Increase In Urinary Albumin Excretion Research Articles

Preventive effects of vasohibin-2-targeting peptide vaccine for diabetic nephropathy.

Diabetic nephropathy remains the leading cause of end-stage kidney disease in many countries, and additional therapeutic targets are needed to prevent its development and progression. Some angiogenic factors are involved in the pathogenesis of diabetic nephropathy. Vasohibin-2 (VASH2) is a novel proangiogenic factor, and our previous study showed that glomerular damage is inhibited in diabetic Vash2 homozygous knockout mice. Therefore, we established a VASH2-targeting peptide vaccine as a tool for anti-VASH2 therapy in diabetic nephropathy. In this study, the preventive effects of the VASH2-targeting peptide vaccine against glomerular injury were examined in a streptozotocin (STZ)-induced diabetic mouse model. The mice were subcutaneously injected with the vaccine at two doses 2 weeks apart and then intraperitoneally injected with 50 mg/kg STZ for 5 consecutive days. Glomerular injury was evaluated 20 weeks after the first vaccination. Treatment with the VASH2-targeting peptide vaccine successfully induced circulating anti-VASH2 antibody without inflammation in major organs. Although the vaccination did not affect blood glucose levels, it significantly prevented hyperglycemia-induced increases in urinary albumin excretion and glomerular volume. The vaccination did not affect increased VASH2 expression but significantly inhibited renal angiopoietin-2 (Angpt2) expression in the diabetic mice. Furthermore, it significantly prevented glomerular macrophage infiltration. The preventive effects of vaccination on glomerular injury were also confirmed in db/db mice. Taken together, the results of this study suggest that the VASH2-targeting peptide vaccine may prevent diabetic glomerular injury in mice by inhibiting Angpt2-mediated microinflammation.

Neutrophil to lymphocyte ratio (NLR) as a surrogate marker of diabetic nephropathy

Background and objectives: Diabetic nephropathy and retinopathy are microvascular complications of diabetes. Nephropathy is clinically manifested as an increase in urine albumin excretion. Total white blood cell count is a crude but sensitive indicator of inflammation and studied in many cardiac and non-cardiac diseases as an inflammatory marker such as acute myocardial infarction, stroke, and heart failure. In this study, the association of neutrophil to lymphocyte ratio (NLR) with diabetic nephropathy and retinopathy. Methods: This was a prospective observational study performed on patients with diabetic nephropathy +/- retinopathy. A total of v104 subjects diagnosed with 3type 2 diabetes mellitus registered in this study. NLR was calculated by analyzing differential leukocyte count in complete blood picture. Spot Albuminuria was tested by immune turbidimetry method. Urine creatinine was tested by jaffe’s kinetic method by which spot urine microalbumin to creatinine ratio is calculated. ANOVA, Independent t-test, chi-square test, Karl Pearson correlation were applied to find significance. P<0.05 was considered as statistically significant. Results: Totally 104 diabetic subjects were registered, 52 subjects had DN and 52 had normal urine albumin. Mean±SD NLR for a normal group is 2.5±1.1 and in DN group is 3.4±1.4 which was highly significant (P =0.001). Conclusion: Our study showed that there was a significant relation between NLR and DN; and positive correlation between NLR and urine microalbumin to creatinine ratio. Therefore, NLR may be considered as a novel surrogate marker of DN.

Azilsartan improves urinary albumin excretion in hypertension mice.

Hypertension is one of the most important risk factors for chronic kidney diseases, leading to hypertensive nephrosclerosis, including excessive albuminuria. Azilsartan, an angiotensin II type 1 receptor blocker, has been widely used for the treatment of hypertension. However, the effects of Azilsartan on urinary albumin excretion in hypertension haven't been reported before. In this study, we investigated whether Azilsartan possesses a beneficial property against albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Compared to the control group, the ANG/HS group had higher blood pressure, oxidative stress, and inflammatory response, all of which were rescued by Azilsartan dose-dependently. Importantly, the ANG/HS-induced increase in urinary albumin excretion and decrease in the expression of occludin were reversed by Azilsartan. Additionally, it was shown that increased fluorescence intensity of FITC-dextran, declined trans-endothelial electrical resistance (TEER) values, and reduction of occludin and krüppel-like factor 2 (KLF2) were observed in ANG/HS-treated human renal glomerular endothelial cells (HrGECs), then prevented by Azilsartan. Moreover, the regulatory effect of Azilsartan on endothelial monolayer permeability in ANG/HS-treated HrGECs was abolished by the knockdown of KLF2, indicating KLF2 is required for the effect of Azilsartan. We concluded that Azilsartan alleviated diabetic nephropathy-induced increase in Uterine artery embolization (UAE) mediated by the KLF2/occludin axis.

