Different Levels Of Albuminuria Research Articles

Misexpression of LINC01410, FOSL1, and MAFB in peripheral blood mononuclear cells associated with diabetic nephropathy

AimsCurrently, diabetic nephropathy (DN) is considered the leading cause of the end-stage renal disease (ESRD). However, its specific molecular mechanism is still unclear, and there is still a lack of effective diagnostic and therapeutic methods. MethodA pathway was assumed after bioinformatics analysis of GEO datasets related to individuals with various levels of DN, LINC01410, MAFB, and FOSL1. Then, 46 patients with type 2 diabetes (T2DM) and different levels of albuminuria, and 12 individuals without diabetes, were selected. qPCR was performed to evaluate gene expression. One-way ANOVA followed by Tukey’s -and linear trend tests were performed to analyze gene expression in different stages of the disease. Moreover, receiver operating characteristic (ROC) curves and the correlation between LINC01410, FOSL1, and MAFB were analyzed. ResultsLINC01410, MAFB, and FOSL1 were selected based on bioinformatics analyses. The qPCR results showed that the expression of LINC01410 decreased, and FOSL1 and MAFB increased in micro-and macroalbuminuria groups compared to normoalbuminuria groups (P < 0.05). ROC curves demonstrated a significant diagnostic accuracy of LINC01410, MAFB, and FOSL1 between DN and participants with normoalbuminuria (P < 0.05). Pearson’s correlation analysis revealed a positive association between the expressions of FOSL1 and MAFB (p = 0.01, r = 0.39). However, there was no correlation between LINC01410 with MAFB and FOSL1 (p = 0.23 and p = 0.21, respectively). ConclusionDysregulation of LINC01410, MAFB, and FOSL1 is related to DN. These results may provide new insights into the role of LINC01410, MAFB, and FOSL1 as potential biomarkers in DN.

Markers of kidney injury, lipid metabolism, and carbonyl stress in patients with type 1 diabetes and different levels of albuminuria

The aim of this work was to study the levels of podocalyxin and β-2-microglobulin and parameters of lipid metabolism and carbonyl stress in type 1 diabetes mellitus (T1DM) patients with different levels of albuminuria.Materials and methods. 56 men of reproductive age with T1DM were divided into two groups: 24 patients with stage A1 albuminuria (group A1) and 32 patients with stage A2 albuminuria (group A2). The control group consisted of 28 healthy men. The levels of renal function markers, lipid metabolism parameters, and methylglyoxal were assessed using enzyme immunoassay and spectrophotometric and fluorometric methods.Results. Higher values for total cholesterol, triacylglycerol, and very-low-density lipoprotein medians in both groups A1 and A2 were found. In these groups, increased podocalyxin and methylglyoxal medians were revealed. Correlation analysis in the group A1 showed the presence of a relationship between the glomerular filtration rate (GFR) and creatinine. In the group A2, correlations between the generally accepted parameters of kidney injury (the albumin / creatinine ratio and GFR) and the duration of the disease and between GFR and the creatinine and methylglyoxal levels in the blood were identified. The podocalyxin level in this group correlated with the β2- microglobulin and methylglyoxal levels and lipid metabolism parameters. The level of β2-microglobulin correlated with the lipid metabolism parameters.Conclusion. Regardless of the level of albuminuria, men with T1DM had significantly increased levels of podocalyxin, lipid metabolism parameters, and methylglyoxal, as well as strong relationships between these parameters. The data of this study can be used for development of potential strategies for prevention and early treatment of diabetic nephropathy.

Markers of oxidative damage lipids and DNA in men with type 1 diabetes mellitus and different levels of albuminuria

