Development Of Microalbuminuria Research Articles

#1405 Salt sensitivity and hypertensive nephropathy: a link to be discovered

Abstract Background and Aims Sodium sensitivity (SS) is a change in blood pressure (BP) depending on Na+ intake, 30% of population has it. Either a salt load test or a sodium dietary protocol can be used to stratify the population into 3 groups based on BP variation: sodium sensitive (SS), sodium resistant (SR), inverse sodium sensitivity (ISS), based on an increase, a non-significant variation or a decrease in BP following the administration of Na+. SNPs located in genes related with Na+ metabolism, aldosterone synthesis and kidney tubular Na+ reabsorption are related to this phenotype. Method We analyzed data collected from the follow-up (FUP) of 127 subjects with a new diagnosis of hypertension, categorized by their profile through acute salt load test. We analyzed the kidney damage by annual decline of eGFR and development of microalbuminuria. Genetic polymorphism analysis has been executed. Results No differences in the decline of eGFR are observed among the groups (−1.3084 ml/min ± 0.16 p-Value 0.372). SR subjects seem to be more prone to develop earlier microalbuminuria (χ 2 10.682, p = 0.005) even with an adequate BP control (P-Anova SBP 0.766; P-Anova DBP 0.856). An inverse correlation exists between pressure-natriuresis ratio and decline in eGFR (R −0.194 p = 0.016). Polymorphism in CYP11B2 (0.72 OR p = 0.045) and NEDD4L (0.74 OR p = 0.027) are protective against eGFR decline. ADD3 polymorphism (3.73 OR p = 0.049) is a risk factor for development of microalbuminuria. KL (0.15 OR p = 0.034), PKD and TRPC6 (p-Value 0.037, p-Value 0.009) polymorphism are protective factor against microalbuminuria. Conclusion SR patients are more at risk of developing hypertensive nephropathy earlier than other groups; steeper pressure natriuresis ratio is involved in quicker decline in renal function possibly accelerating development of hypertensive nephropathy. Further studies with larger sample and standardization in salt sensitivity test are needed to translate this knowledges into clinical setting.

Helicobacter Pylori Infection and Microalbuminuria in Diabetic Patients

Microalbuminuria is defined as an elevated urine albumin to creatinine ratio of 30-300 g/mg. It has been recognized as a strong indicator of the onset of diabetic nephropathy. Damage to vascular endothelium and systemic inflammation can result from H. Pylori infection. Thus, it stands to reason that the resulting glomerular damage might raise the excretion of albumin in the urine. Our goal was to find out if H. pylori and microalbuminuria are related in individuals with diabetes mellitus (DM). This is a case – control observational study conducted in 6 months. Random blood glucose, Urinary Albumin Creatinine Ratio (UACR) and H. Pylori Antigen (H. Pylori antigen) in stool were measured. To minimize possible confounding factors, selecting various matching variables was put consideration when choosing the control group. Therefore, most of the matching variables of the study were comparable in both groups makes the results of studying of H. pylori as a possible risk factor for microalbuminuria greatly accurate. we concluded that H. pylori infection is highly suggested to be an independent risk factor for the development of microalbuminuria in diabetic patients. As proven by the present work; a highly significant statistical relationship between H. pylori infection and the presence of microalbuminuria in patients with diabetes.

Endostatin, soluble tumour necrosis factor receptor 1 and soluble tumour necrosis factor receptor 2 cannot predict new onset of microalbuminuria in patients with type 2 diabetes.

Inflammation and angiogenesis play an important role in the development of early diabetic kidney disease. We investigated the association of soluble Tumour Necrosis Factor Receptor 1 (sTNF-R1), sTNF-R2 and endostatin with new onset microalbuminuria in normoalbuminuric patients with diabetes mellitus type 2. We conducted a case control study to assess serum levels of sTNF-R1, sTNF-R2 and endostatin in 169 patients with new onset microalbuminuria and in 188 matched normoalbuminuric, diabetic controls. Baseline serum samples from participants of the ROADMAP (Randomized Olmesartan and Diabetes Microalbuminuria Prevention) and observational follow-up (ROADMAP-OFU) studies were used. Endostatin and sTNF-R1 but not sTNF-R2 were increased at baseline in patients with future microalbuminuria. In the multivariate analysis, each log2 increment in endostatin levels was associated with an increase of only 6% in the risk of development of microalbuminuria (adjusted HR (95% CI) 1.006 (1.001-1011). sTNF-R1 and sTNF-R2 levels were conversely associated with microalbuminuria, but the results did not reach statistical significance. The respective adjusted HRs (95% CI) were 1.305 (0.928-1.774) and 0.874 (0.711-1.074). sTNF-R1 and sTNF-R2 failed to predict the occurrence of microalbuminuria in normoalbuminuric patients with type 2 diabetes. Likewise, the utility of endostatin in predicting new onset proteinuria is limited.

