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Aim Methods Results Conclusion Although South Asians have an increased risk to develop diabetes, data on the difference in development and progression of diabetic nephropathy between ethnic groups are not consistent. The aim of this study was to evaluate possible differences in the development and progression of albuminuria in South Asians and Western Europeans (WE) with type 2 diabetes in a large closed cohort of South Asians with type 2 diabetes.Data on 1269 South Asians and 2272 Dutch adults with type 2 diabetes who were treated in our diabetes clinic in 2006 or referred thereafter were extracted from electronic medical records. Microalbuminuria and macroalbuminuria were defined separately for men and women based on albumin/creatinine ratios in early morning urine samples. We defined 3 outcomes: (1) no albuminuria, (2) persistent microalbuminuria and (3) macroalbuminuria at the end of follow‐up. Cox proportional hazard models were used to discriminate differences in time from diabetes diagnosis until development and progression of albuminuria between the two ethnic groups, adjusted for retinopathy, hypertension, smoking and age at diabetes diagnosis.South Asians have a higher adjusted risk for developing microalbuminuria: HR 1.4, (95% CI 1.2, 1.6) and macroalbuminuria: HR: 1.2 (1.0, 1.4) compared to Western Europeans. However, mean time to progress from micro‐ to macroalbuminuria was not different between the ethnic groups (3.9 ± 4.0 yrs vs. 3.4 ± 3.9 yrs respectively).South Asians have a higher adjusted risk to develop micro‐ and macroalbuminuria compared with Western Europeans. When microalbuminuria is present, time to progression from micro‐ to macroalbuminuria is not different between the two groups. [ABSTRACT FROM AUTHOR]

Objectives: Renal impairment and some systemic diseases are associated with hearing loss (HL) in adults. However, studies of these relationship in adolescents are rare. The objective of this study was to determine the association between HL and renal or systemic disease in adolescents. Methods: Subjects were extracted from the 5th Korea National Health and Nutrition Examination Survey from 2011 to 2012. We included adolescents aged 10–19 years old with normal tympanic membrane and those who underwent a physical and laboratory examination and pure tone audiometry. HL, high‐frequency hearing loss (HFHL), albuminuria, impaired glomerular filtration rate, hypertension, diabetes, and obesity were evaluated based on the data. Results: Individuals with microalbuminruia (MIA) exhibited higher prevalence of HL (p = 0.003) and HFHL (p = 0.012) than those without MIA. The prevalence of HL and HFHL appeared to increase according to the severity of albuminuria. Additionally, individuals with HL or HFHL showed lower transferrin saturation (TSAT) than individuals without HL (p = 0.002) or HFHL (p = 0.001). And, HFHL was associated with lower ferritin levels (p = 0.017). HL and HFHL were related to MIA (p = 0.004 and p = 0.022, respectively) and TSAT (p = 0.005 and p = 0.011, respectively) after controlling other factors. Conclusion: MIA and TSAT level were independently associated with the HL and HFHL. Since MIA can be easily detected by dipstick test and urine analysis, hearing evaluations for individuals with MIA might be helpful to identify hearing impairments earlier in adolescents. Level of Evidence: 3 (individual cross‐sectional study) Laryngoscope, 134:3329–3334, 2024 [ABSTRACT FROM AUTHOR]

Urinary microalbumin (mALB) serves as an exceptionally sensitive indicator for the early detection of kidney damage, playing a pivotal role in identifying chronic renal failure and kidney lesions in individuals. Nevertheless, the current fluorescent methodologies for point‐of‐care (POC) diagnosis of mALB in real urine still exhibit suboptimal performance. Herein, the development and synthesis of QM‐N2, an albumin‐activated near‐infrared (NIR) aggregation‐induced emission (AIE) fluorescent probe, are presented. The strategic incorporation and positioning of quaternary ammonium salts within the quinoline‐malononitrile (QM) scaffold significantly influence solubility and luminescence characteristics. Specifically, the quaternary ammonium salt‐free variant, QM‐OH, and the quaternary ammonium salt integrated at the donor function group (DFG) site, QM‐N1, display limited solubility in aqueous solutions while demonstrating a distinct fluorescence signal. Conversely, the incorporation of quaternary ammonium salt at the conformational functional group (CFG) site in QM‐N2 imparts superior dispersibility in water and reduces the initial fluorescence. Furthermore, the integration of a well‐defined D‐π‐A structure within QM‐N2 enables itself with near‐infrared emission, which is crucial for mitigating interference from autofluorescence present in urine samples. Upon interaction with albumin, QM‐N2 forms a tight bond with the IIA site of the subdomain of human serum albumin (HSA), inducing alterations in protein configuration and constraining the intrinsic motion of fluorescent molecules. This interaction induces fluorescence, facilitating the sensitive detection of trace albumin. Ultimately, QM‐N2 is applied for POC testing of mALB using portable equipment, particularly in the diagnosis of mALB‐related diseases, notably chronic renal failure. This positioning underscores its potential as an ideal candidate for self‐health measurement at home or in community hospitals. [ABSTRACT FROM AUTHOR]

Microalbuminuria and hyperuricemia management are crucial for the integrated management of hypertensive patients. This retrospective post hoc analysis aims to evaluate the optimal allisartan‐isoproxil‐based combination regimen for hypertensive patients with microalbuminuria or hyperuricemia. A total of 460 hypertensive patients with microalbuminuria and 486 hypertensive patients with hyperuricemia were included in this study. All patients were initially treated with allisartan‐isoproxil for 4 weeks. Thereafter, patients with blood pressure (BP) < 140/90 mmHg continued the monotherapy for 8 weeks; patients with BP ≥140/90 mmHg were randomly assigned in a 1:1 ratio to receive allisartan‐isoproxil + amlodipine (Group A + C) or allisartan‐isoproxil + indapamide (Group A + D) for 8 weeks. The changes of BP, urinary albumin and serum uric acid (UA) were measured. In patients with microalbuminuria, the urinary albumin/creatinine ratio (UACR) significantly decreased by 10.4 mg/g in Group A + C (vs. baseline p =.0035) and 24.2 mg/g in Group A + D (vs baseline p <.0001), intergroup p = NS. In patients with hyperuricemia, serum UA level decreased by 44.5 µmol/L in Group A + C (vs. baseline p =.0003), but increased by 27.2 µmol/L in Group A + D (vs. baseline p =.0167), intergroup p <.0001. The results suggest that for hypertensive patients with microalbuminuria, angiotensin receptor blocker (ARB) + calcium channel blocker (CCB) or ARB+ diuretic both are good choices based on their improvement of microalbuminuria and BP. But for patients with hyperuricemia, ARB + diuretic may further increase the level of UA. [ABSTRACT FROM AUTHOR]

Background: Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) are common complications of type 2 diabetes mellitus (T2DM). Although nerve conduction studies (NCS) and sympathetic skin response (SSR) can detect DPN, the more sensitive method for early diagnosis remains unclear. Furthermore, whether DPN can be used as a predictor for diabetic nephropathy needs clarification. Methods: We evaluated nerve conduction studies, sympathetic skin response, and the diabetic nephropathy indicator microalbuminuria (MAU) in 192 patients with type 2 diabetes mellitus and 50 healthy controls. Results: Patients with type 2 diabetes mellitus showed a lower sensory nerve conduction velocity (SCV), sensory active nerve potential (SNAP), motor nerve conduction velocity (MCV), and compound motor action potential (CMAP) than the controls on NCS. Abnormal rates for nerve conduction studies and sympathetic skin response were 75.0% and 83.3%, respectively, in patients with type 2 diabetes mellitus. Interestingly, 54.2% of patients with normal nerve conduction studies had an abnormal sympathetic skin response. Moreover, we found a positive correlation between sympathetic skin response and microalbuminuria for the first time. The abnormal rate of microalbuminuria was 53.8%, lower than that of abnormal nerve conduction studies or sympathetic skin response patients. Conclusion: Sympathetic skin response is a more sensitive method than nerve conduction studies for the early diagnosis of diabetic peripheral neuropathy. Abnormal sympathetic skin response might serve as an indicator for early diabetic nephropathy. Additionally, diabetic peripheral neuropathy may occur earlier than diabetic nephropathy in the development of type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Aims: Renal dysfunction is one of the most critical risk factors for developing heart failure (HF). However, the association between repeated measures of renal function and incident HF remains unclear. Therefore, this study investigated the longitudinal trajectories of urinary albumin excretion (UAE) and serum creatinine and their association with new‐onset HF and all‐cause mortality. Methods and results: Using group‐based trajectory analysis, we estimated trajectories of UAE and serum creatinine in 6881 participants from the Prevention of Renal and Vascular End‐stage Disease (PREVEND) study and their association with new‐onset HF and all‐cause death during the 11‐years of follow‐up. Most participants had stable low UAE or serum creatinine. Participants with persistently higher UAE or serum creatinine were older, more often men, and more often had comorbidities, such as diabetes, a previous myocardial infarction or dyslipidaemia. Participants with persistently high UAE had a higher risk of new‐onset HF or all‐cause mortality, whereas stable serum creatinine trajectories showed a linear association for new‐onset HF and no association with all‐cause mortality. Conclusion: Our population‐based study identified different but often stable longitudinal patterns of UAE and serum creatinine. Patients with persistently worse renal function, such as higher UAE or serum creatinine, were at a higher risk of HF or mortality. [ABSTRACT FROM AUTHOR]