BACKGROUND : Diabetic nephropathy is a specific kidney damage that affects up to 40% of type 1 diabetes mellitus patients. There is still insufficient knowledge about oxidative stress at the different levels of albuminuria. AIM : To assess the indicators of oxidative damage to lipids, DNA and antioxidant defense in men with type 1 diabetes mellitus and albuminuria different levels. MATERIALS AND METHODS: The study was conducted during 2018–2019. The main group included 56 men of reproductive age with type 1 diabetes mellitus (T1DM) divided into 2 groups: 24 patients with albuminuria level A1 (group A1) and 32 patients with albuminuria level A2 (group A2). The control group consisted of 28 healthy men. The oxidative stress indicators content, as well as the activity of antioxidant defense system various links was evaluated. Spectrophotometric, fluorimetric and enzyme immunoassay methods were used. RESULTS : In patients of the A1 group there were higher values of the median of primary — conjugated dienes, secondary — ketodienes and conjugated trienes, final — Schiff bases products and 8-hydroxy-2 ’ -deoxyguanosine in comparison with the control. Similar changes in patients of the A2 group were found. Intergroup differences related to increased median values of TBARs and 8-hydroxy-2 ’ -deoxyguanosine in patients of the A2 group compared with A1 group. The activity of the antioxidant defense system in A1 group relative to the control by increased values of the glutathione peroxidase, reduced glutathione, oxidized glutathione median, and retinol was characterized. A2 group had higher values of glutathione peroxidase, reduced glutathione and oxidized glutathione medians in comparison with controls. Correlation analysis in A1 group showed the relationships between the duration of the disease and the products of lipid peroxidation, glycated hemoglobin with 8-hydroxy-2 ’ -deoxyguanosine. In A2 group, there was a relationship between the albumin/creatinine ratio and the duration of the disease, glomerular filtration rate and creatinine level. CONCLUSION : In men with T1DM, regardless of the albuminuria level, there are higher values of the oxidative damage lipids and DNA parameters, as well as the presence of close relationships between these parameters and the duration of the disease, which can be used to develop potential strategies for the prevention and early therapy of diabetic nephropathy.

Frequency and Correlation of Serum Uric Acid to Different Stages of Albuminuria in Type II Diabetic Nephropathy

Background: Albuminuria is considered the gold standard of onset and progression of diabetic nephropathy (DN). Higher levels of serum insulin may decrease uric acid clearance by the kidneys leading to hyperuricemia, which has injurious effect on kidneys. Objective: To evaluate the frequency and relationship of uric acid to different levels of albuminuria in type II diabetes mellitus. Patients and Method: This cohort study included 56 T2DM patients classified according to stages of DN into: Group I that including 12 patients with normoalbuminuria, group II included 26 patients with microalbuminuria, and group III including 18 patients with macroalbuminuria. All of them were evaluated for serum creatinine and albumin, CBC, ACR, UAE, HbA1c, ESR, Serum TSH and serum uric acid (SUA). Results: Hyperurecemia frequency was (62.5%) and it had highly statistical significant difference with albuminuria in the three studied groups. There was strong significant positive correlation of SUA with UAE (p < 0.014), Cr (p < 0.037), ACR (p < 0.006), HbA1c (p < 0.017) in macroalbuminuria and UAE (p < 0.042) and ACR (p < 0.043) in microalbuminuria group, and TLC (p < 0.024) in normoalbuminuria group. While there was a significant negative correlation between UA with albumin (p < 0.029) in macroalbuminuria group. Conclusions: Hyperinsulinemia and chronic inflammation associated with type IIDM leads to hyperuricemia, which had high frequency in our study (62.5%) and carry a hazardous effect on kidney function contributing to progressive increase of albuminuria. So we must search for management of elevated UA in these patients to delay onset & progression of its morbidity.

Role of Retinol-binding Protein 4 as an Early Biomarker for Diabetic Nephropathy in Type 2 Diabetic Patients

Assess the relationship and diagnostic performance of retinol-binding protein 4 (RBP-4) as a biomarker ofdiabetic nephropathy (DN) at different levels of albuminuria (normo-, micro- and macro-albuminuria). Acase-control study, that involved 185 participants, 47 were healthy control, and 138 diabetic patients (46were normoalbuminuric patients [NA], 48 patients were microalbuminuria [MiA], and 44 patients weremacroalbuminuria [MaA]). All diabetic patients were treated with antidiabetic medication (metformin and/or oral sulfonylureas), all the participants were interviewed by the researcher, and full medical (history ofliver, kidney, lung, and other diseases), and sociodemographic data taken from them and recorded in thequestionnaire. In the present study, RBP-4 was 14.08±1.82 ng/ml in the control group, 15.98±3.74 ng/mlin the normoalbuminuria (NA) group, 30.38±6.02 ng/ml in the micro-albuminuria (MiA), and 41.01±5.78ng/ml for macro-albuminuria (MaA), there was a significant difference between all their groups comparedto control (p-value &lt;0.001), and between each other (p-value &lt;0.001) except that no significant differencefound between control and normoalbuminuria. In conclusion, RBP4 is an excellent predictor of bothmicroalbuminuria and microalbuminuria, there was an inverse relationship between RBP4 with GFR, whichindicate it is a good predictor for the progression of diabetic kidney impairment.