Evaluation of N-acetyl-β-D-glucosaminidase as a prognostic marker for diabetic nephropathy in type 2 diabetics: systematic review and meta-analysis.

This review aimed to assess the utility of urinary N-acetyl-β-D-glucosaminidase (uNAG) as a prognostic biomarker for nephropathy in patients with type 2 diabetes mellitus. The search for relevant studies was conducted across multiple databases, including PubMed (Medline), EMBASE, LILACS, CENTRAL, IBECS, and gray literature. We employed a random effects model to calculate the standardized mean difference and 95% confidence interval. Furthermore, we assessed heterogeneity using Cochrane's Q test and Higgins' I2 statistics. This review included a total of 16 articles involving 1669 patients, with 13 being case-control studies and three being cohorts. The meta-analysis conducted across all studies revealed significant heterogeneity. However, subgroup analysis of four studies indicated that an increase in uNAG among normoalbuminuric patients was associated with the development of macroalbuminuria (DMP = -1.47; 95% CI = -1.98 to 0.95; p < 0.00001; I2 = 45%). Conversely, it did not demonstrate effectiveness in predicting the development of microalbuminuria (DMP = 0.26; 95% CI = -0.08 to 0.60; p = 0.13; I2 = 17%). Elevated uNAG levels in normoalbuminuric patients may indicate an increased risk for the development of macroalbuminuria, but not microalbuminuria. However, the high heterogeneity observed among the studies highlights the necessity for further research to validate these findings.

Central diastolic blood pressure, plasma aldosterone and uric acid are associated with microalbuminuria in essential hypertension: a case-control study

ObjectiveTo study the development of microalbuminuria (MAU) in essential hypertension (EHT), we investigated the association of MAU with central blood pressure (CBP), direct renin concentration (DRC), plasma aldosterone (PA), and uric acid (UA).MethodWe determined 24 h-urinary albumin excretion (24 h-UAE) in patients with EHT who were hospitalized at TEDA International Cardiovascular Hospital from June 2020 to May 2022. We defined MAU as 24 h-UAE in the range of 30 mg/24 h to 300 mg/24 h. Univariate and multivariate analyses were conducted to determine the associations of MAU with CBP, DRC, PA, and UA in EHT, considering demographic and clinical information. We also plotted receiver operating characteristic curves (ROCs) for predicting MAU using these results.ResultsMore than a quarter of patients (26.5%, 107/404, 95% CI: 22.2–31.1%) were diagnosed with MAU in EHT. A higher body mass index (BMI), longer duration of hypertension, and higher severity were associated with MAU. Also, nearly 10% more creatinine levels were recorded in the MAU group than in the control group (69.5 ± 18.7 µmol/L vs. 64.8 ± 12.5 µmol/L, P = 0.004). The increase was also observed for PA (15.5, 9.7–20.6 ng/dL vs. 12.3, 9.0–17.3 ng/dL, P = 0.024) and UA (419.8 ± 105.6 µmol/L vs. 375.1 ± 89.5 µmol/L, P < 0.001) in the MAU group compared to that in the control group. Several variables were associated with MAU, including central diastolic blood pressure (CDBP) (OR = 1.017, 95% CI: 1.002–1.032, P = 0.027), PA (OR = 1.043, 95% CI: 1.009–1.078, P = 0.012) and UA (OR = 1.005, 95% CI: 1.002–1.008, P < 0.001). For MAU prediction, the area under the curve (AUC) was 0.709 (95% CI: 0.662–0.753; P < 0.001) when CDBP, PA, and UA were used in combination, and the optimal probability of the cut-off value was 0.337.ConclusionWe found that CDBP, PA, and UA, used for MAU prediction, might be associated with its development during EHT.

Association of Both Short-term and Long-term Glycemic Variability With the Development of Microalbuminuria in the ACCORD Trial.

The relative and potential additive effects of long- and short-term glycemic variability on the development of diabetic complications are unknown. We aimed to assess the individual and combined relationships of long-term visit-to-visit glycemic variability, measured as the coefficient of variation of fasting plasma glucose, and short-term glucose fluctuation, estimated by the biomarker 1,5-anhydroglucitol, with the development of proteinuria. Both estimates of glycemic variability were independently associated with microalbuminuria, but only long-term glycemic variability remained significant after adjusting for average hemoglobin A1c. Our findings suggest that longer-term visit-to-visit glucose variability improves renal disease prediction in type 2 diabetes.