Kidney Impairment Prediction Due to Diabetes Using Extended Ensemble Learning Machine Algorithm

Diabetes is the main cause for diabetic kidney disease (dkd), which affects the filtering units of kidneys slowly and stops it’s function finally. This consequence is common for both genetic based (type 1) and lifestyle based (type 2) diabetes. However, type 2 diabetes plays a significant influence in increased urine albumin excretion, decreased glomerular filtration rate (gfr), or both. These causes failure of kidneys stage by stage. Herein, the implementation of extended ensemble learning machine algorithm (eelm) with improved elephant herd optimization (ieho) algorithm helps in identifying the severity stages of kidney damage. The data preprocessing and feature extraction process extracts three vital features such as period of diabetes (in year), gfr (glomerular filtration rate), albumin (creatinine ratio) for accurate prediction of kidney damage due to diabetes. Predicted result ensures the better outcome such as an accuracy of 98.869%, 97.899 % of precision ,97.993 % of recall and f-measure of 96.432 % as a result.

PTEN, MMP2, and NF-κB and Regulating MicroRNA-181 Aggravate Insulin Resistance and Progression of Diabetic Nephropathy: A Case-Control Study

Diabetic nephropathy (DN) is characterized by an increase in urinary albumin excretion, diabetic glomerular lesions, and a decline in glomerular filtration rate (GFR). We assessed the expression of phosphatase and tensin homolog (PTEN), nuclear factor kappa-β (NF-κB), matrix metalloproteinase-2 (MMP2), and microRNA-181 in healthy controls (HC), individuals with type 2 diabetes mellitus (T2DM) without nephropathy, and those with DN. Our study investigated the association between these genes, insulin resistance (IR), and eGFR to gain insight into their roles in the pathogenesis and progression of DN. Anthropometric measurements and biochemical tests were conducted on HC (N = 36), T2DM (N = 38) patients, and DN (N = 35) patients. We used real-time polymerase chain reaction (RT-PCR) for whole blood gene expression analysis and performed bioinformatics analyses, including protein–protein interaction, gene ontology, and co-expression networks. We compared our expression data with other GEO-Microarray datasets. Our study highlights the role of IR in the progression of nephropathy in T2DM via the PTEN-Akt-mTOR signalling pathway. We also observed a decreasing trend in the expression of MMP2 and PTEN and an increasing trend in the expression of NF-κB and miR-181b-5p with the progression of nephropathy to the severe stage. The dysregulated expression of MMP2, PTEN, NF-κB, and miR-181b-5p in patients with T2DM contributes to the progression of T2DM to DN by aggravating IR, inflammation, accelerating basement membrane thickening, mesangial matrix expansion, and renal fibrosis.

Diabetic Nephropathy: Pathogenesis to Cure.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disorder (ESRD). It is defined as the increase in urinary albumin excretion (UAE) when no other renal disease is present. DN is categorized into microalbuminuria and macroalbuminuria. Factors like high blood pressure, high blood sugar levels, genetics, oxidative stress, hemodynamic and metabolic changes affect DN. Hyperglycemia causes renal damage through activating protein kinase C (PKC), producing advanced end glycation products (AGEs) and reactive oxygen species (ROS). Growth factors, chemokines, cell adhesion molecules, inflammatory cytokines are found to be elevated in the renal tissues of the diabetic patient. Many different and new diagnostic methods and treatment options are available due to the increase in research efforts and progression in medical science. However, until now, no permanent cure is available. This article aims to explore the mechanism, diagnosis, and therapeutic strategies in current use for increasing the understanding of DN.

