Pilz, Stefan; Rutters, Femke; Nijpels, Giel
was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS......OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...
Kim, Tae Nyun; Lee, Eun Ju; Hong, Jae Won; Kim, Jung Min; Won, Jong Chul; Kim, Mi Kyung; Noh, Jung Hyun; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Dong-Jun
Abstract Studies have shown that albuminuria, obesity, and sarcopenia may share pathophysiological processes related to cardiovascular disease risk. Their direct relationships, however, have not been examined. This study investigated the association between albuminuria and sarcopenia in a representative fraction of the Korean population. Of the 10,589 people who participated in the 2011 Korea National Health and Nutrition Examination Survey, 2158 participants aged over 19 years had been tested for albumin-to-creatinine ratio and for body composition data using dual-energy x-ray absorptiometry. Albuminuria was defined as an albumin-to-creatinine ratio ≥30 mg/g. Sarcopenia was defined as a skeletal muscle index (SMI) (SMI (%) = total appendicular skeletal muscle mass [kg]/weight [kg] × 100) of less than 1 standard deviation (SD) (grade 1) or 2 SD (grade 2) below the sex-specific mean for a younger reference group. The prevalence of albuminuria was higher in those with grade 2 sarcopenia than in those with a normal SMI or grade 1 sarcopenia (33.3% versus 8.4% and 8.9%; P albuminuria than in those with the upper tertile of normoalbuminuria. In addition, multiple logistic regression analysis showed the odds ratio for albuminuria risk in the grade 2 sarcopenia group was 2.93 (95% confidence interval [CI], 1.46–5.88), compared with normal SMI after adjusting for potential confounding factors, including the presence of obesity, diabetes, and hypertension. Moreover, individuals with albuminuria had an odds ratio of 3.39 (95% [confidence interval], 1.38–8.37) for grade 2 sarcopenia compared with those in the lowest tertile of normoalbuminuria. This is the first study to demonstrate that individuals with sarcopenia exhibited increased risk of albuminuria and vice versa. PMID:26817888
Pilz, S.; Rutters, F.; Nijpels, G.; Stehouwer, C.D.A.; Hojlund, K.; Nolan, J.J.; Balkau, B.; Dekker, J.M.
OBJECTIVE Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases.We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN AND METHODS
... blood test to estimate GFR . GFR stands for glomerular filtration rate. Your GFR number helps determine how well ... related articles Creatinine: What is it? Cystatin C Glomerular Filtration Rate (GFR) Hematuria in Adults Tests to Measure ...
Zanardo, Vincenzo; Bertin, Martina; de Luca, Federico; Zaninotto, Martina; Trevisanuto, Daniele; Cosmi, Erich
Intrauterine growth restriction (IUGR) is associated with hyperfiltration, glomerulosclerosis and albuminuria. Albuminuria may further lead to tubulointerstitial inflammation, fibrosis and tubular atrophy. The time at which this may occur is unknown. This study was designed to assess the relationship between glomerular and tubular damage in IUGR children. We enrolled 50 children, 25 IUGR, categorized by estimated fetal weight 2 SD, and 25 appropriate for gestational age (AGA) controls at 18 months of age. We compared albuminuria among IUGR and AGA children, to assess the relationship between albuminuria and contemporary sodium and lysozyme excretion, as a measure of tubular damage. The albumin-creatinine (mg/g) and sodium-creatinine (μM/L) ratios (3.12 and 441.3, versus 1.39 and 226.1 in AGA; p = 0.002 and p = 0.012, respectively) were significantly higher in the IUGR subjects compared with AGA children, and significantly correlated (rho = 0.593, p = 0.002). Conversely, urinary lysozyme was undetectable or in normal excretion range. Our results show glomerulosclerosis and albuminuria in IUGR children aged 18 months. Elevated sodium excretion in the absence of abnormal lysozymuria may represent a epiphenomenon of glomerulosclerosis and of albuminuria.
Faas, M.M.; van der Schaaf, G.; Borghuis, T.; Jongman, R.M.; van Pampus, Maria; de Vos, P.; van Goor, Harry; Bakker, W.W.
BACKGROUND: As circulating plasma ATP concentrations are increased in pre-eclampsia, we tested whether increased plasma ATP is able to induce albuminuria during pregnancy. METHODS: Pregnant (day 14) and non-pregnant rats were infused with ATP (3000 microg/kg bw) via a permanent jugular vein cannula.
Tylicki, Leszek; Debska-Slizien, Alicja M; Lizakowski, Slawomir; Przybylska, Milena; Heleniak, Zbigniew; Renke, Marcin; Chamienia, Andrzej L; Biedunkiewicz, Bogdan; Rutkowski, Przemyslaw; Małgorzewicz, Sylwia; Rutkowski, Boleslaw
The renoprotective effects of the direct renin inhibitor, aliskiren, in renal transplant recipients have been supposed, but not finally proven. We performed an exploratory double-blind, losartan controlled, cross-over study to evaluate the influence of aliskiren, direct renin inhibitor, on albuminuria and other surrogate markers of kidney injury in patients after renal transplantation. The safety of this therapy was also evaluated. 16 of 18 patients (12 M, 4 F), 48.3 ± 9.0 years, 57.7 ± 9.1 months after kidney transplantation, with hypertension and stable serum creatinine 1.4 ± 0.08 mg/dl without proteinuria, completed the protocol. Each patient underwent two 8-week treatment periods (one with 150 mg of aliskiren, and one with 50 mg of losartan) in random order, allowing an 8-week placebo washout between them. There were no differences in albuminuria, transforming growth factor β-1 and 15-F2t-isoprostanes urine excretion between aliskiren and losartan. Creatinine serum level, eGFR, 24 h systolic and 24 h diastolic blood pressure were stable through the study. There were no differences in haemoglobin and potassium serum concentration between studied drugs. Aliskiren decreases albuminuria in renal transplant recipients with clinically minimal side effects. The effect does not differ from that of losartan.
Deckert, T; Feldt-Rasmussen, B; Borch-Johnsen, K
retinopathy, and severe macroangiopathy suggests a common cause of albuminuria and the severe renal and extrarenal complications associated with it. Enzymes involved in the metabolism of anionic components of the extracellular matrix (e.g. heparan sulphate proteoglycan) vulnerable to hyperglycaemia, seem......Albuminuria in Type 1 (insulin-dependent) diabetes is not only an indication of renal disease, but a new, independent risk-marker of proliferative retinopathy and macroangiopathy. The coincidence of generalised vascular dysfunction and albuminuria, advanced mesangial expansion, proliferative...... to constitute the primary cause of albuminuria and the associated complications. Genetic polymorphism of such enzymes is possibly the main reason for variation in susceptibility....
Rein, Philipp; Saely, Christoph H; Vonbank, Alexander; Fraunberger, Peter; Drexel, Heinz
People with chronic kidney disease frequently experience cardiovascular events. This study sought to investigate whether the presence of albuminuria displays a vascular risk equivalent to that in patients with prior myocardial infarction. Albuminuria was defined as a urinary albumin to creatinine ratio of 30 μg/mg or greater in 852 consecutive patients undergoing coronary angiography. Prospectively, we recorded vascular events over 3.2±1.2 years. From our patients, 513 (60.2%) had neither albuminuria nor a history of MI, 126 (14.8%) had albuminuria without prior MI, 137 (16.1%) did not have albuminuria but had a history of MI, and 76 (8.9%) had both, albuminuria and prior MI. Compared with the incidence of the composite endpoint among normoalbuminuric patients with no prior MI (11.9%), event rates nearly doubled both in patients with albuminuria without prior MI (24.6%; p=0.003) and in normoalbuminuric patients with a history of prior MI (21.2%; p=0.004) and were highest in patients with both, albuminuria and prior MI (36.8%; palbuminuria and no prior history of MI and those with normoalbuminuria but prior MI (p=0.972). Moreover, the event rate in patients with both, albuminuria and history of MI, was significantly higher (palbuminuria is a CAD risk equivalent. Thus, cardiovascular risk factors in albuminuric patients should be treated as aggressively as in patients with prior MI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Methods: An English language literature search using medline (1991-2000) was done to access research/review articles on micro albuminuria. The study design and quality were assessed, with particular ... Large variations, however, occur in urinary albumin excretion rates. Micro albuminuria is associated with systemic ...
Bello, Aminu K.; de Zeeuw, Dick; El Nahas, Meguid; Brantsma, Auke H.; Bakker, Stephan J. L.; de Jong, Paul E.; Gansevoort, Ronald T.
Background. Increased levels of albuminuria have been recognized as a feature of obesity and the metabolic syndrome, and to be associated with an increased risk for cardiovascular and renal disease. The impact of weight change on albuminuria and its possible mechanism has not been studied yet in the
Petrykiv, Sergei I.; de Zeeuw, Dick; Persson, Frederik; Rossing, Peter; Gansevoort, Ron T.; Laverman, Gozewijn D.; Heerspink, Hiddo J. L.
AIMS Albuminuria-lowering drugs have shown different effect size in different individuals. Since urine albumin levels are known to vary considerably from day- to-day, we questioned whether the between-individual variability in albuminuria response after therapy initiation reflects a random
Rabelink, Ton J.; de Zeeuw, Dick
Albuminuria is commonly used as a marker of kidney disease progression, but some evidence suggests that albuminuria also contributes to disease progression by inducing renal injury in specific disease conditions. Studies have confirmed that in patients with cardiovascular risk factors, such as
Martens, Remy J H; Henry, Ronald M A; Houben, Alfons J H M; van der Kallen, Carla J H; Kroon, Abraham A; Schalkwijk, Casper G; Schram, Miranda T; Sep, Simone J S; Schaper, Nicolaas C; Dagnelie, Pieter C; Muris, Dennis M J; Gronenschild, Ed H B M; van der Sande, Frank M; Leunissen, Karel M L; Kooman, Jeroen P; Stehouwer, Coen D A
Albuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction. According to this concept, endothelial dysfunction of the renal microcirculation causes albuminuria by increasing glomerular capillary wall permeability and intraglomerular pressure, the latter eventually leading to glomerular capillary dropout (rarefaction) and further increases in intraglomerular pressure. However, direct evidence for an association between capillary rarefaction and albuminuria is lacking. Therefore, we examined the cross-sectional association between the recruitment of capillaries after arterial occlusion (capillary density during postocclusive peak reactive hyperemia) and during venous occlusion (venous congestion), as assessed with skin capillaroscopy, and albuminuria in 741 participants of the Maastricht Study, including 211 participants with type 2 diabetes. Overall, 57 participants had albuminuria, which was defined as a urinary albumin excretion ≥30 mg/24 h. After adjustment for potential confounders, participants in the lowest tertile of skin capillary recruitment during postocclusive peak reactive hyperemia had an odds ratio for albuminuria of 2.27 (95% confidence interval, 1.07 to 4.80) compared with those in the highest tertile. Similarly, a comparison between the lowest and the highest tertiles of capillary recruitment during venous congestion yielded an odds ratio of 2.89 (95% confidence interval, 1.27 to 6.61) for participants in the lowest tertile. In conclusion, lower capillary density of the skin microcirculation independently associated with albuminuria, providing direct support for a role of capillary rarefaction in the pathogenesis of albuminuria. Copyright © 2016 by the American Society of Nephrology.
Lee, Sung-Ho; Kim, Do Hoon; Kim, Yang-Hyun; Roh, Yong Kyun; Ju, Sang Yhun; Nam, Hyo-Yun; Nam, Ga-Eun; Choi, Jun-Seok; Lee, Jong-Eun; Sang, Jung-Eun; Han, Kyungdo; Park, Yong-Gyu
Abstract This study aimed to estimate the relationship between various lipid abnormalities and albuminuria in hypertensive Korean adults. Data obtained from the Korea National Health and Nutrition Examination Survey in 2011 to 2012 were analyzed. The study included 2330 hypertensive participants. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. Dyslipidemia parameters were defined as high TG ≥200 mg/dL, low HDL-C as HDL-C Albuminuria was defined as a urine albumin to creatinine ratio (ACR) ≥30 mg/g. Women with albuminuria showed significantly higher levels of TG, TC/HDL-C, and TG/HDL-C and a lower level of HDL-C than women without albuminuria (all P albuminuria (OR [95% confidence interval]: 1.53 [1.06–2.21], 1.21 [1.02–1.45], and 1.78 [1.21–2.63], respectively) and HDL-C with a decreased OR for albuminuria (0.78 [0.67–0.92]) after adjusting for all covariates. LogTG, TC/HDL-C, and logTG/HDL-C were associated with an increased prevalence of albuminuria in hypertensive women. Screening and treatment for dyslipidemia may be necessary for hypertensive women to address potential albuminuria. PMID:27100412
Nauta, Ferdau L.; Scheven, Lieneke; Meijer, Esther; van Oeveren, Wim; de Jong, Paul E.; Bakker, Stephan J.L.
Summary Background and objectives Albuminuria is associated with risk for renal and cardiovascular disease. It is difficult to predict which persons will progress in albuminuria. This study investigated whether assessment of urinary markers associated with damage to different parts of the nephron may help identify individuals that will progress in albuminuria. Design, setting, participants, & measurements Individuals were selected from a prospective community-based cohort study with serial follow-up and defined as “progressors” if they belonged to the quintile of participants with the most rapid annual increase in albuminuria, and reached an albuminuria ≥150 mg/d during follow-up. Patients with known renal disease or macroalbuminuria at baseline were excluded. Each progressor was matched to two control participants, based on baseline albuminuria, age, and sex. Furthermore, damage markers were measured in a separate set of healthy individuals. Results After a median follow-up of 8.6 years, 183 of 8394 participants met the criteria for progressive albuminuria. Baseline clinical characteristics were comparable between progressors and matched controls (n=366). Both had higher baseline albuminuria than the overall population. Urinary excretion of the glomerular damage marker IgG was significantly higher in progressors, whereas urinary excretion of proximal tubular damage markers and inflammatory markers was lower in these individuals compared with controls. Healthy individuals (n=109) had the lowest values for all urinary damage markers measured. Conclusions These data suggest that albuminuria associated with markers of glomerular damage is more likely to progress, whereas albuminuria associated with markers of tubulointerstitial damage is more likely to remain stable. PMID:23539232
Petrykiv, Sergei I; de Zeeuw, Dick; Persson, Frederik
AIMS: Albuminuria-lowering drugs have shown different effect size in different individuals. Since urine albumin levels are known to vary considerably from day-to-day, we questioned whether the between-individual variability in albuminuria response after therapy initiation reflects a random...... variability or a true response variation to treatment. In addition, we questioned whether the response variability is drug dependent. METHODS: To determine whether the response to treatment is random or a true drug response, we correlated in six clinical trials the change in albuminuria during placebo...... or active treatment (on-treatment) with the change in albuminuria during wash-out (off-treatment). If these responses correlate during active treatment, it suggests that at least part of the response variability can be attributed to drug response variability. We tested this for enalapril, losartan...
Background: Albuminuria, a kidney marker of microvascular disease, may herald microvascular disease elsewhere, including in the brain. Study Design: Cross sectional. Setting and Participants: Boston, MA (USA) elders receiving home health services to maintain independent living who consented to bra...
young adult offsprings of Nigeria hypertensive adults. Background: On the premise that micro-albuminuria is a predictor of early stage hypertensive disease and the fact that heredity plays an important role in the aetiology of essential hypertension, ...
Full Text Available Morphine has been reported to accelerate the progression of chronic kidney disease. However, whether morphine affects slit diaphragm (SD, the major constituent of glomerular filtration barrier, is still unclear. In the present study, we examined the effect of morphine on glomerular filtration barrier in general and podocyte integrity in particular. Mice were administered either normal saline or morphine for 72 h, then urine samples were collected and kidneys were subsequently isolated for immunohistochemical studies and Western blot. For in vitro studies, human podocytes were treated with morphine and then probed for the molecular markers of slit diaphragm. Morphine-receiving mice displayed a significant increase in albuminuria and showed effacement of podocyte foot processes. In both in vivo and in vitro studies, the expression of synaptopodin, a molecular marker for podocyte integrity, and the slit diaphragm constituting molecules (SDCM, such as nephrin, podocin, and CD2-associated protein (CD2AP, were decreased in morphine-treated podocytes. In vitro studies indicated that morphine modulated podocyte expression of SDCM through opiate mu (MOR and kappa (KOR receptors. Since morphine also enhanced podocyte oxidative stress, the latter seems to contribute to decreased SDCM expression. In addition, AKT, p38, and JNK pathways were involved in morphine-induced down regulation of SDCM in human podocytes. These findings demonstrate that morphine has the potential to alter the glomerular filtration barrier by compromising the integrity of podocytes.
Hong, Jae Won; Ku, Cheol Ryong; Noh, Jung Hyun; Kim, Dong-Jun
Abstract Although the associations between albuminuria and renal and cardiovascular diseases, including diabetes and hypertension, have been extensively studied, few studies have investigated the association between albuminuria and hearing impairment. In this study, we assessed the relationship between albuminuria and hearing impairment in 9786 adult Korean subjects, using data from the Korea National Health and Nutrition Examination Survey (KNHANES) performed in 2011–2012. The range of urinary albumin-to-creatinine ratio (UACR) was divided into 4 grades: grade 1 (first tertile of low-grade albuminuria [LGA]), 0.00 to 1.99 mg/g Cr; grade 2 (second tertile of LGA), 2.00 to 5.49 mg/g Cr; grade 3 (third tertile of LGA), 5.50 to 29.99 mg/g Cr; grade 4 (albuminuria), ≥30.00 mg/g Cr. The age- and sex-adjusted weighted UACR was higher in subjects with hearing impairment compared with those without hearing impairment (26.2 ± 4.7 mg/g Cr vs 14.1 ± 1.5 mg/g Cr, P = 0.020). The age- and sex-adjusted weighted prevalence of albuminuria was also higher in subjects with hearing impairment compared with subjects without hearing impairment. (8.3 ± 0.9% vs 5.8 ± 0.4%, P = 0.013) The age- and sex-adjusted weighted percentage of hearing impairment increased as UACR increased (18.0% ± 0.6%, 20.0% ± 0.8%, 22.2% ± 0.9%, 25.3% ± 2.0%, respectively; P albuminuria, with age, sex, tobacco use, heavy alcohol use, educational background, occupational noise exposure, obesity, hypertension, diabetes, total serum cholesterol, and estimated glomerular filtration rate (eGFR) albuminuria is associated with hearing impairment in the Korean general population, using nationally representative data. Screening for albuminuria would allow for interventions for the prevention of hearing impairment. PMID:26512589
Scheven, Lieneke; Joosten, Michel M.; de Jong, Paul E.; Bakker, Stephan J. L.; Gansevoort, Ron T.
Background-Elevated albuminuria as well as an increased serum uric acid concentration is associated with poor cardiovascular outcome. We questioned whether these 2 variables (albuminuria and serum uric concentration) may be interrelated via tubular uric acid reabsorption. Methods and
Martin-Lorenzo, Marta; Gonzalez-Calero, Laura; Martinez, Paula J.; Baldan-Martin, Montserrat; Lopez, Juan Antonio; Ruiz-Hurtado, Gema; de la Cuesta, Fernando; Segura, Juli?n; Vazquez, Jes?s; Vivanco, Fernando; Barderas, Maria G.; Ruilope, Luis M.; Alvarez-Llamas, Gloria
Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria developme...
Schmieder, Roland E.; Mann, Johannes F. E.; Schumacher, Helmut; Gao, Peggy; Mancia, Giuseppe; Weber, Michael A.; McQueen, Matthew; Koon, Teo; Yusuf, Salim
The degree of albuminuria predicts cardiovascular and renal outcomes, but it is not known whether changes in albuminuria also predict similar outcomes. In two multicenter, multinational, prospective observational studies, a central laboratory measured albuminuria in 23,480 patients with vascular disease or high-risk diabetes. We quantified the association between a greater than or equal to twofold change in albuminuria in spot urine from baseline to 2 years and the incidence of cardiovascular...
Petrykiv, Sergei I.; Laverman, Gozewijn D.; de Zeeuw, Dick; Heerspink, Hiddo J. L.
AIMS: Albuminuria reduction is essential for renal and cardiovascular protection. We characterized the efficacy of dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, on albuminuria. Secondly, we assessed whether the albuminuria-lowering effect varies among patients, and whether this
Rasmussen, Jon B; Thomsen, Jakúp A; Rossing, Peter
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. Al.......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........ 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...
Barzilay, Joshua I; Morgan, Timothy M; Murray, Anne M; Bryan, R Nick; Williamson, Jeff D; Schnall, Adrian; Launer, Lenore J
Albuminuria is associated with cognitive impairment in people with type 2 diabetes mellitus (T2DM). The brain volume correlates of albuminuria in people with T2DM have not been well investigated. We examined 502 individuals with T2DM (9-12 years duration; mean age ~62 years) who had a brain MRI at baseline and at 40 months. Baseline MRI findings were examined by the presence or absence of albuminuria (≥30mg/g creatinine). Changes in MRI findings were examined by whether albuminuria was persistent, intermittent, or absent during follow-up. At baseline, participants with albuminuria (28.7% of the cohort) had more abnormal white matter volume (AWMV) than participants without albuminuria on unadjusted analysis. This difference was attenuated with adjustment for systolic blood pressure, which was higher in participants with albuminuria than in those without albuminuria. During ~3.5 years of follow-up, participants with persistent albuminuria (15.8%) had a greater increase in new AWMV than participants without albuminuria (59.8%) or those with intermittent albuminuria on unadjusted analysis. This difference was attenuated with adjustment for age and systolic blood pressure. There were no significant differences in gray matter volume and total brain volume between participants with or without albuminuria at baseline or during follow-up. There was no significant effect modification of these findings by estimated glomerular filtration rate (eGFR) at baseline or change in eGFR during follow-up. In this diabetic cohort, baseline albuminuria and persistent albuminuria were not independently associated with any significant differences in brain volume measurements compared with participants without albuminuria. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Crews, Deidra C.; Boulware, L. Ebony; Gansevoort, Ron T.; Jaar, Bernard G.
Albuminuria has been associated with increased risk of multiple adverse outcomes, including ESRD, acute kidney injury, cardiovascular disease, and death. Some clinicians advocate for population-based screening of this condition, as a means of identifying individuals at high risk for morbidity and
Dobre, Daniela; Nimade, Sandeep; de Zeeuw, Dick
Purpose of the review To describe the role of albuminuria as a risk marker for heart failure and a predictor for treatment effect on heart failure prognosis. Recent findings The level of albumin in the urine is a predictor of heart failure in the general population and in patients with
Rossing, P; Hommel, E; Smidt, U M
with metoprolol and furosemide. Fall rate in glomerular filtration rate (GFR) was 9.5 +/- 3.8 ml/min/year (mean +/- SD) before and 3.6 +/- 3.6 during antihypertensive treatment. Albuminuria was 1442 (150 to 7564) micrograms/min (median range) in the last year before and 880 (96 to 3310) micrograms...
Full Text Available Although hyperuricemia is shown to accelerate chronic kidney disease, the mechanisms remain unclear. Accumulating studies also indicate that uric acid has both pro- and antioxidant properties. We postulated that hyperuricemia impairs the function of glomerular podocytes, resulting in albuminuria. Hyperuricemic model was induced by oral administration of 2% oxonic acid, a uricase inhibitor. Oxonic acid caused a twofold increase in serum uric acid levels at 8 weeks when compared to control animals. Hyperuricemia in this model was associated with the increase in blood pressure and the wall-thickening of afferent arterioles as well as arcuate arteries. Notably, hyperuricemic rats showed significant albuminuria, and the podocyte injury marker, desmin, was upregulated in the glomeruli. Conversely, podocin, the key component of podocyte slit diaphragm, was downregulated. Structural analysis using transmission electron microscopy confirmed podocyte injury in this model. We found that urinary 8-hydroxy-2′-deoxyguanosine levels were significantly increased and correlated with albuminuria and podocytopathy. Interestingly, although the superoxide dismutase mimetic, tempol, ameliorated the vascular changes and the hypertension, it failed to reduce albuminuria, suggesting that vascular remodeling and podocyte injury in this model are mediated through different mechanisms. In conclusion, vasculopathy and podocytopathy may distinctly contribute to the kidney injury in a hyperuricemic state.
Bentata, Yassamine; Karimi, Ilham; Benabdellah, Nawal; El Alaoui, Fatiha; Haddiya, Intissar; Abouqal, Redouane
Albuminuria is an early marker of renal impairment and a powerful factor of progression of renal disease in type 2 diabetes (T2D). Approximately, one-third of patients with T2D have micro- or macroalbuminuria and these patients have a high risk of progression toward End Stage Renal Disease (ESRD) as well as increased cardiovascular disease. The aim of this study was to determine the prevalence of remission, regression, persistence, and progression of albuminuria, and to evaluate the impact of change in albuminuria on kidney disease and cardiovascular disease in a prospective cohort of patients with T2D. This is a prospective study. The Ethics Committee of Morocco's Mohammed V University in Rabat approved the study protocol. Inclusion criteria targeted patients who were type 2 diabetics with albuminuria >30 mg/day, and who had been regularly followed-up in nephrology consultation for at least 36 months. Five-hundred twenty-four patients were included. 75.8 and 24.6% of all patients had micro- and macroalbuminuria at enrollment in the study. At the end of the study, 91, 141, 199, and 93 patients had remission, regression, persistence, and progression of albuminuria, respectively. Remission of microalbuminuria to normoalbuminuria was observed in 23.6% of cases. Regression of macroalbuminuria to micro- was observed in 29.9% of cases. In our study, the incidence of remission and/or regression of micro- and macroalbuminuria was higher. The incidence of ESRD and the occurrence of cardiac events were greater in the regression, persistence, and progression groups than in the remission of albuminuria group.
Thaisz, Jill; Tsaih, Shirng-Wern; Feng, Minjie; Philip, Vivek M.; Zhang, Yunyu; Yanas, Liane; Sheehan, Susan; Xu, Lingfei; Miller, Darla R.; Paigen, Beverly; Chesler, Elissa J.; Churchill, Gary A.
Albuminuria is an important marker of nephropathy that increases the risk of progressive renal and chronic cardiovascular diseases. The genetic basis of kidney disease is well-established in humans and rodent models, but the causal genes remain to be identified. We applied several genetic strategies to map and refine genetic loci affecting albuminuria in mice and translated the findings to human kidney disease. First, we measured albuminuria in mice from 33 inbred strains, used the data for haplotype association mapping (HAM), and detected 10 genomic regions associated with albuminuria. Second, we performed eight F2 intercrosses between genetically diverse strains to identify six loci underlying albuminuria, each of which was concordant to kidney disease loci in humans. Third, we used the Oak Ridge National Laboratory incipient Collaborative Cross subpopulation to detect an additional novel quantitative trait loci (QTL) underlying albuminuria. We also performed a ninth intercross, between genetically similar strains, that substantially narrowed an albuminuria QTL on Chromosome 17 to a region containing four known genes. Finally, we measured renal gene expression in inbred mice to detect pathways highly correlated with albuminuria. Expression analysis also identified Glcci1, a gene known to affect podocyte structure and function in zebrafish, as a strong candidate gene for the albuminuria QTL on Chromosome 6. Overall, these findings greatly enhance our understanding of the genetic basis of albuminuria in mice and may guide future studies into the genetic basis of kidney disease in humans. PMID:22859403
Wei, Xue-Biao; Liu, Yuan-Hui; He, Peng-Cheng; Yu, Dan-Qing; Zhou, Ying-Ling; Tan, Ning; Chen, Ji-Yan
We explored the impact of albuminuria on clinical outcomes in patients with infective endocarditis (IE). Patients with IE were prospectively enrolled and divided into 3 groups based on albuminuria measured by qualitative dipstick at admission and were followed up for 1y. Univariate and multivariate analysis were performed to evaluate the relationship between albuminuria and mortality. Nine-hundred seventy patients were divided into 3 groups: negative (urine dipstick negative) (n=694), trace (urine dipstick trace) (n=150) and positive (urine dipstick≥1+ protein) (n=126). In-hospital mortality increased with increasing albuminuria (5.2%, 8.0% and 17.5%, palbuminuria, positivity for albuminuria was an independent risk predictor for in-hospital death (OR=2.79, 95% CI=1.41-5.49; p=0.003). The cumulative rate of one-year mortality was higher among albuminuria-positive patients than among albuminuria-negative patients. Multivariate Cox analysis demonstrated that albuminuria positivity was associated with one-year mortality (HR=1.89, 95% CI=1.17-3.04, p=0.010). Albuminuria was independently associated with in-hospital death in IE patients. Urine dipstick≥1+ protein was linked to increased one-year mortality. As a simple and inexpensive marker, albuminuria measured by qualitative dipstick might be helpful for risk stratification in IE. Copyright © 2016 Elsevier B.V. All rights reserved.
Heerspink, H J L; Ninomiya, T; Persson, F
AIMS: To investigate whether the degree of albuminuria reduction observed in the ALTITUDE trial is associated with renal and cardiovascular protection, and secondly, whether the reduction in albuminuria was too small to afford clinical benefit. METHODS: In a post hoc analysis of the ALTITUDE trial...... in 8561 patients with type 2 diabetes and chronic kidney disease or cardiovascular disease we examined the effect of albuminuria changes at 6 months on renal and cardiovascular outcomes using Cox proportional hazard regression. RESULTS: The median change in albuminuria in the first 6 months...... in the aliskiren arm of the trial was -12% (25th to 75th percentile: -48.7_to_ +41.9%) and 0.0% (25th to 75th percentile: -40.2_to_55%) in the placebo arm. Changes in albuminuria in the first 6 months were linearly associated with renal and cardiovascular endpoints: a >30% reduction in albuminuria in the first 6...
Mann, Johannes F. E.; Schumacher, Helmut; Gao, Peggy; Mancia, Giuseppe; Weber, Michael A.; McQueen, Matthew; Koon, Teo; Yusuf, Salim
The degree of albuminuria predicts cardiovascular and renal outcomes, but it is not known whether changes in albuminuria also predict similar outcomes. In two multicenter, multinational, prospective observational studies, a central laboratory measured albuminuria in 23,480 patients with vascular disease or high-risk diabetes. We quantified the association between a greater than or equal to twofold change in albuminuria in spot urine from baseline to 2 years and the incidence of cardiovascular and renal outcomes and all-cause mortality during the subsequent 32 months. A greater than or equal to twofold increase in albuminuria from baseline to 2 years, observed in 28%, associated with nearly 50% higher mortality (HR 1.48; 95% CI 1.32 to 1.66), and a greater than or equal to twofold decrease in albuminuria, observed in 21%, associated with 15% lower mortality (HR 0.85; 95% CI 0.74 to 0.98) compared with those with lesser changes in albuminuria, after adjustment for baseline albuminuria, BP, and other potential confounders. Increases in albuminuria also significantly associated with cardiovascular death, composite cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure), and renal outcomes including dialysis or doubling of serum creatinine (adjusted HR 1.40; 95% CI 1.11 to 1.78). In conclusion, in patients with vascular disease, changes in albuminuria predict mortality and cardiovascular and renal outcomes, independent of baseline albuminuria. This suggests that monitoring albuminuria is a useful strategy to help predict cardiovascular risk. PMID:21719791
Pulido-Olmo, Helena; García-Prieto, Concha F; Álvarez-Llamas, Gloria; Barderas, María G; Vivanco, Fernando; Aranguez, Isabel; Somoza, Beatriz; Segura, Julián; Kreutz, Reinhold; Fernández-Alfonso, María S; Ruilope, Luis M; Ruiz-Hurtado, Gema
Resistant albuminuria, developed under adequate chronic blockade of the renin-angiotensin system, is a clinical problem present in a small number of patients with chronic kidney disease (CKD). The mechanism underlying this resistant albuminuria remains unknown. Matrix metalloproteinases (MMPs) are involved in the pathophysiology of cardiovascular and renal diseases. In the present study we tested the role of MMPs in resistant albuminuria. First we evaluated gelatinase MMP-2 and MMP-9 activity by zymography in the Munich Wistar Frömter (MWF) rat, a model of progressive albuminuria, and subsequently in patients with resistant albuminuria. Markers of oxidative stress were observed in the kidneys of MWF rats, together with a significant increase in pro-MMP-2 and active MMP-9 forms. These changes were normalized together with reduced albuminuria in consomic MWF-8(SHR) rats, in which chromosome 8 of MWF was replaced with the respective chromosome from spontaneously hypertensive rats. The MMP-2 and MMP-9 protein levels were similar in patients with normal and resistant albuminuria; however, high circulating levels of collagen IV, a specific biomarker of tissue collagen IV degradation, were observed in patients with resistant albuminuria. These patients showed a significant increase in gelatinase MMP-2 and MMP-9 activity, but only a significant increase in the active MMP-9 form quantified by ELISA, which correlated significantly with the degree of albuminuria. Although the expression of the tissue inhibitor of MMP-9 (TIMP)-1 was similar, a novel AlphaLISA assay demonstrated that the MMP-9-TIMP-1 interaction was reduced in patients with resistant albuminuria. It is of interest that oxidized TIMP-1 expression was higher in patients with resistant albuminuria. Therefore, increased circulating MMP-9 activity is associated with resistant albuminuria and a deleterious oxidative stress environment appears to be the underlying mechanism. These changes might contribute to the
Ching-Yuang Lin; Shiuh-Ming Huang
We do not yet fully grasp the significance of childhood albuminuria. Based on mass urinary screening (MUS) using albumin-specific dipsticks in school children, we studied the independent association of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in children with chronic kidney disease (CKD). Methods: A prospective cohort of 5351 children with albuminuria detected by school MSU during the period 1992–1996, followed up to 2009...
Gracchi, Valentina; van den Belt, Sophie M; Küpers, Leanne K; Corpeleijn, Eva; de Zeeuw, Dick; Heerspink, Hiddo J L
Microalbuminuria is common in the general adult population, with a prevalence of ∼7%, and is an independent indicator of renal and cardiovascular risks. Whether albuminuria is acquired during life (as a result of hypertension/diabetes) or is congenital and already present at birth is unknown. We studied the prevalence of microalbuminuria in toddlers and compared the distribution of albuminuria with that of the general adult population. In addition, we looked for possible associations between microalbuminuria and antenatal, postnatal and maternal factors. The urinary albumin concentration (UAC) was measured in 1352 children and the urinary albumin:creatinine ratio (UACR) in 1288 children from the Groningen Expert Center for Kids with Obesity (GECKO) Drenthe cohort (age range 20-40 months). Albuminuria distribution was compared with the albuminuria distribution in 40 854 participants of the general adult cohort of the Prevention of Renal and Vascular End stage Disease (PREVEND) study. Associations between albuminuria (expressed as UAC and UACR) and antenatal, postnatal and maternal factors were tested with linear regression analysis. The median UAC in the GECKO study was 2.3 mg/L (5th-95th percentiles: 2.1-25.5) and in the PREVEND study it was 6.0 mg/L (2.3-28.6) (P distribution comparison 0.053). The prevalence of UAC ≥ 20 mg/L was 6.9% in the GECKO study and 7.8% in the PREVEND study (P = 0.195). The prevalence of UACR ≥ 30 mg/g in the GECKO study was 23.4%. UAC and UACR were lower in boys. UAC was not associated with other determinants, but UACR was associated with age and gestational diabetes. The distribution of UAC and the prevalence of UAC > 20 mg/L in toddlers and in the young general adult population are comparable. These findings suggest that microalbuminuria is a congenital condition that may predispose to a higher cardiovascular risk later in life. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Tri Juli Edi Tarigan
Full Text Available Tujuan penelitian ini adalah untuk mengetahui peran magnesium pada nefropati diabetes dan mendapatkan proporsi albuminuria pada pasien DM tipe 2 dengan hipomagnesemia dan magnesium normal serta mendapatkan korelasi kadar Mg dengan albuminuria. Penelitian menggunakan desain cross sectional dengan consecutive sampling pada pasien DM tipe 2 yang terdiagnosis nefropati diabetes di Poliklinik Diabetes RSCM pada bulan Maret-Juni 2014. Dilakukan anamnesis faktor risiko, pemeriksaan fisik, kadar magnesium, albumine creatinine ratio dan A1C. Terdapat 38 subjek yang diikutsertakan dalam penelitian yang sebagian besar berusia lebih 50 tahun dan memiliki kontrol glikemik yang buruk (81,6%. Pada subjek penelitian yang memiliki kadar Mg<1,7 mg/dl 80% mengalami albuminuria, sedangkan pada subjek yang memiliki kadar Mg ≥ 1,7 mg/ dl sebanyak 63,6% mengalami albuminuria. Didapatkan koefisien korelasi sebesar 0,006 yang menunjukkan hubungan yang lemah antara kadar magnesium dalam darah dengan albuminuria. Disimpulkan tidak terdapat korelasi antara kadar magnesium dengan derajat albuminuria. Kata kunci: kadar magnesium, albuminuria, diabetes melitus tipe 2 Correlation between Magnesium Level and Albuminuria in Patients with Type 2 Diabetes Abstract The purposes of this study are to know: the role of magnesium in diabetic nephropathy, the proportion of albuminuria in type 2 DM with hypomagnesemia and normal magnesium level, and correlation between magnesium level and albuminuria. This cross-sectional study was done in Diabetes Clinic RSCM from March to June 2014 with consecutive sampling for type 2 DM patients who had been diagnosed with diabetic nephropathy. History taking, physical exam, albumin creatinine ratio test, and A1c level were done. Thirty eight subjects included in this study were mostly more than 50 years old and had poor glycemic control (81,6%. 80% of subjects with Mg level < 1.7 mg/dl experienced albuminuria and 63.6% of subjects with Mg level
Lin, Wen-Yuan; Pi-Sunyer, F. Xavier; Liu, Chiu-Shong; Li, Chia-Ing; Davidson, Lance E.; Li, Tsai-Chung; Lin, Cheng-Chieh
Background Albuminuria is recognized as a marker of vascular dysfunction. Central obesity increases the risk of cardiovascular disease. Little is known about the association between albuminuria and central obesity in Chinese. We aimed to assess the association between central obesity and prevalence and incidence of albuminuria in a middle-aged population-based cohort study. Methods This is a cross-sectional and longitudinal cohort study. A total of 2350 subjects aged ≥40 years were recruited in 2004 in Taiwan for cross-sectional analysis. Longitudinal analysis included 1432 baseline normoalbuminuria subjects with a mean 2.8 years follow-up, 67 of whom exhibited incident albuminuria. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g creatinine. Multiple logistic regression analyses were used to evaluate the relationship between central obesity and prevalence and incidence of albuminuria after adjustment for age, gender, body mass index, blood pressure, renal function, glucose, high sensitivity c-reactive protein, smoking, betel nut chewing, alcohol drinking, and physical activity. Results At baseline, albuminuria is significantly associated with central obesity. The adjusted odds ratio of having albuminuria among subjects with central obesity was 1.73(95% confidence interval (CI): 1.04–2.85), compared to the subjects without central obesity. In multivariable models, participants with central obesity at baseline had a 112% increase in risk of incident albuminuria (adjusted incidence rate ratio (95% CI): 2.12(1.01–4.44)) compared with participants with non-central obesity. Conclusions Abdominal adiposity was independently associated with increased prevalence and incidence of albuminuria in Chinese. The mechanisms linking adiposity and albuminuria need to be addressed. PMID:23251329
Felix Kröpelin, Tobias; de Zeeuw, Dick; Holtkamp, Frank Arjan; Packham, David Kenneth; L Heerspink, Hiddo J
Albuminuria reduction due to angiotensin receptor blockers (ARBs) predicts subsequent renoprotection. Relating the initial albuminuria reduction to subsequent renoprotection assumes that the initial ARB-induced albuminuria reduction remains stable during follow-up. The aim of this study was to assess individual albuminuria fluctuations after the initial ARB response and to determine whether taking individual albuminuria fluctuations into account improves renal outcome prediction. Patients with diabetes and nephropathy treated with losartan or irbesartan in the RENAAL and IDNT trials were included. Patients with >30% reduction in albuminuria 3 months after ARB initiation were stratified by the subsequent change in albuminuria until Month 12 in enhanced responders (>50% albuminuria reduction), sustained responders (between 20 and 50% reduction), and response escapers (albuminuria exposure until Month 3 was compared with the exposure over the first 12 months using receiver operating characteristics (ROC) curves. Following ARB initiation, 388 (36.3%) patients showed an >30% reduction in albuminuria. Among these patients, the albuminuria level further decreased in 174 (44.8%), remained stable in 123 (31.7%), and increased in 91 (23.5%) patients. Similar albuminuria fluctuations were observed in patients with albuminuria reduction. Renal risk prediction improved when using the albuminuria exposure during the first 12 months versus the initial Month 3 change [ROC difference: 0.78 (95% CI 0.75-0.82) versus 0.68 (0.64-0.72); P albuminuria variability is observed. Hence, incorporating multiple albuminuria measurements over time in risk algorithms may be more appropriate to monitor treatment effects and quantify renal risk. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Background: Variants in CUBN, the gene encoding cubilin, a proximal tubular transport protein, have been associated with albuminuria and vitamin B12 (B12) deficiency. We hypothesized that low levels of B12 would be associated with albuminuria in a population-based cohort. Methods: We analyzed parti...
Scheven, Lieneke; Joosten, Michel M.; de Jong, Paul E.; Bakker, Stephan J. L.; Gansevoort, Ron T.
Background Elevated albuminuria as well as an increased serum uric acid concentration is associated with poor cardiovascular outcome. We questioned whether these 2 variables (albuminuria and serum uric concentration) may be interrelated via tubular uric acid reabsorption. Methods and Results Included were 7688 participants of the PREVEND Study, an observational, general population‐based cohort study. Linear regression analyses were used to test associations of baseline albuminuria with baseline serum uric acid concentration and tubular uric acid reabsorption (calculated as [100−fractional uric acid excretion]%). Cox regression analyses were used to study the association of baseline serum uric acid and albuminuria with incident cardiovascular morbidity and mortality. In cross‐sectional analyses, albuminuria was associated positively with serum uric acid concentration, both crude and after adjustment for potential confounders (both Puric acid reabsorption, again both crude and after adjustment for potential confounders (both Puric acid were associated with incident cardiovascular events (Hazard Ratios 1.09 [1.03 to 1.17], P=0.01 and 1.19 [1.09 to 1.30], Puric acid being less predictive for cardiovascular morbidity and mortality in the presence of high albuminuria and vice versa. Conclusions Albuminuria is strongly associated with tubular uric acid reabsorption, and consequently with serum uric acid concentration. This phenomenon may explain in part why albuminuria is associated with cardiovascular outcome. PMID:24772520
Kröpelin, Tobias F.; de Zeeuw, Dick; Andress, Dennis L.; Bijlsma, Maarten J.; Persson, Frederik; Parving, Hans-Henrik; Lambers Heerspink, Hiddo
BACKGROUND AND OBJECTIVES: Albuminuria change is often used to assess drug efficacy in intervention trials in nephrology. The change is often calculated using a variable number of urine samples collected at baseline and end of treatment. Yet more albuminuria measurements usually occur. Because
Vestergaard Rosenlund, Signe; Willum Hansen, Tine; Rossing, Peter
CONTEXT: The effect of glycaemic control on persisting albuminuria remains unclear. Insulin delivery and glucose variability may be important Objective: To investigate the effect of 1 year treatment with sensor-augmented insulin pump (SAP) or multiple daily injections (MDI) on albuminuria. DESIGN...
Teumer, Alexander; Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y; Li, Man; Li, Yong; Mijatovic, Vladan; Ko, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C; Olden, Matthias; Hiraki, Linda T; Tayo, Bamidele O; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R; Smith, Albert V; Zappa, Allison M; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K; Paulweber, Bernhard; Mitchell, Braxton D; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Mateo Leach, I; Rudan, Igor; Hillege, Hans L; Beckmann, Jacques S; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C; Butterbach, Katja; Launer, Lenore J; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S; Gansevoort, Ron T; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J; Katz, Ronit; Loos, Ruth J F; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R; Parsa, Afshin; Heid, Iris M; Paterson, Andrew D; de Boer, Ian H; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J; Böger, Carsten A; Fox, Caroline S; Pattaro, Cristian; Köttgen, Anna
Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted
Tani, Yoshihiro; Nakayama, Masaaki; Terawaki, Hiroyuki; Iseki, Kunitoshi; Watanabe, Tsuyoshi
Albuminuria is thought to reflect generalized endothelial dysfunction. In hypertensive patients, albuminuria is related to the risk for cardiovascular disease (CVD) events. Thus, screening for albuminuria is critical for risk stratification in hypertensive patients. However, the actual state of albuminuria in Japanese patients without diabetes remains unclear due to insurance coverage. The CLINITEK microalb creatinine test® is a urine test paper that can assess albumin excretion corrected for urine creatinine levels in only 60 seconds without any special equipment. The semi-quantitative albuminuria test and urine proteinuria test were performed on 8,181 Japanese hypertensive patients, and the clinical significance of the test was evaluated by comparison with the urine test strip method. Albumin creatinine ratio (ACR) albuminuria test were present in 70.0%, 25.7%, and 4.3%, respectively, of patients with a negative urine protein test strip result. Furthermore, in patients with a negative urine protein test strip result, ACR ≥ 30 mg/g creatinine was independently associated with previous CVD (odds ratio: 1.25, 95% confidence interval: 1.00 - 1.57, p albuminuria. Easy and quick albuminuria test on the CLINITEK MICROALB CREATININE TEST might be useful test to risk stratification of hypertensive patients compared to urine test strip.
Lee, Sung-Ho; Kim, Do Hoon; Kim, Yang-Hyun; Roh, Yong Kyun; Ju, Sang Yhun; Nam, Hyo-Yun; Nam, Ga-Eun; Choi, Jun-Seok; Lee, Jong-Eun; Sang, Jung-Eun; Han, Kyungdo; Park, Yong-Gyu
This study aimed to estimate the relationship between various lipid abnormalities and albuminuria in hypertensive Korean adults. Data obtained from the Korea National Health and Nutrition Examination Survey in 2011 to 2012 were analyzed. The study included 2330 hypertensive participants. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. Dyslipidemia parameters were defined as high TG ≥200 mg/dL, low HDL-C as HDL-C Albuminuria was defined as a urine albumin to creatinine ratio (ACR) ≥30 mg/g. Women with albuminuria showed significantly higher levels of TG, TC/HDL-C, and TG/HDL-C and a lower level of HDL-C than women without albuminuria (all P albuminuria (OR [95% confidence interval]: 1.53 [1.06-2.21], 1.21 [1.02-1.45], and 1.78 [1.21-2.63], respectively) and HDL-C with a decreased OR for albuminuria (0.78 [0.67-0.92]) after adjusting for all covariates. LogTG, TC/HDL-C, and logTG/HDL-C were associated with an increased prevalence of albuminuria in hypertensive women. Screening and treatment for dyslipidemia may be necessary for hypertensive women to address potential albuminuria.
Gschwend, Simone; Pinto-Sietsma, Sara-Joan; Buikema, Hendrik; Pinto, Yigal M.; van Gilst, Wiek H.; Schulz, Angela; de Zeeuw, Dick; Kreutz, Reinhold
BACKGROUND: Albuminuria is an independent risk factor of coronary artery disease and has been proposed to reflect a general endothelial disorder. The Munich Wistar Frömter (MWF) rat strain develops spontaneous albuminuria and, therefore, may be an interesting experimental model to study alterations
Chen, Szu-Chia; Chang, Jer-Ming; Lin, Ming-Yen; Hou, Meng-Ling; Tsai, Jer-Chia; Hwang, Shang-Jyh; Chen, Hung-Chun
Background and Aim Metabolic syndrome (MetS) and albuminuria increase cardiovascular risk. However, in occupational drivers, the clinical significance of albuminuria and its association with MetS remain unclear. We investigated the prevalence of MetS, albuminuria and cardiovascular risk, and its associated risk factors in occupational drivers; Methods 441 occupational drivers and 432 age- and sex-stratified matched counterpart controls were enrolled. MetS was defined using Adult Treatment Panel III for Asians. Albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g. Cardiovascular disease risk was evaluated by Framingham Risk Score (FRS); Results A significantly higher prevalence of MetS (43.1% vs. 25.5%, p albuminuria (12.0% vs. 5.6%, p = 0.001) and high FRS risk ≥ 10% of 10-year risk (46.9% vs. 35.2%, p albuminuria (odds ratio [OR], 2.75; p = 0.01) were risk factors for MetS, while a history of renal disease, diabetes and hypertension, and MetS (OR, 2.28; p = 0.01) were risk factors for albuminuria in occupational drivers; Conclusions Our study demonstrated that MetS and albuminuria were public health problems in occupational drivers. An education program for promoting healthy lifestyle and a regular occupational health visit for early detection and interventions should be established. PMID:24201129
Lambers Heerspink, Hiddo J.; Kropelin, Tobias F.; Hoekman, Jarno; de Zeeuw, Dick
Albuminuria has been proposed as a surrogate end point in randomized clinical trials of renal disease progression. Most evidence comes from observational analyses showing that treatment-induced short-term changes in albuminuria correlate with risk change for ESRD. However, such studies are prone to
Scheven, Lieneke; Halbesma, Nynke; de Jong, Paul E.; de Zeeuw, Dick; Bakker, Stephan J. L.; Gansevoort, Ron T.
Background Urinary albumin excretion is known to be independently associated with progression of renal and cardiovascular disease. The aim of this study was to identify predictors for progression in albuminuria in the general population. Methods Data were used of the first 4 screening rounds of a community-based prospective cohort study (PREVEND). Included were 5,825 subjects that at baseline had no known renal disease or macroalbuminuria. Subjects were defined as having progressive albuminuria when they belonged to the quintile of subjects with highest absolute increase in urinary albumin excretion per year and a urinary albumin excretion during the last screening in which they participated of ≥150 mg/24 h. Change in urinary albumin excretion per year was calculated as last available urinary albumin excretion minus baseline UAE divided by follow-up time. Results During 9.3 years follow-up 132 subjects had progressive albuminuria. These subjects were significantly older, more often of male gender and had a worse cardiovascular risk profile. In a multivariable model, testing baseline values, significant predictors of progressive albuminuria were male gender (OR 2.23; palbuminuria (OR 5.71; palbuminuria. Conclusion A high baseline albuminuria is by far the most important predictor of progressive albuminuria. Thus, screening for baseline albuminuria will be more important than screening for cardiovascular risk factors in order to identify subjects at risk for progressive albuminuria. PMID:23723966
Heerspink, Hiddo J Lambers; Kröpelin, Tobias F.; Hoekman, Jarno|info:eu-repo/dai/nl/305349929; De Zeeuw, Dick
Albuminuria has been proposed as a surrogate end point in randomized clinical trials of renal disease progression. Most evidence comes from observational analyses showing that treatment-induced shortterm changes in albuminuria correlate with risk change for ESRD. However, such studies are prone to
Holtkamp, Frank A; de Zeeuw, Dick; de Graeff, Pieter A
The long-term cardioprotective effect of angiotensin receptor blockers (ARBs) is associated with the short-term lowering of its primary target blood pressure, but also with the lowering of albuminuria. Since the individual blood pressure and albuminuria response to an ARB varies between and withi...
Heerspink, H. J. L.; Johnsson, E.; Gause-Nilsson, I.; Cain, V. A.; Sjostrom, C. D.
Aims: To characterize the effect of dapagliflozin on albuminuria and estimated glomerular filtration rate (eGFR) and to determine whether effects on albuminuria were mediated through changes in glycated haemoblogin (HbA1c), systolic blood pressure (SBP), body weight or eGFR. Methods: We conducted a
Kröpelin, Tobias Felix; de Zeeuw, Dick; Holtkamp, Frank Arjan; Packham, David Kenneth; Heerspink, Hiddo J. L.
Albuminuria reduction due to angiotensin receptor blockers (ARBs) predicts subsequent renoprotection. Relating the initial albuminuria reduction to subsequent renoprotection assumes that the initial ARB-induced albuminuria reduction remains stable during follow-up. The aim of this study was to
Kröpelin, Tobias F; de Zeeuw, Dick; Andress, Dennis L
BACKGROUND AND OBJECTIVES: Albuminuria change is often used to assess drug efficacy in intervention trials in nephrology. The change is often calculated using a variable number of urine samples collected at baseline and end of treatment. Yet more albuminuria measurements usually occur. Because...... albuminuria shows a large day-to-day variability, this study assessed to what extent the average and the precision of the antialbuminuric drug effect varies with the number of urine collections at each visit and the number of follow-up visits. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study used...... data from three randomized intervention trials (Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy, Selective Vitamin D Receptor Activation for Albuminuria Lowering, and Residual Albuminuria Lowering with Endothelin Antagonist Atrasentan) including patients with type 2 diabetes...
Lin, Ching-Yuang; Huang, Shiuh-Ming
We do not yet fully grasp the significance of childhood albuminuria. Based on mass urinary screening (MUS) using albumin-specific dipsticks in school children, we studied the independent association of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in children with chronic kidney disease (CKD). A prospective cohort of 5351 children with albuminuria detected by school MSU during the period 1992-1996, followed up to 2009. Cumulative mortality rate, prevalence of CKD, and ESRD were higher in children with albuminuria than those without. Albuminuria category was associated with the risk of mortality [hazard ratio (HR) 3.4] and ESRD (HR 3.24). Lower eGFR and albuminuria predicted mortality and ESRD among children with albuminuria and CKD. We found that being below a threshold of 45 mL/min/1.73 m(2) was significantly associated with ESRD. The highest renal function decline, along with the steepest slope of cumulative ESRD number, occurred in Stage 3, the critical point in renal progression. Risk factors for renal progression among different age groups with albuminuria were hypercholesterolemia and low serum albumin at 7-17 years of age. Beyond 18 years of age, besides the risk factor, a higher fasting blood sugar (BS) was also noted. Childhood albuminuria is a risk factor for CKD in later life, albuminuria provides additional prognostic information, and complications of CKD should be defined in each case. Copyright © 2016. Published by Elsevier B.V.
Heerspink, Hiddo J Lambers; Kröpelin, Tobias F; Hoekman, Jarno; de Zeeuw, Dick
Albuminuria has been proposed as a surrogate end point in randomized clinical trials of renal disease progression. Most evidence comes from observational analyses showing that treatment-induced short-term changes in albuminuria correlate with risk change for ESRD. However, such studies are prone to selection bias and residual confounding. To minimize this bias, we performed a meta-analysis of clinical trials to correlate the placebo-corrected drug effect on albuminuria and ESRD to more reliably delineate the association between changes in albuminuria and ESRD. MEDLINE and EMBASE were searched for clinical trials reported between 1950 and April 2014. Included trials had a mean follow-up of ≥1000 patient-years, reported ESRD outcomes, and measured albuminuria at baseline and during follow-up. Twenty-one clinical trials involving 78,342 patients and 4183 ESRD events were included. Median time to first albuminuria measurement was 6 months. Fourteen trials tested the effect of renin-angiotensin-aldosterone-system inhibitors and seven trials tested other interventions. We observed variability across trials in the treatment effect on albuminuria (range, -1.3% to -32.1%) and ESRD (range, -55% to +35% risk change). Meta-regression analysis revealed that the placebo-adjusted treatment effect on albuminuria significantly correlated with the treatment effect on ESRD: for each 30% reduction in albuminuria, the risk of ESRD decreased by 23.7% (95% confidence interval, 11.4% to 34.2%; P=0.001). The association was consistent regardless of drug class (P=0.73) or other patient or trial characteristics. These findings suggest albuminuria may be a valid substitute for ESRD in many circumstances, even taking into account possible other drug-specific effects that may alter renal outcomes. Copyright © 2015 by the American Society of Nephrology.
Okin, Peter M; Wachtell, Kristian; Devereux, Richard B
Although albuminuria and the electrocardiographic (ECG) strain pattern each predict development of heart failure (HF), whether combining albuminuria and strain improves prediction of new HF is unclear.......Although albuminuria and the electrocardiographic (ECG) strain pattern each predict development of heart failure (HF), whether combining albuminuria and strain improves prediction of new HF is unclear....
Kröpelin, Tobias F; de Zeeuw, Dick; Andress, Dennis L; Bijlsma, Maarten J; Persson, Frederik; Parving, Hans-Henrik; Heerspink, Hiddo J Lambers
Albuminuria change is often used to assess drug efficacy in intervention trials in nephrology. The change is often calculated using a variable number of urine samples collected at baseline and end of treatment. Yet more albuminuria measurements usually occur. Because albuminuria shows a large day-to-day variability, this study assessed to what extent the average and the precision of the antialbuminuric drug effect varies with the number of urine collections at each visit and the number of follow-up visits. This study used data from three randomized intervention trials (Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy, Selective Vitamin D Receptor Activation for Albuminuria Lowering, and Residual Albuminuria Lowering with Endothelin Antagonist Atrasentan) including patients with type 2 diabetes and macroalbuminuria. Albuminuria-lowering drug effects were estimated from one, two, or three urine collections at consecutive days before each study visit and reported as albuminuria change from baseline to end of treatment or the change over time considering an average of all follow-up albuminuria measurements. Increasing the number of urine collections for an albuminuria measurement at baseline and end of treatment or using all study visits during follow-up did not alter the average drug effect. The precision of the drug effect increased (decreased SEM) when the number of study visits and the number of urine collections per visit were increased. Using all albuminuria measurements at all study visits led to a 4- to 6-fold reduction in sample size to detect a 30% albuminuria-lowering treatment effect with 80% power compared with using baseline and end-of-treatment albuminuria measurements alone. Increasing the number of urine collections per study visit and the number of visits over time does not change the average drug effect estimate but markedly increases the precision, thereby enhancing statistical power. Thus, clinical trial designs in diabetic
Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS). The mechanisms by which TRPC6 mutations cause kidney disease are not well understood. We used TRPC6-deficient mice to examine the function of TRPC6 in the kidney. We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals. Glomerular histomorphology revealed no abnormalities on both light and electron microscopy. To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days. Although both groups developed similar levels of hypertension, TRPC6-deficient mice had significantly less albuminuria, especially during the early phase of the infusion; this suggested that TRPC6 adversely influences the glomerular filter. We used whole-cell patch-clamp recording to measure cell-membrane currents in primary cultures of podocytes from both wild-type and TRPC6-deficient mice. In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude. Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.
Ruiz-Hurtado, Gema; Ruilope, Luis M; de la Sierra, Alex; Sarafidis, Pantelis; de la Cruz, Juan J; Gorostidi, Manuel; Segura, Julián; Vinyoles, Ernest; Banegas, José R
Nighttime blood pressure (BP) and albuminuria are two important and independent predictors of cardiovascular morbidity and mortality. Here, we examined the quantitative differences in nighttime systolic BP (SBP) across albuminuria levels in patients with and without diabetes and chronic kidney disease. A total of 16,546 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry cohort (mean age 59.6 years, 54.9% men) were analyzed. Patients were classified according to estimated glomerular filtration rate (eGFR), as ≥60 or albuminuria (30-300 mg/g), or very high albuminuria (>300 mg/g). Office and 24-h BP were determined with standardized methods and conditions. High albuminuria was associated with a statistically significant and clinically substantial higher nighttime SBP (6.8 mmHg higher than with normoalbuminuria, P albuminuria among patients with diabetes and low eGFR (16.5 mmHg, P albuminuria than in those with normoalbuminuria (P albuminuria had a 6.1 mmHg greater nighttime SBP than those with high albuminuria (P Albuminuria in hypertensive patients is accompanied by quantitatively striking higher nighttime SBP, particularly in those with diabetes with very high albuminuria and low eGFR. © 2016 by the American Diabetes Association.
