Different Stages Of Nephropathy Research Articles

Association of glycosylated hemoglobin with urinary albuminuria for early detection and progression of renal damage in patients with type 2 diabetes mellitus

Background: Regular screening of levels of glycosylated hemoglobin and microalbuminuria (MA), diabetic nephropathy can be prevented.Recent studies found some of the sensitive and specific biomarker for early detection and progression of nephropathy in type 2 diabetes mellitus (T2DM) patients. Aim and Objectives: This study was carried out to correlation of glycosylated hemoglobin with urinary albuminuria for early detection and progression of nephropathy in patients with T2DM. Materials and Methods: This was a case–control study was conducted at tertiary care institute of India. A total 300 subjects included in the present study diagnosed with T2DM according to American diabetes association criteria and the cases are sub grouped based on albumin creatinine ration, the 100 patients T2DM with normoalbuminuria (NA) (ACR Ratio: <30 mg/dL) and 100 patients T2DM with MA (ACR Ratio: 30–299 mg/dL) along with that 100 healthy subjects were included in the study.FBS, PPBS, Urea, Creatinine, Uric acid, HbA1C, and Urinary Albumin was analyzed using laboratory standard methods. Results: The plasma fasting blood sugar, post-prandial blood sugar, serum urea, creatinine, uric acid, Glycosylated hemoglobin, and urinary albumin levels were increased in two groups of T2DM Patients when compared to healthy controls. Significantly elevated levels of plasma fasting blood sugar, post-prandial blood sugar, serum urea, creatinine, uric acid, Glycosylated hemoglobin, and urinary albumin are observed in all the parameters elevated in between patients T2DM with MA when compared to patients T2DM NA. Conclusion: Elevated levels of Glycated hemoglobin as well as urinary albumin were useful for detection and progression of different stages of nephropathy in patients with T2DM and also this study suggest that continuous monitoring of these investigations were useful for treatment of different stages of T2DM.

Diabetic nephropathy may predict the retinal changes of patients with diabetes: An Indian population-based study

Purpose: This study aimed to study and correlate fundus changes in patients with Type 2 diabetes mellitus with different stages of nephropathy. Materials and Methods: It is a prospective, observational study involving 100 patients at a tertiary health-care institute. Type 2 diabetic patients with diabetic nephropathy (DN) were enrolled. Those with uncontrolled hypertension, history of other ocular diseases, or surgeries were excluded. DN was defined as – microalbuminuria, macroproteinuria, and massive proteinuria based on 24-h urine protein analyser values. Participants underwent complete ophthalmic examination with fundus examination, fundus fluorescein angiography, and optical coherence tomography and were graded into various stages of diabetic retinopathy. The influence of nephropathy on retinal changes was assessed using Pearson's correlation analysis. Results: The study population included those with a median age of 56 years (range 38–79 years). In the group with microalbuminuria, 10 (62%) eyes did not have any retinopathy changes. In the macroproteinuria group, 61 (53%) showed mild-to-moderate nonproliferative diabetic retinopathy (PDR). In addition, 30 eyes of patients (48%) with massive proteinuria had PDR which were all statistically significant. Also in 32 eyes (16%) of DN patients, clinically significant macular edema was present, most of which, i.e., 24 (75%), were in the macroproteinuria group. Conclusions: These findings indicated that the severity of proteinuria was significantly associated with fundus changes in Type 2 diabetic patients. Thus, we conclude that DN is a marker of retinopathy and timely ophthalmic evaluation of patients should be done.

Association of ALOX12 gene polymorphism with all-cause and cardiovascular mortality in diabetic nephropathy.