Aim: Diabetic nephropathy (DN) is a devastating complication of diabetes mellitus (DM). Therefore, screening strategies in order to prevent its development and/or retard its progression are of paramount importance. We investigated if monocyte chemoattractant protein‐1 (MCP‐1) was associated with new onset microalbuminuria‐the earliest sign of the albuminuric phenotype of DN‐ in patients with type 2 DM and normoalbuminuria. Methods: We measured MCP‐1 in serum and urine samples from patients of the Randomized Olmesartan And Diabetes Microalbuminuria Prevention (ROADMAP) study and its Observational Follow‐up (OFU) cohort. A case control design was used with inclusion of 172 patients who developed microalbuminuria (MA) and of 188 well matched controls who remained normoalbuminuric. Results: The median duration of follow‐up for the ROADMAP cohorts was 6.5 years, whereas the mean time until occurrence of MA was 53.2 months. In the multivariate analysis, serum and urine MCP‐1 remained significant predictors of new onset MA. The risk for MA increased continuously with increasing serum and urine MCP‐1 levels but reached statistical significance only in the highest quartiles. The risk associations were stronger with serum MCP‐1. Conclusions: MCP‐1 is a marker and possibly a mediator of early diabetic nephropathy. Further prospective studies are necessary to test whether diabetic patients with elevated MCP‐1 levels would benefit from specific therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of long‐term glycaemic control and glycaemic variability on microvascular complications in adolescents and young adults with childhood‐onset Type 1 diabetes. Methods: Twenty‐six participants took part in a prospective follow‐up study. We used univariate generalised estimating equations (GEE) analysis with first‐order autoregressive AR(1) covariance structure for repeated measurements to evaluate the relationship between emerging diabetic retinopathy (DR) and each single explanatory variable, namely age at developmental stages from late prepuberty until early adulthood, duration of diabetes and long‐term HbA1c. Thereafter, the simultaneous effect of these three explanatory variables to DR was analysed in a multivariate model. Results: Twenty‐five participants developed DR by early adulthood after a median diabetes duration of 16.2 years (range 6.3–24.0). No participants had DR during prepuberty. Each of the three variables was independently associated with emerging DR: age (OR 1.47, 95% CI to 1.25 to 1.74, p < 0.001) stronger than diabetes duration (OR 1.42, 95% CI 1.23 to 1.63, p < 0.001) and HbA1c (OR 1.02, 95% CI 1.001 to 1.05, p = 0.041) in this population. In the multivariate analysis of these three explanatory variables, only age was associated with DR (adjusted OR 1.52, 95% CI 1.10 to 2.10, p = 0.012). Conclusions: The emergence of DR during adolescence and early adulthood is not rare and increases with age in patients with deteriorating metabolic control during puberty and thereafter. This underpins the need to prevent deterioration of glycaemic control from taking place during puberty—seen again in this follow‐up study—in children with diabetes. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to explore the individual and combined effects of obesity and metabolic profile on the impairment of glomerular function among hypertensive subjects. Methods: This is a cross‐sectional study enrolling 499 hypertensive subjects. Based on body mass index values and metabolic profile, they were assigned to one of four metabolic phenotype groups: MHNO: metabolically healthy non‐obese, MHO: metabolically healthy but obese, MUHNO: metabolically unhealthy but non‐obese, and MUHO: metabolically unhealthy and obese. The effect of the interaction between obesity and metabolic profile was tested on an additive scale, for both microalbuminuria and reduced estimated glomerular filtration rate (eGFR). Results: After adjustment for confounding factors, the highest risk of both microalbuminuria and decreased eGFR was found among patients of the MUHO group (OR = 6.0 [2.13], p < 0.0001, OR = 5.4 [1.26], p = 0.03, respectively). Analysis of the additive interaction indicates that 51% and 53% of the risk of microalbuminuria and its combination with low eGFR respectively is explained by the co‐occurrence of obesity and metabolic disorder. The mechanism of this interaction is synergistic (synergy index = 2.6, [1.5.3]). Conclusion: The decline of glomerular function in hypertensive subjects is significantly exacerbated by the interaction between obesity and metabolic disorders. The management of such high‐risk subjects requires, in addition to the therapeutic regimen, an adequate dietary and physical program in order to preserve glomerular function. SUMMARY AT A GLANCE: This cross‐sectional study explored the individual and combined effects of obesity and metabolic profile on kidney function among 499 hypertensive subjects, and found that the odds of microalbuminuria and low eGFR was highest in patients with metabolically unhealthy obesity. The co‐exsitence of obesity and metabolic disorder showed a synergistic interaction for this association. [ABSTRACT FROM AUTHOR]

Aims: Microalbuminuria is an indicator of adverse cardiovascular events and chronic kidney disease. Studies have described an elevated resting heart rate as a risk factor for microalbuminuria in people with cardiovascular disease, but none have clarified its role in microalbuminuria development in people with type 2 diabetes. Therefore, this study investigated the relationship between resting heart rate and new‐onset microalbuminuria in type 2 diabetes. Methods: A total of 788 people from a glycaemic control trial in Taiwan were enrolled. Microalbuminuria was defined as a fasting urine albumin‐to‐creatinine ratio ≥30 mg/g in two consecutive urine tests. Resting heart rate and other covariates were measured at baseline. The quartile of resting heart rates, categorized as <70, 70–74, 75–80 and >80 beats/min, was used for analysis. Cox proportional hazard models were used to evaluate the association between resting heart rate and risk of microalbuminuria. Results: During the follow‐up period, 244 people (31%) developed microalbuminuria. Those who developed microalbuminuria had a longer diabetes duration (median = 3.0 vs. 2.0 years, p < 0.001), higher rate of hypertension (77% vs. 66%, p = 0.003), higher rate of angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker treatment (50% vs. 38%, p = 0.001) and higher baseline HbA1c level (70 vs. 64 mmol/mol, 8.6 vs. 8.0%, p < 0.001). After adjusting for demographics, metabolic profiles and inflammatory markers, developing microalbuminuria was significantly associated with baseline resting heart rate of 70–74, 75–80 and >80 beats/min (with hazard ratios [95% CI] of 2.05 [1.32, 3.18], 2.10 [1.32, 3.32] and 1.62 [1.01, 2.59], respectively) compared to resting heart rates <70 beats/min. An average increased risk of microalbuminuria for increment of 10 beats/min was about 24% among those with hypertension (with hazard ratios of 1.24 [1.05, 1.47] in the multivariable Cox model). Conclusions: This prospective cohort study showed that resting heart rate may be an associative risk factor for developing microalbuminuria in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To investigate the longitudinal association of microalbuminuria with overactive bladder (OAB). Methods: This longitudinal study investigated 561 participants of the Iwaki Health Promotion Project in both 2015 and 2019 in Japan. Microalbuminuria and OAB symptoms were assessed using the urine albuminuria creatinine ratio (ACR) and the overactive bladder symptom score (OABSS), respectively. Urine ACR was defined as high if ≥9.3 mg/gCr. Differences in OABSS between 2015 and 2019 were evaluated as ∆OABSS. Participants were divided into two groups according to ΔOABSS: high (ΔOABSS > 1) and control (≤1). We used baseline data acquired in 2015, such as urine ACR, the Pittsburgh Sleep Quality Index (PSQI), and arterial stiffness expressed by brachial‐ankle pulse wave velocity (baPWV). Predictive factors of a ΔOABSS > 1 were assessed by multivariable logistic regression analysis. Results: This study included 332 women and 229 men. Of those, 86 (34 males and 52 females) were classified into the ΔOABSS > 1 group. There were significant group differences in age, renal function, and hemoglobin A1c. Participants in the ΔOABSS > 1 had a higher prevalence of PSQI > 5, baPWV ≥ 1400 seconds/cm, and urine ACR ≥ 9.3 mg/gCr (49% vs 20%, P =.001) than those in the control group. Multivariable analysis revealed that PSQI > 5 (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.15‐4.60; P =.002) and urine ACR ≥ 9.3 mg/gCr (OR, 1.93; 95% CI, 1.15‐3.23; P =.013) were independent risk factors for ΔOABSS > 1. Conclusions: Microalbuminuria may be an independent risk indicator for OAB symptom exacerbation. [ABSTRACT FROM AUTHOR]

Summary: In daily haematological practice, predicting bleeding in thrombocytopenic patients is difficult, and clinicians adhere to transfusion triggers to guide patients through the aplastic phase of chemotherapy. Platelet count is not the only determinant of bleeding and additional mechanisms for impending haemostasis are likely. Beside clot formation, platelets are essential for the maintenance of integrity of vascular beds. We therefore prospectively investigated associations between biomarkers for endothelial damage (urine albumin excretion) and inflammation (C‐reactive protein) and bleeding (WHO grading) in 88 patients with 116 on‐protocol episodes. We found an increase in grade 2 bleeding with a higher urine albumin/creatinine ratio one day after the measurement [odds ratio (OR) 1·24 for every doubling of the ratio, 95% CI 1·05–1·46, P‐value 0·01] and a 29% increase in the odds of grade 2 bleeding for every doubling of serum C‐reactive protein (CRP) (95% CI 1·04–1·60, P‐value 0·02) after correction for morning platelet count. The 24 h post‐transfusion corrected count increment (CCI24) showed a significant association with these biomarkers: increasing urine albumin/creatinine ratio and CRP were associated with lower CCI24. We report two inexpensive and easy‐to‐apply biomarkers that could be useful in designing a prediction model for bleeding risk in thrombocytopenic patients. [ABSTRACT FROM AUTHOR]

Background: Growth hormone treatment increases glomerular filtration rate (GFR), as serum IGF‐I stimulates the renin‐angiotensin system. Infants born with a low birth weight have a smaller number of nephrons, which cause a lower GFR, a higher blood pressure and a higher albumin‐to‐creatinine ratio in early adulthood. Method: A total of 261 young adults born SGA, previously treated with growth hormone (SGA‐GH), were longitudinally followed. Glomerular filtration rate, based on serum creatinine levels, was determined at cessation of GH treatment and at 6 months, 2 years and 5 years thereafter. Glomerular filtration rate, blood pressure and urinary albumin‐to‐creatinine ratio at 5 years after cessation of GH were compared with untreated age‐matched controls (56 untreated short subjects born SGA [SGA‐S], 118 subjects born SGA with spontaneous catch‐up growth [SGA‐CU], 135 subjects born appropriate for gestational age [AGA]). Results: Glomerular filtration rate decreased significantly only during the first 6 months after cessation of GH treatment, while remaining well within the normal range (124.6 vs 120.2 mL/min/1.73 m2, P < .001). SGA‐GH adults had a similar GFR, blood pressure and urinary albumin‐to‐creatinine ratio as the healthy controls born SGA and AGA. Conclusion: In conclusion, our 5 years longitudinal follow‐up study shows a decrease in GFR during 6 months after GH cessation, but thereafter GFR remained stable and within the normal range. Glomerular filtration rate, blood pressure and urinary albumin‐to‐creatinine ratio at 21 years of age were similar in GH‐treated young adults born SGA and untreated controls born SGA or AGA. We conclude that long‐term GH treatment in children born SGA has no unfavourable effects on kidney function in early adulthood. Précis: We present a longitudinal study on kidney function in the follow‐up of growth hormone‐treated young adults who were born small for gestational age. [ABSTRACT FROM AUTHOR]