Features of biochemical parameters in healthy and patients with type 1 diabetes mellitus with different levels of albumin in the urine

The use of multi-label biochemical panels is justified by the fact that different markers reflect the severity of various pathological processes (disorders of carbohydrate and fat metabolism), which in their interaction are indicators of decompensation of a single pathology – diabetes in particular. The aim of the work was to study the differences in biochemical parameters in healthy and patients with type 1 diabetes mellitus (T1D) depending on the level of albumin in the urine. 78 men and 62 women aged 22-26 years, patients with diabetes mellitus type 1, who were hospitalized in the therapeutic department в № 1 and № 2 of Vinnytsia Regional Highly Specialized Endocrinology Center and 8 practically healthy men and 13 practically healthy women of the same age were examined. The level of microalbuminuria was determined in all patients by enzyme-linked immunosorbent assay. Fasting blood glucose and 2 hours after a meal were determined by enzymatic, amperometric analysis on a biochemical analyzer Biosen C_Line, manufactured by EKF Diagnostic (Germany). The average value of blood glucose was calculated mathematically. To determine glycated hemoglobin (HbA1c), we used the method of high performance liquid chromatography on a D 10 analyzer, manufactured by Bio-Rad (USA). The International Normal Ratio (INR) was determined using a set of reagents to determine the prothrombin time, prothrombin ratio and international sensitivity index, which is specified in the passport to the set (manufacturer of PC-K-TEST "Granum"). Total cholesterol and triglycerides were determined by colorimetric photometric method (using enzymes) on a biochemical analyzer using standard kits from Olympus AU480 (USA). Statistical processing of the results was performed in the license package "Statistica 5.5", using non-parametric evaluation methods. When comparing the level of biochemical parameters between patients with T1D and normo-, microalbuminuria and proteinuria with healthy men or women, patients found higher values: fasting glucose (in men – by 29.1 %, 30.9 % and 42.0 %; in women – by 29.7 %, 33.2 % and 46.0 %); glucose 2 hours after exercise (for men – by 27.4 %, 30.8 % and 36.1 %; for women – by 30.4 %, 32.4 % and 40.2 %); the average value of glucose (for men – by 26.2 %, 30.8 % and 39.3 %; for women – by 28.7 %, 34.0 % and 43.1 %); glycated hemoglobin (47.8 %, 48.8 % and 45.8 % for men; 27.2 %, 50.2 % and 54.4 % for women). Also, in patients with T1D men and proteinuria and women with normoalbuminuria and proteinuria compared with healthy men or women found higher cholesterol values (17.8 % in men and 7.6 % and 26.0 % in women); and in patients with T1D men with proteinuria compared to healthy men – 31.3 % higher triglyceride levels. When comparing the level of biochemical parameters between patients with T1D in men or women with proteinuria, higher values were found: fasting glucose compared with men with normoalbuminuria by 22.2 % and with women with normoalbuminuria by 30.3 % and microalbuminuria by 23.7 %; the average value of glucose compared with men with normoalbuminuria by 20.8 % and microalbuminuria by 14.0 %; glycated hemoglobin compared to women with normoalbuminuria by 15.9 %; compared with men with normoalbuminuria and microalbuminuria – by 24.8 % and 20.3 %, or with women with normoalbuminuria and microalbuminuria – by 24.9 % and 28.0 %; triglycerides compared with men with normoalbuminuria by 23.0 %. When comparing the sex differences in the level of biochemical parameters between healthy or between patients with T1D and normo-, microalbuminuria and proteinuria in men and women, only higher values of glycated hemoglobin by 14.1 % in women with proteinuria and total cholesterol by 8.3 % in women with normoalbuminuria were found. Thus, between healthy and patients with T1D and different levels of albuminuria there are differences in biochemical parameters, and they are greater the higher the level of albumin in the urine.

