Development Of Nephropathy In Patients Research Articles

Comparing two risk scores for predictive ability of contrast-induced nephropathy development in patients presenting with chronic coronary syndrome

Comparing two risk scores for predictive ability of contrast-induced nephropathy development in patients presenting with chronic coronary syndrome

Serum peroxiredoxin-4, a biomarker of oxidative stress, is associated with the development of nephropathy in patients with type 2 diabetes (Zodiac-65)

Oxidative stress is implicated in the development and progression of type 2 diabetes (T2D). Peroxiredoxin-4 is an antioxidant protein, which may serve as biomarker of oxidative stress, and has previously been associated with new-onset T2D. In this study, we investigated associations between circulating peroxiredoxin-4 and the risk of developing new-onset microvascular complications in T2D patients. Serum peroxiredoxin-4 was measured in 536 patients with T2D with (n = 257) and without (n = 279) baseline microvascular complications who participated in a primary-care based cohort study (Zwolle Outpatient Diabetes project Integrating Available Care [ZODIAC] study). Over a median follow-up of 3.4 years, 38 (13.6%) developed nephropathy, defined as albuminuria in two consecutive urine samples. In multivariable Cox proportional hazards regression analyses, peroxiredoxin-4 was associated with new-onset nephropathy (hazard ratio [HR] per doubling 1.78 [95% CI: 1.27–2.49], P < 0.001) after adjustment for potential confounding factors, including age, sex, disease duration, HbA1c levels, macrovascular complications, systolic blood pressure, and even high-sensitive C-reactive protein. There was no interaction of peroxiredoxin-4 with hs-CRP impacting on new-onset nephropathy. No significant associations were found with new-onset retinopathy or neuropathy. In conclusion, circulating peroxiredoxin-4 associates positively with an increased risk of developing nephropathy in T2D independent and irrespective of low-grade inflammation.

The Role of Pan-Immune-Inflammation Value in Predicting Contrast-Induced Nephropathy Development in Patients Undergoing Percutaneous Coronary Intervention Due to NSTEMI.

Contrast-induced nephropathy (CIN), which can develop after procedures involving contrast agents, is a significant cause of patient morbidity and mortality. This study aims to investigate the role of pre-procedural pan-immune-inflammation value (PIV) in predicting CIN development in patients undergoing percutaneous coronary intervention (PCI) due to non-ST segment elevation myocardial infarction (NSTEMI). A total of 1006 NSTEMI patients were included in the study. CIN was defined as an increase of at least 0.5mg/dl or 25% in serum baseline creatinine level 72h after the procedure. Patients were divided into two groups: those with and without CIN. NSTEMI patients who developed CIN, glucose level (P = .01), platelet count (P < .01), monocyte count (P < .001), neutrophil-to-lymphocyte ratio (NLR) (P < .001), systemic immune inflammation index (SII) score (P < .001), and PIV (P < .001) were higher compared with those without CIN. In the multivariate analysis of all these parameters, the Odds ratios of PIV and SII were similar and slightly lower than NLR. Receiver operating characteristic curve analysis (ROC) showed a PIV cut-off value of 448.43 with a sensitivity of 83.1% and a specificity of 72.8% in patients with CIN. Our study demonstrated an independent relationship between PIV at admission and CIN development in NSTEMI patients.

The pathogenetic significance of endothelial dysfunction in the development of diabetic nephropathy in patients with type 2 diabetes mellitus