Cardiovascular (CV) events are the first cause of death in patients with chronic renal disease (CKD) and in patients with type 2 diabetes mellitus (DM2). The combination of CKD and DM2 elevates the risk of both cardiovascular disease (CVD) and death in this high-risk population. Besides traditional risk factors, such as dyslipidemia, smoking, obesity, and carotid atherosclerosis, novel factors are under investigation such as genetic polymorphisms. Lipoxygenases (LOXs) and their genes are of critical importance in oxidative stress, inflammation, and atherosclerosis. The aim of the study is to clarify a potential ALOX12 role in CVD presence and progress of diabetic patients in different stages of nephropathy. We studied 145 patients with a documented history of DM2 for at least 10years and diabetic nephropathy (DN), mean age 68±9years, body mass index 31±5kg/m2, and different stages of renal disease, depending on glomerular filtration rate. The sample population consisted of two groups: 108 DM2 patients with DN in all five stages of CKD and 37 DM2 patients as controls. Anthropometric and clinical characteristics, interview for history of previous CV event, and assessment of carotid intima-media thickness (cIMT) were recorded at baseline. All patients were genotyped for ALOX12 polymorphisms with focus on rs14309. Genotypes (AA, AG, and GG) were evaluated for any possible role in CVD, and grouping was performed on A genotype, which is the dominant model. All participants were followed over a period of 7years, and the end points studied were all-cause mortality, CV mortality, and CV events. CV events were defined as myocardial infarction (MI), stroke, or peripheral artery disease. The GG genotype has been significantly associated with cIMT levels above 0.86mm and with history of MI. Regarding the presence of an atherosclerotic plaque in either carotid artery, no significant association was found when the genotypes were assessed on their own. After grouping, though, GG genotype revealed a significant association between carotid plaque formation and atheromatosis. Kaplan-Meier analysis revealed that ALOX12 gene GG genotype predicted all-cause mortality, CV mortality, and CV events. Similarly, when AA and AG genotypes were grouped, Kaplan-Meier analysis showed that patients with GG genotype presented an even more significant higher all-cause mortality, CV mortality, and CV events compared with AA and AG genotypes combined. After adjustment for several traditional risk factors, multivariate Cox proportional hazard analysis showed that patients with the GG genotype had a significant higher risk of all-cause mortality, a threefold increase in CV mortality, and a twofold increased risk for CV events compared to patients with the AA or the AG genotype. ALOX12 rs14309 GG genotype expression was found to be significantly associated with MI, higher cIMT, increased CV events, CV, and overall mortality. This phenomenon could be partially explained by the increased platelet proaggregatory activity of AA products and the control they exert in thrombotic occurrence and plaque formation.

Postmeal triglyceridemia and variability of HbA1c and postmeal glycemia were predictors of annual decline in estimated glomerular filtration rate in type 2 diabetic patients with different stages of nephropathy

BackgroundThis study examined associations of annual glycemic variability and postprandial dysmetabolism with annual decline in estimated glomerular filtration rate (eGFR) in type 2 diabetic patients with different stages of nephropathy.MethodsIntrapersonal mean and coefficient of variation (CV) of HbA1c, fasting and postmeal concentrations of plasma glucose (FPG and PMPG, respectively) and serum triglycerides (FTG and PMTG, respectively) during the first 12 months after enrollment were calculated in a cohort of 168 type 2 diabetic patients: 53 with optimal albumin/creatinine ratio (ACR < 10 mg/g), 62 with high normal ACR (10–29 mg/g) and 53 with elevated ACR (≧30 mg/g). Annual changes in eGFR were computed using 52 (median) creatinine measurements obtained over a median follow-up of 6.0 years. Multivariate linear regressions assessed the independent correlates of changes in eGFR.ResultsKidney function declined faster in patients with high normal and elevated ACR (−1.47 and −2.01 ml/min/1.73 m2/year, respectively) compared to patients with optimal ACR (0.08 ml/min/1.73 m2/year, p < 0.05). In patients with high normal ACR, age (standardized β、-0.30、p = 0.01), CV-HbA1c (standardized β、-0.66、p < 0.001) and CV-PMPG (standardized β、-0.27、p = 0.01) was associated with annual eGFR decline independently of mean HbA1c and PMPG, sex, BMI, waist circumference, diabetes duration and therapy, means and CVs of FPG and systolic blood pressure, baseline eGFR, log ACR and uses of anti-hypertensive medications (R2 = 0.47). In patients with elevated ACR, PMTG (standardized β、-0.408, p = 0.007) was associated with annual eGFR decline (R2 = 0.15).ConclusionsConsistency of glycemic control and management of postprandial glycemia and lipidemia are important to preserve kidney function in type 2 diabetic patients.