Gut microbiota profile and selected plasma metabolites in type 1 diabetes without and with stratification by albuminuria.

Abnormal gut microbiota and blood metabolome profiles have been reported both in children and adults with uncomplicated type 1 diabetes as well as in adults with type 1 diabetes and advanced stages of diabetic nephropathy. In this study we aimed to investigate the gut microbiota and a panel of targeted plasma metabolites in individuals with type 1 diabetes of long duration without and with different levels of albuminuria. In a cross-sectional study we included 161 individuals with type 1 diabetes and 50 healthy control individuals. Individuals with type 1 diabetes were categorised into three groups according to historically measured albuminuria: (1) normoalbuminuria (<3.39mg/mmol); (2) microalbuminuria (3.39-33.79mg/mmol); and (3) macroalbuminuria (≥33.90mg/mmol). From faecal samples, the gut microbiota composition at genus level was characterised by 16S rRNA gene amplicon sequencing and in plasma a targeted profile of 31 metabolites was analysed with ultra HPLC coupled to MS/MS. Study participants were aged 60 ± 11years (mean ± SD) and 42% were women. The individuals with type 1 diabetes had had diabetes for a mean of 42 ± 15years and had an eGFR of 75 ± 25mlmin-1 (1.73m)-2. Measures of the gut microbial beta diversity differed significantly between healthy controls and individuals with type 1 diabetes, either with micro- or macroalbuminuria. Taxonomic analyses showed that 79 of 324 genera differed in relative abundance between individuals with type 1 diabetes and healthy controls and ten genera differed significantly among the three albuminuria groups with type 1 diabetes. For the measured plasma metabolites, 11 of 31 metabolites differed significantly between individuals with type 1 diabetes and healthy controls. When individuals with type 1 diabetes were stratified by the level of albuminuria, individuals with macroalbuminuria had higher plasma concentrations of indoxyl sulphate and L-citrulline than those with normo- or microalbuminuria and higher plasma levels of homocitrulline and L-kynurenine compared with individuals with normoalbuminuria. Whereas plasma concentrations of tryptophan were lower in individuals with macroalbuminuria compared with those with normoalbuminuria. We demonstrate that individuals with type 1 diabetes of long duration are characterised by aberrant profiles of gut microbiota and plasma metabolites. Moreover, individuals with type 1 diabetes with initial stages of diabetic nephropathy show different gut microbiota and plasma metabolite profiles depending on the level of albuminuria. Graphical abstract.

Differential metabolic profile associated with the condition of normoalbuminuria in the hypertensive population

Background and aimAlbuminuria is an indicator of sub-clinical organ damage and a marker of cardiovascular risk and renal disease. A percentage of hypertensive patients develop albuminuria despite being under chronic suppression of the renin-angiotensin system (RAS). We previously identified urinary metabolites associated with the development of albuminuria. In this study, we searched for metabolic alterations which reflect different levels within the condition of normoalbuminuria. Patients, materials and methodsUrine from 48 hypertensive patients under chronic RAS suppression was analyzed. They were classified according to the albumin / creatinine ratio (ACR) into 3 groups: Normoalbuminuria (<10 mg / g); Normal-high (10–30 mg / g in men, or 20−40 mg / g in women); and moderately high albuminuria (microalbuminuria, 30−200 mg / g or 40−300 mg / g, respectively). The metabolome was analyzed by mass spectrometry and a correlation analysis was performed between altered metabolite levels and ACR. ResultsOxaloacetate, 3-ureidopropionate, guanidoacetate and malate show significant variation between the normo and micro groups. Additionally, these metabolites are able to differentiate between patients in the normo and high-normal range. A significant correlation between metabolites and ACR was found. Observed variations point to alterations in the energy metabolism already in patients with albuminuria in the high-normal range. ConclusionsThe association between the molecular panel consisting of 3-ureidopropionate, oxaloacetate, malate and guanidoacetate and different levels of albuminuria is confirmed. A metabolic fingerprint was also identified showing variations within the condition of normoalbuminuria allowing an earlier molecular stratification of patients.