Association of the rs5186 polymorphism of the AGTR1 gene with decreased eGFR in patients with type 2 diabetes from Mexico City

BackgroundEarly biomarkers search for Diabetic Kidney Disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM), as genetic markers to identify vulnerable carriers of the disease even before Glomerular Filtration Rate (GFR) decline or microalbuminuria development, has been relevant during the last few years.The rs5186 (A116C) polymorphism of the Angiotensin II Receptor Type I gene (AGTR1), has been associated to multiple effects of renal injury risk, commonly detected in patients with Diabetes Mellitus (DM). It has been described that rs5186 could have an effect in stability proteins that assemble Angiotensin II Receptor Type I (AT1), modifying its action, which is why it should be considered as a risk factor for Chronic Kidney Disease (CKD), characterized by a GFR progressive reduction. Even though, the association between rs5186 AGTR1 gene polymorphism and DKD in patients with T2DM has been controversial, inconclusive, and even absent. This disputable issue might be as a result of association studies in which many and varied clinical phenotypes included are contemplated as CKD inductors and enhancers. Although, the sample sizes studied in patients with T2DM are undersized and did not have a strict inclusion criteria, lacking of biochemical markers or KDOQI classification, which have hindered its examination. ObjectiveThe aim of our study was to establish an association between rs5186 AGTR1 gene polymorphism and GFR depletion, assessed as a risk factor to DKD development in patients with T2DM. MethodsWe analyzed 297 not related patients with T2DM, divided into 221 controls (KDOQI 1) and 76 cases (KDOQI 2). Arterial pressure, anthropometric and biochemical parameters were measured. rs5186 of AGTR1 genotyping was performed by TaqMan assay real-time PCR method. Allele and genotype frequencies, and Hardy-Weinberg equilibrium were measured. Normality test for data distribution was analyzed by Shapiro-Wilk test, variable comparison by Student’s t-test for continuous variables, and Chi-squared test for categorical variables; ANOVA test was used for mean comparison of more than two groups. Effect of rs5186 to DKD was estimated by multiple heritability adjustment models for risk variables of DKD. Statistical significance was indicated by p<0.05. Data was analyzed using Statistical Package STATA v11 software. ResultsDominant and Over-dominant models showed a likelihood ratio to GFR depletion of 1.89 (1.05−3.39, p=0.031) and 2.01 (1.08−3.73, p=0.023) in patients with T2DM. Risk factor increased to 2.54 (1.10−5.89) in women in Over-dominant model. ConclusionIn clinical practice, most of nephropathies progress at a slow pace into a total breakdown of renal function, even asymptomatic. This is the first study, reporting that rs5186 polymorphism of AGTR1 gene contribution to GFR depletion, and this could be evaluated as a predisposing factor for DKD in patients with T2DM.

Effect of Neurohypophyseal Hormones on Excretion of Proteins by the Kidneys

Vasopressin (VP) is one of the main factors affecting intraglomerular hemodynamics, filtration pressure and the state of mesangial cells and contributing to the progression of proteinuria. The aim of this work was to study the effect of neurohypophyseal hormones (VP and oxytocin) on urinary protein excretion. Experiments were performed on Wistar rats, healthy and with microalbuminuria caused by minimal damage to the glomerular filter. Microalbuminuria was modeled by administration of D-nitroarginine methyl ester (D-NAME, 50 mg/kg, intraperitoneally). VP (0.05 and 1.5 nmol/kg) and oxytocin (0.15 nmol/kg) were administered to rats intramuscularly, V2-antagonist (15 nmol/kg) and V1a-antagonist (20 nmol/kg) intraperitoneally. To reduce the level of endogenous VP, animals were given water to drink (10 ml/kg), urine was collected for 2 h, and the levels of total protein, albumin, β2-microglobulin, and immunoglobulin G (IgG) were analyzed. In healthy rats, VP at a dose of 0.05 nmol/kg and oxytocin did not affect albumin excretion, but VP at a dose of 1.5 nmol/kg provoked microalbuminuria. In a model of impaired properties of the glomerular filter caused by the D-NAME administration, VP at a dose of 0.05 nmol/kg and oxytocin led to the normalization of albumin excretion, and VP at a dose of 1.5 nmol/kg caused pronounced proteinuria, albumin excretion increased by 100 times, IgG – by 10 times. Blockade of V2 receptors aggravated protein loss caused by D-NAME and VP (1.5 nmol/kg), while blockade of V1a receptors prevented it. Thus, at high concentrations in the blood, VP enhances protein filtration in the kidney. This effect is mediated by V1a receptors and, depending on the barrier properties of the glomerular filter, leads to the development of microalbuminuria or severe proteinuria. Oxytocin and VP at a dose at which it predominantly activates V2 receptors have an antiproteinuric effect. The revealed effects of neurohypophyseal hormones on albumin excretion open up new promising therapeutic targets for the correction of glomerular dysfunctions.