Uric acid in Type 2 Diabetes mellitus with nephropathy

Introduction: Uric acid is an important antioxidant that contributes for around 60% of free radical scavenging capacity of serum. Its role has been controversial in type 2 diabetes mellitus. Earlier studies have reported that renal disease leads to elevation of uric acid in DM, but recently high uric acid levels are reported to be risk factor for the development of diabetes mellitus. Aim of our study is to compare uric acid in type 2 DM with renal disease with non-diabetics and also to compare its levels among patients in different stages of diabetic nephropathy. Methodology: The case control study was conducted in medical college hospital in coastal Karnataka. Data of serum uric acid, renal profile and demographic profiles of 89 type 2 diabetes mellitus patients was collected from the clinical biochemistry laboratory in the year 2016. Data of 80 non-diabetic controls was taken. Transasia XL-640 was used for the estimation.Estimated GFR (eGFR) was calculated using MDRD formula. Results: We found an elevation in uric acid and creatinine levels, extremely significantly lower eGFR in diabetics (P = 0.0195, P=0.0078 and P =0.0001respectively).Odd’s ratio was 3.128 between uric acid and diabetic nephropathy. A highly significant (P < 0.0016) differences was observed in uric acid levels among patients of different stages of diabetic nephropathy. Conclusion: Hyperuricemia was found in diabetic nephropathy patients. There was a significant difference in uric acid was observed among different stages of nephropathy. However causal relationship is inclusive. Prospective studies need to be designed with a serial monitoring of uric acid, GFR and microalbunuria in diabetics till the development of nephropathy to establish which the cause is and which is effect among these two factors (uric acid and diabetic nephropathy. Keywords: Uric acid, eGFR, Diabetes mellitus, Nephropathy

Different Lipid Variables Predict Incident Coronary Artery Disease in Patients With Type 1 Diabetes With or Without Diabetic Nephropathy: The FinnDiane Study

To study the ability of lipid variables to predict incident coronary artery disease (CAD) events in patients with type 1 diabetes at different stages of nephropathy. Patients (n = 3,520) with type 1 diabetes and available lipid profiles participating in the Finnish Diabetic Nephropathy Study (FinnDiane) were included in the study. During a follow-up period of 10.2 years (8.6-12.0), 310 patients suffered an incident CAD event. Apolipoprotein B (ApoB)/ApoA-I ratio was the strongest predictor of CAD in normoalbuminuric patients (hazard ratio 1.43 [95% CI 1.17-1.76] per one SD increase), and ApoB was the strongest in macroalbuminuric patients (1.47 [1.19-1.81]). Similar results were seen when patients were stratified by sex or glycemic control. LDL cholesterol was a poor predictor of CAD in women, normoalbuminuric patients, and patients with HbA1c below the median (8.3%, 67 mmol/L). The current recommended triglyceride cutoff of 1.7 mmol/L failed to predict CAD in normoalbuminuric patients, whereas the cohort median 0.94 mmol/L predicted incident CAD events. In patients with type 1 diabetes, the predictive ability of the lipid variables differed substantially depending on the patient's sex, renal status, and glycemic control. In normoalbuminuric patients, the ratios of atherogenic and antiatherogenic lipoproteins and lipids were the strongest predictors of an incident CAD event, whereas in macroalbuminuric patients, no added benefit was gained from the ratios. Current treatment recommendations may need to be revised to capture residual CAD risk in patients with type 1 diabetes.