Perfil metabolómico diferenciador asociado a la condición de normoalbuminuria en la población hipertensa

Background and aimAlbuminuria is an indicator of sub-clinical organ damage and a marker of cardiovascular risk and renal disease. A percentage of hypertensive patients develop albuminuria despite being under chronic suppression of the renin-angiotensin system (RAS). We previously identified urinary metabolites associated with the development of albuminuria. In this study, we searched for metabolic alterations which reflect different levels within the condition of normoalbuminuria. Patients, materials and methodsUrine from 48 hypertensive patients under chronic RAS suppression was analysed. They were classified according to the albumin/creatinine ratio (ACR) into 3groups: Normoalbuminuria (<10mg/g); high-normal (10-30mg/g in men, or 20-40mg/g in women); and moderately high albuminuria (microalbuminuria, 30-200mg/g or 40-300mg/g, respectively). The metabolome was analysed by mass spectrometry and a correlation analysis was performed between altered metabolite levels and ACR. ResultsOxaloacetate, 3-ureidopropionate, guanidoacetate and malate show significant variation between the normo and micro groups. Additionally, these metabolites are able to differentiate between patients in the normo and high-normal range. A significant correlation between metabolites and ACR was found. Observed variations point to alterations in the energy metabolism already in patients with albuminuria in the high-normal range. ConclusionsThe association between the molecular panel consisting of 3-ureidopropionate, oxaloacetate, malate and guanidoacetate and different levels of albuminuria is confirmed. A metabolic fingerprint was also identified showing variations within the condition of normoalbuminuria allowing an earlier molecular stratification of patients.

Effects of SGLT2 Inhibition Treatment on Different Levels of Albuminuria in Patients With Type 2 Diabetes

Effects of SGLT2 Inhibition Treatment on Different Levels of Albuminuria in Patients With Type 2 Diabetes

Effect of Canagliflozin on Renal and Cardiovascular Outcomes across Different Levels of Albuminuria: Data from the CANVAS Program.

If SGLT2 inhibitors protect the kidneys by reducing albuminuria as hypothesized, people with type 2 diabetes mellitus (T2DM) with higher albuminuria should benefit more. We conducted a post-hoc analysis of data from the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, which randomized 10,142 participants with T2DM and high cardiovascular risk to canagliflozin or placebo. We assessed effects of canagliflozin on renal, cardiovascular, and safety outcomes by baseline albuminuria. The trial included 2266 participants (22.3%) with moderately increased albuminuria (urinary albumin/creatinine ratio [UACR] 30-300 mg/g) and 760 (7.5%) with severely increased albuminuria (UACR >300 mg/g) at baseline. Canagliflozin lowered albuminuria with greater proportional reductions in those with moderately and severely increased albuminuria (P heterogeneity<0.001). After week 13, canagliflozin slowed the annual loss of kidney function across albuminuria subgroups, with greater absolute reductions in participants with severely increased albuminuria (placebo-subtracted difference 3.01 ml/min per 1.73 m2 per year; P heterogeneity<0.001). Heterogeneity for the renal composite outcome of 40% reduction in eGFR, ESKD, or renal-related death was driven by lesser effects in participants with moderately increased albuminuria (P heterogeneity=0.03), but no effect modification was observed when albuminuria was fitted as a continuous variable (P heterogeneity=0.94). Cardiovascular and safety outcomes were mostly consistent across albuminuria levels including increased risks for amputation across albuminuria subgroups (P heterogeneity=0.66). Greater absolute risk reductions in the renal composite outcome were observed in participants with severely increased albuminuria (P heterogeneity=0.004). The proportional effects of canagliflozin on renal and cardiovascular outcomes are mostly consistent across patients with different levels of albuminuria, but absolute benefits are greatest among those with severely increased albuminuria.