Objective: to determine the level of circulating markers of endothelial dysfunction (endothelin‑1, von Willebrand factor (vfV), endothelial NO-synthase (e‑NOS)) in the blood serum of patients with type 2 diabetes mellitus (DM), as well as to assess the pathogenetic significance endothelial dysfunction in the development of diabetic nephropathy.Materials and methods: the study included 93 patients with type 2 DM, including 28 men (30.1%) and 65 women (69.9%), aged 30 to 79 years, the average age of patients was 59.7±8.4 of the year. The main group included patients with both newly diagnosed type 2 DM and a long-term diabetic history. The duration of the disease averaged 9.5±7.5 years. The majority of patients with DM type 2 (92.5%) at the time of inclusion in the study had various variants of microvascular complications of diabetes, only a small number of patientsin this group (7.5%) had no signs of diabetic angiopathy. Signs of various stages of diabetic nephropathy were observed in 60 patients (69.2%). The comparison group consisted of 30 patients with essential arterial hypertension, including 12 men (40%) and 18 women (60%), aged 34 to 70 years, on average 56.1 ± 8.1 years. The control group consisted of 32 apparently healthy individuals. In all patients, along with routine methods of clinical, laboratory and instrumental examination, the level of circulating markers of endothelial dysfunction (endothelin‑1, von Willebrand factor (vWF), endothelial NO-synthase (e‑NOS)) in blood serum was measured using enzyme-linked immunosorbent assay (ELISA).Results: in patients with DM type 2 and diabetic nephropathy, a statistically significant increase in the concentration of circulating markers of endothelial dysfunction was revealed in comparison with hypertensive patients and healthy individuals. An increase in the level of endothelin‑1 relative to the borderline reference value was found in 73 (78.5±4.1%), vfV in 63 (67.7±4.8%) and e‑NOS in 65 (69.9±4.7%) of patients with DM type 2. In the groups of participants with hypertension and healthy individuals, endothelial imbalance was noted by us significantly less often than in patients with DM type 2, the levels of endothelin‑1 and vfV in people with hypertension were increased in more cases than in healthy individuals. It was noted that the levels of circulating markers of endothelial dysfunction increase with an increase in the duration of DM type 2, and also significantly increase under conditions of carbohydrate decompensation.Conclusion: the results obtained confirm the pathogenetic role of endothelial dysfunction in the development of diabetic nephropathy in patients with type 2 diabetes, increasing endothelial imbalance in persons with a long diabetic history and lack of compensation for carbohydrate metabolism.

The effect of whole blood viscosity on contrast-induced nephropathy development in patients undergoing percutaneous coronary intervention

ABSTRACT Objective In our study, we aimed to investigate how whole blood viscosity (WBV) affects the development of contrast-induced nephropathy (CIN) in patients undergoing percutaneous coronary intervention (PCI). Methods In our study, 500 patients who applied to the cardiology clinic and underwent PCI for elective procedure, ST segment elevation myocardial infarction (STEMI), and non-STEMI were prospectively included. Before the procedure, we calculated WBV using the formula [(0.12× hematocrit) + (0.17×(total protein – 2.07)]. We defined CIN as the absolute (≥0.5 mg/dl) or relative increase (≥25%) in serum creatinine 48–72 h after exposure to a contrast agent compared with baseline serum creatinine values. Results CIN was developed in 69 (13.6%) of the 500 patients in the study. PCI was performed in 206 patients (41.2%) electively, 175 (35%) due to non-STEMI, and 119 (23%) due to STEMI. CIN was observed in 20.2% of the STEMI group, 13.7% of the non-STEMI group, and 10.2% of the elective PCI group. Multivariate logistic regression analysis results show that the independent predictors of CIN are low ejection fraction [OR:0.95 (95% CI:0.92–0.97); p < 0.001], low glomerular filtration rate [OR:0.96 (95% CI:0.95–0.98); p < 0.001], and increased amount of contrast agent [OR:1.008 (95% CI:1.004–1.01); p < 0.001]. When all patients were examined, no significant relationship was found between WBV and CIN. However, in the subgroup evaluation, it was concluded that low WBV was an independent predictor in elective PCI patients [OR:0.60 (95% CI:0.36–0.99); p = 0.04] for CIN. Conclusion We found that low WBV was an independent predictor of CIN in patients undergoing elective PCI(NCT04703049).