Full Text Available Abstract Background Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. We analyzed whether homocysteine and uric acid were associated with glomerular filtration rate (GFR and albuminuria independently of each other. We also investigated the association of MTHFR polymorphisms related to homocysteine with albuminuria to get further insight into causality. Methods This was a cross-sectional population-based study in Caucasians (n = 5913. Hyperhomocysteinemia was defined as total serum homocysteine ≥ 15 μmol/L. Albuminuria was defined as urinary albumin-to-creatinine ratio > 30 mg/g. Results Uric acid was associated positively with homocysteine (r = 0.246 in men and r = 0.287 in women, P P for trend P P = 0.004 were significantly associated with albuminuria, independently of hypertension and type 2 diabetes. The 2-fold higher risk of albuminuria associated with hyperhomocysteinemia was similar to the risk associated with hypertension or diabetes. MTHFR alleles related to higher homocysteine were associated with increased risk of albuminuria. Conclusions In the general adult population, elevated serum homocysteine and uric acid were associated with albuminuria independently of each other and of renal function.
Nakhjavani, Manouchehr; Morteza, Afsaneh; Jenab, Yaser; Ghaneei, Azam; Esteghamati, Alireza; Karimi, Maryam; Farokhian, Alireza
The value of urinary albumin excretion in the prediction of myocardial ischemia in men and women with type 2 diabetes is not well understood. We questioned whether gender influences the albuminuria-ischemic heart disease relationship in patients with type 2 diabetes. We designed a matched case-control study of 926 patients with albuminuria (cases) and 926 age and body mass index matched patients without albuminuria (controls). Ischemic heart disease was defined as the presence of (1) history of angina pectoris or angina equivalent symptoms and critical care unit admission, (2) myocardial infarction and/or electrocardiographic evidence of Q-wave myocardial infarction, (3) coronary revascularization and/or stenting, (4) positive myocardial single-photon emission computed tomography scan, (5) ischemic ST-segment or T-wave changes, and (6) positive stress testing. Patients with albuminuria had a lower glomerular filtration rate and a longer diabetes duration than patients without albuminuria. In the group of cases, there were a greater number of men with ischemic heart disease (120 of 370; 32.4%) compared to women (97 of 559; 17.4%) (Pischemic heart disease according to the presence or absence of albuminuria was 1.25 [95% CI: 1.01-1.56] (Pischemic heart disease compared to women. This may be related to the role of high-density lipoprotein on the albuminuria-gender relationship.
Shah, Ravi V; Allison, Matthew A; Lima, Joao A C; Abbasi, Siddique A; Mongraw-Chaffin, Morgana; Jerosch-Herold, Michael; Ding, Jingzhong; Budoff, Matthew J; Murthy, Venkatesh L
To measure association between hepatic fat and albuminuria (an early marker of renal injury) in individuals without diabetes or hypertension. 2,281 individuals in the Multi-Ethnic Study of Atherosclerosis without diabetes or hypertension, renal disease, or excess alcohol consumption underwent computed tomography (CT) for assessment of liver attenuation (marker of hepatic lipid content) and urinalysis (for albuminuria) at initial study visit, with assessment of incident and prevalent albuminuria by logistic regression in follow-up. After adjustment for age, gender, race, smoking, blood pressure, insulin resistance, and body mass index, individuals with less liver fat (higher liver CT attenuation) had a lower probability of having albuminuria at Exam 1 (OR per 10 unit increase in attenuation 0.77, 95 % CI 0.61-0.97, P = 0.02). At median 9.3 years follow-up, albuminuria was identified in 129 individuals were (5.8 %). In fully adjusted models (with age, smoking, body mass index, blood pressure, diabetes and hypertension as time-dependent covariates), lower liver attenuation (greater liver fat) was associated with higher risk of incident albuminuria (OR 0.79, 95 % CI 0.66-0.94, P = 0.008). Hepatic attenuation is associated with prevalent and incident albuminuria, an early, potent risk factor for renal risk in a population not clearly at risk for future renal failure.
Fried, Linda F; Lewis, Julia
Albuminuria is a risk factor for progression of kidney disease. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers slow the progression to ESRD, an effect that is correlated with reduction in albuminuria. This has led to the hypothesis that albuminuria should be a target for therapy. This work argues that there are issues with this hypothesis. The previously reported studies were not designed to test the hypothesis that achieving a specific albuminuria target would be beneficial in and of itself irrespective the mechanism used to achieve that goal. One cannot assume that the beneficial effect observed was causally related to the effect on albuminuria or that it would extend to other interventions. Most importantly, it is not known if the approach of maximizing therapy to reduce proteinuria is safe. Recent studies have shown that combining renin-angiotensin system therapies decreases albuminuria without significant clinical benefit but with increased risk of adverse events. More studies are needed, but at this time, albuminuria has not jumped the hurdle needed to be accepted as a surrogate end point or target for treatment. Primum non nocere, first do no harm. Copyright © 2015 by the American Society of Nephrology.
Lambers Heerspink, Hiddo J; Gansevoort, Ron T
The presence of elevated levels of albuminuria is associated with an increased risk of progressive renal function loss over time. This association is found in various pathophysiological conditions, including diabetic nephropathy, hypertensive nephropathy, and various primary renal diseases, but also, the general, otherwise healthy population. Emerging data report that elevated albuminuria causes tubulointerstitial damage through activation of proinflammatory mediators, which ultimately leads to a progressive decline in renal function. Nowadays, various drugs are available that decrease the rate of GFR loss in patients with kidney disease. Well known are renin-angiotensin-aldosterone system inhibitors, but there are also other drugs and interventions, like intensive glucose control, anti-inflammatory agents (pentoxifylline), or a low-protein diet. These interventions have an additional effect beyond their original target, namely lowering albuminuria. Analyses from clinical trials show that the reduction in albuminuria observed during the first months of treatment with these drugs correlates with the degree of long-term renal protection: the larger the initial reduction in albuminuria, the lower the risk of ESRD during treatment. In addition, in treated patients, residual albuminuria is again the strongest risk marker for renal disease progression. These observations combined provide a strong argument that albuminuria is an appropriate therapeutic target in patients with CKD. Copyright © 2015 by the American Society of Nephrology.
Nishimura, Akihiro; Kasai, Takatoshi; Kikuno, Shota; Nagasawa, Kaoru; Okubo, Minoru; Narui, Koji; Mori, Yasumichi
Sleep-disordered breathing (SDB) can induce hyperglycemia, hypertension, and oxidative stress, conditions that are known to cause kidney damage. Therefore, SDB may exacerbate albuminuria, which is an established marker of early-stage kidney damage in patients with type 2 diabetes mellitus (T2DM). The association between SDB and albuminuria in patients with T2DM was investigated in this study. This cross-sectional study included 273 patients with T2DM who underwent portable sleep testing and measurement of urine albumin to creatinine ratio (UACR). The association between the severity of SDB and albuminuria was investigated. Patients were divided into three groups according to the respiratory event index (REI): the no or mild group (REI < 15 events/h), moderate (REI 15 to < 30 events/h), and severe (REI ≥ 30 events/h). Albuminuria was defined as UACR ≥ 3.4 mg/mmol creatinine. Logistic regression analysis for albuminuria included the categorical REI as the independent variable. The median (interquartile range) REI of all patients (age 57.9 ± 11.9 years, mean ± standard deviation, male sex 81.7%, body mass index 26.7 [24.2-29.5] kg/m 2 , estimated glomerular filtration rate 82 [65-97] mL/min/1.73 m 2 ) was 13.0 (7.0-24.2) events/h. The REI, as a categorical variable, was significantly associated with albuminuria after adjustment for other risk factors for albuminuria; REI 15 to < 30 events/h: odds ratio (OR) 3.35, 95% confidence interval (95% CI), 1.68-6.67, P < .001; REI ≥ 30: OR 8.52, 95% CI, 3.52-20.63, P < .001). In addition, the natural logarithm-transformed REI of all patients also correlated significantly with albuminuria. The severity of SDB is associated with albuminuria in patients with T2DM. © 2018 American Academy of Sleep Medicine.
Izaks, Gerbrand J.; Slaets, Joris P.J.; de Jong, Paul E.; Visser, Sipke T.; Bilo, Henk J.G.; Gansevoort, Ron T.
Summary Background and objectives Recent studies found different associations of cognitive function with albuminuria or estimated GFR (eGFR). Most studies were limited to the elderly or did not take both renal variables into account. Therefore, this study analyzed the association of cognitive function with albuminuria and eGFR in community-dwelling persons aged 35 to 82 years. Design, setting, participants, & measurements This was a cross-sectional study comprising 4095 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Cognitive function, measured with the Ruff Figural Fluency Test (RFFT), was treated as the dependent variable, and albuminuria and eGFR were treated as independent variables. Results The prevalence of albuminuria albuminuria and age, analyses were performed per age tertile. After multivariate adjustment, albuminuria ≥ 30 mg/24 h, but not eGFR, was associated with lower RFFT score in the youngest tertile (B −5.3; 95% CI, −0.6 to −9.2; P = 0.05), but not in older tertiles. Moreover, subjects in the youngest tertile with increasing albuminuria (5–15 and >15 mg/24 h) before RFFT measurement had lower mean RFFT scores than subjects with stable albuminuria: mean difference −4.9 (P = 0.3) and −6.7 (P = 0.03), respectively. Conclusions In this community-based cohort, elevated albuminuria was associated with worse cognitive function in young but not in old persons. There was no association of eGFR with cognitive function. PMID:21566108
Samuel, Susan M.; Palacios-Derflingher, Luz; Tonelli, Marcello; Manns, Braden; Crowshoe, Lynden; Ahmed, Sofia B.; Jun, Min; Saad, Nathalie; Hemmelgarn, Brenda R.
Background: Despite a low prevalence of chronic kidney disease (estimated glomerular filtration rate [GFR] albuminuria contributes to the progression of chronic kidney disease to kidney failure among First Nations people. Methods: We identified all adult residents of Alberta (age ≥ 18 yr) for whom an outpatient serum creatinine measurement was available from May 1, 2002, to Mar. 31, 2008. We determined albuminuria using urine dipsticks and categorized results as normal (i.e., no albuminuria), mild, heavy or unmeasured. Our primary outcome was progression to kidney failure (defined as the need for chronic dialysis or kidney transplantation, or a sustained doubling of serum creatinine levels). We calculated rates of progression to kidney failure by First Nations status, by estimated GFR and by albuminuria category. We determined the relative hazard of progression to kidney failure for First Nations compared with non–First Nations participants by level of albuminuria and estimated GFR. Results: Of the 1 816 824 participants we identified, 48 669 (2.7%) were First Nations. First Nations people were less likely to have normal albuminuria compared with non–First Nations people (38.7% v. 56.4%). Rates of progression to kidney failure were consistently 2- to 3-fold higher among First Nations people than among non–First Nations people, across all levels of albuminuria and estimated GFRs. Compared with non–First Nations people, First Nations people with an estimated GFR of 15.0–29.9 mL/min per 1.73 m2 had the highest risk of progression to kidney failure, with similar hazard ratios for those with normal and heavy albuminuria. Interpretation: Albuminuria confers a similar risk of progression to kidney failure for First Nations and non–First Nations people. PMID:24295865
Kim, Peter S.; Woods, Christian; Dutcher, Lauren; Georgoff, Patrick; Rosenberg, Alice; Mican, Jo Ann M.; Kopp, Jeffrey B.; Smith, Margo A.; Hadigan, Colleen
Objective HIV and type 2 diabetes are known risk factors for albuminuria, but no previous reports have characterized albuminuria in HIV-infected patients with diabetes. Research Design and Methods We performed a cross-sectional study including 73 HIV-infected adults with type 2 diabetes, 82 HIV-infected non-diabetics, and 61 diabetic control subjects without HIV. Serum creatinine >1.5 mg/dL was exclusionary. Albuminuria was defined as urinary albumin/creatinine ratio >30 mg/g. Results The pre...
Hansen, H P; Rossing, P; Tarnow, L
The aim of our study was to evaluate the diurnal relationship between arterial blood pressure and albuminuria, and some potential mechanisms responsible for impaired nocturnal blood pressure reduction (non-dippers, groups I and II) in diabetic nephropathy (DN). Twenty-four-hour ambulatory blood......-118); P albuminuria [microgram/min; median (range)] was observed; [Day: group I, 1467 (235-3933); group II, 695 (170-6719); group III, 875 (228-3173). Night: group I, 1079 (279-4665); group II, 572 (113-3807); group...... III, 659 (81-2493)]. A significant correlation between MABP and albuminuria was demonstrated during day- (rho = 0.50, P
Wang, Shen-tian; Xu, Jian-min; Wang, Meng; Chen, Fu-lian; Ding, Gang
The aim of the present study was to determine the plasma osteoprotegerin (OPG) levels in Type 1 diabetic patients with albuminuria. A total of 80 Type 1 diabetic subjects and 30 control subjects were enrolled. Diabetic subjects were divided into normoalbuminuric group, microalbuminuric group and macroalbuminuric group according to urinary albumin excretion rate (UAER) and serum creatinine measurements. Plasma osteoprotegerin level was measured by enzyme-linked immunoassay. The serum OPG levels were significantly elevated in patients with microalbuminuria (3.62 ± 0.70 ng/l) and macroalbuminuria (4.45 ± 0.76 ng/l) as compared with patients with normoalbuminuria (2.77 ± 0.78 ng/l) and control subjects (2.29 ± 0.37 ng/l). And the plasma osteoprotegerin level in macroalbuminuric group was also higher than that in microalbuminuria group. The plasma osteoprotegerin level had a positive correlation with the fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), glycohemoglobin A1c (HbA1C), highly sensitive C-reactive protein (hsCRP)and UAER. Multivariate regression analysis revealed that the plasma osteoprotegerin level was an independent factor associated with albuminuria in Type 1 diabetes. The plasma values of osteoprotegerin were elevated in Type 1 diabetic patients with nephropathy and gradually increased with the severity, so there is a association between plasma osteoprotegerin levels and the presence and severity of diabetic nephropathy. This finding supports the growing concept that osteoprotegerin may act as an important regulatory molecule in the angiopathy, and particularly, that it may be involved in the development of nephropathy in Type 1 diabetes.
Greenberg, Sharon; Shenhar-Tsarfaty, Shani; Rogowski, Ori; Shapira, Itzhak; Zeltser, David; Weinstein, Talia; Lahav, Dror; Vered, Jaffa; Tovia-Brodie, Oholi; Arbel, Yaron; Berliner, Shlomo; Milwidsky, Assi
Microalbuminuria (MA) is a known marker for endothelial dysfunction and future cardiovascular events. Exercise-induced albuminuria (EiA) may precede the appearance of MA. Associations between EiA and metabolic syndrome (MS) have not been assessed so far. Our aim was to investigate this association in a large sample of apparently healthy individuals with no baseline albuminuria. This was a cross-sectional study of 2,027 adults with no overt cardiovascular diseases who took part in a health survey program and had no baseline MA. Diagnosis of MS was based on harmonized criteria. All patients underwent an exercise test (Bruce protocol), and urinary albumin was measured before and after the examination. Urinary albumin-to-creatinine ratio (ACR) values before and after exercise were 0.40 (0.21-0.89) and 1.06 (0.43-2.69) mg/g for median (interquartile range) respectively. A total of 394 (20%) subjects had EiA; ACR rose from normal rest values (0.79 mg/g) to 52.28 mg/g after exercise (P metabolic equivalents (P < 0.001), higher baseline blood pressure (P < 0.001), and higher levels of fasting plasma glucose, triglycerides, and body mass index (P < 0.001). Multivariate binary logistic regression model showed that subjects with MS were 98% more likely to have EiA (95% confidence interval: 1.13-3.46, P = 0.016). In conclusion, EiA in the absence of baseline MA is independently related to MS. Copyright © 2016 the American Physiological Society.
Full Text Available Objective. Albuminuria in type 2 diabetes mellitus (T2DM patients increases the risk of diabetic nephropathy, the leading cause of end-stage renal disease worldwide. Because albuminuria is modifiable, identifying relevant risk factors could facilitate prevention and/or management. This cross-sectional study investigated whether body constitution (BC independently predicts albuminuria. Method. Patients with T2DM (n=846 received urinalysis, a blood test, and diabetic retinopathy examination. Albuminuria was defined by an elevated urinary albumin/creatinine ratio (≥30 μg/mg. BC type (Yang deficiency, Yin deficiency, and Phlegm stasis was assessed using a body constitution questionnaire (BCQ. Traditional risk factors for albuminuria were also recorded. Odds ratios (ORs of albuminuria for BC were estimated using multivariate logistic regression. Results. Albuminuria was more prevalent in patients with Yang deficiency or Phlegm stasis (both P<0.01. After adjustment, patients with both Yang deficiency and Phlegm stasis exhibited a significantly higher risk of albuminuria (OR = 3.037; 95% confidence interval = 1.572–5.867, and P<0.001. Conclusion. BC is strongly associated with albuminuria in T2DM patients. Using a BCQ to assess BC is noninvasive, convenient, and inexpensive and can provide information for health care professionals to identify T2DM patients who are at a high risk of albuminuria.
Rasmussen, Jon B; Nordin, Lovisa S; Thomsen, Jakúp A; Rossing, Peter; Bygbjerg, Ib C; Christensen, Dirk L
The objective of this cross-sectional study was to investigate risk markers indicating the presence of albuminuria in patients with hypertension in rural sub-Saharan Africa (SSA). Urine albumin-creatinine ratio, glycated hemoglobin (HbA1c ), blood pressure, anthropometry, and other patient characteristics including medications were assessed. We identified 160 patients with hypertension, of whom 68 (42.5%) were co-diagnosed with diabetes mellitus (DM). Among the included participants, 57 (35.6%) had albuminuria (microalbuminuria [n=43] and macroalbuminuria [n=14]). A backward multivariate logistic regression model identified age (per 10-year increment) (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.03-1.95), HbA1c >53 compared with albuminuria. Only dysregulated DM and age were the conventional risk markers that seemed to suggest albuminuria among patients with hypertension in rural SSA. © 2015 Wiley Periodicals, Inc.
Discussion: Among ART-naïve adults with persistent albuminuria at a referral center in Western Kenya, we observed no cases of HIVAN. AIN was the most common cause of persistent proteinuria in this setting.
Lambers Heerspink, H J; Agarwal, R; Coyne, D W
BACKGROUND: Patients with diabetic nephropathy are at high risk for further progressive renal function loss. Treatments that decrease albuminuria have been linked with renal and cardiovascular protection. However, even when taking optimal treatment, residual renal and cardiovascular risk remains ...
Lambers Heerspink, Hiddo; Gansevoort, Ron T.
The presence of elevated levels of albuminuria is associated with an increased risk of progressive renal function loss over time. This association is found in various pathophysiological conditions, including diabetic nephropathy, hypertensive nephropathy, and various primary renal diseases, but
de Zeeuw, Dick; Coll, Blai; Andress, Dennis
Despite optimal treatment, including renin-angiotensin system (RAS) inhibitors, patients with type 2 diabetic nephropathy have high cardiorenal morbidity and mortality related to residual albuminuria. We evaluated whether or not atrasentan, a selective endothelin A receptor antagonist, further re...
Han, Eugene; Lee, Yong-Ho; Kim, Gyuri; Kim, So Ra; Lee, Byung-Wan; Kang, Eun Seok; Ahn, Chul Woo; Cha, Bong-Soo
Although sarcopenia is associated with metabolic disorders, its influence on albuminuria has not been determined. The aim of this study was to identify the relationship between sarcopenia and albuminuria in the general population. This was a population-based, cross-sectional study using a nationally representative sample of 2326 subjects aged ≥20years from the Korea National Health and Nutrition Examination Surveys of 2008-2011. Appendicular skeletal muscle (ASM) measured by dual-energy X-ray absorptiometry was used to assess sarcopenia, which was defined as ASM divided by body mass index, as recommended by the international consensus meeting of the National Institutes of Health. Albuminuria was defined as an albumin-to-creatinine ratio of ≥30mg/g using random spot urine samples. A total of 385 (16.5%) subjects were classified as having albuminuria. Sarcopenic subjects showed a higher proportion of albuminuria than subjects without sarcopenia (odds ratios [ORs]=2.17-3.26, all Palbuminuria risk was comparable between insulin-sensitive subjects with sarcopenia and insulin-resistant subjects with preserved muscle mass. A multiple logistic regression analysis also demonstrated that sarcopenia was independently associated with albuminuria (OR=1.61, 95% confidence interval [CI]=1.04-2.48, Palbuminuria remained strong in the elderly population (ORs=1.80-2.68, Palbuminuria was much higher in sarcopenic obese subjects than in other groups (OR=4.90, 95% CI=3.23-7.43, Palbuminuria independent of hypertension, diabetes, and metabolic syndrome. Sarcopenia and obesity had a synergistic impact on the increased risk of albuminuria. This suggests that sarcopenic obesity as well as sarcopenia alone may be considered as novel risk factors for albuminuria. Copyright © 2016 Elsevier Inc. All rights reserved.
Åkerblom, Axel; Clare, Robert M; Lokhnygina, Yuliya; Wallentin, Lars; Held, Claes; Van de Werf, Frans; Moliterno, David J; Patel, Uptal D; Leonardi, Sergio; Armstrong, Paul W; Harrington, Robert A; White, Harvey D; Aylward, Philip E; Mahaffey, Kenneth W; Tricoci, Pierluigi
Albuminuria is associated with cardiovascular (CV) outcomes. We evaluated albuminuria, alone and in combination with estimated glomerular filtration rate (eGFR), as a predictor of mortality and CV morbidity in 12,944 patients with non-ST-segment elevation acute coronary syndromes. Baseline serum creatinine and urinary dipsticks were obtained, with albuminuria stratified into no/trace albuminuria, microalbuminuria (≥30 but albuminuria and creatinine values were available in 9473 patients (73.2%). More patients with macroalbuminuria, versus no/trace albuminuria, had diabetes (66% vs 27%) or hypertension (86% vs 68%). Rates for CV death and overall mortality per strata were 3.1% and 4.8% (no/trace albuminuria); 5.8% and 9.0% (microalbuminuria); and 7.7% and 12.6% (macroalbuminuria) at 2 years of follow-up. Corresponding rates for CV death or MI were 12.2%, 16.9%, and 23.5%, respectively. Observed acute kidney injury rates were 0.6%, 1.2%, and 2.9% (n = 79), respectively. Adjusted HRs for macroalbuminuria on CV mortality were 1.65 (95% CI 1.15-2.37), and after adjustment with eGFR, 1.37 (95% CI 0.93-2.01). Corresponding HRs for overall mortality were 1.82 (95% CI 1.37-2.42) and 1.47 (95% CI 1.08-1.98). High-risk patients with non-ST-segment elevation acute coronary syndromes and albuminuria have increased morbidity and increased overall mortality independent of eGFR. Copyright © 2016 Elsevier Inc. All rights reserved.
Røndbjerg, Anne K; Omerovic, Emina; Vestergaard, Henrik
YKL-40 is involved in inflammation and endothelial dysfunction, and is increased in patients with type 1 diabetes, with an independent association between increasing YKL-40 levels and increasing levels of albuminuria. YKL-40 is associated with atherosclerosis and an increased cardiovascular...... mortality in the general population. In the present study YKL-40 levels were examined in patients with type 2 diabetes (T2D) with increasing levels of albuminuria, known to be associated with an increased risk of cardiovascular disease....
Kim, Tae Nyun; Lee, Eun Ju; Hong, Jae Won; Kim, Jung Min; Won, Jong Chul; Kim, Mi Kyung; Noh, Jung Hyun; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Dong-Jun
Studies have shown that albuminuria, obesity, and sarcopenia may share pathophysiological processes related to cardiovascular disease risk. Their direct relationships, however, have not been examined. This study investigated the association between albuminuria and sarcopenia in a representative fraction of the Korean population.Of the 10,589 people who participated in the 2011 Korea National Health and Nutrition Examination Survey, 2158 participants aged over 19 years had been tested for albumin-to-creatinine ratio and for body composition data using dual-energy x-ray absorptiometry. Albuminuria was defined as an albumin-to-creatinine ratio ≥30 mg/g. Sarcopenia was defined as a skeletal muscle index (SMI) (SMI (%) = total appendicular skeletal muscle mass [kg]/weight [kg] × 100) of less than 1 standard deviation (SD) (grade 1) or 2 SD (grade 2) below the sex-specific mean for a younger reference group.The prevalence of albuminuria was higher in those with grade 2 sarcopenia than in those with a normal SMI or grade 1 sarcopenia (33.3% versus 8.4% and 8.9%; P albuminuria than in those with the upper tertile of normoalbuminuria. In addition, multiple logistic regression analysis showed the odds ratio for albuminuria risk in the grade 2 sarcopenia group was 2.93 (95% confidence interval [CI], 1.46-5.88), compared with normal SMI after adjusting for potential confounding factors, including the presence of obesity, diabetes, and hypertension. Moreover, individuals with albuminuria had an odds ratio of 3.39 (95% [confidence interval], 1.38-8.37) for grade 2 sarcopenia compared with those in the lowest tertile of normoalbuminuria.This is the first study to demonstrate that individuals with sarcopenia exhibited increased risk of albuminuria and vice versa.
Massicotte-Azarniouch, David; Bader Eddeen, Anan; LazoLanger, Alejandro; Molnar, Amber O; Lam, Ngan N; McCallum, Megan K; Bota, Sarah; Zimmerman, Deborah; Garg, Amit X; Harel, Ziv; Perl, Jeffery; Wald, Ron; Sood, Manish M
The risk for venous thromboembolism (VTE) is elevated with albuminuria or a low estimated glomerular filtration rate (eGFR). However, the VTE risk due to the combined effects of eGFR and albuminuria are unknown. Population-based cohort study. 694,956 adults in Ontario, Canada, from 2002 to 2012. eGFR and albumin-creatinine ratio (ACR). VTE. 15,180 (2.2%) VTE events occurred during the study period. Both albuminuria and eGFR were independently associated with VTE. The association of albuminuria and VTE differed by level of eGFR (P for ACR × eGFR interaction 90mL/min/1.73m 2 ) and heavy albuminuria (ACR>300mg/g) compared with those with normal eGFRs and no albuminuria (subdistribution HR, 1.61; 95% CI, 1.38-1.89). Among those with reduced kidney function (eGFR, 15-29mL/min/1.73m 2 ), the risk for VTE was only minimally increased, irrespective of albuminuria (subdistribution HRs of 1.23 [95% CI, 1-1.5] and 1.09 [95% CI, 0.82-1.45] for ACR300mg/g, respectively). Only single determinations of ACR and eGFR were used. Diagnostic/International Classification of Diseases codes were used to define VTE. Albuminuria increases the risk for VTE markedly in patients with normal eGFRs compared with those with lower eGFRs. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Gil-Ortega, M; García-Prieto, C F; Ruiz-Hurtado, G; Steireif, C; González, M C; Schulz, A; Kreutz, R; Fernández-Alfonso, M S; Arribas, S; Somoza, B
The Munich Wistar Frömter (MWF) rat strain represents an experimental model to study cardiovascular alterations under conditions of progressive albuminuria. The aim of this study was to evaluate the association between genetic predisposition to albuminuria and the development of arterial stiffness and/or vascular remodelling. Experiments were performed in mesenteric arteries from 12-week-old MWF, Wistar Kyoto (WKY) and consomic MWF-6(SHR) and MWF-8(SHR) rats in which chromosomes 6 or 8 associated with albuminuria from MWF were replaced by the respective chromosome from spontaneously hypertensive rats (SHR). Incremental distensibility, wall stress and strain were reduced, and arterial stiffness was significantly increased in albuminuric MWF compared with WKY. Albuminuria suppression in both consomic strains was associated with lower β-values in MWF-8(SHR) and MWF-6(SHR) compared with MWF. Moreover, elastin content was significantly lower in MWF external elastic lamina compared with WKY and both consomic strains. In addition, a reduction in arterial external and internal diameter and cross-sectional area was detected in MWF compared with WKY, thus exhibiting an inward hypotrophic remodelling. However, these alterations remained unchanged in both consomic strains. These data demonstrate that albuminuria in MWF is associated with increased arterial stiffness due to a reduction of elastin content in the external elastic lamina. Moreover, inward hypotrophic remodelling in MWF is not directly associated with albuminuria. In contrast, we demonstrated that two major genetic loci affect both the development of albuminuria and arterial stiffness, thus linking albuminuria and impairment of mechanical properties of resistance arteries. © 2015 The British Pharmacological Society.
Han, Seung Seok; Bae, Eunjin; Ahn, Shin Young; Kim, Sejoong; Park, Jung Hwan; Shin, Sung Joon; Lee, Sang Ho; Choi, Bum Soon; Chin, Ho Jun; Lim, Chun Soo; Kim, Suhnggwon; Kim, Dong Ki
Although adiponectin levels have been reported to be correlated with albuminuria, this issue remains unresolved in non-diabetic hypertensive subjects, particularly when urinary adiponectin is considered. Urinary adiponectin levels were examined using an enzyme-linked immunosorbent assay in 229 participants. who used olmesartan as a hypertensive agent. Their albuminuria levels were measured for 16 weeks after randomization and initiation of conventional or intensive diet education. Linear or logistic regression models were applied, as appropriate, to explore the relationship with albuminuria itself or its response after the intervention. Urinary adiponectin levels were positively related to baseline albuminuria level (r = 0.529). After adjusting for several covariates, the adiponectin level was associated with the albuminuria level (β = 0.446). Among the 159 subjects with baseline macroalbuminuria, the risk of consistent macroalbuminuria (> 300 mg/day) at 16 weeks was higher in the 3(rd) tertile of adiponectin than in the 1(st) tertile (odds ratio = 6.9), despite diet education. In contrast, among all subjects, the frequency of the normoalbuminuria achievement (< 30 mg/day) at 16 weeks was higher in the 1(st) tertile than in the 3(rd) tertile (odds ratio = 13.0). Urinary adiponectin may be a useful biomarker for albuminuria or its response after treatment in non-diabetic hypertensive patients.
Sellers, Elizabeth A C; Hadjiyannakis, Stasia; Amed, Shazhan; Dart, Allison B; Dyck, Roland F; Hamilton, Jill; Langlois, Valerie; Panagiotopoulos, Constadina; Dean, Heather J
To determine the prevalence and the clinical features associated with persistent albuminuria in Canadian children aged albuminuria in children with type 2 diabetes were reported during a 24-month period from 2010 to 2012. Persistent albuminuria was defined as an elevated albumin-to-creatinine ratio in a minimum of 2 out of 3 urine samples obtained at least 1 month apart over 3-6 months and confirmed with a first morning sample. Descriptive statistics were used to illustrate demographic and clinical features of the population. The prevalence of persistent albumuria was estimated using data from a previous national surveillence study of type 2 diabetes in children. Fifty cases were reported over the 24-month study period. The estimated prevalence of persistent albuminuria in children with type 2 diabetes in Canada was 5.1%. The median duration of diabetes at the time of diagnosis of albuminuria was 21 days (IQR, 0-241 days). Almost two-thirds (64%) were female, 80% were of Canadian First Nations heritage, and 76% were from Manitoba. Exposure to gestational or pregestational diabetes in utero occurred in 65%, and 48% had a family history of diabetes-related renal disease. Structural anomalies of the kidney were found in 37%. Persistent albuminuria occurs in youths with type 2 diabetes in the first year after diagnosis, demonstrates regional variation, and is associated with First Nations heritage and exposure to maternal diabetes during pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.
Erman, Orit; Erman, Arie; Vodonos, Alina; Gafter, Uzi; van Dijk, David J
Proteinuria and albuminuria are markers of kidney injury and function, serving as a screening test as well as a means of assessing the degree of kidney injury and risk for cardiovascular disease and death in both the diabetic and the non-diabetic general population. To evaluate the association between proteinuria below 300 mg/24 hours and albuminuria, as well as a possible association with kidney function in patients with diabetes mellitus (DM). The medical files of patients with type 1 and type 2 DM with proteinuria below 300 mg/24 hours at three different visits to the Diabetic Nephropathy Clinic were screened. This involved 245 patient files and 723 visits. The data collected included demographics; protein, albumin and creatinine levels in urine collections; blood biochemistry; and clinical and treatment data. The association between proteinuria and albuminuria is non-linear. However, proteinuria in the range of 162-300 mg/24 hours was found to be linearly and significantly correlated to albuminuria (P albuminuria cutoff of 30 mg/24 hours, was found to be 160.5 mg/24 hr. Body mass index (BMI) was the sole independent predictor of proteinuria above 160.5 mg/24 hr. Changes in albuminuria, but not proteinuria, were associated with changes in creatinine clearance. A new cutoff value of 160.5 mg/hr was set empirically, for the first time, for abnormal proteinuria in diabetic patients. It appears that proteinuria below 300 mg/24 hr is not sufficient as a sole prognostic factor for kidney failure.
Lin, Diaozhu; Qi, Yiqin; Xu, Mingtong; Li, Na; Huang, Chulin; Ren, Meng; Li, Yan; Yan, Li
Background Serum γ - glutamyltransferase (GGT) is implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. Albuminuria is a marker of endothelial damage and correlated with structural and functional integrity of the vasculature. Our objective was to evaluate the association between serum GGT level and prevalence of albuminuria in a Chinese population. Materials and Methods We conducted a population-based cross-sectional study in 9,702 subjects aged 40 years or older. Increased urinary albumin excretion was defined according to the urinary albumin-to-creatinine ratio (ACR) ranges greater or equal than 30 mg/g. Low-grade albuminuria was defined according to the highest quartile of ACR in participants without increased urinary albumin excretion. Results The prevalence of low-grade albuminuria and increased urinary albumin excretion were respectively 23.4% and 6.6% in this population and gradually increased across the sex-specific serum GGT quartiles (all P for trend albuminuria and 1.55 (95% CI, 1.18–2.04) for increased urinary albumin excretion. In subgroup analysis, significant relationship of serum GGT level with both low-grade albuminuria and increased urinary albumin excretion were detected in women, younger subjects, overweight subjects and in those with hypertension or glomerular filtration rate greater than 90 (all P <0.05). Conclusion Serum GGT level is associated with urinary albumin excretion in middle-aged and elderly Chinese. PMID:25500578
Full Text Available Albuminuria contributes to the progression of tubulointerstitial fibrosis. Although it has been demonstrated that ongoing albuminuria leads to tubular injury manifested by the overexpression of numerous proinflammatory cytokines, the mechanism remains largely unknown. In this study, we found that the inflammasome activation which has been recognized as one of the cornerstones of intracellular surveillance system was associated with the severity of albuminuria in the renal biopsies specimens. In vitro, bovine serum albumin (BSA could also induce the activation of NLRP3 inflammasome in the cultured kidney epithelial cells (NRK-52E. Since there was a significant overlap of NLRP3 with the ER marker calreticulin, the ER stress provoked by BSA seemed to play a crucial role in the activation of inflammasome. Here, we demonstrated that the chemical chaperone taurine-conjugated ursodeoxycholic acid (TUDCA which was proved to be an enhancer for the adaptive capacity of ER could attenuate the inflammasome activation induced by albuminuria not only in vitro but also in diabetic nephropathy. Taken together, these data suggested that ER stress seemed to play an important role in albuminuria-induced inflammasome activation, elimination of ER stress via TUDCA might hold promise as a novel avenue for preventing inflammasome activation ameliorating kidney epithelial cells injury induced by albuminuria.
Bouchi, Ryotaro; Fukuda, Tatsuya; Takeuchi, Takato; Minami, Isao; Yoshimoto, Takanobu; Ogawa, Yoshihiro
Sarcopenia, defined as age-related loss of skeletal muscle mass and function, increases the risk of albuminuria. However, it has still unknown whether sarcopenia could increase the risk for the progression of albuminuria. A total 238 patients with type 2 diabetes (mean age 64 ± 12 years; 39.2% women) were studied in the present retrospective observational study. The prevalence of sarcopenia was 17.6%. During the median follow-up period of 2.6 years, albuminuria was measured 5.8 ± 1.8 times, and progression of albuminuria was observed in 14.9% of patients with normoalbuminuria, as was 11.5% in those with microalbuminuria. Sarcopenia was significantly associated with both progression (hazard ratio 2.61, 95% confidence interval 1.08-6.31, P = 0.034) and regression (hazard ratio 0.23, 95% confidence interval 0.05-0.98, P = 0.048) of albuminuria by multivariate Cox regression analysis. The present data suggest that sarcopenia is an important determinant of both progression and regression of albuminuria in patients with type 2 diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
Tanner, Rikki M; Woodward, Mark; Peralta, Carmen; Warnock, David G; Gutiérrez, Orlando; Shimbo, Daichi; Kramer, Holly; Katz, Ronit; Muntner, Paul
We previously developed an 8-item self-assessment tool to identify individuals with a high probability of having albuminuria. This tool was developed and externally validated among non-Hispanic Whites and non-Hispanic Blacks. We sought to validate it in a multi-ethnic cohort that also included Hispanics and Chinese Americans. This is a cross-sectional study. Data were collected using standardized questionnaires and spot urine samples at a baseline examination in 2000-2002. The 8 items in the self-assessment tool include age, race, gender, current cigarette smoking, history of diabetes, hypertension, or stroke, and self-rated health. Of 6,814 community-dwelling adults aged 45-84 years participating in the Multi-Ethnic Study of Atherosclerosis (MESA), 6,542 were included in the primary analysis. Albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g at baseline. Among non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Chinese Americans, the prevalence of albuminuria was 6.0%, 11.3%, 11.6%, and 10.8%, respectively. The c-statistic for discriminating participants with and without albuminuria was .731 (95% CI: .692, .771), .728 (95% CI: .687, .761), .747 (95% CI: .709, .784), and .761 (95% CI: .699, .814) for non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Chinese Americans, respectively. The self-assessment tool over-estimated the probability of albuminuria for non-Hispanic Whites and Blacks, but was well-calibrated for Hispanics and Chinese Americans. The albuminuria self-assessment tool maintained good test characteristics in this large multi-ethnic cohort, suggesting it may be helpful for increasing awareness of albuminuria in an ethnically diverse population.
Kohan, Donald E; Lambers Heerspink, Hiddo J; Coll, Blai; Andress, Dennis; Brennan, John J; Kitzman, Dalane W; Correa-Rotter, Ricardo; Makino, Hirofumi; Perkovic, Vlado; Hou, Fan Fan; Remuzzi, Giuseppe; Tobe, Sheldon W; Toto, Robert; Parving, Hans-Henrik; de Zeeuw, Dick
Endothelin A receptor antagonists (ERAs) decrease residual albuminuria in patients with diabetic kidney disease; however, their clinical utility may be limited by fluid retention. Consequently, the primary objective of this study was to identify predictors for ERA-induced fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs. A post hoc analysis was conducted of the phase IIb atrasentan trials assessing albuminuria reduction in 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) who were randomly assigned to receive placebo (n=50) or atrasentan 0.75 mg/d (n=78) or 1.25 mg/d (n=83) for 12 weeks. Changes in body weight and hemoglobin (Hb) after 2 weeks of treatment were used as surrogate markers of fluid retention. Baseline predictors of weight gain after 2 weeks of atrasentan treatment were higher atrasentan dose, lower eGFR, higher glycated hemoglobin, higher systolic BP, and lower homeostatic metabolic assessment product. Higher atrasentan dose and lower eGFR also predicted decreases in Hb. There were no changes in B-type natriuretic peptide. There was no correlation between reduction in albuminuria after 2 weeks of atrasentan treatment and changes in body weight or Hb. In the Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan/JAPAN trials, atrasentan-associated fluid retention was more likely in patients with diabetes and nephropathy who had lower eGFR or received a higher dose of atrasentan. Finding that albuminuria reduction was not associated with changes in body weight and Hb suggests that the albuminuria-reducing efficacy of atrasentan is not impaired by fluid retention. Copyright © 2015 by the American Society of Nephrology.
Tankeu, Aurel T; Kaze, François Folefack; Noubiap, Jean Jacques; Chelo, David; Dehayem, Mesmin Yefou; Sobngwi, Eugene
AIM To investigate the relationship between circadian variations in blood pressure (BP) and albuminuria at rest, and during exercise in non-hypertensive type 2 diabetes (T2D) patients. METHODS We conducted a cross-sectional study in well controlled T2D patients, non-hypertensive, without clinical proteinuria and normal creatinine clearance. In each participant, we recorded the BP using ambulatory blood pressure monitoring (ABPM) for 24-h, and albuminuria at rest and after a standardized treadmill exercise. RESULTS We enrolled 27 type 2 patients with a median age of 52; and a mean duration of diabetes and HbA1c of 3.6 ± 0.8 years and 6.3% ± 0.5% respectively. Using a 24-h ABPM, we recorded a mean diurnal systolic blood pressure (SBP) of 128 ± 17 mmHg vs nocturnal of 123 ± 19 mmHg (P = 0.004), and mean diurnal diastolic blood pressure (DBP) of 83 ± 11 mmHg vs nocturnal 78 ± 14 mmHg (P = 0.002). There was a significant difference between albuminuria at rest [median = 23 mg, interquartile range (IQR) = 10-51] and after exercise (median = 35 mg, IQR = 23-80, P albuminuria had an increase in nocturnal BP values on all three components (128 mmHg vs 110 mmHg, P = 0.03 for SBP; 83 mmHg vs 66 mmHg, P = 0.04; 106 vs 83, P = 0.02 for mean arterial pressure), as well as albuminuric patients at rest. Moreover, exercise induced albuminuria detect a less increase in nocturnal DBP (83 vs 86, P = 0.03) than resting albuminuria. CONCLUSION Exercise induced albuminuria is associated with an increase in nocturnal BP values in T2D patients. PMID:28729969
Seliger, Stephen L; Salimi, Shabnam; Pierre, Valerie; Giffuni, Jamie; Katzel, Leslie; Parsa, Afshin
Impairment in glomerular endothelial function likely plays a major role in the development of albuminuria and CKD progression. Glomerular endothelial dysfunction may reflect systemic microvascular dysfunction, accounting in part for the greater cardiovascular risk in patients with albuminuria. Prior studies of vascular function in CKD have focused on conduit artery function or those with ESRD, and have not examined microvascular endothelial function with albuminuria. We conducted a cross-sectional study among older hypertensive male veterans with stage 1-4 CKD, and hypertensive controls without CKD. Microvascular function was quantified by two distinct Laser-Doppler flowmetry (LDF) measures: peak responses to 1) post-occlusive reactive hyperemia (PORH) and 2) thermal hyperemia (TH), measured on forearm skin. Associations of each LDF measure with albuminuria, eGFR, and CKD status were estimated using correlation coefficients and multiple linear regression, accounting for potential confounders. Among 66 participants (mean age 69.2 years), 36 had CKD (mean eGFR 46.1 cc/min/1.73 m(2); 30.6 % with overt albuminuria). LDF responses to PORH and TH were 43 and 39 % significantly lower in multivariate analyses among those with macroalbuminuria compared to normoalbuminuria, (β= - 0.42, p = 0.009 and β= -0.37, p = 0.01, respectively). Those with CKD had a 23.9 % lower response to PORH compared to controls (p = 0.02 after adjustment). In contrast, TH responses did not differ between those with and without CKD. Microvascular endothelial function was strongly associated with greater albuminuria and CKD, independent of diabetes and blood pressure. These findings may explain in part the excess systemic cardiovascular risk associated with albuminuria and CKD.
Nazim, J; Małachowska, B; Fendler, W; Starzyk, J
Microalbuminuria reflects generalized vascular dysfunction and the risk of cardiovascular disease. The study aim was to examine the relationship between low-grade albuminuria and the selected risk factors for atherosclerosis, markers of endothelial dysfunction and inflammation in diabetic children and adolescents. In 154 children with diabetes duration of at least 5 years we assessed: HbA1c, lipid profile, apolipoproteins, lipoprotein (a), asymmetric dimethylarginine (ADMA), von Willebrand factor, fibrinogen, uric acid, cystatin C, creatinine, 24-h blood pressure monitoring (ABPM) and albuminuria. Median albuminuria in the whole group was 2.02 μg/min. No correlations were found between albuminuria and lipids, apolipoproteins, fibrinogen, von Willebrand factor, cystatin C and GFR, HbA1c, and uric acid. A significant negative correlation was found between AER and ADMA (R=-0.24, p=0.0023) and positive correlation with all ABPM variables: mean SBP (R=0.23, p=0.0049), mean DBP (R=0.24, p=0.0023), daytime MAP (R=0.31, p=0.0001), nocturnal MAP (r=0.31, palbuminuria and Lp(a) (R=0.15, p=0.059) and BMI Z-score (R=0.14, p=0.089).Children with albuminuria below 5 μg/min. had significantly lower level of fibrinogen (2.96±0.57 g/l vs. 3.29±0.66 g/l, p=0.0167) and mean 24-h systolic and diastolic blood pressure, mean day and nocturnal blood pressure in comparison to the subjects with higher albuminuria. diabetic children with acceptable diabetes control but high-normal albuminuria together with higher level of Lp(a), fibrinogen and blood pressure may require more attention in terms of prevention of early macroangiopathy development. © Georg Thieme Verlag KG Stuttgart · New York.
Bentata, Yassamine; Abouqal, Redouane
Increased urinary albumin excretion (UAE) is a marker of renal and cardiovascular risk in patients with type 2 diabetes (DT2). What about the obese patient with DT2? Does albuminuria predict the progression of renal disease and/or cardiovascular disease? The objective of this study is to determine the link between albuminuria, renal risk and cardiovascular risk in a cohort of obese DT2 patients. This is a prospective study begun in September 2006. It included DT2 patients presenting obesity defined by a body mass index (BMI)>30 Kg/m(2). Three groups of patients were defined: normo-albuminuria (Urinary Albumin Excretion UAE300 mg/day or ACR>300 mg/g). Data on 144 obese DT2 patients were compiled: The mean age of our patients was 59 ± 9 years and the sex ratio 0.26. The incidence of ESRD was higher in the macro-albuminuria group than in the two other groups (26.5% vs. 1.2%, pcardiovascular events was 15.4%, 14.3% and 23.5% in the normo, micro and macro-albuminuria groups (p=0.48). A history of cardiovascular comorbidities was the main cardiovascular risk in multivariate analysis (0R=15.07; 95% CI=5.30-42.82; pcardiovascular risk in the obese DT2 patient, according to our results. However, to accurately demonstrate the link albuminuria - renal risk and albuminuria - cardiovascular risk in the obese DT2 patient, additional studies using very strict criteria of selection and judgment are needed.
Keyzer, Charlotte A; Lambers-Heerspink, Hiddo J; Joosten, Michel M; Deetman, Petronella E; Gansevoort, Ron T; Navis, Gerjan; Kema, Ido P; de Zeeuw, Dick; Bakker, Stephan J L; de Borst, Martin H
Low circulating 25-hydroxyvitamin D [25(OH)D] and high sodium intake are both associated with progressive albuminuria and renal function loss in CKD. Both vitamin D and sodium intake interact with the renin-angiotensin-aldosterone system. We investigated whether plasma 25(OH)D or 1,25-dihydroxyvitamin D [1,25(OH)2D] is associated with developing increased albuminuria or reduced renal function and whether these associations depend on sodium intake. Baseline plasma 25(OH)D and 1,25(OH)2D were measured by liquid chromatography tandem mass spectrometry, and sodium intake was assessed by 24-hour urine collections in the general population-based Prevention of Renal and Vascular End-Stage Disease cohort (n=5051). Two primary outcomes were development of urinary albumin excretion >30 mg/24 h and eGFR (creatinine/cystatin C-based CKD Epidemiology Collaboration) albuminuria or reduced eGFR and potential interaction with sodium intake. During a median follow-up of 10.4 (6.2-11.4) years, 641 (13%) participants developed increased albuminuria, and 268 (5%) participants developed reduced eGFR. Plasma 25(OH)D was inversely associated with increased albuminuria (fully adjusted hazard ratio [HR] per SD higher, 0.86; 95% confidence interval [95% CI], 0.78 to 0.95; P=0.003) but not reduced eGFR (HR, 0.99; 95% CI, 0.87 to 1.12; P=0.85). There was interaction between 25(OH)D and sodium intake for risk of developing increased albuminuria (P interaction =0.03). In participants with high sodium intake, risk of developing increased albuminuria was inversely associated with 25(OH)D (lowest versus highest quartile: adjusted HR, 1.81; 95% CI, 1.20 to 2.73, Palbuminuria or reduced eGFR. Low plasma 25(OH)D is associated with higher risk of developing increased albuminuria, particularly in individuals with high sodium intake, but not of developing reduced eGFR. Plasma 1,25(OH)2D is not associated with risk of developing increased albuminuria or reduced eGFR. Copyright © 2015 by the American
Full Text Available Background. There is a little published data regarding the association between salt intake and albuminuria as an important alarm for progression of cardiovascular and renal dysfunction. We aimed to assess this relationship to emphasize the major role of restricting salt intake to minimize albuminuria and prevent these life-threatening events. Methods. The study population comprised 820 individuals. Participants were assigned to groups as follows: normal albuminuria, slight albuminuria, and clinical albuminuria. Daily salt intake was assessed on the basis of 24-hour urinary sodium excretion, since urinary sodium excretion largely equals sodium intake. Results. In normotensive participants, the mean level of urine albumin was higher in those who had higher amounts of salt intake with a significantly upward trend (the mean urinary albumin level in low-salt-diet group, in medium-salt-intake group, and in high-salt-intake group was 42.70±36.42, 46.89±38.91, and 53.38±48.23, resp., (P=0.017. There was a significant positive correlation between 24-hour urinary sodium secretion and the level of urine albumin (beta = 0.130, P<0.001. The amount of salt intake was significantly associated with urine albumin concentration (beta = 3.969, SE = 1.671, P=0.018. Conclusion. High salt intake was shown to be associated with higher level of microalbuminuria even adjusted for potential underlying risk factors.
Ferris, Maria; Hogan, Susan L; Chin, Hyunsook; Shoham, David A; Gipson, Debbie S; Gibson, Keisha; Yilmaz, Sema; Falk, Ronald J; Jennette, J Charles
Obesity has been associated with kidney disease in adults. This study was designed to evaluate the association of obesity with an early marker of kidney disease, albuminuria, among young adults. Urinalysis (n = 9371), albumin-to-creatinine ratio (n = 4463), and body mass index (kg/m2) were measured in the Add Health Wave III cohort (2001 to 2002), a multiethnic sample of young adults followed for approximately 6 yr. Multivariate logistic regression modeled the association of sex-specific albuminuria with body mass index, adjusted for sample weights, sex, race, ethnicity, and glycosuria. Urinalysis revealed that 0.8% had proteinuria, 4.6% had hematuria, 0.2% had combined hematuria and proteinuria, and 1.5% had glycosuria. Albuminuria prevalence was 4.4%. Mean body mass index was higher among those with albuminuria compared with those without. There were no associations between body mass index categories of 25 to or = 35 kg/m2) was associated with albuminuria, compared with the lowest category (OR = 1.76, 95% CI: 1.02 to 3.04). Glycosuria (OR = 4.0; 95% CI: 1.5 to 11.1, p adults is particularly concerning. Obesity may be a target for primary prevention of kidney and cardiovascular disease.
Long, Y S; Zheng, S; Kralik, P M; Benz, F W; Epstein, P N
The importance of proximal tubules dysfunction to diabetic albuminuria is uncertain. OVE26 mice have the most severe albuminuria of all diabetic mouse models but it is not known if impaired tubule uptake and processing are contributing factors. In the current study fluorescent albumin was used to follow the fate of albumin in OVE26 and normal mice. Compared to normal urine, OVE26 urine contained at least 23 times more intact fluorescent albumin but only 3-fold more 70 kD fluorescent dextran. This indicated that a function other than size selective glomerular sieving contributed to OVE26 albuminuria. Imaging of albumin was similar in normal and diabetic tubules for 3 hrs after injection. However 3 days after injection a subset of OVE26 tubules retained strong albumin fluorescence, which was never observed in normal mice. OVE26 tubules with prolonged retention of injected albumin lost the capacity to take up albumin and there was a significant correlation between tubules unable to eliminate fluorescent albumin and total albuminuria. TUNEL staining revealed a 76-fold increase in cell death in OVE26 tubules that retained fluorescent albumin. These results indicate that failure to process and dispose of internalized albumin leads to impaired albumin uptake, increased albuminuria, and tubule cell apoptosis.
Cho, Eun Bin; Shin, Hee-Young; Park, Sang Eon; Chun, Phillip; Jang, Hye Ryoun; Yang, Jin-ju; Kim, Hee Jin; Kim, Yeo Jin; Jung, Na-Yeon; Lee, Jin San; Lee, Juyoun; Jang, Young Kyoung; Jang, Eun Young; Kang, Mira; Lee, Jong-Min; Kim, Changsoo; Min, Ju-Hong; Ryu, Seungho; Na, Duk L; Seo, Sang Won
We tested the hypothesis that decreased glomerular filtration rate and albuminuria have different roles in brain structure alterations. We enrolled 1,215 cognitively normal individuals, all of whom underwent high-resolution T1-weighted volumetric magnetic resonance imaging scans. The cerebral small vessel disease burdens were assessed with white matter hyperintensities (WMH), lacunes, and microbleeds. Subjects were considered to have an abnormally elevated urine albumin creatinine ratio if the value was ≥17 mg/g for men and ≥25 mg/g for women. Albuminuria, but not estimated glomerular filtration rate (eGFR), was associated with increased WMH burdens (p = 0.002). The data was analyzed after adjusting for age, sex, education, history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, total cholesterol level, body mass index, status of smoking and alcohol drinking, and intracranial volume. Albuminuria was also associated with cortical thinning, predominantly in the frontal and occipital regions (both p albuminuria was associated with frontal thinning partially mediated by WMH burdens. The assessment of albuminuria is needed to improve our ability to identify individuals with high risk for cognitive impairments, and further institute appropriate preventive measures.
Odutayo, Ayodele; Hsiao, Allan J; Emdin, Connor A
Numerous studies have reported an association between albuminuria and adverse outcomes in adults with chronic heart failure (CHF). However, the prevalence of albuminuria in adults with established CHF remains unclear. This study was a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2012. Adults aged ≥18 years were included, and diagnosis of CHF was based on participant self-report. The primary outcome was the prevalence of microalbuminuria (albumin-to-creatinine ratio 30-300 mg/g) and macroalbuminuria (albumin-to-creatinine ratio >300 mg/g) in adults with CHF. The secondary outcome was the adjusted odds ratio of any albuminuria in adults with and without CHF. During the study period, 37,961 adults did not have CHF and 1,214 adults had CHF. In adults with CHF, 22.1% (95% confidence interval [CI] 19.6%-24.7%) had microalbuminuria and 10.4% (95% CI 8.1%-12.7%) macroalbuminuria. In adjusted analyses, the odds of albuminuria in adults with CHF was 1.89-fold higher (95% CI 1.59-2.26; P albuminuria is more common in adults with CHF than in those without CHF, even after adjustment for important demographic and clinical confounders. Copyright © 2016 Elsevier Inc. All rights reserved.
Tanaka, Nobue; Babazono, Tetsuya; Takagi, Michino; Yoshida, Naoshi; Toya, Kiwako; Nyumura, Izumi; Hanai, Ko; Uchigata, Yasuko
The first clinical manifestation of diabetic kidney disease is usually the development of microalbuminuria. However, recent studies have focused on diabetic patients with reduced glomerular filtration rate (GFR) without albuminuria. To evaluate the association of albuminuria and GFR with renal outcomes, we performed an observational study. A total of 3231 type 2 diabetic patients were included in this study between 2003 and 2005. There were 1249 women and the mean age was 59 ± 12 years. The renal endpoints were defined as the initiation of renal replacement therapy (RRT) or 50% reduction from the baseline of estimated GFR (eGFR). At baseline, 669 (20.7%) patients had eGFR albuminuria. During the mean follow-up period of 5.9 ± 1.6 years, 107 patients initiated RRT. A 50% reduction of eGFR from the baseline value was found in 279 patients. None of the normoalbuminuric subjects with or without reduced eGFR required RRT during the observational period (P Albuminuria was a significant predictor for the evaluated renal endpoints, but the impact of eGFR is likely to be less than that of albuminuria. © 2015 Asian Pacific Society of Nephrology.
Nauta, Ferdau L.; Bakker, Stephan J. L.; van Oeveren, Wim; Navis, Gerjan; Homan van der Heide, Jaap J.; van Goor, Harry; de Jong, Paul E.; Gansevoort, Ron T.
Proteinuria is an established marker of decreased kidney function after kidney transplant. It recently has been suggested that albuminuria might be a more reliable marker. Although albuminuria often is regarded as a marker of glomerular damage, because chronic renal allograft damage is believed to
Kröpelin, Tobias F; de Zeeuw, Dick; Remuzzi, Giuseppe; Bilous, Rudy; Parving, Hans-Henrik; Heerspink, Hiddo J L
Albuminuria class transition (normo- to micro- to macroalbuminuria) is used as an intermediate end point to assess renoprotective drug efficacy. However, definitions of such class transition vary between trials. To determine the most optimal protocol, we evaluated the approaches used in four clinical trials testing the effect of renin-angiotensin-aldosterone system intervention on albuminuria class transition in patients with diabetes: the BENEDICT, the DIRECT, the ALTITUDE, and the IRMA-2 Trial. The definition of albuminuria class transition used in each trial differed from the definitions used in the other trials by the number (one, two, or three) of consecutively collected urine samples at each study visit, the time interval between study visits, the requirement of an additional visit to confirm the class transition, and the requirement of a percentage increase in albuminuria from baseline in addition to the class transition. In Cox regression analysis, neither increasing the number of urine samples collected at a single study visit nor differences in the other variables used to define albuminuria class transition altered the average drug effect. However, the SEM of the treatment effect increased (decreased precision) with stricter end point definitions, resulting in a loss of statistical significance. In conclusion, the optimal albuminuria transition end point for use in drug intervention trials can be determined with a single urine collection for albuminuria assessment per study visit. A confirmation of the end point or a requirement of a minimal percentage change in albuminuria from baseline seems unnecessary. Copyright © 2016 by the American Society of Nephrology.
Baldan-Martin, Montserrat; de la Cuesta, Fernando; Alvarez-Llamas, Gloria; Gonzalez-Calero, Laura; Ruiz-Hurtado, Gema; Moreno-Luna, Rafael; Mourino-Alvarez, Laura; Sastre-Oliva, Tamara; Segura, Julian; Padial, Luis R; Vivanco, Fernando; Ruilope, Luis M; Barderas, Maria G
High albuminuria is a strong predictor of development of cardiovascular events in hypertensive patients. The search for predictors identifying patients at risk of developing high albuminuria or presenting a more rapid progression in this parameter may represent an effective strategy for adequate intervention and better outcome. Initially we investigated 24 patients presenting with normoalbuminuria, de novo albuminuria and sustained albuminuria. Plasma proteomics disclosed an upregulation of ceruloplasmin (CP), haptoglobin (HP) and alpha 1-acid glycoprotein (ORM1) that in a second step were selected for validation using turbidimetry assay in a cohort of 105 subjects. The validation showed that HP and ORM1 proteins were increased in patients presenting with very high albuminuria and potential irreversible kidney damage. CP and HP correlated positively with albuminuria values in normoalbuminuric patients. Finally, the levels of ORM1 and CP were increased in patients who progressed in their levels of albuminuria. Our findings show that these proteins may potentially be useful for predicting the development of high albuminuria and to monitor renal damage. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Nauta, Ferdau L.; Bakker, Stephan J. L.; van Oeveren, Wim; Navis, Gerjan; van der Heide, Jaap J. Homan; van Goor, Harry; de Jong, Paul E.; Gansevoort, Ron T.