Association of Retinopathy with Chronic Kidney Disease in Diabetes Mellitus

Background: Diabetic retinopathy (DR) and nephropathy are two major complications of diabetes mellitus carrying significant morbidity and mortality. In this study DR was investigated in different stages of chronic kidney disease (CKD) to find out possible association of these two devastating complications.Methods: This cross-sectional study was conducted in 150 diabetic patients having CKD in BIRDEM. CKD was defined as estimated glomerular filtration rate (eGFR) of &lt;60ml/min/1.73m2and/or urinary albumin excretion rate (UAER) &gt;30 mg/day in at least two occasions in 3 months apart. Retinopathy was assessed by direct fundoscopic examination and confirmed by color fundus photography. Severe DR (SDR) included proliferative diabetic retinopathy, severe non-proliferative DR and maculopathy; whereas microaneurysm regarded as non-severe retinopathy.Results: Majority (68%) of the respondents had some form of retinopathy (38.35% SDR and 29.65% nonsevere). There was strong association between different levels of albuminuria (UAER) and DR (p&lt;0.0001). On the contrary DR did not correspond with stages of CKD (P=0.349). Hypertension (79.5%) and dyslipidaemia (59%) were common co-morbidities.Conclusion: This study concluded that DR prevalence was more in nephropathy along with significant association with UAER. Whereas different stages of CKD was not associated with stages of DR . This finding focused the necessity of regular retinal examination irrespective of the stage of renal involvement.Birdem Med J 2018; 8(3): 210-214

Elevated levels of netrin-1 in the serum of patients with diabetic nephropathy: Relationship with renal function and inflammation

Netrin-1, a survival factor, is highly induced and excreted after renal injury in animal experiments. We aimed to research the relationship between serum netrin-1 and parameters of renal tubule function as well as circulating inflammatory cytokines and to evaluate effect factors for netrin-1 in humans with type 2 diabetes mellitus (T2DM) undergoing different levels of albuminuria. In total, 81 T2DM patients were included and divided into three groups according to their amount of 24-h urine albumin excretion (UAE) after receiving consent. Plasma netrin-1, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were quantified by commercially available enzyme-linked immunosorbent assay kits and the data were analyzed to assess whether serum netrin-1 correlates significantly with disease progression. The results showed that plasma netrin-1 level in patients with macroalbuminuria was significantly higher than that in those with microalbuminuria and normoalbuminuria. Plasma netrin-1 level was significantly associated with UAE, estimated glomerular filtration rate (eGFR), IL-6, and TNF-α independently of age, sex, diabetes duration, and glycosylated hemoglobin (HbA1c). However, no correlation was found between netrin-1 and β2-microglobulin (β2-MG). Our studies may suggest that serum netrin-1 concentrations are increased with diabetic nephropathy progression, particularly in patients with macroalbuminuria, which are associated with renal insufficiency and compensatory responses after inflammation.

Pregnancy Outcomes in Women with Type 1 Diabetes Depending on the Different Modes of Insulin Therapy

The aim of the study was to evaluate the features of the effect of different modes of insulin therapy on pregnancy outcomes in women with type 1 diabetes mellitus (T1DM) with different levels of albuminuria. The study involved 155 women with T1DM during pregnancy, using various modes of insulin, and 42 infants born to women with T1DM. In order to identify a possible relationship between the level of proinflammatory cytokines and growth factors in pregnant women with T1DM and terms of delivery, we measured the daily urinary excretion of IL-1β, MCP-1, and TGF-β1 in 21 women at different trimesters of pregnancy. The use of continuous subcutaneous insulin infusion (CSII) in pregnant women with T1DM allows to prolong the pregnancy for 2–4 weeks as compared to the timing of delivery of pregnant women with T1DM receiving multiple subcutaneous injections of insulin (MPII). Pregnant women with MPII in 100% cases of the presence of microalbuminuria and proteinuria had premature delivery. Elevated levels of proinflammatory cytokines (IL-1β and MCP-1) and TGF-β1 may possibly serve as a predictor of pre-term delivery in pregnant women with diabetes type 1, starting with the early stages of pregnancy. The use of insulin by CSII in pregnant women with T1DM reduces the percentage of pre-term deliveries, regardless of the stage of diabetic nephropathy. It improves the condition of infants born at term in women with T1DM using a therapy with insulin pumps compared to that with MPII such as less common manifestation of diabetic fetopathy as macrosomia and hypoglycemia at birth, reducing the need for resuscitation in newborns.