Протизапальний ефект нефропротекторної терапії у хворих на діабетичну нефропатію

Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of chronic kidney disease worldwide. The majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy. The progression of fibrotic processes in the diabetic kidneys occurs with the participation of universal mediators of inflammation. Given the clinical and social significance of diabetic kidney damage, the determination of interleukin-1β and interleukin-6 in blood serum may expand the understanding of this problem, as well as help in the development of individualized therapeutic approaches. The purpose of the study is to investigate interleukin-1β and interleukin-6 levels in the serum of patients with type 2 diabetes mellitus, depending on kidney functional state in the dynamics of therapy and with additional prescription of dapagliflozin. Materials and methods. 72 patients with type 2 diabetes were examined. The control group consisted of 20 healthy individuals. The patients were divided into the following groups: group I – type 2 diabetic patients with normal glomerular filtration rate and without albuminuria (n = 25); group II – patients with type 2 diabetes with normal glomerular filtration rate and albuminuria (n = 23); group III – patients with type 2 diabetes with decreased glomerular filtration rate and albuminuria (n = 24). The complex pathogenetic therapy of patients of group 1 included renin-angiotensin-aldosterone system blockers, metformin and hypolipidemic agents. Patients of group 2 were additionally prescribed dapagliflozin. The control was carried out after 6 months. Results and discussion. According to the results of the study, the development of diabetic nephropathy in patients with type 2 diabetes is accompanied by a significant increase in the level of interleukin-1β and interleukin-6 in the blood plasma compared with the control and in patients with diabetes without signs of nephropathy. Nephroprotective therapy contributed to a significant decrease of interleukin-1β and interleukin-6 levels in the blood serum in all groups of patients. The highest response to treatment was observed in patients with diabetic nephropathy and albuminuria. Most significant decrease of albuminuria, normalization of blood pressure and lipid spectrum improvement were observed in patients with the initial stages of the disease. Additional using of dapagliflozin leads to a more significant decrease in the content of proinflammatory cytokines in the blood serum of patients with type 2 diabetes mellitus with diabetic nephropathy. Conclusion. The results of the study indicate the advisability of using interleukin-1β and interleukin-6 as a diagnostic marker of cardiac disorders, assessment of prognosis, and improvement of the cardionephroprotective strategy in diabetic patients. The therapeutic potential of dapagliflozin in the treatment of diabetic nephropathy and the prevention of cardiovascular events in patients with diabetes is of great scientific interest and requires further research

Relationship between biochemical parameters and glomerular filtration rate by Cockcroft-Gault, CKD EPI and cystatin C in patients with type 1 diabetes

Annotation. The aim of research is to study correlations of biochemical parameters with glomerular filtration rate according to Cockcroft-Gault, CKD EPI and cystatin C in patients with type 1 diabetes (T1D). 78 men and 62 women aged 22-26 years with T1D were examined. The control group consisted of 8 almost healthy men and 13 almost healthy women of the same age. The level of microalbuminuria and cystatin C was determined in all patients by enzyme-linked immunosorbent assay. Biochemical evaluation of fasting blood glucose, glucose 2 h after exercise, mean value of glucose, creatinine, GFR according to Cockcroft-Gault, CKD EPI and GFR according to cystatin C. Correlation analysis between the series of indicators was calculated using Spearman statistics in the license package “Statistica 5.5”. In patients with T1D, there is no significant correlation in normoalbuminuria between urinary albumin levels and GFR by Cockcroft-Gault (in women), CKD EPI and cystatin C (in all study groups). No significant correlations were found between urinary albumin levels and GFR by Cockcroft-Gault, CKD EPI and cystatin C in the proteinuria group. The correlation analysis revealed in the general group and in women with proteinuria an association between the average value of blood glucose and low GFR levels by Cockcroft-Gault, CKD EPI (negative medium strength correlation r = from -0.31 to -0.46) and elevated creatinine (positive strong correlation r=0.62 and r=0.91), indicating an unfavorable role of hyperglycemia in the development of nephropathy in patients with T1D. Higher correlations of cystatin C with GFR by cystatin C (r= -1.0) than by creatinine with GFR by Cockcroft-Gault (r = from - 0.63 to 0.99) and by CKD EPI (r = from -0.73 to -0.99) were demonstrated. The strength of the correlations increases from GFR by Cockcroft-Gault to GFR by cystatin C. Correlations between creatinine and GFR by Cockcroft-Gault and CKD EPI were characterized by sex differences (greater in women) and an increase in their strength synchronously with an increase in urinary microalbumin. At the same time, there is a consistently high identical value (r= -1.0) of correlations of the level of cystatin C with GFR on cystatin C in all comparison groups. Neither the sex factor nor the degree of albuminuria affected the change in their strength. Only men with microalbuminuria had moderate feedback between creatinine and cystatin C (r= -0.46). In all groups of women, in the general group and in men with normoalbuminuria and proteinuria, the correlations are close to zero, which may indicate the absence of a linear relationship between these indicators. When dividing the sample according to the level of cystatin C between the level of creatinine and the level of cystatin C, the following were found: medium feedback (r= -0.37) in the general group with normoalbuminuria and cystatin C&gt;0.9; moderate feedback (r= -0.37) in the general group and in men with proteinuria and cystatin C&lt;0.9 strong feedback (r= -0.90 and r= -0.88). Thus, in the course of correlation analysis it was found: microalbuminuria is not an independent marker of diabetic nephropathy (DN), starting from preclinical and ending with a clinically manifested stage of this complication; for timely and adequate diagnosis of DN it is necessary to measure the level of albumin, creatinine and cystatin C, which are independent markers of renal dysfunction; cystatin C gives a more accurate approximation to the actual values of GFR than creatinine; cystatin C is more sensitive in the early stages, and creatinine is a marker of later stages of DN development; hyperglycemia is the main initiating metabolic factor in the development and progression of DN.