Serum osteoprotegerin and tumor necrosis factor related apoptosis inducing-ligand (TRAIL) are elevated in type 2 diabetic patients with albuminuria and serum osteoprotegerin is independently associated with the severity of diabetic nephropathy

Osteoprotegerin (OPG) and tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) have recently been reported to be associated with diabetic nephropathy in an in vitro study. However, the literature regarding serum OPG and TRAIL in type 2 diabetes mellitus patients is scarce. To investigate the role of OPG/TRAIL in diabetic nephropathy, we measured the serum concentrations of OPG and TRAIL in type 2 diabetes mellitus patients with different stages of nephropathy by enzyme-linked immunosorbent assay. One hundred seventy-nine subjects with type 2 diabetes mellitus were studied and stratified according to urinary microalbumin and serum creatinine measurements. The serum concentrations of OPG and TRAIL were significantly elevated in patients with microalbuminuria (OPG, 2154.2 ± 922.1 pg/mL; TRAIL, 80.2 ± 24.1 pg/mL) and macroalbuminuria (OPG, 2251.5 ± 925.7 pg/mL; TRAIL, 88.1 ± 23.8 pg/mL) as compared with patients with normoalbuminuria (OPG, 1690.1 ± 627.2 pg/mL; TRAIL, 70.7 ± 23.3 pg/mL). Serum OPG and TRAIL levels were increased in parallel and were significantly associated with each other. Using multivariate stepwise regression analysis, serum OPG was found to be an independent factor associated with the severity of diabetic nephropathy. Our results suggested that serum OPG may be a marker for the severity of diabetic nephropathy. Further studies are necessary to investigate the role of elevated serum OPG in the pathogenesis of diabetic nephropathy.

The ratio between kidney volume and function increases with the progression of nephropathy in Type 2 diabetes

In Type 2 diabetes, it is not clear if renal size is constantly related to the glomerular filtration rate. In addition, it is not known if kidney volume (KV) is associated with an increased urinary albumin and IgG excretion. The relationship between kidney volume, creatinine clearance (CrCl), urinary albumin and IgG excretion in 95 Type 2 diabetic patients with different stages of nephropathy (1 - 4 Stage sec NKDF-QD) was elevated and compared to 85 non-diabetic subjects with similar degree of kidney function. In Type 2 diabetic patients the KV/CrCl ratio was increased, in comparison with the control subjects, from about 15% in Stage 1 to 53% in Stage 4. In T2D subjects, significant correlations were found between KV and urinary albumin excretion (r = 0.665, p < 0.05), and between KV and urinary IgG excretion (r = 0.800, p < 0.001). The present study finds that Type 2 diabetic subjects, are characterized by an increased ratio between KV/CrCl, throughout the different progressive stages of nephropathy. In Type 2 diabetes relationships between KV and urinary albumin and between KV and IgG excretion also were found to be significant, suggesting a role for the impaired size selectivity of proteinuria as a possible determinant of KV.

Renal excretion of insulin-like growth factor 1 and vascular endothelial growth factor in patients with type 1 diabetes with nephropathy

Thе aim of the investigation was to study the urinary excretion of insulin-like growth factor 1 (ICF-1) and vascular endothelial growth factor (VEGF) at different stages of nephropathy in 57 patients with type 1 diabetes, including 22 patients with normal albuminuria, 23 with microalbuminuria, and 12 with proteinuria. The excretion of IGF-1 and VEGF was increased in the microalbu-minuric and proteinuric patients as compared with the controls (1GF-1: p = 0.004 and p = 0.00005; VEGF: p = 0.06 and p = 0.02). That of growth factors inversely correlated with glomerular filtration rates and hemoglobin levels (IGF-1: r = -0.43 and r = -0.41; VEGF: r = -0.14 and r - -0.27). In the normo- and microalbuminuric patients, IGF-1 excretion was associated with the thickness of glomerular and tubular basement membranes (r = 0.59 and r = 0.53, respectively) and with the number of podocytic foot processes (r = -0.69). VEGF correlated with the volume of the mesangium (r = 0.69) and the thickness of the glomerular basement membrane (r = 0.53). IGF-1 rather than VEGF positively correlated with HbA1c (r = 0.47 and r = 0.02). It has been concluded that in patients with type I diabetes, the increased urinary excretion of IGF-1 and VEGF is associated with the development of nephropathy and may be used for the early diagnosis of this complication.