Background: Proteinuria is an established marker of decreased kidney function after kidney transplant. It recently has been suggested that albuminuria might be a more reliable marker. Although albuminuria often is regarded as a marker of glomerular damage, because chronic renal allograft damage is
HOOGENBERG, K; DULLAART, RPF
Submaximal exercise provokes an abnormal elevation in albuminuria in type 1 (insulin-dependent) diabetes mellitus. Plasma catecholamines might be involved in this phenomenon by a renal vasoconstrictive effect. Twelve healthy subjects (Controls: albuminuria It is concluded that the exercise-induced
Hansen, H P; Rossing, P; Tarnow, L
The aim of our study was to evaluate the diurnal relationship between arterial blood pressure and albuminuria, and some potential mechanisms responsible for impaired nocturnal blood pressure reduction (non-dippers, groups I and II) in diabetic nephropathy (DN). Twenty-four-hour ambulatory blood...... pressure, heart rate (HR) variation (autonomic nervous function) and extracellular fluid volume (ECV) were measured, and urine samples were collected three times during the corresponding day- and nighttimes in 47 insulin-dependent diabetic (IDDM) patients with DN. Mean arterial blood pressure (MABP) during...... was about the same in the three groups. Our study indicated an association between blood pressure and albuminuria, but the mechanisms involved in the reduction of albuminuria from day to night was not unraveled. A relative lack of sympathetic withdrawal during sleep seems to be an important feature...
Lovato, James F.; Murray, Anne M.; Williamson, Jeff; Ismail-Beigi, Faramaz; Karl, Diane; Papademetriou, Vasilios; Launer, Lenore J.
Summary Background and objectives Diabetes mellitus is associated with increased risk of cognitive impairment. This study examines whether microvascular disease, as measured by albuminuria and decline in estimated GFR (eGFR), is associated with cognitive decline during 3.3 years of follow-up in individuals with diabetes with a normal baseline eGFR (approximately 90 ml/min per 1.73 m2). Design, setting, participants, & measurements Participants were from the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes study (N=2977; mean age 62.5±5.8 years; recruitment from August 2003 to December 2005, followed through June 2009), which examined the association of intensive versus standard glucose control on cognitive function. Participants underwent three neuropsychologic tests at baseline, 20 months, and 40 months. Tests included information processing speed, verbal memory, and executive function. Mixed-effects models were used to assess the association of albuminuria and eGFR on the percentage decline in each test. Results Participants with albuminuria at baseline and follow-up (persistent albuminuria) (−5.8% [95% confidence interval (CI), −7.3 to −4.2]) and participants with albuminuria at follow-up but none at baseline (progressive albuminuria) (−4.1% [95% CI, −5.6 to −2.7]) had greater percentage declines on information processing speed than participants without albuminuria at baseline and at follow-up (no albuminuria) (−2.6% [95% CI, −3.4 to −1.9]) (P=0.001 and P=0.10, respectively). There were borderline percentage changes in the test of verbal memory (4.8% [95% CI, 2.4 to 7.1] and 4.7% [95% CI, 2.5 to 7.0] versus 7.1% [95% CI, 6.0 to 8.3]; P=0.11 and P=0.08, respectively). On logistic regression analysis, persistent albuminuria (odds ratio, 1.37 [95% CI, 1.09 to 1.72]) and progressive albuminuria (odds ratio, 1.25 [95% CI, 1.02 to 1.56]) were associated with a ≥5% decline in information processing speed scores but not with
Delea, Thomas E; Sofrygin, Oleg; Palmer, James L
The Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial demonstrated that adding aliskiren, an oral direct renin inhibitor, at a dosage of 300 mg/d to the highest approved dosage of losartan and optimal antihypertensive therapy reduces albuminuria over 6 mo among patients with type...... 2 diabetes, hypertension, and albuminuria. The cost-effectiveness of this therapy, however, is unknown. Here, we used a Markov model to project progression to ESRD, life years, quality-adjusted life years, and lifetime costs for aliskiren plus losartan versus losartan. We used data from the AVOID...... aliskiren to losartan and optimal therapy in patients with type 2 diabetes, hypertension, and albuminuria may be cost-effective from a US health care system perspective....
Fuhrman, Dana Y; Schneider, Michael F; Dell, Katherine M; Blydt-Hansen, Tom D; Mak, Robert; Saland, Jeffrey M; Furth, Susan L; Warady, Bradley A; Moxey-Mims, Marva M; Schwartz, George J
The role of albuminuria as an indicator of progression has not been investigated in children with CKD in the absence of diabetes. Children were enrolled from 49 centers of the CKD in Children study between January of 2005 and March of 2014. Cross-sectional multivariable linear regression ( n =647) was used to examine the relationship between urine protein-to-creatinine (UP/C [milligrams per milligram]) and albumin-to-creatinine (ACR [milligrams per gram]) with eGFR (milliliters per minute per 1.73 m 2 ). Parametric time-to-event analysis ( n =751) was used to assess the association of UP/C, ACR, and urine nonalbumin-to-creatinine (Unon-alb/cr [milligrams per gram]) on the time to the composite endpoint of initiation of RRT or 50% decline in eGFR. The median follow-up time was 3.4 years and 202 individuals experienced the event. Participants with a UP/C≥0.2 mg/mg and ACR≥30 mg/g had a mean eGFR that was 16 ml/min per 1.73 m 2 lower than those with a UP/C2.0 mg/mg], RT=0.09 for ACR [>1333 mg/g], RT=0.07 for Unon-alb/cr [>715 mg/g]) levels to the lowest levels. A similar trend was seen when categories were created on the basis of clinically meaningful cutoff values of ACR (300 mg/g). In children with CKD without diabetes, the utility of an initial UP/C, ACR, and Unon-alb/cr for characterizing progression is similar. Copyright © 2017 by the American Society of Nephrology.
Few data are available on the extent of albuminuria in diabetic populations in the Middle East generally and in Lebanon specifically. We conducted this study to determine the prevalence of albuminuria and its major risk factors in a cohort of diabetic patients in Lebanon. Patients and Diabetic patients followed in the outpatient department at the American University of Beirut Medical Center (AUBMC) were included in a prospective observational study. AUBMC is a tertiary referral center and the outpatient department typically handles patients of low socioeconomic status with advanced disease. Patients were classified according to their urinary albumin-to-creatinine ratio (ACR) as having normoalbuminuria (ACR<30 mg/g creatinine), microalbuminuria (ACR=30 to <300 mg/g creatinine), or macro-albuminuria (ACR 2300 mg/g creatinine). The three groups were compared to analyze the association between albuminuria and its risk factors. In addition, independent predictors of albuminuria were determined using multivariate logistic regression and presented as an odds ratio.Microalbuminuria and macroalbuminuria were present in 33.3% and 12.7% of 222 patients (mean age 56.4 years, mean deviation of diabetes 8.6 years, 58.7% women, 43.8% obese), respectively. Factors significantly associated with microalbuminuria included glycemic control, insulin use, and total and LDL cholesterol.Those associated with macroalbuminuria included in addition to glycemic control and insulin use, duration of diabetes, hypertension, elevated mean arterial pressure (MAP), and presence of neuropathy, retinopathy and peripheral vascular disease by bivariate analysis. Only glycemic control was an independent risk factor for both in addition to MAP and retinopathy for macroalbuminuria by multivariate analysis. Albuminuria is highly prevalent among this cohort of diabetic patients in Lebanon. Both glyce-mic control and blood pressure need to be better targeted in its management (Author).
de Beus, Esther; Meijs, Matthijs F L; Bots, Michiel L; Visseren, Frank L J; Blankestijn, Peter J
Increased left ventricular mass (LVM) is known to predict cardiovascular morbidity and mortality. LVM is high in patients with advanced kidney disease. Our aim was to study the relationship between renal parameters and LVM in hypertensive subjects at high risk of cardiovascular disease. Cardiac MRI was performed in 527 patients participating in the single-centre SMART cohort study. Participants free from previous symptomatic coronary heart disease but with a history of hypertension were recruited. Subjects were screened for cardiovascular risk factors in a standardized way. Multivariable linear regression was used to study the relationship of both estimated glomerular filtration rate (eGFR) and presence of albuminuria with left ventricular mass. Mean LVM was 121 g for men (SD 26) and 87 g for women (SD 20). Mean eGFR was 82 mL/min/1.73 m(²) (SD 19). A total of 73 patients (14%) had albuminuria. After adjusting for known determinants of LVM (height, weight, sex and age) eGFR did not relate to LVM while presence of albuminuria did (mean change in LVM per 10 mL/min/1.73 m(2) change in eGFR 0.79 g, 95% CI -0.33 to 1.91, P = 0.17, mean change in LVM in presence vs. absence of albuminuria 9.9 g, 95% CI 4.33 to 15.45, P = 0.001). Additional adjustment for systolic blood pressure did not change results (B for eGFR 0.54, 95% CI -0.58 to 1.66, P = 0.35, B for albuminuria 9.09, 95% CI 3.57 to 14.60, P = 0.001). In this study in hypertensive patients with high vascular risk, albuminuria was related to increased LVM and eGFR was not. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.
Heerspink, H J L; Johnsson, E; Gause-Nilsson, I; Cain, V A; Sjöström, C D
To characterize the effect of dapagliflozin on albuminuria and estimated glomerular filtration rate (eGFR) and to determine whether effects on albuminuria were mediated through changes in glycated haemoblogin (HbA1c), systolic blood pressure (SBP), body weight or eGFR. We conducted a post hoc analysis of data pooled from two phase III clinical trials in hypertensive patients with type 2 diabetes (T2DM) on stable angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, randomly assigned to dapagliflozin 10 mg/day or matched placebo. This analysis included only patients with microalbuminuria or macroalbuminuria at baseline. Patients were randomized to receive dapagliflozin 10 mg (n = 167) or placebo (n = 189). Dapagliflozin resulted in greater 12-week reductions in albuminuria compared with placebo: -33.2% [95% confidence interval (CI) -45.4, -18.2]. The reduction in albuminuria was also present after adjusting for age, sex and changes in HbA1c, SBP, body weight and eGFR: -23.5% (95% CI -37.6, -6.3). There was a decrease in eGFR with dapagliflozin versus placebo that was readily reversed 1 week after last dose. No serious renal-related adverse events were observed in any group. Dapagliflozin was effective in lowering albuminuria in patients with T2DM and hypertension using renin-angiotensin system blockade therapy. Reductions in albuminuria were still present after adjusting for changes in HbA1c, SBP, body weight and eGFR. Dapagliflozin-induced improvements in glycaemic control and reductions in SBP, coupled with other potentially beneficial renal effects, may lead to a reduced long-term renal and cardiovascular risk. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
Heerspink, H J L; Ninomiya, T; Persson, F; Brenner, B M; Brunel, P; Chaturvedi, N; Desai, A S; Haffner, S M; Mcmurray, J J V; Solomon, S D; Pfeffer, M A; Parving, H-H; de Zeeuw, D
To investigate whether the degree of albuminuria reduction observed in the ALTITUDE trial is associated with renal and cardiovascular protection, and secondly, whether the reduction in albuminuria was too small to afford clinical benefit. In a post hoc analysis of the ALTITUDE trial in 8561 patients with type 2 diabetes and chronic kidney disease or cardiovascular disease we examined the effect of albuminuria changes at 6 months on renal and cardiovascular outcomes using Cox proportional hazard regression. The median change in albuminuria in the first 6 months in the aliskiren arm of the trial was -12% (25th to 75th percentile: -48.7_to_ +41.9%) and 0.0% (25th to 75th percentile: -40.2_to_55%) in the placebo arm. Changes in albuminuria in the first 6 months were linearly associated with renal and cardiovascular endpoints: a >30% reduction in albuminuria in the first 6 months was associated with a 62% reduction in renal risk and a 25% reduction in cardiovascular risk compared with an increase in albuminuria. The association between changes at 6 months in albuminuria and renal or cardiovascular endpoints was similar in the two treatment groups (p for interaction >0.1 for both endpoints). The addition of aliskiren to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy resulted in albuminuria changes that were associated with renal and cardiovascular risk changes. This did not translate into renal or cardiovascular protection because the overall reduction in albuminuria in the aliskiren arm was too small and nearly similar to that in the placebo arm. © 2015 John Wiley & Sons Ltd.
Knudsen, Søren Tang; Jeppesen, Peter; Frederiksen, Christian Alcaraz
examined. We examined the relation between PP, markers of endothelial activation and albuminuria in Type 2 diabetic patients. METHODS: In 46 Type 2 diabetic patients and 19 non-diabetic subjects, we performed 24-h ambulatory blood pressure (AMBP) monitoring. Urinary albumin excretion rate was measured......: Increased PP is associated with endothelial activation and albuminuria in Type 2 diabetic patients. Thus, endothelial dysfunction may represent a pathophysiological link between an elevated PP and microvascular complications in these subjects. Prospective studies are needed to further elucidate...
Tyson, Crystal C; Barnhart, Huiman; Sapp, Shelly; Poon, Victor; Lin, Pao-Hwa; Svetkey, Laura P
We evaluated whether low-grade albuminuria or black race modulates ambulatory blood pressure (BP) or nocturnal BP response to the DASH diet. Among 202 adults enrolled in the DASH multicenter trial who were fed the DASH or control diet for 8 weeks, reductions in 24-hour daytime and nighttime SBP and DBP were significantly larger for DASH compared to control. Median changes in nocturnal BP dipping were not significant. Compared to urine albumin excretion of DASH on ambulatory BP in the presence of low-grade albuminuria. ©2018 Wiley Periodicals, Inc.
Bentata, Yassamine; Karimi, Ilham; Benabdellah, Nawal; Alaoui, Fatiha El; Haddiya, Intissar; Abouqal, Redouane
Diabetic nephropathy is the primary cause of chronic kidney disease and is associated with increased cardiovascular mortality. Cigarette smoking is probably the most complex and the least understood among the risk factors for chronic kidney disease and cardiovascular disease in diabetic patients. The aim of this study was to determine the impact of smoking on progression of nephropathy and cardiovascular disease in type 2 diabetic patients with albuminuria and those without albuminuria. This is a prospective study. The Ethics Committee of Morocco's Mohammed V University in Rabat approved the study protocol. Inclusion criteria targeted patients who were type 2 diabetics and who had nephrology follow up for at least 36 months. A total of 671 cases of T2D were included. Mean age of all patients was 65 ± 11 years and 12.1% were smokers. There was no statistically significant difference between T2D patients with albuminuria according to absence of presence of smoking at the time of enrollment, at 1 year and 3 years of follow-up, concerning the median albumin excretion rate (mg/day): 98 [56-281] vs. 124 [56-323] (p=0.59); 98 [56-281] vs. 124 [56-323] (p=0.15) and 98 [56-281] vs. 124 [56-323] (p=0.52) respectively. There was a statistically significant difference between T2D patients with albuminuria according to absence or presence of smoking at the time of enrollment and the end of follow-up, concerning cardiovascular events: 56 (12.3%) vs. 19 (28.4%) (prisk factors for progression of renal and cardiovascular disease in diabetic patients, thus adding to the burden of morbimortality.
Gansevoort, Ron T; Meijer, Esther; Chapman, Arlene B; Czerwiec, Frank S; Devuyst, Olivier; Grantham, Jared J; Higashihara, Eiji; Krasa, Holly B; Ouyang, John; Perrone, Ronald D; Torres, Vicente E
The TEMPO 3:4 Trial results suggested that tolvaptan had no effect compared with placebo on albuminuria in autosomal-dominant polycystic kidney disease (ADPKD) patients. However, the use of categorical 'albuminuria events' may have resulted in a loss of sensitivity to detect changes. The aim of this study is to investigate the effects of tolvaptan on albuminuria as a continuous variable. Post hoc analysis of a 3-year prospective, blinded randomized controlled trial, including 1375 ADPKD patients. Albuminuria was measured in a spot morning urine sample prior to tolvaptan dosing and expressed as albumin-to-creatinine ratio (ACR). Baseline median (interquartile range) ACR was 3.2 (1.7-7.1) mg/mmol. Of note, 47.9% of ADPKD patients had normal, 48.7% moderately increased and 3.4% severely increased ACR. Subjects with higher baseline ACR had higher blood pressure and total kidney volume (TKV) and lower estimated glomerular filtration rate (eGFR). During follow-up, higher baseline ACR was associated with more rapid eGFR loss (P albuminuria was associated with more eGFR loss. Tolvaptan decreased albuminuria compared with placebo, independent of blood pressure. Treatment efficacy of tolvaptan on changes in TKV and eGFR was more readily detected in patients with higher albuminuria. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Choi, H S; Hong, J W; Lee, J H; Noh, J H; Kim, D J
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. To investigate whether an elevated heart rate is an independent factor associated with albuminuria in the general adult population of Korea. 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). 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 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. The prevalence of albuminuria is independently associated with heart rate in the general adult population of Korea. © 2014 Royal Australasian College of Physicians.
Rossing, P; Hommel, E; Smidt, U M
filtration rate and diastolic blood pressure (r = 0.52, P multiple linear regression analysis only showed a significant correlation between the rate of decline in glomerular filtration rate and diastolic blood pressure...... (P multiple regression analysis showed that albuminuria and not blood pressure was correlated significantly with rate of decline in glomerular filtration rate. Patients were stratified by average value...
Bakker, Stephan J. L.; Gansevoort, Ron T.; de Zeeuw, Dick
Albuminuria is an early marker for diabetic nephropathy in patients with diabetes, and has a clear place in patient care. It also predicts cardiovascular events and mortality in diabetic patients and in the general population, and is slowly becoming accepted in population screening for
Bakker, Stephan J L; Gansevoort, Ron T; de Zeeuw, Dick
Albuminuria is an early marker for diabetic nephropathy in patients with diabetes, and has a clear place in patient care. It also predicts cardiovascular events and mortality in diabetic patients and in the general population, and is slowly becoming accepted in population screening for
Long, David A; Kolatsi-Joannou, Maria; Price, Karen L; Dessapt-Baradez, Cecile; Huang, Jennifer L; Papakrivopoulou, Eugenia; Hubank, Mike; Korstanje, Ron; Gnudi, Luigi; Woolf, Adrian S
Normally, the glomerular filtration barrier almost completely excludes circulating albumin from entering the urine. Genetic variation and both pre- and postnatal environmental factors may affect albuminuria in humans. Here we determine whether glomerular gene expression in mouse strains with naturally occurring variations in albuminuria would allow identification of proteins deregulated in relatively ‘leaky' glomeruli. Albuminuria increased in female B6 to male B6 to female FVB/N to male FVB/N mice, whereas the number of glomeruli/kidney was the exact opposite. Testosterone administration led to increased albuminuria in female B6 but not female FVB/N mice. A common set of 39 genes, many expressed in podocytes, were significantly differentially expressed in each of the four comparisons: male versus female B6 mice, male versus female FVB/N mice, male FVB/N versus male B6 mice, and female FVB/N versus female B6 mice. The transcripts encoded proteins involved in oxidation/reduction reactions, ion transport, and enzymes involved in detoxification. These proteins may represent novel biomarkers and even therapeutic targets for early kidney and cardiovascular disease. PMID:23447063
Lambers Heerspink, Hiddo J.
Achieving optimal blood pressure and albuminuria control is a major therapeutic treatment goal in patients with renal insufficiency. Angiotensin-converting enzyme-inhibitors (ACEIs) and angiotensin-receptor blockers (ARB) are the mainstay of therapy in these patients. However, despite these
Scheven, Lieneke; Halbesma, Nynke; de Jong, Paul E.; de Zeeuw, Dick; Bakker, Stephan J. L.; Gansevoort, Ron T.
Background: Urinary albumin excretion is known to be independently associated with progression of renal and cardiovascular disease. The aim of this study was to identify predictors for progression in albuminuria in the general population. Methods: Data were used of the first 4 screening rounds of a
Gansevoort, Ron T; Nauta, Ferdau L; Bakker, Stephan J L
PURPOSE OF REVIEW: Screening for chronic kidney disease frequently starts with assessment of estimated glomerular filtration rate (eGFR). In current approaches, further evaluation will only include measurement of albuminuria in case of eGFR less than 60 ml/min/1.73 m. We will review whether this
Heringa, S.M.; van den Berg, E; Dekker, J.M.; Nijpels, G.; Kessels, R.P.C.; Kappelle, L.J.; Stehouwer, C.D.A.; Biessels, G.J.
Background/Aims: Markers of vascular disease elsewhere in the body may reflect vascular abnormalities in the brain relevant to age-related cognitive decline and dementia. We examined the association between albuminuria, as a marker of microvascular damage, and cognition in older individuals.
Gansevoort, Ron T.; Nauta, Ferdau L.; Bakker, Stephan J. L.
Purpose of review Screening for chronic kidney disease frequently starts with assessment of estimated glomerular filtration rate (eGFR). In current approaches, further evaluation will only include measurement of albuminuria in case of eGFR less than 60 ml/min/1.73m(2). We will review whether this
Jensen, Magnus Thorsten; Sogaard, Peter; Andersen, Henrik Ullits
OBJECTIVES: The purpose of this study was to investigate if systolic myocardial function is reduced in all patients with type 1 diabetes (T1DM) or only in patients with albuminuria. BACKGROUND: Heart failure is a common cause of mortality in T1DM, and a specific diabetic cardiomyopathy has been s...
Vart, Priya; Scheven, Lieneke; Lambers Heerspink, Hiddo J; de Jong, Paul E; de Zeeuw, Dick; Gansevoort, Ron T
Background: New guidelines advocate the use of albumin-creatinine ratio (ACR) in a urine sample instead of 24-hour urinary albumin excretion (UAE) for staging albuminuria. Concern has been expressed that this may result in misclassification for reasons including interindividual differences in
Keyzer, Charlotte A; Lambers-Heerspink, Hiddo J; Joosten, Michel M; Deetman, Petronella E; Gansevoort, Ron T; Navis, Gerjan; Kema, Ido P; de Zeeuw, Dick; Bakker, Stephan J L; de Borst, Martin H
Background and objectives Low circulating 25-hydroxyvitamin D [25(OH)D] and high sodium intake are both associated with progressive albuminuria and renal function loss in CKD. Both vitamin D and sodium intake interact with the renin-angiotensin-aldosterone system. We investigated whether plasma
Ebaa Al Ozairi
In conclusion, this study shows significantly improvement in albuminurea with sustained improvement in HbA1c through better carbohydrate skills. DAFNE course should prove cost effective with sustained glycemic profile and improvement of albuminuria and should become more widely available.
O-charoen, Pichaya; Ndhlovu, Lishomwa C; Gangcuangco, Louie Mar A; Keating, Sheila M; Norris, Philip J; Ng, Roland C K; Mitchell, Brooks I; Shikuma, Cecilia M; Chow, Dominic C
Albuminuria among HIV-infected individuals has been found to be associated with cardiovascular disease (CVD) and mortality. Inflammation has been associated with albuminuria. The pathophysiology of albuminuria in HIV-infected individuals is poorly understood. We investigated the association of albuminuria with inflammatory biomarkers among HIV-infected individuals on combination antiretroviral therapy (cART). This is a cross-sectional analysis of participants enrolled in the Hawaii Aging with HIV-Cardiovascular Cohort. Plasma inflammatory biomarkers were assessed using the Milliplex Human Cardiovascular disease multiplex assays. A random urine sample was collected for albumin measurement. Albuminuria was defined as urine albumin-to-creatinine ratio of ≥30 mg/g. Framingham risk score was calculated and divided into three classes. Simple and multivariable logistic regression analyses were utilized to assess the correlation between plasma inflammatory biomarkers and albuminuria and were adjusted for Framingham risk category. Among 111 HIV-infected patients [median (IQR) age of 52 (46-57) years, 86% male, median (IQR) CD4 count of 489 (341-638) cells/mm(3), 85% with HIV RNA <50 copies/ml], 18 subjects (16.2%) had moderately increased albuminuria (albuminuria range between 30 and 300 mg/g) and 2 subjects (1.8%) had severely increased albuminuria (albuminuria more than 300 mg/g). In multivariable logistic models, sE-selectin, sVCAM-1, CRP, SAA, and SAP remained significantly associated with albuminuria after adjustment of CVD risk factors. This study showed an association between inflammation and albuminuria independent of previously reported risk factors for albuminuria in HIV-infected subjects who were on combination antiretroviral therapy (cART). Chronic inflammation despite potent antiretroviral treatment may contribute to higher rates of albuminuria among HIV-infected patients.
O-charoen, Pichaya; Ndhlovu, Lishomwa C.; Gangcuangco, Louie Mar A.; Keating, Sheila M.; Norris, Philip J.; Ng, Roland C.K.; Mitchell, Brooks I.; Shikuma, Cecilia M.
Abstract Albuminuria among HIV-infected individuals has been found to be associated with cardiovascular disease (CVD) and mortality. Inflammation has been associated with albuminuria. The pathophysiology of albuminuria in HIV-infected individuals is poorly understood. We investigated the association of albuminuria with inflammatory biomarkers among HIV-infected individuals on combination antiretroviral therapy (cART). This is a cross-sectional analysis of participants enrolled in the Hawaii Aging with HIV-Cardiovascular Cohort. Plasma inflammatory biomarkers were assessed using the Milliplex Human Cardiovascular disease multiplex assays. A random urine sample was collected for albumin measurement. Albuminuria was defined as urine albumin-to-creatinine ratio of ≥30 mg/g. Framingham risk score was calculated and divided into three classes. Simple and multivariable logistic regression analyses were utilized to assess the correlation between plasma inflammatory biomarkers and albuminuria and were adjusted for Framingham risk category. Among 111 HIV-infected patients [median (IQR) age of 52 (46–57) years, 86% male, median (IQR) CD4 count of 489 (341–638) cells/mm3, 85% with HIV RNA albuminuria (albuminuria range between 30 and 300 mg/g) and 2 subjects (1.8%) had severely increased albuminuria (albuminuria more than 300 mg/g). In multivariable logistic models, sE-selectin, sVCAM-1, CRP, SAA, and SAP remained significantly associated with albuminuria after adjustment of CVD risk factors. This study showed an association between inflammation and albuminuria independent of previously reported risk factors for albuminuria in HIV-infected subjects who were on combination antiretroviral therapy (cART). Chronic inflammation despite potent antiretroviral treatment may contribute to higher rates of albuminuria among HIV-infected patients. PMID:25205472
Liu, Gang; Sun, Qi; Zhu, Mingjiang; Sun, Liang; Wang, Zhenzhen; Li, Huaixing; Li, Zi; Chen, Yan; Yin, Huiyong; Lin, Xu
High exposure to nickel could induce renal dysfunction in rodents and occupational workers. However, little is known about the effects of non-occupational exposure to nickel on renal health in the general population. We aimed to examine the associations of urinary nickel concentrations with albuminuria and β2-microglobulinuria in Chinese adults. 2115 non-institutionalised Chinese men and women aged 55-76 years from Beijing and Shanghai were included. Urinary nickel concentrations were assessed by inductively coupled plasma mass spectroscopy. Plasma uric acid, urea nitrogen, C reactive protein and urinary albumin, β2-microglobulin and creatinine were measured. Albuminuria was defined as urinary albumin ≥30 mg/g creatinine, and β2-microglobulinuria was defined as urinary β2-microglobulin ≥200 µg/g creatinine. Median concentration of urinary nickel was 3.95 μg/g creatinine (IQR: 2.57-6.71 μg/g creatinine), and prevalence of albuminuria, β2-microglobulinuria and both albuminuria and β2-microglobulinuria was 22.1%, 24.5% and 9.7%, respectively. Comparing the highest with the lowest quartile of urinary nickel, the ORs (95% CIs) were 1.99 (1.46 to 2.78) for albuminuria, 1.44 (1.07 to 1.95) for β2-microglobulinuria, and 2.95 (1.74 to 4.97) for both albuminuria and β2-microglobulinuria, after adjustment for demographic characteristics, lifestyle behaviours, body mass index, hypertension and diabetes. The association remained significant when further controlling for inflammatory markers or other heavy metals (all p trend nickel levels were positively associated with albuminuria and β2-microglobulinuria in Chinese men and women, who had relatively low background nickel exposure. More prospective studies are needed to confirm our findings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Lv, Xiaofei; Sun, Wanwan; Huang, Xiaolin; Chen, Ying; Ding, Lin; Lin, Lin; Chen, Yuhong; Lu, Jieli; Xu, Min; Bi, Yufang; Wang, Weiqing; Ning, Guang; Xu, Yu
Fetuin-A is an important hepatokine associated with many cardiometabolic abnormities. The association between fetuin-A and albuminuria has not been investigated in a prospective cohort. The objective of the study was to prospectively investigate whether serum fetuin-A levels were associated with albuminuria in middle-aged and elderly Chinese. A community-based study was conducted at baseline in 2009, including 3102 individuals aged 40 years or older and followed up for 4 years. Baseline and follow-up urine samples were collected to measure urinary albumin and creatinine concentrations. Albuminuria was defined as urinary albumin to creatinine ratio (UACR) of 30 mg/g or greater. A total of 194 participants (8.5%) developed albuminuria during the follow-up. Men who developed albuminuria had significantly higher baseline levels of fetuin-A compared with those who did not (338.2 vs 292.9 mg/L, P = .02). Among men, after adjustment for traditional risk factors, each 1-SD increase of fetuin-A level (131.6 mg/L) was associated with a 32% higher risk for developing albuminuria (odds ratio 1.32, 95% confidence interval 1.07-1.62). In addition, among men, compared with participants in the lowest tertile (338.2 mg/L) had a 2-fold risk for developing albuminuria (odds ratio 2.07, 95% confidence interval 1.04-4.12) after multivariate adjustment. No association between fetuin-A levels and incident albuminuria was observed in women. High serum fetuin-A levels were independently associated with an increased risk of developing albuminuria in middle-aged and elderly men, whereas no significant associations were found in women.
Hasanato, Rana M
To compare a less cumbersome random albumin creatinine ratio (RACR) with 24-hour urinary albumin excretion (UAE) for detection of renal damage in patients with type 2 diabetes mellitus (T2DM). This retrospective study performed between March 2013 and June 2014 at the Department of Pathology, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia included 122 patients (mean age 54 ± 15, 104 females and 18 males) with T2DM. Urine albumin levels of less than 30 mg/g was considered normal, from 30-300 mg/g considered as micro-albuminuria, and over 300 mg/g considered as macro-albuminuria. Concordance between the 2 assays was observed in 114 (93.4%) samples. The sensitivity of RACR assay was 100%, specificity was 91.3% with a positive predictive value (PPV) of 95%, and a negative predictive value (NPV) of 100% in micro-albuminuria range. For macro-albuminuria, RACR had a sensitivity of 100%, specificity of 94.1% with PPV of 94% and NPV of 100%. Receiver operating characteristic (ROC) curves analysis cut-off values of 40 mg/g-300 mg/g for micro- and greater than 300 mg/g for macro-albuminuria revealed 100% sensitivity, 97.5% specificity, 95% PPV, and 100% NPV for micro-albuminuria, and 100% sensitivity, 94% specificity, 76% PPV, and 100% NPP for macro-albuminuria. The area under the curve for micro-albuminuria was 100% and 98.2% for macro-albuminuria. Performance of RACR was comparable to 24 hour UAE assay particularly in excluding renal damage in T2DM.
Li, Ming; McDermott, Robyn
To document albuminuria prevalence and its associated factors in Aboriginal and Torres Strait Islander (TSI) adults with high renal and metabolic risks from 19 rural and remote north Queensland communities. One thousand nine hundred seventy-one indigenous adults were enrolled in 1998 and 566 completed follow up in 2007 in this population-based study. Measurements included weight, waist circumference (WC), blood pressure (BP), fasting glucose, lipids, gamma-glutamyltransferase (GGT), urinary albumin creatinine ratio (UACR), smoking, alcohol intake and physical activity (PA). Albuminuria was defined as an UACR > =2.5 g/mol in males and > =3.5 g/mol in females. The association between albuminuria and biomedical factors was assessed with generalised linear modelling. Baseline albuminuria prevalence was 19.7 % (95 % CI: 18.0-21.6 %). Follow up prevalence was 42.4 % (95 % CI: 38.4-46.5 %) among the 566 adults having the 2(nd) UACR measurements. Follow-up albuminuria was associated with fasting glucose of 5.4 mmol/L (OR 2.5, 95 % CI 1.5-4.2), GGT tertiles in a dose-response manner (OR 2.0 for 2(nd) and 3.7 for 3(rd) tertile, p for trend albuminuria compared to TSI counterparts, while TSI smokers had twice the likelihood (95 % CI 1.2-3.2). At both baseline and follow up, albuminuria was more prevalent among older participants. Indigenous Australians in north Queensland are at high risk of albuminuria. Overweight and obesity, glycaemia, increased GGT, and smoking were associated with albuminuria at baseline and/or follow up.
Gonzalez-Calero, Laura; Martin-Lorenzo, Marta; Martínez, Paula J; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Segura, Julian; de la Cuesta, Fernando; Barderas, Maria G; Ruilope, Luis M; Vivanco, Fernando; Alvarez-Llamas, Gloria
Hypertension (HTN) is increasing in prevalence, and albuminuria is a strong indicator of cardiovascular risk and renal damage progression. Despite blood pressure control with chronic treatment, a relevant subgroup of patients develop albuminuria. However, the biological factors responsible for albuminuria development and progression are underexplored. We aimed to identify key metabolic targets and biological pathways involved in the negative progression of cardiovascular and renal damage in hypertensives undergoing chronic treatment. A series of 1533 patients were followed for 5 years to investigate the evolution of albuminuria. Patients were classified as: (1) patients with persistent normoalbuminuria; (2) patients developing de novo albuminuria; and (3) patients with maintained albuminuria. At the end of follow-up, urine from 30 nonhypertensive subjects (control group) and a representative cohort of 118 patients was collected for metabolomic analysis. Metabolic patterns of interest were identified in a first discovery phase by nuclear magnetic resonance and further confirmed by liquid chromatography-mass spectrometry. Metabolites corresponding to HTN or albuminuria were measured in a prospective study carried out in 35 individuals still in normoalbuminuria, to evaluate their potential as predictors of albuminuria development. Nine metabolites were significantly altered, linking β-alanine metabolism, arginine and proline metabolism, and tricarboxylic acid cycle. The prospective study revealed a panel composed of guanidinoacetate, glutamate, and pantothenate, which was able to predict development of albuminuria. These metabolic signatures open new possibilities in hypertensive therapy and cardiovascular risk control, providing prompt and more efficient intervention, particularly in patients with worse cardiovascular prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.
Kanamaru, Takuya; Suda, Satoshi; Muraga, Kanako; Okubo, Seiji; Watanabe, Yoko; Tsuruoka, Syuichi; Kimura, Kazumi
Reduced glomerular filtration rate (GFR) and albuminuria have been independently associated with an increased risk of stroke and unfavorable long-term outcomes. However, the association between GFR, albuminuria, and early neurological deterioration (END) in patients with ischemic stroke has not been well studied to date. We therefore investigated the ability of estimated GFR (eGFR) and albuminuria to predict END in patients with acute ischemic stroke. We retrospectively enrolled 294 patients that were admitted to our stroke center with acute ischemic stroke between January 2011 and September 2012. General blood and urine examinations, including eGFR and urinary albumin/creatinine ratio (UACR) measurements, were performed on admission. Kidney dysfunction was defined by a low eGFR value (albuminuria (≥30mg/g creatinine). END was defined as a ≥2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within 7days after admission. Kidney dysfunction was diagnosed in 200 of the 294 patients (68.0%). END was observed in 60 patients (20.4%). Age, blood glucose level on admission, UACR on admission, and NIHSS score on admission were significantly associated with END, while no relationship between eGFR on admission and END was identified. A multivariable logistic regression analysis showed that END was positively associated with high UACR (≥39.6mg/g creatinine) and a high NIHSS score (≥6 points). Our data suggest that high UACR on admission may predict END in patients with acute ischemic stroke. Larger prospective studies are required to validate the correlation between albuminuria and END. Copyright © 2016 Elsevier B.V. All rights reserved.
Ritte, Rebecca; Luke, Joanne; Nelson, Craig; Brown, Alex; O'Dea, Kerin; Jenkins, Alicia; Best, James D; McDermott, Robyn; Daniel, Mark; Rowley, Kevin
Chronic kidney disease (CKD) and end-stage-kidney disease (ESKD) continue to be under-diagnosed and a major burden for Aboriginal communities in central Australia. The aim of this study was to examine the risk of poor clinical outcomes associated with elevated albumin-to-creatinine ratio (ACR) among Aboriginal people in central Australia. Cox proportional hazards models were used to estimate the risk of end stage kidney disease (ESKD), dialysis, CVD (cardiovascular disease) and mortality associated with participants' baseline albuminuria reading from a 10-year cohort study of Aboriginal people (n = 623) from three communities in central Australia. Predictors of progression of albuminuria were also examined in the context of the Kidney Health Australia (KHA) Risk Matrix. A baseline ACR level of ≥3.5 mg/mmol was associated with an almost 10-fold increased risk of ESKD (95%CI 2.07-43.8) and a 15-fold risk of dialysis (95%CI 1.89-121). Albuminuria ≥3.5 mg/mmol was also associated with a borderline 63 % increased risk of CVD (95%CI 0.98-2.71). No significant association was observed with mortality from all-causes or chronic disease. Diabetes and a waist-to-hip ratio ≥0.90 independently predicted a two-fold increased risk of a progression to higher ACR levels. A single measure of moderately increased albuminuria was a strong predictor of renal failure in this population. A single spot urine ACR analysis in conjunction with the KHA Risk Matrix may be a useful and efficient strategy to screen for risk of CKD and progression to dialysis in remote communities. A focus on individuals with diabetes and/or central obesity for strategies to avoid increases in albuminuria may also prevent future CKD and CVD complications.
Uslu, Ali Ugur; Yonem, Ozlem; Aydin, Bahattin; Uncu, Tunahan; Seven, Dogan; Balta, Sevket; Cicekli, Emre
Systematic inflammation, enhanced oxidative stress, and endothelial dysfunction are important for evolution and progression of renal damage, and they cause an increase in red cell distribution width (RDW). Familial Mediterranean fever (FMF) patients who are in the attack-free period and its relation with albuminuria and performance on assessment of microalbuminuria. One hundred and seventy-seven patients who had been diagnosed in accordance with Tel-hoshmer criteria and were in the attack-free period, and 143 age- and sex-matched healthy individuals were enrolled in our study. RDW values of FMF patients were higher compared with those of the controls (13.85 ± 1.07 and 13.15 ± 0.91, respectively; p albuminuria (r = 0.185, p = 0.014). When assessing microalbuminuria with RDW in the patients, a cutoff value of 13.85 with sensitivity of 60%, specificity of 62%, and p = 0.002 (area under curve: 0.651, 95% confidence interval 0.563-0.738), was observed according to receiver-operating characteristic curve analysis. Among the various variables associated with albuminuria in multivariate logistic regression analyses, RDW remained an independent predictor of albuminuria (95% confidence interval 0.479-0.942, p = 0.021). RDW may be associated with albuminuria in FMF patients and it can be a predictor of microalbuminuria. Copyright © 2016. Published by Elsevier Taiwan.
Kröpelin, Tobias F; de Zeeuw, Dick; Remuzzi, Giuseppe
Albuminuria class transition (normo- to micro- to macroalbuminuria) is used as an intermediate end point to assess renoprotective drug efficacy. However, definitions of such class transition vary between trials. To determine the most optimal protocol, we evaluated the approaches used in four...... baseline in addition to the class transition. In Cox regression analysis, neither increasing the number of urine samples collected at a single study visit nor differences in the other variables used to define albuminuria class transition altered the average drug effect. However, the SEM of the treatment...... effect increased (decreased precision) with stricter end point definitions, resulting in a loss of statistical significance. In conclusion, the optimal albuminuria transition end point for use in drug intervention trials can be determined with a single urine collection for albuminuria assessment per...
Wensink, G. Emerens; Schoffelen, Annelot F.; Tempelman, Hugo A.; Rookmaaker, Maarten B.; Hoepelman, Andy I. M.; Barth, Roos E.
Context As life expectancy improves among Human Immunodeficiency Virus (HIV) patients, renal and cardiovascular diseases are increasingly prevalent in this population. Renal and cardiovascular disease are mutual risk factors and are characterized by albuminuria. Understanding the interactions
Ibsen, H.; Olsen, M.H.; Wachtell, K.
In type 2 diabetes the degree of albuminuria is strongly related to progression of diabetic renal disease, as well as to the risk for cardiovascular complications. If normoalbuminuria is maintained, the risk of diabetic nephropathy is very low. In individuals with microalbuminuria, the rate...... of decline in glomerular filtration rate is closely related to the degree of albuminuria, and regression to normoalbuminuria slows down the rate of decline in renal function. Data from the LIFE-diabetes subgroup showed that levels of albuminuria well below what is usually defined as microalbuminuria......, strongly predicted risk for cardiovascular complications. This indicates that when albuminuria is used as a risk predictor for cardiovascular events, so called normal values should be redefined. Traditional values for normo-micro-macroalbuminuria are primarily defined as predictors for the risk...
Gao, Peggy; Clase, Catherine M.; Mente, Andrew; Mann, Johannes F.E.; Sleight, Peter; Yusuf, Salim; Teo, Koon K.
Summary Background and objectives The microvascular circulation plays an important role in bone health. This study examines whether albuminuria, a marker of renal microvascular disease, is associated with incident hip and pelvic fractures. Design, setting, participants, & measurements This study reanalyzed data from the Ongoing Telmisartan Alone and in combination with Ramipril Global End Point Trial/Telmisartan Randomized Assessment Study in Angiotensin-Converting Enzyme Intolerant Subjects with Cardiovascular Disease trials, which examined the impact of renin angiotensin system blockade on cardiovascular outcomes (n=28,601). Albuminuria was defined as an albumin-to-creatinine ratio≥30 mg/g (n=4597). Cox proportional hazards models were used to determine the association of albuminuria with fracture risk adjusted for known risk factors for fractures, estimated GFR, and rapid decline in estimated GFR (≥5%/yr). Results There were 276 hip and pelvic fractures during a mean of 4.6 years of follow-up. Participants with baseline albuminuria had a significantly increased risk of fracture compared with participants without albuminuria (unadjusted hazard ratio=1.62 [1.22, 2.15], P<0.001; adjusted hazard ratio=1.36 [1.01, 1.84], P=0.05). A dose-dependent relationship was observed, with macroalbuminuria having a large fracture risk (unadjusted hazard ratio=2.01 [1.21, 3.35], P=0.007; adjusted hazard ratio=1.71 [1.007, 2.91], P=0.05) and microalbuminuria associating with borderline or no statistical significance (unadjusted hazard ratio=1.52 [1.10, 2.09], P=0.01; adjusted hazard ratio=1.28 [0.92, 1.78], P=0.15). Estimated GFR was not a predictor of fracture in any model, but rapid loss of estimated GFR over the first 2 years of follow-up predicted subsequent fracture (adjusted hazard ratio=1.47 [1.05, 2.04], P=0.02). Conclusions Albuminuria, especially macroalbuminuria, and rapid decline of estimated GFR predict hip and pelvic fractures. These findings support a
Full Text Available BACKGROUND AND AIM: Metabolic syndrome (MetS, albuminuria, and the Framingham Risk Score (FRS are significant predictors for cardiovascular disease (CVD. However, the relationship and clinical significance of these CVD predictors in individuals with a family history of end-stage renal disease (ESRD are unclear. We investigated the association of relatives of hemodialysis (HD patients with MetS, albuminuria, and the FRS. METHODS: One hundred and sixty-six relatives of HD patients and 374 age- and sex- matched community controls were enrolled. MetS was defined using the Adult Treatment Panel III for Asians. Albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g. CVD risk was evaluated by the FRS. RESULTS: A significantly higher prevalence of MetS (19.9% vs. 12.5%, P = 0.026, albuminuria (12.7% vs. 5.1%, P = 0.002 and high FRS risk ≥ 10% of 10-year risk (15.7% vs. 8.5%, P = 0.013 was found in relatives of HD patients compared to their counterpart controls. In multivariate analysis, being relatives of HD patients (vs. controls was an independent determinant for MetS (odds ratio [OR], 1.785; 95% confidence interval [CI], 1.045 to 3.050, albuminuria (OR, 2.891; 95% CI, 1.431 to 5.841, and high FRS risk (OR, 1.863; 95% CI, 1.015 to 3.418. Higher low-density lipoprotein cholesterol (OR, 1.034; 95% CI, 1.017 to 1.052 and betel nut chewing (OR, 13.994; 95% CI, 3.384 to 57.871 were independent determinants for having a high FRS risk in relatives of HD patients. CONCLUSIONS: Being relatives of HD patients was independently associated with MetS, albuminuria and high FRS risk, suggesting family members of ESRD patients may have higher CVD risks through the interactions of renal risk factors. Proactive surveillance of these CVD predictors and preventive strategies should be targeted to this high-risk population.
Full Text Available Abstract Background Both diabetic and non-diabetic end stage renal disease (ESRD are more common among Canadian First Nations people than among the general Canadian population. The purpose of this research was to determine the prevalence of and risk factors for albuminuria in a Canadian First Nation population at high risk for ESRD and dialysis. Methods Data from a community-based screening study of 483 residents of a Plains Ojibway First Nation in Manitoba was used. Participants provided random urine samples. Proteinuria was defined as any dipstick positive for protein (≥1 g/L or those with ACR in the macroalbuminuric range (≥30 mg/mmol on at least one sample. Microalbuminuria was defined as ACR ≥2 mg/mmol for males and ≥2.8 mg/mmol for females. Other measures included fasting glucose, haemoglobin A1c, triglycerides, cholesterol, blood pressure, height, weight and waist and hip circumferences. Results Twenty percent of study participants had albuminuria, (5% proteinuria and 15% microalbuminuria. Of participants with diabetes, 42% (56/132 had albuminuria compared to 26% (7/27 among those with impaired fasting glucose and 10% (30/303 among those with normal glucose tolerance. Only 5.3% of those with albuminuria were aware of any degree of renal disease. In a multivariate logistic regression, independent associations with albuminuria were male gender [p = 0.002], increasing fasting glucose [p Conclusions The independent association between BMI and albuminuria has not been previously reported among indigenous populations. There is a high prevalence of albuminuria in this Canadian First Nation population; the high proportion of patients with diabetes and undiagnosed kidney disease demonstrates the need for screening, education and intervention to halt the progression and development of albuminuria and ultimately ESRD and CVD.
Grau-Perez, Maria; Pichler, Gernot; Galan-Chilet, Inma; Briongos-Figuero, Laisa S; Rentero-Garrido, Pilar; Lopez-Izquierdo, Raul; Navas-Acien, Ana; Weaver, Virginia; García-Barrera, Tamara; Gomez-Ariza, Jose L; Martín-Escudero, Juan C; Chaves, F Javier; Redon, Josep; Tellez-Plaza, Maria
The interaction of cadmium with genes involved in oxidative stress, cadmium metabolism and transport pathways on albuminuria can provide biological insight on the relationship between cadmium and albuminuria at low exposure levels. We tested the hypothesis that specific genotypes in candidate genes may confer increased susceptibility to cadmium exposure. Cadmium exposure was estimated by inductively coupled plasma mass spectrometry (ICPMS) in urine from 1397 men and women aged 18-85years participating in the Hortega Study, a representative sample of a general population from Spain. Urine albumin was measured by automated nephelometric immunochemistry. Abnormal albuminuria was defined as urine albumin greater than or equal to 30mg/g. The weighted prevalence of abnormal albuminuria was 6.3%. The median level of urine cadmium was 0.39 (IQR, 0.23-0.65) μg/g creatinine. Multivariable-adjusted geometric mean ratios of albuminuria comparing the two highest to the lowest tertile of urine cadmium were 1.62 (95% CI, 1.43-1.84) and 2.94 (95% CI, 2.58-3.35), respectively. The corresponding odds ratios of abnormal albuminuria were 1.58 (0.83, 3.02) and 4.54 (2.58, 8.00). The association between urine cadmium and albuminuria was observed across all participant subgroups evaluated including participants without hypertension, diabetes or chronic kidney disease. We observed Bonferroni-corrected statistically significant interactions between urine cadmium levels and polymorphisms in gene SLC30A7 and RAC1. Increasing urine cadmium concentrations were cross-sectionally associated with increased albuminuria in a representative sample of a general population from Spain. Genetic variation in oxidative stress and cadmium metabolism and transport genes may confer differential susceptibility to potential cadmium effects. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available The occurrence of Chronic Kidney Disease (CKD of unknown etiology in autochthonous child populations residing along the Lake Chapala lakeshore is endemic (Jalisco, México. The objective of this study was to determine the prevalence of albuminuria in the pediatric population and to measure the glomerular filtration rate in children with two positive albuminuria tests. Urinary albumin was measured in 394 children. Subjects with two or more positive albuminuria test donated blood samples for the determination of serum biomarkers. From a rural community with 565 children under the age of 17 years, 394 (69.7% participated with first morning urine samples. A total of 180 children were positive (with two or more positive albuminuria tests. The prevalence of albuminuria among the children participating in the study was 45.7%. Of the 180 children with persistent albuminuria, 160 (88.9% were tested for serum creatinine, urea, and cystatin C. The 68.1% of the children studied, were found in stages 3a and 3b of the Kidney Disease Improving Global Outcomes (KDIGO classification (mean glomerular filtration rate (GFR 51.9 and 38.4 mL/min/1.73 m2 respectively. The lowest frequencies were for classifications 1 and 4. None of the subjects was classified as grade 5. The prevalence of albuminuria in children from this rural community is 3–5 times higher than reported in international literature. Regarding GFR, more than 50% of children studied are under 60 mL/min/1.73 m2. It is a priority to find the causes of albuminuria and CKD in this Mexican region.
Belmar Vega, L; Rodrigo Calabia, E; Gómez Román, J J; Ruiz San Millán, J C; Martín Penagos, L; Arias Rodríguez, M
Antibody-mediated rejection is the main cause of deterioration of kidney transplants and frequently is detected only by means of protocol biopsies. The aim of this study was to relate the presence of albuminuria throughout the 1st year to the histologic findings detected by 1-year protocol biopsies in kidney graft recipients. Retrospective observational study of 86 protocol biopsies 1 year after transplantation. Albuminuria was measured at 3, 6, 9, and 12 months in urine samples and expressed as albumin/creatinine (mg/g). Analysis of biopsies, reflected according to the Banff criteria, the following categories: fibrosis and tubular atrophy, 35 (40.7%); cellular rejection, 13 (15.1%); antibody-mediated rejection, 8 (9.3%); chronic glomerulopathy, 10 (11.6%); normal, 14 (16.3%); recurrence, 1 (1.2%); and other, 5 (5.8%). The proportions of patients with albuminuria for Banff scale scores (0 vs ≥1, respectively) at 6 and 12 months, respectively, after transplantation, were: for marker glomerulitis, 45.5% versus 59.3% (P = .021) and 36.4% versus 70.4% (P albuminuria after renal transplantation is common, especially in patients with proteinuria. Persistent albuminuria after transplantation, even at low levels, can be indicative of subclinical antibody-mediated rejection. Additional broader studies to relate the albuminuria to histologic changes observed in protocol biopsies are required. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Yi, Bin; Huang, Jing; Zhang, Wei; Li, Ai Mei; Yang, Shi Kun; Sun, Jian; Wang, Jian Wen; Li, Yan Chun; Zhang, Hao
Inflammation plays an important role in albuminuria in type 2 diabetes mellitus (T2DM). The vitamin D receptor (VDR) has potent anti-inflammatory activities. To investigate the correlation between VDR expression and albuminuria in T2DM. Renal biopsies from T2DM patients with albuminuria (n = 8) and nondiabetic subjects (n = 4) were compared for VDR expression by immunohistochemistry. Recruited T2DM patients (n = 242; estimated glomerular filtration rate > 60 mL/min/1.73 m 2 ) were divided into three groups based on urinary albumin-to-creatinine ratio (uACR): normal albuminuria (uACR albuminuria. VDR mRNA and protein levels were both negatively correlated with uACR, and VDR mRNA was inversely correlated with TNF-α and miR-346 in PBMCs from T2DM patients. TNF-α reduced VDR while inducing miR-346 in cultured PBMCs. TNF-α suppressed VDR by up-regulating miR-346 in HK2 cells. VDR down-regulation in PBMCs is independently associated with the severity of albuminuria in T2DM. TNF-α suppression of VDR in PBMCs and HK2 cells is mediated by miR-346.
Gu, Dongmei; Xu, Pengcheng; Yuan, Yuhua; Fu, Hongwei
To evaluate the possibility of albuminuria as a screening biomarker for seniors or general population with hypertension and diabetes. 478 health check-up individuals were enrolled. Albumin to creatinine ratio (ACR) was calculated by testing urinary albumin and creatinine of spot urine sample. Each urine sample was also analyzed by the routine urine test in parallel with ACR. Potential risk factors associated with the presence of albuminuria were analyzed using independent t-test or chi-square test. The total prevalence of albuminuria was 11.9%, and women had a higher positive rate (14.0%) than men (10.6%). Ageing, fasting plasma glucose, and systolic blood pressure were significantly associated with the presence of albuminuria. Individuals are highly probable to have albuminuria when their routine urine test shows positive of urea glucose, red blood cells or urea protein. Albuminuria should be suggested as a potential health screening biomarker in senior citizens and general population with hypertension and diabetes.
Neyra, Javier A; Li, Xilong; Yessayan, Lenar; Adams-Huet, Beverley; Yee, Jerry; Toto, Robert D
Acute kidney injury (AKI) is a frequent complication of sepsis, a pro-inflammatory state that alters tubular handling of filtered albumin. We hypothesized that dipstick albuminuria (DA) is associated with a lower rate of AKI recovery in septic patients. This was a single-centre, retrospective cohort study of adults with sepsis-associated AKI in an urban academic intensive care unit (ICU). Patients with unknown baseline serum creatinine (SCr), absent urinalysis, and those with estimated glomerular filtration rate (eGFR) albuminuria ≥30 mg/dL is independently associated with lower rate of AKI recovery at 30 days post-discharge. Our findings emphasize the potential utility of a simple routine test of DA in the risk-stratification of AKI recovery in ICU septic patients. © 2015 Asian Pacific Society of Nephrology.
Full Text Available BACKGROUND: The relationship between hypertension and kidney disease is complicated. Clinical trials found intense blood pressure control was not associated with alterations in glomerular filtration rate (GFR in all patients but did slow the rate of GFR decline among those with a higher baseline proteinuria. However, the underlying mechanism has been unclear. METHODS: We tested the hypothesis that the association between high blood pressure and renal function is modified by albuminuria status by conducting analyses in a cross-sectional study with 12,440 adult participants without known kidney diseases, diabetes or cardiovascular diseases, participating in the National Health and Nutrition Examination Survey (NHANES 1999-2006. RESULTS: 1226 out of 12440 were found to have unknown high blood pressure and 4494 were found to have reduced renal function. Overall, a moderate association was found between high blood pressure and renal function insufficiency in all participants analyzed. However, among participants with albuminuria, the prevalence of moderate-severe renal insufficiency substantially and progressively increased from normal subjects to prehypertensive and undiagnosed hypertensive subjects (1.43%, 3.44%, 10.96%, respectively, P for trend<0.0001; on the other hand, the prevalence of undiagnosed hypertension was also significantly higher among subjects with moderate-severe renal insufficiency than those with mild renal insufficiency (35.54% Vs 19.09%, P value <0.05, supporting an association between hypertension and renal function damage. In contrast, no association between hypertension and renal insufficiency was observed among those without albuminuria in this population. Similar findings were observed when the CKD-EPI equation was used. CONCLUSIONS: The association between high blood pressure and reduced renal function could be dependent upon the albuminuria status. This finding may provide a possible explanation for results observed in
Hansen, J M; Olsen, Niels Vidiendal; Feldt-Rasmussen, B
The mechanism of proteinuria at high altitude is unclear. Renal function and urinary excretion rate of albumin (Ualb) at rest and during submaximal exercise and transcapillary escape rate of 125I-labeled albumin (TERalb) were investigated in 12 normal volunteers at sea level and after rapid and p....... The elevated TERalb suggests an overall increase in capillary permeability, including the glomerular endothelium, as the critical factor in high-altitude induced albuminuria....
Lee, Eng Sing; Tang, Wern Ee
Microalbuminuria is an early sign of kidney damage. The prevalence of microalbuminuria in Singapore has been reported to be 36.0%-48.5%. However, the prevalence of microalbuminuria reported in these studies was determined with one urine sample using a qualitative urine test. The aim of this study was to determine the prevalence of micro- and macroalbuminuria using a more stringent criterion of two positive quantitative urine albumin-creatinine ratio (ACR) tests. We conducted a cross-sectional study of patients with type 2 diabetes mellitus (T2DM) who were followed up at a primary care clinic in Singapore. Patients were diagnosed to have albuminuria if they had two positive ACR tests within a seven-month period. A total of 786 patients with T2DM met the study's inclusion criteria. 55.7% were already on an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB). The prevalence rates of micro- and macroalbuminuria were 14.2% and 5.7%, respectively. Patients with albuminuria were more likely to have hypertension (odds ratio [OR] 3.47, 95% confidence interval [CI] 1.55-7.80). Diabetics with poorer diabetic control (OR 1.88, 95% CI 1.26-2.79), and higher systolic (OR 1.69, 95% CI 1.14-2.49) and diastolic (OR 1.96, 95% CI, 1.20 to 3.22) blood pressures were more likely to have albuminuria. In the present study, the prevalence of microalbuminuria is significantly lower than that previously reported in Singapore. The presence of hypertension, poor diabetic control and suboptimal blood pressure control are possible risk factors for albuminuria in patients with T2DM.