Acute kidney injury and diabetic kidney disease in children with acute complications of diabetes

BackgroundDiabetic ketoacidosis (DKA) and hyperglycaemia without ketoacidosis are common acute complications of diabetes. Their association with acute kidney injury (AKI) and diabetic kidney disease (DKD) was studied.MethodsThe study group consisted of 197 children with type 1 diabetes with average diabetes duration of 8.08 ± 2.32 years. The medical history of the patients was retrospectively reviewed. The number of children with severe hyperglycaemia, DKA and AKI was assessed. The association with the risk of chronic kidney disease (CKD) was analysed.ResultsAKI was found in 14% of cases hospitalised for DKA and 8% of cases hospitalised for hyperglycaemia. Patients with AKI showed a significantly increased corrected sodium (141.23 ± 5.09 mmol/L, p = 0.035). Patients with AKI in DKA showed a significant increase in WBC (20.73 ± 8.71 × 103/µL, p = 0.0009). Follow-up analysis after a minimum of 5 years of diabetes revealed that a single episode of DKA was found in 63 patients and a single episode of AKI in 18 patients. Two or more episodes of DKA were found in 18 patients, and nine cases were complicated by AKI. These patients showed a significant increase in urinary albumin excretion (44.20 ± 64.21 mg/24 h), the highest values of eGFR and the worst glycaemic control.ConclusionsDiabetic children can develop AKI in the course of DKA and hyperglycaemia without ketoacidosis, which is associated with volume depletion and reflected by corrected sodium concentration. AKI in DKA seems to be complicated by stress and inflammation activation. AKI and poor glycaemic control with repeated DKA episodes can magnify the risk of progression to DKD.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Nicotinamide mononucleotide ameliorates adriamycin-induced renal damage by epigenetically suppressing the NMN/NAD consumers mediated by Twist2

The activation of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, Sirt1, after the administration of nicotinamide mononucleotide (NMN) suppresses many diseases. However, the role of NMN and Sirt1 in focal glomerulosclerosis (FSGS) has not yet been elucidated. This study aimed to assess the protective effect of NMN treatment in mice with adriamycin (ADR)-induced FSGS. Transient short-term NMN treatment was administered to 8-week-old ADR- or saline-treated BALB/c mice (Cont group) for 14 consecutive days. NMN alleviated the increase in urinary albumin excretion in the ADR-treated mice. NMN treatment mitigated glomerulosclerosis and ameliorated the reduced Sirt1 expression and elevated Claudin-1 expression in the kidneys of the mice. Moreover, this treatment improved the decrease in histone methylation and the expression level of Dnmt1 and increased the concentration of NAD+ in the kidney. Dnmt1 epigenetically suppressed the expression of the NMN-consuming enzyme nicotinamide mononucleotide adenyltransferase1 (Nmnat1) by methylating the E-box in the promoter region and repressing the NAD-consuming enzyme PARP1. Additionally, NMN downregulated the expression of Nmnat1 in the ADR-treated mice. Short-term NMN treatment in FSGS has epigenetic renal protective effects through the upregulation of Sirt1 and suppression of the NAD and NMN consumers. The present study presents a novel treatment paradigm for FSGS.

Comparison the Role of Some Novel Biomarkers in Predicting Diabetic Nephropathy Between Diabetic Type 2 and Chronic Kidney Diseases Patients in Kirkuk City

