty patients with T1DM ≤18 years were divided into 2 groups according to the presence of micro-vascular complications and compared with 40 age- and sex-matched healthy controls. Fasting blood glucose, high sensitivity C-reactive protein (hs-CRP), HbA1c, urinary albumin creatinine ratio (UACR), OPN, CIMT, and AIMT were assessed. Both CIMT and AIMT were significantly higher in patients with and without micro-vascular complications compared with healthy controls (P < .001). OPN concentrations were significantly elevated in all diabetic patients compared with controls (P = .002). OPN was also significantly higher in patients with micro-vascular complications than patients without (P < .001) but levels were comparable among those without complications and controls (P = .322). Receiver operating characteristic curve analysis revealed that OPN cut-off value 90 ng/mL could differentiate patients with and without micro-vascular complications with 81.7% sensitivity and 95.8% specificity. Significant positive correlations were found between OPN and HbA1c, UACR, CIMT, and AIMT. OPN could be considered a marker of vasculopathy and subclinical atherosclerosis in pediatric T1DM.

A study in prevalence of diabetic nephropathy in recently detected cases of type 2 diabetes mellitus as evidenced by altered creatinine clearance, urinary albumin and serum creatinine, with special emphasis on hypertension, hypercholesterolemia and obesity

Background: Diabetic nephropathy is one of the commonest and most dreaded complications of Diabetes. The Aim was to evaluate the significance of microalbuminuria and creatinine clearance for detecting incipient diabetic nephropathy, and to find out the prevalence of nephropathy among freshly detected Type 2 diabetic patients with vs. those without hypertension, hypercholesterolemia and/or obesity.Methods: In this prospective study, 100 recently diagnosed diabetics were studied. Group A had 50 patients with at least one risk factor are hypertension, hypercholesterolemia and obesity. Group B had 50 patients without any of the aforementioned factors. Patients were investigated for presence of Diabetic nephropathy with abnormal serum Creatinine, creatinine clearance and urinary albumin levels.Results: As many as 43 out of 100 patients were found to have Diabetic nephropathy. The number was significantly higher in group A compared to group B (34/50 vs. 9/50). Incidence of nephropathy was higher with higher number of associated risk factors. Urinary microalbuminuria was the commonest abnormality, Serum creatinine was found in only 30.23% of total positive cases.Conclusions: Incidence of diabetic nephropathy is much larger than imagined in freshly diagnosed/new onset cases of DM type 2. Author also conclude that hypertension, obesity and hypercholesterolemia can contribute to development of nephropathy (68% vs. 18% in those who had the factors vs. those who didn’t). Also, urinary microalbuminuria appears to be much more sensitive than serum creatinine as screening tool.

The efficacy and safety of Chinese herbal medicine combined with ACEI/ARB for treatment of incipient diabetic nephropathy: A meta-analysis

The efficacy and safety of Chinese herbal medicine combined with ACEI/ARB for treatment of incipient diabetic nephropathy: A meta-analysis

Paeoniflorin attenuates incipient diabetic nephropathy in streptozotocin-induced mice by the suppression of the Toll-like receptor-2 signaling pathway.

Toll-like receptors (TLRs) may be involved in diabetic nephropathy (DN). Paeoniflorin (PF) is an effective Chinese traditional medicine with anti-inflammatory and immunoregulatory effects that may inhibit the TLR2 signaling pathway. In this study, we investigated the effects of PF on the kidneys of mice with streptozotocin-induced type 1 diabetes mellitus using TLR2 knockout mice (TLR2−/−) and wild-type littermates (C57BL/6J-WT). After 12 weeks of intraperitoneal injection of PF at doses of 25, 50, and 100 mg/kg once a day, diabetic mice had significantly reduced albuminuria and attenuated renal histopathology. These changes were associated with substantially alleviated macrophage infiltration and decreased expression of TLR2 signaling pathway biomarkers. These data support a role of TLR2 in promoting inflammation and indicate that the effect of PF is associated with the inhibition of the TLR2 pathway in the kidneys of diabetic mice. PF thus shows therapeutic potential for the prevention and treatment of DN.

Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes

Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. α-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function.

Osteopontin Is a Strong Predictor of Incipient Diabetic Nephropathy, Cardiovascular Disease, and All-Cause Mortality in Patients With Type 1 Diabetes

Osteopontin (OPN) is a multifunctional protein suggested to be a player in the arterial disease of patients with type 2 diabetes. However, its role for complications in patients with type 1 diabetes (T1D) is unknown. We therefore investigated the associations between OPN and diabetic vascular complications and all-cause mortality in patients with T1D. Serum OPN was measured in 2,145 adults with T1D without end-stage renal disease (ESRD; dialysis or transplantation) as part of the Finnish Diabetic Nephropathy (FinnDiane) Study. Data on renal status, cardiovascular disease (CVD), and all-cause mortality during follow-up were verified from medical files, hospital discharge registries, and the Finnish National Death Registry, respectively. The median follow-up time was 10.5 (interquartile range 8.9-11.8) years. Serum OPN was higher at baseline in patients who developed incident microalbuminuria (16.0 ± 0.9 vs. 14.1 ± 0.2 µg/L; P = 0.04), progressed to ESRD (28.3 ± 1.7 vs. 15.4 ± 0.2 µg/L; P < 0.001), suffered an incident CVD event (20.2 ± 1.2 vs. 15.5 ± 0.2 µg/L; P < 0.001), or died (23.3 ± 1.4 vs. 15.8 ± 0.2 µg/L; P < 0.001) during follow-up. In multivariate Cox regression analysis, OPN was independently associated with the development of incident microalbuminuria, an incident CVD event, and death, after adjustments for associated risk factors. Even after calculating reclassification indexes, OPN was predictive of CVD and all-cause mortality beyond the Framingham risk score covariates and hs-CRP. Serum OPN is a strong predictor of incipient diabetic nephropathy, a first-ever CVD event, and all-cause mortality in patients with T1D. Serum OPN may be of clinical significance for the risk prediction of CVD events in patients with T1D.

PHYSIOLOGICAL AND BIOCHEMICAL MARKERS TO ASSESS THE RISK FACTORS FOR DIABETIC NEPHROPATHY: A RETROSPECTIVE RURAL HOSPITAL BASED CASE CONTROL STUDY

Diabetic nephropathy (DN) is a major contributor to chronic kidney diseases globally as well as in India andi s associated with increased cardiovascular risk. The aim of this study is to estimate HbA 1 c, Fasting Insulin, total lipid profile, renal parameters and anthropometric parameters in assessing the most common complications of Diabetic Nephropathy. Two hundre d fifty type 2 diabetes mellitus and non diabetes subjects were studied for their anthropometric and biochemical parameters. Independent paired t - test was used to compare mean differences between parameters and p - value < 0.05 was considered significant. Di abetic patients had higher BMI, WHR and higher insulin levels compared to non diabetics. Significant relation was observed between HbA 1 c and HDL - C in diabetic patients. Higher values of fasting insulin, HbA 1 c, lipid profile with anthropometric measurement s and other biochemical parameters were significantly associated with commonest conflict of diabetic nephropathy. It further predicts CVD mortality in patients with diabetic nephropathy. Early screening for incipient diabetic nephropathy and aggressive man agement of these risk factors is important in optimizing the renal outcome of patients with diabetes mellitus. These results indicate that the risk of developing diabetes is certainly higher in non - diabetes subjects.