Value of the NOS3 gene Т786С polymorphism for early diagnosis of kidney damage in patients with essential arterial hypertension

Background . Essential arterial hypertension (AH) is a global problem of the healthcare system. Kidney damage could aggravate the course of the disease, and genetic factors play an important role in the development of hypertensive nephropathy: approximately 50% of patients are carriers of genetic polymorphisms that predispose to the occurrence of hypertensive nephropathy. Objective . Studying the relationship between genetical disorders and features of intrarenal blood flow among patients with AH. Design and methods . 114 patients (49 men and 65 women) aged 35 to 58 years with stage I–II hypertension and 1–3 degrees of arterial hypertension were examined. Duplex scanning of renal arteries was performed using a Vivid-7 Dimension ultrasound scanner, genotyping of the Т786С polymorphism of the NOS3 gene using a real-time polymerase chain reaction; the calculated glomerular filtration rate (using the CKD-EPI formula) was analyzed. The examined patients were divided into 2 groups: the 1st group included individuals with glomerular filtration rate (GFR) greater than or equal to 60 ml/min/1,73 m 2 (32 men and 40 women), the 2nd group — with GFR 45–59 ml/min/1,73 m 2 (17 men and 25 women). Results . In patients with hypertension with GFR 45–59 ml/min/1,73 m2 , the predominance of the CC genotype and allele- C was found, and among patients with GFR greater than or equal to 60 ml/min/1,73 m 2 , the TC genotype and allele- Т prevailed. In the second group, higher values of peripheral resistance indices were observed in comparison with the first group. It was also found that individuals with TC and CC genotypes had higher indices of peripheral resistance of intrarenal blood flow compared to patients with TT genotype. Conclusion . The presence in the genotype of patients with arterial hypertension of the 786C allele and the CC genotype of the NOS3 gene can predispose to early kidney damage, and an increase in the indices of peripheral resistance of blood flow in the interlobar renal arteries can serve as a criterion for the development of hypertensive nephropathy in patients with arterial hypertension.

The place of hydration using intravenous fluid in patients at risk of developing contrast-associated nephropathy.

There has been a significant rise in the incidence of contrast-associated nephropathy caused by administration of contrast media during cardiac interventions. This is one of the major complications of percutaneous coronary interventions, which may proceed to acute renal failure. Risk factors, including pre-existing renal dysfunction, older age and use of high osmolar contrast media, predispose patients to the development of contrast-associated nephropathy. Different risk-reduction strategies have been used to prevent contrast-associated nephropathy, including use of low osmolar contrast media, N-acetylcysteine, alkalisation of tubular fluid with intravenous sodium bicarbonate, and oral and intravenous hydration with isotonic solution. Hydration using intravenous saline is one of the main treatments used to prevent the development of nephropathy in patients receiving contrast media during cardiac interventions. Prehydration, before administering contrast media, seems to be crucial. The results of studies of the relative efficacy of sodium bicarbonate and/or N-acetylcysteine in reducing the development of contrast-associated nephropathy are not consistent and any beneficial effects may depend on the pre-existing state of the kidney. This review discusses hydration of patients who are at risk of developing contrast-associated nephropathy using intravenous fluid.