Background: Diabetes mellitus most dangerous metabolic disorder and have high morbidity and mortality complications, the most DM complication is diabetic nephropathy. Diabetic nephropathy( DN) is an irreversible progressive disorder characterized by increased urine albumin excretion and/or impaired GFR. DM causes about 50 % of kidndiseasesase. An increase in prevalence of diabetes is projected to lead to a significant increase in patients with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT), and up to 50% of the dialysis population is diabetic. We study 30 Diabetic patients with Chronic kidney diseases with hemodialysis ,30 diabetic patient with chronic kidney disease with out hemodialysis , 15 patient with diabetes only , and 15 control group .we measured kidney injury molecule-1 , liver type fatty acid binding protein ,zinc alpha 2 glycoprotein , serum creatinine ,uric acid .blood urea and random blood sugar .results showed that highest KIM-1 concentration in diabetic nephropathy with hemodialysis group (2.325± 1.095) followed by control group (1.842 ±0.866 ab )and followed with diabetes group (1.572 ±0.752 b ) and lowest mean level was diabetic nephropathy without hemodialysis group (1.344 ±0.623 b ) with highly significant differences (p < 0.001) of KIM-1 among groups .The highest mean level of L-FABP was recorded in diabetic nephropathy with hemodialysis group (254.6 ± 29.6 a ) followed by the control group (235.8 ± 28.9) and followed by diabetic group ( 9210.3 ± 28.7 ab )and the lowest mean level was diabetic nephropathy without hemodialysis group (149.5 ±25.9 a) with significant difference (P<0.002) of L-FABP among groups .The study showed that the highest mean level of ZAG recorded in diabetic nephropathy with hemodialysis group (140.1 ± 23.6 a) followed by control group( 130.9 ±11.5 a)and the lowest mean level was in diabetes group (88.3 ± 14.0 b ) and diabetic nephropathy without hemodialysis group (87.4 ± 19.60 b ) respectively with highly significant difference (P<0.0003). Aims: Role of biomarkers (KIM-1, L-FABP, ZAG) in detection early development of diabetic nephropathy .Correlation between biomarkers (KIM-1, L-FABP, ZAG) and progression of diabetic nephropathy to end stage of renal disease .Estimate how much relationship between biomolecules (creatinine , urea and uric acid ) with diabetes and its complication Methodology :The study included 90 individuals from Kirkuk city / Blood sample collected from patient and analysis was conducted to estimate concentration using Enzyme Linked Immunosorbent Assay (ELISA),and biochemicals using spectrophotometers . Keywords: Diabetes, diabetic nephropathy , chronic kidney disease ,kidney biomarkers

Pre-screening to guide coronary artery calcium scoring for early identification of high-risk individuals in the general population.

To evaluate the ability of Systematic COronary Risk Estimation 2 (SCORE2) and other pre-screening methods to identify individuals with high coronary artery calcium score (CACS) in the general population. Computed tomography-based CACS quantification was performed in 6530 individuals aged 45 years or older from the general population. Various pre-screening methods to guide referral for CACS were evaluated. Miss rates for high CACS (CACS ≥300 and ≥100) were evaluated for various pre-screening methods: moderate (≥5%) and high (≥10%) SCORE2 risk, any traditional coronary artery disease (CAD) risk factor, any Risk Or Benefit IN Screening for CArdiovascular Disease (ROBINSCA) risk factor, and moderately (>3 mg/24 h) increased urine albumin excretion (UAE). Out of 6530 participants, 643 (9.8%) had CACS ≥300 and 1236 (18.9%) had CACS ≥100. For CACS ≥300 and CACS ≥100, miss rate was 32 and 41% for pre-screening by moderate (≥5%) SCORE2 risk and 81 and 87% for high (≥10%) SCORE2 risk, respectively. For CACS ≥300 and CACS ≥100, miss rate was 8 and 11% for pre-screening by at least one CAD risk factor, 24 and 25% for at least one ROBINSCA risk factor, and 67 and 67% for moderately increased UAE, respectively. Many individuals with high CACS in the general population are left unidentified when only performing CACS in case of at least moderate (≥5%) SCORE2, which closely resembles current clinical practice. Less stringent pre-screening by presence of at least one CAD risk factor to guide CACS identifies more individuals with high CACS and could improve CAD prevention.

Reflux nephropathy and scarring nephropathy: So close and yet so different

ObjectivesReflux nephropathy is a radiologic condition commonly used to express the existence of renal morphological lesions in patients who have or had vesicoureteral reflux (VUR). This morphological concept is used based on the image data collected, without conducting basic complementary renal function studies. The present study was designed to demonstrate that patients with active VUR present different functional renal alterations from those shown by patients with disappeared VUR. MethodsLongitudinal descriptive retrospective analysis including 89 children (46M, 43F) with VUR diagnosis through a standard voiding cystourethrogram (VCUG). The basic renal function tests collected were the maximum urinary osmolality (UOsm) and the urinary albumin/creatinine and NAG/creatinine ratios. The data collected corresponded to two moments, when VUR was diagnosed and when it had already disappeared. ResultsQuantitative differences were verified in the three functional parameters when comparing those corresponding to both moments of the study. In the qualitative analysis, in relation to the intensity of the VUR, differences were observed in UOsm at diagnosis and in the albumin/creatinine ratio once the VUR had cured. At this last moment, a significant increase in the albumin/creatinine ratio was observed in patients with loss of renal parenchyma in relation to those without residual morphological lesions. ConclusionsConcentrating ability defect is the most frequent finding in children with active reflux (true reflux nephropathy), whereas the most frequent functional disturbance found, once VUR has cured, is an increase in urinary albumin excretion, related to parenchymal damage. The term dysplastic-scarring nephropathy, could be more appropriate for patients with residual morphological lesions and impaired renal function, once VUR is cured.