Martens, Remy J H; Kooman, Jeroen P; Stehouwer, Coen D A; Dagnelie, Pieter C; van der Kallen, Carla J H; Koster, Annemarie; Kroon, Abraham A; Leunissen, Karel M L; Nijpels, Giel; van der Sande, Frank M; Schaper, Nicolaas C; Sep, Simone J S; van Boxtel, Martin P J; Schram, Miranda T; Henry, Ronald M A
Reduced estimated glomerular filtration rate (eGFR) and albuminuria have been associated with worse cognitive performance. However, few studies have examined whether these associations are confined to older individuals or may be extended to the middle-aged population. Cross-sectional analyses of a prospective population-based cohort study. 2,987 individuals aged 40 to 75 years from the general population (The Maastricht Study). eGFR and urinary albumin excretion (UAE). Memory function, information processing speed, and executive function. Analyses were adjusted for demographic variables (age, sex, and educational level), lifestyle factors (smoking behavior and alcohol consumption), depression, and cardiovascular disease risk factors (glucose metabolism status, waist circumference, total to high-density lipoprotein cholesterol ratio, triglyceride level, use of lipid-modifying medication, systolic blood pressure, use of antihypertensive medication, and prevalent cardiovascular disease). UAE was albuminuria was not. However, significant interaction terms (P for interaction albuminuria was most strongly and extensively associated with cognitive performance in older individuals. Mean (±SD) eGFR, estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine-cystatin C equation (eGFR cr-cys ), was 88.4±14.6 mL/min/1.73m 2 . eGFR cr-cys was not associated with any of the domains of cognitive performance after full adjustment. However, significant interaction terms (P for interaction albuminuria was independently associated with lower information processing speed, whereas eGFR cr-cys was not associated with cognitive performance. However, both were more strongly and extensively associated with cognitive performance in older individuals. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Gonzalez-Calero, Laura; Martin-Lorenzo, Marta; de la Cuesta, Fernando; Maroto, Aroa S; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Pulido-Olmo, Helena; Segura, Julian; Barderas, Maria G; Ruilope, Luis M; Vivanco, Fernando; Alvarez-Llamas, Gloria
Hypertension is a multi-factorial disease of increasing prevalence and a major risk factor for cardiovascular mortality even in the presence of adequate treatment. Progression of cardiovascular disease (CVD) occurs frequently during chronic renin-angiotensin-system (RAS) suppression, and albuminuria is a marker of CV risk. High prevalence of albuminuria in treated hypertensive patients has been demonstrated, but there are no available markers able to predict evolution. The aim of this study was the identification of novel indicators of albuminuria progression measurable in urine of diabetic and non-diabetic patients. 1143 hypertensive patients under chronic treatment were followed for a minimum period of 3 years. Among them, 105 diabetic and non-diabetic patients were selected and classified in three groups according to albuminuria development during follow-up: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Differential urine analysis was performed by 2D gel electrophoresis (2D-DIGE) and further confirmed by liquid chromatography-mass spectrometry. Non-parametric statistical tests were applied. CD59 glycoprotein and alpha-1 antitrypsin (AAT) resulted already altered in patients developing albuminuria de novo, with a similar response in those with maintained albuminuria. A prospective study in a sub-group of normoalbuminuric patients who were clinically followed up for at least 1 year from urine sampling, revealed CD59 and AAT proteins significantly varied in the urine collected from normoalbuminurics who will negatively progress, serving as predictors of future albuminuria development. CD59 and AAT proteins are significantly altered in hypertensive patients developing albuminuria. Interestingly, CD59 and AAT are able to predict, in normoalbuminuric individuals, who will develop albuminuria in the future, being potential predictors of vascular damage and CV risk. These findings
Hsieh, Ya-Mei; Lee, Wen-Jane; Sheu, Wayne H-H; Li, Yu-Hsuan; Lin, Shih-Yi; Lee, I-Te
There is a high hospitalization rate for diabetic patients. Since retinopathy and albuminuria are both important manifestations of microvascular disease in diabetes, our aim was to investigate the effect of retinopathy and albuminuria on long-term mortality in type 2 diabetic inpatients through this observational cohort study. Type 2 diabetic inpatients given a primary diagnosis of poor glucose control were consecutively enrolled during their hospitalization periods. Clinical information was collected through review of each patient's medical records, and mortality data were obtained from the national registry in Taiwan. A total of 761 type 2 diabetic inpatients were enrolled in the study with a median follow-up period of 6.6 years (interquartile range, 4.0-9.6 years). Patients in the Albuminuria(-)/Retinopathy(+), Albuminuria(+)/Retinopathy(-) and Albuminuria(+)/Retinopathy(+) groups had significantly higher risks of all-cause mortality and cardiovascular mortality than those in the Albuminuria(-)/Retinopathy(-) group. However, among patients with albuminuria, there was no significant difference in cumulative mortality between those with and without retinopathy (P = 0.821). A decrease in the estimated glomerular filtration rate (eGFR), but not retinopathy, was an independent predictor of all-cause mortality (95% CI 0.647‒0.893; P diabetic inpatients with albuminuria. Albuminuria in type 2 diabetic inpatients is a strong predictor of long-term mortality after discharge from the hospital. Retinopathy is an independent predictor of mortality in type 2 diabetic inpatients without albuminuria but not in those with albuminuria. A low eGFR is a better predictor of mortality than retinopathy in type 2 diabetic inpatients with albuminuria.
Ashitani, Aki; Ueno, Toshinori; Nakashima, Ayumu; Doi, Shigehiro; Yamane, Kiminori; Masaki, Takao
High-normal albuminuria is an important risk factor for incident chronic kidney disease in diabetic populations, in contrast to an uncertain association in nondiabetic populations. This study aimed to reveal the relationship between high-normal albuminuria and incident chronic kidney disease in a Japanese nondiabetic population. A 10-year follow-up retrospective cohort study was performed involving 1378 Japanese men (mean age 44 ± 5.3 years) without chronic kidney disease and diabetes mellitus. Chronic kidney disease was diagnosed as either estimated glomerular filtration rate chronic kidney disease over the 10-year follow-up period. Median annual estimated glomerular filtration rate decline showed a deterioration with increasing quartiles of baseline albumin-to-creatinine ratio (P = 0.004). Participants who had a baseline albumin-to-creatinine ratio in the highest quartile (5.9-28.9 mg/g) were more likely to develop micro- or macroalbuminuria (odds ratio: 16.23, 95% confidence interval 6.56-54.03), chronic kidney disease (odds ratio: 2.48, 95% confidence interval 1.64-3.82), and hypertension (odds ratio 2.06, 95% confidence interval 1.30-3.31), but not diabetes mellitus compared with those who had an albumin-to-creatinine ratio in the lowest quartile (1.3-3.6 mg/g) after adjustment for potential confounders. High-normal albuminuria was associated with incident chronic kidney disease in this Japanese nondiabetic male population.
Oh, Se Won; Koo, Ho Seok; Han, Kum Hyun; Han, Sang Youb; Chin, Ho Jun
Sodium intake is associated with obesity and metabolic disorder in the general population. However, sodium intake is significantly reduced according to the decrease of energy intake in older adults although the prevalence of obesity is higher than younger adults. We evaluate the association of sodium excretion (UNa) with blood pressure, obesity, metabolic disorders, and albuminuria according to age. An observational study using data from the Korean National Health and Nutrition Examination Survey IV-V (2008-2011) was performed (N = 18,146). The 24 hour UNa was estimated from a single fasting urine sample.Participants aged≥75 years showed the highest risk for hypertension (HTN) in the highest quartile of UNa (1.769, 95% CI, 1.174-2.665), and the risks for HTN increased with advancing age. Obesity was not associated with UNa in participants aged≥75 years, and hypertriglyceridemia and body fat were not related to UNa in participants aged≥65 years, although these values were significantly associated with UNa in participants agedalbuminuria in those aged 20-39 years (95% CI, 1.130-12.630), and a 1.885 fold increased risk (95% CI, 1.156-3.075) among participants aged 40-64 years. In participants aged≥65 years, albuminuria was not associated with UNa. In contrast with HTN, UNa was not associated with albuminuria, obesity, hypertriglyceridemia, IFG, and IR in older adults despite a strong association in younger adults.
Barska, Iga; Mikołajczyk, Melania; Paradowski, Marek
Urinary albumin excretion is an established risk factor for renal and cardiovascular events. Measurement of albumin in the urine daily collection is the gold standard in assessing albuminuria. The 24-hour urine collection is cumbersome procedure that generates a lot of mistakes, therefore other methods have been proposed. The aim of the study was to compare the assessment of albuminuria in the 24-hour urine collection and in the second morning urine sample as well as to determine UACR. The study included 32 patients, from whom the daily and the second morning urine samples were collected. In both samples, the albumin and creatinine concentrations were determined and the urinary albumin: creatinine ratio (UACR) was calculated. An excellent correlation between the UACR determined from the 24-hour urine collection and the other portion of the second morning sample was obtained within a wide range of albuminuria values (r = 0.9825). Furthermore, a better correlation between the same characteristics was obtained in urine of patients with normoalbuminuria when UACR did not exceed 30 mg/g creatinine (r = 0.9771). Above this value, the correlation was slightly lower for micro- and macroalbuminuria and equalled 0.9249 and 0.9332, respectively. On the basis of the obtained results it can be concluded that the second morning urine sample with the determination of UACR is a good alternative to the 24-hour urine collection and the first morning urine sample which are burdened with a preanalytical error.
von Scholten, Bernt Johan; Persson, Frederik; Rosenlund, Signe
-regional pro-atrial natriuretic peptide (MR-proANP); and 5) Copeptin, in type 2 diabetes patients with albuminuria. In a randomised, double-blind, placebo-controlled, cross-over trial we enrolled patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio (UACR) > 30 mg......We assessed the effects of liraglutide treatment on five cardiovascular risk biomarkers, reflecting different pathophysiology: 1) Tumour necrosis factor-alpha (TNF-alpha); 2) Soluble urokinase plasminogen activator receptor (suPAR); 3) Mid-regional pro-adrenomedullin (MR-proADM); 4) Mid....../g) and estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m(2) . Patients received liraglutide (1.8 mg/d) and matched placebo for 12 weeks in random order. Primary endpoint was change in albuminuria; this is a prespecified sub-study. Thirty-two patients were randomised, 27 completed the study. TNF...
Yan, Ping; Zhu, Xiangzhu; Li, Haiming; Shrubsole, Martha J; Shi, Haiming; Zhang, Ming-zhi; Harris, Raymond C; Hao, Chuan-Ming; Dai, Qi
The relationship between hypertension and kidney disease is complicated. Clinical trials found intense blood pressure control was not associated with alterations in glomerular filtration rate (GFR) in all patients but did slow the rate of GFR decline among those with a higher baseline proteinuria. However, the underlying mechanism has been unclear. We tested the hypothesis that the association between high blood pressure and renal function is modified by albuminuria status by conducting analyses in a cross-sectional study with 12,440 adult participants without known kidney diseases, diabetes or cardiovascular diseases, participating in the National Health and Nutrition Examination Survey (NHANES) 1999-2006. 1226 out of 12440 were found to have unknown high blood pressure and 4494 were found to have reduced renal function. Overall, a moderate association was found between high blood pressure and renal function insufficiency in all participants analyzed. However, among participants with albuminuria, the prevalence of moderate-severe renal insufficiency substantially and progressively increased from normal subjects to prehypertensive and undiagnosed hypertensive subjects (1.43%, 3.44%, 10.96%, respectively, P for trendhigh blood pressure and reduced renal function could be dependent upon the albuminuria status. This finding may provide a possible explanation for results observed in clinical trials of intensive blood pressure control. Further studies are warranted to confirm our findings.
Baldan-Martin, Montserrat; Mourino-Alvarez, Laura; Gonzalez-Calero, Laura; Moreno-Luna, Rafael; Sastre-Oliva, Tamara; Ruiz-Hurtado, Gema; Segura, Julian; Lopez, Juan Antonio; Vazquez, Jesus; Vivanco, Fernando; Alvarez-Llamas, Gloria; Ruilope, Luis M; de la Cuesta, Fernando; Barderas, Maria G
Albuminuria is a risk factor strongly associated with cardiovascular disease, the first cause of death in the general population. It is well established that renin-angiotensin system suppressors prevent the development of new-onset albuminuria in naïf hypertensive patients and diminish its excretion, but we cannot forget the percentage of hypertensive patients who develop de novo albuminuria. Here, we applied multiple proteomic strategy with the purpose to elucidate specific molecular pathways involved in the pathogenesis and provide predictors and chronic organ damage indicators. Briefly, 1143 patients were followed up for a minimum period of 3 years. One hundred and twenty-nine hypertensive patients chronically renin-angiotensin system suppressed were recruited, classified in 3 different groups depending on their albuminuria levels (normoalbuminuria, de novo albuminuria, and sustained albuminuria), and investigated by multiple proteomic strategies. Our strategy allowed us to perform one of the deepest plasma proteomic analysis to date, which has shown 2 proteomic signatures: (1) with predictive value of de novo albuminuria and (2) sustained albuminuria indicator proteins. These proteins are involved in inflammation, immune as well as in the proteasome activation occurring in situations of endoplasmic reticulum stress. Furthermore, these results open the possibility of a future strategy based on anti-immune therapy to treat hypertension which could help to prevent the development of albuminuria and, hence, the progression of kidney damage. © 2016 American Heart Association, Inc.
Uzu, Takashi; Araki, Shin-Ichi; Kashiwagi, Atsunori; Haneda, Masakazu; Koya, Daisuke; Yokoyama, Hiroki; Kida, Yasuo; Ikebuchi, Motoyoshi; Nakamura, Takaaki; Nishimura, Masataka; Takahara, Noriko; Obata, Toshiyuki; Omichi, Nobuyuki; Sakamoto, Katsuhiko; Shingu, Ryosuke; Taki, Hideki; Nagai, Yoshio; Tokuda, Hiroaki; Kitada, Munehiro; Misawa, Miwa; Nishiyama, Akira; Kobori, Hiroyuki; Maegawa, Hiroshi
In patients with diabetes, albuminuria is a risk marker of end-stage renal disease and cardiovascular events. An increased renin-angiotensin system activity has been reported to play an important role in the pathological processes in these conditions. We compared the effect of aliskiren, a direct renin inhibitor (DRI), with that of angiotensin receptor blockers (ARBs) on albuminuria and urinary excretion of angiotensinogen, a marker of intrarenal renin-angiotensin system activity. We randomly assigned 237 type 2 diabetic patients with high-normal albuminuria (10 to albuminuria. Twelve patients dropped out during the observation period, and a total of 225 patients were analyzed. During the study period, the systolic and diastolic blood pressures were not different between the groups. The changes in the urinary albumin-to-creatinine ratio from baseline to the end of the treatment period in the DRI and ARB groups were similar (-5.5% and -6.7%, respectively). In contrast, a significant reduction in the urinary excretion of angiotensinogen was observed in the ARB group but not in the DRI group. In the subgroup analysis, a significant reduction in the albuminuria was observed in the ARB group but not in the DRI group among high-normal albuminuria patients. DRI and ARB reduced albuminuria in hypertensive patients with type 2 diabetes. In addition, ARB, but not DRI, reduced albuminuria even in patients with normal albuminuria. DRI is not superior to ARB in the reduction of urinary excretion of albumin and angiotensinogen.
Georgakis, Marios K; Dimitriou, Nikolaos G; Karalexi, Maria A; Mihas, Constantinos; Nasothimiou, Efthimia G; Tousoulis, Dimitrios; Tsivgoulis, Georgios; Petridou, Eleni Th
Cerebral microvascular disease is considered to contribute to cognitive dysfunction. We opted to explore whether albuminuria, a marker of systemic microangiopathy, is associated with cognitive impairment, dementia, and cognitive function. Systematic review; independent reviewers screened 2359 articles, derived through the search strategy, for identification of observational studies quantifying an association of albuminuria with the outcomes of interest, abstracted data on study characteristics and results and evaluated studies on quality using the Newcastle-Ottawa scale. Community. Adults. Cognitive impairment and dementia, defined by validated neuropsychological tests or clinical guidelines, respectively, and cognitive function, assessed by validated instruments. Thirty-two eligible studies were identified. Albuminuria was associated with cognitive impairment (Odds Ratio (OR): 1.35, 95% Confidence Interval (CI): 1.19-1.53; 7,852 cases), dementia (OR: 1.35, 95% CI: 1.10-1.65; 5,758 cases), clinical Alzheimer's disease (OR: 1.37, 95% CI: 1.11-1.69; 629 cases) and vascular dementia (OR: 1.96, 95% CI: 1.16-3.31; 186 cases); the effect remained significant among longitudinal, population-based and high quality studies. Time-to-event analysis on prospective studies of non-demented at baseline individuals also showed a significant association with incident dementia (Risk Ratio: 1.52, 95% CI: 1.16-1.99; 971 cases). Worse global cognitive performance (Hedge's g: -0.13, 95% CI: -0.18, -0.09; 68,348 subjects) and accelerated cognitive decline (g: -0.20, 95% CI: -0.34, -0.07; 31,792 subjects) were noted among subjects with albuminuria, who also scored lower in executive function, processing speed, verbal fluency, and verbal memory. Albuminuria was independently associated with cognitive impairment, dementia and cognitive decline. The stronger effects for vascular dementia and cognitive performance in domains primarily affected by microvascular disease support that the
Klisic, Aleksandra; Kocic, Gordana; Kavaric, Nebojsa; Jovanovic, Milovan; Stanisic, Verica; Ninic, Ana
Xanthine oxidase (XO) is an important enzyme responsible for conversion of purine bases to uric acid and represents the major source of reactive oxygen species (ROS) production in circulation. Since pathophysiological mechanism of the relationship between XO activity and urinary albumin excretion (UAE) rate is not well elucidated, we aimed to investigate this association in patients with diabetes mellitus type 2 (DM2). In addition, we wanted to examine whether uric acid itself plays an independent role in albuminuria onset and progression, or it is only mediated through XO activity. A total of 83 patients with DM2 (of them 56.6% females) were included in this cross-sectional study. Anthropometric, biochemical parameters and blood pressure were obtained. Multivariate logistic regression analysis showed that uric acid and XO were the independent predictors for albuminuria onset in patients with DM2 [odds ratio (OR) 1.015, 95% CI (1.008-1.028), p = 0.026 and OR 1.015, 95% CI (1.006-1.026), p = 0.040, respectively]. Rise in uric acid for 1 µmol/L enhanced the probability for albuminuria by 1.5%. Also, elevation in XO activity for 1 U/L increased the probability for albuminuria for 1.5%. A total of 66.7% of variation in UAE could be explained with this Model. Both XO and uric acid are independently associated with albuminuria in diabetes. Better understanding of pathophysiological relationship between oxidative stress and albuminuria could lead to discoveries of best pharmacological treatment of XO- and/or uric acid-induced ROS, in order to prevent albuminuria onset and progression.
Özyilmaz, Akin; de Jong, Paul E; Bakker, Stephan J L; Visser, Sipke T; Thio, Chris; Gansevoort, Ron T
We investigated whether initial population screening for elevated albuminuria with subsequent screening for hypertension in case albuminuria is elevated may be of help to identify subjects at risk for accelerated decline in kidney function. We included subjects who participate in the PREVEND observational, general population-based cohort study and had two or more glomerular filtration rate (eGFR) measurements available during follow-up. Elevated albuminuria was defined as an albumin concentration ≥20 mg/L in a first morning urine sample confirmed by an albumin excretion ≥30 mg/day in two 24-h urines. Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or use of blood pressure-lowering drugs. eGFR was estimated with the CKD-EPI creatinine-cystatin C equation. Overall, 6471 subjects were included with a median of 4 [95% confidence interval (CI) 2-5] eGFR measurements during a follow-up of 11.3 (95% CI 4.0-13.7) years. Decline in eGFR was greater in the subgroups with elevated albuminuria. This held true, not only in subjects with known hypertension (-1.84 ± 2.27 versus -1.16 ± 1.45 mL/min/1.73 m 2 per year, P albuminuria had higher blood pressure than subjects with normoalbuminuria, and in subjects with elevated albuminuria as yet undiagnosed hypertension was twice as prevalent as diagnosed hypertension. Initial screening for elevated albuminuria followed by screening for hypertension may help to detect subjects with increased risk for a steeper decline in kidney function.
Lin, L; Lu, J; Huang, X; Ding, L; Huang, Y; Wang, P; Peng, K; Zhang, D; Xu, Y; Xu, M; Chen, Y; Bi, Y; Wang, W; Xu, Y
Nonalcoholic fatty liver disease (NAFLD) was associated with higher risk of cardiovascular disease (CVD). Low-grade albuminuria was recognized as an early indicator of CVD. Epidemiological studies investigating the association between NAFLD and low-grade albuminuria were limited. To determine whether NAFLD is independently associated with the presence of low-grade albuminuria in Chinese adults. A cross-sectional community-based population study was performed in 8270 Chinese adults aged 40 years or older. A first-voided early morning spot urine sample was obtained for urinary albumin and creatinine measurements. The highest quartile of urinary albumin-to-creatinine ratio was defined as low-grade albuminuria, after excluding the participants with micro- or macroalbuminuria. NAFLD was diagnosed by using ultrasonography findings after the exclusion of alcohol abuse and other liver diseases. The prevalence of low-grade albuminuria was significantly higher in participants with NAFLD than in those without NAFLD (33.6% vs. 21.3% in men and 30.4% vs. 22.8% in women, respectively). Multivariate-adjusted logistic regression analysis revealed that NAFLD was significantly associated with increased odds ratio of low-grade albuminuria in men (odds ratio, 1.47; 95% CI, 1.16-1.87) after adjusting for multiple confounders. The significant association was not detected in women. NAFLD was significantly associated with an increased risk of present low-grade albuminuria in middle-aged and elderly Chinese men. © The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: email@example.com.
Lin, Cheng-Chieh; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Lin, Chih-Hsueh; Lai, Ming-May; Lee, Yih-Dar; Chen, Ching-Chu; Yang, Chuan-Wei; Li, Tsai-Chung
The objective of this study was to assess the association of glycemic status and decreased renal function as determined by estimated glomerular filtration rate (eGFR) and albuminuria in an adult Taiwanese metropolitan population. We did a cross-sectional survey in a representative sample of 2,350 Taiwanese adults aged 40 years and over living in a metropolitan city in Taiwan from 2004 to 2005. Glycemic status was classified as normal glycemia, hyperglycemia, and type 2 diabetes (T2D). Renal function was assessed with eGFR using modified Modification of Diet in Renal Disease Study equation for Chinese. Albuminuria was determined by the urinary albumin-creatinine ratio. Decreased renal function was defined as eGFR creatinine ratio >30 mg g(-1) creatinine. 593 (25.23%) had hyperglycemia and 287 (12.21%) had T2D. As glycemia level increased, the prevalence of albuminuria and decreased eGFR increased. After adjustment, T2D was associated with an OR of 2.93 (95% CI: 2.11-4.07) for albuminuria, and an OR of 2.05 (95% CI: 1.18-3.58) for decreased eGFR. In a representative sample from a metropolitan city in Taiwan, T2D was associated with albuminuria and decreased eGFR.
Liang, Ching-Chao; Lin, Pi-Chen; Lee, Mei-Yueh; Chen, Szu-Chia; Shin, Shyi-Jang; Hsiao, Pi-Jung; Lin, Kun-Der; Hsu, Wei-Hao
Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015-1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084-1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM.
DULLAART, RPF; BEUSEKAMP, BJ; MEIJER, S; VANDOORMAAL, JJ; SLUITER, WJ
OBJECTIVES - To determine the long-term effects of an LPD on albuminuria and renal hemodynamics in IDDM patients without nephropathy. RESEARCH DESIGN AND METHODS - We selected 31 patients with overnight albuminuria between 10 and 200 g/min and without hypertension from a referral-based diabetic
Hellemons, M.E.; Denig, P.; Voorham, J.; Heerspink, H.J.L.; de Zeeuw, Dick
Failure of diagnosing and treatment of albuminuria play a role in morbidity and mortality in type 2 diabetes (T2DM). We evaluated guideline adherence and factors associated with albuminuria screening and treatment in T2DM patients in primary care. Guidelines recommend annual measurement of
Jain, Nidhi; Khullar, Bhavya; Oswal, Neelam; Banoth, Balaji; Joshi, Prashant; Ravindran, Balachandran; Panda, Subrat; Basak, Soumen; George, Anna; Rath, Satyajit; Bal, Vineeta; Sopory, Shailaja
Transient albuminuria induced by pathogen-associated molecular patterns (PAMPs) in mice through engagement of Toll-like receptors (TLRs) is widely studied as a partial model for some forms of human nephrotic syndrome (NS). In addition to TLRs, CD80 has been shown to be essential for PAMP-mediated albuminuria. However, the mechanistic relationships between TLRs, CD80 and albuminuria remain unclear. Here, we show that albuminuria and CD80-uria induced in mice by many TLR ligands are dependent on the expression of TLRs and their downstream signalling intermediate MyD88 exclusively in hematopoietic cells and, conversely, on CD80 expression exclusively in non-hematopoietic cells. TNFα is crucial for TLR-mediated albuminuria and CD80-uria, and induces CD80 expression in cultured renal podocytes. IL-10 from hematopoietic cells ameliorates TNFα production, albuminuria and CD80-uria but does not prevent TNFα-mediated induction of podocyte CD80 expression. Chitohexaose, a small molecule originally of parasite origin, mediates TLR4-dependent anti-inflammatory responses, and blocks TLR-mediated albuminuria and CD80-uria through IL-10. Thus, TNFα is a prominent mediator of renal CD80 induction and resultant albuminuria in this model, and small molecules modulating TLR-mediated inflammatory activation might have contributory or adjunct therapeutic potential in some contexts of NS development. © 2016. Published by The Company of Biologists Ltd.
de Zeeuw, Dick; Agarwal, Rajiv; Amdahl, Michael
Despite treatment with renin–angiotensin–aldosterone system (RAAS) inhibitors, patients with diabetes have increased risk of progressive renal failure that correlates with albuminuria. We aimed to assess whether paricalcitol could be used to reduce albuminuria in patients with diabetic nephropathy....
Lindhardt, Morten; Persson, Frederik; Oxlund, Christina
BACKGROUND: The mineralocorticoid receptor antagonist spironolactone significantly reduces albuminuria in patients with diabetes. Prior studies have shown large between-patient variability in albuminuria treatment response. We previously developed and validated a urinary proteomic classifier...... that predicts onset and progression of chronic kidney disease. Here, we tested whether the proteomic classifier based on 273 urinary peptides (CKD273) predicts albuminuria response to spironolactone treatment. METHODS: We performed a post hoc analysis in a double-blind randomized clinical trial with allocation...... to either spironolactone 12.5-50 mg/day (n = 57) or placebo (n = 54) for 16 weeks. Patients were diagnosed with type 2 diabetes and resistant hypertension. Treatment was an adjunct to renin-angiotensin system inhibition. Primary endpoint was the percentage change in urine albumin to creatinine ratio (UACR...
Bernard, A.; Lauwerys, R.; Ouled Amor, A. (Catholic Univ. of Louvain, Brussels (Belgium). Unit of Industrial Toxicology and Occupational Medicine)
The relationship between proteinuria and glomerular polyanion (GPA) charge has been studied in a model of experimental cadmium (Cd) nephropathy. Female Sprague-Dawley rats were administered Cd in drinking water for up to 18 months. From month 2, the animals showed an elevation of albuminuria preceding by about 6 months the rise of urinary [beta][sub 2]-microglobulin and IgG. The nephrotoxic action of Cd was not readily detectable on the basis of the urinary output of [beta]-N-acetylglucosaminidase, alanine aminopeptidase and lactate dehydrogenase. The enzymes showed either little variation or were affected late in the intoxication process. Administration of Cd for 12 or 18 months did not impair the GFR. The glomerular origin of the albuminuria induced by Cd was demonstrated by estimating the glomerular filtration of rat or human (injected intravenously) albumin in rats whose tubular reabsorption had been blocked by a saturating dose of cytochrome C. The GPA charge was assessed by measuring the binding of the cationic dye, Alcian blue (AB), to membranes of isolated glomeruli. The sialic and sulfate content of these membranes was also determined. The Cd induced-albuminuria was negatively correlated with the AB binding to glomerular membranes, their sialic acid content but not with their sulfate content. A negative correlation was also observed between the albuninaria and red blood cell membrane negative charges largely contributed by sialic acid. All these observations can be interpreted as the evidence that Cd enhances the glomerular filtration of proteins through a GPA depletion involving mainly sialic acid. (orig.).
Boels, Margien G S; Avramut, M Cristina; Koudijs, Angela; Dane, Martijn J C; Lee, Dae Hyun; van der Vlag, Johan; Koster, Abraham J; van Zonneveld, Anton Jan; van Faassen, Ernst; Gröne, Hermann-Josef; van den Berg, Bernard M; Rabelink, Ton J
Atrasentan, a selective endothelin A receptor antagonist, has been shown to reduce albuminuria in type 2 diabetes. We previously showed that the structural integrity of a glomerular endothelial glycocalyx is required to prevent albuminuria. Therefore we tested the potential of atrasentan to stabilize the endothelial glycocalyx in diabetic apolipoprotein E (apoE)-deficient mice in relation to its antialbuminuric effects. Treatment with atrasentan (7.5 mg/kg/day) for 4 weeks reduced urinary albumin-to-creatinine ratios by 26.0 ± 6.5% (P < 0.01) in apoE knockout (KO) mice with streptozotocin-induced diabetes consuming an atherogenic diet, without changes in gross glomerular morphology, systemic blood pressure, and blood glucose concentration. Endothelial cationic ferritin surface coverage, investigated using large-scale digital transmission electron microscopy, revealed that atrasentan treatment increases glycocalyx coverage in diabetic apoE KO mice from 40.7 ± 3.2% to 81.0 ± 12.5% (P < 0.05). This restoration is accompanied by increased renal nitric oxide concentrations, reduced expression of glomerular heparanase, and a marked shift in the balance of M1 and M2 glomerular macrophages. In vitro experiments with endothelial cells exposed to laminar flow and cocultured with pericytes confirmed that atrasentan reduced endothelial heparanase expression and increased glycocalyx thickness in the presence of a diabetic milieu. Together these data point toward a role for the restoration of endothelial function and tissue homeostasis through the antialbuminuric effects of atrasentan, and they provide a mechanistic explanation for the clinical observations of reduced albuminuria with atrasentan in diabetic nephropathy. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Climie, Rachel E D; Srikanth, Velandai; Keith, Laura J; Davies, Justin E; Sharman, James E
Exercise-induced albuminuria is common in patients with type 2 diabetes mellitus (T2DM) in response to maximal exercise, but the response to light-moderate exercise is unclear. Patients with T2DM have abnormal central hemodynamics and greater propensity for exercise hypertension. This study sought to determine the relationship between light-moderate exercise central hemodynamics (including aortic reservoir and excess pressure) and exercise-induced albuminuria. Thirty-nine T2DM (62 ± 9 yr; 49% male) and 39 nondiabetic controls (53 ± 9 yr; 51% male) were examined at rest and during 20 min of light-moderate cycle exercise (30 W; 50 revolutions/min). Albuminuria was assessed by the albumin-creatinine ratio (ACR) at rest and 30 min postexercise. Hemodynamics recorded included brachial and central blood pressure (BP), aortic stiffness, augmented pressure (AP), aortic reservoir pressure, and excess pressure integral (Pexcess). There was no difference in ACR between groups before exercise (P > 0.05). Exercise induced a significant rise in ACR in T2DM but not controls (1.73 ± 1.43 vs. 0.53 ± 1.0 mg/mol, P = 0.002). All central hemodynamic variables were significantly higher during exercise in T2DM (i.e., Pexcess, systolic BP and AP; P exercise Pexcess was associated with postexercise ACR (r = 0.51, P = 0.002), and this relationship was independent of age, sex, body mass index, heart rate, aortic stiffness, antihypertensive medication, and ambulatory daytime systolic BP (β = 0.003, P = 0.003). Light-moderate exercise induced a significant rise in ACR in T2DM, and this was independently associated with Pexcess, a potential marker of vascular dysfunction. These novel findings suggest that Pexcess could be important for appropriate renal function in T2DM. Copyright © 2015 the American Physiological Society.
Kim, Gyu Ah; Park, Se Hee; Ko, Jaesang; Lee, Si Hyung; Bae, Hyoung Won; Seong, Gong Je; Kim, Chan Yun
Systemic vascular dysfunction has been suggested to contribute to glaucomatous damage. Albuminuria is a surrogate marker of endothelial injury, including vessels. However, their relationship is not well understood. This study aimed to investigate the association between albuminuria and the prevalence of open-angle glaucoma (OAG) in nondiabetic subjects. We conducted a cross-sectional study of 4186 nondiabetic participants aged 19 years or older from the 2011-2012 Korea National Health and Nutrition Examination Survey. OAG was defined based on the criteria of the International Society for Geographic and Epidemiologic Ophthalmology. Urinary albumin excretion was assessed by the urinary albumin-to-creatinine ratio (UACR). A multivariate logistic regression analysis was performed to evaluate the relationship between albuminuria and OAG. Among the subjects, 124 had OAG. The weighted prevalences of microalbuminuria (UACR of 30-299 mg/g creatinine [Cr]) and macroalbuminuria (UACR ≥ 300 mg/g Cr) were 3.2 ± 0.3% and 0.4 ± 0.1%, respectively. The percentages of OAG increased in accordance with increasing UACR tertiles. Compared with subjects in the lower UACR tertile, those in the upper tertile showed an increased prevalence of OAG (odds ratio, 1.963; 95% confidence interval 1.072-3.595, P = 0.029) after adjusting for demographic factors, laboratory parameters, kidney function, and intraocular pressure. Furthermore, even after excluding 155 subjects with microalbuminuria and 19 subjects with macroalbuminuria, a positive association persisted between the upper UACR tertile (low-grade albuminuria) and an increased prevalence of OAG (odds ratio, 2.170; 95% confidence interval, 1.174-4.010, P = 0.014). Albuminuria, even low-grade, was significantly associated with OAG in nondiabetic subjects. This result implies the role of vascular endothelial dysfunction in the pathogenic mechanism of OAG and suggests that careful monitoring of OAG is required in nondiabetic subjects with
Context As life expectancy improves among Human Immunodeficiency Virus (HIV) patients, renal and cardiovascular diseases are increasingly prevalent in this population. Renal and cardiovascular disease are mutual risk factors and are characterized by albuminuria. Understanding the interactions between HIV, cardiovascular risk factors and renal disease is the first step in tackling this new therapeutic frontier in HIV. Methods In a rural primary health care centre, 903 HIV-infected adult patients were randomly selected and data on HIV-infection and cardiovascular risk factors were collected. Glomerular filtration rate (eGFR) was estimated. Albuminuria was defined as an Albumin-Creatinine-Ratio above 30 mg/g. Multivariate logistic regression analysis was used to analyse albuminuria and demographic, clinical and HIV-associated variables. Results The study population consisted of 903 HIV-infected patients, with a median age of 40 years (Inter-Quartile Range (IQR) 34–48 years), and included 625 (69%) women. The median duration since HIV diagnosis was 26 months (IQR 12–58 months) and 787 (87%) received antiretroviral therapy. Thirty-six (4%) of the subjects were shown to have diabetes and 205 (23%) hypertension. In the cohort, 21% had albuminuria and 2% an eGFR Albuminuria was associated with hypertension (adjusted odds ratio (aOR) 1.59; 95% confidence interval (CI) 1.05–2.41; palbuminuria was common amongst HIV-infected patients in rural South Africa. Both cardiovascular and HIV-specific variables were associated with albuminuria. Improved cardiovascular risk prevention as well as adequate virus suppression might be the key to escape the vicious circle of renal failure and cardiovascular disease and improve the long-term prognosis of HIV-infected patients. PMID:26309226
Nam, Ga Eun; Han, Kyungdo; Park, Yong Gyu; Kim, Yang Hyun; Lee, Kyung Shik; Cho, Kyung Hwan; Choi, Youn Seon; Kim, Seon Mee; Kim, Do Hoon
The effects of obesity on the kidney, apart from diabetes or hypertension, have not drawn much attention. Moreover, only a few studies have reported the relationship between obesity status and albuminuria in Asian countries, including South Korea. Therefore, this study aimed to investigate the association between obesity status and albuminuria in Korean adults. We analyzed data from the 2011 Korea National Health and Nutrition Examination Survey. Of the 4,979 subjects included in the general-population group, 3,274 were sorted into a nondiabetic and nonhypertensive population group. Obesity status was measured by body mass index and waist circumference. Albuminuria was defined as a urine albumin-to-creatinine ratio ≥30 mg/g. Abdominally obese women were at higher risk for albuminuria than were women without abdominal obesity both in the general population (odds ratio [OR], 95% confidence interval [CI]: 2.08 [1.04-4.16]) and in the nondiabetic and nonhypertensive population (OR [95% CI]: 6.96 [2.34-20.64]) after further adjustment for confounders. Among generally nonobese women, abdominally obese women were at higher risk for albuminuria than were women without abdominal obesity both in the general population (OR [95% CI]: 2.82 [1.51-5.29]) and in the nondiabetic and nonhypertensive population (OR [95% CI]: 5.32 [1.47-19.22]). Abdominal obesity is associated with an increased risk for albuminuria in Korean women, independently of diabetes or hypertension. Screening for abdominal obesity, especially in women, may therefore provide earlier identification of individuals at risk for developing renal disease and cardiovascular disease, even those who are nondiabetic and nonhypertensive.
Full Text Available Estimated glomerular filtration rate (eGFR is used for diagnosis of chronic kidney disease (CKD. The eGFR models based on serum creatinine or cystatin C are used more in clinical practice. Albuminuria and neck circumference are associated with CKD and may have correlations with eGFR.We explored the correlations and modelling formulates among various indicators such as serum creatinine, cystatin C, albuminuria, and neck circumference for eGFR.Cross-sectional study.We reviewed the records of patients with high cardiovascular risk from 2010 to 2011 in Taiwan. 24-hour urine creatinine clearance was used as the standard. We utilized a decision tree to select for variables and adopted a stepwise regression method to generate five models. Model 1 was based on only serum creatinine and was adjusted for age and gender. Model 2 added serum cystatin C, models 3 and 4 added albuminuria and neck circumference, respectively. Model 5 simultaneously added both albuminuria and neck circumference.Total 177 patients were recruited in this study. In model 1, the bias was 2.01 and its precision was 14.04. In model 2, the bias was reduced to 1.86 with a precision of 13.48. The bias of model 3 was 1.49 with a precision of 12.89, and the bias for model 4 was 1.74 with a precision of 12.97. In model 5, the bias could be lower to 1.40 with a precision of 12.53.In this study, the predicting ability of eGFR was improved after the addition of serum cystatin C compared to serum creatinine alone. The bias was more significantly reduced by the calculation of albuminuria. Furthermore, the model generated by combined albuminuria and neck circumference could provide the best eGFR predictions among these five eGFR models. Neck circumference can be investigated potentially in the further studies.
Liu, Yan; Tan, Rong-Shao; Zhou, Dao-Yuan; Xiao, Xiao; Ran, Jian-Min; Qin, Dan-Ping; Zhong, Xiao-Shi; Hu, Jian-Guang; Liu, Yun; Zheng, Yuan-Yuan
Chronic kidney disease (CKD) is a serious condition associated with early mortality, decreased quality of life, and increased health-care expenditures. Data from the National Health and Nutrition Examination Survey (NHANES) collected from 1999 to 2012 were used. Subjects were divided into 4 estimated glomerular filtration rate (eGFR) categories: stage 1: eGFR≥90mL/min/1.73m 2 , stage 2: eGFR 60-89, stage 3: eGFR 30-59, and stage 4/5: eGFRprotein intake and albuminuria were determined. A total of 45,259 subjects were included. Despite decreasing protein intake, there was a significant increase in the prevalence of albuminuria with decreasing levels of eGFR. Multivariable analysis showed that albuminuria was associated with daily protein intake in patients ≥65years old with stage 1 disease, and that diabetes was associated with albuminuria in patients ≥65years old with stage 2 and 3 diseases. Overall, albuminuria in patients with stage 1 disease was associated with hours of sitting per day and blood glucose level. Albuminuria was associated with daily protein intake in patients of 45-64years old with stage 1 CKD disease, and was associated with hours of sitting per day and blood glucose level. These data further support the importance of lifestyle changes in the management of CKD, especially in patients with early-stage disease. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Kohan, Donald E; Lambers Heerspink, Hiddo J; Coll, Blai
-induced fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A post hoc analysis......) for 12 weeks. Changes in body weight and hemoglobin (Hb) after 2 weeks of treatment were used as surrogate markers of fluid retention. RESULTS: Baseline predictors of weight gain after 2 weeks of atrasentan treatment were higher atrasentan dose, lower eGFR, higher glycated hemoglobin, higher systolic BP...
Peralta, Carmen A; Bibbins-Domingo, Kirsten; Vittinghoff, Eric; Lin, Feng; Fornage, Myriam; Kopp, Jeffrey B; Winkler, Cheryl A
Variants in the APOL1 gene are associated with kidney disease in blacks. We examined associations of APOL1 with incident albuminuria and kidney function decline among 3030 young adults with preserved GFR in the Coronary Artery Risk Development in Young Adults (CARDIA) study. eGFR by cystatin C (eGFRcys) and albumin-to-creatinine ratio were measured at scheduled examinations. Participants were white (n=1700), high-risk black (two APOL1 risk alleles, n=176), and low-risk black (zero/one risk allele, n=1154). Mean age was 35 years, mean eGFRcys was 107 ml/min per 1.73 m(2), and 13.2% of blacks had two APOL1 alleles. The incidence rate per 1000 person-years (95% confidence interval) for albuminuria over 15 years was 15.6 (10.6-22.1) for high-risk blacks, 7.8 (6.4-9.4) for low-risk blacks, and 3.9 (3.1-4.8) for whites. Compared with whites, the odds ratio (95% confidence interval) for incident albuminuria was 5.71 (3.64-8.94) for high-risk blacks and 2.32 (1.73-3.13) for low-risk blacks. Adjustment for risk factors attenuated the difference between low-risk blacks and whites (odds ratio 1.21, 95% confidence interval 0.86-1.71). After adjustment, high-risk blacks had a 0.45% faster yearly eGFRcys decline over 9.3 years compared with whites. Low-risk blacks also had a faster yearly eGFRcys decline compared with whites, but this difference was attenuated after adjustment for risk factors and socioeconomic position. In conclusion, blacks with two APOL1 risk alleles had the highest risk for albuminuria and eGFRcys decline in young adulthood, whereas disparities between low-risk blacks and whites were related to differences in traditional risk factors. Copyright © 2016 by the American Society of Nephrology.
Melsom, Toralf; Stefansson, Vidar; Schei, Jørgen; Solbu, Marit; Jenssen, Trond; Wilsgaard, Tom; Eriksen, Bjørn O
Hyperfiltration at the single-nephron level has been proposed as an early stage of kidney dysfunction of different origins. Evidence supporting this hypothesis in humans is lacking, because there is no method of measuring single-nephron GFR in humans. However, increased whole-kidney GFR in the same individual implies an increased single-nephron GFR, because the number of nephrons does not increase with age. We hypothesized that an increase in GFR would be associated with an increased albumin-to-creatinine ratio in a cohort of the general population. We measured GFR by iohexol clearance at baseline in 2007-2009 and follow-up after 5.6 years in a representative sample of 1246 persons (aged 50-62 years) who were nondiabetic from the general population of Tromso, northern Norway. Participants were without cardiovascular disease, kidney disease, or diabetes at baseline. We investigated the association between change in GFR and change in albumin-to-creatinine ratio. Increased GFR was defined as a positive change in GFR (change in GFR>0 ml/min) from baseline to follow-up. An albumin-to-creatinine ratio >30 mg/g was classified as albuminuria. Change in GFR was positively associated with a change in albumin-to-creatinine ratio in the entire cohort in the multiple linear regression. The albumin-to-creatinine ratio follow-up -to-albumin-to-creatinine ratio baseline ratio increased by 8.0% (95% confidence interval, 1.4 to 15.0) per SD increase in change in GFR. When participants with increased GFR (n=343) were compared with those with a reduced GFR (n=903), the ratio increased by 16.3% (95% confidence interval, 1.1 to 33.7). The multivariable adjusted odds ratio for incident albuminuria (n=14) was 4.98 (95% confidence interval, 1.49 to 16.13) for those with an increased GFR (yes/no). Increasing GFR is associated with an increase in albumin-to-creatinine ratio and incident albuminuria in the general nondiabetic population. These findings support single-nephron hyperfiltration
Rasmussen, Jon Bjarke Jarløv; Nordin, Lovisa S.; Thomsen, Jakup Andreas
characteristics including medications were assessed. We identified 160 patients with hypertension, of whom 68 (42.5%) were co-diagnosed with diabetes mellitus (DM). Among the included participants, 57 (35.6%) had albuminuria (microalbuminuria [n=43] and macroalbuminuria [n=14]). A backward multivariate logistic...... regression model identified age (per 10-year increment) (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.03-1.95), HbA1c >53 compared with treatment with dihydropyridine calcium channel blockers (OR, 2.59; 95% CI, 1.09-6.16) as the variables...
Varis, Juha; Metsärinne, Kaj; Koivisto, Veikko; Niskanen, Leo; Rissanen, Aila; Virkamäki, Antti; Appelroth, Tina; Pöntynen, Nora; Poussa, Tuija; Kantola, Ilkka
Risk of cardiovascular events within the diabetic population has decreased and survival increased with patients living longer and thus facing the development of end-stage renal disease (ESRD). This calls for good care of patient with diabetes with a focus on hypertension. Patient data were collected from 42 Finnish primary care centres. Each was asked to enrol 10-12 consecutive patients with type-2 diabetes between March 2011 and August 2012. Along with the office blood pressure measurements and laboratory tests, the presence of albuminuria was measured and glomerular filtration rate estimated (eGFR). The 2013 ESH criteria for diabetic hypertensive patients (albuminuria and hence ESRD prevention was achieved.
Persson, Frederik; Rossing, Peter; Reinhard, Henrik
with type 2 diabetes, hypertension, and albuminuria (>100 mg/day) were randomly assigned to four 2-month treatment periods in random order with placebo, 300 mg aliskiren once daily, 300 mg irbesartan once daily, or the combination using identical doses. Patients received furosemide in a stable dose...... antiproteinuric in type 2 diabetic patients with albuminuria than monotherapy.......OBJECTIVE: We investigated whether the antiproteinuric effect of the direct renin inhibitor aliskiren is comparable to that of irbesartan and the effect of the combination. RESEARCH DESIGN AND METHODS: This was a double-blind, randomized, crossover trial. After a 1-month washout period, 26 patients...
Haswell-Elkins, Melissa; Satarug, Soisungwan; O'Rourke, Peter; Moore, Michael; Ng, Jack; McGrath, Victor; Walmby, Maria
Objectives: Indigenous people of the Torres Strait (Australia) have greater potential for cadmium exposure and renal damage than other Australians due to high cadmium in some traditional seafood and a high prevalence of Type 2 diabetes, hypertension, smoking, and obesity. This study explored associations between albuminuria and an index of cadmium exposure (urinary cadmium excretion) in the presence and absence of Type 2 diabetes. Research design and methods: Two population-based, cross-sectional studies were undertaken in the Torres Strait to obtain data on body mass index (BMI), blood pressure, chronic disease, smoking, urinary cadmium, and albumin creatinine ratio (ACR). Results: Age- and BMI-adjusted urinary cadmium levels were significantly higher (p<0.01) among people with diabetes and albuminuria (n=22, geometric mean (GM) 1.91 μg Cd/g creatinine) compared to those with diabetes and normal ACR (n=21, GM 0.74 μg Cd/g creatinine). Urinary cadmium was also strongly associated (p<0.001) with ACR among people with diabetes in regression models and remained significant after controlling for age, sex, BMI, smoking status, and hypertension (or continuous systolic and diastolic measurements). Conclusions: While the study has methodological limitations and the nature of the association is unclear, the striking dose-dependent links between markers of cadmium exposure and of Type 2 diabetic nephropathy highlight the need for further definitive research on the health effects of cadmium in the presence of diabetes
Ren, Meng; Sun, Kan; Li, Feng; Qi, Yi Qin; Lin, Diao Zhu; Li, Na; Li, Yan; Yan, Li
The effects of obesity on the micro vascular diseases have drawn much attention. The aim of the study was to investigate the relationship between obesity measures and albuminuria in Chinese population. We conducted a population-based cross-sectional study in 8600 subjects aged 40 years or older from a community in Guangzhou. Urinary albumin excretion and creatinine were measured and urinary albumin-to-creatinine ratio (ACR) was calculated as urinary albumin divided by creatinine. Low-grade albuminuria was classified as the highest quartile of ACR in participants without increased urinary albumin excretion. Increased urinary albumin excretion was defined according to the ACR ranges greater or equal than 30 mg/g. Pearson's correlation analysis and multivariate linear regression analysis revealed that body mass index (BMI), waist circumference and body fat content were significantly correlated with ACR (all Palbuminuria and increased urinary albumin excretion gradually increased across the BMI, waist circumference and body fat content quartiles (all P for trendalbuminuria and increased urinary albumin excretion in logistic regression analysis after adjustment for age, sex, physical activity, fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol and HbA1c (all P<0.05). Obesity measures are associated with urinary albumin excretion in middle-aged and elderly Chinese. Copyright © 2016 Elsevier Inc. All rights reserved.
Li, Fengqin; Guo, Hui; Zou, Jianan; Chen, Weijun; Lu, Yijun; Zhang, Xiaoli; Fu, Chensheng; Xiao, Jing; Ye, Zhibin
Increasing evidence has shown that albuminuria is related to serum uric acid. Little is known about whether this association may be interrelated via renal handling of uric acid. Therefore, we aim to study urinary uric acid excretion and its association with albuminuria in patients with chronic kidney disease (CKD). A cross-sectional study of 200 Chinese CKD patients recruited from department of nephrology of Huadong hospital was conducted. Levels of 24 h urinary excretion of uric acid (24-h Uur), fractional excretion of uric acid (FEur) and uric acid clearance rate (Cur) according to gender, CKD stages, hypertension and albuminuria status were compared by a multivariate analysis. Pearson and Spearman correlation and multiple regression analyses were used to study the correlation of 24-h Uur, FEur and Cur with urinary albumin to creatinine ratio (UACR). The multivariate analysis showed that 24-h Uur and Cur were lower and FEur was higher in the hypertension group, stage 3-5 CKD and macro-albuminuria group (UACR> 30 mg/mmol) than those in the normotensive group, stage 1 CKD group and the normo-albuminuria group (UACRuric acid is negatively associated with albuminuria in patients with CKD. This phenomenon may help to explain the association between albuminuria and serum uric acid.
Keyzer, Charlotte A; van Breda, G Fenna; Vervloet, Marc G; de Jong, Maarten A; Laverman, Gozewijn D; Hemmelder, Marc H; Janssen, Wilbert M T; Lambers Heerspink, Hiddo J; Kwakernaak, Arjan J; Bakker, Stephan J L; Navis, Gerjan; de Borst, Martin H
Reduction of residual albuminuria during single-agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)-controlled, crossover trial, 45 patients with nondiabetic CKD stages 1-3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BPalbuminuria (geometric mean) was 1060 (95% confidence interval, 778 to 1443) mg/24 h during RS + PLAC and 990 (95% confidence interval, 755 to 1299) mg/24 h during RS + PARI ( P =0.20 versus RS + PLAC). LS + PLAC reduced albuminuria to 717 (95% confidence interval, 512 to 1005) mg/24 h ( P albuminuria to 683 (95% confidence interval, 502 to 929) mg/24 h ( P albuminuria reduction ( P =0.04 LS + PARI versus LS + PLAC). Dietary adherence was good as reflected by urinary excretion of 174±64 mmol Na + per day in the combined RS groups and 108±61 mmol Na + per day in the LS groups ( P albuminuria during fixed dose angiotensin-converting enzyme inhibition. The additional effect of PARI was small and nonsignificant. Copyright © 2017 by the American Society of Nephrology.
Romundstad, Solfrid; Hatlen, Gudrun; Hallan, Stein I
Knowledge on how changing risk factors influence the progression of albuminuria over time is still limited. Furthermore, large population-based cohorts are needed to study the association between albuminuria change and mortality risk in nondiabetic study participants. We evaluated changes of albuminuria in 6282 nondiabetic individuals from the Norwegian population-based Nord-Trøndelag Health study. Using three albumin/creatinine ratios (ACR), we studied the influence of cardiovascular risk factors on ACR change from baseline to follow-up 11 years later. We evaluated the next 8-year mortality risk by using flexible parametric methods to identify nonlinear main effects and their two-way interactions. Mean albuminuria increased significantly over 11 years (1.82-3.02 mg/mmol, P albuminuria. Study participants in the upper quartile of the increasing group had mean adjusted hazard ratio 1.31 (P = 0.004) for all-cause mortality compared with those with stable ACR. Those with decreasing ACR also had increased mortality, but the risk was strongly attenuated when adjusting for comorbidity. It also decreased the first 3 years before increasing. There was a strong interaction between baseline ACR and ΔACR. Increasing albuminuria had strongest effect on mortality in study participants with moderately increased baseline values. Both increasing and decreasing albuminuria are significant independent predictors of mortality in nondiabetic individuals, but must be interpreted in light of baseline values. Cutoffs and clinical usefulness in nondiabetic study participants should be further investigated.
Pijls, L.T.J.; de Vries, H.; Donker, A.J.M.; van Eijk, J.T.M.
Background. A randomized trial was conducted to assess whether protein restriction helps to delay the onset of renal disorders in type 2 diabetic patients. Methods. Included in the trial were 121 type 2 diabetic patients with microalbuminuria or at least detectable albuminuria, or diabetes of
Greve, Sara V; Blicher, Marie K; Blyme, Adam
atherosclerotic plaques or albuminuria defined as urine albumin/creatinine ratio at least 90th percentile of 0.73/1.06 mg/mmol men/women. In 2006, the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization for ischemic heart disease was recorded (n...
Kropelin, Tobias F.; de Zeeuw, Dick; Remuzzi, Giuseppe; Bilous, Rudy; Parving, Hans-Henrik; Heerspink, Hiddo J. L.
Albuminuria class transition (normo-to micro-to macroalbuminuria) is used as an intermediate end point to assess renoprotective drug efficacy. However, definitions of such class transition vary between trials. To determine the most optimal protocol, we evaluated the approaches used in four clinical
Wang, Hua-Bin; Li, Rong; Liu, Rui; Cui, Xiao-Fan; Pan, Wen-Jie; Sun, Ao
Albumin/creatinine ratio (ACR) from a first morning urine is recommended as a early indicator for diabetic nephropathy. However, it is not always feasible to collect the first morning urine for outpatients. We aimed to explore whether ACR from a second morning urine had a good consistency with that from a first morning urine to predict albuminuria in Chinese elderly citizens. One hundred and ninety-one elderly citizens (≧60 years old) from Junliangcheng community, Dongli district, Tianjin, China were included. A first and second morning urine was collected from each participants, successfully and detected the urinary albumin and creatinine of each urine sample. Albumin to creatinine ratio from a first morning urine (ACR1) was compared with that from a second morning urine (ACR2), and the ability of ACR1 and ACR2 to predict albuminuria was assessed. ACR1 and ACR2 were highly correlated (r = 0.901), especially in male and hypertension group (r = 0.938 and 0.904). The slope and intercept were 0.93 and 0.11 after log-transformed. And there was no statistical difference between values of ACR1 and ACR2 (P = 0.271). Overall, 26.2% participants were detected with albuminuria when judged by ACR1 and 28.3% by ACR2. A good concordance of ACR category (normal or albuminuria) was found between ACR1 and ACR2 (Kappa value = 0.815 in overall; in male and hypertension group were 0.900 and 0.850). A second morning urine ACR could be the alternative to a first morning urine ACR for albuminuria detection in elderly population. © 2015 Wiley Periodicals, Inc.
Gansevoort, Ron T.; Matsushita, Kunihiro; van der Velde, Marije; Astor, Brad C.; Woodward, Mark; Levey, Andrew S.; de Jong, Paul E.; Coresh, Josef
Both low eGFR and albuminuria are known risk factors for ESRD. This paper focuses on their joint contribution to ESRD and other kidney outcomes. We performed a collaborative meta-analysis of 9 general population cohorts with 845,125 participants and 8 cohorts with 173,892 participants selected because of high risk for chronic kidney disease. Both eGFR and albuminuria were tested as risk factors for ESRD, acute kidney injury and progressive chronic kidney disease. In general population cohorts, the risk for ESRD was unrelated to eGFR at values 75–105 ml/min/1.73m2 and increased exponentially at lower eGFR. Hazard ratios (95% confidence interval) at eGFR 60, 45, and 15 (versus 95) ml/min/1.73m2 were 3.69 (2.36–5.76), 29.3 (19.5–44.1) and 454.9 (112.4–1840.2), respectively, after adjustment for albumin-to-creatinine ratio and cardiovascular risk factors. Albuminuria was associated with ESRD risk linearly without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios 30, 300 and 1000 (versus 5) mg/g were 4.87 (2.30–10.3), 13.4 (5.49–32.7) and 28.4 (14.9–54.2), respectively. eGFR and albuminuria were multiplicatively associated with ESRD, without evidence for interaction. Similar, but numerically less pronounced associations were observed for acute kidney injury and progressive chronic kidney disease. The findings in high risk cohorts were generally comparable to those in general population cohorts. In conclusion, lower eGFR and higher albuminuria are risk factors for ESRD, acute kidney injury and progressive chronic kidney disease independent of each other and of cardiovascular risk factors, both in the general population and high risk cohorts. PMID:21289597
Yanagisawa, Naoki; Ando, Minoru; Tsuchiya, Ken; Nitta, Kosaku
Highly active antiretroviral therapy (HAART) has contributed to the longevity of human immunodeficiency virus (HIV)-infected patients; however, improved survival has been accompanied by an increase in the prevalence of kidney disease. Kidney disease may be partly responsible for higher morbidity in HIV-infected patients than in HIV-uninfected subjects. A total of 515 well-controlled HIV-infected men on HAART was enrolled in a 3-year prospective cohort study. The incidence of cancer and CVD was investigated over time. The impact of cystatin C elevation and albuminuria at baseline on the incidence of each disease was examined. Albuminuria was estimated by determining the albumin-to-creatinine ratio (ACR). The cumulative incidence of cancer and CVD was analyzed using the Kaplan-Meier method, stratified by the presence and absence of elevated cystatin C and albuminuria biomarkers. Cox proportional hazards analysis was used to calculate the hazards ratio (HR) and 95% incidence interval (CI) of each biomarker, adjusted for known risk factors. All participants completed the 3-year follow-up study. During the follow-up period, cancers and CVD developed in 13 (2.5%) and 14 (2.7%) participants, respectively. The Kaplan-Meier estimates were significantly increased for cancer incidence in patients with cystatin C elevation and for CVD in those with albuminuria. The HR (95% CI) of cystatin C elevation for occurrence of cancer was 6.09 (1.30 - 24.6) and the HR (95% CI) of ACR ≥ 20 mg/g for CVD was 8.97 (2.20 - 60.8). Cystatin C elevation and/or albuminuria at baseline in HIV-infected men undergoing HAART may be associated with poor prognosis.