A single-centered study of factors affecting colistin related nephropathy

Background: Colistin is an old antibiotic and used for resistant gram-negative infections. Nephrotoxicity is the most common side effect and restricts clinicians to use it. Many risk factors suggested for the development of nephropathy. It could be better to know risks to prevent nephropathy development. Objectives: In this study, we aimed to evaluate factors that affecting the development of nephropathy in patients who were hospitalized in hematology, oncology, palliative care, and intensive care units. Methods: 125 patients aged 20-93 years old were enrolled in this retrospective study. Data were obtained from the pharmacy of the university hospital and information management system of the hospital. Results: Among 125 patients included in the study, 15 developed KDIGO stage 1 nephropathy, 21 stages two nephropathies, and four stages three nephropathies, respectively. Age, albumin level, and bilirubin levels were shown to be related to nephropathy. We found the cut off value of albumin 3.05 mg/dl for development of nephropathy (sensitivity 70%; specificity 66%; CI=95%, p=0.003) and mortality (sensitivity 69%; specificity 61%; CI=95%, p&lt;0.001). We revealed that age and bilirubin levels independently affected the development of nephropathy in linear regression analysis (r2 =0.131, p=0.032; p=0.015). Also, mortality was denoted to be related to albumin and bilirubin levels independently in linear regression analysis (r2 =0.161, p=0.03; p=0.004). Conclusions: Older age, hypoalbuminemia, and hyperbilirubinemia were risk factors for colistin related nephropathy and mortality. Further studies will be better to elucidate relationships more clearly.   

Functional methylome analysis of human diabetic kidney disease.

In patients with diabetes mellitus, poor metabolic control has a long-lasting impact on kidney disease development. Epigenetic changes, including cytosine methylation, have been proposed as potential mediators of the long-lasting effect of adverse metabolic events. Our understanding of the presence and contribution of methylation changes to disease development is limited because of the lack of comprehensive base-resolution methylome information of human kidney tissue samples and site-specific methylation editing. Base resolution, whole-genome bisulfite sequencing methylome maps of human diabetic kidney disease (DKD) tubule samples, and associated gene expression measured by RNA sequencing highlighted widespread methylation changes in DKD. Pathway analysis highlighted coordinated (methylation and gene expression) changes in immune signaling, including tumor necrosis factor alpha (TNF). Changes in TNF methylation correlated with kidney function decline. dCas9-Tet1-based lowering of the cytosine methylation level of the TNF differentially methylated region resulted in an increase in the TNF transcript level, indicating that methylation of this locus plays an important role in controlling TNF expression. Increasing the TNF level in diabetic mice increased disease severity, such as albuminuria. In summary, our results indicate widespread methylation differences in DKD kidneys and highlights epigenetic changes in the TNF locus and its contribution to the development of nephropathy in patients with diabetes mellitus.

LncRNA PRINS is involved in the development of nephropathy in patients with diabetes via interaction with Smad7.

Long non-coding RNA psoriasis-susceptibilityrelated RNA gene induced by stress (PRINS) is known to be involved in kidney ischemia reperfusion injury. The aim of the current study was to investigate the potential role of PRINS in diabetic nephropathy. The relative mRNA expression level of PRINS and SMAD family member 7 (Smad7) was examined in patients with diabetes, including patients without obvious complications (n=43), patients with diabetic nephropathy (n=33), diabetic retinopathy (n=37), diabetic cardiomyopathy (n=29), diabetic lung disease (n=38) and healthy controls (n=48). Correlation analysis between the expression level of PRINS and Smad7 was analyzed by Pearson's correlation analysis. In addition, overexpression of PRINS was confirmed in mouse podocyte cells and cell viability and Smad7 protein expression was detected by MTT assay and western blot analysis, respectively. The expression levels of PRINS and Smad7 were significantly increased in patients with diabetes compared with healthy controls. In addition, the expression levels of PRINS and Smad7 were significantly increased in patients with diabetic nephropathy compared with other diabetic complications. The expression level of PRINS in mouse podocyte cells was upregulated following treatment with high glucose. A significant positive correlation between the expression level of PRINS and Smad7 was observed in patients with diabetic nephropathy. However, there was no correlation was observed in other patient groups compared with healthy controls. Overexpression of PRINS decreased the viability of mouse podocyte cells and enhanced Smad7 protein expression. Taken together, these results suggest that PRINS may be involved in the development of nephropathy in patients with diabetes.