Effects of Ramadan Fasting on Diabetic Nephropathy in Type 2 Diabetic Patients

Abstract Background Type 2 diabetes is a chronic metabolic disease that has a significant impact on the health, quality of life, and life expectancy of patients, as well as on the health care system. Diabetic nephropathy is one of the major complications of diabetes, characterized by proteinuria and renal insufficiency. The development of microalbuminuria is an early marker for diabetic nephropathy, which is potentially modifiable through lifestyle changes and pharmacological interventions targeting blood glucose and blood pressure, specifically through the renin angiotensin system. Aim of the Work The aim of this work is to study the effect of Ramadan fasting on diabetic nephropathy in type 2 diabetic patients. Patients and Methods Our study conducted on 90 type 2 diabetic patients, their age between 40-60 years; all of them are welling to fast the whole month of Ramadan, selected from the outpatient clinic of endocrinology, Ain Shams University Hospitals. Results There was a highly statistically significant increase in Creatinine (p &amp;lt; 0.001) as well as a highly statistically significant increase in urea after Ramdan in all studied group (P &amp;lt; 0.001). The Percentage change in GFR was significantly higher in macroalbuminuria. The Percentage change in A/C ratio in micro and macroalbuminuria were significantly lower when compared to normoalbuminuria, as well as in macroalbuminuria when compared to microalbuminuria groups. (P = 0.001). There were no significant differences found regarding, body mass index;, systolic blood pressure, diastolic blood pressure fasting blood glucose, postprandial blood glucose, HbA1c before and after Ramadan. Conclusion Ramadan fasting has no harmful impact on albuminuria among patients with T2DM. However, fasting leads to a significant decline in renal function parameters among diabetic patients with albuminuria. This decline is more prominent in patients with macroalbuminuria than patients with microalbuminuria. Thus, fasting should be avoided in patients with a severe decline in renal functions. Patients should be advised regarding adequate hydration and dietary modification during Pre-Ramadan health care education. On the other hand, Ramadan fasting has no negative impacts on glycemic control and other metabolic parameters. Nevertheless, further trials that assess the role of fasting in at-risk patients are still needed.

#5482 CIRCULATING BIOMARKERS OF COLLAGEN REMODELING AS MARKERS FOR DEVELOPMENT OF MICROALBUMINURIA IN TYPE 2 DIABETES: THE PRIORITY TRIAL

Abstract Background and Aims Kidney disease progression is characterized by extensive deposition of extracellular matrix components such as collagen. Therefore, we assessed the effect of spironolactone on collagen remodeling biomarkers and investigated the association between the markers and development of microalbuminuria in serum of persons with type 2 diabetes and normoalbuminuria. Method We measured collagen type III (PRO-C3), VI (PRO-C6; endotrophin), VII (PRO-C7), and XXVIII (PRO-C28) formation, and a fragment of degraded crosslinked collagen type III (CTX-III) in serum of persons with high-risk (stratified by a urinary proteomics classifier, CKD273) for development of microalbuminuria, randomized to either spironolactone 25 mg or placebo. Crude and adjusted Cox models were applied to investigate the association between baseline biomarker levels and development of the primary outcome, persistent microalbuminuria, and development of microalbuminuria in at least one morning void sample, used as a secondary outcome. Results In the PRIORITY trial, spironolactone treatment did not prevent progression to microalbuminuria compared to placebo. All biomarkers were measured in 154 participants at baseline and 117 at end-of-study (week 208). Treatment with spironolactone did not affect serum levels of any of the investigated collagen remodeling biomarkers compared to placebo, and there were no differences in delta-biomarker levels between baseline and end-of-study (p ranging 0.277-0.875). In crude analyses, serum endotrophin was associated with both the primary (n = 44) and secondary outcome (n = 74) (HR per two-fold higher level: 1.58, 95% CI: 1.03-2.44, p = 0.037 and 1.62, 1.12-2.35, p = 0.010), whereas serum PRO-C3 was only associated with the secondary outcome (1.89, 1.19-2.99, p = 0.007). After adjustment for sex, baseline age, systolic blood pressure, estimated glomerular filtration rate, urinary albumin-creatinine ratio, and HbA1c, serum endotrophin and PRO-C3 remained significantly associated with the secondary outcome (1.52, 1.03-2.24, p = 0.036 and 1.73, 1.08-2.78, p = 0.022). Levels of PRO-C7, PRO-C28, and CTX-III were not associated with the specified outcomes. Neither baseline levels of serum endotrophin nor PRO-C3 correlated with baseline CKD273 levels (R: 0.00-0.06, p&amp;gt;0.47). Conclusion Treatment with spironolactone did not change serum levels of collagen remodeling biomarkers. Serum endotrophin, reflecting collagen type VI formation and the pro-fibrotic molecule endotrophin, and PRO-C3, a marker of collagen type III formation, were associated with development of microalbuminuria in at least one urine sample, suggesting that these biomarkers are relevant risk markers for kidney disease development in type 2 diabetes.