Vart, Priya; Scheven, Lieneke; Lambers Heerspink, Hiddo J; de Jong, Paul E; de Zeeuw, Dick; Gansevoort, Ron T
New guidelines advocate the use of albumin-creatinine ratio (ACR) in a urine sample instead of 24-hour urinary albumin excretion (UAE) for staging albuminuria. Concern has been expressed that this may result in misclassification for reasons including interindividual differences in urinary creatinine excretion. Prospective longitudinal cohort study. We examined 7,623 participants of the PREVEND and RENAAL studies for reclassified when using ACR instead of 24-hour UAE, the characteristics of reclassified participants, and their outcomes. Albuminuria was categorized into 3 ACR and UAE categories: 300mg/g or mg/24 h, respectively. Baseline ACR and 24-hour UAE. Cardiovascular (CV) morbidity and mortality and all-cause mortality. When using ACR in the early morning void instead of 24-hour UAE, 88% of participants were classified in corresponding albuminuria categories. 307 (4.0%) participants were reclassified to a higher, and 603 (7.9%), to a lower category. Participants who were reclassified to a higher ACR category in general had a worse CV risk profile compared with nonreclassified participants, whereas the reverse was true for participants reclassified to a lower ACR category. Similarly, Cox proportional hazards regression analyses showed that reclassification to a higher ACR category was associated with a tendency for increased risk for CV morbidity and mortality and all-cause mortality, whereas reclassification to a lower ACR category was associated with a tendency for lower risk. Net reclassification improvement, adjusted for age, sex, and duration of follow-up, was 0.107 (P=0.002) for CV events and 0.089 (P<0.001) for all-cause mortality. Early morning void urine collection instead of spot urine collection. Our results indicate that there is high agreement between early morning void ACR and 24-hour UAE categories. Reclassification is therefore limited, but when present, is generally indicative of the presence of CV risk factors and prognosis. Copyright © 2016
Gao, Xiaoyu; Cleary, Patricia A.; Bebu, Ionut; Lachin, John M.; Molitch, Mark E.; Orchard, Trevor; Paterson, Andrew D.; Perkins, Bruce A.; Steffes, Michael W.; Zinman, Bernard
Background and objectives In trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes. Design, setting, participants, & measurements We studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (<60 ml/min per 1.73 m2 on two consecutive visits), and subclinical cardiovascular disease. Results At least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95% confidence intervals [95% CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95% CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95% CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95% CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification
Gunzler, Douglas; Bleyer, Anthony J; Thomas, Robert L; O'Brien, Alicia; Russell, Gregory B; Sattar, Abdus; Iyengar, Sudha K; Thomas, Charles; Sedor, John R; Schelling, Jeffrey R
Diabetic nephropathy is a growing clinical problem, and the cause for >40% of incident ESRD cases. Unfortunately, few modifiable risk factors are known. The objective is to examine if albuminuria and history of diabetic nephropathy (DN) in a sibling are associated with early DN progression or mortality. In this longitudinal study of adults >18 yrs with diabetes monitored for up to 9 yrs (mean 4.6 ± 1.7 yrs), 435 subjects at high risk (DN family history) and 400 at low risk (diabetes >10 yrs, normoalbuminuria, no DN family history) for DN progression were evaluated for rate of eGFR change using the linear mixed effects model and progression to ESRD. All-cause mortality was evaluated by Kaplan-Meier analyses while controlling for baseline covariates in a Cox proportional hazards model. Covariates included baseline eGFR, age, gender, race, diabetes duration, blood pressure, hemoglobin A1c and urine albumin:creatinine ratio. Propensity score matching was used to identify high and low risk group pairs with balanced covariates. Sensitivity analyses were employed to test for residual confounding. Mean baseline eGFR was 74 ml/min/1.73 m2 (86% of cohort >60 ml/min/1.73 m2). Thirty high risk and no low risk subjects developed ESRD. eGFR decline was significantly greater in high compared to low risk subjects. After controlling for confounders, change in eGFR remained significantly different between groups, suggesting that DN family history independently regulates GFR progression. Mortality was also significantly greater in high versus low risk subjects, but after controlling for baseline covariates, no significant difference was observed between groups, indicating that factors other than DN family history more strongly affect mortality. Analyses of the matched pairs confirmed change in eGFR and mortality findings. Sensitivity analyses demonstrated that the eGFR results were not due to residual confounding by unmeasured covariates of a moderate effect size in the
Solini, Anna; Manca, Maria Laura; Penno, Giuseppe; Pugliese, Giuseppe; Cobb, Jeff E; Ferrannini, Ele
Renal disease in type 2 diabetes mellitus (T2DM) is associated with excess morbidity/mortality. Although estimated glomerular filtration rate (eGFR) and albuminuria are routine for assessing renal impairment, novel biomarkers could improve risk stratification and prediction. To identify specific biomarkers of progression of renal dysfunction. Prospective observational. Academic diabetes clinics. A total of 286 T2DM patients (age, 62 ± 8 y; glycosylated hemoglobin, 7.2 ± 0.9%; eGFR, 85 ± 20 mL · min(-1) · 1.73 m(2)). None. Progression of eGFR and albuminuria. We performed screening metabolomics in serum and urine samples by gas chromatography/mass spectroscopy (MS) and ultra-high performance liquid chromatography/MS/MS. Biomarker identification was performed by random forest using an eGFR cutoff of fasting glucose, and baseline eGFR) predicted outcome, with receiver operator characteristics curve (ROC) = 0.671. The five serum metabolites best correlated with either eGFR < 60 or ACR ≥ 30 at baseline were tested for their ability to improve clinical prediction. The sum of C-glycosyl tryptophan, pseudouridine, and N-acetylthreonine (MetIndex) raised the ROC to 0.739 (P < .0001). eGFR decline was predicted by the top MetIndex quartile (odds ratio = 5.48 [95% confidence interval, 2.23-14.47]). MetIndex also predicted an ACR increase with an odds ratio of 2.82 [1.20-7.03] and a ROC of 0.750. Top urine metabolites did not add significant predictivity. A limited number of circulating intermediates of amino acid and nucleotide pathways carry clinically significant predictivity for deterioration of renal function in well-controlled T2DM.
Ebert, Natalie; Jakob, Olga; Gaedeke, Jens; van der Giet, Markus; Kuhlmann, Martin K; Martus, Peter; Mielke, Nina; Schuchardt, Mirjam; Tölle, Markus; Wenning, Volker; Schaeffner, Elke S
Although CKD is said to increase among older adults, epidemiologic data on kidney function in people ≥70 years of age are scarce. The Berlin Initiative Study (BIS) aims to fill this gap by evaluating the CKD burden in older adults. The BIS is a prospective population-based cohort study whose participants are members of Germany's biggest insurance company. This cross-sectional analysis (i) gives a detailed baseline characterization of the participants, (ii) analyses the representativeness of the cohort's disease profile, (iii) assesses GFR and albuminuria levels across age categories, (iv) associates cardiovascular risk factors with GFR as well as albuminuria and (v) compares means of GFR values according to different estimating equations with measured GFR. A total of 2069 participants (52.6% female, mean age 80.4 years) were enrolled: 26.1% were diabetic, 78.8% were on antihypertensive medication, 8.7% had experienced a stroke, 14% a myocardial infarction, 22.6% had cancer, 17.8% were anaemic and 26.5% were obese. The distribution of comorbidities in the BIS cohort was very similar to that in the insurance 'source population'. Creatinine and cystatin C as well as the albumin:creatinine ratio (ACR) increased with increasing age. After multivariate adjustments, reduced GFR and elevated ACR were associated with most cardiovascular risk factors. The prevalence of a GFR <60 mL/min/1.73 m 2 ranged from 38 to 62% depending on the estimation equation used. The BIS is a very well-characterized, representative cohort of older adults. Participants with an ACR ≥30 had significantly higher odds for most cardiovascular risk factors compared with an ACR <30 mg/g. Kidney function declined and ACR rose with increasing age.
Kim, Ha Yeon; Bae, Eun Hui; Ma, Seong Kwon; Chae, Dong Wan; Choi, Kyu Hun; Kim, Yong-Soo; Hwang, Young-Hwan; Ahn, Curie; Kim, Soo Wan
Adiponectin, a peptide hormone secreted from adipocytes, exerts anti-diabetic, anti-atherogenic, and anti-inflammatory properties. We aimed to determine the relationship between serum adiponectin levels and albuminuria, and evaluate determinant factors for serum adiponectin in patients with chronic kidney disease (CKD). In total, 1442 CKD patients were included and divided into three groups according to their albumin-to-creatinine ratios: patients with normoalbuminuria (N = 228), microalbuminuria (N = 444), and macroalbuminuria (N = 761). Serum adiponectin was specifically assayed with a commercially available enzyme-linked immunosorbent assay kit. Serum adiponectin was significantly higher in patients with macroalbuminuria than in those without macroalbuminuria (9.7 ± 6.0, 12.4 ± 9.0, and 14.9 ± 11.0 μg/mL in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively). Univariate linear regression analysis showed that the serum adiponectin concentrations were correlated with age, the albumin-to-creatinine ratio, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, whereas they were negatively correlated with body mass index, the estimated glomerular filtration rate, and serum albumin and triglyceride levels. The stepwise regression multiple analysis showed that sex; the estimated glomerular filtration rate; body mass index; total cholesterol, high-density lipoprotein cholesterol, and triglyceride levels; and logarithm of the albumin-to-creatinine ratio were independently associated with the logarithm of serum adiponectin levels (r = 0.55, p albuminuria, and these levels are associated with renal insufficiency and lipid profiles.
Dennis Sung Chul Hong
Full Text Available Background/Aims: Either protein-to-creatinine ratio (PCR or albumin-to-creatinine ratio (ACR can be adopted for estimation of proteinuria in patients with chronic kidney disease (CKD. Estimated protein excretion rate (ePER and estimated albumin excretion rate (eAER may be superior to ACR and PCR. Reports show that urine albumin-to-protein ratio (APR may be useful in detecting tubular proteinuria, but should be compared with urine protein electrophoresis (PEP. Methods: Both 24-h urine and spot urine were collected from 77 stable CKD patients for measurement of albumin, protein, and creatinine, and PEP. Based on MDRD and CKD-EPI equations, ePERMDRD, ePERCKD-EPI, eAERMDRD and eAERCKD-EPI were calculated to estimate daily proteinuria and albuminuria. Glomerular CKD was defined by clinical and/or pathological evidence. Results: ACR correlated significantly with PCR. However, microalbuminuria was present in patients without pathologic proteinuria. Twenty-four-hour urine albumin correlated better with eAERMDRD and eAERCKD-EPI than ACR, and 24-h urine protein correlated better with ePERMDRD and ePERCKD-EPI than PCR. APR significantly but not well correlated with the albumin fraction in urine PEP. The albumin fraction obtained from urine PEP was significantly higher in patients with glomerulopathy than those with non-glomerular CKD, whereas there were no differences in APR between groups. In contrast with APR, the albumin fraction in urine PEP was independently associated with glomerular CKD. Conclusions: Both PCR and ACR are useful in evaluation of proteinuria. In quantifying daily proteinuria and albuminuria, ePER and eAER are superior to PCR and ACR, respectively. Compared with APR, urine PEP is more useful in diagnosing glomerular proteinuria.
Zimmet Paul Z
Full Text Available Abstract Background Indigenous Australians have an incidence of end stage kidney disease 8-10 times higher than non-Indigenous Australians. The majority of research studies concerning Indigenous Australians have been performed in rural or remote regions, whilst the majority of Indigenous Australians actually live in urban settings. We studied prevalence and factors associated with markers of kidney disease in an urban Indigenous Australian cohort, and compared results with those for the general Australian population. Methods 860 Indigenous adult participants of the Darwin Region Urban Indigenous Diabetes (DRUID Study were assessed for albuminuria (urine albumin-creatinine ratio≥2.5 mg/mmol males, ≥3.5 mg/mmol females and low eGFR (estimated glomular filtration rate 2. Associations between risk factors and kidney disease markers were explored. Comparison was made with the AusDiab cohort (n = 8,936 aged 25-64 years, representative of the general Australian adult population. Results A high prevalence of albuminuria (14.8% was found in DRUID, whilst prevalence of low eGFR was 2.4%. Older age, higher HbA1c, hypertension, higher C-reactive protein and current smoking were independently associated with albuminuria on multiple regression. Low eGFR was independently associated with older age, hypertension, albuminuria and higher triglycerides. Compared to AusDiab participants, DRUID participants had a 3-fold higher adjusted risk of albuminuria but not of low eGFR. Conclusions Given the significant excess of ESKD observed in Indigenous versus non-Indigenous Australians, these findings could suggest either: albuminuria may be a better prognostic marker of kidney disease than low eGFR; that eGFR equations may be inaccurate in the Indigenous population; a less marked differential between Indigenous and non-Indigenous Australians for ESKD rates in urban compared to remote regions; or that differences in the pathophysiology of chronic kidney disease exist
Xu, Xiqi; He, Jinggui; Wang, Shuxia; Zhu, Ping; Chen, Qian; Zhang, Xiujin; Tao, Tao; Wang, Hao; Liu, Jianfeng; Wang, Haijun; Li, Xiaoying
Our study aimed to explore whether the ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) were associated with albuminuria in community-based Han Chinese. Total 2127 subjects (860 men and 1267 women) aged 60 years and over were recruited in Beijing. Albuminuria was assessed by the urinary albumin-to-creatinine ratio (UACR) of ≥30 mg/g. BaPWV was divided by quartile. The logistic regression was used to determine the odds ratio (OR) and 95% confidence intervals (CIs) of ABI and baPWV with albuminuria. ABI was associated with albuminuria in the interaction model (OR 0.89, 95% CI 0.81-0.99 by every 0.1 unit increase of ABI), especially in hypertension (OR 0.82, 95% CI 0.73-0.92) and diabetes (OR 0.83, 95% CI 0.68-0.98) groups. BaPWV groups were also significantly associated with albuminuria, ORs of having albuminuria for baPWV quartile II, III, and IV were 1.02(0.65-1.52), 1.05(0.72-1.61), and 1.18(1.04-1.47) in the interaction model. For hypertension and diabetes patients, only the baPWV quartile IV group had higher OR. ABI and baPWV were associated with albuminuria after adjusting for other risk factors in Chinese community-based elderly Han population. The association of ABI with albuminuria was stronger in hypertension and diabetes patients.
Özyilmaz, Akin; Boersma, Cornelis; Visser, Sipke T; Postma, Maarten J; de Jong-van den Berg, Lolkje Tw; Lambers-Heerspink, Hiddo J; de Jong, Paul E; Gansevoort, Ron T
It is not clear which hypercholesterolemic patients benefit most from β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitors with respect to the prevention of cardiovascular events. Early signs of atherosclerotic vascular damage may identify high-risk patients. We studied whether subjects with hypercholesterolemia will benefit more from starting statin treatment in the case of high albuminuria and/or high-sensitivity C-reactive protein (hsCRP). Included were subjects who had hypercholesterolemia at baseline, a negative cardiovascular disease history and who were not treated with statins. In total, 2011 subjects were analysed, of whom 695 started with a statin during a follow-up of 7.0 ± 1.7 years. Adjusted hazard ratios (HRs) for cardiovascular events were calculated in subjects who started versus those who did not start a statin stratified for albuminuria less than or ≥ 15 mg/day and/or hsCRP less than or ≥ 3 mg/L. The start of a statin was associated with a beneficial effect on cardiovascular risk in subjects with high albuminuria (HR 0.38 (0.23-0.60)), while the effect of starting a statin was non-significant in subjects with low albuminuria (HR 0.74 (0.44-1.24), P for interaction albuminuria and hsCRP subgroups, the start of statin treatment was associated with a lower risk of cardiovascular events dependent on albuminuria and not on the hsCRP level. The start of statin treatment is associated with a significantly lower absolute as well as relative risk of cardiovascular events in subjects with hypercholesterolemia and elevated albuminuria, whereas these drugs had less effect in subjects with normal albuminuria. © The European Society of Cardiology 2015.
Noh, Hye-Mi; Kim, Un-Young; Park, Yong Soon; Song, Young Rim; Oh, Hye-Young; Park, Kyung-Hee; Paek, Yu-Jin; Roh, Yong Kyun; Song, Hong Ji
The association between obesity and albuminuria in the general population remains unclear. We aimed to identify the association between obesity and albuminuria as well as sex differences regarding the associations using several obesity indices, including waist circumference (WC), body mass index (BMI), and waist-to-height ratio (WHR). This study included 3841 subjects (1730 males and 2111 females; age 20-80 years) who participated in the Fifth Korea National Health and Nutrition Examination Survey conducted in 2011. Subjects with hypertension, diabetes, renal failure, or a malignant tumor and those who were pregnant or menstruating were excluded. Albuminuria was defined as a urinary albumin-to-creatinine ratio ≥30 mg/g. Anthropometric parameters were categorized into sex-specific quartiles. Logistic regression models were used to assess the associations between each anthropometric parameter and albuminuria. All of the obesity indices of the fourth quartile group of females showed a twofold higher risk for albuminuria than the second quartile group, and it was persistently significant after adjusting for age, smoking, and physical activity. After further adjustment for high blood pressure and impaired fasting glucose and triglyceride levels, WC and BMI of the fourth quartile group of females still showed a significantly higher risk for albuminuria than the second quartile group (odds ratios 1.96 and 2.24; 95 % confidence intervals 1.03-3.74 and 1.15-4.37). None of the associations between albuminuria and the obesity indices were significant in males. Higher WC and BMI were significantly associated with the risk of albuminuria among females, but not males.
Hsieh, Ya-Mei; Lee, Wen-Jane; Sheu, Wayne H.-H.; Li, Yu-Hsuan; Lin, Shih-Yi; Lee, I.-Te
Background There is a high hospitalization rate for diabetic patients. Since retinopathy and albuminuria are both important manifestations of microvascular disease in diabetes, our aim was to investigate the effect of retinopathy and albuminuria on long-term mortality in type 2 diabetic inpatients through this observational cohort study. Methods Type 2 diabetic inpatients given a primary diagnosis of poor glucose control were consecutively enrolled during their hospitalization periods. Clinic...
Wijaya, Indra; Yunir, Em; Dharmeizar, Dharmeizar; Wijaya, Ika Prasetya; Setiati, Siti
to develop a scoring system and measure the diagnostic added value of albuminuria to estimate CIMT. cross-sectional study was done in Endocrine Outpatient Clinic Cipto Mangunkusumo Hospital between March-May 2012 in T2DM patients without history of cerebrocardiovascular event, CKD stage ≥ III, and smoking. Bivariate analysis and multivariate (logistic regression) analysis was done, followed by developing the scoring system. from 71 subjects, there were 67.6% with increased CIMT and 73.3% with albuminuria. From 48 subjects with increased CIMT, 87.5% had albuminuria. Albuminuria measurement had high sensitivity (87.5%). Adding albuminuria measurement will increase the AUC as 2.3%. Estimation score for duration of DM, hypertension, dyslipidemia were as follows 1, 2, 1 respectively. Probability score of increased CIMT for score 2 was as follows 15%, 57%, and 90%. albuminuria measurement increase the diagnostic value of CIMT. Scoring system can be used as a screening tool to estimate the increased of CIMT in type 2 DM patients without history of cerebrocardiovascular event, CKD stage ≥ III, and smoking.
Kitagawa, Noriyuki; Okada, Hiroshi; Tanaka, Muhei; Hashimoto, Yoshitaka; Kimura, Toshihiro; Nakano, Koji; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto; Fukui, Michiaki
The aim of this study was to investigate whether central systolic blood pressure (SBP) was associated with albuminuria, defined as urinary albumin excretion (UAE) ≥30 mg/g creatinine, and, if so, whether the relationship of central SBP with albuminuria was stronger than that of peripheral SBP in patients with type 2 diabetes. The authors performed a cross-sectional study in 294 outpatients with type 2 diabetes. The relationship between peripheral SBP or central SBP and UAE using regression analysis was evaluated, and the odds ratios of peripheral SBP or central SBP were calculated to identify albuminuria using logistic regression model. Moreover, the area under the receiver operating characteristic curve (AUC) of central SBP was compared with that of peripheral SBP to identify albuminuria. Multiple regression analysis demonstrated that peripheral SBP (β=0.255, Palbuminuria. In addition, AUC of peripheral SBP was significantly greater than that of central SBP to identify albuminuria (P=0.035). Peripheral SBP is superior to central SBP in identifying albuminuria, although both peripheral and central SBP are associated with UAE in patients with type 2 diabetes. © 2016 Wiley Periodicals, Inc.
Nargesi, Arash Aghajani; Shalchi, Majid; Nargesi, Reihaneh Aghajani; Sadeghpour, Niloofar; Zarifkar, Mitra; Mozaffari, Majid; Imani, Mehrnaz; Esteghamati, Alireza; Nakhjavani, Manouchehr
We aimed to study the relation between plasma levels of stress-induced heat shock protein 70 (HSPA1A) with plasminogen activator inhibitor-1 (PAI-1) and high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1), and HDL-C/Apo-A1 ratio. In a matched case-control study on patients with diabetes (40 patients with albuminuria and 40 without albuminuria matched for age, sex, and body mass index), we observed that plasma levels of HSPA1A and PAI-1 are increased in patients with albuminuria (0.55 ± 0.02 vs. 0.77 ± 0.04 ng/ml, p value albuminuria (r = 0.28; p value = 0.04), but not in those with albuminuria (r = 0.07; p value = 0.63). No association was found between HSPA1A and HDL-C, between HSPA1A and Apo-A1, or between HSPA1A and HDL-C/Apo-A1 ratio. We concluded that there is a direct correlation between plasma HSPA1A and PAI-1 levels in patients with diabetes, which is lost when they develop albuminuria.
de la Cuesta, Fernando; Baldan-Martin, Montserrat; Moreno-Luna, Rafael; Alvarez-Llamas, Gloria; Gonzalez-Calero, Laura; Mourino-Alvarez, Laura; Sastre-Oliva, Tamara; López, Juan A.; Vázquez, Jesús; Ruiz-Hurtado, Gema; Segura, Julian; Vivanco, Fernando; Ruilope, Luis M.; Barderas, Maria G.
Despite of the great advances in anti-hypertensive therapies, many patients under Renin-Angiotensin- System (RAS) suppression develop albuminuria, which is a clear indicator of therapeutic inefficiency. Hence, indicators of vascular function are needed to assess patients’ condition and help deciding future therapies. Proteomic analysis of circulating extracellular vesicles (EVs) showed two proteins, kalirin and chromodomain-helicase-DNA-binding protein 7 (CHD7), increased in albuminuric patients. A positive correlation of both with the expression of the endothelial activation marker E-selectin was found in EVs. In vitro analysis using TNFα-treated adult human endothelial cells proved their involvement in endothelial cell activation. Hence, we propose protein levels of kalirin and CHD7 in circulating EVs as novel endothelial dysfunction markers to monitor vascular condition in hypertensive patients with albuminuria. PMID:28152519
Nelson, Lærke Marie; Andreassen, Arne Kristian; Andersson, Bert; Gude, Einar; Eiskjær, Hans; Rådegran, Göran; Dellgren, Göran; Gullestad, Lars; Gustafsson, Finn
Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or CNI-free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown. We tested if measured glomerular filtration rate (mGFR, by chrome-ethylenediaminetetraacetic acid clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the Scandinavian Heart Transplant Everolimus De Novo Study With Early Calcineurin Inhibitor Avoidance trial, where de novo HTx patients (n = 115) were randomized to EVR with complete CNI elimination 7 to 11 weeks post-HTx or standard CNI immunosuppression. In 66 patients, UACR measures were available at 1 year. In 7 patients in the EVR group, a CNI was reintroduced within 12 months. Median mGFR was significantly higher in the EVR group both 1 and 3 years post-HTx (P = 0.0004 and P = 0.03, respectively). Median UACR at 1 year was significantly higher in the EVR group (P = 0.002). There was no correlation between log(UACR) at 1 year and mGFR at 1 or 3 years (r = -0.01, P = 0.9 and r = 0.15, P = 0.26, respectively) and in the EVR group between log(UACR) at 1 year and change in mGFR (Δ1-3 years) (r = 0.27, P = 0.14). Excluding patients in the EVR group in whom a CNI was reintroduced did not significantly change the results. The effects of EVR with early CNI withdrawal after HTx on albuminuria and renal function seem dissociated; hence, the clinical significance of albuminuria in this setting is uncertain and should not necessarily rule out EVR-based immunosuppression.
Deo, Rajat; Khodneva, Yulia A; Shlipak, Michael G; Soliman, Elsayed Z; Judd, Suzanne E; McClellan, William M; Brown, Todd M; Rhodes, J David; Gutiérrez, Orlando M; Shah, Sanjiv J; Albert, Christine M; Safford, Monika M
Moderate-to-severe kidney disease increases risk for sudden cardiac death (SCD). Limited studies have evaluated how mild degrees of kidney dysfunction impact SCD risk. The purpose of this study was to evaluate the association of albuminuria, which is one of the earliest biomarkers of kidney injury, and SCD. The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study is a prospective, population-based cohort of U.S. adults. Associations between albuminuria, which is categorized using urinary albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and SCD were assessed independently and in combination. After median follow-up of 6.1 years, we identified 335 SCD events. Compared to participants with ACR 30 mg/g, HR 1.56, 95% CI 1.17-2.11). In contrast, compared to the group with eGFR >90 mL/min/1.73 m 2 , the adjusted risk of SCD was significantly elevated only among those with eGFR 30 mg/g (n = 4040 [14.8%] were far more common. In the analysis that combined ACR and eGFR categories, albuminuria consistently identified individuals with eGFR ≥60 mLmin/1.73 m 2 who were at significantly increased SCD risk. Low levels of kidney injury as measured by ACR predict an increase in SCD risk. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Full Text Available Background: Kidney dysfunction and albuminuria may be associated with BMD. However, little evidence has been reported on relationships between BMD and eGFR and albuminuria. Methods: A total of 8,992 subjects aged 50 years or older participated in a survey conducted. Participants had their lumbar spine and femoral neck BMD measured by a Lunar Prodigy bone densitometer (GE, Madison, WI. Kidney function was assessed using MDRD eGFR and diagnosis of albuminuria was based on albumin-creatinine ratio. Results: ACR was negatively associated with lumbar spine and femur neck BMD in females (lumbar spine: 1.001, 0.988, 0.974 and 0.979 g/cm2, p 2, p = 0.002, but not in males, after adjusting for covariates. Additionally, eGFR was shown to be negatively associated with lumbar spine BMD after adjusting for covariates (male: 1.181, 1.166, 1.152 and 1.149 g/cm2, p = 0.001; female: 0.997, 0.980, 0.979 and 0.982 g/cm2, p = 0.005, but demonstrated no association with femur BMD. Conclusions: ACR in females was negatively associated with lumbar spine and femur neck BMD, but not in males. eGFR was negatively associated with lumbar spine BMD in both males and females.
Full Text Available Background/Aims: Albuminuria is a well-established marker of subclinical organ damage. Pulse-wave analysis (PWA employs the technique of applanation tonometry to obtain a peripheral pulse pressure waveform, from which central hemodynamic data are derived by application of the transfer function. Using PWA we can measure the subendocardial viability ratio (SEVR and ejection duration (ED. SEVR or the Buckberg index is a non-invasive estimate of myocardial workload, oxygen supply and perfusion and a measure of the ability of the arterial system to meet the heart`s energy requirements. ED is the duration of ventricular ejection. The objective of this study was to evaluate the relationship between albuminuria and PWA parameters in chronic kidney disease (CKD patients. Methods: We studied 86 CKD patients aged 59.8±13.5 years, 56 (65.1% were male. PWA analysis and 24-hour ambulatory blood pressure (24hABP monitoring were performed. The following parameters were calculated: (1 aortic augmentation index with and without correction for a heart rate of 75 (Aix and AIx@ HR75, (2 SEVR, calculated as the ratio of the diastolic pressure time index and the systolic pressure time index, (3 ED, (4 estimated central aortic systolic and diastolic pressure and (5 central aortic pulse pressure calculated as the difference between estimated aortic systolic and diastolic BP. Blood samples and urine albumin-to-creatinine ratio (UACR were analyzed; UACR values were natural log transformed (lnUACR. Results: Using CKD-EPI creatinine-cystatin C formula the eGFR in patients was 7-130 ml/min/1.73m2 (mean 32.6; SD±24.6. We found statistically significant correlation between lnUACR and cystatin C (r=0.308; P=0.004, eGFR (r=-0.219; P=0.04, hemoglobin (r=-0.255; P=0.02, phosphorus (r=0.222; P=0.04, iPTH (r=0.268; P=0.01, SEVR (r=-0.254; P=0.02 and ED (r=0.315; P=0.003. No statistically significant correlations between lnUACR and cardiac biomarkers TnI, NT-proBNP, central aortic
Pugia, M J; Lott, J A; Kajima, J; Saambe, T; Sasaki, M; Kuromoto, K; Nakamura, R; Fusegawa, H; Ohta, Y
Beginning in 1974, the Japanese Ministry of Health Welfare directed the screening of schoolchildren for proteinuria. We studied their procedure and methods in 6197 school children and also evaluated a new urine dipstick that measures albumin concentrations down to about 10 mg/l and creatinine down to about 300 mg/l. We used specimens from adult in- and outpatients to test the accuracy of the dipsticks. Based on the quantitative results, we set as cutoffs 150 mg/l for protein and or = "150" mg/l or an albumin of I "30" mg/l indicated increased risk of developing or having a genitourinary disorder. The sensitivity/specificity of the protein dipstick was 95.1%/95.5%, and the same for the albumin dipstick was 83.8%/93.8%. The cut-off for the albumin dipsticks probably should be set somewhat lower to reduce the number of false negatives and increase the sensitivity of the dipstick. When we compared the quantitative albumin to the protein dipsticks with the above cut-offs, we found the sensitivity/specificity to be 79.3%/94.4%, i.e., much like the albumin dipstick results. The many reports on the association of albuminuria and risk of renal disease recommend that screening should be done for albumin rather than protein. Based on the data from the school children, we estimate that a dipstick albumin of "30" mg/l is borderline increased risk, and that a protein dipstick of "150" mg/l is the same. If we call the dipstick "10" mg/l albumin, "30" mg/l albumin and the "150" mg/l protein results "low risk," then we estimate the prevalence of albuminuria in the school children to be about 2.1% and proteinuria to be about 4.3%. Children with these values should have a quantitative test for albumin and protein. We also tested a dipstick for creatinine and found increasing values with increasing age in both genders; the older boys had significantly higher creatinine values than the older girls and younger boys. For the albumin/creatinine ratio, we found 6028 children with a ratio
Bakris, George L; Agarwal, Rajiv; Chan, Juliana C; Cooper, Mark E; Gansevoort, Ron T; Haller, Hermann; Remuzzi, Giuseppe; Rossing, Peter; Schmieder, Roland E; Nowack, Christina; Kolkhof, Peter; Joseph, Amer; Pieper, Alexander; Kimmeskamp-Kirschbaum, Nina; Ruilope, Luis M
Steroidal mineralocorticoid receptor antagonists, when added to a renin-angiotensin system blocker, further reduce proteinuria in patients with chronic kidney disease but may be underused because of a high risk of adverse events. To evaluate the safety and efficacy of different oral doses of the nonsteroidal mineralocorticoid receptor antagonist finerenone, given for 90 days to patients with diabetes and high or very high albuminuria who are receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Randomized, double-blind, placebo-controlled, parallel-group study conducted at 148 sites in 23 countries. Patients were recruited from June 2013 to February 2014 and the study was completed in August 2014. Of 1501 screened patients, 823 were randomized and 821 received study drug. Participants were randomly assigned to receive oral, once-daily finerenone (1.25 mg/d, n = 96; 2.5 mg/d, n = 92; 5 mg/d, n = 100; 7.5 mg/d, n = 97; 10 mg/d, n = 98; 15 mg/d, n = 125; and 25 mg/d, n = 119) or matching placebo (n = 94) for 90 days. The primary outcome was the ratio of the urinary albumin-creatinine ratio (UACR) at day 90 vs at baseline. Safety end points were changes from baseline in serum potassium and estimated glomerular filtration rate. The mean age of the participants was 64.2 years; 78% were male. At baseline, 36.7% of patients treated had very high albuminuria (UACR ≥300 mg/g) and 40.0% had an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or lower. Finerenone demonstrated a dose-dependent reduction in UACR. The primary outcome, the placebo-corrected mean ratio of the UACR at day 90 relative to baseline, was reduced in the finerenone 7.5-, 10-, 15-, and 20-mg/d groups (for 7.5 mg/d, 0.79 [90% CI, 0.68-0.91; P = .004]; for 10 mg/d, 0.76 [90% CI, 0.65-0.88; P = .001]; for 15 mg/d, 0.67 [90% CI, 0.58-0.77; Ppatients with diabetic nephropathy, most receiving an angiotensin-converting enzyme
David A Shoham
Full Text Available BACKGROUND: End-stage renal disease rates rose following widespread introduction of high fructose corn syrup in the American diet, supporting speculation that fructose harms the kidney. Sugar-sweetened soda is a primary source of fructose. We therefore hypothesized that sugary soda consumption was associated with albuminuria, a sensitive marker for kidney disease. METHODOLOGY/PRINCIPAL FINDINGS: Design was a cross-sectional analysis. Data were drawn from the National Health and Nutrition Examination Survey (NHANES, 1999-2004. The setting was a representative United States population sample. Participants included adults 20 years and older with no history of diabetes mellitus (n = 12,601; after exclusions for missing outcome and covariate information (n = 3,243, the analysis dataset consisted of 9,358 subjects. Exposure was consumption of two or more sugary soft drinks, based on 24-hour dietary recall. The main outcome measure was Albuminuria, defined by albumin to creatinine ratio cutpoints of >17 mg/g (males and >25 mg/g (females. Logistic regression adjusted for confounders (diet soda, age, race-ethnicity, gender, poverty. Interactions between age, race-ethnicity, gender, and overweight-obesity were explored. Further analysis adjusted for potential mediators: energy intake, basal metabolic rate, obesity, hypertension, lipids, serum uric acid, smoking, energy expenditure, and glycohemoglobin. Alternative soda intake definitions and cola consumption were employed. RESULTS: Weighted albuminuria prevalence was 11%, and 17% consumed 2+ sugary soft drinks/day. The confounder-adjusted odds ratio for sugary soda was 1.40 (95% confidence interval: 1.13, 1.74. Associations were modified by gender (p = 0.008 and overweight-obesity (p = 0.014. Among women, the OR was 1.86 (95% CI: 1.37, 2.53; the OR among males was not significant. In the group with body mass under 25 kg/m(2, OR = 2.15 (95% confidence interval: 1.42, 3.25. Adjustment for potential
Full Text Available Micro-albuminuria has been well established as one of the risk factors of metabolic syndrome (MetS. However, the association of MetS and its components with low-grade albuminuria among those with normal urinary albumin excretion has not been clearly elucidated in Chinese population.A cross-sectional study was conducted among 9,579 participants with normal urinary albumin excretion, who were recruited from Jia Ding District, Shanghai, China. The single-void first morning urine sample was collected for urinary albumin and creatinine measurements, and urinary albumin-to-creatinine ratio (UACR was calculated as urinary albumin divided by creatinine. Low-grade albuminuria was classified as sex-specific upper UACR quartile in this population. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence of MetS and its components increased across the UACR quartiles (all P trend <0.01. A multivariable adjusted logistic regression analysis revealed that the prevalence of MetS was gradually elevated according to the UACR quartiles (adjusted odds ratios [ORs] were 1.14, 1.24 and 1.59 for UACR quartiles 2, 3 and 4, compared with the lowest quartile; P trend<0.0001. In the further stratified logistic regression analyses, the associations between low-grade albuminuria and MetS were significant in both sex strata (male and female, both age strata (<60 and ≥60 years, both body mass index strata (<24 and ≥24 kg/m(2, and both diabetes strata (yes and no. Compared to the lowest UACR quartile, the participants in the highest quartile of UACR had the highest prevalence of central obesity (OR = 1.43; 95%CI = 1.25-1.63, high blood pressure (OR = 1.64; 95%CI = 1.43-1.87, hyperglycemia (OR = 1.52; 95%CI = 1.30-1.78 and high triglycerides (OR = 1.19; 95%CI = 1.04-1.37.Low-grade albuminuria was significantly associated with the increasing prevalence of MetS and its
Zhang, Zhi; Li, Ziqiang; Cao, Kaijin; Fang, Dailong; Wang, Fazhan; Bi, Gang; Yang, Jian; He, Yingju; Wu, Jinhui; Wei, Yuquan; Song, Xiangrong
Blockade of the renin-angiotensin II (Ang II) system by AT1 blockers (ARBs) and angiotensin-converting enzyme inhibitors retards the progression of chronic kidney disease (CKD) by reducing albuminuria/proteinuria. However, many patients with CKD suffer from residual albuminuria/proteinuria, which is an independent risk factor for CKD progression. The aim of the current study is to investigate the effect of pitavastatin, one of the adjunctive agents to ARBs, on the reduction of albuminuria/proteinuria and further renoprotection mediated by telmisartan in spontaneously hypertensive rats. Forty-two-week-old spontaneously hypertensive rats were grouped randomly and received 8 weeks of treatments with vehicle, telmisartan, pitavastatin or a combination of telmisartan and pitavastatin. Both albuminuria and proteinuria were inhibited significantly in the telmisartan-treated group, but an obviously residual albuminuria was maintained. The combination treatment with telmisartan and pitavastatin displayed a more effective decrease in albuminuria and proteinuria, even to the normal level. Enhanced nephroprotection was also observed in this combination group, which was independent of the cholesterol-lowering effects. Further mechanistic studies revealed that the combination therapy greatly attenuated the expression of intrarenal Ang II and AT1, thereby decreasing the activation of TGF-β-Smad and NF-κB and inhibiting fibrosis and inflammation. Adjunctive therapy with pitavastatin dramatically reduced residual albuminuria/proteinuria and enhanced nephroprotection, likely by downregulating the expression of intrarenal Ang II and AT1. It could be concluded that statins might be a promising adjunctive therapeutic agent to conventional ARB treatment in hypertensive renal damage.
Yee, Marianne E; Lane, Peter A; Archer, David R; Joiner, Clinton H; Eckman, James R; Guasch, Antonio
Sickle cell nephropathy begins with hyperfiltration and microalbuminuria and may progress to renal failure. The aim of this study was to determine the effects of losartan on glomerular function and albumin excretion in sickle cell anemia (SCA). Individuals with SCA on hydroxyurea with persistent albuminuria were enrolled in a 1-year study of losartan. Glomerular filtration rate (GFR) measured by iohexol clearance, albumin excretion rate (AER), and fractional clearance of dextran were assessed at baseline, short-term (1-2month), and long-term (≥12month) intervals. Twelve subjects (6 microalbuminuria, 6 macroalbuminuria) completed short-term studies; 8 completed long-term studies. Baseline GFR was 112ml/min/1.73m 2 (71-147ml/min/1.73m 2 ). AER decreased significantly at the short-term (median decrease -134 mcg/min, p=0.0063). GFR was not significantly-different at short-term or long-term intervals. Dextran clearance improved for diameters smaller than albumin (therapy for ≥1year in sickle nephropathy results in lower albumin excretion with stable GFR. Filtration of neutral molecules ≥36Å was not changed by losartan, suggesting that the effect of losartan is a mechanism other than alteration of glomerular filtration size-selectivity. Copyright © 2017 Elsevier Inc. All rights reserved.
Fagerudd, J A; Pettersson-Fernholm, K J; Riska, M K; Grönhagen-Riska, C; Groop, P H
In non-insulin-dependent diabetes mellitus (NIDDM), there is a clustering of an elevated urinary albumin excretion rate (U-AER) in nondiabetic relatives of albuminuric patients. Whether this is also the case in insulin-dependent diabetes mellitus (IDDM) is unknown. Overnight U-AER was measured in 186 nondiabetic first-degree relatives of 80 IDDM patients with diabetic nephropathy (U-AER > 200 microg/min or 300 mg/24 hours; DN+) and in 52 relatives of 25 IDDM patients without nephropathy (U-AER therapy, and smoking habits. No difference was found in overnight U-AER between relatives of patients with DN+ and DN- [median (range), 3.4 (0.1 to 372) vs. 4.0 (0.2 to 62) microg/min, respectively, P = NS]. The proportion of relatives with a U-AER = 10 microg/min was 12% in DN+ compared with 8% in DN- (P = NS). Among relatives of DN+, those with antihypertensive treatment (AHT+) had higher U-AER compared with those without [AHT+ vs. AHT-, 5.0 (0.5 to 372) vs. 3.4 (0.1 to 26.5) microg/min, P AER in nondiabetic relatives of patients with nephropathy. This is different from what has been reported in NIDDM, and suggests heterogeneity in the genesis of albuminuria in diabetes.
Laura A. Maile
Full Text Available This study determined if blocking ligand occupancy of the αVβ3 integrin could inhibit the pathophysiologic changes that occur in the early stages of diabetic nephropathy (DN. Diabetic rats were treated with either vehicle or a monoclonal antibody that binds the β3 subunit of the αVβ3 integrin. After 4 weeks of diabetes the urinary albumin to creatinine ratio (UACR increased in both diabetic animals that subsequently received vehicle and in the animals that subsequently received the anti-β3 antibody compared with control nondiabetic rats. After 8 weeks of treatment the UACR continued to rise in the vehicle-treated rats; however it returned to levels comparable to control nondiabetic rats in rats treated with the anti-β3 antibody. Treatment with the antibody prevented the increase of several profibrotic proteins that have been implicated in the development of DN. Diabetes was associated with an increase in phosphorylation of the β3 subunit in kidney homogenates from diabetic animals, but this was prevented by the antibody treatment. This study demonstrates that, when administered after establishment of early pathophysiologic changes in renal function, the anti-β3 antibody reversed the effects of diabetes normalizing albuminuria and profibrotic proteins in the kidney to the levels observed in nondiabetic control animals.
Kornhauser, C; Malacara, J-M; Macías-Cervantes, M-H; Rivera-Cisneros, A-E
Exercise may be useful to detect patients with diabetes prone to develop persistent microalbuminuria. We studied the relationship between exercise intensity, measured as maximal oxygen consumption (VO(2)max), and microalbuminuria in patients with Type 1 diabetes mellitus patients. We studied 10 patients, age range 10-18 years, with Type 1 diabetes who were normotensive and normoalbuminuric, with less than 10 years since diagnosis. Patients had normal renal function, without infections or clinical evidence of complications. Metabolic control was intensively adjusted in all patients. They underwent three consecutive physical exercise tests, reaching 100, 80 and 60% of the maximal cardiac frequency response. Eight patients had adequate to regular metabolic control. All patients had lower than predicted VO(2)max values. At 60%, only three patients showed microalbuminuria in excess of 20 μg/min, two of them had inadequate metabolic control. Post-exercise microalbuminuria exceeded normal values in nine, seven and three patients when submitted to 100, 80 and 60% of exercise intensity, respectively. Microalbuminuria increased with exercise intensity. Sex, body composition and VO(2)max were the main factors associated with microalbuminuria. The prognostic significance of albuminuria induced by intense exercise in these subjects with Type 1 diabetes is not yet known. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.
Muntner, Paul; Woodward, Mark; Carson, April P; Judd, Suzanne E; Levitan, Emily B; Mann, Devin; McClellan, William; Warnock, David G
Background The prevalence of albuminuria in the general population is high, but awareness of it is low. Therefore, we sought to develop and validate a self-assessment tool that allows individuals to estimate their probability of having albuminuria. Study Design Cross-sectional study Setting & Participants The population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study for model development and the National Health and Nutrition Examination Survey 1999-2004 (NHANES 1999-2004) for model validation. US adults ≥ 45 years of age in the REGARDS study (n=19,697) and NHANES 1999-2004 (n=7,168) [nijsje 1]Factor Candidate items for the self-assessment tool were collected using a combination of interviewer- and self-administered questionnaires. Outcome Albuminuria was defined as a urinary albumin to urinary creatinine ratio ≥ 30 mg/g in spot samples. Results Eight items were included in the self-assessment tool (age, race, gender, current smoking, self-rated health, and self-reported history of diabetes, hypertension, and stroke). These items provided a c-statistic of 0.709 (95% CI, 0.699 – 0.720) and a good model fit (Hosmer-Lemeshow chi-square p-value = 0.49). In the external validation data set, the c-statistic for discriminating individuals with and without albuminuria using the self-assessment tool was 0.714. Using a threshold of ≥ 10% probability of albuminuria from the self-assessment tool, 36% of US adults ≥ 45 years of age in NHANES 1999-2004 would test positive and be recommended screening. The sensitivity, specificity, and positive and negative predictive values for albuminuria associated with a probability ≥ 10% were 66%, 68%, 23% and 93%, respectively. Limitations Repeat urine samples were not available to assess the persistency of albuminuria. Conclusions Eight self-report items provide good discrimination for the probability of having albuminuria. This tool may encourage individuals with a high probability to request
Hong, Jae Won; Ku, Cheol Ryong; Noh, Jung Hyun; Kim, Dong-Jun
Although the associations between albuminuria and renal and cardiovascular diseases, including diabetes and hypertension, have been extensively studied, few studies have investigated the association between albuminuria and hearing impairment. In this study, we assessed the relationship between albuminuria and hearing impairment in 9786 adult Korean subjects, using data from the Korea National Health and Nutrition Examination Survey (KNHANES) performed in 2011-2012. The range of urinary albumin-to-creatinine ratio (UACR) was divided into 4 grades: grade 1 (first tertile of low-grade albuminuria [LGA]), 0.00 to 1.99 mg/g Cr; grade 2 (second tertile of LGA), 2.00 to 5.49 mg/g Cr; grade 3 (third tertile of LGA), 5.50 to 29.99 mg/g Cr; grade 4 (albuminuria), ≥30.00 mg/g Cr.The age- and sex-adjusted weighted UACR was higher in subjects with hearing impairment compared with those without hearing impairment (26.2 ± 4.7 mg/g Cr vs 14.1 ± 1.5 mg/g Cr, P = 0.020). The age- and sex-adjusted weighted prevalence of albuminuria was also higher in subjects with hearing impairment compared with subjects without hearing impairment. (8.3 ± 0.9% vs 5.8 ± 0.4%, P = 0.013) The age- and sex-adjusted weighted percentage of hearing impairment increased as UACR increased (18.0% ± 0.6%, 20.0% ± 0.8%, 22.2% ± 0.9%, 25.3% ± 2.0%, respectively; P albuminuria, with age, sex, tobacco use, heavy alcohol use, educational background, occupational noise exposure, obesity, hypertension, diabetes, total serum cholesterol, and estimated glomerular filtration rate (eGFR) albuminuria is associated with hearing impairment in the Korean general population, using nationally representative data. Screening for albuminuria would allow for interventions for the prevention of hearing impairment.
BACKGROUND: The aims of this study were to examine the relationship between proteinuria and albuminuria and to assess the equivalence between the albumin to creatinine ratio (ACR) and the protein to creatinine ratio (PCR) at the cut-offs recommended by the National Institute for Health and Clinical Excellence (NICE) guidance on chronic kidney disease. The sensitivity and specificity of the reagent strips used in our laboratory for the detection of clinical proteinuria was also assessed. METHODS: Urine samples (n = 117) were screened for protein using the Bayer Multistix 10SG and read manually. Urinary total protein and creatinine was measured on the Roche P Modular by the benzethonium chloride and kinetic Jaffe methods, respectively. Urinary albumin was measured by immunoturbidimetry on the Roche Cobas Mira. RESULTS: The relationship between urinary protein and albumin loss was non-linear (P < 0.05). As urinary protein loss increased the percentage of albumin to total protein increased. At the NICE guidance recommended cut-offs for clinical proteinuria (ACR > or =30 mg\\/mmol and PCR > or =50 mg\\/mmol) there was one discordant result between ACR and PCR (ACR <30 mg\\/mmol and PCR >50 mg\\/mmol). The Bayer Multistix 10SG had a sensitivity and specificity of 97% and 62%, respectively, for the detection of clinical proteinuria compared with ACR. CONCLUSIONS: The proportion of urinary total protein attributable to albumin changes with concentration. There was only one discordant result between ACR and PCR: therefore either ratio may be used for the identification of clinical proteinuria. As a screening test for proteinuria, the Bayer Multistix 10SG had an acceptable sensitivity but poor specificity.
Chang, Alex R; Miller, Edgar R; Anderson, Cheryl A; Juraschek, Stephen P; Moser, Melissa; White, Karen; Henry, Bobbie; Krekel, Caitlin; Oh, Susan; Charleston, Jeanne; Appel, Lawrence J
Little is known about the effects of phosphorus additives on patients with kidney disease. Randomized, double-blind, crossover trial. 31 adults with early stages of presumed chronic kidney disease (estimated glomerular filtration rate ≥ 45mL/min/1.73m 2 ; urine albumin-creatinine ratio sex-specific cutoff points: men ≥ 17mg/g, women ≥ 25mg/g). Higher versus lower phosphorus intake for 3 weeks. Higher phosphorus intake was achieved by the addition of commercially available diet beverages and breakfast bars to diet. Change in 24-hour urine albumin excretion and plasma fibroblast growth factor 23 level. Two 24-hour urine collections and a single fasting blood draw at the end of each period. Mean baseline values for phosphorus intake, 24-hour urine phosphorus excretion, and estimated glomerular filtration rate were 1,113±549 (SD) mg/d, 688±300mg/d, and 74.6±22.0mL/min/1.73m 2 . Median urine albumin excretion of 82.7 (IQR, 39.6-174.1) mg/d. Although phosphorus intake from study products increased by 993mg/d (Pphosphorus additive period, background phosphorus intake decreased by 151mg/d (P=0.004). Higher phosphorus additive consumption increased 24-hour urine phosphorus excretion by 505 (95% CI, 381 to 629) mg/d (Pphosphorus food additives did not significantly increase albuminuria. Further studies are needed to confirm these results. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Carrero, Juan Jesús; Grams, Morgan E; Sang, Yingying; Ärnlöv, Johan; Gasparini, Alessandro; Matsushita, Kunihiro; Qureshi, Abdul R; Evans, Marie; Barany, Peter; Lindholm, Bengt; Ballew, Shoshana H; Levey, Andrew S; Gansevoort, Ron T; Elinder, Carl G; Coresh, Josef
Current guidelines for chronic kidney disease (CKD) recommend using albuminuria as well as estimated glomerular filtration rate (eGFR) to stage CKD. However, CKD progression is solely defined by change in eGFR with little regard to the risk implications of change in albuminuria. This is an observational study from the Stockholm CREAtinine Measurements (SCREAM) project, a health care utilization cohort from Stockholm, Sweden, with laboratory measures from 2006-2011 and follow-up through December 2012. Included were 31,732 individuals with two or more ambulatory urine albumin to creatinine ratio (ACR) tests. We assessed the association between change in ACR during a baseline period of 1, 2, or 3 years and end-stage renal disease (ESRD) or death. Using a 2-year baseline period, there were 378 ESRD events and 1712 deaths during a median of 3 years of follow-up. Compared to stable ACR, a 4-fold increase in ACR was associated with a 3.08-times (95% confidence interval 2.59 to 3.67) higher risk of ESRD while a 4-fold decrease in ACR was associated with a 0.34-times (0.26 to 0.45) lower risk of ESRD. Similar associations were found in people with and without diabetes mellitus, with and without hypertension, and also when adjusted for the change in eGFR during the same period. The association between change in ACR and mortality was weaker: ACR increase was associated with mortality, but the relationship was largely flat for ACR decline. Results were consistent for 1-, 2-, and 3-year ACR changes. Thus, changes in albuminuria are strongly and consistently associated with the risk of ESRD and death. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Full Text Available The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE in patients with diabetes. Skin autofluorescence (AF assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/ and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P<0.0001. Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r=0.37, P<0.02 and r=0.60, P<0.0001, but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R2=0.38. Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established.
Full Text Available BACKGROUND: Hyperuricemia is now regarded as a risk factor for cardiovascular disease. Micro-albuminuria is associated with increased risk for cardiovascular disease and chronic kidney disease. We hypothesized that elevated serum uric acid (UA is associated with development of micro-albuminuria in the general population. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a community-based prospective cohort study. A total of 1862 subjects from southern Taiwan, all older than 40 years, were screened and 993 of these participants without micro-albuminuria were followed for 4 years. Urinary albumin-to-creatinine ratio was measured two times per year. A multiple linear regression model indicated that serum UA was independently associated with ln(ACR after adjustment for 8 factors (age, sex, and 6 metabolic metrics (β = 0.194, p<0.01. Logistic regression analysis indicated that each 1 mg/dL increase of UA was associated with a 1.42-fold increased risk of micro-albuminuria after adjustment for the same 8 factors (OR = 1.42, 95% CI: 1.27-1.59, p<0.01. A Cox regression model using subjects with serum UA less than 5 mg/dL as reference group indicated higher hazard ratios (HRs only found in subjects with serum UA more than 7 mg/dL (HR = 3.54, 95% CI: 2.11-5.93, p<0.01 and not in subjects with serum UA of 5 to 7 mg/dL (HR = 1.30, 95% CI: 0.82-2.07, p = 0.15. CONCLUSION: Hyperuricemia is significantly associated with micro-albuminuria in middle-aged and elderly males and females from a general population in Taiwan. Elevated serum UA is an independent predictor for development of micro-albuminuria in this population.
Dorajoo, Sreemanee Raaj; Ng, Joceline Shi Ling; Goh, Jessica Hui Fen; Lim, Su Chi; Yap, Chun Wei; Chan, Alexandre; Lee, Joyce Yu Chia
To evaluate the association between HbA1c coefficient of variation (HbA1c-CV) and 3-year new-onset albuminuria risk. A retrospective cohort study involving 716 normoalbuminuric type 2 diabetes patients was conducted between 2010 and 2014. HbA1c-CV was used to categorize patients into low, moderate or high variability groups. Multivariate logistic models were constructed and validated. Integrated discrimination (IDI) and net reclassification (NRI) improvement indices were used to quantify the added predictive value of HbA1c-CV. The mean age of our cohort was 56.1±12.9years with a baseline HbA1c of 8.3±1.3%. Over 3-years of follow-up, 35.2% (n=252) developed albuminuria. An incremental risk of albuminuria was observed with moderate (6.68-13.43%) and high (above 13.44%) HbA1c-CV categories demonstrating adjusted odds ratios of 1.63 (1.12-2.38) and 3.80 (2.10-6.97) for 3-year new-onset albuminuria, respectively. Including HbA1c-CV for 3-year new-onset albuminuria prediction improved model discrimination (IDI: 0.023, NRI: 0.293, palbuminuria. Together with mean HbA1c, baseline urine albumin-to-creatinine ratio and presence of hypertension, accurate 3-year new-onset albuminuria prediction may be possible. Copyright © 2017 Elsevier B.V. All rights reserved.
Toyama, Tadashi; Furuichi, Kengo; Ninomiya, Toshiharu; Shimizu, Miho; Hara, Akinori; Iwata, Yasunori; Kaneko, Shuichi; Wada, Takashi
Background Precise effects of albuminuria and low estimated glomerular filtration rate (eGFR) on cardiovascular mortality, all-cause mortality, and renal events in diabetic patients are uncertain. Materials and Methods A systematic review was conducted of the literature through MEDLINE, EMBASE, and CINHAL from 1950 to December 2010. Cohort studies of diabetic patients providing adjusted relative risk (RR) of albuminuria and eGFR for risks of cardiovascular mortality, all-cause mortality, and renal events were selected. Two reviewers screened abstracts and full papers of each study using standardized protocol. Results We identified 31 studies fulfilling the criteria from 6546 abstracts. With regard to the risk of cardiovascular mortality, microalbuminuria (RR 1.76, 95%CI 1.38–2.25) and macroalbuminuria (RR 2.96 95%CI 2.44–3.60) were significant risk factors compared to normoalbuminuria. The same trends were seen in microalbuminuria (RR 1.60, 95%CI 1.42–1.81), and macroalbuminuria (RR 2.64, 95%CI 2.13–3.27) for the risk of all-cause mortality, and also in microalbuminuria (RR 3.21, 95%CI 2.05–5.02) and macroalbuminuria (RR 11.63, 95%CI 5.68–23.83) for the risk of renal events. The magnitudes of relative risks associated with low eGFR along with albuminuria were almost equal to multiplying each risk rate of low eGFR and albuminuria. No significant factors were found by investigating potential sources of heterogeneity using subgroup analysis. Conclusions High albuminuria and low eGFR are relevant risk factors in diabetic patients. Albuminuria and low eGFR may be independent of each other. To evaluate the effects of low eGFR, intervention, or race, appropriately designed studies are needed. PMID:24147148
Lindhardt, Morten; Persson, Frederik; Oxlund, Christina; Jacobsen, Ib A; Zürbig, Petra; Mischak, Harald; Rossing, Peter; Heerspink, Hiddo J L
The mineralocorticoid receptor antagonist spironolactone significantly reduces albuminuria in patients with diabetes. Prior studies have shown large between-patient variability in albuminuria treatment response. We previously developed and validated a urinary proteomic classifier that predicts onset and progression of chronic kidney disease. Here, we tested whether the proteomic classifier based on 273 urinary peptides (CKD273) predicts albuminuria response to spironolactone treatment. We performed a post hoc analysis in a double-blind randomized clinical trial with allocation to either spironolactone 12.5-50 mg/day (n = 57) or placebo (n = 54) for 16 weeks. Patients were diagnosed with type 2 diabetes and resistant hypertension. Treatment was an adjunct to renin-angiotensin system inhibition. Primary endpoint was the percentage change in urine albumin to creatinine ratio (UACR). Capillary electrophoresis mass spectrometry was used to quantify urinary peptides at baseline. The previously validated combination of 273 known urinary peptides was used as proteomic classifier. Spironolactone reduced UACR relative to placebo by 50%, although with a large between-patient variability in UACR response (5th to 95th percentile, 7 to 312%). An interaction was detected between CKD273 and treatment assignment (β = -1.09, P = 0.026). Higher values of CKD273 at baseline were associated with a larger reduction in UACR in the spironolactone group (β = -0.70, P = 0.049), but not in the placebo group (β = 0.39, P = 0.25). Stratified in tertiles of baseline CKD273, reduction in UACR was greater in the highest tertile, 63% (95% confidence interval: 35-79%), as compared with the two other tertiles combined, 16% (-17 to 40%) (P = 0.011). A urinary proteomics classifier can be used to identify individuals with type 2 diabetes who are more likely to show an albuminuria-lowering response to spironolactone treatment. These results suggest that urinary
Relationship between Kidney Dysfunction and Ischemic Stroke Outcomes: Albuminuria, but Not Estimated Glomerular Filtration Rate, Is Associated with the Risk of Further Vascular Events and Mortality after Stroke.
Lee, Seung-Jae; Lee, Dong-Geun
Estimated glomerular filtration rate (eGFR) and albuminuria are known to be associated with ischemic stroke outcomes. In this study, we investigated the longitudinal relationships of the two markers with mortality, vascular events and functional outcomes in a stroke cohort. A total of 295 patients with acute ischemic stroke were prospectively recruited in a single center between May 2012 and February 2015. Renal dysfunction was defined as a decreased eGFR (albuminuria (urine albumin-to-creatinine ratio ≥ 30 mg/g). Good functional outcome at 6 months was defined as a modified Rankin scale score ≤ 2, and the occurrence of major vascular events (stroke, acute coronary syndrome or peripheral artery occlusion) or death was monitored. The associations between renal dysfunction and mortality, major vascular events, and 6-month functional outcome were evaluated by the Cox proportional hazards model and logistic regression analysis. Unadjusted and adjusted hazards ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were obtained. A Kaplan-Meier survival curve for composite adverse events (major vascular events or death) was also computed according to the presence or absence of albuminuria. Albuminuria, not eGFR, was significantly associated with mortality (P = 0.028; HR 2.15; 95% CI 1.09-4.25) and major vascular events (P = 0.044; HR 2.24; 95% CI 1.02-4.94) in the multivariate Cox proportional hazards models adjusting for age, sex, diabetes, hypertension, current smoking, atrial fibrillation, previous stroke, alcohol history, initial National Institutes of Health Stroke Scale (NIHSS) score and eGFR. In addition, albuminuria was negatively associated with 6-month functional outcome in the multivariate logistic regression analysis adjusting for age, sex, diabetes, hypertension, current smoking, atrial fibrillation, previous stroke, alcohol history and eGFR (P = 0.001; OR 0.36; 95% CI 0.20-0.65), but the association disappeared when NIHSS score was
João Soares Felício
Full Text Available BackgroundSome studies suggest an association between diabetic kidney disease (DKD and vitamin D (VD, but there is no data about the effect of high dose of VD on DKD in type 1 diabetes mellitus (T1DM. Our pilot study aims to evaluate albuminuria reduction in patients with T1DM supplemented with high dose of VD.Methods22 patients received doses of 4,000 and 10,000 IU/day of cholecalciferol for 12 weeks according to patient’s previous VD levels. They were submitted to continuous glucose monitoring system, 24 hours ambulatory blood pressure monitoring and urine albumin-to-creatinine ratio before and after VD supplementation.ResultsThere was a reduction of DKD prevalence at the end of the study (68 vs 32%; p = 0.05, with no changes on insulin doses, glycated hemoglobin, glycemic variability and blood pressure values. A correlation between percentage variation of VD levels (ΔVD and albuminuria at the end of the study was presented (r = −0.5; p < 0.05. Among T1DM patients with DKD at the beginning of the study, 8/13 (62% had their DKD stage improved, while the other five ones (38% showed no changes (p < 0.05.ConclusionOur pilot study suggests an association between VD high dose supplementation, lower prevalence and improvement in stages of DKD in T1DM.