Serum Lipids and the Progression of Nephropathy in Type 1 Diabetes

Dyslipidemia contributes to the progression of microvascular disease in diabetes. However, different lipid variables may be important at different stages of nephropathy. This study examines the pattern of dyslipidemia associated with the progression of nephropathy in patients with type 1 diabetes. A total of 152 patients with type 1 diabetes were recruited in order to represent various phases of nephropathy. Patients were followed for 8-9 years, during which time they received standard care. Renal progression was defined a priori as a doubling in albumin excretion (in patients with normo- or microalbuminuria) or a decline in creatinine clearance (in those with macroalbuminuria). A panel of lipid variables was determined and correlated with indexes of progression. In patients with normoalbuminuria (n = 66), progression was associated with male sex (P < 0.05), borderline albuminuria (P = 0.02), and LDL-free cholesterol (P = 0.02). In patients with microalbuminuria (n = 51), progression was independently associated with triglyceride content of VLDL and intermediate-density lipoprotein (both P < 0.05). In patients with macroalbuminuria (n = 36), a significant decline in the renal function (>3 ml x min(-1) x year(-1)) was independently associated with poor glycemic control, hypertension, and LDL size (P < 0.05). When all patients with progressive nephropathy were analyzed together, only LDL cholesterol was predictive on multivariate analysis (P < 0.05), which masked the importance of triglyceride enrichment in microalbuminuria. Lipid variables are associated with progression of diabetic kidney disease, but the relationship is not the same at all stages. This finding has implications for the design of renoprotective strategies and the interpretation of clinical trials in type 1 diabetes.

Lessons Learned from Recent Hypertension Trials about Kidney Disease

This article reviews BP trials with primary or secondary cardiovascular (CV) or renal end points. It focuses on how results of recent trials have influenced guidelines and clinical practice with specific reference to two issues: ( 1 ) Achievement of goal BP in patients with chronic kidney disease and ( 2 ) emerging data on the importance of decreasing proteinuria to prevent CV events and slow kidney disease progression. Each study is evaluated on its strengths and weaknesses as well as extrapolation of findings to the general population. The tenants of this article are that the baseline level of proteinuria and the magnitude of proteinuria reduction are important determinants of renal outcome in addition to lowering BP and should be consider in all future trials. Second, comparing trials of people with different stages of nephropathy and unknown or differing levels of proteinuria is limited in generalizing the CV or renal outcome to a more global population. As a preamble to this article, two observations are noteworthy: First, use of antihypertensive therapy in those with stage 3 nephropathy, i.e. , GFR of <60 ml/min, will not slow the rate of decline in kidney function to the same extent as in patients with normal kidney function (stage 1). Studies to address the aforementioned questions will not be performed, however, because of low event rates, relatively higher numbers of participants, and longer duration of follow-up, hence, higher cost than currently completed studies. Thus, we are faced with extrapolating from studies to clinical practice that may not be very appropriate. Second, observations from a number of clinical studies suggest that both risk for kidney disease progression as well as CV events may be inversely related to the level of kidney function and directly related to the amount of proteinuria (macroalbuminuria), defined as >300 mg/d of protein (1– …

Urinary adiponectin excretion is increased in patients with overt diabetic nephropathy

Adiponectin, a novel adipose-derived adipocytokine, has beneficial effects not only on improvement of insulin sensitivity but also on mitigation of vascular damage. To evaluate whether adiponectin is implicated in the pathogenesis of diabetic nephropathy characterized by microvascular damage, we examined urinary and serum adiponectin levels in type 2 diabetic patients with different stages of nephropathy. We first confirmed adiponectin is excreted into urine through Western blot analysis, followed by measurements of urinary and serum adiponectin levels by radioimmunoassay. Interestingly, urinary adiponectin excretion levels were markedly increased in patient group with overt nephropathy relative to the groups without nephropathy and with incipient nephropathy. Surprisingly, serum adiponectin levels were also elevated in patient group with overt nephropathy. Increased urinary adiponectin excretion may result from elevations in circulating adiponectin levels and enhanced filtration of circulating adiponectin through the damaged kidney. Furthermore, adiponectin synthesis in adipose tissue and its secretion into circulating blood may be enhanced to mitigate microvascular damage in the advanced stage of diabetic nephropathy.