#4391 SALT SENSITIVITY AND HYPERTENSIVE NEPHROPATHY: A LINK TO BE DISCOVERED

Abstract Background and Aims Sodium sensitivity is defined as a change in blood pressure depending on sodium intake, which is present in about 30% of the adult population. According to blood pressure variation in salt load test we can classify the population in 3 categories: sodium sensitive (SS), sodium resistant (SR), inverse sodium sensitivity (ISS), based on, respectively, an increase, a non-significant variation or a decrease in the blood pressure values following the administration of sodium. It is reported that SS subjects have, independently from other risk factors, an increased risk of cardiovascular diseases. Moreover, SNPs located in genes related with Na+ metabolism, aldosterone synthesis and tubular sodium reabsorption in the kidney are related to salt sensitivity phenotype. The aim of this study is to analyze the relationship between sodium sensitivity and the development of hypertensive kidney damage in patients with primary hypertension. Method A cohort of 712 naïve hypertensive patients were classified for salt-sensitivity using acute saline test (NaCl 308 mEq / 2h / iv).127 patients (follow-up &amp;gt; 5 years- median 11) were selected for the present analysis (SS, n = 40; 0 SR, n = 46; RSS, n = 41). We analyzed annual decline of the eGFR (CDK-EPI) (Delta-eGFR) and development of microalbuminuria (MicrAlb) as renal outcome. Moreover, genetic polymorphism involved in salt sensitive hypertension has been investigated. Results No differences in Delta-eGFR was observed among the groups. However, SR subjects develop earlier microalbuminuria (P = .002) even with an adequate pressure control. Genotypes analysis revealed: polymorphism in CYP11B2 and NEDD4L to be protective against decline in eGFR. For microalbuminuria HSD3B1 and ADD3 seem to be a risk factors, whereas KL, PKD and TRPC6 polymorphism result protective factors. Conclusion Unexpectedly these finding suggests that SR patients are more at risk of developing hypertensive nephropathy than other groups of patients. Moreover genotypes associated with salt sensitivity play different and complex role in kidney damage in hypertension. Improvement in salt sensitivity testing and standardization will be needed to allow all this pathophysiological knowledge to be translated in a clinical setting.

SALT SENSITIVITY AND HYPERTENSIVE NEPHROPATHY: A LINK TO BE DISCOVERED

Objective: Sodium sensitivity is defined as a change in blood pressure depending on sodium intake, which is present in about 30% of the adult population. According to blood pressure variation in salt load test we can classify the population in 3 categories: sodium sensitive (SS), sodium resistant (SR), inverse sodium sensitivity (ISS), based on, respectively, an increase, a non-significant variation or a decrease in the blood pressure values following the administration of sodium. It is reported that SS subjects have, independently from other risk factors, an increased risk of cardiovascular diseases. Moreover, SNPs located in genes related with Na+ metabolism, aldosterone synthesis and tubular sodium reabsorption in the kidney are related to salt sensitivity phenotype. The aim of this study is to analyze the relationship between sodium sensitivity and the development of hypertensive kidney damage in patients with primary hypertension. Design and method: A cohort of 712 naïve hypertensive patients were classified for salt-sensitivity using acute saline test (NaCl 308 mEq / 2h / iv).127 patients (follow-up &gt; 5 years- median 11) were selected for the present analysis (SS, n = 40; 0 SR, n = 46; RSS, n = 41). We analyzed annual decline of the eGFR (CDK-EPI) (Delta-eGFR) and development of microalbuminuria (MicrAlb) as renal outcome. Moreover, genetic polymorphism involved in salt sensitive hypertension has been investigated. Results: No differences in Delta-eGFR was observed among the groups. However, SR subjects develop earlier microalbuminuria (p = 0.002) even with an adequate pressure control. Genotypes analysis revealed: polymorphism in CYP11B2 and NEDD4L to be protective against decline in eGFR. For microalbuminuria HSD3B1 and ADD3 seem to be a risk factors, whereas KL, PKD and TRPC6 polymorphism result protective factors. Conclusions: Unexpectedly these finding suggests that SR patients are more at risk of developing hypertensive nephropathy than other groups of patients. Moreover genotypes associated with salt sensitivity play different and complex role in kidney damage in hypertension. Improvement in salt sensitivity testing and standardization will be needed to allow all this pathophysiological knowledge to be translated in a clinical setting

STUDY OF MICROALBUMINURIAAND ALBUMIN - CREATININE RATIO IN TYPE 2 DIABETES MELLITUS AND THEIR CORRELATION WITH GFR AND OTHER BIOCHEMICAL PARAMETERS