Background and Aim: Renal abnormalities can occur at any time point during the course of Wilson disease (WD). We aimed to fill a literature gap in this respect by studying urinary abnormalities in children and adolescents with WD. Methods: This study included 60 children with WD presenting to the Pediatric Hepatology Unit, Cairo University. The following data were retrieved from the patients' files including age, sex, liver function tests, serum ceruloplasmin, 24‐h urinary copper, serum creatinine, blood urea nitrogen, urinalysis, urinary albumin/creatinine ratio, urinary calcium/creatinine ratio, urinary β2‐microglobulin, liver and renal biopsy results when available. Results: All studied cases had no symptoms related to renal involvement. Microscopic hematuria was detected in 11% and 12% at baseline and within 5 years of therapy, respectively. Moderate microalbuminuria was detected in 34%, 50%, and 33% at baseline, within 5 years and > 5 years after therapy, respectively. Hypercalciuria was detected in 23% at baseline, 34% in those patients treated for up to 5 years and 37.5% > 5 years of therapy. Age and international normalized ratio were significantly higher in patients with high calcium/creatinine ratio compared with those with normal values at initial evaluation. Frequency of elevated urinary β2‐microglobulin was 36%, 36%, and 37% in patients at baseline, up to 5 years and > 5 years of therapy, respectively. Conclusion: Asymptomatic urinary abnormalities are present in patients with WD at any time point of the disease and during treatment with d‐penicillamine. They have to be searched for, as early intervention may prevent progression to renal insufficiency. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Microalbuminuria (MA) has been demonstrated as a biomarker for microvascular dysfunction. This study is aimed to evaluate the association of glycaemic status with MA in prehypertensive and ideal BP subjects and to evaluate the interaction between glycaemic and blood pressure status as risk factors for MA prevalence. Methods: 1059 subjects aged 40–70 with non‐hypertension who were recruited from six districts of Tianjin were divided into a prehypertensive group (622 cases) and an ideal blood BP group (437 cases). Subjects of the prehypertensive group and the ideal BP group were divided respectively into three subgroups: normoglycaemia subgroup, prediabetes subgroup and diabetes subgroup. The prevalence of MA in the above three subgroups of subjects with prehypertension and ideal BP were assessed. We performed a statistical analysis for interaction test between glycaemia and BP status on microalbuminuria in the overall study sample by a multivariate logistic regression model. The association of glycaemic status (defined as normoglycaemia, prediabetes, and diabetes) with MA was evaluated separately in prehypertensive and ideal BP subjects. Results: Results showed that the prevalence of MA in both prehypertensive and ideal BP groups rose with the increasing of classification of glycaemic level of subgroups (32.6%, 18.3%, 14.8% vs. 23.1%, 16.2%, 13.4%), the differences in prehypertensive group were statistically significant (Pearson χ2 = 15.24, P < 0.001). The ORs (95% CI) of MA were 1.25 (0.86–1.83) for prediabetes and 2.56 (1.62–4.03) for diabetes in the fully adjusted model. There was no interaction between prediabetes and BP status regarding MA (P = 0.237) but we found a significant interaction between diabetes and BP status (P < 0.001). In the prehypertensive group, multivariate logistic regression models showed that the diabetes subgroup had a significant association with MA, and the adjusted odds ratio of the diabetes subgroup to the normoglycaemia subgroup was 2.68 (95%CI 1.54–4.67) (P < 0.001). However, there was no significant association of glycaemic status with MA in the ideal BP group. Stratified analysis by a multivariate logistic regression model in the whole study population showed that people with both prehypertension and diabetes had the highest risk of MA (adjusted OR = 2.50, 95%CI 1.16–5.36; P = 0.019), compared with those with ideal BP and normoglycaemia (reference group). Conclusions: Our findings suggest that there was a statistically significant association between diabetes and microalbuminuria only in prehypertensive subjects. In addition, our study highlights the interaction between prehypertension and diabetes as a risk factor for MA. [ABSTRACT FROM AUTHOR]

Aim: To review indications and use of angiotensin-converting enzyme-inhibitor (ACEI) therapy for the treatment of persistent microalbuminuria (MA) and/or hypertension (HTN) in adolescents with type 1 diabetes mellitus (T1DM).Methods: Retrospective chart review of adolescent patients with T1DM seen within the paediatric diabetes service in Auckland, New Zealand, from 2006 to 2016. MA, HTN, patient demographic characteristics and ACEI prescribing and monitoring indices were examined.Results: Five hundred adolescents with T1DM were included. There were 26 patients (5%) with MA and/or HTN. MA alone was present in 16, HTN alone in 3 and both HTN and MA in 7. The 5-year MA/HTN-free rate was 98%, and the 10-year MA/HTN-free rate was 93%. Longer disease duration and earlier diagnosis were predictors of MA/HTN. There was no significant difference in standard clinical indices between study patients and others. ACEI was prescribed for 17 of 26 patients for either HTN or MA. Within 6 weeks of ACEI commencement, less than half of the subjects had repeat serum creatinine and MA screens and no record of repeat blood pressure measurement. Despite this, all patients had 3-monthly reviews within outpatient clinics where adjustments of ACEI doses were made.Conclusion: In our regional adolescent population with T1DM, there were low rates of both MA and/or HTN. In those who required treatment with ACEI, clinical monitoring post-commencement of therapy was inconsistent. Local consensus guidelines for the management of persistent MA in children and adolescents with diabetes mellitus were developed in response to this study. [ABSTRACT FROM AUTHOR]

Abstract: Aim: We examined body mass index (BMI) and gestational weight gain (GWG) patterns of pregnant women and investigated the impact of these factors on the urinary albumin‐creatinine ratio (ACR) during pregnancy. Methods: The data of 163 women whose basal BMI and ACR were measured during the first trimester were used in this study. Body weight alone between 12–16 weeks and body weight together with ACR after 37 weeks of gestation were measured. Results: Overall, 46% of women were overweight or obese, 60.7% had excessive weight gain and 16.6% had inadequate weight gain. Only 22.7% of women gained weight within the recommended range. There was no difference in weight gain patterns with respect to BMI. ACR during the third trimester was significantly higher than during the first trimester (7.08 [0.00–1180.90] mg/g vs 4.73 [0.00–275.00] mg/g, respectively; P = 0.001). The ACR of obese women was higher than in normal weight subjects during the third trimester (16.79 mg/g [0.01–1180.90] vs 8.07 mg/g [0.10–402.14] respectively; adjusted P = 0.015). Both ACR change and third trimester ACR were weakly but significantly correlated with basal BMI (r: 0.228 P: 0.003 and r: 0.301 P < 0.001, respectively) but not with GWG or GWG rate. Basal BMI was not associated with first‐trimester ACR. Conclusion: Obesity is associated with an increase in urinary albumin excretion during the course of pregnancy. Distinction of this relationship during pregnancy offers an opportunity for further research on pathophysiological mechanisms. The alarmingly high rate of non‐compliance with IOM guidelines in pregnant women is a concern. Prompt measures for counseling of women before and during pregnancy in order to maintain healthy weight are needed. [ABSTRACT FROM AUTHOR]

Aims/Introduction To compare the incidence rate of renal dysfunction between patients with fulminant type 1 diabetes and those with acute-onset type 1 diabetes. Materials and Methods The present retrospective cohort study included patients with fulminant type 1 diabetes and acute-onset type 1 diabetes diagnosed during April 1993 to March 2016 at a national center in Japan. Glycated hemoglobin levels, incidence rates of renal dysfunction defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 and microalbuminuria were examined. Results In total, 115 patients with type 1 diabetes (10 with fulminant type 1 diabetes and 105 with acute-onset type 1 diabetes) were included. The median glycated hemoglobin levels were significantly lower in patients with fulminant type 1 diabetes than in those with acute-onset type 1 diabetes 0, 3, 6 and 9 years after diabetes onset (6.5 vs 12.7%, 6.5 vs 7.9%, 6.7 vs 8.2%, 7.5 vs 8.5%, respectively). Kaplan-Meier analysis showed a significantly higher incidence rate of renal dysfunction in patients with fulminant type 1 diabetes than in those with acute-onset type 1 diabetes (hazard ratio 1.72, 95% confidence interval 1.01-2.97, P = 0.037). The incidence rate of microalbuminuria did not significantly differ between the groups (hazard ratio 0.97, 95% confidence interval 0.34-2.77, P = 0.95). Sensitivity analysis using age- and sex-matched patients with fulminant type 1 diabetes and acute-onset type 1 diabetes yielded similar results. Conclusions The risk of developing renal dysfunction is higher in patients with fulminant type 1 diabetes than in those with acute-onset type 1 diabetes, despite better glycemic control. [ABSTRACT FROM AUTHOR]