Comparison of zwolle, cadillac and syntax-2 risk scores in predicting contrast nephropathy development in patients with ST elevation

Aim: It is known that early prediction of the patients who may develop contrast-induced is nephropathy (CIN) and initiate prophylactic treatment to reduce the risk of morbidity-mortality, hospitalization and prolonged length of stay. In our study, we aimed to compare the Zwolle, Cadillac and Syntax 2 (SS-2) risk scores that are currently used in the management of and predict mortality in patients with ST elevation myocardial infarction (STEMI) in terms of predicting CIN development.Material and Methods: We enrolled 1622 patients who were diagnosed as STEMI and underwent primary coronary angiography between July 2014 and December 2018. 1381 patients were taken to the final analysis and two groups; CIN - (n=1295) and CIN + (n=86) were formed. Risk scores were compared in terms of CIN prediction.Results: The mean age of the patients was 62±8 years and 72% of them were males. SS-2, Zwolle and Cadillac scores were significantly higher in CIN+ group (all p values 0.001). A comparative ROC curve analysis was performed for the estimation and clinical use of CIN. In the ROC curve analysis, the cut-off value for SS-2 was 16.7 (AUC:0.82) with a sensitivity of 80.1% and a specificity of 58%. The cut-off value for Cadillac was 1.5 (AUC:0.80), 78% sensitivity and 58% specificity. For Zwolle, the cut-off value was 2.5 (AUC:0.75) and the sensitivity was 73% and the specificity was 69%.Conclusions: CIN, which develops after coronary angiography in STEMI patients, causes an increase in morbidity and mortality. The risk scores used in STEMI patients, in particular SS-2, may be more useful in predicting the development of CIN than in the Zwolle and Cadillac scores.Keywords: Zwolle; Cadillac; Syntax 2 score; contrast induced nephropathy.

Effect of Atrial Fibrillation on Contrast-Induced Nephropathy Development in Patients With Non-ST-Segment Elevation Myocardial Infarction.

We investigated the relationship between atrial fibrillation (AF) and contrast-induced nephropathy (CIN) in patients with non-ST-segment elevation myocardial infarction (NSTEMI); 1045 consecutive patients undergoing percutaneous coronary interventions were enrolled. Risk factors for CIN were investigated. Baseline characteristics, except oral anticoagulant use, were similar between patients with and without AF. Patients with CIN show higher presence of diabetes mellitus (DM), coronary artery bypass graft surgery history, Mehran score, baseline creatinine levels, baseline glomerular filtration rate (GFR), peak troponin levels, left ventricular ejection fraction (LVEF), and presence of AF ( P < .05). In multivariate logistic regression analyses, the presence of DM (odds ratio [OR], 2.333; 95% confidence interval [CI], 1.222-4.457; P = .010), Mehran score (OR, 1.269; 95% CI, 1.152-1.398; P < .001), baseline GFR (OR, 0,954; 95% CI, 0.944-0.964 P < .001), left anterior descending artery originated infarction (OR, 1.594; 95% CI, 1.061-2.398; P = .025), LVEF value (OR, 0.956; 95% CI, 0.926-0.986; P = .005), and the presence of AF (OR, 3.830; 95% CI, 1.239-11.839; P = .020) were independent predictors of CIN. Atrial fibrillation can be related to CIN development in patients with NSTEMI.

Incidence and Risk Factors Involved in the Development of Nephropathy in Patients with Type 1 Diabetes Mellitus: Follow Up Since Onset.

Estimation of the incidence of nephropathy as well as potential risk factors involved in its onset in a cohort of patients with type 1 diabetes who were followed from diagnosis. We studied 716 patients, who were followed for a mean (standard deviation [SD]) of 10.1 (SD: 5.3) years. We analyzed the influence of demographic characteristics and levels of glycated hemoglobin (A1C), lipids and blood pressure during the course of the disease by univariate and multivariate survival methods. The cumulative incidence of nephropathy was 2.6%, 6.3% and 11.9% at 5, 10 and 15 years of evolution, respectively. The factors associated with increased risk for nephropathy were systolic blood pressure and A1C levels. An increment of 10 mm Hg in systolic blood pressure increases the risk by 36%, and an increment of 1% in A1C levels raises the risk by 13% at 5 years since onset and 68% at 10 years, and it doubles the risk at 15 years. Women have higher risk than men (hazard ratio 1.79; p=0.024). Our study suggests that female gender and high levels of A1C and systolic blood pressure throughout the course of the disease are the main factors associated with an increased risk for development of nephropathy in patients with type 1 diabetes mellitus.