Diabetes mellitus (DM) is one of the primary risk factors for developing renal impairment globally. The development of microalbuminuria has been considered to be one of the rst clinical signs of a classic course of diabetic nephropathy, which leads to macroalbuminuria and then to progressive loss of glomerular ltration rate (GFR) and eventually end-stage renal disease. Both type 1 and type 2 DM may lead to chronic complication of diabetic nephropathy (DN). The development of microalbuminuria has been considered to be one of the rst clinical signs of a classic course of diabetic nephropathy, which leads to macroalbuminuria and then to progressive loss of glomerular ltration rate (GFR) and eventually end-stage renal disease. Persistent macroalbuminuria predicts loss of kidney function and, more importantly, interventions that reduce macroalbuminuria also slow the loss of glomerular ltration rate. this prospective observational study was designed in an attempt to evaluate the relationship between microalbuminuria, albumin-creatinine ratio with other biochemical parameters in type 2 DM and to examine whether this relation differs from that of non-diabet

Presence of retinopathy and incident kidney and cardiovascular events in type 2 diabetes with normoalbuminuria – A post-hoc analysis of the PRIORITY randomized clinical trial

AimsBaseline diabetic retinopathy (DR) and risk of development of microalbuminuria, kidney function decline, and cardiovascular events (CVEs) in type 2 diabetes. MethodsPost-hoc analysis of the PRIORITY study including 1758 persons with type 2 diabetes and normoalbuminuria followed for a median of 2.5 (IQR: 2.0–3.0) years. DR diagnosis included non-proliferative and proliferative abnormalities, macular oedema, or prior laser treatment. Cox models were fitted to investigate baseline DR presence with development of persistent microalbuminuria (urinary albumin-creatinine ratio > 30 mg/g); chronic kidney disease (CKD) G3 (eGFR <60 ml/min/1.73m2); and CVE. Models were adjusted for relevant risk factors. ResultsAt baseline, 304 (17.3 %) had DR. Compared to persons without DR, they were older (mean ± SD: 62.7 ± 7.7 vs 61.4 ± 8.3 years, p = 0.019), had longer diabetes duration (17.9 ± 8.4 vs. 10.6 ± 7.0 years, p < 0.001), and higher HbA1c (62 ± 13 vs. 56 ± 12 mmol/mol, p < 0.001). The adjusted hazard ratios of DR at baseline for development of microalbuminuria (n = 197), CKD (n = 166), and CVE (n = 64) were: 1.50 (95%CI: 1.07, 2.11), 0.87 (95%CI: 0.56, 1.34), and 2.61 (95%CI: 1.44, 4.72), compared to without DR. ConclusionsPresence of DR in normoalbuminuric type 2 diabetes was associated with an increased risk of developing microalbuminuria and CVE, but not with kidney function decline.

The Relationship with Disease Severity of Ischemia-Modified Albumin Levels in Diabetic Nephropathy

Background: While type 2 diabetes (T2DM) is increasing rapidly, developing diabetic complications are the leading cause of morbidity and mortality. Biochemical markers are important for early diagnosis and treatment of nephropathy, which is a common complication. The aim of this study is to evaluate serum ischemia-modified albumin (IMA) levels in the development of diabetic nephropathy in T2DM patients and to determine the effectiveness of this parameter in predicting the presence and severity of nephropathy. Materials and Methods: 68 adult patients diagnosed with T2DM and 30 healthy controls were included in this study. The T2DM group consisted of 34 patients without microalbuminuria (&lt;30 mg/g) and 34 patients with microalbuminuria (30–300 mg/g) according to albumin/creatinine ratio (UACR). Biochemical data and serum IMA levels of the patient and control groups were measured and compared. Results: In terms of IMA levels, the difference between T2DM patients with microalbuminuria (0.55 ± 0.08 ABSU) and without microalbuminuria (0.42 ± 0.05 ABSU) and control (0.37 ± 0.08 ABSU) groups was significant (p&lt;0.0001). The T2DM group with microalbuminuria had the highest glucose, HbA1c, UACR, and IMA levels. There was a positive correlation between IMA levels and UACR (r = 0.541, p &lt; 0.001). IMA had a weak correlation with HbA1c (r = 0.345, p = 0.002). ROC analysis was performed and the IMA test had a high diagnostic value in the diagnostic differentiation of T2DM patients with microalbuminuria. According to multiple logistic regression analysis, IMA levels were an independent risk factor for DN (p = 0.003). Conclusions: Our data showed that IMA values increased significantly in diabetic patients, especially in those with microalbuminuria, and this increase was correlated with UACR levels. This study has shown that increased IMA levels are an important marker for the presence and severity of microalbuminuria in diabetic patients and therefore may be important in the early detection of renal dysfunction in T2DM. We even think that it can be used as an important marker in the follow-up of diabetic patients, even before the development of microalbuminuria.

Clinical Profile of Nonproteinuric Kidney Disease in Type 2 Diabetic Patients in India.