Microalbuminuria is an early biomarker of kidney injury, the aim of this study was to investigate the impact of high sensitivity C-reactive protein (hs-CRP) on microalbuminuria in adults with cardiovascular disease (CVD) risk factors. A total of 5667 subjects who voluntarily attended annual health screenings in the Third Xiangya Hospital of Central South University were included in the study. Logistic regression was used to determine the validity of hs-CRP to predict the presence of microalbuminuria. In the unadjusted regression analysis, male gender (OR 2.23), age (OR 1.71), smoking status (OR 1.48), obesity (OR 2.41), hypertension(OR 4.03), diabetes (OR 4.61), hyperuricemia (OR 1.83), and high hs-CRP(OR 1.61) were associated with microalbuminuria. Multivariate logistic regression analysis showed that the adjusted odds ratios (OR) of diabetes, hypertension, male, abdominal obesity, and high hs-CRP for microalbuminuria were 2.71, 2.57, 1.51, 1.28 and 1.41 in all subjects, respectively ( P < 0.01). ROC analysis indicated that the cut-off for hs-CRP with better properties for screening of microalbuminuria was identified as ≥0.85 mg/L. The ORs of microalbuminuria were 1.97, 1.49, 1.32 and 1.71 times in male, abdominal obesity, diabetes and hypertension subjects with hs-CRP ≥ 0.85 mg/L, respectively, compared with those without elevated hs-CRP ( P < 0.01). Elevated hs-CRP level was associated with microalbuminuria independent of cardiovascular risk factors. In addition, elevated hs-CRP increased the risk of developing microalbuminuria in subjects with CVD risk factors, indicating that chronic inflammation could amplify the deterioration of kidney by effect of CVD risk factors. [ABSTRACT FROM AUTHOR]

Aims/Introduction Individuals with type 2 diabetes mellitus are vulnerable to micro- and macrovascular complications in the presence of microalbuminuria. Adipocyte fatty acid-binding protein (A-FABP) was proposed as an indicator for albuminuria in patients with diabetes. The present study aimed to explore the associations between serum A-FABP levels and microalbuminuria in the hyperglycemic population. Materials and Methods Serum A-FABP levels were detected using sandwich enzyme-linked immunosorbent assay. Microalbuminuria was identified by urinary albumin-to-creatinine ratio (UACR), when the value was between 30-300 mg/g. The participants were divided into the subgroups based on sex and the status of impaired glucose regulation or newly diagnosed type 2 diabetes mellitus. Results A total of 939 participants, consisting of 436 men and 503 women, were enrolled. Serum levels of A-FABP were much higher in participants with microalbuminuria than those without microalbuminuria. This result held true for all subgroups (all P < 0.05). For Spearman's correlation analyses, serum A-FABP levels showed a positive relationship with the UACR in men and women (both P < 0.01). Multiple stepwise regression analysis showed that serum A-FABP levels were independently and positively correlated with UACR in both sexes (men: standardized β = 0.256, P < 0.001; women: standardized β = 0.155, P = 0.001). This relationship remained significant in every subgroup (all P < 0.01). Conclusions For hyperglycemic individuals, serum A-FABP levels increased in the presence of microalbuminuria. Serum A-FABP levels were identified as an independent factor positively associated with the UACR. [ABSTRACT FROM AUTHOR]

Background: Evidence links the lectin pathway of complement activation to diabetic kidney disease. Upon carbohydrate-recognition by pattern-recognition molecules, eg, mannan-binding lectin (MBL), the MBL-associated serine protease (MASP-2) is activated and initiates the complement cascade. The MASP2 gene encodes MASP-2 and the alternative splice product MBL-associated protein 19 (MAp19). Both MAp19 and MASP-2 circulate in complex with MBL. We tested the hypothesis that MAp19 and MASP-2 concentrations predict the risk of incident microalbuminuria.Methods: Baseline MAp19 and MASP-2 were measured in 270 persons with newly diagnosed type 1 diabetes tracked for incidence of persistent microalbuminuria in a prospective observational 18-year-follow-up study.Results: Seventy-five participants (28%) developed microalbuminuria during follow-up. MBL-associated protein 19 concentrations were higher in participants that later progressed to microalbuminuria as compared with those with persistent normoalbuminuria (268 ng/mL [95% CI, 243-293] vs 236 ng/mL [95% CI, 223-250], P = .02). Participants with MAp19 concentration within the highest quartile of the cohort had an increased risk of microalbuminuria as compared with participants with MAp19 concentration within the combined lower 3 quartiles in unadjusted Cox analysis, hazard ratio 1.86 ([95% CI, 1.17-2.96], P = .009). This remained significant in adjusted models, eg, adjusting for age, sex, HbA1c , systolic blood pressure, urinary albumin excretion, smoking, serum creatinine, and serum cholesterol. MBL-associated serine protease concentration was not associated with incidence of microalbuminuria.Conclusions: In conclusion, the results show an association between baseline MAp19 concentration and the incidence of microalbuminuria in an 18-year-follow-up study on persons with newly diagnosed type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aims: Chronic kidney disease (CKD) and microalbuminuria are associated with incident heart failure (HF), but their relative contributions to HF with preserved vs. reduced EF (HFpEF and HFrEF) are unknown. We sought to evaluate the associations of CKD and microalbuminuria with incident HF subtypes in the community-based Framingham Heart Study (FHS).Methods and Results: We defined CKD as glomerular filtration rate <60 mL/min/1.73 m2 , and microalbuminuria as a urine albumin to creatinine ratio (UACR) ≥17 mg/g in men and ≥25 mg/g in women. We observed 754 HF events (324 HFpEF/326 HFrEF/104 unclassified) among 9889 FHS participants with serum creatinine measured (follow-up 13 ± 4 years). In Cox models adjusted for clinical risk factors, CKD (prevalence = 9%) was associated with overall HF [hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.01-1.51], but was not significantly associated with individual HF subtypes. Among 2912 individuals with available UACR (follow-up 15 ± 4 years), 192 HF events (91 HFpEF/93 HFrEF/8 unclassified) occurred. Microalbuminuria (prevalence = 17%) was associated with a higher risk of overall HF (HR 1.71, 95% CI 1.25-2.34) and HFrEF (HR 2.10, 95% CI 1.35-3.26), but not HFpEF (HR 1.26, 95% CI 0.78-2.03). In cross-sectional analyses, microalbuminuria was associated with LV systolic dysfunction (odds ratio 3.19, 95% CI 1.67-6.09).Conclusions: Microalbuminuria was associated with incident HFrEF prospectively, and with LV systolic dysfunction cross-sectionally in a community-based sample. In contrast, CKD was modestly associated with overall HF but not differentially associated with HFpEF vs. HFrEF. The mechanisms responsible for the relationship of microalbuminuria to future development of HFrEF warrant further investigation. [ABSTRACT FROM AUTHOR]

Aim: Glomerular hyperfiltration is an early marker of sickle cell nephropathy and can lead to microalbuminuria and renal failure. Our aim was to identify the associated risk factors, as these could be of preventative importance.Methods: We recruited 150 children with sickle cell anaemia (SCA), aged two to 18 years and living in Kinshasa, the Democratic Republic of Congo. Hyperfiltration and microalbuminuria were defined as an estimated glomerular filtration rate of less than 140 mL/min/1.73 m² and an albumin creatinine ratio of between 30 and 299 mg/g, respectively. Independent determinants of hyperfiltration were assessed using logistic regression analysis.Results: Glomerular hyperfiltration was observed in 60 (40%) children, who were significantly older (10.2 ± 4.1 versus 7.9 ± 4.3 years, p = 0.001) and had a lower body mass index level (14.7 ± 2.3 versus 15.0 ± 2.3 kg/m2 ) than the 60% without. A higher proportion had microalbuminuria (25.0 versus 13.3%), but the difference was not statistically significant (p>0.05). Increased age and decreased body mass index were the main independent factors associated with glomerular hyperfiltration in the multivariate analysis. A quarter (25%) of the 60 children with SCA with glomerular hyperfiltration had microalbuminuria.Conclusion: Glomerular hyperfiltration was a common finding in this study and was significantly associated with age. [ABSTRACT FROM AUTHOR]

Objectives We aimed to investigate serum cystatin C (cysC) levels in primary Sjögren's syndrome (p SS) patients, and evaluate its correlation with renal involment. Materials and methods Eighty-six p SS patients and 65 age- and gender-matched healthy controls were enrolled into the study. Serum cysC, urea, serum creatinine (SCr), creatinine clearance (CrCl), glomerular filtration rates (GFR), Na, K, Mg, Ca, uric acid, P, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-Ro/SS-A, anti-La/SS-B, antinuclear antibodies, 24-h urinary poteinuria and microalbuminuria were evaluated. Results Mean serum cysC levels did not differ between the patients and healthy controls ( P > 0.05). Nine patients with p SS had proteinuria over 150 mg (and microalbuminuria over 30 mg) per 24 h. In patients with proteinuria, serum cysC levels correlated with serum K ( r = 0.279, P = 0.024), ESR ( r = 0.405, P = 0.001) and the disease duration ( r = 0.235, P = 0.04), respectively. Patients with positive anti-Ro/SS-A and anti-La/SS-B antibodies had higher SCr levels compared to those with negative serology ( r = 0.292, P = 0.009, and r = 0.259, P = 0.022, respectively). Nine patients with proteinuria and anti-Ro/SS-A, anti-La/SS-B positivity tended to have lower K and Mg levels which suggests subclinical renal tubular acidosis. Conclusion There were no associations between serum cysC levels and renal involvement in patients with p SS. However, in patients with proteinuria, serum cysC levels were correlated with acute-phase reactants, suggesting an association with disease activity in terms of degree of inflammation. [ABSTRACT FROM AUTHOR]

Kidney disease is a serious development in diabetes mellitus and poses an increasing clinical problem. Despite increasing incidence and prevalence of diabetic kidney disease, there have been no new therapies for this condition in the last 20 years. Mounting evidence supports a biological role for C-peptide, and findings from multiple studies now suggest that C-peptide may beneficially affect the disturbed metabolic and pathophysiological pathways leading to the development of diabetic nephropathy. Studies of C-peptide in animal models and in humans with type 1 diabetes all suggest a renoprotective effect for this peptide. In diabetic rodents, C-peptide reduces glomerular hyperfiltration and albuminuria. Cohort studies of diabetic patients with combined islet and kidney transplants suggest that maintained C-peptide secretion is protective of renal graft function. Further, in short-term studies of patients with type 1 diabetes, administration of C-peptide is also associated with a lowered hyperfiltration rate and reduced microalbuminuria. Thus, the available information suggests that type 1 diabetes should be regarded as a dual hormone deficiency disease and that clinical trials of C-peptide in diabetic nephropathy are both justified and urgently required. [ABSTRACT FROM AUTHOR]