TRPC6 Inactivation Reduces Albuminuria Induced by Protein Overload in Sprague Dawley Rats.

Canonical transient receptor potential-6 (TRPC6) channels have been implicated in familial and acquired forms of focal and segmental glomerulosclerosis (FSGS), and in renal fibrosis following ureteral obstruction in mice. TRPC6 channels also appear to play a role in driving glomerular disease in aging and in autoimmune glomerulonephritis. In the present study, we examine the role of TRPC6 in the proteinuric state caused by prolonged albumin overload (AO) in Sprague Dawley rats induced by daily injections of exogenous albumin. This was assessed in rats with a global and constitutive inactivation of TRPC6 channels (Trpc6del/del rats) and in wild-type littermates (Trpc6wt/wt rats). AO for 14 and 28 days caused increased urine albumin excretion that was significantly attenuated in Trpc6del/del rats compared to Trpc6wt/wt controls. AO overload did not induce significant glomerulosclerosis or azotemia in either genotype. AO induced mild tubulointerstitial disease characterized by fibrosis, hypercellularity and increased expression of markers of fibrosis and inflammation. Those changes were equally severe in Trpc6wt/wt and Trpc6del/del rats. Immunoblot analysis of renal cortex indicated that AO increased the abundances of TRPC3 and TRPC6, and caused a nearly complete loss of TRPC5 in Trpc6wt/wt rats. The increase in TRPC3 and the loss of TRPC5 occurred to the same extent in Trpc6del/del rats. These data also suggest that TRPC6 plays a role in the normal function of the glomerular filtration barrier. However, whether TRPC6 inactivation protects the tubulointerstitial compartments in Sprague Dawley rats depends on the disease model examined.

432-P: Single and Joint Impact of Type 2 Diabetes and of Coronary Artery Disease on Albuminuria

Albuminuria is a characteristic feature of diabetic nephropathy, and increased urine albumin excretion is associated with an increased risk of coronary artery disease (CAD) . However, type 2 diabetes (T2DM) and CAD frequently coincide, and the single and joint effects of T2DM and angiographically determined CAD with albuminuria are unclear. This issue therefore was addressed in the present study. We investigated 831 patients with angiographically proven CAD, of whom 261 had T2DM (CAD+/T2DM+) and 570 did not have diabetes (CAD+/T2DM-) and 263 controls without CAD, of whom 63 had T2DM (CAD-/T2DM+) and 200 did not have diabetes (CAD-/T2DM-) . The albumin / creatinine ratio (ACR) was 37±1in CAD-/T2DM- patients. Compared to this group it was higher in CAD-/T2DM+ patients (193±642; p<0,001) , but not in CAD+/T2DM- patients (52±184; p=0,421) , in whom it was significantly lower than in CAD-/T2DM+ patients (p<0.001) . In CAD+/T2DM+ patients the ACR (162±466) was higher than in CAD-/T2DM- (p<0,001) and in CAD+/T2DM- patients (p<0,001) , but did not differ significantly to that in CAD-/T2DM+ patients (p=0,225) . In multivariate analysis of covariance, T2DM but not CAD proved to be an independent predictor of ACR after adjustment for age, sex, body mass index, LDL-C, smoking, hypertension and the use of ACE inhibitors /AT2-antagonists and statins (F=22.06; p<0.0 and F=0.520; p=0.471, respectively) . We conclude that T2DM but not CAD is an independent determinant of albuminuria. Disclosure M.Maechler: None. L.Sprenger: None. A.Mader: None. B.Larcher: None. A.Vonbank: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None. C.H.Saely: None.