Diabetic kidney disease (DKD) is the commonest cause of end-stage renal disease (ESRD) across the world. Development of microalbuminuria is the earliest marker of DKD and predicts progressive decline in estimated glomerular filtration rate (eGFR). However, recent evidence has suggested that a significant proportion of type 2 diabetic patients have chronic kidney disease (CKD) without proteinuria. In this single-center, prospective observational study, 400 consecutive type 2 diabetic patients with either overt proteinuria (>500 mg/day) and/or renal dysfunction eGFR <60 ml/min/1.73 m2) were recruited. Baseline demographic and clinical data were recorded. eGFR and proteinuria were recorded at 6 months and 1 year. Patients with proteinuric (proteinuria >0.5 g/day) and nonproteinuric phenotypes were compared for progression of renal dysfunction in terms of doubling of serum creatinine and need for dialysis. In our study cohort, 106 (26.5%) were nonproteinuric. Both the groups were similar in terms of gender, duration of diabetes, comorbidities, body mass index (BMI), blood pressure control, and glycemic control. The nonproteinuric group was older (56.5 ± 2.1 vs. 54.7 ± 11.6 years, P = 0.012), had lesser prevalence of diabetic retinopathy (49 [46.2%] vs. 218 [74.1%], P < 0.001), higher hemoglobin levels (11.3 ± 1.7 vs. 10.5 ± 2.0 g/dl, P < 0.001), and higher cholesterol levels (169.3 ± 43.3 vs 157.1 ± 58.1 mg/dl, P = 0.025). The nonproteinuric phenotype had higher eGFR at baseline, 6 months, and 1 year. However, doubling of serum creatinine (10 [9.4%] vs. 48 [16.3%]) and progression to ESRD (5 [4.7%] vs. 19 [6.5%], P = 0.159) were not different between the two phenotypes. Nonproteinuric DKD is common. Patients with nonproteinuric DKD tend to be older with a slower decline in eGFR.

A Project work on Recent approches in the Treatment of Diabetic Nepheropathy

Renal failure is a common long-torm complication of diabetes mellitus. Stages of diabetic nephropathy have been described that characterize its clinical course. Diabetic nephropathy develops secondary to long- changes that damage the glomeruli’s. Therapy that focuses on the control of glomerular pressures and systemic hypertension can slow the progression of proteinuria and deterioration of renal function. Angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers have been demonstrated to be effective in the management of diabetic nephropathy. A systematic approach to the patient with diabetes with help identify those individuals early in the course of disease when proper therapy may be most helpful. Diabetic nephropathy is the leading cause of chronic renal disease and a major cause of cardiovascular mortality. Diabetic nephropathy has been categorized into stages: micro albuminuria and macro albuminuria. The cut-off values of micro- and macro albuminuria are arbitrary and their values have been questioned. Subjects in the upper-normal range of albuminuria seem to be at high risk of progression to micro- or macro albuminuria and they also had a higher blood pressure than normoalbuminuric subjects in the lower norm albuminuria range. Diabetic nephropathy screening is made by measuring albumin in spot urine. If abnormal, it should be confirmed in two out three samples collected in a three to six-months interval. Additionally, it is recommended that glomerular filtration rate be routinely estimated for appropriate screening of nephropathy, because some patients present a decreased glomerular filtration rate when urine albumin values are in the normal range. The two main risk factors for diabetic nephropathy are hyperglycemia and arterial hypertension, but the genetic susceptibility in both type 1 and type 2 diabetes is of great importance. Other risk factors are smoking, dyslipidemia, proteinuria, glomerular hyper filtration and dietary factors. Nephropathy is pathologically characterized in individuals with type 1 diabetes by thickening of glomerular and tubular basal membranes, with progressive meningeal expansion (diffuse or nodular) leading to progressive reduction of glomerular filtration surface. Concurrent interstitial morphological alterations and hyalinization of afferent and efferent glomerular arterioles also occur. Podocytes abnormalities also appear to be involved in the glomerulosclerosis process. In patients with type 2 diabetes, renal lesions are heterogeneous and more complex than in individuals with type 1 diabetes. Treatment of diabetic nephropathy is based on a multiple risk factor approach, and the goal is retarding the development or progression of the disease and to decrease the subject's increased risk of cardiovascular disease. Achieving the best metabolic control, treating hypertension (&lt;130/80 mmHg) and dyslipidemia (LDL cholesterol &lt;100 mg/dl), using drugs that block the renin-angiotensin-aldosterone system, are effective strategies for preventing the development of micro albuminuria, delaying the progression to more advanced stages of nephropathy and reducing cardiovascular mortality in patients with diabetes.

Effect of the nurse-led program on blood glucose control and microalbuminuria development in type 2 diabetic populations.