Background Growing evidence shows that inflammation plays a pivotal role in the pathophysiology of essential hypertension ( EH). Although it is acknowledged that target organ damage involves an inflammatory response, most work has focused on the role of macrophages. However, recently, platelets were identified as inducing inflammation partly by releasing cytokines. The goal of our study was to evaluate the role of platelets as inflammatory cells in the pathogenesis of EH. Methods Thirty-nine patients with EH and 30 healthy normotensive controls have been examined. Expression of platelet CD40 was measured by flow cytometry. Serum levels of monocyte chemoattractant protein 1 ( MCP-1) and sCD40L were measured via a multiplexing assay. In in vitro experiments, activated platelets were cocultured with human umbilical vein endothelial cells ( HUVEC) in the presence and absence of anti- CD154 antibodies. MCP-1 in the supernatants was measured by EIA. Results Essential hypertension patients showed significantly enhanced MCP-1 levels with highest levels in EH patients with microalbuminuria. EH patients showed increased expression of platelet CD40. In the cell coculture model, activated platelets were able to significantly induce MCP-1 release from HUVEC in a CD40L-dependent manner. EH patients showed elevated sCD40L levels with a positive correlation with MCP-1 levels. Conclusions Platelets can contribute to enhanced MCP-1 levels in EH. MCP-1 is markedly elevated in serum of EH patients with highest levels in patients with microalbuminuria, one early sign of renal target organ damage. Further studies are required to test whether MCP-1 blocking or antiplatelet strategies may represent new therapeutic options in preventing hypertensive target organ damage. [ABSTRACT FROM AUTHOR]

The management of non-renal pediatric solid organ transplant recipients has become complex over the last decade with innovations in immunosuppression and surgical techniques. Post-transplantation follow-up is essential to ensure that children have functioning allografts for as long as possible. CKD is highly prevalent in these patients, often under recognized, and has a profound impact on patient survival. These practice recommendations focus on the early detection and management of hypertension, proteinuria, and renal dysfunction in non-renal pediatric solid organ transplant recipients. We present seven practice recommendations. Renal function should be monitored regularly in organ transplant recipients, utilizing assessment of serum creatinine and cystatin C. GFR should be calculated using the new Schwartz formula. Transplant physicians should also monitor blood pressure using automated oscillometric devices and confirm repeated abnormal measures with manual blood pressure readings and ambulatory 24-h blood pressure monitoring. Proteinuria and microalbuminuria should also be assessed regularly. Referrals to a pediatric nephrologist should be made for non-renal organ transplant recipients with repeated blood pressures >95th percentile using the Fourth Task Force reference intervals, microalbumin/creatinine ratio >32.5 mg/g (3.7 mg/mmol) creatinine on repeated testing and/or GFR <90 mL/min/1.73 m2. [ABSTRACT FROM AUTHOR]

Background Hypertension and albuminuria often coexist in Greyhounds, suggesting generalized vascular dysfunction that could contribute to the development of a variety of diseases in this breed. Eicosanoid metabolites of arachidonic acid ( AA) mediate endothelial function, vascular reactivity, and proteinuria in humans and in rodent models. Hypothesis The eicosanoid profile of Greyhounds is shifted toward metabolites that promote vascular dysfunction, hypertension, and proteinuria. Animals Healthy Greyhounds (n = 20) and non-Greyhound (n = 20) dogs that were consecutively enrolled in a blood donor program. Methods Prospective study. Plasma eicosanoid metabolites were assayed by liquid chromatography/electrospray ionization mass spectrometry ( LC/ ESI/ MS) and compared to systolic blood pressure ( SP) measurements and urine albumin concentration. Results Isomers of hydroxyeicosatetraenoic acid ( HETE) were higher in Greyhounds than non-Greyhounds (median, range in pmol/mL: 5(S) HETE 19.82, 8.55-32.95 versus 13.54, 4.33-26.27, P = .033; 8(S) HETE 9.39, 3.28-19.84 versus 5.80, 2.25-17.66, P = .002; 9(S) HETE 9.46, 2.43-13.79 versus 5.82, 1.50-17.16, P = .026; 12(S) HETE 10.17, 3.81-40.06 versus 7.24, 2.9-16.16, P = .022). Dihydroxyeicosatrienoic acid ( DHET) isomers also were higher in Greyhounds compared to non-Greyhounds (mean ± SD in pmol/mL: 8,9 DHET 5.78 ± 2.13 versus 4.03 ± 1.36, P = .004; 11,12 DHET 11.98 ± 2.86 versus 8.90 ± 3.48, P = .004; 14,15 DHET 7.23 ± 2.19 versus 5.76 ± 1.87, P = .028). Albuminuria correlated with total DHET (rs = 0.46, P = .003). SP was positively correlated with 11,12 EET (rs = 0.42, P = .006) and 20(S) HETE (rs = 0.38, P = .017). SP and 8,9 EET were inversely correlated (rs = −0.49, P = .001). Conclusions and Clinical Importance Plasma eicosanoid profile in Greyhounds was consistent with activation of metabolic pathways known to promote vascular dysfunction and might contribute to higher blood pressures and albuminuria. Inhibition of these eicosanoid pathways should be evaluated as therapeutic targets in Greyhounds. [ABSTRACT FROM AUTHOR]

Aim: Hydronephrosis caused by ureteropelvic junction obstruction (UPJO) is an important problem in children and young adults. The aim of this pilot study was to determine the urine profiles of a number of lysosomal exoglycosidases to see whether they indicated tubular renal damage in children with UPJO.Methods: We measured lysosomal exoglycosidases urine activities in 32 patients with UPJO, dividing them into three groups. The surgical group comprised 16 children with severe hydronephrosis who required surgery, the nonsurgical group comprised 16 patients with mild hydronephrosis, and the reference group comprised 42 healthy children. The following indicators were measured: N-acetyl-β-hexosaminidase and its A and B isoenzymes, α-fucosidase, β-galactosidase, α-mannosidase and β-glucuronidase.Results: The urine activities of all exoglycosidases were significantly higher in children with UPJO than children in the reference group (p < 0.01). A strong positive correlation was also found between most of the urine exoglycosidases and the urine albumin/creatinine ratio (p < 0.01).Conclusion: Our findings demonstrated that children with UPJO showed increased renal activities of assessed exoglycosidases, which correlated positively with the urine albumin/creatinine ratio. A larger multicentre study is required to confirm the clinical applications of these observations. [ABSTRACT FROM AUTHOR]

Background This study was aimed at evaluating the effectiveness of serum cystatin C and microalbuminuria as diagnostic markers for acute kidney injury (AKI) in major burn patients. Materials and methods Major burn adult patients admitted to the burn intensive care unit within 24 h from the onset of injury were enrolled. Serum cystatin C and microalbuminuria (albumin-creatinine ratio, ACR) were obtained at postburn days 1, 3, 7, 14, 21 and 28. The patients were divided into two groups of the AKI group and the nonacute kidney injury group. Results A total of 97 patients were enrolled in this study. Acute kidney injury was diagnosed in 40 patients (41·2%) at postburn day 17·3 ± 7·9. The area under the curve of the receiver operating characteristic curve for serum cystatin C was 0·808 (95% CI, 0·711-0·905, P < 0·001) at postburn day 7 and 0·908 (95% CI, 0·843-0·973, P < 0·001) at postburn day 14. The results were 0·610 (95% CI, 0·497-0·724, P = 0·069) for ACR at postburn day 7 and 0·694 (95% CI, 0·589-0·798, P = 0·001) at postburn day 14. The optimal cut-off value of serum cystatin C at postburn day 14 and ACR at postburn day 14 were 0·85 mg/L (sensitivity, 89·5%; specificity, 82·5%) and 41·51 mg/g cre (sensitivity, 60·5%; specificity, 61·4%), respectively. Serum cystatin C at postburn day 14 was the only significant factor in relation to AKI. Conclusions Serum cystatin C is a valuable diagnostic marker, whereas microalbuminuria is a relatively less significant marker for AKI in major burn patients. [ABSTRACT FROM AUTHOR]

Background Albuminuria is associated with increased risk of multiple adverse health outcomes, such as progressive renal failure, cardiovascular disease and death. However, in the general population, it is uncertain whether albuminuria is associated with elevated heart rate, which is an independent and powerful risk factor for cardiovascular disease. Aim To investigate whether an elevated heart rate is an independent factor associated with albuminuria in the general adult population of Korea. Methods A cross-sectional analysis was carried out on 5198 Korean adults aged 19 years or older who participated in the fifth (2011) Korea National Health and Nutrition Examination Survey ( KNHANES V-2). Results The prevalence of albuminuria showed an increasing trend throughout the whole range of heart rate, even after adjusting for confounders ( P = 0.002). The increment was most profound at the heart rate of 70-75 and >76 beats per minute (b.p.m.; P = 0.011). In multiple logistic regression analysis, age ( P < 0.001), hypertension ( P < 0.001), diabetes ( P < 0.001), hypertriglyceridaemia ( P = 0.025), estimated glomerular filtration rate ( P = 0.028) and heart rate ( P = 0.023) were independently associated with the presence of albuminuria in Korean adults. Compared with participants with heart rate ≤64 b.p.m., the odds ratio (95% CI) for albuminuria was 1.50 (1.15-1.96) for those with heart rate ≥76 b.p.m. Conclusions The prevalence of albuminuria is independently associated with heart rate in the general adult population of Korea. [ABSTRACT FROM AUTHOR]