Mervi E. Hyvönen
Full Text Available The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.
Full Text Available Background/Aims: While experimental models that emulate diabetic nephropathy are valuable tools for elucidating pathogenetic mechanisms and developing novel therapies, existing models imperfectly recapitulate human disease. In diabetes, hyperglycemia and hemodynamic forces act in concert to induce renal injury. Accordingly, in the present study, we combined streptozotocin-induced diabetes with surgical ablation of 5/6 of the kidney mass with the aim of evaluating their additive effects on renal function and glomerular morphology. Methods: Female F344 rats were randomized to undergo subtotal nephrectomy (SNx either at baseline or following 4 weeks of diabetes. Results: In comparison to sham rats, rats with diabetes or rats after SNx surgery, diabetic subtotally nephrectomized (DM-SNx rats demonstrated an increase in systolic blood pressure, glomerular volume and mesangial matrix. Albuminuria was synergistically increased by hyperglycemia and renal mass ablation associated with decreased nephrin expression. In contrast, glomerular capillary rarefaction and glomerular filtration rate were similarly reduced in SNx and DM-SNx rats. Conclusion: The DM-SNx rat recapitulates some of the features of human disease, most notably augmented albuminuria. Since this model avoids the deletion or overexpression of gene(s linked to the pathogenesis of nephropathy, the DM-SNx rat model represents a complementary tool for the trial of novel therapies.
Wang, Huaiyu; Yang, Li; Wang, Fang; Zhang, Luxia
Screening for persistent albuminuria among the high-risk population is important for early detection of CKD while studies regarding screening protocol and related cost-effectiveness analysis are limited. This study explored a feasible and cost-efficient screening strategy for detecting persistent albuminuria among the high-risk population. A cohort study including 157 clinically stable outpatients with a risk factor of CKD and whose laboratory tests revealed an albumin-creatinine-ratio (ACR) between 30 and 300 mg/g of creatinine during the previous 12 months was conducted to assess the validity of alternative screening strategies. Each participant collected three first morning urine samples in three consecutive months. These samples were labeled as DAY-1, MONTH-2 and MONTH-3. In the first month, a random spot sample in the afternoon of the first day and another morning sample on the second day were collected and labeled as Random and DAY-2. Persistent albuminuria was defined by abnormal ACR (≥30 mg/g creatinine) for DAY-1, MONTH-2 and MONTH-3. Alternative strategies were DAY-1; Random; DAY-1 + Random; DAY-1 + DAY-2; and DAY-1 + Random + DAY-2. To evaluate the economic performance of those alternative strategies, a hybrid decision tree/Markov model was developed based on the cohort study to simulate both clinical and cost-effectiveness outcomes. Sensitivity analyses were conducted to investigate assumptions of the model and to examine the model's robustness. Altogether, 82 patients exhibited persistent albuminuria. All of the five strategies had sensitivity higher than 90%. Of these strategies, Random had the lowest specificity (46.7%), and DAY-1 + Random + DAY-2 had the highest specificity (81.3%). Estimated cost for each quality adjusted life year (QALYs) gained were ¥112,335.88 for DAY-1 + Random, ¥8134.69 for Random and ¥10,327.99 for DAY-1 + Random + DAY-2. When compared with DAY-1 strategy, the sensitivity and
Full Text Available BACKGROUND Snakebites and accidents caused by venomous arthropods are important public health problem. Envenomation by snakebite, independently of the species responsible for the bite, enforces medical emergencies since different organs and tissues can be affected at the same time. The hypothesis for pathogenesis of venom-induced AKI includes both a direct cytotoxic action of the venom on different renal structures and a secondary response of the whole organism resulting from systemic envenomation. The aim of the study is to assess the early predictors for acute kidney injury due to snakebite by comparing it with the patients who had not developed acute kidney injury after the snakebite. MATERIALS AND METHODS A prospective comparative study was undertaken at the Government Medical College Hospital, Salem, during the period of April 2015-March 2016. A total of 115 patients were included in the study in which 42 patients were having AKI due to snakebite and 73 patients were without AKI after snakebite. Haematological and biochemical investigations were performed in all patients, including haemoglobin, complete and differential leukocyte counts, platelet count, peripheral blood smear, bleeding and clotting times, Prothrombin Time (PT and Activated Partial Thromboplastin Time (APTT, blood urea, serum creatinine, serum electrolytes, liver function tests and urine examination. RESULTS Thrombocytopenia and albuminuria, which is to be considered as the major early marker for acute kidney injury among snakebite patients was found to be present in 85.7% and 100% in our patients with AKI whereas it was only 1.3% and 4.1% respectively among the patients without AKI and the difference was found to be statistically significant (p<.05. The survival rate was higher among the patients without AKI when compared to the patients with AKI and the difference is statistically significant (p<.05. CONCLUSION Early detection of AKI due to snakebite should be assessed by
Full Text Available Fatty acid-binding protein 4 (FABP4/A-FABP/aP2 is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP, in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated.Subjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n = 392, male/female: 166/226 were enrolled. Urinary FABP4 (U-FABP4 and urinary albumin-to-creatinine ratio (UACR were measured. Change in estimated glomerular filtration rate (eGFR was followed up one year later.In 93 (23.7% of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4, triglycerides, hemoglobin A1c (HbA1c, urinary FABP1 (U-FABP1 and UACR (r = 0.360, p<0.001. Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile.Urinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.
Astor, Brad C; Matsushita, Kunihiro; Gansevoort, Ron T
We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected...
Gaede, P; Poulsen, H E; Parving, H H
AIMS: Elevated levels of urinary albumin excretion rate (AER) predict high risk for progressing to end-stage renal disease. In streptozotocin-induced diabetes, supplementation with vitamin C or E reduces albuminuria and glomerular hypertrophy. We tested the hypothesis that supplementation of both...
Olde Engberink, Rik H. G.; Heerspink, Hiddo J. L.; de Zeeuw, Dick; Vogt, Liffert
It has been suggested that sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status,
Engberink, Rik H. G. Olde; Heerspink, Hiddo J. L.; de Zeeuw, Dick; Vogt, Liffert
AIMS: It has been suggested that sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL
Martínez, María A; Garcia-Puig, Juan; Loeches, Maria P; Mateo, Maria C; Utiel, Isaías; Torres, Rosa
To compare the efficacy of two strategies of blood pressure (BP) measurement-based follow-up in hypertension and albuminuria control. Multicentre, prospective, randomised, open trial with a parallel-group design. Nineteen primary care centres and a hospital clinic participated. Adult type 2 diabetics with systolic BP ≥140mmHg without relevant renal disease were randomised to one of two follow-up strategies: 1) standard follow up, with a clinic BP target <140/90mmHg and 2) self-monitoring home BP (SMHBP)-based follow up, with a BP target <135/85mmHg. Biochemical standard blood variables, albuminuria, and 24-h ambulatory BP monitoring were performed at entry, 12 and 24 months. The main outcome measurement was 24-h ambulatory systolic BP variation. Albuminuria change was analysed as a secondary outcome. 116 patients were analysed (mean age: 66.8 years). Mean systolic ambulatory 24- h BP change in two years was 3.9mmHg (95% CI 1.8-6.1). We did not find significant differences between both groups (p=0.706). Similarly, no differences were found when we compared other ambulatory BP values. Initial albuminuria was similar in both groups and did not significantly changed throughout the follow-up period. In type 2 diabetics without relevant nephropathy a SMHBP- based follow up was equivalent to a standard clinic-based BP follow up in BP and albuminuria control. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.
Zanchi, Cristina; Macconi, Daniela; Trionfini, Piera; Tomasoni, Susanna; Rottoli, Daniela; Locatelli, Monica; Rudnicki, Michael; Vandesompele, Jo; Mestdagh, Pieter; Remuzzi, Giuseppe; Benigni, Ariela; Zoja, Carlamaria
Renal fibrosis is a common complication of diabetic nephropathy and is a major cause of end-stage renal disease. Despite the suggested link between renal fibrosis and microRNA (miRNA) dysregulation in diabetic nephropathy, the identification of the specific miRNAs involved is still incomplete. The aim of this study was to investigate miRNA profiles in the diabetic kidney and to identify potential downstream targets implicated in renal fibrosis. miRNA expression profiling was investigated in the kidneys of 8-month-old Zucker diabetic fatty (ZDF) rats during overt nephropathy. Localisation of the most upregulated miRNA was established by in situ hybridisation. The candidate miRNA target was identified by in silico analysis and its expression documented in the diabetic kidney associated with fibrotic markers. Cultured tubule cells served to assess which of the profibrogenic stimuli acted as a trigger for the overexpressed miRNA, and to investigate underlying epigenetic mechanisms. In ZDF rats, miR-184 showed the strongest differential upregulation compared with lean rats (18-fold). Tubular localisation of miR-184 was associated with reduced expression of lipid phosphate phosphatase 3 (LPP3) and collagen accumulation. Transfection of NRK-52E cells with miR-184 mimic reduced LPP3, promoting a profibrotic phenotype. Albumin was a major trigger of miR-184 expression. Anti-miR-184 counteracted albumin-induced LPP3 downregulation and overexpression of plasminogen activator inhibitor-1. In ZDF rats, ACE-inhibitor treatment limited albuminuria and reduced miR-184, with tubular LPP3 preservation and tubulointerstitial fibrosis amelioration. Albumin-induced miR-184 expression in tubule cells was epigenetically regulated through DNA demethylation and histone lysine acetylation and was accompanied by binding of NF-κB p65 subunit to miR-184 promoter. These results suggest that miR-184 may act as a downstream effector of albuminuria through LPP3 to promote tubulointerstitial
Chang, Yun-Peng; Sun, Bei; Han, Zhe; Han, Fei; Hu, Shao-Lan; Li, Xiao-Yu; Xue, Mei; Yang, Yang; Chen, Li; Li, Chun-Jun; Chen, Li-Ming
The dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin has been found to reduce progressive albuminuria, but the exact mechanism of inhibition is unclear. Podocyte epithelial-to-mesenchymal transition (EMT) has emerged as a potential pathway leading to proteinuria in diabetic nephropathy (DN). Stromal cell-derived factor-1α (SDF-1α), one of the substrates of DPP-4, can activate the protein kinase A pathway and subsequently inhibit its downstream effector, transforming growth factor-β1 (TGF-β1), which induces podocyte EMT. Thus, this study was designed to test the hypothesis that saxagliptin reduces progressive albuminuria by preventing podocyte EMT through inhibition of SDF-1α cleavage in DN. The results of a series of assays, including ELISA, western blotting, and immunochemistry/immunofluorescence, showed that saxagliptin treatment obviously ameliorated urinary microalbumin excretion and renal histological changes in high-fat diet/streptozotocin-induced diabetic rats. Furthermore, saxagliptin-treated diabetic rats presented with suppression of DPP-4 activity/protein expression accompanied by restoration of SDF-1α levels, which subsequently hindered NOX2 expression and podocyte EMT. In vitro , we consistently observed that saxagliptin significantly inhibited increased DPP-4 activity/expression, oxidative stress and podocyte EMT. Application of an SDF-1α receptor inhibitor (AMD3100) to cultured podocytes further confirmed the essential role of SDF-1α in podocyte EMT inhibition. In sum, we demonstrated for the first time that saxagliptin treatment plays an essential role in ameliorating progressive DN by preventing podocyte EMT through a SDF-1α-related pathway, suggesting that saxagliptin could offer renoprotection and that SDF-1α might be a potential therapeutic target for DN.
Beverly A Schaefer
Full Text Available Discovery and validation of genetic variants that influence disease severity in children with sickle cell anemia (SCA could lead to early identification of high-risk patients, better screening strategies, and intervention with targeted and preventive therapy. We hypothesized that newly identified genetic risk factors for the general African American population could also impact laboratory biomarkers known to contribute to the clinical disease expression of SCA, including variants influencing the white blood cell count and the development of albuminuria and abnormal glomerular filtration rate. We first investigated candidate genetic polymorphisms in well-characterized SCA pediatric cohorts from three prospective NHLBI-supported clinical trials: HUSTLE, SWiTCH, and TWiTCH. We also performed whole exome sequencing to identify novel genetic variants, using both a discovery and a validation cohort. Among candidate genes, DARC rs2814778 polymorphism regulating Duffy antigen expression had a clear influence with significantly increased WBC and neutrophil counts, but did not affect the maximum tolerated dose of hydroxyurea therapy. The APOL1 G1 polymorphism, an identified risk factor for non-diabetic renal disease, was associated with albuminuria. Whole exome sequencing discovered several novel variants that maintained significance in the validation cohorts, including ZFHX4 polymorphisms affecting both the leukocyte and neutrophil counts, as well as AGGF1, CYP4B1, CUBN, TOR2A, PKD1L2, and CD163 variants affecting the glomerular filtration rate. The identification of robust, reliable, and reproducible genetic markers for disease severity in SCA remains elusive, but new genetic variants provide avenues for further validation and investigation.
Full Text Available We evaluated the efficacy of a neutralizing anti-high mobility group box 1 (HMGB1 monoclonal antibody in MRL/lpr lupus-prone mice. The anti-HMGB1 monoclonal antibody (5 mg/kg weight or class-matched control immunoglobulin G2a (IgG2a was administered intravenously twice a week for 4–15 weeks. Urine albumin was monitored, and histological evaluation of the kidneys was conducted at 16 weeks. Lymphadenopathies were evaluated by 1-(2′-deoxy-2′-[18F]fluoro-β-D-arabinofuranosylcytosine ([18F]FAC positron emission tomography/computed tomography (PET/CT at 12 weeks. Following 4-week treatment, [18F]FAC-PET/CT showed similar accumulation in cervical and axillary lymph nodes at 12 weeks of age. However, anti-HMGB1 monoclonal antibody sufficiently inhibited the increase in albuminuria compared to an isotype control following 15-week treatment. Complement deposition was also improved; however, there were no significant differences in IgG deposition and renal pathological scores between the two groups. Anti-double-stranded DNA (dsDNA antibody titers and cytokine and chemokine levels were also unaltered. Although there were no significant differences in glomerular macrophage infiltration, neutrophil infiltration was significantly decreased by the anti-HMGB1 monoclonal antibody. Antagonizing HMGB1 treatment suppressed HMGB1 translocation from nuclei in the kidney and suppressed neutrophil extracellular traps. The anti-HMGB1 monoclonal antibody demonstrated therapeutic potential against albuminuria in lupus nephritis by inhibiting neutrophil recruitment and neutrophil extracellular traps.
Elajami, Tarec K; Alfaddagh, Abdulhamied; Lakshminarayan, Dharshan; Soliman, Michael; Chandnani, Madhuri; Welty, Francine K
Albuminuria is a marker of inflammation and an independent predictor of cardiovascular morbidity and mortality. The current study evaluated whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation attenuates progression of albuminuria in subjects with coronary artery disease. Two-hundred sixty-two subjects with stable coronary artery disease were randomized to either Lovaza (1.86 g of EPA and 1.5 g of DHA daily) or no Lovaza (control) for 1 year. Percent change in urine albumin-to-creatinine ratio (ACR) was compared. Mean (SD) age was 63.3 (7.6) years; 17% were women and 30% had type 2 diabetes mellitus. In nondiabetic subjects, no change in urine ACR occurred in either the Lovaza or control groups. In contrast, ACR increased 72.3% ( P diabetic subjects not receiving Lovaza, whereas those receiving Lovaza had no change. In diabetic subjects on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker, those receiving Lovaza had no change in urine ACR, whereas those not receiving Lovaza had a 64.2% increase ( P type 2 diabetes mellitus and coronary artery disease, most of whom were on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker. Thus, EPA and DHA supplementation should be considered as additional therapy to an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker in subjects with type 2 diabetes mellitus and coronary artery disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01624727. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Østergaard, Mette V; Pinto, Vanda; Stevenson, Kirsty; Worm, Jesper; Fink, Lisbeth N; Coward, Richard J M
Diabetic nephropathy (DN) is the leading cause of kidney failure in the world. To understand important mechanisms underlying this condition, and to develop new therapies, good animal models are required. In mouse models of type 1 diabetes, the DBA/2J strain has been shown to be more susceptible to develop kidney disease than other common strains. We hypothesized this would also be the case in type 2 diabetes. We studied db/db and wild-type (wt) DBA/2J mice and compared these with the db/db BLKS/J mouse, which is currently the most widely used type 2 DN model. Mice were analyzed from age 6 to 12 wk for systemic insulin resistance, albuminuria, and glomerular histopathological and ultrastructural changes. Body weight and nonfasted blood glucose were increased by 8 wk in both genders, while systemic insulin resistance commenced by 6 wk in female and 8 wk in male db/db DBA/2J mice. The urinary albumin-to-creatinine ratio (ACR) was closely linked to systemic insulin resistance in both sexes and was increased ~50-fold by 12 wk of age in the db/db DBA/2J cohort. Glomerulosclerosis, foot process effacement, and glomerular basement membrane thickening were observed at 12 wk of age in db/db DBA/2J mice. Compared with db/db BLKS/J mice, db/db DBA/2J mice had significantly increased levels of urinary ACR, but similar glomerular histopathological and ultrastructural changes. The db/db DBA/2J mouse is a robust model of early-stage albuminuric DN, and its levels of albuminuria correlate closely with systemic insulin resistance. This mouse model will be helpful in defining early mechanisms of DN and ultimately the development of novel therapies. Copyright © 2017 the American Physiological Society.
Full Text Available Penyebab utama morbiditas dan mortalitas pada pasien Penyakit Ginjal Kronik adalah insiden kardiovaskuler yang didasari oleh proses aterosklerosis yang menyebabkan meningkatnya morbiditas dan mortalitas. Ginjal merupakan tempat utama sintesa 1,25 Dihydroxyvitamin D (Calcitriol, sehingga dengan adanya kerusakan ginjal menyebabkan defisiensi 1,25 Dihydroxyvitamin D (Calcitriol. Pada pasien Penyakit Ginjal Kronik terjadi peningkatan Fibroblast Growth Factor-23 dan Albuminuria akibat dari aktifitas Renin Angiotensin Aldosteron Sistem. Aktifitas RAAS mempengaruhi 1,25 Dihydroxy vitamin D (Calcitriol, Fibroblast Growth Factor-23 melalui Angiotensin 2 dengan cara menghambat reseptor Angiotensin I (AT1 melalui Nicotinmide Adenine Dinucleotide Phosphate Oxidase (NADPH Oksidase dan Stress Oxidativ. Beberapa penelitian menyimpulkan pemberian 1,25 Dihydroxyvitamin D (Calcitriol mempunyai efek renoprotektif, anti inflamasi dan antiproteinuric dengan cara menghambat reseptor Angoitensin I (AT1 sehingga mengakibatkan menurunnya albuminuria. Tujuan Penelitian ini adalah untuk membuktikan pemberian 1,25 Dihydroxyvitamin D (Calcitriol dapat menurunkan kadar Fibroblas Growth Factor-23 dan albuminuria pada pasien Penyakit Ginjal Kronik stadium V yang menjalani hemodialisis. Penelitian ini merupakan penelitian eksperimen dengan randomisasi, subyek penelitian 30 orang, dibagi dalam dua kelompok sampel, kelompok plasebo 15 orang dan kelompok perlakuan 15 orang. Dalam perjalanan, kelompok placebo drop out 4 pasien karena keluarga pasien tidak menyetujui untuk melanjutkan penelitian dan satu lagi mengalami perburukan, sehingga jumlah sampel menjadi 26 orang, terbagi menjadi kelompok placebo sebanyak 11 orang yang diberi placebo dan kelompok perlakuan 15 orang diberi calcitriol 1x0,5 μg peroral selama 4 minggu. Karakteristik penelitian yang berupa variabel kualitatif, uji homogenitas dilakukan menggunakan uji Chi Square. Uji beda dua Rerata menggunakan uji t pada p<0
Liu, Jian-Jun; Pek, Sharon Li Ting; Ang, Kevin; Tavintharan, Subramaniam; Lim, Su Chi
Abnormal angiogenesis plays an important role in pathogenesis of diabetic kidney disease (DKD). Leucine-rich α-2 glycoprotein 1 (LRG1) is a newly identified angiogenic factor. To study whether plasma LRG1 may independently predict progression of DKD in individuals with type 2 diabetes mellitus (T2DM). Prospective cohort study in a regional hospital. In total, 1226 T2DM participants were followed for a mean ± standard deviation (SD) of 3.1 ± 0.4 years. Albuminuria progression was defined as elevation in albuminuria level to a higher category. Chronic kidney disease (CKD) progression [rapid estimated glomerular filtration rate (eGFR) decline] was defined as a 40% or greater deterioration in eGFR in 3 years. Both participants with albuminuria progression and those with CKD progression had higher plasma LRG1 levels at baseline. LRG1 independently predicted albuminuria progression above traditional risk factors, including baseline eGFR and urine albumin to creatinine ratio. A 1-SD increment in LRG1 was associated with a 1.26-fold [95% confidence interval (CI), 1.04 to 1.53, P = 0.018] higher adjusted risk for albuminuria progression. The association of LRG1 with microalbuminuria to macroalbuminuria progression was stronger than its association with normoalbuminuria to microalbuminuria progression [odds ratio (OR), 1.51; 95% CI, 1.04 to 2.18, P = 0.029 vs OR, 1.09; 95% CI, 0.86 to 1.37, P = 0.486, per 1-SD LRG1 increment]. Also, LRG1 independently predicted CKD progression above traditional risk factors. A 1-SD increment in LRG1 was associated with a 1.48-fold (95% CI, 1.04 to 2.11, P = 0.032) higher adjusted risk for CKD progression. Plasma LRG1 predicts both albuminuria and CKD progression beyond traditional risk factors. It may play a role in the pathologic pathway leading to progression of DKD in T2DM.
Rossing, P; Tarnow, L; Boelskifte, S
Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) versus an ACE inhibitor (lisinopril) on albuminuria, arterial blood pressure, and glomerular filtration rate (GFR) in hypertensive IDDM patients with diabetic nephropathy. We performed a 1-year, double......-blind, double-dummy, randomized, controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 52 hypertensive IDDM subjects with diabetic nephropathy. Three patients dropped out, and results for the remaining 49 (25 nisoldipine, 24 lisinopril) are presented. Diuretics...... were required in 10 nisoldipine- and 8 lisinopril-treated patients. Every 3 months, 24-h ambulatory blood pressure (TM2420, A&D, Tokyo, Japan) and albuminuria in three 24-h samples (enzyme immunoassay) were measured; GFR (51Cr-EDTA plasma clearance) was recorded every 6 months. Mean arterial blood...
Vaňourková, Z.; Kramer, H. J.; Husková, Z.; Červenka, L.; Vaněčková, Ivana
Roč. 59, č. 3 (2010), s. 339-345 ISSN 0862-8408 Grant - others:GA ČR(CZ) GA305/07/0167; GA ČR(CZ) GC305/07/J004 Institutional research plan: CEZ:AV0Z50110509 Keywords : Ren- rats * albuminuria * RAS blockade Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.646, year: 2010
Liao, Li-Na; Liu, Chiu-Shong; Li, Chia-Ing; Lin, Wen-Yuan; Lin, Chih-Hsueh; Li, Tsai-Chung; Lin, Cheng-Chieh
early-stage elevated albuminuria can be effectively detected by a spot urine albumin-to-creatinine ratio (UACR). Elevated albuminuria is a key predictor of diabetic nephropathy, progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD), plus risk of cardiovascular disease (CVD) and mortality. Understanding these detectors may prevent future renal and cardiovascular disease. This study estimates three-year incidence in a representative sample of Taiwanese metropolitan adults to explore predictors. the Taichung Community Health Study (TCHS) is a representative sample of 2359 Chinese adults aged 40 years and over living in a metropolitan city during 2004-2005. In 2007-2009, a total of 1648 (71.3%) individuals participated in follow-up. This study includes only individuals with normal albumin excretion at baseline examination. Three-year incidence and baseline factors linked with elevated albuminuria were evaluated. about 87.0% (n = 1434) of subjects exhibited normal albumin excretion at baseline. Three-year age- and gender-weighted incidence was 4.5% (95% CI: 3.4-5.6%). Multivariate logistic regression showed subjects with elevated waist-to-hip ratio (WHR) (OR: 2.2, 95% CI: 1.2-3.9), abnormal creatinine (OR: 3.7, 95% CI: 1.1-12.6), hyperuricaemia (OR: 1.8, 95% CI: 1.0-3.3) and elevated baseline UACR (OR: 4.0, 95% CI: 1.1-14.3 for UACR of 3.20-6.39 mg/g; OR: 16.7, 95% CI: 5.0-55.5 for UACR of 6.40-29.99 mg/g) were more likely to have elevated albuminuria. this is the first population-based longitudinal study to rate incidence of elevated albuminuria and identify associated factors in a random sample of a Chinese population. Central obesity, renal function, hyperuricaemia and baseline UACR are independent risk factors. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Mitchell, Brooks I; Byron, Mary Margaret; Ng, Roland C; Chow, Dominic C; Ndhlovu, Lishomwa C; Shikuma, Cecilia M
High rates of albuminuria are observed among HIV-infected individuals on stable antiretroviral therapy (ART). Though pro-inflammatory and pro-fibrotic responses are described as components of albuminuria in the general population, it is unclear how these responses are associated to albuminuria in ART-treated chronic HIV. We investigated the relationship of monocyte subsets and urine inflammatory and fibrotic biomarkers to albuminuria in ART-treated HIV-infected participants. Cross-sectional analyses were performed on Hawaii Aging with HIV-cardiovascular disease study cohort participants who were required at entry to be ≥40 years old and on ART ≥3 months. Monocyte subpopulations were determined in banked peripheral blood mononuclear cells (PBMC) using multi-parametric flow-cytometry. Entry random urine samples were assessed for albumin-to-creatinine ratios (UACR). Urine samples were measured for inflammatory and fibrotic biomarkers using Luminex technology. Among 96 HIV-infected subjects with measured UACR (87% male, 59% Caucasian, and 89% undetectable HIV RNA with median CD4 of 495.5 cells/μL), 18 patients (19%) had albuminuria. Non-classical (CD14low/+CD16++) monocytes were significantly elevated in subjects with albuminuria (p = 0.034) and were correlated to UACR (r = 0.238, p = 0.019). Elevated non-classical monocyte counts were significant predictors of worsening albuminuria, independent of traditional- and ART-associated risk factors (β = 0.539, p = 0.007). Urine TGF-β1 and collagen-IV were significantly higher in albuminuric compared to non-albuminuric participants (TGF-β1; p = 0.039 and collagen-IV; p = 0.042). Urine TGF-β1 was significantly correlated with non-classical monocyte counts (r = 0.464, p = 0.017). Alterations in monocyte subpopulations and urine pro-fibrotic factors may play a role in kidney dysfunction during chronic HIV infection and warrants further study.
Differences in risk factors for the onset of albuminuria and decrease in glomerular filtration rate in people with Type 2 diabetes mellitus: implications for the pathogenesis of diabetic kidney disease.
Takagi, M; Babazono, T; Uchigata, Y
To determine differences in predictors of albuminuria and decreased estimated GFR in Japanese people with Type 2 diabetes mellitus without chronic kidney disease. This single-centre observational cohort study involved 1802 Japanese people with Type 2 diabetes with normoalbuminuria and estimated GFR ≥ 60 ml/min/1.73 m(2) (740 women; mean ± sd age 58 ± 12 years). Two separate outcomes were evaluated: onset of albuminuria ( ≥ 30 mg/g creatinine, albuminuria cohort; n = 1655) and decrease in estimated GFR ( albuminuria cohort and 8.0 years for the estimated GFR cohort, 181 and 316 individuals reached the respective outcome. The 5-year cumulative incidence of albuminuria was 8.3%, and that of decreased estimated GFR was 10.4%. In the multivariate Cox model, greater urinary albumin-to-creatinine ratio, presence of diabetic retinopathy and higher HbA1c levels were associated with both outcomes. Unique risk factors for onset of albuminuria were male gender and higher uric acid levels; those for decreased estimated GFR were older age, greater systolic blood pressure, and lower baseline estimated GFR and HDL cholesterol levels. Identification of both common and distinct predictive factors for onset of albuminuria and decreased estimated GFR support the hypothesis that both common and distinct pathophysiological mechanisms are involved in the development of these two manifestations of chronic kidney disease in diabetes. © 2015 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.
Pilemann-Lyberg, Sascha; Persson, Frederik; Frystyk, Jan
Background Epidemiological studies indicate that uric acid (UA) is a risk factor for development and progression of CKD. Whether UA lowering with allopurinol changes urinary albumin excretion rate (UAER) or GFR in patients with type 1 diabetes (T1D) suffering from diabetic nephropathy is not known....... Methods We conducted a randomized, placebo-controlled, double-blinded, cross-over trial enrolling patients with T1D and a plasma uric acid ≥ 4.4 mg/dL, persistent albuminuria (urinary albumin creatinine ration) ≥30 mg/g and an eGFR ≥ 40 ml/min/1.73m2 on stable RAS blocking intervention. The participants...... placebo (p=0.51). Glycemic control 24h-blood pressure and RAS blockade was stable. We found no significant association (p=0.45) between uric acid and UAER. In an unadjusted linear model, UA was significantly associated with the level of GFR (51Cr-EDTA) in the placebo treatment period (R2=0.2, p=0...
Lee, Min-Kyung; Han, Kyung-Do; Lee, Jae-Hyuk; Sohn, Seo-Young; Hong, Oak-Kee; Jeong, Jee-Sun; Kim, Mee-Kyoung; Baek, Ki-Hyun; Song, Ki-Ho; Kwon, Hyuk-Sang
Albuminuria is closely associated with diabetic retinopathy (DR), but the precise role of the albumin-to-creatinine ratio (ACR) in screening for DR remains to be determined. This study aimed to investigate an ACR threshold for predicting DR in patients with type 2 diabetes. A cross-sectional study was conducted on 1,102 type 2 diabetes patients, aged ≥30 years and recruited from the Korea National Health and Nutrition Examination Survey, 2010-2011. Participants were grouped by stage of DR: mild-to-moderate nonproliferative DR (NPDR), severe NPDR, and proliferative diabetic retinopathy (PDR). An early morning spot urine sample was obtained for ACR measurement. ROC curve analysis revealed that the optimal cut-off value of ACR for predicting DR was 2.26 mg/mmol (20 μg/mg). The prevalence of ACR ≥ 2.26 mg/mmol tended to increase with severity of DR. The risk for DR in patients with ACR ≥ 2.26 mg/mmol was higher than in those with ACR predict the risk for DR development and progression in patients with type 2 diabetes.
Xu, Min; Bi, Yufang; Huang, Ya; Xie, Lan; Hao, Mingli; Zhao, Zhiyun; Xu, Yu; Lu, Jieli; Chen, Yuhong; Sun, Yimin; Qi, Lu; Wang, Weiqing; Ning, Guang
Type 2 diabetes (T2D) is a risk factor for dysregulation of glomerular filtration rate (GFR) and albuminuria. However, whether the association is causal remains unestablished. We performed a Mendelian Randomization (MR) analysis in 11,502 participants aged 40 and above, from a well-defined community in Shanghai during 2011-2013, to explore the causal association between T2D and decreased estimated GFR (eGFR) and increased urinary albumin-to-creatinine ratio (uACR). We genotyped 34 established T2D common variants in East Asians, and created a T2D-genetic risk score (GRS). We defined decreased eGFR as eGFRgenetically determined T2D and decreased eGFR (OR=1.47, 95% CI: 1.15, 1.88, P=0.0003). When grouping the genetic loci according to their relations with either insulin secretion (IS) or insulin resistance (IR), we found both IS_GRS and IR_GRS were significantly related to decreased eGFR (both P<0.02). In addition, T2D_GRS and IS_GRS were significantly associated with Log-uACR (both P=0.04). Our results provide novel evidence for a causal association between T2D and decreased eGFR by using MR approach in a Chinese population. Copyright © 2016. Published by Elsevier B.V.
Pan, C Y; Ho, L T; Soegondo, S; Prodjosudjadi, W; Suwanwalaikorn, S; Lim, S C; Chan, T M; Chow, K W Steven; Thoenes, M; Choi, D S
Microalbuminuria (MA) is a risk marker for diabetic nephropathy and cardiovascular (CV) disease (CVD) in patients with diabetes. This study aimed to describe the prevalence of albuminuria, CV risk factors, and treatments for renal and CV protection in an Asian population with type 2 diabetes. This cross-sectional study conducted in eight Asian countries enrolled normotensive/hypertensive adults with type 2 diabetes without known proteinuria and/or non-diabetic kidney disease. Exclusion criteria were type 1 diabetes, menstruation, pregnancy, and acute fever. A single random urinary albumin/creatinine test was carried out in all patients. Of 8,561 patients, 14% had diabetic retinopathy, and 17% and 21% had history of CV disease and smoking, respectively. Normoalbuminuria was seen in 44%, MA in 44%, and macroalbuminuria in 12%. Target glycosylated hemoglobin (HbA1c) (patients with available values. Diabetes was managed by diet alone in 6%, while others received oral hypoglycemic drugs and/or insulin. In total, 75% did not reach target blood pressure (BP) of patients, respectively. Asian patients with type 2 diabetes had a high prevalence of MA and reduced kidney function. Furthermore, BP and HbA1c control was only achieved in a minority of patients. Aggressive risk management by administration of reno- and cardioprotective treatments is urgently needed.
Gopee, Esha; van den Oever, Eva L M; Cameron, Fergus; Thomas, Merlin C
Although a diagnosis of coeliac disease (CD) may be confronting to children with type 1 diabetes and their families, we hypothesize that children with CD have lower urinary albumin excretion, a marker of renal dysfunction. Twenty-four children with type 1 diabetes and biopsy-proven CD, on a gluten-free diet for at least 1 yr, were recruited from a single paediatric diabetes clinic alongside 55 children with type 1 diabetes but without CD matched for age, gender, duration of diabetes, and glycaemic control. Despite comparable diabetes exposure, glycaemic control and nutritional status, children with type 1 diabetes and CD had a lower urinary albumin creatinine ratio than in diabetic subjects without CD (0.9 ± 0.3 mg/mmol vs. 1.6 ± 0.3 mg/mmol; p = 0.01). Participants with CD also showed slower progression in albuminuria over 5-yr of follow-up while a small but significant increase was observed in the children with diabetes alone (1.6 ± 0.3 mg/mmol; follow-up 2.4 ± 0.5 mg/mmol; p = 0.02). As urinary albumin excretion is continuously associated with the risk of kidney disease, it is possible to speculate that CD or its management confers a degree of renoprotection. Larger studies are required to test this hypothesis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Ejaz, Muslima; Ahmed, Ejaz; Mubarak, Muhammed; Hatcher, Juanita; Jaffar, Tazeen
Hypertension is a major public health problem worldwide and a key factor for chronic kidney disease (CKD). Detection and treatment of CKD is of paramount importance. Albuminuria is one of the earliest screening markers recommended in patients at increased risk for CKD. We conducted this study to determine the prevalence of persistent albuminuria (PA) in newly diagnosed hypertensive subjects and to study its associated risk factors. A total of 173 (72%) of 240 subjects among 1340 newly diagnosed hypertensive subjects from an ongoing community-based cohort study who had been screened once for the presence of albuminuria were retested for the presence of PA in this study. Urinary albumin concentration (UAC) in mg/L and albumin-to-creatinine ratio (ACR) in mg/g creatinine were determined in a spot morning urine sample by nephelometry. The prevalence of PA signifying CKD was 9.3% with 95% confidence interval (CI) of 7.8-10.8% by UAC and 8.1% by ACR method (95% CI: 6.6-8.4%). Subjects with PA had mean age of 56.4 ± 11.4 years and 50% were males. Factors independently associated were male gender (odds ratio [OR], 1.92 (95% CI: 1.24-2.97)) and age less than 55 years with positive family history of kidney disease (OR, 15.51; 95% CI: 7.35-32.97). Among measurable variables, high cholesterol levels (p = 0.001), and progressively higher levels of systolic blood pressure (p < 0.001) were associated with risk of PA. Hypertensive kidney damage is already present in a significant number of newly diagnosed hypertensives suggesting late detection of hypertension.
Rani Padmaja K
Full Text Available Abstract Background The concordance of microalbuminuria and diabetic retinopathy (DR has been well reported in persons with type 1 diabetes; however, for type 2 diabetes, there is paucity of data especially from population-based studies. The aim of this study was to estimate the prevalence of albuminuria (micro - and macroalbuminuria among persons with type 2 diabetes and determine its role as a risk factor for presence and severity of DR. Methods A population-based cross sectional study was conducted in cohort of 1414 subjects with type 2 diabetes from Chennai metropolis. All the subjects underwent comprehensive eye examination including 45 degrees four-field stereoscopic digital photography. DR was clinically graded using Early Treatment Diabetic Retinopathy Study scales. A morning urine sample was tested for albuminuria. Subjects were considered to have microalbuminuria, if the urinary albumin excretion was between 30 and 300 mg/24 hours, and macroalbuminuria at more than 300 mg/24 hours. The statistical software used was SPSS for Windows, Chicago, IL. Student t-test for comparing continuous variables, and χ2 test, to compare proportions amongst groups were used. Results The prevalence of microalbuminuria in the study subjects was 15.9% (226/1414, and that of macroalbuminuria, 2.7% (38/1414. Individuals with macroalbuminuria in comparison to micro- or normoalbuminuria showed a greater prevalence of DR (60.5% vs. 31.0% vs. 14.1%, p Conclusions Every 6th individual in the population of type 2 diabetes is likely to have albuminuria. Subjects with microalbuminuria were around 2 times as likely to have DR as those without microalbuminuria, and this risk became almost 6 times in the presence of macroalbuminuria.
Kong, Alice P S; Xiao, Kang; Choi, Kai Chow; Wang, Gang; Chan, Michael H M; Ho, Chung Shun; Chan, Iris; Wong, Chun Kwok; Chan, Juliana C N; Szeto, Cheuk Chun
Pathogenetic mechanisms underlying albuminuria are not completely understood. Heavy metals might lead to atherosclerosis and kidney damage. miR-21, 126, 155 and 221 regulated endothelial function and might contribute to the development of albuminuria. To date, no clinical trial has explored the relationship between miRNAs, microalbuminuria and heavy metals in human. In this study, we aimed to examine the association between microalbuminuria, miRNAs and heavy metals in adolescents. From a cross-sectional, population-recruited study, we identified 60 school children aged 12-19 years with microalbuminuria (defined as spot urine albumin-creatinine ratio >3.5 mg/mmol). We compared the urine heavy metals (arsenic, mercury, cadmium and lead) and miRNAs levels (miR-21,126, 155 and 221) with another 60 age-and sex-matched normoalbuminuric adolescents as control. Mean age of the study cohort was 15.5±2.1 years. 43% were boys. Among the four miRNAs tested, only miR-21 was associated with microalbuminuria (p=0.02). Urinary arsenic and lead levels had a negative association with both miR-21 and miR-221. No significant association was found between heavy metals examined and microalbuminuria. The results of our study suggest an association between microalbuminuria, miR-21 and heavy metals (arsenic and lead). This might imply that miR-21 is involved in the pathogenetic mechanisms linking heavy metals exposure and albuminuria. Copyright © 2012 Elsevier B.V. All rights reserved.
Vestergaard Rosenlund, Signe; Hansen, Tine Willum; Andersen, Steen
on diabetes duration, gender, HbA1c and normo-, micro- or macroalbuminuria at baseline. Urinary albumin/creatinine ratio (UACR) was measured yearly and annual change assessed from linear regression. RESULTS: CSII- vs. MDI-treated patients were comparable at baseline. After 4 years, HbA1c was 62 ± 11 vs. 68......AIM: The effect of insulin pump [continuous subcutaneous insulin infusion (CSII)] treatment on diabetes complications in a modern clinical setting is largely unknown. We investigated the effect of 4 years CSII treatment on HbA1c, albuminuria and kidney function compared with multiple daily...
Svenningsen, Per; Andersen, Henrik; Nielsen, Lise H
and diabetic nephropathy; blood pressure is salt-sensitive in conditions with microalbuminuria/proteinuria; and extracellular volume is expanded, plasma atrial natriuretic peptide (ANP) concentration is increased, and diuretics, like amiloride and spironolactone, are effective blood pressure-reducing add......-ons. Active plasmin in urine has been demonstrated in diabetes, preeclampsia, and nephrosis. Urine from these patients activates, plasmin-dependently, amiloride-sensitive inward current in vitro. The concept predicts that patients with albuminuria may benefit particularly from reduced salt intake with RAS...
Hong, Jae Won; Ku, Cheol Ryong; Noh, Jung Hyun; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Dong-Jun
Background Recent studies have indicated that low UACR levels (albuminuria’) are associated with cardiovascular morbidity and mortality in the general population. Methods We studied 9,736 participants with albuminuria in the normal range from the 2011–2012 Korea National Health and Nutrition Examination Survey (KNHANES). Results The weighted prevalences of metabolic syndrome (MS) and the 10-year risk for coronary heart disease measured using the Framingham risk score (FRS) ≥ 20% (high risk) were 22.5 ± 0.7% and 14.5 ± 0.7%, respectively, in males and 23.3 ± 0.8% and 8.5 ± 0.4%, respectively in females. Weighted comparisons among the tertiles of UACR revealed that the prevalences of MS and high-risk FRS increased with increasing UACR (MS: males, 15.9 ± 1.1, 20.2 ± 1.2, 32.4 ± 1.5%, respectively; P albuminuria was significantly associated with estimated cardiovascular risk and MS in a nationally representative sample of Koreans. PMID:25742159
DULLAART, RPF; BEUSEKAMP, BJ; MEIJER, S; HOOGENBERG, K; VANDOORMAAL, JJ; SLUITER, WJ
We conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10 and
Brooks I Mitchell
Full Text Available High rates of albuminuria are observed among HIV-infected individuals on stable antiretroviral therapy (ART. Though pro-inflammatory and pro-fibrotic responses are described as components of albuminuria in the general population, it is unclear how these responses are associated to albuminuria in ART-treated chronic HIV. We investigated the relationship of monocyte subsets and urine inflammatory and fibrotic biomarkers to albuminuria in ART-treated HIV-infected participants.Cross-sectional analyses were performed on Hawaii Aging with HIV-cardiovascular disease study cohort participants who were required at entry to be ≥40 years old and on ART ≥3 months. Monocyte subpopulations were determined in banked peripheral blood mononuclear cells (PBMC using multi-parametric flow-cytometry. Entry random urine samples were assessed for albumin-to-creatinine ratios (UACR. Urine samples were measured for inflammatory and fibrotic biomarkers using Luminex technology.Among 96 HIV-infected subjects with measured UACR (87% male, 59% Caucasian, and 89% undetectable HIV RNA with median CD4 of 495.5 cells/μL, 18 patients (19% had albuminuria. Non-classical (CD14low/+CD16++ monocytes were significantly elevated in subjects with albuminuria (p = 0.034 and were correlated to UACR (r = 0.238, p = 0.019. Elevated non-classical monocyte counts were significant predictors of worsening albuminuria, independent of traditional- and ART-associated risk factors (β = 0.539, p = 0.007. Urine TGF-β1 and collagen-IV were significantly higher in albuminuric compared to non-albuminuric participants (TGF-β1; p = 0.039 and collagen-IV; p = 0.042. Urine TGF-β1 was significantly correlated with non-classical monocyte counts (r = 0.464, p = 0.017.Alterations in monocyte subpopulations and urine pro-fibrotic factors may play a role in kidney dysfunction during chronic HIV infection and warrants further study.
Qamar, A.; Ahmad, T.M.; Hayat, A.; Khan, M.A.; Rehman, S. Z.
To compare e-GFR estimated by creatinine or cystatin C based and combined creatinine and cystatin C based equations in type 2 diabetics in different stages of albuminuria. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Chemical Pathology, Army Medical College Rawalpindi in collaboration with endocrinology outpatient department Military Hospital Rawalpindi, from Nov 2015 to Nov 2016. Material and Methods: A total of 119 type 2 diabetic subjects of either gender, aged 30- 60 years were enrolled in the study with duration of diabetes less than 15 years and were divided into further sub groups on the basis of degree of albuminuria determined by spot urine albumin to creatinine ratio (uACR). Fifty age matched disease free controls with no history of any systemic disease were also included in the study. Known patients of type 1 diabetes, chronic inflammatory disorders, uncontrolled hypertension, thyroid disease, chronic kidney disease, on lipid lowering drugs, steroids, ACE inhibitors and pregnant ladies were excluded from the study. Serum creatinine serum cystatin C were assessed on fully automated chemistry analyzer selectra. E-GFR was calculated by online GFR calculator by National Kidney Foundation. Comparison of means of e-GFR calculated by various equations was carried out by one way ANOVA and post-hoc Tukey tests. Degree of agreement between various equations for the estimation of GFR was assessed by kappa statistics. A p-value less than 0.05 were considered statistically significant. Results: Mean e-GFR (ml/min/1.73m2) was lowest in cystatin C based CKD-EPI equation (89.56 +- 39.84) followed by combined cystatin C and creatinine based CKD-EPI (92.34 +- 37.88). Values of e-GFR by creatinine based CKD-EPI equation (95.84 +- 27.24), and by creatinine based MDRD equation (105.37 +- 64.98) were both higher. In creatinine based MDRD, equation normo albuminuria and micro albuminuria groups did not show statistically
Gerasimova, Maria; Rose, Michael A.; Masuda, Takahiro; Satriano, Joseph; Mayoux, Eric; Koepsell, Hermann; Thomson, Scott C.; Rieg, Timo
Our previous work has shown that gene knockout of the sodium-glucose cotransporter SGLT2 modestly lowered blood glucose in streptozotocin-diabetic mice (BG; from 470 to 300 mg/dl) and prevented glomerular hyperfiltration but did not attenuate albuminuria or renal growth and inflammation. Here we determined effects of the SGLT2 inhibitor empagliflozin (300 mg/kg of diet for 15 wk; corresponding to 60–80 mg·kg−1·day−1) in type 1 diabetic Akita mice that, opposite to streptozotocin-diabetes, upregulate renal SGLT2 expression. Akita diabetes, empagliflozin, and Akita + empagliflozin similarly increased renal membrane SGLT2 expression (by 38–56%) and reduced the expression of SGLT1 (by 33–37%) vs. vehicle-treated wild-type controls (WT). The diabetes-induced changes in SGLT2/SGLT1 protein expression are expected to enhance the BG-lowering potential of SGLT2 inhibition, and empagliflozin strongly lowered BG in Akita (means of 187–237 vs. 517–535 mg/dl in vehicle group; 100–140 mg/dl in WT). Empagliflozin modestly reduced GFR in WT (250 vs. 306 μl/min) and completely prevented the diabetes-induced increase in glomerular filtration rate (GFR) (255 vs. 397 μl/min). Empagliflozin attenuated increases in kidney weight and urinary albumin/creatinine ratio in Akita in proportion to hyperglycemia. Empagliflozin did not increase urinary glucose/creatinine ratios in Akita, indicating the reduction in filtered glucose balanced the inhibition of glucose reabsorption. Empagliflozin attenuated/prevented the increase in systolic blood pressure, glomerular size, and molecular markers of kidney growth, inflammation, and gluconeogenesis in Akita. We propose that SGLT2 inhibition can lower GFR independent of reducing BG (consistent with the tubular hypothesis of diabetic glomerular hyperfiltration), while attenuation of albuminuria, kidney growth, and inflammation in the early diabetic kidney may mostly be secondary to lower BG. PMID:24226524
Gambaro, Giovanni; Kinalska, Ida; Oksa, Adrian; Pont'uch, Peter; Hertlová, Miluse; Olsovsky, Jindrich; Manitius, Jacek; Fedele, Domenico; Czekalski, Stanislaw; Perusicová, Jindriska; Skrha, Jan; Taton, Jan; Grzeszczak, Wladyslaw; Crepaldi, Gaetano
Diabetic nephropathy may be effectively prevented and treated by controlling glycemia and administering angiotensin-converting enzyme (ACE) inhibitors. However, strict metabolic control can be difficult, and ACE inhibitors may be poorly tolerated and only partially effective, particularly in diabetes mellitus type 2 (DM2), warranting the search for ancillary treatment. Sulodexide is a glycosaminoglycan, a new class of drug that has demonstrated nephroprotective activity in experimental investigations. The Di.N.A.S. study was a randomized, double-blind, placebo-controlled, multicenter, dose-range finding trial to evaluate the extent and duration of the hypoalbuminuric effect of oral sulodexide in diabetic patients. A total of 223 microalbuminuric and macroalbuminuric DM1 and DM2 patients with serum creatinine Treatment with 200 mg/d sulodexide for 4 mo significantly reduced log albumin excretion rate (logAER) from 5.25 +/- 0.18 at T0 to 3.98 +/- 0.11 at T4 (P DM2, microalbuminuric versus macroalbuminuric, or on concomitant ACE inhibitors versus not on ACE inhibitors) demonstrated similar findings. These effects were obtained without any significant variation in metabolic control and BP or serum creatinine. Very few adverse events were reported; none were serious. In conclusion, a 4-mo course of high doses of sulodexide significantly and dose-dependently improves albuminuria in DM1 and DM2 patients and micro- or macroalbuminuric patients with or without concomitant ACE inhibition. The effect on albuminuria is long-lasting and seemingly additive to the ACE inhibitory effect.
Yamamoto-Kabasawa, Keiko; Hosojima, Michihiro; Yata, Yusuke; Saito, Mariko; Tanaka, Noriko; Tanaka, Junta; Tanabe, Naohito; Narita, Ichiei; Arakawa, Masaaki; Saito, Akihiko
Albuminuria is a biomarker for chronic kidney disease and an independent predictor of cardiovascular and all-cause mortality. A recent meta-analysis concluded that these risks increase with urinary albumin concentration, even when below the microalbuminuria threshold. Thus, minimizing urinary albumin may be a valuable therapeutic goal regardless of disease status. We investigated the benefits and safety of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise for reducing albuminuria in 295 normoalbuminuric or microalbuminuric Japanese adults, including 30 with type 2 diabetes mellitus (T2DM), 104 with metabolic syndrome (MS), and 145 with hypertension (HT). In the study population, the urinary albumin:creatinine ratio (UACR) was reduced significantly (ΔUACR -3.8 ± 16.8 mg/g, P < 0.001) with no change in estimated glomerular filtration rate (eGFR) (ΔeGFR -0.4 ± 7.4 mL/min/1.73 m(2), P = 0.343). The reduction in UACR was associated with decreased fasting plasma glucose (P < 0.05). The UACR was also reduced in the T2DM, MS, and HT groups with no change in eGFR. Reduced UACR was associated with decreased fasting plasma glucose in the MS group and decreased systolic blood pressure in the HT group. The UACR was also reduced in 46 subjects using renin-angiotensin system inhibitors with no change in eGFR. Our 12-week lifestyle modification program reduced UACR, maintained eGFR, and improved multiple fitness findings in Japanese subjects including T2DM, MS, and HT patients.
Gaede, P; Poulsen, H E; Parving, H H
AIMS: Elevated levels of urinary albumin excretion rate (AER) predict high risk for progressing to end-stage renal disease. In streptozotocin-induced diabetes, supplementation with vitamin C or E reduces albuminuria and glomerular hypertrophy. We tested the hypothesis that supplementation of both...... vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with persistent micro/macroalbuminuria. METHODS: Thirty Type 2 diabetic patients with AER 30-300 mg/24 h were included in a double-blind randomised, cross-over trial. Patients received vitamin C (1250 mg) and vitamin E (680 IU......) per day or matching placebo for 4 weeks with a 3-week wash-out period between treatment periods in random order. RESULTS: Combined treatment with vitamin C and E reduced AER by 19% (95% CI 6-34%) (p = 0.04), geometric mean 197 mg/24 h (95% CI 114-341 mg/24 h) vs. 243 mg/24 h (146-404 mg/24 h...
Simone Costa Alarcon Arias
Full Text Available Treatments that effectively prevent chronic kidney disease (CKD when initiated early often yield disappointing results when started at more advanced phases. We examined the long-term evolution of renal injury in the 5/6 nephrectomy model (Nx and the effect of an association between an AT-1 receptor blocker, losartan (L, and hydrochlorothiazide (H, shown previously to be effective when started one month after Nx. Adult male Munich-Wistar rats underwent Nx, being divided into four groups: Nx+V, no treatment; Nx+L, receiving L monotherapy; Nx+LH, receiving the L+H association (LH, and Nx+AHHz, treated with the calcium channel blocker, amlodipine, the vascular relaxant, hydralazine, and H. This latter group served to assess the effect of lowering blood pressure (BP. Rats undergoing sham nephrectomy (S were also studied. In a first protocol, treatments were initiated 60 days after Nx, when CKD is at a relatively early stage. In a second protocol, treatments were started 120 days after Nx, when glomerulosclerosis and interstitial fibrosis are already advanced. In both protocols, L treatment promoted only partial renoprotection, whereas LH brought BP, albuminuria, tubulointerstitial cell proliferation and plasma aldosterone below pretreatment levels, and completely detained progression of renal injury. Despite normalizing BP, the AHHz association failed to prevent renal damage, indicating that the renoprotective effect of LH was not due to a systemic hemodynamic action. These findings are inconsistent with the contention that thiazides are innocuous in advanced CKD. In Nx, LH promotes effective renoprotection even at advanced stages by mechanisms that may involve anti-inflammatory and intrarenal hemodynamic effects, but seem not to require BP normalization.
Arias, Simone Costa Alarcon; Valente, Carla Perez; Machado, Flavia Gomes; Fanelli, Camilla; Origassa, Clarice Silvia Taemi; de Brito, Thales; Camara, Niels Olsen Saraiva; Malheiros, Denise Maria Avancini Costa; Zatz, Roberto; Fujihara, Clarice Kazue
Treatments that effectively prevent chronic kidney disease (CKD) when initiated early often yield disappointing results when started at more advanced phases. We examined the long-term evolution of renal injury in the 5/6 nephrectomy model (Nx) and the effect of an association between an AT-1 receptor blocker, losartan (L), and hydrochlorothiazide (H), shown previously to be effective when started one month after Nx. Adult male Munich-Wistar rats underwent Nx, being divided into four groups: Nx+V, no treatment; Nx+L, receiving L monotherapy; Nx+LH, receiving the L+H association (LH), and Nx+AHHz, treated with the calcium channel blocker, amlodipine, the vascular relaxant, hydralazine, and H. This latter group served to assess the effect of lowering blood pressure (BP). Rats undergoing sham nephrectomy (S) were also studied. In a first protocol, treatments were initiated 60 days after Nx, when CKD is at a relatively early stage. In a second protocol, treatments were started 120 days after Nx, when glomerulosclerosis and interstitial fibrosis are already advanced. In both protocols, L treatment promoted only partial renoprotection, whereas LH brought BP, albuminuria, tubulointerstitial cell proliferation and plasma aldosterone below pretreatment levels, and completely detained progression of renal injury. Despite normalizing BP, the AHHz association failed to prevent renal damage, indicating that the renoprotective effect of LH was not due to a systemic hemodynamic action. These findings are inconsistent with the contention that thiazides are innocuous in advanced CKD. In Nx, LH promotes effective renoprotection even at advanced stages by mechanisms that may involve anti-inflammatory and intrarenal hemodynamic effects, but seem not to require BP normalization. PMID:23431367
García-Nieto, Víctor M; Fortich, Fernán; Luis-Yanes, M Isabel; Tripodi, Cinzia; Arango-Sancho, Pedro
The G1 stage of chronic kidney disease (CKD) is defined in the 2012 KDIGO Guideline as kidney damage characterized by structural or functional kidney abnormalities without deterioration of glomerular filtration rate. Albuminuria and electrolyte abnormalities due to tubular disorders are considered functional markers of kidney damage. Changes in renal water handling are not explicitly cited in these guidelines. A large sample of children with abnormal dimercaptosuccinic acid (DMSA) scan located in the G1 stage was used in this study. Ambispective, cross-sectional study to evaluate the clinical histories of 116 pediatric patients. 100 patients were included in the first group (G1 stage) and 16 patients in the G2-G5 stages according to the classification of CKD Guideline KDIGO. All the patients had a renal pathologic DMSA scan. GFR, maximum urine osmolality and albumin/creatinine and NAG/creatinine ratios were determined. The patients with normal GFR, in relation to those with reduced GFR, had significantly higher values of maximum urine osmolality and significantly reduced values of urine volume and albumin/creatinine and NAG/creatinine ratios. The most frequently observed alterations in children in the KDIGO G1 stage were those involving the water renal management such as urinary concentrating ability defect (29%) and increased urinary volume (20%). The frequency of children with increased urinary elimination of albumin (12%) and NAG (3%) was more lower. All children in KDIGO G2-G5 stages had alterations in water renal management. The parameters related with the water renal management are affected more frequently than albumin urinary excretion in children who have loss of parenchyma and normal GFR.
Full Text Available Aim To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2 inhibition on renal function and albuminuria in patients with type 2 diabetes. Methods We conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR and/or urine albumin/creatinine ratio (ACR changes. Data were synthesized using the random-effects model. Results Forty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD, −0.33 ml/min per 1.73 m2, 95% CI [−0.90 to 0.23] or in patients with chronic kidney disease (CKD (WMD −0.78 ml/min per 1.73 m2, 95% CI [−2.52 to 0.97]. SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD −0.98 ml/min per 1.73 m2, 95% CI [−1.42 to −0.54], and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]. Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD −7.24 mg/g, 95% CI [−15.54 to 1.06], but was significant in patients with CKD (WMD −107.35 mg/g, 95% CI [−192.53 to −22.18]. Conclusions SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.