MO608: INV-202, A CB1 Receptor Blocker, Reduces Renal Injury in A Murine Model of Streptozotocin (STZ)-Induced Type-1 Diabetes

Abstract BACKGROUND AND AIMS Renal diseases remain a burden for Public Health and chronic kidney disease (CKD) affects several millions of individuals worldwide. Diabetic Nephropathy (DN) is the most frequent consequence of diabetes and is characterized by an increase in urinary albumin excretion and progressive loss of renal function associated with glomerular basement membrane thickening, mesangial expansion, nodular glomerular sclerosis and tubulointerstitial fibrosis. To date, there are few treatments that can prevent its progression. Indeed, current therapeutic approaches including RAAS blockers, SGLT2 inhibitors or both approaches combined do not fully abrogate DN progression. A growing body of experimental evidence suggests that modulation of the endocannabinoid system, and in particular its type 1 receptor (CB1R), may be a therapeutic tool in the management of CKD and more particularly DN. CB1R blockade represents a potential therapeutic modality in the fight against obesity, diabetes and their metabolic sequelae. In kidney, CB1R inhibition promotes a reduction in albuminuria, renal fibrosis and preserves renal function in both obesity-induced and diabetic nephropathy in mice mainly through a direct action of CB1R in podocytes and/or proximal tubules. INV-202 is a peripherally acting Cannabinoid receptor-1 (CB1r) inverse agonist that is under clinical development for the treatment of diseases associated with diabetes and metabolic syndrome. Here we report the effects of INV-202 on renal function and associated parameters in a preclinical model of diabetic nephropathy. METHOD Twelve weeks after the initiation of diabetes using streptozotocin, C57BL6/J mice (8 per treatment group) were randomized to receive a daily oral dose of INV-202, 0.3 mg/kg and 3 mg/kg or vehicle for 4 weeks. Five mice not treated with STZ were used as a nondiabetic control. At the end of treatment, animals were sacrificed. Urinary albumin-to-creatinine ratio (ACR), renal matrix remodelling, glomerular filtration and interstitial fibrosis were assessed in addition to glucose levels, body weight and organ weights. RESULTS After 28 days of treatment, there was no significant effect on hyperglycemia or body weight with either dose of INV-202. Renal and hepatic weights were reduced while heart weight was unaffected. This remained true when normalizing for tibial length. Compared with vehicle-treated diabetic mice, INV-202-challenged mice displayed a marked decrease in many clinical features of DN such as albuminuria, albumin-to-creatinine ratio, urinary urea, loss of glomerular filtration rate and renal hypertrophy. Interestingly, we also found an improvement in both podocyte and proximal tubular cells morphology and health markers that were likely responsible for the improvement previously mentioned. In addition, INV-202 led to a downregulation of the angiotensin II receptor expression as well as a reduced urinary excretion, suggesting an inhibitory effect of this compound on the angiotensin II-mediated renal dysfunction in the context of DN. Furthermore, INV-202 also led to a drastic reduction in renal inflammation and oxidative stress markers that are known to be highly involved in the pathogenesis of DN. Finally, despite the limitation of our model in regard to interstitial fibrosis development, we could observe a marked anti-fibrotic effect of INV-202. CONCLUSION Treatment with INV-202 reduced the progression of nephropathy in STZ-induced diabetic mice. Improvements in kidney size, function and histology, with corresponding gene expression, were noted with both doses of INV-202. Further work to explore the effect of INV-202 in humans is warranted.

Elevated Serum Levels of Carbohydrate Antigen 72-4 in Diabetic Kidney Disease.

The aim of this study was to determine whether carbohydrate antigen 72-4 (CA72-4) is elevated in diabetic kidney disease (DKD), and examine the association between urinary albumin-to-creatinine ratio (UACR) and CA72-4 in patients with type 2 diabetes mellitus (T2DM). Non-dialysis patients with T2DM (n=296) and 90 healthy controls were recruited in this study. CA72-4 level was measured by electrochemiluminescence immunoassay. DKD was defined as UACR≥ 30 mg/g in the absence of a urinary infection or other renal diseases. We found that patients with DKD had significantly higher serum CA72-4 levels compared to those with normoalbuminuria and healthy controls. Positive rates of CA72-4 increased gradually and markedly from normoalbuminuria to microalbuminuria and to macroalbuminuria in diabetic patients (7.5, 11.2, and 17.4%, respectively; P for trend< 0.05). CA72-4 also showed a positive correlation with UACR (r=0.288, P< 0.01). Logistic regression analysis revealed the association of increased UACR with an increased odds ratio of elevation of CA72-4 levels (P for trend< 0.05) after multivariable adjustment. In conclusion, serum levels of CA72-4 increase abnormally with the increase in urinary albumin excretion, which affects the specificity of diagnosis of malignancies. An appropriate interpretation of CA72-4 is essential to prevent unnecessary and even hazardous diagnostic procedures in patients with T2DM.