Effects of various stages of nephropathy on wound healing in patients with diabetes: an observational cohort study encompassing 731 diabetics.

In diabetics genetic predisposition, poor glycemic control and arterial hypertension contribute to nephropathy development in patients affected by diabetes mellitus. We set up the hypothesis that diabetic nephropathy and incisional hernia formation may have in common alterations of collagen composition and tested whether the occurrence of diabetic nephropathy coincides with wound healing disturbance (incisional herniation) or connective tissue diseases (inguinal herniation, umbilical herniation, aortic aneurysm, varicose veins, disc herniation). A questionnaire on surgical procedures, wound healing and connective tissue disorders was performed with 731 diabetics. Furthermore, test results for kidney function and damage (creatinine clearance, proteinuria) and blood sugar control (HbA1c) were recorded. Correlations between aforementioned connective tissue diseases and "advanced" diabetic nephropathy were calculated. "Advanced" diabetic nephropathy was assumed in patients with macroproteinuria, CKD stage 5 and/or end-stage renal disease. All diabetics with CKD stages 1 and 2 without proteinuria were included in the "control" group. A subgroup analysis on incisional hernia formation coinciding with diabetic nephropathy was performed in patients with previously performed abdominal surgery. In patients with advanced nephropathy, some diseases with connective tissue alterations, such as inguinal herniation, aortic aneurysms and varicose veins, did not occur more frequently than in patients without nephropathy. In diabetics with nephropathy, umbilical herniation (3 vs. 8.2 %, p = 0.04) and disc herniation rates (5.7 vs. 16.1 %, p = 0.002) were significantly lower. Subgroup analysis of patients with previously performed abdominal surgery (n = 381) revealed significantly higher incisional herniation rates when "advanced" diabetic nephropathy was present (16 % compared to 5.7 % without nephropathy, p = 0.016). Our findings support the hypothesis that incisional hernia formation and diabetic nephropathy are positively correlated. Conversely, umbilical and disc herniation pathomechanisms are distinct, as these negatively correlate with the presence of advanced diabetic nephropathy.

Abstract 13316: Statin Therapy Prevents the Development of Contrast-induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes

Introduction: Contrast-induced nephropathy (CIN) is often encountered following percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) and is associated with high in- hospital morbidity and mortality. Statins may prevent the development of CIN, however their efficacy in patients with ACS has not been evaluated. Hypothesis: We conducted a meta-analysis of randomized controlled trials (RCTs) to assess statin efficacy in the prevention of CIN in patients undergoing PCI for ACS. Methods: PubMed, EMBASE, MEDLINE and the Cochrane Central Register were searched for RCTs from inception to September 2014 to compare high-dose statins (rosuvastatin 40mg/day, atorvastatin 80mg/day or simvastatin 80mg/day) with low-dose (atorvastatin 10mg/day, simvastatin 10mg/day) o placebo treatment in patients with ACS, undergoing PCI. Study-specific odds ratios (ORs) were calculated, and between-study heterogeneity was assessed using the I2 statistic. We used a random effects model meta-analysis to pool the OR. Results: Seven RCTs, including 5174 patients were included in the analysis. CIN occurred in 126 (4.9 patients in the high dose statin group and in 232 (8.9%) patients in the low dose or placebo group (OR: 0.50, 95% confidence interval: 0.38- 0.66, p&lt;0.001). The observed heterogeneity between the included studies was low (I2=19%, p=0.28). Conclusions: High-dose statin therapy is effective at preventing the development of CIN in the high-risk population of patients undergoing PCI for ACS.

Increased urinary Smad3 is significantly correlated with glomerular hyperfiltration and a reduced glomerular filtration rate and is a new urinary biomarker for diabetic nephropathy.