Ji Suk Han
Full Text Available Anemia is a common complication among patients with chronic kidney disease (CKD, and it is associated with unfavorable clinical outcomes in patients with CKD independent of the estimated glomerular filtration rate (eGFR. We assessed the association of the urinary albumin-to-creatinine ratio (ACR and eGFR with anemia in CKD patients.We conducted a cross-sectional study using baseline data from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD. Multiple regression analysis was performed to identify the independent association of albuminuria with anemia. Furthermore, odds ratios for anemia were calculated by cross-categorization of ACR and eGFR.Among 1,456 patients, the mean age was 53.5 ± 12.4 years, and the mean eGFR and ACR were 51.9 ± 30.5 mL/min per 1.73 m2 and 853.2 ± 1,330.3 mg/g, respectively. Anemia was present in 644 patients (40.5%. Multivariate analysis showed that the odds ratio of anemia increased according to ACR levels, after adjusting for age, sex, eGFR, body mass index, pulse pressure, cause of CKD, use of erythropoiesis stimulating agents, serum calcium and ferritin (ACR < 30 mg/g as a reference group; 30-299 mg/g, adjusted odds ratio (OR = 1.43, 95% confidence interval (CI = 0.88-2.33; ≥300 mg/g, adjusted OR = 1.86, 95% CI = 1.12-3.10. In addition, graded associations were observed in cross-categorized groups of a higher ACR and eGFR compared to the reference group with an ACR <30 mg/g and eGFR ≥60 mL/min per 1.73 m2.The present study demonstrated that albuminuria was a significant risk factor for anemia in CKD patients independent of the eGFR.
In the treatment of diabetic nephropathy, ACE inhibitor therapy reduces albumin excretion and slows the rate of decline in glomerular filtration rate (GFR). Our study was designed to investigate whether these effects lay in amelioration of the underlying glomerular structural abnormalities. A total of 54 type 1 diabetic patients with albuminuria and blood pressure (BP) AER), and HbA1c were measured every 6 months. Enalapril lowered AER after 6 months by 26% (P AER. GFR decreased by a similar average rate of 4.1 ml x min(-1) x year(-1) (95% CI 2.6-5.6) in all three groups. BP and HbA1c were unchanged throughout the study in all groups. At baseline, nearly all biopsies showed classic appearances of diabetic glomerulopathy. There was no detectable effect of enalapril compared with either nifedipine or placebo on renal structure over 3 years. However, we found that patients with increased AER have established glomerulopathy and a progressive average decline in GFR of 4.1 ml x min(-1) x year(-1) in the absence of overt hypertension, and baseline AER appeared predictive of subsequent mesangial volume fraction (r = 0.20, P = 0.0018). In this small cohort of nonhypertensive patients studied for 3 years, disease evolution appears unaffected by treatment with either enalapril or nifedipine.
Han, Ji Suk; Lee, Mi Jung; Park, Kyoung Sook; Han, Seung Hyeok; Yoo, Tae-Hyun; Oh, Kook-Hwan; Park, Sue Kyung; Lee, Joongyub; Hyun, Young Youl; Chung, Wookyung; Kim, Yeong Hoon; Ahn, Curie; Choi, Kyu Hun
Anemia is a common complication among patients with chronic kidney disease (CKD), and it is associated with unfavorable clinical outcomes in patients with CKD independent of the estimated glomerular filtration rate (eGFR). We assessed the association of the urinary albumin-to-creatinine ratio (ACR) and eGFR with anemia in CKD patients. We conducted a cross-sectional study using baseline data from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). Multiple regression analysis was performed to identify the independent association of albuminuria with anemia. Furthermore, odds ratios for anemia were calculated by cross-categorization of ACR and eGFR. Among 1,456 patients, the mean age was 53.5 ± 12.4 years, and the mean eGFR and ACR were 51.9 ± 30.5 mL/min per 1.73 m2 and 853.2 ± 1,330.3 mg/g, respectively. Anemia was present in 644 patients (40.5%). Multivariate analysis showed that the odds ratio of anemia increased according to ACR levels, after adjusting for age, sex, eGFR, body mass index, pulse pressure, cause of CKD, use of erythropoiesis stimulating agents, serum calcium and ferritin (ACR anemia in CKD patients independent of the eGFR.
Espironolactona reduz a pressão arterial e a albuminúria de hipertensos obesos com síndrome metabólica Spironolactone reduces blood pressure and albuminuria of obese hypertensive patients with metabolic syndrome
Danielle Guedes Andrade Ezequiel
in this syndrome has been suggested. However, the treatment with antagonists of mineralocorticoid receptor in these individuals has not properly addressed. OBJECTIVE: To evaluate the effects of mineralocorticoid receptor blockade on blood pressure, inflammatory, metabolic and renal parameters in non-diabetic hypertensive individuals with the metabolic syndrome. METHODS: Twenty nine patients with metabolic syndrome were enrolled in a prospective protocol that consisted of 2 periods: baseline (2 weeks in which demographic data were obtained and antihypertensive medicines were withdrawn, and treatment period when the individuals were treated with spironolactone 25-50 mg once-a-day, for 16 weeks. In both periods, inflammatory, metabolic and renal parameters were assessed and the 24-hour ambulatory blood pressure monitorization was performed. RESULTS: After spironolactone treatment, 24 hour systolic and diastolic blood pressure decreased from 143.5 ± 15.17 mmHg to 133.2 ± 17.34 mmHg (p = 0.025 and from 85.2 ± 11.10 mmHg to 79.3 ± 11.78 mmHg (p = 0.026, respectively. HDL-cholesterol increased from 44.0 ± 8.67 mg/dl to 49.0 ± 6.75mg/dl (p = 0.000 and C-reactive protein decreased significantly from 6.3 ± 7.54 mg/l to 4.6 ± 6.3 mg/l (p = 0.009. Fasting plasma glucose, insulin, HOMA-IR and triglycerides did not change significantly after mineralocorticoid receptor blockade. Estimated glomerular filtration rate did not change whereas the logarithm of albuminuria decreased significantly from 2.5 ± 0.92 to 2.0 ± 0.9 (p = 0.028. CONCLUSION: In hypertensive subjects with MS the administration of spironolactone in monotherapy was effective for hypertension control, decreased uri nary albumin excretion and increased HDL-cholester ol plasma.
Cardiovascular disease (CVD) and chronic kidney disease (CKD) are common health problems and originates predominantly from generalized atherosclerosis. Diabetes, hypertension, and hypercholesterolemia are well known risk factors for atherosclerosis. Screening for and treatment of these risk factors
Lambers Heerspink, Hiddo Jan
Large scale randomized clinical trials are needed to detect small but meaningful effects of new drugs. However, large scale randomized clinical trials are expensive undertakings and they are in imbalance with the scientific output. As a consequence there is a strong voice for more efficacious
Introduction: We sought to report the 5-year incidence of proteinuria and risk factors for the progression of diabetic nephropathy in Egyptians with type 2 diabetes mellitus (DM). Methods: Five-hundred and twelve Egyptians with type 2 diabetes were evaluated at baseline and after 5-years of follow-up by a timed urine sample ...
de Zeeuw, Dick
Both renal and cardiovascular morbidity and mortality is increased markedly in patients with type 2 diabetes. Besides the classic risk factors and markers such as glucose, blood pressure, blood lipid profile, and lifestyle (smoking, overweight), novel risk markers are identified, among them urine
Ohsawa, Masato; Tamura, Kouichi; Wakui, Hiromichi; Kanaoka, Tomohiko; Azushima, Kengo; Uneda, Kazushi; Haku, Sona; Kobayashi, Ryu; Ohki, Kohji; Haruhara, Kotaro; Kinguchi, Sho; Toya, Yoshiyuki; Umemura, Satoshi
In non-dialysis chronic kidney disease (CKD) patients with dyslipidemia, statin therapy is recommended to prevent cardiovascular complications. Dyslipidemia has been also shown to be an independent risk factor for the progression of CKD. However, it is still unclear whether statin therapy exerts an inhibitory effect on renal deterioration in CKD patients with dyslipidemia. The purpose of the present study was to examine possible therapeutic effects of statin add-on therapy on renal function as well as parameters of lipid and glucose metabolism, arterial stiffness and oxidative stress, in comparison to diet therapy, in CKD patients with dyslipidemia. This study was a randomized, open-label, and parallel-group trial consisted of a 12-months treatment period in non-dialysis CKD patients with alubuminuria and dyslipidemia. Twenty eight patients were randomly assigned either to receive diet counseling alone (diet therapy group) or diet counseling plus pitavastatin (diet-plus-statin therapy group), to achieve the LDL-cholesterol (LDL-C) target of dyslipidemia.
Sexton, D J
The nephrotic syndrome is associated with an increased risk of venous and arterial thrombosis. There are little published data on the distribution, interpretation or determinants of serum D-dimer levels in patients with the nephrotic syndrome. We aimed to describe this relationship.
Forman, John P; Fisher, Naomi D L; Schopick, Emily L; Curhan, Gary C
Higher levels of albumin excretion within the normal range are associated with cardiovascular disease in high-risk individuals. Whether incremental increases in urinary albumin excretion, even within the normal range, are associated with the development of hypertension in low-risk individuals is unknown. This study included 1065 postmenopausal women from the first Nurses' Health Study and 1114 premenopausal women from the second Nurses' Health Study who had an albumin/creatinine ratio who did not have diabetes or hypertension. Among the older women, 271 incident cases of hypertension occurred during 4 yr of follow-up, and among the younger women, 296 incident cases of hypertension occurred during 8 yr of follow-up. Cox proportional hazards regression was used to examine prospectively the association between the albumin/creatinine ratio and incident hypertension after adjustment for age, body mass index, estimated GFR, baseline BP, physical activity, smoking, and family history of hypertension. Participants who had an albumin/creatinine ratio in the highest quartile (4.34 to 24.17 mg/g for older women and 3.68 to 23.84 mg/g for younger women) were more likely to develop hypertension than those who had an albumin/creatinine ratio in the lowest quartile (hazard ratio 1.76 [95% confidence interval 1.21 to 2.56] and hazard ratio 1.35 [95% confidence interval 0.97 to 1.91] for older and younger women, respectively). Higher albumin/creatinine ratios, even within the normal range, are independently associated with increased risk for development of hypertension among women without diabetes. The definition of normal albumin excretion should be reevaluated.
Forman, John P.; Fisher, Naomi D.L.; Schopick, Emily L.; Curhan, Gary C.
Higher levels of albumin excretion within the normal range are associated with cardiovascular disease in high-risk individuals. Whether incremental increases in urinary albumin excretion, even within the normal range, are associated with the development of hypertension in low-risk individuals is unknown. This study included 1065 postmenopausal women from the first Nurses’ Health Study and 1114 premenopausal women from the second Nurses’ Health Study who had an albumin/creatinine ratio
Jorsal, Anders; Petersen, Emilie Hein; Tarnow, Lise
AIM: Urinary adiponectin (u-adiponectin) excretion has been suggested to reflect early glomerular damage. Inspired by this, we studied the levels of u-adiponectin in type 1 diabetic patients with different levels of urinary albumin excretion (UAE). METHODS: U-adiponectin was analysed by ELISA in ...
Bakris, George L; Agarwal, Rajiv; Chan, Juliana C; Cooper, Mark E; Gansevoort, Ron T; Haller, Hermann; Remuzzi, Giuseppe; Rossing, Peter; Schmieder, Roland E; Nowack, Christina; Kolkhof, Peter; Joseph, Amer; Pieper, Alexander; Kimmeskamp-Kirschbaum, Nina; Ruilope, Luis M
IMPORTANCE: Steroidal mineralocorticoid receptor antagonists, when added to a renin-angiotensin system blocker, further reduce proteinuria in patients with chronic kidney disease but may be underused because of a high risk of adverse events. OBJECTIVE: To evaluate the safety and efficacy of
The aim of the study was to evaluate the influence of light to moderate dynamic work (450 kpm/min followed by 600 kpm/min during 20 min each) on the blood pressure and renal protein handling in insulin-dependent diabetic patients with incipient nephropathy (D3) (elevated baseline albumin excretio...
Full Text Available Introduction: Cardiovascular disease is the leading cause of death in type2 diabetes (DM. Microalbuminuria (MAis strongly associated with cardiovascular complications in type2 diabetes. Impaired cardiovascular autonomicfunction and increased albumin excretion are related in patients with diabetes. So this study is designed toinvestigate the relationship between cardiovascular autonomic function and microalbuminuria in type2 diabetes.Methods: The study comprised of 180 subjects of age group>50 years, classified into 3 groups of 60 subjects each.DM without MA, DM with MA and controls. The tests performed were 1 Heart rate response to deep breathing,valsalva maneuver and standing; 2 Blood pressure response to standing and to sustained handgrip. Individual testswere given score of 0, 1, or 2 and an overall autonomic test score of 0-10 was obtained.Results: Mean autonomic score in control, DM without MA and DM with MA are 1.97 ± 0.81, 5.73 ± 1.26 and 7.00± 1.80 respectively. The Coefficient of variation (% of control, DM without MA, DM with MA is 41.1, 21.9 and25.7 respectively. A significant difference in autonomic score was observed in the DM without MA (P<0.01 andDM with MA (P<0.01 when compared to controls.Conclusion: In conclusion type2 diabetic individuals should be diagnosed early to prevent disease progression tomicroalbuminuria and thus minimize complications.
Hansen, J M; Olsen, Niels Vidiendal; Feldt-Rasmussen, B
and passive ascent to 4,350 m. The calcium antagonist isradipine (5 mg/day; n = 6) or placebo (n = 6) was administered to abolish hypoxia-induced rises in blood pressure. Lithium clearance and urinary excretion of beta 2-microglobulin were used to evaluate renal tubular function. High altitude increased Ualb...
Igo, Robert P; Iyengar, Sudha K; Nicholas, Susanne B; Goddard, Katrina A B; Langefeld, Carl D; Hanson, Robert L; Duggirala, Ravindranath; Divers, Jasmin; Abboud, Hanna; Adler, Sharon G; Arar, Nedal H; Horvath, Amanda; Elston, Robert C; Bowden, Donald W; Guo, Xiuqing; Ipp, Eli; Kao, W H Linda; Kimmel, Paul L; Knowler, William C; Meoni, Lucy A; Molineros, Julio; Nelson, Robert G; Pahl, Madeline V; Parekh, Rulan S; Rasooly, Rebekah S; Schelling, Jeffrey R; Shah, Vallabh O; Smith, Michael W; Winkler, Cheryl A; Zager, Philip G; Sedor, John R; Freedman, Barry I
Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals. A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations. Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10(-5), LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies. These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN. Copyright © 2011 S. Karger AG, Basel.
Bowling, C Barrett; Bromfield, Samantha G; Colantonio, Lisandro D; Gutiérrez, Orlando M; Shimbo, Daichi; Reynolds, Kristi; Wright, Nicole C; Curtis, Jeffrey R; Judd, Suzanne E; Franch, Harold; Warnock, David G; McClellan, William; Muntner, Paul
Falls are common and associated with adverse outcomes in patients on dialysis. Limited data are available in earlier stages of CKD. We analyzed data from 8744 Reasons for Geographic and Racial Differences in Stroke Study participants ≥65 years old with Medicare fee for service coverage. Serious fall injuries were defined as a fall-related fracture, brain injury, or joint dislocation using Medicare claims. Hazard ratios (HRs) for serious fall injuries were calculated by eGFR and albumin-to-creatinine ratio (ACR). Among 2590 participants with CKD (eGFRfall injury compared with age-matched controls without a fall injury was calculated. Overall, 1103 (12.6%) participants had a serious fall injury over 9.9 years of follow-up. The incidence rates per 1000 person-years of serious fall injuries were 21.7 (95% confidence interval [95% CI], 20.3 to 23.2), 26.6 (95% CI, 22.6 to 31.3), and 38.3 (95% CI, 31.2 to 47.0) at eGFR levels ≥60, 45-59, and fall injuries were 0.91 (95% CI, 0.76 to 1.09) and 1.09 (95% CI, 0.86 to 1.37) for eGFR=45-59 and fall and age-matched controls were 21.0% and 5.5%, respectively. Elevated ACR but not lower eGFR was associated with serious fall injuries. Evaluation for fall risk factors and fall prevention strategies should be considered for older adults with elevated ACR. Copyright © 2016 by the American Society of Nephrology.
Seok Hui Kang
Full Text Available Background/Aims: The objective of the present study was to evaluate the clinical association between periodontitis and a high urinary albumin/creatinine ratio (UACR in individuals without diabetes mellitus. Methods: Data from the Korean National Health and Nutrition Examination Survey were used for this analysis. A high UACR was defined as UACR≥3.9 mg/g for men and UACR≥7.5 mg/g for women. The WHO community periodontal index (CPI was used to define periodontitis and assess its severity. Results: The numbers of participants without and with periodontitis were 3,046 and 8,571, respectively. The UACR values were higher in participants with periodontitis than in those without periodontitis. Logistic regression showed that the OR for a high UACR with the presence of periodontitis was 1.14 (P=0.044 on multivariate analysis. CPI score was positively associated with UACR. Conclusions: Periodontitis was associated with UACR in the non-diabetic participants in this study. Therefore, participants with periodontitis should be closely monitored for UACR, which can function as an early marker for renal injury.
Tapp, R J; Zimmet, P Z; Harper, C A
We examined the association of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG) and HbA1c with retinopathy and microalbuminuria using both deciles of glycaemia and change point models, to validate current diagnostic criteria for diabetes and to identify therapeutic thresholds for glycaemic...
Methods. Eighty children aged 5 -15 years with sickle cell anaemia (SCA) (HbSS) in a steady state attending the Lagos State University ... The sensitivity and specificity of the Micral-Test make it a good screening tool to detect MA in children with SCA. The Micral- .... The average cost of performing the Micral-Test was USD5.
The aim of the study was to evaluate the influence of light to moderate dynamic work (450 kpm/min followed by 600 kpm/min during 20 min each) on the blood pressure and renal protein handling in insulin-dependent diabetic patients with incipient nephropathy (D3) (elevated baseline albumin excretion...... but without clinical proteinuria). Fifteen male diabetic patients (D3) with a mean age of 26.5 +/- 4.8 years (SD) and a diabetes duration of 15.6 +/- 3.4 years (SD), 11 comparable diabetic patients with normal urinary albumin excretion (D2), and ten non-diabetic subjects (C) were studied. In D3 baseline....../min in D3 (193.0 mm Hg +/- 23.0) compared to D2 (170.5 +/- 17.3, 2P = 1.2%) and C (157.5 mm Hg +/- 20.9, 2P = 0.07%). Baseline albumin excretion in D3 was 82.6 micrograms/min X/ divided by 2.5 (geometric mean X/ divided by tolerance factor) and during exercise the maximal albumin excretion rose to 195...
Hellemons, Merel E.; Mazagova, Magdalena; Gansevoort, Ron T.; Henning, Robert H.; de Zeeuw, Dick; Bakker, Stephan J. L.; Lambers-Heerspink, Hiddo J.; Deelman, Leo E.
OBJECTIVE-Development of micro- or macroalbuminuria is associated with increased risk of cardiorenal complications, particularly in diabetes. For prevention of transition to micro- or macroalbuminuria, more accurate prediction markers on top of classical risk markers are needed. We studied a
White, Sarah L; Yu, Richard; Craig, Jonathan C; Polkinghorne, Kevan R; Atkins, Robert C; Chadban, Steven J
Urine dipsticks, an inexpensive accessible test for proteinuria, are widely advocated for mass screening; however, their diagnostic accuracy in the general community is largely unknown. Evaluation of diagnostic test accuracy in a cross-sectional cohort. AusDiab, a representative survey of Australian adults 25 years and older (conducted in 1999/2000). Stratified cluster random sampling from 11,247 individuals participating in the biomedical examination; complete urinalysis data available for 10,944. Urine dipsticks (Bayer Multistix), with a positive result defined as ≥1+ or trace or higher protein. Albumin-creatinine ratio (ACR), measured on a random spot urine sample. Reference test positivity was defined as ACR ≥30 mg/g or ACR ≥300 mg/g. Numbers of participants with ACR men and 0.7775 ± 0.0131 in women (P men and 0.9950 ± 0.0016 in women (P = 0.02). Dipstick result ≥1+ identified ACR ≥30 mg/g with 57.8% sensitivity (95% CI, 54.1%-61.4%) and 95.4% specificity (95% CI, 95.0%-95.8%) and identified ACR ≥300 mg/g with 98.9% sensitivity (99% CI, 92.1%-100%) and 92.6% specificity (99% CI, 92.0%-93.3%). A dipstick result of trace or higher identified ACR ≥30 mg/g with 69.4% sensitivity (95% CI, 65.9%-72.7%) and 86.8% specificity (95% CI, 86.1%-87.4%) and identified ACR ≥300 mg/g with 100% sensitivity (99% CI, 94.3%-100%) and 83.7% specificity (99% CI, 82.8%-84.6%). A negative dipstick result (less than trace) had a negative predictive value of 97.6% (95% CI, 97.2%-97.9%) for ACR ≥30 mg/g and a negative predictive value of 100% (99% CI, 99.9%-100%) for ACR ≥300 mg/g. The probability of an ACR ≥30 mg/g confirmed on laboratory investigation was 47.2% (95% CI, 43.9%-50.5%) based on a dipstick result ≥1+ and 27.1% (95% CI, 25.1%-29.2%) based on a trace or higher result. Isolated urine samples precluded assessment of test reproducibility. Urine specific gravity and pH were not recorded; therefore, the effect of urine concentration on test performance was not assessed. A dipstick test result <1+ or less than trace has a high negative predictive value in the general community setting, with minimal risk of a missed diagnosis of macroalbuminuria. High false-positive rates emphasize the need for laboratory confirmation of positive results. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Habibi, Anoosha; Stehlé, Thomas; Di Liberto, Gaetana; Rakotoson, Marie Georgine; Gellen-Dautremer, Justine; Loric, Sylvain; Moutereau, Stéphane; Sahali, Dil; Wagner-Ballon, Orianne; Remy, Philippe; Lang, Philippe; Grimbert, Philippe; Audureau, Etienne; Godeau, Bertrand; Galacteros, Frédéric
The earliest symptom of glomerular injury in patients with sickle cell disease (SCD) is microalbuminuria. The effect of hydroxyurea (HU) on urine albumin-to-creatinine ratio (ACR) is unclear and should be determined, because increasing numbers of patients with SCD take this drug to improve red blood cell function. In this cohort study of 58 SS-homozygous adults with SCD who initiated HU therapy, we evaluated ACR changes and relationships of these changes with demographic, clinical, and biologic parameters at HU initiation (baseline) and 6 months later (follow-up). Between baseline and follow-up, ACR declined significantly for the entire population (3.0–1.7 mg/mmol; P<0.01), but this was primarily driven by the ACR reduction in the microalbuminuria subgroup (8.1–2.3 mg/mmol; P=0.03; n=23). According to bivariate analyses on 39 patients who did not receive a blood transfusion during the study period, the baseline to follow-up ACR decline was strongly associated with decreases in levels of hemolysis markers, percentage of dense red blood cells, and systolic BP. Bivariate analysis also revealed a close association between the ACR decrease and high baseline levels of hemolysis markers and percentage of dense red blood cells. These results show that urine ACR decreased significantly after 6 months of HU and confirm a close relationship between ACR and hemolysis evolution in patients with SCD. PMID:26586692
Beentjes, JAM; Dullaart, RPF
Minor elevations in urinary albumin excretion rate (Ualb.V) are likely to be associated with renal function loss and increased cardiovascular risk. Since urinary albumin excretion is affected by the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis, we evaluated the effect of 6 months GH
Christensen, Cramer; Mogensen, C E
. In the acute study, using placebo/metoprolol 10 mg i.v. in patients with normal UAE, the maximal SBP at 600 kpm/min was reduced by 17 mmHg +/- 10 (SD) (2p less than 1.0%) and the maximal SBP at 600 kpm/min in the patients with incipient nephropathy was reduced by 15 mmHg +/- 11 (SD) (2p less than 1.......0%). However, no difference was observed in UAE, in patients with normal UAE or those with incipient nephropathy. Five of the patients with incipient nephropathy were followed with repeated exercise tests before and during 2.6 years of antihypertensive treatment, using metoprolol 200 mg/24 h and subsequently...
Thomas, W; Shen, Y; Molitch, M E; Steffes, M W
The Diabetes Control and Complications Trial (DCCT) enrolled 1441 participants to address the role of intensive therapy for type 1 diabetes mellitus on the onset and progression of microvascular complications. To examine the timing of elevated systolic BP (SBP) and diastolic BP (DBP) and increased albumin excretion rate (AER) in the progression to clinical diabetic nephropathy (AER > 300 mg/24 h on two consecutive visits from a baseline of AER AER and hemoglobin A(1c), but who did not progress to clinical diabetic nephropathy-matched controls. In the conventional treatment group, the 21 progressors exhibited a significant rise in mean AER (above their own baseline levels and above values in the matched controls) at year 2 of the DCCT. In contrast, the progressors' mean DBP and SBP were not significantly higher than baseline until year 3 (DBP) or year 4 (SBP) and not significantly higher than the matched controls until year 4 (both DBP and SBP). On the individual level, 19 of 21 (90%) progressors reached clinical diabetic nephropathy before the diagnosis of hypertension (140/90 mmHg). In the intensive treatment group, however, the rise in DBP preceded the rise in AER by 1 to 2 yr among the six progressors. Both intensively treated progressors who experienced hypertension reached this before AER > 300 mg/24 h. These results underline the early and prognostic rise in AER in diabetic patients, but only in those who received conventional treatment. The evolution of diabetic renal disease may follow a different course in patients who receive intensive diabetic treatment.
Deckert, T; Kofoed-Enevoldsen, A; Vidal, P
albumin excretion rate was normal in group D1; 30-100 mg/24 h in group D2; 101-300 mg/24 h in group D3 and greater than 300 mg/24 h in groups D4 and D5. Group D5 had elevated serum creatinine (above 110 mumol/l). Glomerular filtration rate and renal plasma flow were determined by constant infusion...
Nelson, Laerke M; Andreassen, Arne K; Andersson, Bert
early CNI withdrawal in de novo HTx is unknown. METHODS: We tested if measured glomerular filtration rate (mGFR, by chrome-ethylenediaminetetraacetic acid clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the Scandinavian Heart Transplant...
Persson, Frederik; Lewis, Julia B; Lewis, Edmund J
Elevated BP contributes to development and progression of proteinuria and decline in renal function in patients with type 2 diabetes. Our post hoc analysis assessed the baseline BP influence on the antiproteinuric effect in the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) study....
Nørgaard, K; Jensen, T; Feldt-Rasmussen, B
The effects of the calcium channel blocker, isradipine, on BP, urinary albumin excretion, plasma lipoproteins and natriuresis in albuminuric Type 1 (insulin-dependent) diabetic patients were assessed. Fifteen Type 1 diabetic patients aged 22-52 years were studied. All had elevated urinary albumin...... or placebo for eight weeks. Then, after 4 weeks (the wash-out period), each patient received the drug he or she had not taken before for another 8 weeks. Systolic blood pressure was lowered by 8 mmHg from 127 (114-139) mmHg (P less than 0.01) and diastolic by 5 mmHg from 81 (70-87) mmHg (P less than 0...... cholesterol and triglyceride decreased significantly (P less than 0.01) and the level of HDL cholesterol increased, but not significantly (P = 0.08). In conclusion, treatment of Type 1 diabetic patients, at risk of progressive clinical nephropathy, with the calcium channel blocker, isradipine, had beneficial...
Christensen, Cramer; Mogensen, C E
The aim of the study was to clarify whether antihypertensive treatment could affect the systolic blood pressure (SBP) and urinary albumin excretion (UAE) in diabetics during exercise (450 kpm/min, followed by 600 kpm/min, 20 min each). Young male insulin-dependent diabetics with normal UAE (n = 9...
Kröpelin, Tobias Felix
The worldwide increase in the number of patients with diabetic kidney disease needs to be tackled due to the consequences of the disease. Improving the quality of life and survival of this growing number of patients requires timely access to novel and effective treatments. Timely access to novel
Greve, Sara V; Blicher, Marie K; Sehestedt, Thomas
OBJECTIVES: The aim of this study was to investigate whether subclinical vascular damage improved traditional risk prediction, reclassifying individuals with regard to primary prevention. METHODS: Two thousand and fifty-nine healthy individuals aged 41, 51, 61, and 71 years were divided into age,...
Parving, H H; Andersen, A R; Smidt, U M
nephropathy. Mean age of the patients was 30 yr. All patients had a diastolic blood pressure greater than or equal to 95 mm Hg. Metoprolol, hydralazine, and furosemide or thiazide were used as antihypertensives. During the 12-mo treatment period, BP decreased from 151/104 to 133/85 mm Hg (P less than 0...
Rossing, P; Hommel, E; Smidt, U M
Diabetic nephropathy is the main cause of increased mortality and morbidity in IDDM patients. The effect of antihypertensive treatment on the progression of the nephropathy is highly variable. The aim of this study was to evaluate putative predictors of the progression in diabetic nephropathy dur...
van der Velde, Marije; Bello, Aminu K.; Brantsma, Auke H.; El Nahas, Meguid; Bakker, Stephan J. L.; de Jong, Paul E.; Gansevoort, Ronald T.
Background. To investigate the added value of elevated urinary albumin excretion (UAE) and high high-sensitive C-reactive protein (hs-CRP) in predicting new-onset type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and chronic kidney disease (CKD) in addition to the present metabolic
Hansen, J M; Kanstrup, I L; Richalet, J P
Renal function and the urinary excretion rate of albumin (Ualb) at rest and during infusion of dopamine (3 micrograms kg-1 min-1) were investigated in eight normal volunteers at sea level and 48 h after a rapid, passive ascent to an altitude of 4350 m. Oxygen saturation decreased to 81% (77...... increased ERPF, GFR, CLi, CNa, and decreased the filtration fraction in both environments. Infusion of dopamine further increased Ualb to 10.5 micrograms min-1 (5.5-64.8) (p
Dimitriadis, K; Tsioufis, C; Kasiakogias, A; Miliou, A; Poulakis, M; Kintis, K; Bafakis, I; Benardis, E; Tousoulis, D; Stefanadis, C
Emerging evidence suggests that the soluble receptor for advanced glycation end-products (sRAGE) is implicated in the development of vascular disease. We investigated the interrelationships of sRAGE with albumin to creatinine ratio (ACR) and arterial stiffness in essential hypertension. In 309 untreated non-diabetic hypertensives, ACR values were determined as the mean of three non-consecutive morning spot urine samples and aortic stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (c-f PWV). In all subjects, venous blood sampling was performed for the estimation of sRAGE levels. Patients with low (n = 155) compared to those with high sRAGE values (n = 154) had greater 24-h systolic BP (140 ± 8 vs. 134 ± 7 mmHg, p involvement of sRAGE in the progression of hypertensive vascular damage. Copyright © 2011 Elsevier B.V. All rights reserved.
Pilemann-Lyberg, S; Persson, F; Frystyk, J
Significant improvements have been made in the management of Type 1 diabetes over the last three decades . We wanted to examine if uric acid lowering with allopurinol changes the urinary albumin excretion rate (UAER) or 51 Cr EDTA GFR in people with Type 1 diabetes and diabetic nephropathy...
Rathcke, Camilla Noelle; Persson, Frederik; Tarnow, Lise
-40 levels correlated with the urinary albumin-to-creatinine ratio in the total group of participants (r2 = 0.25, P diastolic blood pressure, A1C, and serum creatinine. After adjustment for significant covariates...
Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a new biomarker for the early identification of acute kidney injury (AKI). There is also increasing evidence of an association between urinary albumin\\/creatinine ratio (ACR) and AKI. The primary aim of this study was to evaluate the clinical utility of these biomarkers to predict AKI in a population of perioperative patients treated with goal-directed haemodynamic therapy (GDHT). Secondary aims were to examine NGAL and ACR as sensitive biomarkers to detect the effects of GDHT and to investigate the association of these biomarkers with secondary outcomes.
Stolzenburg Oxlund, Christina; Kurt, Birgül; Schwarzensteiner, Ilona
The proteinase prostasin is a candidate mediator for aldosterone-driven proteolytic activation of the epithelial sodium channel (ENaC). It was hypothesized that the aldosterone-mineralocorticoid receptor (MR) pathway stimulates prostasin abundance in kidney and urine. Prostasin was measured in pl...
Weir, Matthew R; Hollenberg, Norman K; Zappe, Dion H
The blood pressure (BP)-lowering response to renin-angiotensin-aldosterone system blockade in hypertensive African-Americans is typically less than in whites. To determine whether higher than conventional doses of renin-angiotensin-aldosterone system blockade can improve BP reduction in African-A...
Hellemons, Merel E; Persson, Frederik; Bakker, Stephan J L
We aimed to investigate the individual impact of initial responses in urinary albumin excretion (UAE) and systolic blood pressure (SBP) to angiotensin II receptor blocker (ARB) treatment on long-term renal outcome in patients with type 2 diabetes and microalbuminuria....
Krajcoviechova, Alena; Tremblay, Johanne; Wohlfahrt, Peter; Bruthans, Jan; Tahir, Muhmmad Ramzan; Hamet, Pavel; Cifkova, Renata
The impact of metabolic phenotypes on the association of uricemia with urinary albumin/creatinine ratio (uACR) remains unresolved. We evaluated the association between serum uric acid and uACR in persons with 0, and 1-2 metabolic syndrome (MetS) components and determined the modification effects of visceral adiposity index (VAI), mean arterial pressure (MAP), and fasting glucose on this association. Using data from a cross-sectional survey of a representative Czech population aged 25-64 years (n = 3612), we analyzed 1,832 persons without decreased glomerular filtration rate <60ml/min/1.73 m2, diabetes, and MetS. MetS components were defined using the joint statement of the leading societies. Of the 1,832 selected participants, 64.1% (n = 1174) presented with 1-2 MetS components (age 46.3±11.2; men 51.7%), whereas 35.9% (n = 658) were free of any component (age 39.4±10.0; men 34.2 %). In fully adjusted multiple linear regression models for uricemia, uACR was an independent factor for increase in uric acid levels only in persons with 1-2 MetS components (standardized beta (Sβ) 0.048; P = 0.024); however, not in those without any component (Sβ 0.030; P = 0.264). Uric acid levels increased by the interaction of uACR with VAI (Sβ 0.06; P = 0.012), and of uACR with MAP (Sβ 0.05; P = 0.009). Finally, the association of uACR with uricemia was confined to persons whose VAI together with MAP were ≥the median of 1.35 and 98mm Hg, respectively (Sβ 0.190; P < 0.001). We demonstrated a strong modification effect of VAI and MAP on the association between uACR and uricemia, which suggests obesity-related hypertension as the underlying mechanism. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: firstname.lastname@example.org
Hugo You-Hsien Lin
Full Text Available Cisplatin-induced acute kidney injury (AKI is a major concern among clinicians in prescribing cisplatin-based chemotherapy. This study evaluated and compared the ability of urinary biomarkers, including urinary neutrophil gelatinase-associated lipocalin (NGAL, cystatin C, and the urinary albumin to creatinine ratio (ACR to predict cisplatin-induced AKI. Thirty-three cancer patients receiving cisplatin-based chemotherapy were prospectively studied, including 10 (30% who developed AKI (the study group. Changes of urinary biomarkers were compared at 4 hours, 8 hours, and 12 hours, and 1 day, 2 days, 3 days, and 4 days after cisplatin intravenous infusions (75 mg/m2 versus the baseline. There was a significant increase in urinary NGAL levels from 12 hours to 4 days (p<0.05 compared to baseline after cisplatin infusion in the AKI group. The magnitude of these changes over time differed significantly by group (p<0.001. The area under the receiver operating curve describing the relationship between urinary NGAL levels and AKI within 12 hours was 0.865 (95% confidence interval=0.691–1.000. Urinary NGAL levels independently predicted AKI 12 hours after cisplatin (p=0.045 after adjustments for age, gender, body mass index, baseline serum creatinine, and urinary total protein. Urinary NGAL levels may be an early biomarker of AKI in patients receiving cisplatin-based treatment.
Søraas, Camilla L; Wachtell, Kristian; Okin, Peter M
Regression of left ventricular (LV) hypertrophy and albuminuria in hypertension has previously been shown to reduce clinical cardiovascular events and death. We aimed to investigate the associations of regression of electrocardiographic (ECG) LV hypertrophy and albuminuria with the incidence...
Laverman, GD; Andersen, S; Rossing, P; Navis, G; de Zeeuw, D; Parving, HH
Background. AT1-receptor blockade dose dependently lowers blood pressure (BP) and albuminuria. Reduction of BP and albuminuria are independent treatment targets for renoprotection, but whether this requires similar dose titration is unknown. Methods. We tested this in two studies designed to find
Vart, Priya; Gansevoort, Ron T.; Joosten, Michel M.; Bultmann, Ute; Reijneveld, Sijmen A.
CONTEXT: Evidence on the strength of the association between low SES and chronic kidney disease (CKD; measured by low estimated glomerular filtration rate [eGFR], high albuminuria, low eGFR/high albuminuria, and renal failure) is scattered and sometimes conflicting. Therefore, a systematic review
von Scholten, Bernt J; Persson, Frederik; Rosenlund, Signe
AIMS: Among patients with type 2 diabetes and albuminuria, cardiorenal morbidity and mortality are high despite multifactorial treatment. Short-term reduction in albuminuria is considered suggestive of long-term renoprotective effects. We evaluated the renal effects of the glucagon-like peptide-1...
Schutte, Elise; Gansevoort, Ron T.; Benner, Jacqueline; Lutgers, Helen L.; Lambers Heerspink, Hiddo J.
Diabetic kidney disease is diagnosed and staged by albuminuria and estimated glomerular filtration rate. Although albuminuria has strong predictive power for renal function decline, there is still variability in the rate of renal disease progression across individuals that are not fully captured by
Schievink, Bauke; de Zeeuw, Dick; Smink, Paul A.; Andress, Dennis; Brennan, John J.; Coll, Blai; Correa-Rotter, Ricardo; Hou, Fan Fan; Kohan, Donald; Kitzman, Dalane W.; Makino, Hirofumi; Parving, Hans-Henrik; Perkovic, Vlado; Remuzzi, Giuseppe; Tobe, Sheldon; Toto, Robert; Hoekman, Jarno; Heerspink, Hiddo J. Lambers
BACKGROUND: A recent phase II clinical trial (Reducing Residual Albuminuria in Subjects with Diabetes and Nephropathy with AtRasentan trial and an identical trial in Japan (RADAR/JAPAN)) showed that the endothelin A receptor antagonist atrasentan lowers albuminuria, blood pressure, cholesterol,
Tershakovec, A.M.; Keane, W.F.; Zhang, Z.
Renal pathology and dyslipidemia commonly coexist. Treatments that lower albuminuria/proteinuria may lower lipids, but it is not known whether lipid lowering independent of lessening albuminuria/proteinuria slows progression of kidney disease. We examined the association between LDL cholesterol...
Heerspink, Hiddo J. L.; Desai, Mehul; Jardine, Meg; Balis, Dainius; Meininger, Gary; Perkovic, Vlado
Sodium-glucose cotransporter 2 inhibition with canagliflozin decreases HbA1c, body weight, BP, and albuminuria, implying that canagliflozin confers renoprotection. We determined whether canagliflozin decreases albuminuria and reduces renal function decline independently of its glycemic effects in a
Conclusion: The risk of DR exists in patients with type 2 diabetes even in normoalbuminuric individuals. Close monitoring is particularly needed if patients have longer duration of diabetes, hypertension, anemia, or high normal albuminuria. Keywords: Albuminuria, Diabetic retinopathy, Predictors, Type 2 diabetes mellitus ...
Awua-Larbi, Stella; Wong, Tien Y; Cotch, Mary Frances; Durazo-Arvizu, Ramon; Jacobs, David R; Klein, Barbara E K; Klein, Ronald; Lima, Joao; Liu, Kiang; Kramer, Holly
Changes in retinal microvascular caliber, which occur prior to onset of retinopathy, may indicate presence of kidney damage. This study examined the association between retinal arteriolar [central retinal artery equivalent (CRAE)] and venular caliber [central retinal venule equivalent (CRVE)] and presence of albuminuria (micro- or macroalbuminuria) among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of adults aged 45-84 years without baseline clinical cardiovascular disease. During the second MESA exam, digital fundus photography was completed in 5897 participants who provided spot urine specimens. Albuminuria was defined by spot urine albumin/creatinine ratios ≥ 30 mg/g. Multivariable adjusted odds of albuminuria by quintiles of CRAE and CRVE were determined using logistic regression. Analyses were repeated after stratifying by presence of type 2 diabetes. Albuminuria was noted in 11.5% (n = 675) and included 584 subjects with microalbuminuria and 91 with macroalbuminuria. A significant U-shaped pattern was seen with higher prevalence of albuminuria across quintile extremes in CRAE (15.7, 8.8 and 10.6% in CRAE Quintiles 1, 3 and 5, respectively; P <0.0001). After adjustment for covariates, both narrower CRAE [odds ratios (OR) 1.55; 95% confidence interval (CI) 1.17-2.04, Quintile 1 versus 3) and wider CRAE (OR 1.44; 95% CI 1.07-1.93, Quintile 5 versus 3) were significantly associated with albuminuria. Associations appeared substantially stronger in adults with than without type 2 diabetes but the interaction term for diabetes and CRAE on presence of albuminuria did not meet statistical significance (P = 0.3). No association was noted between CRVE quintiles and albuminuria. Albuminuria is associated with narrower and wider arteriolar caliber. Future studies should determine whether variation in arteriolar caliber predicts incident albuminuria and whether associations are mediated by hypertension and diabetes. Such information could
Jae Hee Ahn
Full Text Available BackgroundDiabetic nephropathy is a leading cause of end stage renal disease and is associated with an increased risk of cardiovascular mortality. It manifests as albuminuria or impaired glomerular filtration rate (GFR, and the prevalence of diabetic nephropathy varies with ethnicity. The prevalence of diabetic nephropathy and its determinants in Korean adults have not previously been studied at the national level. This cross-sectional study was undertaken to ascertain the prevalence and determinants of albuminuria and chronic kidney disease (CKD in Korean patients with diabetes.MethodsThe Korea National Health and Nutrition Examination Survey (KNHANES V, conducted in 2011, was used to define albuminuria (n=4,652, and the dataset of KNHANES IV-V (2008-2011 was used to define CKD (n=21,521. Selected samples were weighted to represent the entire civilian population in Korea. Albuminuria was defined as a spot urine albumin/creatinine ratio >30 mg/g. CKD was defined as a GFR <60 mL/min/1.73 m2.ResultsAmong subjects with diabetes, 26.7% had albuminuria, and 8.6% had CKD. Diabetes was associated with an approximate 2.5-fold increased risk of albuminuria, with virtually no difference between new-onset and previously diagnosed diabetes. Only systolic blood pressure was significantly associated with albuminuria, and old age, high serum triglyceride levels, and previous cardiovascular disease (CVD were related with CKD in subjects with diabetes.ConclusionKorean subjects with diabetes had a higher prevalence of albuminuria and CKD than those without diabetes. Blood pressure was associated with albuminuria, and age, triglyceride level, and previous CVD were independent determinants of CKD in subjects with diabetes.
Tershakovec, A.M.; Keane, W.F.; Zhang, Z.
Renal pathology and dyslipidemia commonly coexist. Treatments that lower albuminuria/proteinuria may lower lipids, but it is not known whether lipid lowering independent of lessening albuminuria/proteinuria slows progression of kidney disease. We examined the association between LDL cholesterol...... of losartan- versus placebo-based antihypertensive therapy in patients with type 2 diabetes and nephropathy. LDL cholesterol lowering was associated with a lower risk of ESRD; however, this seemed to be largely an association with the reduction in albuminuria Udgivelsesdato: 2008/3...
Comparison of the antialbuminuric effects of benidipine and hydrochlorothiazide in Renin-Angiotensin System (RAS) inhibitor-treated hypertensive patients with albuminuria: the COSMO-CKD (COmbination Strategy on Renal Function of Benidipine or Diuretics TreatMent with RAS inhibitOrs in a Chronic Kidney Disease Hypertensive Population) study.
Ando, Katsuyuki; Nitta, Kosaku; Rakugi, Hiromi; Nishizawa, Yoshiki; Yokoyama, Hitoshi; Nakanishi, Takeshi; Kashihara, Naoki; Tomita, Kimio; Nangaku, Masaomi; Takahashi, Katsutoshi; Isshiki, Masashi; Shimosawa, Tatsuo; Fujita, Toshiro
This study evaluated the non-inferiority of renoprotection afforded by benidipine versus hydrochlorothiazide in hypertensive patients with chronic kidney disease (CKD). In this prospective, multicenter, open-labeled, randomized trial, the antialbuminuric effects of benidipine and hydrochlorothiazide were examined in renin-angiotensin system (RAS) inhibitor-treated patients with blood pressure (BP) readings of ≥ 130/80 mmHg and ≤ 180/110 mmHg, a urinary albumin to creatinine ratio (UACR) of ≥ 300 mg/g, and an estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73m(2). Patients received benidipine (n = 176, final dose: 4.8 mg/day) or hydrochlorothiazide (n = 170, 8.2 mg/day) for 12 months. Benidipine and hydrochlorothiazide exerted similar BP- and eGFR-decreasing actions. The UACR values for benidipine and hydrochlorothiazide were 930.8 (95% confidence interval: 826.1, 1048.7) and 883.1 (781.7, 997.7) mg/g at baseline, respectively. These values were reduced to 790.0 (668.1, 934.2) and 448.5 (372.9, 539.4) mg/g at last observation carried forward (LOCF) visits. The non-inferiority of benidipine versus hydrochlorothiazide was not demonstrated (benidipine/hydrochlorothiazide ratio of LOCF value adjusted for baseline: 1.67 (1.40, 1.99)). The present study failed to demonstrate the non-inferiority of the antialbuminuric effect of benidipine relative to that of hydrochlorothiazide in RAS inhibitor-treated hypertensive patients with macroalbuminuria.
Santiago Cedeño Mora
Conclusion: The cardiovascular risk scores (FRS-CVD and ASCVD [AHA/ACC 2013] can estimate the probability of atherosclerotic cardiovascular events in patients with CKD regardless of renal function, albuminuria and previous cardiovascular events.
Jørgensen, Peter Godsk; Biering-Sørensen, Tor; Mogelvang, Rasmus
diabetes from two secondary care centres and stratified according to albuminuria status in normo-, micro-, and macroalbuminuria. We performed comprehensive echocardiography including conventional imaging, tissue Doppler imaging, and 2D speckle tracking. Cardiac remodelling occurred in patients...
Heba M Yossef
Hypomagnesemia is prevalent in diabetic patients. It is associated with diabetic complications and poor glycemic control. High plasma triglycerides, total cholesterol, creatinine level, albuminuria, HbA1c, FBS, and 2-h PPBS are independent correlates of hypomagnesemia.
Discussion: In conclusion, while accounting for baseline eGFR, albuminuria, and covariables, CKD273 adds to the prediction of stage 3 chronic kidney disease, at which point intervention remains an achievable therapeutic target.
Néstor Gabriel Toapanta Gaibor
Conclusions: In our group of elderly patients, impairment of renal function is slow, particularly in CKD-5 patients. Albuminuria and PTH at baseline levels are prognostic factors in the evolution of renal function.
Discussion: DKD is associated with altered fuel substrate use and remodeling of sphingolipid metabolism in T2DM with DKD. Associations of albuminuria and impaired filtration function with distinct metabolomic signatures suggest different pathophysiology underlying these 2 manifestations of DKD.
Persson, Frederik; Rossing, Peter
Approximately 20% to 40% of patients with type 1 or type 2 diabetes mellitus develop diabetic kidney disease. This is a clinical syndrome characterized by persistent albuminuria (> 300 mg/24 h, or > 300 mg/g creatinine), a relentless decline in glomerular filtration rate (GFR), raised arterial......). Untreated microalbuminuria will gradually worsen, reaching clinical proteinuria or severely increased albuminuria (albuminuria grade A3) over 5 to 15 years. The GFR then begins to decline, and without treatment, end-stage renal failure is likely to result in 5 to 7 years. Although albuminuria is the first...... sign of diabetic nephropathy, the first symptom is usually peripheral edema, which occurs at a very late stage. Regular, systematic screening for diabetic kidney disease is needed in order to identify patients at risk of or with presymptomatic diabetic kidney disease. Annual monitoring of urinary...
Poulsen, Per Løgstrup; Hansen, Klavs Würgler; Gaede, Peter Haulund
The documentation for the beneficial effects of antihypertensive treatment in patients with diabetes is overwhelming. Most patients will require three or four antihypertensive drugs to achieve blood pressure (BP) goals. The regime should include an agent that blocks the renin angiotensin...... aldosterone system. Reduction in albuminuria during antihypertensive treatment is indicative of renal and cardiovascular protection. Thus, if the level of albuminuria remains high, the treatment should be intensified, even in the light of achieved BP goals. Options for intensification are dual blockade...
Full Text Available Antihypertensive treatment mitigates the progression of chronic kidney disease. Here, we comparatively assessed the effects of antihypertensive agents in normotensive and hypertensive diabetic patients with microalbuminuric kidney disease.MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs comparing oral antihypertensive agents in adult diabetic patients with microalbuminuria. The primary efficacy outcome was reduction in albuminuria, and the primary safety outcomes were dry cough, presyncope, and edema. Random-effects pairwise and Bayesian network meta-analyses were performed to produce outcome estimates for all RCTs, only hypertensive RCTs, or only normotensive RCTs. Surface under the cumulative ranking (SUCRA probability rankings were calculated for all outcomes. Sensitivity analyses on type 2 diabetes status, age, or follow-up duration were also performed.A total of 38 RCTs were included in the meta-analyses. The angiotensin-converting enzyme inhibitor-calcium channel blocker (ACEI-CCB combination therapy of captopril+diltiazem was most efficacious in reducing albuminuria irrespective of blood pressure status. However, the ACEI-angiotensin receptor blocker (ACEI-ARB combination therapy of trandolapril+candesartan was the most efficacious in reducing albuminuria for normotensive patients, while the ACEI-CCB combination therapy of fosinopril+amlodipine was the most efficacious in reducing albuminuria for hypertensive patients. The foregoing combination therapies displayed inferior safety profiles relative to ACEI monotherapy with respect to dry cough, presyncope, and edema. With respect to type 2 diabetic patients with microalbuminuria, the Chinese herbal medicine Tangshen formula followed by the ACEI ramipril were the most efficacious in reducing albuminuria.Trandolapril+candesartan appears to be the most efficacious intervention for reducing albuminuria
Xu, Chang; Chang, Anthony; Hack, Bradley K; Eadon, Michael T; Alper, Seth L; Cunningham, Patrick N
Severe sepsis is often accompanied by acute kidney injury (AKI) and albuminuria. Here we studied whether the AKI and albuminuria associated with lipopolysaccharide (LPS) treatment in mice reflects impairment of the glomerular endothelium with its associated endothelial surface layer. LPS treatment decreased the abundance of endothelial surface layer heparan sulfate proteoglycans and sialic acid, and led to albuminuria likely reflecting altered glomerular filtration permselectivity. LPS treatment decreased the glomerular filtration rate (GFR), while also causing significant ultrastructural alterations in the glomerular endothelium. The density of glomerular endothelial cell fenestrae was 5-fold lower, whereas the average fenestrae diameter was 3-fold higher in LPS-treated than in control mice. The effects of LPS on the glomerular endothelial surface layer, endothelial cell fenestrae, GFR, and albuminuria were diminished in TNF receptor 1 (TNFR1) knockout mice, suggesting that these LPS effects are mediated by TNF-α activation of TNFR1. Indeed, intravenous administration of TNF decreased GFR and led to loss of glomerular endothelial cell fenestrae, increased fenestrae diameter, and damage to the glomerular endothelial surface layer. LPS treatment decreased kidney expression of vascular endothelial growth factor (VEGF). Thus, our findings confirm the important role of glomerular endothelial injury, possibly by a decreased VEGF level, in the development and progression of AKI and albuminuria in the LPS model of sepsis in the mouse.
Kim, Eun Sook; Kwon, Hyuk Sang; Ahn, Chul Woo; Lim, Dong Jun; Shin, Jeong Ah; Lee, Seung Hwan; Cho, Jae Hyoung; Yoon, Kun Ho; Kang, Moo Il; Cha, Bong Yun; Son, Ho Young
To determine the relationship between serum uric acid, metabolic syndrome (MetS), and albuminuria in type 2 diabetic patients. A total of 504 Korean patients with type 2 diabetes aged 57.3 years were retrospectively evaluated for clinical histories, anthropometric measurements, and biochemical studies. Urinary albumin excretion (UAE) was measured by a 24-h urine collection. Prevalence of MetS increased according to the quartiles of uric acid levels (≤3.7, 3.8 to 4.5, 4.6 to 5.5, and >5.5 mg/dl; 52.1%, 52.1%, 57.5%, and 71.6%, respectively, Puric acid levels. Serum uric acid levels had significantly increased risk of albuminuria [odds ratio (OR) 1.425, 95% confidence interval (CI) 1.085-1.873] after adjusting for age, gender, and conventional risk factors. Uric acid level remains a significant predictor for abnormal albuminuria after adjusting for MetS presence as well as the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) (OR 1.414, 95% CI 1.071-1.868). An elevated uric acid level was significantly associated with MetS and was an independent predictor of albuminuria after adjusting for conventional risk factors and MetS. Regular measurements of uric acid level could give information for predicting the presence of MetS and albuminuria in Korean type 2 diabetic patients. Copyright © 2011 Elsevier Inc. All rights reserved.
Sandsmark, Danielle K; Messé, Steven R; Zhang, Xiaoming; Roy, Jason; Nessel, Lisa; Lee Hamm, Lotuce; He, Jiang; Horwitz, Edward J; Jaar, Bernard G; Kallem, Radhakrishna R; Kusek, John W; Mohler, Emile R; Porter, Anna; Seliger, Stephen L; Sozio, Stephen M; Townsend, Raymond R; Feldman, Harold I; Kasner, Scott E
Chronic kidney disease is associated with an increased risk of cardiovascular events. However, the impact of chronic kidney disease on cerebrovascular disease is less well understood. We hypothesized that renal function severity would be predictive of stroke risk, independent of other vascular risk factors. The study population included 3939 subjects enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study, a prospective observational cohort. Stroke events were reported by participants and adjudicated by 2 vascular neurologists. Cox proportional hazard models were used to compare measures of baseline renal function with stroke events. Multivariable analysis was performed to adjust for key covariates. In 3939 subjects, 143 new stroke events (0.62 events per 100 person-years) occurred over a mean follow-up of 6.4 years. Stroke risk was increased in subjects who had worse baseline measurements of renal function (estimated glomerular filtration rate and total proteinuria or albuminuria). When adjusted for variables known to influence stroke risk, total proteinuria or albuminuria, but not estimated glomerular filtration rate, were associated with an increased risk of stroke. Treatment with blockers of the renin-angiotensin system did not decrease stroke risk in individuals with albuminuria. Proteinuria and albuminuria are better predictors of stroke risk in patients with chronic kidney disease than estimated glomerular filtration rate. The impact of therapies targeting proteinuria/albuminuria in individuals with chronic kidney disease on stroke prevention warrants further investigation. © 2015 American Heart Association, Inc.
Peixoto, Elisa B M I; Papadimitriou, Alexandros; Lopes de Faria, Jacqueline M; Lopes de Faria, Jose B
In diabetic hypertensive rats, tempol reduces albuminuria by restoring the redox imbalance. Increased formation of reactive oxygen species leading to activation of poly(ADP-ribose) polymerase (PARP)-1 and podocyte loss by apoptosis contribute to albuminuria in diabetes mellitus (DM). In the present study, we investigated the hypothesis that in DM tempol reduces albuminuria by inhibition of PARP-induced podocyte apoptosis. DM was induced in 4-week-old spontaneously hypertensive rats by streptozotocin. Mouse and human podocyte cell lines were cultured in normal or high-glucose conditions, with or without tempol and/or a PARP-1 inhibitor, PJ34. In diabetic rats, tempol treatment did not affect plasma glucose levels or systolic blood pressure. Albuminuria was higher in diabetic rats, and it was reduced by tempol. DM leads to an elevation of glomerular apoptotic cells and to podocyte loss; both were prevented by tempol treatment. DM increases the expression of poly(ADP-ribose)-modified proteins in isolated glomeruli, and it was reduced by tempol. In vitro, high glucose increased caspase-3 activity and led to a higher number of apoptotic cells that were prevented by tempol and the PARP-1 inhibitor. In DM, tempol reduces albuminuria associated with reduction of podocyte apoptosis and decreasing oxidative stress via PARP signaling. Copyright © 2012 S. Karger AG, Basel.
Pena, Michelle J; Jankowski, Joachim; Heinze, Georg
OBJECTIVE: Micro and macroalbuminuria are strong risk factors for progression of nephropathy in patients with hypertension or type 2 diabetes. Early detection of progression to micro and macroalbuminuria may facilitate prevention and treatment of renal diseases. We aimed to develop plasma...... and the Steno Diabetes Center. Cases transitioned from normo to microalbuminuria, or from micro to macroalbuminuria. Controls, matched for age, sex, and baseline albuminuria stage, did not transition. Follow-up was 3.0 ± 0.9 years. Plasma proteomics profiles were measured by liquid chromatography......-electrospray-trap mass-spectrometry. Classifiers were developed and cross-validated for prediction of transition in albuminuria stage. Improvement in risk prediction was tested on top of a reference model of baseline albuminuria, estimated glomerular filtration rate, and renin-angiotensin-aldosterone system intervention...
Wachtell, K.; Olsen, M.H.
at baseline and had normoalbuminuria by conventional definitions. The study showed that quartiles of albuminuria beyond the lowest quartile were increasingly predictive of subsequent hypertensive disease, even at levels well below what is conventionally considered to be the normal range. This commentary......This Practice Point commentary discusses a recent study by Forman et al. that examined the association between baseline urinary albumin:creatinine ratio and the risk of developing hypertension among 2,179 women in the first and second Nurses' Health Studies who did not have hypertension or diabetes...... highlights the importance of evaluating albuminuria as an indicator of target organ damage and a risk factor for cardiovascular disease. Patients without hypertension, diabetes or other cardiovascular diseases who have albuminuria should be considered at risk of cardiovascular disease and should undergo...
Heerspink, Hiddo J L; Makino, Hirofumi; Andress, Dennis
AIMS: The selective endothelin (ET) A receptor antagonist atrasentan has been shown to lower albuminuria in North American and Asian patients with type 2 diabetes and nephropathy. As drug responses to many drugs may differ between North American and Asian populations, we assessed the influence...... change in albuminuria. Bodyweight change, a proxy of fluid retention, was used as a safety endpoint. Pharmacodynamics were determined in Asians (N = 77) and North Americans (N = 134). Atrasentan plasma concentration was measured in 161 atrasentan-treated patients. RESULTS: Mean albuminuria reduction...... in Asian, compared to North American, patients was, respectively, -34.4% vs -26.3% for 0.75 mg/d ( P = .44) and -48.0% vs -28.9% for 1.25 mg/d ( P = .035). Bodyweight gain did not differ between North American and Asian populations. Atrasentan plasma concentrations were higher in Asians compared to North...
Jensen, Jan Skov; Feldt-Rasmussen, Bo; Borch-Johnsen, Knut
with type 2 diabetes) and 42 healthy controls. All were randomly recruited. MAIN OUTCOME MEASURE: We used an in vivo method for measurement of transvascular transport of low-density lipoprotein (LDL). Autologous 131I-LDL was reinjected iv, and the 1-h fractional escape rate was taken as an index...... of transvascular transport. RESULTS: Transvascular LDL transport was 1.8 (1.6-2.0), 2.3 (2.0-2.6), and 2.6 (1.3-4.0)%/[h x (liter/m2)] in healthy controls, diabetic controls, and diabetes patients with systolic hypertension or albuminuria, respectively (P = 0.013; F = 4.5; df =2; ANOVA). These differences most......CONTEXT: Diabetes is associated with a highly increased risk of atherosclerosis, especially if hypertension or albuminuria is present. OBJECTIVE: We hypothesized that the increased transvascular lipoprotein transport in diabetes may be further accelerated if hypertension or albuminuria is present...