Relation between pre-procedural increase in urinary albumin excretion and changes in estimated glomerular filtration rate after coronary angiography in diabetic patients

Abstract Background Contrast-induced nephropathy (CIN), is an acute impairment in renal function, and typically occurs within 3 days following the exposure to a contrast medium (CM). It is associated with increased hospital stay and increased morbidity and mortality, Adult patients with diabetes have a higher risk than the general population for developing contrast induced nephropathy. Methods The current study includes 40 patients with diabetes mellitus, scheduled for coronary angiography with estimated GFR &amp;gt;60 ml/min .the patients were divided according to their pre-procedural urinary albumin creatinine ratio (ACR) results into 3 groups: Group 1 included patients with pre-procedure urinary albumin creatinine ratio &amp;lt; 30mg/g, Group 2 included patients with pre- procedure albumin creatinine ratio 30- 300 mg/g and Group 3 included patients with pre-procedure albumin creatinine ratio &amp;gt;300 mg/g . Estimated GFR (glomerular filtration rate) calculated using MDRD and serum creatinine were measured at day 2 and 3 (Day +2 +3) after coronary angiography. Results There was no statistically significant difference in the age and gender distribution, the use of ACEIs (angiotension converting enzyme inhibitors) or diuretics between the cases who developed and who didn’t develop CIN. The mean ACR in the group with no contrast induced nephropathy was 225.38 ± 209.53 which was statistically significantly lower when compared with the cases with contrast induced nephropathy (420.43± 348.52) (p = 0.033). The mean HbA1c in no contrast induced nephropathy group was 7.11 ± 0.64 and in contrast induced nephropathy group it was 9.09 ± 0.66 which is significantly higher (P &amp;gt; 0.001).With univariate regression analysis, ACR, HbA1c and number of vessels affected were shown to be risk factors for occurrence of CIN after use of contrast, but with multivariate analysis, both ACR and HbA1c were shown to be risk factors for CIN. Conclusion An increase in albumin creatinine ratio in itself can be a risk factor for development of contrast induced nephropathy in diabetic patients.

Nefropatía de reflujo y nefropatía cicatricial. Dos entidades tan cercanas pero funcionalmente tan distintas

ObjectivesReflux nephropathy is a radiologic condition commonly used to express the existence of renal morphological lesions in patients who have or had vesicoureteral reflux (VUR). This morphological concept is used based on the image data collected, without conducting basic complementary renal function studies. The present study was designed to demonstrate that patients with active VUR present different functional renal alterations from those shown by patients with disappeared VUR. Patients and methodsLongitudinal descriptive retrospective analysis including 89 children (46M, 43F) with VUR diagnosis through a standard voiding cystourethrogram (VCUG). The basic renal function tests collected were the maximum urinary osmolality (UOsm) and the urinary albumin/creatinine and NAG/creatinine ratios. The data collected corresponded to two moments, when VUR was diagnosed and when it had already disappeared. ResultsQuantitative differences were verified in the three functional parameters when comparing those corresponding to both moments of the study. In the qualitative analysis, in relation to the intensity of the VUR, differences were observed in UOsm at diagnosis and in the albumin/creatinine ratio once the VUR had cured. At this last moment, a significant increase in the albumin/creatinine ratio was observed in patients with loss of renal parenchyma in relation to those without residual morphological lesions. ConclusionsConcentrating ability defect is the most frequent finding in children with active reflux (true reflux nephropathy), whereas the most frequent functional disturbance found, once VUR has cured, is an increase in urinary albumin excretion, related to parenchymal damage. The term dysplastic-scarring nephropathy, could be more appropriate for patients with residual morphological lesions and impaired renal function, once VUR is cured.