BackgroundDiabetic nephropathy is one of the major microvascular complications of diabetes. We investigated the association between urinary Smad3 (usmad3) levels, glomerular hyperfiltration, and the development of nephropathy in patients with type 2 diabetes mellitus (T2DM).MethodsThe usmad3 level was determined by enzyme-linked immunosorbent assay in 245 well-characterised patients with T2DM and 82 healthy control subjects. The associations of the usmad3 level with glomerular hyperfiltration, glucose and lipid profiles, and renal function were evaluated.ResultsThe usmad3 level was significantly higher in patients with diabetes than in the control group. The level in the hyperfiltration group was higher than that in the normofiltering group, regardless of whether patients were in the normoalbuminuric or the proteinuria groups. Pearson’s correlation analysis suggested that the usmad3 level was significantly correlated with age, systolic blood pressure, fasting plasma glucose, insulin, C-peptide, glycated haemoglobin, and estimated glomerular filtration rate (eGFR). A multiple linear stepwise regression analysis revealed that usmad3 levels in patients with T2DM and an eGFR ≥90 ml/min/1.73 m2 were independently and positively correlated with eGFR, whereas in patients with T2DM and eGFR <90 ml/min/1.73 m2, the levels were independently and negatively correlated with eGFR.ConclusionsThe usmad3 level was significantly correlated with biphasic changes in the GFR (both glomerular hyperfiltration and reduced eGFR) in patients with T2DM. Usmad3 may serve as a novel marker for hyperfiltration and for screening patients with T2DM for nephropathy.

Growth Hormone Induces Transforming Growth Factor-Beta-Induced Protein in Podocytes: Implications for Podocyte Depletion and Proteinuria.

The glomerular podocytes form a major size selective barrier for the filtration of serum proteins and reduced podocyte number is a critical event in the pathogenesis of proteinuria during diabetic nephropathy (DN). An elevated level of growth hormone (GH) is implicated as a causative factor in the development of nephropathy in patients with type 1 diabetes mellitus. We have previously shown that podocytes express GH receptor and are a target for GH action. To elucidate the molecular basis for the effects of GH on podocyte depletion, we conducted PCR-array analyses for extracellular matrix and adhesion molecules in podocytes. Our studies reveal that GH increases expression of a gene that encodes transforming growth factor-beta-induced protein (TGFBIp) expression. Similarly, microarray data retrieved from the Nephromine database revealed elevation of TGFBIp in patients with DN. Treatment with GH results in increased secretion of extracellular TGFBIp by podocytes. Both GH and TGFBIp induced apoptosis and epithelial mesenchymal transition (EMT) of podocytes. Exposure of podocytes to GH and TGFBIp resulted in increased migration of cells and altered podocyte permeability to albumin across podocyte monolayer. Administration of GH to rats induced EMT and apoptosis in the glomerular fraction of the kidney. Therefore, we conclude that the GH-dependent increase in TGFBIp in the podocyte is one of the mechanisms responsible for podocyte depletion in DN.

The quest for an animal model of diabetic nephropathy and the role of taurine deficiency.

Diabetic nephropathy is the leading cause of end stage renal disease in man. Despite efforts, an ideal animal model that can reproduce the characteristics of human diabetic nephropathy has not been developed. To this end, we hypothesize that taurine deficiency is one of the critical risk factors for development of nephropathy in patients with diabetes mellitus. This hypothesis can be tested in vivo in TauT knockout (TauT −/−) C57BL/6 background mice. We asked whether taurine deficiency would enhance disease in the streptozotocin-treated mouse. We provide evidence that alteration of the TauT gene has a substantial effect on the susceptibility to diabetic kidney disease development in a TauT −/− mouse model of diabetes. These animals specifically developed characteristic renal histological changes that included glomerulosclerosis, nodular lesions, arteriosclerosis, arteriolar dilation, and tubulointerstitial fibrosis. Immunohistochemical staining of molecular markers such as smooth muscle actin, CD34, Ki67, and collagen IV confirmed these observations and were abnormal. The results demonstrated that TauT gene deletion predisposes C57BL/6 mice to develop end-stage diabetic kidney disease, which closely replicates the pathological features of diabetic nephropathy in human diabetic patients and, thus, can serve as a model for therapeutic strategies.