RNA oxidation and albuminuria in type 1 diabetes patients

We examined the relationship between urinary excretion of the RNA oxidation marker 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and kidney injury comparing type 1 diabetes patients with different levels of albuminuria (normoalbuminuria: N=58, microalbuminuria: N=46, macroalbuminuria: N=46) and a nondiabetic control group (N=57). Urinary 8-oxoGuo was measured in spot urine samples using ultraperformance liquid chromatography and tandem mass spectrometry. Urinary 8-oxoGuo was significantly higher in the patients [2.85 (2.45–3.33) vs. 2.49 (2.12–2.96) nmol/mmol creatinine, P=0.01]. However, after adjustment for possible confounders of oxidative stress, the differences reduced slightly and became statistically nonsignificant (P=0.07). There were no significant differences in the level of 8-oxoGuo between the three groups of patients (P=0.53) and there were no significant associations between 8-oxoGuo and estimated glomerular filtration rate or albumin–creatinine ratio. In conclusion, urinary excretion of the RNA oxidation marker 8-oxoGuo does not differ between type 1 diabetes patients with different levels of albuminuria.

YKL‐40 in type 2 diabetic patients with different levels of albuminuria

Type 2 diabetic patients with albuminuria have an increased risk for vascular complications. Albuminuria is related to endothelial dysfunction and plaque instability. YKL-40 is also associated with both and elevated in nondiabetic vascular patients. We investigated YKL-40 and its association with vascular disease in type 2 diabetic patients with albuminuria. Two hundred and four patients with type 2 diabetes were included in a cross-sectional study: One hundred and six normo- (No-A), 64 micro- (Mi-A) and 34 macroalbuminuric (Ma-A) patients that did not differ for age, diabetes duration, HbA1c, body-mass-index, blood pressure, lipids and creatinine. YKL-40 was measured in serum samples and determined by ELISA. YKL-40 was significantly different in No-A: 87±57 vs. Mi-A 119±68 vs. Ma-A 157±75ng mL(-1) ; P<0·001. Patients with macrovascular disease showed higher YKL-40 than those without: 115±72 vs. 87±49ng mL(-1) , P=0·003. In correlation analysis, YKL-40 was associated with urinary albumin excretion rate (AER), plasma creatinine, creatinine clearance (CC) and age. Two multivariate regression analyses were conducted: in the first one, AER and CC remained associated with YKL-40 and in the second one AER and age. This is the first report of a significant elevation of YKL-40 in type 2 diabetic patients with albuminuria. In addition, we observed a significant association with macrovascular disease. Because we detected an association between YKL-40 with renal, micro- and macrovascular disease, this protein could play an important for the increased risk of type 2 diabetic patients with albuminuria for the development of cardiovascular disease.

Neutrophil Gelatinase‐Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM1) in patients with diabetic nephropathy: a cross‐sectional study and the effects of lisinopril

Our aim was to evaluate the markers of tubulointerstitial damage, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule1 (KIM1) in Type 1 diabetic patients with different levels of albuminuria and in control subjects. In addition, the effect of renoprotective treatment on urinary NGAL was evaluated in diabetic nephropathy. This was a cross-sectional study in 58 normoalbuminuric (u-albumin <30 mg/24 h), 45 microalbuminuric (30-300 mg/24 h) and 45 macroalbuminuric (>300 mg/24 h) Type 1 diabetic patients and 55 non-diabetic control subjects. Furthermore, in a second study, urine-NGAL was measured in a randomized cross-over study of 56 Type 1 diabetic patients with diabetic nephropathy treated with lisinopril 20, 40 and 60 mg daily. Urine-NGAL levels were [geometric mean (95% CI)]: control subjects 74 (52-104) (pg/mmol creatinine), normoalbuminuric 146 (97-221), microalbuminuric 222 (158-312) and macroalbuminuric group 261 (175-390). Urine-NGAL increased significantly from the normo- to the micro- and further to the macroalbuminuric group (P<0.05). Urine-NGAL was higher in normoalbuminuric vs. control subjects (P<0.01). Plasma-NGAL was significantly higher in the normoalbuminuric and macroalbuminuric groups than in the control group. Urine-KIM1 was higher in all diabetic groups than in the control group (P<0.001), with no difference between diabetic groups. During lisinopril treatment, urine-NGAL was reduced (95% CI) 17% (11-50) (not significant). Urine-NGAL and urine-KIM1 (u-KIM1) are elevated in Type1 diabetic patients, with or without albuminuria, indicating tubular damage at an early stage. Urine-NGAL increases significantly with increasing albuminuria. The ACE inhibitor lisinopril reduced urine-NGAL, but this was not statistically significant.