The spectrum of circadian blood pressure changes in type I diabetic patients.

The objective of the present study was to characterize the spectrum of circadian blood pressure changes in type I diabetes at different stages of nephropathy by using two monitorings in each patient in order to avoid intra-individual variability. A total of 80 type I diabetic subjects and the same number of age, sex and awake mean blood pressure (BP)-matched controls were included. According to urinary albumin excretion, there were 57 normoalbuminurics, 15 persistent microalbuminurics and eight proteinurics. Two 24 h ambulatory blood pressure monitorings were performed at the same urinary albumin excretion stage in absence of antihypertensive treatment for each diabetic subject and for their respective control. Blood pressure and heart rate averages during 24 h, awake, sleep, and day: night ratio were calculated. Seven of the eight proteinuric subjects were hypertensives, whereas hypertension was absent in the normoalbuminuric and microalbuminuric groups. The intraindividual reproducibility in diabetics showed repeatability coefficients for the 24 h systolic and diastolic pressure of 33 and 42%, respectively. This reproducibility for the day: night ratio was generally worse, 57% for systolic and 59% for diastolic. A progressive increment in the mean ambulatory BP was observed across the three groups of diabetics and the differences in BP observed were most evident during the night-time period. Though no differences in the 24 h circadian pattern were present between the normoalbuminurics and their controls, nocturnal differences were observed, not only in microalbuminurics for systolic BP (P < 0.05), but also in proteinurics for both systolic BP (P < 0.01) as well as diastolic BP (P < 0.05). No differences were observed in heart rate among the diabetic groups. The non-dipping pattern in the two monitorings was observed in 80, 58, 18 and 10% of the proteinurics, microalbuminurics, normoalbuminurics and control groups, respectively. Persistent abnormal circadian variability seems to be an early and frequent characteristic of type I diabetics with an increased urinary albumin excretion. Although present in some normalbuminuric subjects, the frequency of this abnormality increases as the incipient nephropathy progresses. By the time proteinuria is established, nearly all subjects present the abnormal pattern.

Urinary Copper Excretion in Type 2 Diabetic Patients with Nephropathy

Background/Aims: The aim of this study was to examine the relationship between the degree of urinary copper excretion and stages of diabetic nephropathy. Methods: Copper, ceruloplasmin and albumin concentrations were measured in serum and urine samples from 41 type 2 diabetic outpatients with different stages of nephropathy and from 10 healthy controls. The copper/albumin and copper/ceruloplasmin ratios in serum and urine were determined. Furthermore, we examined whether free copper ions are dissociated from ceruloplasmin under various pH conditions. Results: Urinary copper concentrations significantly increased only in macroalbuminuric patients. The copper/ceruloplasmin and copper/albumin ratios in urine were consistently greater than those in serum which were not different between patients and healthy controls except the copper/albumin ratio in macroalbuminuric patients. The ratios in urine decreased in parallel with the progression of nephropathy. Copper was found to be released from ceruloplasmin under acidic conditions. Conclusion: Urinary copper excretion in healthy controls may be the result of dissociation from the albumin-copper complex of serum during its passage through the kidney. In diabetic patients with advanced nephropathy, urinary copper excretion may be due to dissociations from both copper-albumin and ceruloplasmin-copper complexes filtered through the damaged glomerulus. Overloading of urinary copper to damaged renal tubules may play some roles in the progression of nephropathy in patients with advanced nephropathy.