. Purpose: To determine the prevalence and risk factors for retinopathy in a nondiabetic population. Methods: The study population included 5869 participants without diabetes aged 38-87 years from the Tromsø Eye Study, a substudy of the population-based Tromsø Study in Norway. Retinal images from both eyes were graded for retinopathy. We collected data on risk factors from self-report questionnaires, clinical examinations, laboratory measurements and case note reviews. The cross-sectional relationship between potential risk factors and retinopathy was assessed using logistic regression analysis. Results: The overall prevalence of retinopathy was 14.8%. Men had a higher prevalence of retinopathy compared with women (15.9% versus 14.0%, p = 0.04). In men, retinopathy was associated with hypertension (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.24-2.04) and HbA1c (OR per %, 1.41; 95% CI, 1.01-1.96). In women, retinopathy was associated with age (OR per 10 years, 1.32; 95% CI, 1.14-1.52), log-transformed urinary albumin excretion (OR per log unit, 1.46; 95% CI, 1.14-1.87) and hypertension (OR, 1.36; 95% CI, 1.08-1.71). In women, retinopathy was associated with very low levels of urinary albumin excretion (urinary albumin/creatinine ratio >0.43 mg/mmol). Conclusion: This study confirms results from previous studies on the strong association between blood pressure and retinopathy. A novel finding is the sex differences in risk factors for retinopathy, suggesting a sex difference in the pathogenesis leading to retinopathy. [ABSTRACT FROM AUTHOR]

Background Markedly overweight people can develop progressive proteinuria and kidney failure secondary to obesity-related glomerulopathy ( ORG). Glomerular lesions in dogs with experimentally induced obesity are similar to those in people with ORG. Objectives The aim of this study was to evaluate if urine protein and albumin excretion is greater in overweight and obese dogs than in dogs of ideal body condition. Methods Client-owned dogs were screened for underlying health conditions. These dogs were assigned a body condition score ( BCS) using a 9-point scoring system. Dogs with a BCS of ≥ 6 were classified as being overweight/obese, and dogs with a BCS of 4 or 5 were classified as being of ideal body weight. The urine protein:creatinine ratio ( UPC) and urine albumin:creatinine ratio ( UAC) were then determined, and compared between 20 overweight/obese dogs and 22 ideal body weight control dogs. Results Median UPC (0.04 [range, 0.01-0.14; interquartile range, 0.07]) and UAC (0.41 [0-10.39; 3.21]) of overweight/obese dogs were not significantly different from median UPC (0.04 [0.01-0.32; 0.07]) and UAC (0.18 [0-7.04; 1.75]) in ideal body weight dogs. Conclusions Clinicopathologic abnormalities consistent with ORG were absent from overweight/obese dogs in this study. [ABSTRACT FROM AUTHOR]

Background Elevated serum uric acid (UA) could be a risk factor for hypertension, type 2 diabetes mellitus and cardiovascular disease. In addition, elevated serum UA may be associated with impaired renal function. However, it is unclear whether elevated serum UA is a cause of microalbuminuria or not. Therefore, we performed a prospective cohort study of the temporal relationship between baseline elevated serum UA and the development of microalbuminuria in Korean men. Design and methods A microalbuminuria-free cohort of 1743 healthy Korean men, who had their urine albumin-creatinine ratio (UACR) calculated for a medical check-up programme in 2005, was followed until 2010. Microalbuminuria was defined as a urine albumin-creatinine ratio between 30 and 300 μg/mg. Cox proportional hazards model was performed. Results During 5884·6 person-years of follow-up, 96 incident cases of microalbuminuria developed between 2006 and 2010. After adjusting for multiple covariates, the hazard ratios (95% confidence intervals) for incident microalbuminuria when comparing the second tertile to the third tertile of serum UA levels vs. the first tertile were 1·52 (0·86-2·70) and 2·27 (1·30-3·98), respectively ( P for trend = 0.005). Conclusion Elevated serum UA level was independent risk factor for the development of microalbuminuria during a 5-year follow-up in Korean men. [ABSTRACT FROM AUTHOR]

. Purpose: To determine the prevalence of visual impairment, retinopathy and macular oedema, and assess risk factors for retinopathy in persons with diabetes. Methods: The present study included 514 participants with diabetes aged 46-87 years from the Tromsø Eye Study, a sub-study of the population-based Tromsø Study in Norway. Visual acuity was measured using an auto-refractor. Retinal images from both eyes were graded for retinopathy and macular oedema. We collected data on risk factor exposure from self-report questionnaires, clinical examinations, laboratory measurements and case note reviews. Regression models assessed the cross-sectional relationship between potential risk factors and diabetic retinopathy. Results: The prevalence of visual impairment (corrected Snellen visual acuity <20/60 in the better-seeing eye) was 1.6%. The prevalence of diabetic retinopathy was 26.8% and macular oedema 3.9%. In a multivariable logistic regression model, retinopathy was associated with longer diabetes duration (odds ratio, OR 1.07, 95% CI 1.03-1.11), insulin use (OR 2.14, 95% CI 1.19-3.85), nonfasting glucose (OR 1.07, 95% CI 1.00-1.15) and microalbuminuria (OR 1.89, 95% CI 1.28-2.81). Sub-group analyses showed association between retinopathy and even low levels of microalbuminuria (1.16 mg/mmol). Conclusion: The findings suggest that low levels of microalbuminuria may be a useful risk predictor for identifying individuals with diabetes at high risk of retinopathy. The study confirms previous findings that insulin use, longer diabetes duration and higher levels of blood glucose are associated with retinopathy in persons with diabetes. The prevalence of diabetic retinopathy was similar as reported in other studies. [ABSTRACT FROM AUTHOR]

Background The aims of the present study were to determine the frequency of delayed gastric emptying in children and adolescents with type 1 diabetes mellitus ( T1DM) and to investigate the relationship between gastric emptying rate and other contributing factors (e.g. serum HbA1c, duration of diabetes and microalbuminuria) in these patients. Methods This was a clinical trial evaluating the rate of gastric emptying of solid meals in 33 children and adolescents with T1DM and in 26 healthy peers using a radionuclide method. Three consecutive overnight urine collections were used to calculate the albumin excretion rate. Results There was no significant difference in the gastric half-emptying time ( GE t½) between patients and controls (151.7 ± 154.5 vs 109.8 ± 60.5 min, respectively; P = 0.885) or the frequency of delayed gastric emptying (36.4% vs 30.8%, respectively; P = 0.433). There was a moderately positive correlation between GE t½ and the duration of diabetes ( r = 0.380; P = 0.029). There was no correlation between GE t½ and microalbumin levels in T1DM patients. In these patients, the body mass index standard deviation scores were significantly lower than in patients with normal gastric emptying (-0.13 ± 0.87 vs 0.7 ± 1.23, respectively; P = 0.044). Conclusion Progression of delayed gastric emptying is more likely to be related to a longer duration of diabetes than glycemic control in children and adolescents with T1DM. Patients with delayed gastric emptying are thinner compared with patients with a normal rate of gastric emptying; they may also be asymptomatic. [ABSTRACT FROM AUTHOR]

Objective To assess albuminuria in rural Zambia among patients with diabetes mellitus only ( DM group), hypertension only ( HTN group) and patients with combined DM and HTN ( DM/ HTN group). Methods A cross-sectional survey was conducted at St. Francis Hospital in the Eastern province of Zambia. Albumin-creatinine ratio in one urine sample was used to assess albuminuria. Other information obtained included age, sex, body mass index (BMI), waist circumference (WC), blood pressure (BP), glycosylated haemoglobin ( HbA1c), random capillary glucose, time since diagnosis, medication and family history of DM or HTN. Results A total of 193 participants were included ( DM group: n = 33; HTN group: n = 92; DM/ HTN group: n = 68). The participants in the DM group used insulin more frequently as diabetes medication than the DM/ HTN group ( P < 0.05). Furthermore, the DM group was younger and had lower BMI, WC and BP than the two other groups. In the DM group, HTN group and DM/ HTN group, microalbuminuria was found in 12.1%, 19.6% and 29.4% ( P = 0.11), and macroalbuminuria was found in 0.0%, 3.3% and 13.2% ( P = 0.014), respectively. The urine albumin ( P = 0.014) and albumin-creatinine ratio ( P = 0.0006) differed between the three groups. Conclusion This hospital-based survey in rural Zambia found a lower frequency of albuminuria among the participants than in previous studies of patients with DM or HTN in urban sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background and purpose Hemorrhagic transformation (HT) is one of the most problematic complications to arise from intravenous thrombolysis ( IVT). This study was conducted to assess whether micro- and macroalbuminuria could be associated with HT after IVT in patients with acute ischaemic stroke, and to investigate whether the value of urinary albumin-to-creatinine ratios would correlate with the degree of HT. Methods This was a retrospective study of stroke patients who had undergone IVT within 3 h of symptom onset. Albuminuria assessment was based on random morning spot urine collection with patients in a fasting state, the first morning after IVT. Multiple logistic regression analysis was used to evaluate whether the presence of micro- and macroalbuminuria might be independent predictors of HT. Results One-hundred and fifty-four patients were included in the study. Fifty-one patients had HT. The presence of micro- or macroalbuminuria was associated with HT after adjustment for variables with clinical significance (adjusting for age, atrial fibrillation, platelet counts, baseline National Institutes of Health Stroke Scale score, hypertension and diabetes mellitus; odds ratio, 2.542; 95% confidence interval, 1.106-5.841; P = 0.028). There were significant relationships between the presence of micro- and macroalbuminuria and types of HT. Conclusion In conclusion, the results of this study suggest that the presence of micro- and macroalbuminuria after IVT could be a predictor of severe HT in patients with acute ischaemic stroke. [ABSTRACT FROM AUTHOR]