Disorders of Kidney Function in Chronic Heart Failure

The formation of cardiorenal syndrome (CRS) in patients with chronic heart failure (CHF) is a naturalmanifestation of a functionally interrelated process at the organ level. Moreover, impaired renal function is acommon and independent factor in the progression of the disease, a high incidence of cardiovascular eventsand death in a population of patients with asymptomatic and / or clinically manifested CHF, which is dueto the pathogenetic features of the formation of cattle in patients with CHF of ischemic genesis. The articleprovides an overview of studies on the pathogenesis of kidney damage in CHF, the role of various markersin the early diagnosis of cattle. A decrease in glomerular filtration rate (GFR) and an increase in urinaryalbumin excretion are currently considered as “renal” markers of a poor prognosis within the cardiorenalcontinuum. In this regard, for stratification of patients by stages of chronic kidney disease (CKD) and,consequently, for assessing the risks of increased overall and cardiovascular mortality in patients with CHF,the accuracy of calculating GFR, as the main indicator reflecting the severity of formed kidney damage, is ofgreat importance. Microalbuminuria is one of the early signs of CKD, the main cause of which is glomerularcapillary endothelial dysfunction that occurs in most patients with CHF. The presence and persistence ofsubclinical renal dysfunction during treatment, even with the achievement of risk factors (RF) control andregression of organ lesions, can adversely affect the patient’s prognosis. Assessment of the functional stateof the kidneys is important for early diagnosis, selection of effective preventive measures and treatment. Thetherapeutic strategy in patients with CHF in combination with CKD should be based on the nephroprotectiveeffects of drugs.

VX-765 ameliorates inflammation and extracellular matrix accumulation by inhibiting the NOX1/ROS/NF-κB pathway in diabetic nephropathy.

This study explores the potential role of a highly selective caspase-1 inhibitor, VX-765, on extracellular matrix (ECM) accumulation and inflammation in diabetic nephropathy (DN) and the underlying mechanisms. DN rats, induced via high-fat diet/streptozotocin, were used to assess the effects of VX-765. Parallel experiments were carried out on rat mesangial cell line HBZY-1 exposed to high glucose (HG) to reveal the molecular mechanism of VX-765 in preventing DN. Survival analysis, biochemical parameters and renal oxidative stress of rats were observed, and Western blotting and immunofluorescence were evaluated. In vitro, Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX)1 silencing by RNA interference and quantitative real-time PCR (qPCR) assays were conducted in HBZY-1 cells exposed to HG levels. In vivo, VX-765 significantly reduced the increase in urine albumin excretion and ECM accumulation. The phosphorylation of nuclear factor kappa-B (NF-κB) and the expression of pro-inflammatory cytokines IL-1β, IL-6 and tumor necrosis factor (TNF)-α were significantly down-regulated. Furthermore, the generation of reactive oxygen species (ROS), phosphorylation of NF-κB and the expression of the NOX1 gene or protein were significantly decreased in HBZY-1 with VX-765 (5 μM) treatment in vitro. Our results demonstrated that VX-765 exerts favourable effects on DN via the simultaneous alleviation of systemic metabolic syndrome and down-regulating the renal NOX1/ROS/NF-κB pathway, suggesting that it has therapeutic potential for DN.

Vaccination Against Receptor for Advanced Glycation End Products Attenuates the Progression of Diabetic Kidney Disease.

Effective treatment of diabetic kidney disease (DKD) remains a large unmet medical need. Within the disease's complicated pathogenic mechanism, activation of the advanced glycation end products (AGEs)-receptor for AGE (RAGE) axis plays a pivotal role in the development and progression of DKD. To provide a new therapeutic strategy against DKD progression, we developed a vaccine against RAGE. Three rounds of immunization of mice with the RAGE vaccine successfully induced antigen-specific serum IgG antibody titers and elevated antibody titers were sustained for at least 38 weeks. In addition, RAGE vaccination significantly attenuated the increase in urinary albumin excretion in streptozotocin-induced diabetic mice (type 1 diabetes model) and leptin-receptor-deficient db/db mice (type 2 diabetes model). In microscopic analyses, RAGE vaccination suppressed glomerular hypertrophy and mesangial expansion in both diabetic models and significantly reduced glomerular basement membrane thickness in streptozotocin-induced diabetic mice. Results of an in vitro study indicated that the serum IgG antibody elicited by RAGE vaccination suppressed the expression of AGE-induced vascular cell adhesion molecule 1 and intracellular adhesion molecule 1 in endothelial cells. Thus, our newly developed RAGE vaccine attenuated the progression of DKD in mice and is a promising potential therapeutic strategy for patients with DKD.