Current study was to evaluate whether the nurse-led program can improve glycated hemoglobin (HbA1c) control and reduce the incidence of microalbuminuria in type 2 diabetic mellitus (DM2) populations. A total of 150 DM2 subjects were randomly assigned to the usual-care group and nurse-led program group. Study endpoints included the HbA1c value, the percentage of subjects with HbA1c < 7.0%, the incidence of microalbuminuria, and the rate of adhering to antidiabetic drug at 6 months’ follow-up. At baseline, there was no difference in fasting plasma glucose, HbA1c, proportion of subjects with HbA1c < 7.0%, the use of antidiabetic drug, and urinary albumin-creatinine ratio between these two groups. After 6 months’ follow-up, the mean fasting plasma glucose and HbA1c were lower in the nurse-led program group, as was the proportion of subjects with HbA1c < 7.0%. The median urinary albumin-creatinine ratio and rate of incident microalbuminuria were also lower in the nurse-led program. The nurse-led program was associated with higher odds of achieving HbA1c < 7.0% and a lower incidence of microalbuminuria. After adjusted for covariates, the nurse-led program was still associated with 32% higher odds of achieving HbA1c < 7.0% and 11% lower incidence of microalbuminuria. These benefits were consistent by sex and age, while greater in those with obesity or hypertension (P interaction < .05). The nurse-led program is beneficial for blood glucose control and prevention of microalbuminuria.

Prevalence of Microalbuminuria and Cardiovascular Risk Factors in Patients With Diabetes Mellitus Type-II in Al-Khobar, Kingdom of Saudi Arabia.

Background Type 2 diabetes mellitus (T2DM) is a common disorder worldwide. Impaired control of glucose levels predisposes to renal dysfunction, detected by a diagnosis of microalbuminuria. Several other risk factors have been identified in the development of microalbuminuria, such as hypertension, smoking, dyslipidemia, and obesity. Objective Assessment of microalbuminuria and cardiovascular risk factors in type-II diabetic patients who attended the outpatient clinic for the internal medicine department at King Fahd University Hospital, Al-Khobar. Methods A retrospective cross-sectional and an observational study included data from 2014 to 2022 collected from medical records. Patients with diabetes type-II and aged ≥18 years were included. The following were reviewed (age, sex, height, weight, body mass index, waist, hip, waist-hip ratio, systolic and diastolic blood pressure, smoking, sedentary lifestyle, diagnosis of dyslipidemia/hypertension, diabetes duration in years) and laboratory results (fasting blood glucose, HbA1C%, estimated glomerular filtration rate, serum creatinine, serum cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides). Microalbuminuria was measured by the urine albumin to creatinine ratio and was diagnosed if levels were 30-300 mg/g. Results Among 301 studied patients, the prevalence of microalbuminuria was found at 36.8%. The mean age was 57.8 ± 12.6 years, and females were 45%. The mean ± SD fasting blood glucose was 165.9 ± 71.9 mg/dL, while HbA1C% was 8.8 ± 5.6. Microalbuminuria was significantly associated with age, diabetes duration, systolic blood pressure, HbA1C%, fasting blood glucose, and triglyceride levels (p≤0.05). Conclusion Microalbuminuria in T2DM patients was high in this study, which emphasizes the need for early detection of microalbuminuria. The study suggests the need for effective diabetes control and the prevention of associated cardiovascular risk factors.

Association of Lipopolysaccharide-Toll-Like Receptor 4 Signaling and Microalbuminuria in Patients with Type 2 Diabetes Mellitus.

PurposeIntestinal flora imbalance has been implicated in the activation of innate immunity in the kidneys. However, little is known about the potential links between lipopolysaccharide (LPS)-toll-like. receptor 4 (TLR4) signaling activated by intestinal barrier dysfunction and microalbuminuria in type 2 diabetes mellitus (T2DM).Patients and Methods61 patients with T2DM were stratified based on the absence (n=32) or presence (n=29) of microalbuminuria. There were also 28 control subjects. Urinary albumin excretion rate (UAER), serum levels of LPS, D-lactic acid (DLA), diamine oxidase (DAO), fasting blood glucose (FBG), interleukin-6 (IL-6), glycosylated hemoglobin A1 (HbA1c), and high-sensitivity C-reactive protein (hs-CRP), and TLR4 expression in peripheral blood mononuclear cells (PBMCs) were measured.Resultshs-CRP, IL-6, LPS, DLA, DAO, and TLR4 were markedly increased in subjects with T2DM compared to the controls (P < 0.05 for all). Moreover, LPS was positively correlated with FBG, HbA1c, hs-CRP, IL-6, UAER, DLA, DAO, and TLR4 (P < 0.05 for all). In addition, TLR4 was positively correlated with UAER, hs-CRP, FBG, DLA, HbA1c, and LPS (P < 0.05 for all). In regression analyses, TLR4, LPS, HbA1c, and hs-CRP were independently associated with UAER (P < 0.05 for all), while FBG, LPS, TLR4, and hs-CRP (P < 0.05 for all) were found to be risk factors for microalbuminuria in T2DM.ConclusionIntestinal integrity is compromised in subjects with T2DM, and the activation of LPS-TLR4 signaling might play an important role in the development of microalbuminuria in T2DM.