Small urinary protein loss (low-grade albuminuria or microalbuminuria) may reflect altered permeability of the glomerular filtration barrier. In the present study, it was hypothesized that children with obstructive sleep apnea have an increased risk of microalbuminuria compared with control subjects without sleep-disordered breathing. Albumin-to-creatinine ratio was measured in morning spot urine specimens collected from consecutive children with or without snoring who were referred for polysomnography. Three groups were studied: (i) control subjects (no snoring, apnea-hypopnea index < 1 episode h−1; n = 31); (ii) mild obstructive sleep apnea (snoring, apnea-hypopnea index = 1-5 episodes h−1; n = 71); and (iii) moderate-to-severe obstructive sleep apnea (snoring, apnea-hypopnea index > 5 episodes∙h−1; n = 27). Indications for polysomnography in control subjects included nightmares, somnambulism and morning headaches. An albumin-to-creatinine ratio > median value in the control group (1.85 mg of albumin per g of creatinine) was defined as elevated. Logistic regression analysis revealed that children with moderate-to-severe obstructive sleep apnea, but not those with mild obstructive sleep apnea, had increased risk of elevated albumin-to-creatinine ratio relative to controls (reference) after adjustment for age, gender and presence of obesity: odds ratio 3.8 (95% confidence interval 1.1-12.6); P = 0.04 and 1.5 (0.6-3.7); P > 0.05, respectively. Oxygen desaturation of hemoglobin and respiratory arousal indices were significant predictors of albumin-to-creatinine ratio ( r = 0.31, P = 0.01; and r = 0.43, P < 0.01, respectively). In conclusion, children with moderate-to-severe obstructive sleep apnea are at significantly higher risk of increased low-grade excretion of albumin in the morning urine as compared with control subjects without obstructive sleep apnea. These findings may reflect altered permeability of the glomerular filtration barrier related to nocturnal hypoxemia and sympathetic activation which are induced by obstructive sleep apnea. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate microalbuminuria at mid-pregnancy, using the albumin-to-creatinine ratio (ACR), as a predictor of pre-eclampsia. Material and Methods: This prospective observational study was carried out on 144 normotensive women, aged < 35 years, body mass index < 25 kg/m2, and live singleton pregnancy between 24 and 28 weeks. In all, the ACR was measured in spot random urine samples. Normoalbuminuria was an ACR of <30 mg/g, whereas microalbuminuria was an ACR of 30-299 mg/g creatinine. All were followed till delivery. Primary outcome was the development of pre-eclampsia. The secondary outcome measures were preterm births and neonatal birthweight. Statistical analysis was done with Fisher's exact and t-tests. Results: Of all, 77.1% (111/144) had normoalbuminuria and 22.9% (33/144) had microalbuminuria. Of 33 microalbuminuric women, the mean blood pressure was significantly higher in those who subsequently developed pre-eclampsia ( P < 0.001). The mean ACR (mg/g) in this cohort was 60.6 ± 29.4. The mean ACR (mg/g) in women who subsequently developed pre-eclampsia was significantly higher than in women who remained normotensive ( P = 0.003). Of 33 microalbuminuric women, 12 (36.4%) developed pre-eclampsia, and eight (24.2%) had preterm births. The mean birthweight (kg ± standard deviation) was significantly lower in the microalbuminuria group (2.45 ± 0.6) as compared to the normoalbuminuria group (2.8 ± 0.37), P < 0.001. Conclusion: Microalbuminuria in mid-pregnancy may be a significant predictor of development of subsequent pre-eclampsia, preterm birth and low-birthweight babies. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2012 Abstract Aims The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), encoded by the OLR1 gene, has been implicated in the pathogenesis of atherosclerosis. We therefore evaluated the genotyping of OLR1 gene in a sample of 55 patients with Metabolic Syndrome, a clinical condition characterized by a high cardiovascular risk. Methods and Patients The genotyping of the LOX-1 was performed by polymerase chain reaction (PCR) analysis of the IVS4-14 A>G OLR1 polymorphism embedded within the OLR1 Linkage Disequilibrium block. Patients were assessed for routine serum parameters, microalbuminuria, insulin resistance (HOMA) and oxidative stress (thiobarbituric acid reactive substances, TBARs and thioredoxin). Results The allele or genotype distribution of the OLR1 IVS4-14 A>G was not statistically different between MS and controls subjects. A positive association was found between IVS4-14 GG genotype, microalbuminuria and fasting glycaemia as well as a higher frequency of type 2 diabetes, elevated microalbuminuria, fasting serum glucose and HOMA index in the same subjects. Thioredoxin values were higher in patients with MS but did not differ in relation to OLR1 IVS4-14 A>G genotype. The TBARs/Cholesterol ratio was higher in MS both in IVS4-14 GG and in IVS4-14 AG. Conclusion IVS4-14 GG genotype seems to be related to glucose metabolism disturbance, elevated insulin level and lipid peroxidation in patients with MS. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2012; 42 (12): 1272-1277 Abstract Background HERMEX is a population-based study which try to evaluate the relative weight of cardiovascular risk factors in the population of Extremadura. This report provides the data obtained about microalbuminuria in a large Spanish population. Design and methods Observational, cross-sectional, population-based study. A total of 3402 subjects were randomly selected from the Health Care System of Extremadura. The final sample included 2813 subjects (mean age 51·2 years, 53·5% female). Urinary albumin excretion rate (UAER) in first morning urine sample was analysed. Microalbuminuria was diagnosed when UAER was ≥ 22 in men or ≥ 31 mg/g in women. Results Prevalence of abnormal UAER in general population was 5·5% (microalbuminuria: 4·7%; proteinuria 0·8%). Microalbuminuria grew slightly in patients between 65 and 74 years and showed a dramatic increase in subject older than 75 years ( P < 0·001). Men showed a high prevalence of microalbuminuria (5·8% vs. women 3·6%; P = 0·006 chi-squared test). Increased UAER was more common in obese subjects (6·7% vs. 2·3%, P < 0·001), hypertensive patients (8·3% vs. 2·3%, P < 0·001) and diabetic ones (10·9% vs. 3·7%, P < 0·001). The multivariate analysis showed a positive correlation of abnormal UAER with body mass index (BMI), systolic blood pressure, plasma creatinine and triglyceride levels. Conclusions A low frequency of abnormal UAER was detected in a randomly selected sample of Spanish general population. This finding agreed with the low rates of cardiovascular mortality and morbidity observed in Spain in spite of a high prevalence of classic cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background Physiologic peculiarities of Greyhounds as compared to other dogs make interpretation of laboratory results in this breed challenging for veterinarians. Hypertension in retired racing Greyhounds ( RRG) can contribute to microalbuminuria ( MA), overt proteinuria, and renal histologic lesions. Objectives To evaluate clinicopathologic findings, hemodynamic status, and renal histology in a population of healthy RRG. Animals RRG presented to Ohio State University College of Veterinary Medicine for inclusion in a spay and neuter program. Methods Cross-sectional study. RRG were classified as normotensive (<160 mmHg) or hypertensive (>160 mmHg) based on blood pressure ( BP) determinations using Doppler and oscillometric methods. Of the dogs evaluated, 62% (n = 29) were hypertensive and 38% (n = 18) were normotensive. Health status was evaluated using routine clinicopathologic tests ( CBC, serum biochemistry, urinalysis) as well as evaluation of fractional excretion of electrolytes and MA determinations. Adequate renal biopsy specimens (n = 15) were evaluated using light, immunofluoresence, and electron microscopy. Results All serum biochemistry results were normal in 45/49 dogs, but MA was more common in hypertensive (84% positive for MA) as compared with normotensive (18% positive for MA) RRG. Observed renal lesions were mild and renal biopsy scores were low in this sample of RRG. Conclusions Hypertension is common in RRG and might be breed-related. It is associated with MA, but observed renal lesions are mild. Whether or not hypertension and MA in RRG leads to progressive renal damage requires longitudinal study. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 1043-1046 (2012) Aim To evaluate the prevalence of increased renal resistive index and related factors among patients with Type 2 diabetes with different levels of creatinine clearance and urinary albumin excretion. Methods Laboratory analyses, including calculation of 24-h urinary albumin excretion and 24-h creatinine clearance, and renal doppler ultrasonography to measure renal resistive index, were carried out for patients newly diagnosed with Type 2 diabetes mellitus. Results Participants were classified into four groups according to 24-h creatinine clearance and 24-h urinary albumin excretion levels. Group 1 was composed of 73 patients (54.1%) with normal 24-h creatinine clearance and 24-h urinary albumin excretion. Group 2 was composed of 34 (25.2%) patients with normal 24-h creatinine clearance and increased 24-h urinary albumin excretion. Group 3 was composed of 14 (10.4%) patients with decreased 24-h creatinine clearance and normal 24-h urinary albumin excretion. Group 4 was composed of 14 (10.4%) patients with both decreased 24-h creatinine clearance and increased 24-h urinary albumin excretion . In total, 41 patients (30.4%) had increased renal resistive index levels. Comparison of the four groups with respect to increased renal resistive index revealed: among group 1 patients, 10 (13.7%) had increased renal resistive index levels; among group 2 patients, 14 (41.2%) had increased renal resistive index levels; among group 3 patients, eight (57.1%) had increased renal resistive index levels; among group 4 patients, nine (64.3%) had increased renal resistive index levels ( P < 0.0001 for trend). In multivariate regression, 24-h creatinine clearance ( P < 0.0001), but not 24-h urinary albumin excretion, was related to increased renal resistive index levels. Conclusion Renal resistive index levels were highest in patients with Type 2 diabetes with both decreased 24-h creatinine clearance and increased 24-h urinary albumin excretion, whereas they were lowest in patients with normal creatinine clearance and normal urinary albumin excretion. [ABSTRACT FROM AUTHOR]