Serum Cystatin C Is a Better Marker for Renal Function Than Serum Creatinine in Children with Sickle Cell Disease.

High serum creatinine is a late manifestation for patients (pts) with sickle cell disease (SCD) who develop severe renal dysfunction, because creatinine is secreted by the renal tubules. Serum cystatin C is a cysteine proteinase inhibitor, that is produced by all nucleated cells in the body, does not undergo tubular secretion, and reflects glomerular filtration rate (GFR)accurately. Normal levels for serum cystatin C are 0.5–1.3 mg/L for children 1–17 years, and 0.5–1 mg/L for adults. The purpose of this study was to compare serum cystatin C and serum creatinine as markers of GFR in children with SCD with different levels of albuminuria. Twenty pts (mean age 16.4, range 9–21 years) had serum creatinine, serum cystatin, and 24-hour urine for creatinine clearance. Pts with normoalbuminuria (N=11) had mean serum creatinine of 0.55±0.14 mg/L, creatinine clearance of 168±36 ml/min/1.73m2, normal serum cystatin C 0.78±0.16 mg/L, and normal estimated GFR derived from cystatin of 106±27 ml/min/1.73m2. In contrast, pts with proteinuria (N=4) had higher or abnormal serum cystatin C (mean 1.25 ±0.34, range 0.9–1.7 mg/L) and reduced estimated GFR (mean 59±21, range 35–85) consistent with poor kidney function; nevertheless, the serum creatinine (0.7±0.2) and creatinine clearance remained normal (125±27). Pts with only microalbuminuria (N=5) maintained normal levels of cystatin C and estimated GFR by cystatin. We conclude that serum cystatin C discriminated better for kidney dysfunction than serum creatinine and creatinine clearance with significantly different values between patients with normoalbuminuria and macroalbuminuria (p=0.038). More studies are warranted in order to investigate further the value of serum cystatin C in the monitoring of patients with SCD and albuminuria.

Glomerular Structure in Nonproteinuric IDDM Patients With Various Levels of Albuminuria

Although microalbuminuria is known to foretell the later development of overt proteinuria in patients with insulin-dependent diabetes mellitus (IDDM), different investigators have reported different levels of albuminuria as being predictive. However, whether different levels of albuminuria reflect differences in glomerular structure is not well known. In this study, we divided a cohort of 66 nonproteinuric long-standing (duration 20 +/- 7 years) IDDM patients, who had both renal functional and structural studies performed, into four groups according to their urinary albumin excretion rate (AER). The several different levels of microalbuminuria previously reported to be predictive served to demarcate these groups: group I, AER < or = 22 mg/24 h (upper limit for normal in our laboratory) (33 patients); group II, AER 23-45 mg/24 h (11 patients); group III, AER 46-100 mg/24 h (13 patients); and group IV, AER 101-220 mg/24 h (9 patients). Creatinine clearance was similar in groups I, II, and III but was lower in group IV. Systemic hypertension was present in five patients in group I, one in group II, seven in group III, and five in group IV. Mean values for glomerular basement membrane (GBM) width and volume fraction of the mesangium [Vv(mes/glom)] were greater in all groups than in a group of 52 age-matched normal kidney donors (P < 0.0001). Also, filtration surface density [Sv(PGBM)], inversely related to Vv(mes/glom) (r = 0.61, P < 0.0001), was reduced in all diabetic groups compared with the normal group (P < 0.0001). Structural measures were identical in group I and II.(ABSTRACT TRUNCATED AT 250 WORDS)