Markers of and Risk Factors for the Development and Progression of Diabetic Kidney Disease

Diabetic kidney disease (DKD) occurs in 25%-40% of patients with diabetes. Given the dual problems of a significant risk of progression from DKD to end-stage renal disease (ESRD) and increased cardiovascular morbidity and mortality, it is important to identify patients at risk of DKD and ESRD and initiate protective renal and cardiovascular therapies. The importance of preventive therapy is emphasized further by worldwide increases in the incidence of diabetes. This review summarizes the evidence regarding the prognostic value and benefits of targeting established and novel risk markers for DKD development and progression. Family history of DKD, smoking history, and glycemic, blood pressure, and plasma lipid level control are established factors for identifying people at greatest risk of DKD development and progression. Absolute albumin excretion rate (AER) and glomerular filtration rate (GFR) measurements also are important, although AER categorization generally lacks the necessary specificity and sensitivity, and estimates of declining GFR are compromised by methodological limitations for GFRs in the normal-to-high range. Emerging risk markers for progressive loss of kidney function include markers of oxidation and inflammation, profibrotic cytokines, uric acid, advanced glycation end products, functional and structural markers of vascular dysfunction, kidney structural changes, and tubular biomarkers. Among these, the most promising are serum uric acid and soluble tumor necrosis factor receptor (type 1 and type 2) levels, especially in relation to GFR changes. At present, these can only be considered as risk markers because they only identify an individual at increased risk of progressive DKD and not necessarily related to the causal pathway promoting kidney damage. Further work is needed to establish whether modulating these factors improves the prognosis in DKD. Although change in urinary peptidome levels also is a promising marker, there currently is neither a clinical assay nor adequate studies defining its prognostic value. Until these or other novel markers become available for clinical use, predictive accuracy often may be increased with greater attention to established markers.

Prevalence of proteinuria among type 2 diabetic patients in Menoufia governorate, Egypt

Objective The aim of the study was to determine the prevalence and risk factors of proteinuria among type 2 diabetic patients in Menoufia governorate. Background Type 2 diabetes is the leading cause of end-stage renal disease worldwide. Microalbuminuria or incipient diabetic nephropathy is one of the initial clinical manifestations of early diabetic nephropathy. Patients and methods A total of 234 type 2 diabetic patients were included in this study; they attended the outpatient clinics of the Family Health Center of 'Kafr Tanbedy' and Internal Medicine Department of Faculty of Medicine, Menoufia University, for routine follow-up. Patients were classified according to their urinary albumin-to-creatinine ratio (ACR) as having normoalbuminuria (ACR Results Prevalence of microalbuminuria (incipient diabetic nephropathy) was 34.2% and that of macroalbuminuria (overt diabetic nephropathy) was 12.8% in the studied group. Conclusion The overall prevalence rate of albuminuria was considerably high (47.01%) among the studied diabetic patients. Therefore, regular screening for microalbuminuria is recommended for all diabetic patients, as early treatment is critical for reducing cardiovascular risks and slowing the progression to late stages of diabetic nephropathy (overt proteinuria and end-stage renal disease).

Urinary Exosomal MicroRNAs in Incipient Diabetic Nephropathy

MicroRNAs (miRNAs), a class of small non-protein-encoding RNAs, regulate gene expression via suppression of target mRNAs. MiRNAs are present in body fluids in a remarkable stable form as packaged in microvesicles of endocytic origin, named exosomes. In the present study, we have assessed miRNA expression in urinary exosomes from type 1 diabetic patients with and without incipient diabetic nephropathy. Results showed that miR-130a and miR-145 were enriched, while miR-155 and miR-424 reduced in urinary exosomes from patients with microalbuminuria. Similarly, in an animal model of early experimental diabetic nephropathy, urinary exosomal miR-145 levels were increased and this was paralleled by miR-145 overexpression within the glomeruli. Exposure of cultured mesangial cells to high glucose increased miR-145 content in both mesangial cells and mesangial cells-derived exosomes, providing a potential mechanism for diabetes-induced miR-145 overexpression. In conclusion, urinary exosomal miRNA content is altered in type 1 diabetic patients with incipient diabetic nephropathy and miR-145 may represent a novel candidate biomarker/player in the complication.