Peripheral polyneuropathy (PN) is a frequent complication of diabetes. However, mechanisms underlying the development of PN are multifactorial and not well understood. Our aim was to examine the association of plasma homocysteine (Hcy) with the prevalence and grade of peripheral PN in patients with type 2 diabetes (T2DM). We studied a cohort of 196 subjects with T2DM classified according to the grade of PN (Neuropathy Disability Score, NDS). Subjects with the highest grade of PN were older and had significantly increased levels of creatinine, microalbuminuria, HbA1c, and plasma Hcy compared to the other two groups. The differences in plasma Hcy values were maintained after correcting for confounding factors. Plasma Hcy, HbA1c, duration of diabetes, and age were predictors of the grade of PN. In conclusion, for each increase of 1 µmol in plasma Hcy there was a 23% increase of the risk of diabetic PN evaluated by NDS. Moreover, the grade of PN was predicted by plasma Hcy and HbA1c values, age and duration of diabetes. Further prospective studies should be conducted to confirm the association of plasma Hcy levels with the grade of PN in subjects with T2DM. [ABSTRACT FROM AUTHOR]

Diabet. Med. 28, 1182-1187 (2011) Abstract Aims Renin-angiotensin inhibitors in Type 2 diabetes and microalbuminuria reduce renal and cardiovascular risk, but evidence supporting use of maximal tolerated dose is unclear. We aimed to determine the extent of renin-angiotensin inhibitor dose-dependent effects from randomized trials carried out in a clinical setting. Methods In a meta-analysis of randomized clinical trials, alternate doses of angiotensin receptor blockers or angiotensin converting enzyme inhibitors in patients with Type 2 diabetes and microalbuminuria were compared. MEDLINE, EMBASE and the Cochrane Register of Controlled Trials were searched from January 2006 to August 2010. Trials prior to January 2006 were identified from a prior systematic review. Identified outcomes were albumin excretion rate, progression and regression of albuminuria and adverse events. Results Four trials including 1051 patients compared doses of angiotensin receptor blockers. No trials compared doses of angiotensin converting enzyme inhibitor. The percentage decline in albumin excretion rate from baseline was greater with higher doses (18% higher, 95% CI 8-28%), the regression to normoalbuminuria was greater (OR 1.66, 95% CI 1.22-2.27), with less progression to macroalbuminuria (OR 0.62, CI 0.38-1.02). Adverse events were fewer with lower-dose angiotensin receptor blockers (OR 1.32, 95% CI 0.90-1.92). Conclusions Higher-dose compared with lower-dose angiotensin receptor blockers in Type 2 diabetes with microalbuminuria are associated with significantly reduced albumin excretion rate and increased regression to normoalbuminuria. Adverse events are more frequent, but not significantly so. There is potential for trials to determine clinical cardiovascular and renal outcomes at differing doses. Our findings support current recommendations to titrate renin-angiotensin inhibitors to maximum dose whilst considering risk of adverse side effects with higher doses. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aim: Obstructive uropathies (OU) in childhood constitute one of the major causes of chronic renal insufficiency. Transforming growth factor-β1 (TGF-β1) is considered to be the major fibrogenic growth factor. The aim of the present study was to investigate urinary TGF-β1 levels in children with obstructive and non-obstructive uropathies (NOU). Methods: This study involved 19 children with OU, 11 children with non-obstructive hydronephrosis and 21 healthy children. Urinary TGF-β1, proteinuria, microalbuminuria and urinary α1-microglobulin were measured, and renal function was assesed. The results were statistically analyzed. Results: Mean urinary TGF-β1 concentrations in patients with OU were significantly higher than those with NOU (4.14 ± 0.67 creatinine vs 1.80 ± 0.24 pg/mmol creatinine, P < 0.05) and healthy controls (1.66 ± 0.28 pg/mmol creatinine, P < 0.05). Positive correlations of urinary TGF-β1 concentrations with proteinuria ( r = 0.87, P < 0.0001) and urinary α1-microglobulin ( r = 0.82, P = 0.0002) were found in patients with OU. Conclusion: Children with OU have higher urinary TGF-β1 than children with NOU. Urinary TGF-β1 may be a useful non-invasive tool for the differential diagnosis between OU and NOU in children. A positive correlation of TGF-β1 with markers of renal tissue damage in patients with OU was found. [ABSTRACT FROM AUTHOR]

Aims Asymmetric dimethylarginine (ADMA) is an independent risk factor for cardiovascular disease and its concentrations are increased in several diseases, including diabetes. However, there is limited information on this plasma marker in young people, particularly in those with Type 1 diabetes. The aim of the present study was therefore to perform a longitudinal evaluation of plasma ADMA and of its determinants in young people with childhood-onset Type 1 diabetes. Methods For measurement of ADMA using mass spectrometry, 1018 longitudinal stored blood samples were available from 330 young people with Type 1 diabetes followed in the Oxford Regional Prospective Study. Additional data concerning annual assessments of HbA1c, height, weight, insulin dose and three early morning urine samples for measurement of the albumin/creatinine ratio were available. Results ADMA levels were significantly higher in males than in females (mean ± sd: 0.477 ± 0.090 vs. 0.460 ± 0.089 μmol /l, P = 0.002) and declined with chronological age (estimate ± se: -0.0106 ± 0.0008, P < 0.001). A significant inverse association was detected between ADMA and HbA1c (estimate ± se: -0.0113 ± 0.001, P < 0.001). ADMA levels were lower in subjects developing microalbuminuria (mean ± sd: 0.455 ± 0.093 vs. 0.476 ± 0.087 μmol /l, P = 0.001) than in subjects with normoalbuminuria, but this difference disappeared after adjusting for HbA1c. Conclusions In this longitudinal study, ADMA concentrations decreased with age and were significantly higher in males and lower in subjects developing microalbuminuria. These associations were largely explained by a paradoxical negative association between HbA1c and ADMA. We suggest that chronic hyperglycaemiamight down-regulate mechanisms implicated in ADMA production or stimulate its metabolism confounding short-term associations with complications risk. [ABSTRACT FROM AUTHOR]

Kappelle PJWH, Gansevoort RT, Hillege JL, Wolffenbuttel BHR, Dullaart RPF on behalf of the PREVEND study group (University Medical Center Groningen and University of Groningen, Groningen, The Netherlands). Apolipoprotein B/A-I and total cholesterol/high-density lipoprotein cholesterol ratios both predict cardiovascular events in the general population independently of nonlipid risk factors, albuminuria and C-reactive protein. J Intern Med 2011; : 232-242. The total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and apolipoprotein (apo) B/A-I ratios predict major adverse cardiovascular events (MACEs). The extent to which these associations are modified by high-sensitivity C-reactive protein (hs-CRP) and albuminuria is largely unknown. We compared the strength of these ratios with first MACE in the general population and determined whether these associations remain when taking account of these risk markers. A prospective case-cohort study was performed among 6948 subjects (PREVEND cohort) without previous cardiovascular disease and who did not use lipid-lowering drugs initially. Fasting serum TC, low-density lipoprotein cholesterol (LDL-C), HDL-C, non-HDL-C, apoB, apoA-I, triglycerides, hs-CRP and albuminuria were measured at baseline. The composite endpoint was incident MACE. A total of 362 first cardiovascular events occurred during 7.9 years of follow-up. All pro- and anti-atherogenic measures of lipoproteins and apos predicted MACEs in age- and sex-adjusted Cox proportional hazard analyses ( P = 0.018 to P < 0.001). The age- and sex-adjusted hazard ratio (HR) was 1.37 [95% confidence interval (CI), 1.26-1.48] for the apoB/apoA-I ratio and 1.24 (95% CI, 1.18-1.29) for the TC/HDL-C ratio (both P < 0.001). These relationships were essentially unaltered after additional adjustment for triglyceride levels. Pair-wise comparison revealed that these ratios were of similar importance in age- and sex-adjusted analysis ( P = 0.397). The HRs of apoB/apoA-I ( P < 0.001) and TC/HDL-C ( P < 0.001) for risk of MACEs were only marginally attenuated by additional controlling for traditional risk factors (hypertension, diabetes, obesity and smoking), hs-CRP and albuminuria. First MACE is associated with both the fasting serum apoB/apoA-I ratio and the TC/HDL-C ratio in the general population, independently of triglycerides, hs-CRP and albuminuria. [ABSTRACT FROM AUTHOR]

Aims To compare the renal effects of low-vs. high-dose atorvastatin in patients with Type 2 diabetes mellitus and optimally managed early renal disease. Methods We compared the 2-year progression of nephropathy in a double-blind randomized controlled trial of atorvastatin 80 mg/ day (n = 60) vs. 10 mg / day (n = 59) in patientswith Type 2 diabeteswithmicroalbuminuria or proteinuria [mean (sd): age 64 years (10 years); HbA1c 7.7% (1.3%), 61 mmol / mol (10 mmol / mol); blood pressure 131 / 73 mmHg; renin-angiotensin system blocker use > 80%; dual blockade > 67%] recruited from diabetes clinics in Greater Manchester. Results Over (mean) 2.1 years of follow-up, the Modification of Diet in Renal Disease estimated glomerular filtration rate declined by 3 ml min-1 1.73 m-2 in the combined group. The mean (95%CI) between-group difference during follow-up was not significant [2.2 ml min-1 1.73 m-2 (-1.1 to 5.4 ml min-1 1.73 m-2), P = 0.20] after adjusting for baseline differences in renal function; positive difference favours 80 mg dose. Similarly, there was no significant difference in creatinine clearance by Cockcroft and Gault [2.5 ml / min (-2.4 to 7.3 ml / min), P = 0.32]; serum creatinine / 24-h urine collections [4.0 ml / min ()4.8 to 12.7 ml / min), P = 0.38]; cystatin C (P = 0.69); or 24-h urine protein or albumin excretion (P = 0.92; P = 0.93). We recorded no significant between-group differences in deaths or adverse events. Conclusions In patients with Type 2 diabetes with early renal disease, we found no statistical difference in renal function between those taking high- or low-dose atorvastatin over 2 years. We cannot exclude a beneficial effect of < 1.6 ml min-1 1.73 m-2 year-1 on Modification of Diet in Renal Disease estimated glomerular filtration rate, or if blood pressure management or if renin-angiotensin system blocker use had not been optimized. [ABSTRACT FROM AUTHOR]