Jensen, Magnus Thorsten; Søgaard, Peter; Andersen, Henrik Ullits
PURPOSE: Cardiovascular disease is the most common cause of mortality in type 1 diabetes; patients with albuminuria are at greatest risk. We investigated myocardial function and premature myocardial impairment in type 1 diabetes patients with and without albuminuria compared to controls. METHODS...... in type 1 diabetes compared to controls (e.g. E/e' = 8; 9.2 years [normoalbuminuria], 17.3 years [microalbuminuria] and 41.4 years [macroalbuminuria] prematurely, respectively). CONCLUSION: In type 1 diabetes patients with albuminuria, both systolic and diastolic functions are impaired, whereas......: This study included a cross-sectional survey of 1093 type 1 diabetes patients from Steno Diabetes Center and 200 healthy controls. Conventional and tissue Doppler echocardiographic measurements were analysed in multivariable models in normoalbuminuria (n = 760), microalbuminuria (n = 227...
Full Text Available BACKGROUND: To assess the association of albuminuria and retinopathy with metabolic syndrome (MetS and the related metabolic components defined by various criteria in Chinese community-based subjects. METHODS: A total of 3240 Chinese subjects were recruited from urban communities and classified into subgroups with isolated or concomitant state of the two microvascular diseases. MetS was defined according to the standard of International Diabetes Federation, the National Cholesterol Education Program's Adult Treatment Panel III and Chinese Diabetes Society (CDS, separately. Albuminuria was defined as an elevated morning urine albumin-to-creatinine ratio. Retinopathy were identified with nonmydriatic retinal photographs according to the Diabetic Retinopathy Disease Severity Scale. Logistic regression was performed to analyze the contributive risk factors. RESULTS: The subgroup of isolated retinopathy was the oldest (P<0.05, with higher blood pressure (P<0.001 and larger waist circumference (P<0.05. After adjusting for age, sex and other metabolic components, individuals with blood pressure over 130/85 mmHg were prone to have isolated albuminuria (OR: 1.51, P = 0.0001; while individuals with fasting plasma glucose over 5.6 mmol/L were in high risk of retinopathy concomitant with albuminria (OR: 3.04, P = 0.006. Larger waist circumference was a potential risk factors for isolated albuminuria and isolated retinopathy, though not significant after further adjustment of other metabolic components. The risk for albuminuria and retinopathy increased with the aggregation of three or more metabolic components. However, the MetS per se did not have synergic effect and only the MetS defined by CDS remained as a risk factor. CONCLUSIONS: Albuminuria and retinopathy were highly associated with accumulated metabolic abnormalities including sub-clinical elevated blood pressure and elevated fasting plasma glucose.
Hansen, Troels Krarup; Gall, Mari-Anne; Tarnow, Lise
We evaluated the relationship between serum mannose-binding lectin (MBL) and mortality and incident albuminuria in 326 patients with type 2 diabetes mellitus (T2DM). During 15 years of follow-up, 169 patients died. In a multivariate analysis, MBL was a significant risk factor for death from any...... cause and added to the predictive power of CRP. Normoalbuminuric patients with both high MBL and high C-reactive protein (CRP) levels had a significantly increased risk of developing albuminuria. We conclude that MBL alone or in combination with CRP can provide prognostic information on mortality...
Vaia D. Raikou
Full Text Available Background: The influence of metabolic syndrome (MetS on kidneys is related to many complications. We aimed to assess the association between MetS and chronic renal disease defined by a poor estimated glomerular filtration rate (eGFR and/or the presence of microalbuminuria/macroalbuminuria. Methods: 149 patients (77 males/72 females were enrolled in the study. Chronic renal disease was defined according to KDIGO 2012 criteria based on eGFR category and classified albuminuria. MetS was studied as a dichotomous variable (0 to 5 components including hypertension, waist circumference, low HDL-cholesterol, high triglycerides, and high glucose. Results: The association between clustering MetS and both classified eGFR and classified albuminuria (x2 = 50.3, p = 0.001 and x2 = 26.9, p = 0.003 respectively was found to be significant. The MetS presence showed an odds 5.3-fold (1.6–17.8 higher for low eGFR and 3.2-fold (1.2–8.8 higher for albuminuria in combination with the presence of diabetes mellitus, which also increased the risk for albuminuria by 3.5-fold (1.1–11.3. Albuminuria was significantly associated with high triglycerides, hypertension, high glucose (x2 = 11.8, p = 0.003, x2 = 11.4, p = 0.003 and x2 = 9.1, p = 0.01 respectively, and it was mildly associated with a low HDL-C (x2 = 5.7, p = 0.06. A significant association between classified eGFR and both high triglycerides and hypertension (x2 = 9.7, p = 0.04 and x2 = 16.1, p = 0.003 respectively was found. Conclusion: The clustering of MetS was significantly associated with chronic renal disease defined by both classified eGFR and albuminuria. The definition of impaired renal function by classified albuminuria was associated with more MetS components rather than the evaluation of eGFR category. MetS may contribute to the manifestation of albuminuria in patients with diabetes mellitus.
Ushenko, O. G.; Dubolazov, O. V.; Pidkamin, L. Y.; Sidor, M. I.; Pavlyukovich, N.; Pavlyukovich, O.
The paper consists of two parts. The first part presents short theoretical basics of the method of Jones-matrix mapping with the help of reference wave. It was provided experimentally measured coordinate distributions of modulus of Jones-matrix elements of polycrystalline film of bile. It was defined the values and ranges of changing of statistic moments, which characterize such distributions. The second part presents the data of statistic analysis of the distributions of matrix elements of polycrystalline film of urine of donors and patients with albuminuria. It was defined the objective criteria of differentiation of albuminuria.
Nielsen, Stine E; Sugaya, Takeshi; Tarnow, Lise
OBJECTIVE: We studied tubular and glomerular damage in type 1 diabetic patients by measuring urinary-liver fatty acid binding protein (U-LFABP) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on U-LFABP in patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: We......, 46, and 40% with increasing doses of lisinopril (NS). CONCLUSIONS: An early and progressive increase in tubulointerstitial damage as reflected by increased U-LFABP levels occurs in type 1 diabetic patients and is associated with albuminuria. Furthermore, ACE inhibition reduces the tubular...
Schulz, Angela; Weiss, Judith; Schlesener, Maria
In a cross between the Munich Wistar Frömter (MWF) rat and spontaneously hypertensive rats (SHR), a major quantitative trait locus (QTL) was identified on rat chromosome 6 (RNO6) that demonstrated the strongest linkage to albuminuria among several QTL identified. The QTL represented the only locu...... in MWF is determined by a complex interplay of several QTL, our data demonstrate that genetic exchange of one locus on RNO6 leads to marked suppression of early-onset albuminuria and renal damage in MWF. Udgivelsesdato: 2007-Jan...
R A Bolarinwa
Full Text Available Renal abnormalities in adult Nigerians with sickle cell anemia (SCA have not been extensively studied. To determine the prevalence, pattern and the associated risk factors of renal disease, 72 subjects with SCA from two centers in the southwestern Nigeria were investigated. Socio-demographic data, body mass index and clinical findings were documented. The urine analysis, serum bio-chemistry, hemogram and renal factors attributable to SCA were determined. Presence of albuminuria of at least 1+ or microalbuminuria in those negative with dipstick; and the estimated glomerular filtration rate (eGFR using the Cockcroft-Gault formula categorized subjects to various stages of chronic kidney disease (CKD. Subjects with and without albuminuria were compared to determine the relative risk associated with renal disease. Four (5.6% subjects had macro-albuminuria, while 32 (44.4% had micro-albuminuria and 30 (41.7% had hemoglobinuria. In the subjects with albuminuria, age, hematocrit, systolic blood pressure, serum creatinine, urea and creatinine clearance were numerically higher while the eGFR was numerically lower. There was no significant difference in the clinical parameters studied in the two groups of subjects. The diastolic blood pressure was significantly higher in the albuminuric group. Based on eGFR, 22 (30.6% subjects had hyperfiltration (GFR > 140 mL/min/1.73 m2, of whom 36.4% had albuminuria, 18 (25.0% had stage 1 CKD, 30 (41.7% had stage 2 CKD and two (2.7% subjects had stage 3 CKD with albuminuria. None had stage 4 and 5 CKD. We conclude that renal abnormalities, importantly albuminuria, is common in adult Nigerians with SCA and the pattern and incidence are similar to those reported from other parts of the world. Regular blood pressure monitoring, early diagnosis and active intervention are advocated to delay progression to end-stage kidney disease in view of poor outcomes of renal replacement therapy in SCA patients with nephropathy.
Parvanova, Aneliya; Trillini, Matias; Podestà, Manuel A; Iliev, Ilian Petrov; Ruggiero, Barbara; Abbate, Manuela; Perna, Annalisa; Peraro, Francesco; Diadei, Olimpia; Rubis, Nadia; Gaspari, Flavio; Carrara, Fabiola; Stucchi, Nadia; Belviso, Antonio; Bossi, Antonio C; Trevisan, Roberto; Remuzzi, Giuseppe; de Borst, Martin; Ruggenenti, Piero
BACKGROUND: Macroalbuminuria predicts renal and cardiovascular events in patients with type 2 diabetes. We aimed to assess the albuminuria-lowering effects of salt restriction, paricalcitol therapy, or both, in this population. METHODS: In this randomised, double-blind, placebo-controlled, crossover
Jørgensen, Mette; Mainz, Jan; Carinci, Fabrizio
process performance measures of diabetes care, including blood pressure monitoring (RR=.98, CI=.96-.99), treatment with antihypertensive drugs (RR=.83, CI=.70-.97) and angiotensin-converting enzyme/angiotensin II receptor inhibitors (RR=.72, CI=.55-.93), screening for albuminuria (RR=.96, CI=.93-.99), eye...
Rabkin, I.Kh.; Matevosov, A.L.; Gotman, L.N.
Experience of using roentgenoendovascular occlusion (REO) of vessels in clinical medicine have been analysed. Literary data are presented, experience in closure of vessel aneurysm, blocking of pathological arteriovenous anastomoses, functional exclusion of kidney at chronic renal insufficiency with hypertension and albuminuria, before kidney transplantation, functional splenectomy at hematologic diseases and hypersplenism and also of adducting arteries aimed at artificial ischemisation of neoplasms, is presented
Stoltze Gaborit, Freja; Bosselmann, Helle; Kistorp, Caroline
and 24-h urinary albumin excretion (albuminuria). METHODS: We prospectively enrolled 132 patients with reduced left ventricular ejection fraction (LVEF) referred to an outpatient HF clinic. The patients had a median age of 70 years (interquartile rage: 64-75), 26.5 % were female, median LVEF was 33 % (27...
Jacobsen, P; Rossing, K; Rossing, P
serum creatinine [mean (95% CI)] 8 (4 to 12)/9 (3 to 16)/8 (0 to 16) % (ANOVA, NS), respectively. Adjusting for differences in reduction in MABP did not change the association between decrease in albuminuria and ACE/ID genotypes (P multiple linear regression analysis revealed that the ACE...
Provoost, AP; Shiozawa, M; Van Dokkum, RPE; Jacob, HJ
The genetically hypertensive fawn-hooded (FHH/Eur) rat is characterized by the early presence of systolic and glomerular hypertension, progressive proteinuria (UPV), and albuminuria (UAV), and focal glomerulosclerosis, resulting in premature death from renal failure. Previous studies showed that at
Blaauwwiekel, EE; Beusekamp, BJ; Sluiter, WJ; Hoogenberg, K; Dullaart, RPF
The effect of the apolipoprotein (apo) E genotype on the lipoprotein response to a 1 year low cholesterol diet (200 mg cholesterol per day) was evaluated in 36 patients with Type 1 diabetes mellitus with albuminuria between 10 and 200 mu g min(-1). Apo E genotype was characterized by polymerase
Conclusión: La prevalencia de HTA resistente aumenta con la edad, el grado de ERC y la albuminuria. Estrategias como el tratamiento con antagonistas de receptores de aldosterona se asocian con un mejor control tensional en este grupo de pacientes y disminuyen su prevalencia.
Zobel, Emilie Hein; von Scholten, Bernt Johan; Lindhardt, Morten
AIMS/HYPOTHESIS: Management of diabetic nephropathy includes reduction of albuminuria, blood pressure and weight. The GLP-1 receptor agonist liraglutide may possess these pleiotropic effects in addition to the glucose lowering effect. We aimed to elucidate the individual liraglutide treatment res...
Takenaka, Tsuneo; Kishimoto, Miyako; Ohta, Mari; Tomonaga, Osamu; Suzuki, Hiromichi
The effects of sodium-glucose co-transporter type 2 inhibitors on home blood pressure were examined in type 2 diabetes with nephropathy. The patients with diabetic nephropathy were screened from medical records in our hospitals. Among them, 52 patients who measured home blood pressure and started to take sodium-glucose co-transporter type 2 inhibitors were selected. Clinical parameters including estimated glomerular filtration rate, albuminuria and home blood pressure for 6 months were analysed. Sodium-glucose co-transporter type 2 inhibitors (luseogliflozin 5 mg/day or canagliflozin 100 mg/day) reduced body weight, HbA1c, albuminuria, estimated glomerular filtration rate and office blood pressure. Although sodium-glucose co-transporter type 2 inhibitors did not alter morning blood pressure, it reduced evening systolic blood pressure. Regression analyses revealed that decreases in evening blood pressure predicted decrements in albuminuria. The present data suggest that sodium-glucose co-transporter type 2 inhibitors suppress sodium overload during daytime to reduce evening blood pressure and albuminuria.
Vogt, Liffert; Navis, Gerjan; Koester, Juergen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick
Objective To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized
Liang, Wei; Chen, Cheng; Shi, Jing; Ren, Zhilong; Hu, Fengqi; van Goor, Harry; Singhal, Pravin C.; Ding, Guohua
Background. Several studies in patients with primary aldosteronism (PA) have suggested that aldosterone (ALD) is directly contributing to albuminuria. However, there are limited data pertaining to the direct role of ALD in (EPL), telmisartan (TEL) and amlodipine (AML) on ALD-induced renal structural
Vogt, Liffert; Navis, Gerjan; Köster, Jürgen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick
To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized study. The
Dobre, Daniela; Lambers Heerspink, Hiddo J.; de Zeeuw, Dick
Progressive decline of renal function in chronic kidney disease (CKD), measured by a reduced glomerular filtration rate or albuminuria, is linked to an increased risk of cardiovascular (CV) disease. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), most
Patients on regular dialysis and those who had received a Nidney ... Patient's baseline evaluation included a structured clinical interview to. Emergence and Progression of Albuminuria in a Cohort of Egyptian Patients with. Type 2 Diabetes .... of any proteinuria and education, insulin dose, peripheral neuropathy, use of ...
de Vries, Laura V.; Dobrowolski, Linn C.; van den Bosch, Jacqueline J. O. N.; Riphagen, Ineke J.; Krediet, C. T. Paul; Bemelman, Frederike J.; Bakker, Stephan J. L.; Navis, Gerjan
In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore
de Vries, Laura V; Dobrowolski, Linn C; van den Bosch, Jacqueline J O N; Riphagen, Ineke J; Krediet, C T Paul; Bemelman, Frederike J; Bakker, Stephan J L; Navis, Gerjan
BACKGROUND: In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown.
Roscioni, Sara S.; de Zeeuw, Dick; Bakker, Stephan J. L.; Lambers Heerspink, Hiddo J.
Mineralocorticoid-receptor antagonists (MRAs) reduce blood pressure and albuminuria in patients treated with angiotensin-converting-enzyme inhibitors or angiotensin-II-receptor blockers. The use of MRAs, however, is limited by the occurrence of hyperkalaemia, which frequently occurs in patients
Heerspink, Hiddo J. Lambers; de Zeeuw, Dick
Makani and colleagues report that dual blockade of the renin-angiotensin-aldosterone system is associated with harm despite previous studies showing that this approach decreases blood pressure and albuminuria. Do these results imply that we should abandon surrogate markers? Or should we become more
Pinto-Sietsma, SJ; Janssen, WMT; Hillege, HL; Navis, G; De Zeeuw, D; De Jong, PE
Microalbuminuria (MA) is an important early sign of diabetic nephropathy. Hyperfiltration and impaired filtration in relation to albuminuria has been well investigated in diabetic subjects. This study tested the hypothesis that an increased urinary albumin excretion (UAE) is associated with renal
Dec 1, 2011 ... Severity of Proteinuria in SCD patients. In terms of severity of proteinuria the majority had microalbuminuria. This is consistent with the findings of Alvarez and colleagues.11 They however had a higher proportion (17.4%) of their patients with macro- albuminuria and the upper- age- limit was 18 years.
Conclusion: The results of this study showed that higher serum levels of obestatin were associated with macro albuminuria suggesting that obestatin may have a role in underlying pathogenic mechanisms that leads to diabetic nephropathy. Key words: Diabetes mellitus type 2, diabetic nephropathy, obestatin, omentin ...
... obesity and micro- or macroalbuminuria. HbA1c%, ALP, cholesterol, triglycerides and LDLC were higher in diabetics than controls. In contrast, urea, creatinine and HDLC were lower in diabetics. Keywords: Clinical and Biochemical Features, Gaza Strip, Type 2 Diabetes, Lipids, albuminuria, Family history, complications.
In the present preliminary study the insertion/deletion polymorphism within angiotensin converting enzyme gene is not likely to be associated with nephropathy in type 2 diabetic patients of Punjabi population of Pakistan. Key words: Angiotensin converting enzymes, insertion/deletion polymorphism, albuminuria and type 2 ...
We examined association of uVEGFs, pIGFs concentrations with fasting glucose level, glycemic control index (HbA1c %), urinary measured renal parameters i.e. creatinine, creatinine clearance and albuminuria as well as lipogram parameters in 75 type 2 diabetic patients and 25 healthy controls. Study subjects were ...
Santiago Cedeño Mora
Conclusiones: Las escalas de predicción de RCV (FRS-CVD y ASCVD [AHA/ACC 2013] pueden estimar la probabilidad de sufrir ECV ateroscleróticos en pacientes con ERC independientemente de la función renal, albuminuria y antecedente de ECV.
Néstor Gabriel Toapanta Gaibor
Conclusiones: En nuestro grupo de pacientes de edad avanzada el deterioro de la función renal es muy lento, especialmente en los pacientes en estadio 5. La albuminuria y la PTH al inicio del seguimiento son factores pronósticos en la evolución de su función renal.
Background: Microalbuminuria is an early indicator of Diabetic nephropathy and cerebrovascular disease. Objective: To evaluate ... Significant negative correlations exist between microalbuminuria, ... duration, ethnicity, HBA1c, TC, TG, HDL-C and LDL/HDL ratio are independent predictors of albuminuria. Keywords: ...
Bakker, Stephan J L
Albuminuria is rapidly gaining recognition as a marker of the presence and of the progression of chronic kidney disease (CKD). In a new study, Naresh et al. attempt to define cut-off values for percentage change in urinary albumin:creatinine ratio that reflect changes in CKD status rather than
Lopes van Balen, Veronica Agatha; Spaan, Julia Jeltje; Cornelis, Tom; Spaanderman, Marc Erich August
Preeclampsia (PE), an endothelial disease that affects kidney function during pregnancy, is correlated to an increased future risk of cardiovascular and chronic kidney disease. The Kidney Disease Improving Global Outcomes (KDIGO) 2012 guideline emphasizes the combined role of glomerular filtration rate (GFR) and albuminuria in determining the frequency of monitoring of kidney function. In this study we evaluated the prevalence of CKD in women with a history of PE. We investigated how many seemingly healthy women required monitoring of kidney function according to the KDIGO guideline. We included 775 primiparous women with a history of PE. They were at least 4 months postpartum, and had no pre-existing hypertension, diabetes or kidney disease. We estimated GFR by the CKD-Epidemiology equation and urinary albumin loss by albumin creatinine ratio in a 24-h urine collection. Most women, 669 (86.3 %), had a normal GFR and absent albuminuria. Based on the KDIGO guideline, 13.7 % would require at least yearly monitoring of kidney function. Only 1.4 % were classified to be at high risk for kidney function deterioration. Monitoring of kidney function seems relevant for about one in seven women with a history of PE, mainly due to albuminuria. Albuminuria should be evaluated postpartum to identify those women that need further monitoring of kidney function.
In conclusion, CKD is prevalent in patients with the metabolic syndrome and may be due to a synergistic effect of the various components of the syndrome. Diastolic blood pressure and obesity may predict CKD in MetS patients. Albuminuria may also be prevalent in MetS patients; increasing with increasing number of MetS traits.
Full Text Available Background/Aims: This study aims to assess the cumulative incidence of elevated albuminuria, hypertension and decreased estimated glomerular filtration rate (eGFR to identify possible renal injury in children with SFK. Methods: Forty-two children with SFK (23 boys; 27 congenital were included in a prospective follow-up study. Blood pressure, albuminuria and eGFR were assessed repeatedly and the cumulative incidence rate of various forms of renal injury, overall and by type of etiology, were evaluated. Finally, renal injury-free survival was analyzed. Results: Mean follow-up was until age 11.3 years (SD 6.3 years. During follow-up, 16 (38.1% patients met the criteria for renal injury, defined as hypertension (10; 23.8%, severely increased albuminuria (3; 7.1% and a significantly impaired eGFR (2 (5; 11.9% and/or use of antihypertensive or antiproteinuric medication (11; 26.2%. Children with CAKUT in SFK had a significantly higher incidence of renal injury. The median time to develop renal injury was 12.8 years. Conclusion: A substantial proportion of children with SFK develop renal injury during childhood, especially those with CAKUT in the SFK. Therefore, close follow-up of albuminuria, blood pressure and eGFR are warranted to identify chronic kidney disease in its early stages.
Zhu Wei; Yang Yuzhi; Li Xianhou; Feng Kun; Wang Dan
Objective: To investigate the relationship between serum adiponectin concentration and diabetic nephropathy in patients with type 2 diabetes mellitus. Methods: The serum adiponectin concentrations were measured with RIA in 163 patients with type 2 diabetes mellitus and 50 controls. Results: In the diabetic patients, serum adiponectin concentrations were significantly higher in patients with macro albuminuria (n = 54) than those inpatients with microalbuminuria (n = 57) (P <0.01), normal albuminuria (n = 52) and controls (P < 0.001). Adiponectin concentrations were higher in patients with micro albuminuria than in patients with normal albuminuria (P < 0.05 ). Serum adiponectin concentrations were significantly positively correlated with serum creatinine, HbA1c, TC, SBP, DBP, TG and UAER levels (P < 0.05), and adiponectin concentrations were not obviously correlated with age, HDL-C levels and BMI (P > 0.05). Adiponectin concentrations were higher in women than in men, but there was no significant difference (P > 0.05). Conclusion: Serum adiponectin concentrations are increased in type 2 diabetic patients with advanced nephropathy. The kidney seems to be involved in the metabolism and excretion of adiponectin. Adiponectin may play important roles in the onset and development of diabetic nephropathy. (authors)
Mahmoodi, Khan; Yatsuya, Hiroshi; Matsushita, Kunihiro; Sang, Yinying; Gottesman, Rebecca F.; Astor, Brad C.; Woodward, Mark; Longstreth, W. T.; Psaty, Bruce M.; Shlipak, Michael G.; Folsom, Aaron R.; Gansevoort, Ronald; Coresh, Josef
Background and purpose-Although low glomerular filtration rate (GFR) and albuminuria are associated with increased risk of stroke, few studies compared their contribution to risk of ischemic versus hemorrhagic stroke separately. We contrasted the association of these kidney measures with ischemic
Jan 19, 2012 ... associated with nephropathy in type 2 diabetic patients of Punjabi population of Pakistan. Key words: Angiotensin converting enzymes, insertion/deletion polymorphism, albuminuria and type 2 diabetes mellitus. INTRODUCTION. Diabetic nephropathy is a leading cause of diabetic. *Corresponding author.
Full Text Available Diet is one of the largest modifiable risk factors for chronic kidney disease (CKD-related death and disability. CKD is largely a progressive disease; however, it is increasingly appreciated that hallmarks of chronic kidney disease such as albuminuria can regress over time. The factors driving albuminuria resolution remain elusive. Since albuminuria is a strong risk factor for GFR loss, modifiable lifestyle factors that lead to an improvement in albuminuria would likely reduce the burden of CKD in high-risk individuals, such as patients with diabetes. Dietary therapy such as protein and sodium restriction has historically been used in the management of CKD. Evidence is emerging to indicate that other nutrients may influence kidney health, either through metabolic or haemodynamic pathways or via the modification of gut homeostasis. This review focuses on the role of diet in the pathogenesis and progression of CKD and discusses the latest findings related to the mechanisms of diet-induced kidney disease. It is possible that optimizing diet quality or restricting dietary intake could be harnessed as an adjunct therapy for CKD prevention or progression in susceptible individuals, thereby reducing the burden of CKD.
Li, Kun; Zou, Jianan; Ye, Zhibin; Di, Jianzhong; Han, Xiaodong; Zhang, Hongwei; Liu, Weijie; Ren, Qinggui; Zhang, Pin
Obesity is an independent risk factor of development and progression of chronic kidney disease (CKD). Data on the benefits of bariatric surgery in obese patients with impaired kidney function have been conflicting. To explore whether there is improvement in glomerular filtration rate (GFR), proteinuria or albuminuria after bariatric surgery. We comprehensively searched the databases of MEDLINE, Embase, web of science and Cochrane for randomized, controlled trials and observational studies that examined bariatric surgery in obese subjects with impaired kidney function. Outcomes included the pre- and post-bariatric surgery GFR, proteinuria and albuminuria. In obese patients with hyperfiltration, we draw conclusions from studies using measured GFR (inulin or iothalamate clearance) unadjusted for BSA only. Study quality was evaluated using the Newcastle-Ottawa Scale. 32 observational studies met our inclusion criteria, and 30 studies were included in the meta-analysis. No matter in dichotomous data or in dichotomous data, there were statistically significant reduction in hyperfiltration, albuminuria and proteinuria after bariatric surgery. The main limitation of this meta-analysis is the lack of randomized controlled trials (RCTs). Another limitation is the lack of long-term follow-up. Bariatric surgery could prevent further decline in renal function by reducing proteinuria, albuminuria and improving glomerular hyperfiltration in obese patients with impaired renal function. However, whether bariatric surgery reverses CKD or delays ESRD progression is still in question, large, randomized prospective studies with a longer follow-up are needed.
van Hateren, Kornelis J J; Landman, Gijs W D; Groenier, Klaas H; Bilo, Henk J G; Kleefstra, Nanne
There is limited evidence with respect to the between-group effects of various angiotensin receptor blockers (ARBs) on blood pressure and albuminuria in patients with type 2 diabetes mellitus. Therefore, we aimed to investigate the effects of differing ARBs on systolic blood pressure (SBP) and the albumin-creatinine ratio after 1 year in a large cohort of patients with type 2 diabetes mellitus. In 2007, 24 940 primary care patients with type 2 diabetes mellitus participated in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study, a prospective observational cohort study. Patients were included in the current study if they were prescribed an ARB in 2007 and if 1-year follow-up data were available. The final study population comprised 3610 patients. Multivariate mixed-model analyses were performed to estimate effects of the various ARBs on SBP and albuminuria. Stratified subgroup analyses were performed according to baseline hypertension and albuminuria. SBP decreased in all groups, the largest decrease being observed in the group receiving telmisartan. No significant or relevant changes over time were observed among groups for SBP and albuminuria. In the subgroup (n=1225) of normotensive patients, telmisartan was associated with a larger decrease in SBP after 1 year compared to other ARBs, without different effects on the albumin-creatinine ratio. We observed no differences in effects on SBP and the albumin-creatinine ratio among differing ARBs in patients with type 2 diabetes mellitus. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.
Nielsen, S E; Schjoedt, K J; Astrup, A S
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...
Neal, Bruce; Perkovic, Vlado; Mahaffey, Kenneth W.; de Zeeuw, Dick; Fulcher, Greg; Erondu, Ngozi; Shaw, Wayne; Law, Gordon; Desai, Mehul; Matthews, David R.
BACKGROUND: Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. METHODS: The CANVAS
Mann, Johannes F E; Ørsted, David D; Brown-Frandsen, Kirstine
of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer...
..., or limitation of exertion 80 Constant albuminuria with some edema; or, definite decrease in kidney... (greater than two times/year), and/or requiring continuous intensive management 30 Long-term drug therapy, 1-2 hospitalizations per year and/or requiring intermittent intensive management 10 [59 FR 2527, Jan...
Pena, Michelle J; Heinzel, Andreas; Rossing, Peter
. LASSO and ridge regression were performed to develop the classifier. Improvement in albuminuria response prediction was assessed by calculating differences in R(2) between a reference model of clinical parameters and a model with clinical parameters and the classifier. The classifier was externally...
Westland, R.; Schreuder, M.F.; Bokenkamp, A.; Spreeuwenberg, M.D.; Wijk, J.A. van
BACKGROUND: Children with a solitary functioning kidney (SFK) have an increased risk of developing hypertension, albuminuria and chronic kidney disease in later life. This renal injury is hypothesized to be caused by glomerular hyperfiltration that follows renal mass reduction in animal studies.
Kolvek, Gabriel; Podracka, Ludmila; Rosenberger, Jaroslav; Stewart, Roy E.; van Dijk, Jitse P.; Reijneveld, Sijmen A.
BACKGROUND/AIMS: This study aims to assess the cumulative incidence of elevated albuminuria, hypertension and decreased estimated glomerular filtration rate (eGFR) to identify possible renal injury in children with SFK. METHODS: Forty-two children with SFK (23 boys; 27 congenital) were included in a
Castoldi, Giovanna; di Gioia, Cira Rt; Bombardi, Camila
Aim of the study was to evaluate the effect of compound 21 (C21), selective AT2 receptor agonist, in diabetic nephropathy and the potential additive effect of C21, when associated to losartan treatment, on the development of albuminuria and renal fibrosis in Zucker diabetic fatty (ZDF) rats. The ...
Petrykiv, Sergei; Sjostrom, C. David; Greasley, Peter J.; Xu, John; Persson, Frederik; Heerspink, Hiddo J. L.
BACKGROUND AND OBJECTIVE: Sodium glucose cotransporter 2 inhibition with dapagliflozin decreases hemoglobin A1c (HbA1c), body weight, BP, and albuminuria (urinary albumin-to-creatinine ratio). Dapagliflozin also modestly increases hematocrit, likely related to osmotic diuresis/natriuresis. Prior
Full Text Available Abstract Background Kidney disease is associated with an increased total mortality and cardiovascular morbimortality in the general population and in patients with Type 2 diabetes. The aim of this study is to determine the prevalence of kidney disease and different types of renal disease in patients with type 2 diabetes (T2DM. Methods Cross-sectional study in a random sample of 2,642 T2DM patients cared for in primary care during 2007. Studied variables: demographic and clinical characteristics, pharmacological treatments and T2DM complications (diabetic foot, retinopathy, coronary heart disease and stroke. Variables of renal function were defined as follows: 1 Microalbuminuria: albumin excretion rate & 30 mg/g or 3.5 mg/mmol, 2 Macroalbuminuria: albumin excretion rate & 300 mg/g or 35 mg/mmol, 3 Kidney disease (KD: glomerular filtration rate according to Modification of Diet in Renal Disease 2 and/or the presence of albuminuria, 4 Renal impairment (RI: glomerular filtration rate 2, 5 Nonalbuminuric RI: glomerular filtration rate 2 without albuminuria and, 5 Diabetic nephropathy (DN: macroalbuminuria or microalbuminuria plus diabetic retinopathy. Results The prevalence of different types of renal disease in patients was: 34.1% KD, 22.9% RI, 19.5% albuminuria and 16.4% diabetic nephropathy (DN. The prevalence of albuminuria without RI (13.5% and nonalbuminuric RI (14.7% was similar. After adjusting per age, BMI, cholesterol, blood pressure and macrovascular disease, RI was significantly associated with the female gender (OR 2.20; CI 95% 1.86–2.59, microvascular disease (OR 2.14; CI 95% 1.8–2.54 and insulin treatment (OR 1.82; CI 95% 1.39–2.38, and inversely associated with HbA1c (OR 0.85 for every 1% increase; CI 95% 0.80–0.91. Albuminuria without RI was inversely associated with the female gender (OR 0.27; CI 95% 0.21–0.35, duration of diabetes (OR 0.94 per year; CI 95% 0.91–0.97 and directly associated with HbA1c (OR 1.19 for every
Younes, Naji; Cleary, Patricia A; Steffes, Michael W; de Boer, Ian H; Molitch, Mark E; Rutledge, Brandy N; Lachin, John M; Dahms, William
The objective of this study was to compare random urine albumin-creatinine ratio (ACR) with timed urine albumin excretion rate (AER) in patients with type 1 diabetes. A total of 1186 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study provided spot urine specimens concurrent with 4-hour timed urine collections. ACR and AER were compared using Bland-Altman plots, cross-classification of albuminuria status and its change over time, and within-person variability. Despite moderate correlation (r=0.62), ACR levels (mg/g) were lower than AER levels (mg/24 hr). This difference was greatest for men. Gender-specific estimated AER (eAER) values were empirically derived from ACR. Comparing the eAER with measured AER, agreement of prevalent microalbuminuria and macroalbuminuria classification was fair to moderate, and classification of change in albuminuria status over time was different. Intraclass correlations were 0.697 for ACR and 0.803 for AER. Effects of DCCT intensive versus conventional diabetes therapy on urine albumin excretion or classification of albuminuria were similar using the eAER versus measured AER, as were the effects of the previous glycosylated hemoglobin. Systematic differences exist between urine ACR and AER, related to gender and other determinants of muscle mass. Use of ACR (or eAER) versus AER yields differences in classification of prevalent albuminuria states and changes in albuminuria states over time. These findings support the use of consistent ascertainment methods over time and further efforts to standardize and optimally interpret measurement of urine albumin excretion.
Russo, Giuseppina T; De Cosmo, Salvatore; Viazzi, Francesca; Pacilli, Antonio; Ceriello, Antonio; Genovese, Stefano; Guida, Pietro; Giorda, Carlo; Cucinotta, Domenico; Pontremoli, Roberto; Fioretto, Paola
Despite the achievement of blood glucose, blood pressure, and LDL cholesterol (LDL-C) targets, the risk for diabetic kidney disease (DKD) remains high among patients with type 2 diabetes. This observational retrospective study investigated whether diabetic dyslipidemia-that is, high triglyceride (TG) and/or low HDL cholesterol (HDL-C) levels-contributes to this high residual risk for DKD. Among a total of 47,177 patients attending Italian diabetes centers, 15,362 patients with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 , normoalbuminuria, and LDL-C ≤130 mg/dL completing a 4-year follow-up were analyzed. The primary outcome was the incidence of DKD, defined as either low eGFR (30% and/or albuminuria. Overall, 12.8% developed low eGFR, 7.6% an eGFR reduction >30%, 23.2% albuminuria, and 4% albuminuria and either eGFR 30%. TG ≥150 mg/dL increased the risk of low eGFR by 26%, of an eGFR reduction >30% by 29%, of albuminuria by 19%, and of developing one abnormality by 35%. HDL-C 30%, with a 24% higher risk of developing albuminuria and a 44% risk of developing one abnormality. These associations remained significant when TG and HDL-C concentrations were examined as continuous variables and were only attenuated by multivariate adjustment for numerous confounders. In a large population of outpatients with diabetes, low HDL-C and high TG levels were independent risk factors for the development of DKD over 4 years. © 2016 by the American Diabetes Association.
Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K; Kramer, Holly; Rosas, Sylvia E; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L
Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity. We analyzed data from the NHANES 1999-2010 for 6918 young adults ages 20-40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria. Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4%) versus Mexican-Americans (40.6%) or non-Hispanic whites (37.4%) (P-value = 0.004). Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6-12.2), p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease. Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease.
Full Text Available Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity.We analyzed data from the NHANES 1999-2010 for 6918 young adults ages 20-40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria.Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4% versus Mexican-Americans (40.6% or non-Hispanic whites (37.4% (P-value = 0.004. Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6-12.2, p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease.Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease.
Full Text Available In patients with diabetic kidney disease, it is well documented that RAS blockade is associated with an improved outcome. This observational, multicenter study examined the "real-world" use of ACEI/ARB in patients with type 2 diabetes (T2DM in China.Data from the China Cardiometabolic Registries on blood pressure, blood lipid and blood glucose in Chinese T2DM patients (CCMR-3B were used for the present study. Consecutive outpatients with T2DM for more than 6 months were recruited to this non-interventional, observational, cross-sectional study. Albuminuria was defined as urine albumin creatinine ratio (ACR ≥ 30 mg/g.A total of 25,454 outpatients with T2DM from 6 regions in China were enrolled, 47.0% were male, and 59.8% had hypertension. ACR was measured in 6,383 of these patients and 3,231 of them ≥ 30 mg/L. Among patients with hypertension, 73.0% were on antihypertensives, and 39.7% used ACEI/ARB. Of the 2,157 patients with hypertension and albuminuria, only 48.3% used ACEI/ARB. Among the non-hypertensive patients with albuminuria, ACEI/ARB usage was < 1%. Multivariate analysis revealed that comorbidities, region, hospital tier, physician specialty and patient's educational level were associated with ACEI/ARB use.In T2DM with hypertension and albuminuria in China, more than half of them were not treated with ACEI/ARB. This real world evidence suggests that the current treatment for patients with diabetes coexisting with hypertension and albuminuria in China is sub-optimal.
Verdalles, Úrsula; Goicoechea, Marian; Garcia de Vinuesa, Soledad; Quiroga, Borja; Galan, Isabel; Verde, Eduardo; Perez de Jose, Ana; Luño, José
Resistant hypertension (RH) is a common problem in patients with chronic kidney disease (CKD). A decline in the glomerular filtration rate (GFR) and increased albuminuria are associated with RH; however, there are few published studies about the prevalence of this entity in patients with CKD. To estimate the prevalence of RH in patients with different degrees of kidney disease and analyse the characteristics of this group of patients. A total of 618 patients with hypertension and CKD stages i-iv were enrolled, of which 82 (13.3%) met the criteria for RH. RH prevalence increased significantly with age, the degree of CKD and albuminuria. The prevalence of RH was 3.2% in patients under 50 years, 13.8% between 50-79 years and peaked at 17.8% in patients older than 80 years. Renal function prevalence was 4, 15.8 and 18.1% in patients with an estimated glomerular filtration rate (GFR) of > 60, 30-59 and 300mg/g respectively. In a logistic regression model, the characteristics associated with resistant hypertension were age, history of cardiovascular disease, GFR, albuminuria and diabetes mellitus. A total of 47.5% of patients with resistant hypertension had controlled BP (<140/90mmHg) with 4 or more antihypertensive drugs. These patients were younger, with better renal function, less albuminuria and received more aldosterone antagonists. RH prevalence increases with age, the degree of CKD and albuminuria. Strategies such as treatment with aldosterone receptor antagonists are associated with better blood pressure control in this group of patients, leading to reduced prevalence. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.
Pacilli, Antonio; Viazzi, Francesca; Fioretto, Paola; Giorda, Carlo; Ceriello, Antonio; Genovese, Stefano; Russo, Giuseppina; Guida, Pietro; Pontremoli, Roberto; De Cosmo, Salvatore
Patients with type 1 diabetes mellitus are at increased risk of death. This risk appears to be modulated by kidney dysfunction. The aim of this study was to evaluate the prevalence of diabetic kidney disease (DKD), its traits, and clinical correlates in a large sample of patients with type 1 diabetes. Clinical data of 20 464 patients with type 1 diabetes were extracted from electronic medical records. Estimated glomerular filtration rate (eGFR) and increased urinary albumin excretion were considered. Mean age of the patients was 46 ± 16 years, 55.0% were males, and duration of diabetes 19 ± 13 years. The frequency of diabetic kidney disease, low eGFR, and albuminuria was 23.5%, 8.1%, and 19.5%, respectively. In the multivariate analysis the presence of diabetic kidney disease was associated with age (odds ratio [OR] = 1.14, 95% confidence interval [CI]: 1.10-1.18), duration of diabetes (OR = 1.05, 95% CI: 1.03-1.07), and worse glycemic control (OR = 1.24, 95% CI: 1.21-1.28, for every 1% glycated hemoglobin increase). Diabetic kidney disease was also independently associated with an atherogenic lipid profile and increased systolic blood pressure. Glucose control, systolic blood pressure, triglycerides, and high density lipoprotein cholesterol were associated with both low eGFR and albuminuria. Male gender, retinopathy and smoke were related to albuminuria, being female was related to low eGFR, while SUA levels were associated with DKD, low eGFR and albuminuria. In our sample of patients with type 1 diabetes, diabetic kidney disease entails an unsafe cardiovascular risk profile. Hyperglycemia, arterial hypertension, and atherogenic lipid profile affected both low eGFR and albuminuria. Retinopathy and smoking were related only to albuminuria while being female and elevated serum uric acid were associated only with low eGFR. Copyright © 2016 John Wiley & Sons, Ltd.
Liu, Dong-Wei; Wan, Jia; Liu, Zhang-Suo; Wang, Pei; Cheng, Gen-Yang; Shi, Xue-Zhong
Dyslipidemia, a well-known risk factor for cardiovascular disease, is common in patients with kidney disease. Recent studies discerned that dyslipidemias play a critical role in renal damage progression in renal diseases, but the association between dyslipidemias and chronic kidney disease (CKD) in the general population remains unknown. Thus, we assessed whether the growing prevalence of dyslipidemia could increase the risk of CKD. A total of 4779 middle-aged and elderly participants participated in this study. Dyslipidemias were defined by the 2007 Guidelines in Chinese Adults. Incident CKD was defined as albuminuria and/or reduced estimated glomerular filtration rate (eGFR, dyslipidemia and albuminuria/reduced eGFR. Participants with hypercholesterolemia exhibited a greater prevalence of albuminuria and reduced eGFR (10.0% vs. 6.1%, P = 0.001; 4.0% vs. 2.4%, P = 0.028, respectively). Both hypercholesterolemia and low high density lipoprotein cholesterol (HDL-C) were independently associated with albuminuria (odds ratio (OR) 1.49; 95% confidence interval (CI) 1.08 - 2.07 and OR 1.53; 95%CI 1.13 - 2.09, respectively). The multivariable adjusted OR of reduced eGFR in participants with hypercholesterolemia was 1.65 (95%CI 1.03 - 2.65). As the number of dyslipidemia components increased, so did the OR of CKD: 0.87 (95%CI 0.65 - 1.15), 1.29 (95%CI, 0.83 - 2.01), and 7.87 (95%CI, 3.75 - 16.50) for albuminuria, and 0.38 (95%CI 0.21 - 0.69), 1.92 (95%CI 1.14 - 3.25), and 5.85 (95%CI 2.36 - 14.51) for reduced eGFR, respectively. Our findings indicate that dyslipidemias increase the risk of CKD in the middle-aged and elderly Chinese population. Hypercholesterolemia plays an important role in reducing total eGFR. Both low HDL-C and hypercholesterolemia are associated with an increased risk for albuminuria.
Laverman, Gozewijn Dirk; Andersen, Steen; Rossing, Peter
BACKGROUND: AT1-receptor blockade dose dependently lowers blood pressure (BP) and albuminuria. Reduction of BP and albuminuria are independent treatment targets for renoprotection, but whether this requires similar dose titration is unknown. METHODS: We tested this in two studies designed to find...... arterial pressure (MAP) were measured. Patients were divided into "good" and "poor" BP responders (BP+, BP-) according to BP response above or below group median. RESULTS: Baseline MAP in the BP- groups was 102 (97, 104) mm Hg in DM (median, 95% CI) and 91 (80, 108) mm Hg in ND. The top of the dose...... response for BP (obtained at losartan 100 mg) in the BP- groups was -2 (-4, 3) mm Hg in DM and -1 (-6, 2) mm Hg in ND, versus -15 (-18, -12) mm Hg and -16 (-26, -18) mm Hg in BP+ groups (both P
Andersen, Steen; Jacobsen, Peter; Tarnow, Lise
of losartan treatment and stabilized after 7 days (Parterial blood pressure and albuminuria are concordant, which suggests that systemic and renal haemodynamic mechanisms are of primary......BACKGROUND: Blockade of the renin-angiotensin system is the primary target in the treatment of diabetic kidney disease. Angiotensin II subtype 1 (AT1) receptor antagonists reduce albuminuria and lower blood pressure, but the initial time course of these effects after initiation of treatment...... is unknown. We evaluated the time course of the antihypertensive and antialbuminuric effect after initiation of AT1 receptor blockade by losartan in diabetic nephropathy. METHODS: Ten hypertensive type 1 diabetic patients with diabetic nephropathy were included in the study. After a washout period of 4 weeks...
Yacoub, Rabi; Kaji, Deepak; Patel, Shanti N; Simoes, Priya K; Busayavalasa, Deepthi; Nadkarni, Girish N; He, John C; Coca, Steven G; Uribarri, Jaime
Data from experimental animals suggest that probiotic supplements may retard CKD progression. However, the relationship between probiotic use, frequent yogurt consumption (as a natural probiotic source), and kidney parameters have not been evaluated in humans. We utilized NHANES data, and analyzed the association of probiotic alone (1999-2012) and yogurt/probiotic (2003-2006) use with albuminuria and eGFR after adjustment for demographic and clinical parameters. Frequent yogurt consumption was defined as thrice or more weekly over the year prior to the interview. Frequent yogurt/probiotic consumers had lower adjusted odds of developing combined outcome (albuminuria and/or eGFR yogurt and/or probiotics use is associated with decreased odds of proteinuric kidney disease. These hypothesis-generating results warrant further translational studies to further delineate the relationship between yogurt/probiotics with kidney dysfunction, as well as microbiome and dysbiosis as potential mediators.
Dieperink, H; Eshøj, O; Leyssac, P P
Segmental tubular sodium reabsorption in Type 1 (insulin-dependent) diabetes was measured in 36 patients in a cross-sectional study including one group (n = 13) without significant albuminuria (UalbV 1), one group (n = 16) with albuminuria in the range from 30 to 300 mg 24 h-1......, and a group (n = 7) with nephropathy (UalbV > 300 mg 24 h-1). Lithium clearance was used to measure end proximal delivery. From end proximal delivery, 51Cr-EDTA clearance (GFR) and sodium clearance, segmental tubular reabsorption was calculated. For all patients, GFR was directly correlated with end proximal...... delivery (r = 0.62, p 1, the direct correlation between GFR and end proximal delivery was also significant (r = 0.77, p
Poulsen, Per Løgstrup; Hansen, Klavs Würgler; Gaede, Peter Haulund
The documentation for the beneficial effects of antihypertensive treatment in patients with diabetes is overwhelming. Most patients will require three or four antihypertensive drugs to achieve blood pressure (BP) goals. The regime should include an agent that blocks the renin angiotensin...... aldosterone system. Reduction in albuminuria during antihypertensive treatment is indicative of renal and cardiovascular protection. Thus, if the level of albuminuria remains high, the treatment should be intensified, even in the light of achieved BP goals. Options for intensification are dual blockade......, supramaximal doses of ACE-I or ARB, or addition of aldosterone or renin-blocking agents. Long-term data are awaited regarding the optimal strategy for combination therapy. Patients on intensive antihypertensive treatment should be monitored regularly....
Parving, H H; Rossing, P
reduces albuminuria, delays the progression of nephropathy, and postpones renal insufficiency in diabetic nephropathy. Calcium antagonists and angiotensin converting enzyme inhibitors induce an acute increase in the glomerular filtration rate, renal plasma flow, and renal sodium excretion......Roughly 40% of all diabetic patients, whether insulin dependent or not, develop persistent albuminuria (over 300 mg/24 hr), a decrease in the glomerular filtration rate, and elevated blood pressure, ie, diabetic nephropathy. Diabetic nephropathy is the single most important cause of end stage renal...... disease in the Western world, and accounts for over a quarter of all end stage renal disease. It also is a major cause of the increased morbidity and mortality seen in diabetic patients; for example, the cost of end stage renal care in the United States currently exceeds +1.8 billion per year for diabetic...
Rossing, Peter; Hansen, Birgitte V.; Nielsen, Flemming S.
OBJECTIVE: Recent studies in nondiabetic kidney diseases suggest that dietary supplementation with n-3 polyunsaturated fatty acids (fish oil) may have beneficial effects on albuminuria, kidney function, arterial blood pressure, and dyslipidemia. Therefore, we evaluated the long-term effect of fish...... oil in diabetic nephropathy. RESEARCH DESIGN AND METHODS: A 1-year double-blind randomized controlled study comparing fish oil (4.6 g n-3 fatty acids/day) with placebo (olive oil) was performed in an outpatient clinic in a tertiary referral center. Thirty-six normotensive IDDM patients with diabetic...... nephropathy were included; 18 were treated with fish oil. Seven patients dropped out (four received fish oil), and results for the remaining 29 are presented. Albuminuria (enzyme immunoassay), glomerular filtration rate (51Cr-labeled EDTA plasma clearance), 24-h ambulatory blood pressure, and lipid profile...
Rossing, P; Hansen, B V; Nielsen, F S
oil in diabetic nephropathy. RESEARCH DESIGN AND METHODS: A 1-year double-blind randomized controlled study comparing fish oil (4.6 g n-3 fatty acids/day) with placebo (olive oil) was performed in an outpatient clinic in a tertiary referral center. Thirty-six normotensive IDDM patients with diabetic......OBJECTIVE: Recent studies in nondiabetic kidney diseases suggest that dietary supplementation with n-3 polyunsaturated fatty acids (fish oil) may have beneficial effects on albuminuria, kidney function, arterial blood pressure, and dyslipidemia. Therefore, we evaluated the long-term effect of fish...... nephropathy were included; 18 were treated with fish oil. Seven patients dropped out (four received fish oil), and results for the remaining 29 are presented. Albuminuria (enzyme immunoassay), glomerular filtration rate (51Cr-labeled EDTA plasma clearance), 24-h ambulatory blood pressure, and lipid profile...
Full Text Available The sodium-glucose-cotransporter-2 (SGLT2 inhibitor dapagliflozin (DAPA induces glucosuria and osmotic diuresis via inhibition of renal glucose reabsorption. Since increased diuresis retards the progression of polycystic kidney disease (PKD, we investigated the effect of DAPA in the PCK rat model of PKD. DAPA (10 mg/kg/d or vehicle was administered by gavage to 6 week old male PCK rats (n=9 per group. Renal function, albuminuria, kidney weight and cyst volume were assessed after 6 weeks of treatment. Treatment with DAPA markedly increased glucose excretion (23.6 ± 4.3 vs 0.3 ± 0.1 mmol/d and urine output (57.3 ± 6.8 vs 19.3 ± 0.8 ml/d. DAPA-treated PCK rats had higher clearances for creatinine (3.1 ± 0.1 vs 2.6 ± 0.2 ml/min and BUN (1.7 ± 0.1 vs 1.2 ± 0.1 ml/min after 3 weeks, and developed a 4-fold increase in albuminuria. Ultrasound imaging and histological analysis revealed a higher cyst volume and a 23% higher total kidney weight after 6 weeks of DAPA treatment. At week 6 the renal cAMP content was similar between DAPA and vehicle, and staining for Ki67 did not reveal an increase in cell proliferation. In conclusion, the inhibition of glucose reabsorption with the SGLT2-specific inhibitor DAPA caused osmotic diuresis, hyperfiltration, albuminuria and an increase in cyst volume in PCK rats. The mechanisms which link glucosuria to hyperfiltration, albuminuria and enhanced cyst volume in PCK rats remain to be elucidated.
Endres, Bradley T; Sandoval, Ruben M; Rhodes, George J; Campos-Bilderback, Silvia B; Kamocka, Malgorzata M; McDermott-Roe, Christopher; Staruschenko, Alexander; Molitoris, Bruce A; Geurts, Aron M; Palygin, Oleg
Hypertension is one of the most prevalent diseases worldwide and a major risk factor for renal failure and cardiovascular disease. The role of albuminuria, a common feature of hypertension and robust predictor of cardiorenal disorders, remains incompletely understood. The goal of this study was to investigate the mechanisms leading to albuminuria in the kidney of a rat model of hypertension, the Dahl salt-sensitive (SS) rat. To determine the relative contributions of the glomerulus and proximal tubule (PT) to albuminuria, we applied intravital two-photon-based imaging to investigate the complex renal physiological changes that occur during salt-induced hypertension. Following a high-salt diet, SS rats exhibited elevated blood pressure, increased glomerular sieving of albumin (GSC alb = 0.0686), relative permeability to albumin (+Δ16%), and impaired volume hemodynamics (-Δ14%). Serum albumin but not serum globulins or creatinine concentration was decreased (-0.54 g/dl), which was concomitant with increased filtration of albumin (3.7 vs. 0.8 g/day normal diet). Pathologically, hypertensive animals had significant tubular damage, as indicated by increased prevalence of granular casts, expansion and necrosis of PT epithelial cells (+Δ2.20 score/image), progressive augmentation of red blood cell velocity (+Δ269 µm/s) and micro vessel diameter (+Δ4.3 µm), and increased vascular injury (+Δ0.61 leakage/image). Therefore, development of salt-induced hypertension can be triggered by fast and progressive pathogenic remodeling of PT epithelia, which can be associated with changes in albumin handling. Collectively, these results indicate that both the glomerulus and the PT contribute to albuminuria, and dual treatment of glomerular filtration and albumin reabsorption may represent an effective treatment of salt-sensitive hypertension. Copyright © 2017 the American Physiological Society.
Podocyte-specific overexpression of metallothionein mitigates diabetic complications in the glomerular filtration barrier and glomerular histoarchitecture: a transmission electron microscopy stereometric analysis.
Carlson, Edward C; Chhoun, Jennifer M; Laturnus, Donna I; Bikash, K C; Berg, Brittany; Zheng, Shirong; Epstein, Paul N
We previously demonstrated that cellular and extracellular components of the blood-urine barrier in renal glomeruli are susceptible to damage in OVE transgenic mice, a valuable model of human diabetic nephropathy that expresses profound albuminuria. To test our hypothesis that glomerular filtration barrier damage in OVE mice may be the result of oxidative insult to podocytes, 150-day-old bi-transgenic OVENmt diabetic mice that overexpress the antioxidant metallothionein specifically in podocytes were examined by enzyme-linked immunosorbent assay for albuminuria mitigation and by unbiased transmission electron microscopy (TEM) stereometry for protection from chronic structural diabetic complications. Although blood glucose and HbA(1c) levels were indistinguishable in OVE and OVENmt animals, albuminuria was significantly reduced (average >7-fold) in OVENmt mice through 8 months of age. Interestingly, the Nmt transgene provided significant glomerular protection against diabetic nephropathic complications outside of the podocyte. Glomerular filtration barrier damage was reduced in OVENmt mice, including significantly increased area occupied by endothelial luminal fenestrations (~13%), significantly reduced glomerular basement membrane (GBM) thickening (~17%) and significantly less podocyte effacement (~18%). In addition, OVENmt mice exhibited significantly reduced glomerular volume (~50%), fewer glomerular endothelial cells (~33%), fewer mesangial cells (~57%) and fewer total glomerular cells (~40%). These results provide evidence of oxidative damage to podocytes induces primary diabetic nephropathic features including severe and sustained albuminuria, specific glomerular filtration barrier damage and alterations in glomerular endothelial and mesangial cell number. Importantly, these diabetic complications are significantly mitigated by podocyte targeted metallothionein overexpression. Copyright © 2012 John Wiley & Sons, Ltd.
Han, Kyungdo; Nam, Ga Eun; Kim, Do Hoon; Park, Jun-Beom; Ko, Youngkyung; Roh, Yong Kyun; Cho, Kyung Hwan; Park, Yong Gyu
Abstract Albuminuria and periodontitis are both commonly associated with systemic inflammation. However, the association between urinary albumin excretion (UAE) and periodontitis in patients with type 2 diabetes has not been fully investigated. This study aimed to investigate the association between UAE and periodontitis in Korean adults with type 2 diabetes. This study performed a cross-sectional analysis and used hierarchical multivariable logistic regression analysis models. Data from the 2012 Korean National Health and Nutrition Examination Survey were analyzed. A total of 547 patients, with type 2 diabetes without renal impairment, were included in this study. UAE was assessed using the urinary albumin to creatinine ratio (UACR). A community periodontal index greater than or equal to code 3 was used to define periodontitis. The risk of periodontitis tended to increase as UACR increased even after adjustment for potential confounders (P for trend in the odds ratios = 0.05 in model 1; 0.02 in model 2; and 0.01 in model 3). In a subgroup analysis, the prevalence of periodontitis was significantly higher in the patients with albuminuria (UACR >30 mg/g) than in those without albuminuria among patients younger than 65 years (P = 0.03), those with newly diagnosed diabetes (P = 0.04), or those without obesity (P = .04). UAE was positively associated with the risk of periodontitis in Korean adults with type 2 diabetes. In the patients who were younger, were newly diagnosed with diabetes, or had normal body mass index, individuals with albuminuria were more likely to have a higher prevalence of periodontitis. Early identification of periodontitis may be helpful in Korean diabetic adults with increased UAE. PMID:26496329
Mbodj, M.; Seck Gassama, S.; Ndong, B.; Ndoye, O.; Toure Sow, H.; Senghor, S.R.; Diop, S.N.; Solanki, K.K.
Aim: to sensitize at the same time experts and public authorities on the interest of the establishment of nuclear cardiology in Senegal. Material and method: the radioimmunoassay of micro-albuminuria, early marker of cardiovascular morbid-mortality was carried out in the nuclear medicine department of Dakar on a population of 100 diabetic patients (74 of type 1 and 26 of type 2) presenting one or more traditional cardiovascular risk factors. Out of these patients, 39% had abnormal rest ECG, asymptomatic in half of the cases. Results: prevalence of micro-albuminuria is high (24%). There is no significant difference in distribution between type I and type 2. Micro-albuminuria > 30 mg/24 h exists in 16,3% of patients with lipid abnormalities (ratio: total cholesterol/HDL cholesterol > 5), 30% of obese, 75% of hypertensive patients and 43,6% of patients with abnormal rest ECG, who would benefit from myocardial perfusion imaging (MPI): about 17% of patients involved in this study. No or weak correlation is found between micro-albuminuria and traditional risk factors. Conclusion: From these results and available epidemiological data in 2005, the estimate of the requirements in nuclear cardiology for the Senegalese diabetic population, indicates that 3740 patients should have benefited that year from it. Considering that this figure underestimates the real needs, taking into account the needs brought back to a population of 10 million inhabitants and the expect expansion of the diabetic disease, it appears justified to include the nuclear cardiology in the national programmes of prevention of the public health in Senegal. (author)
Joseph Fomusi Ndisang
Collectively, these data suggest that hemin ameliorates nephropathy by potentiating the expression of proteins of repair/regeneration, abating oxidative/inflammatory mediators, reducing renal histo-pathological lesions, while enhancing nephrin, podocin, podocalyxin, CD2AP and creatinine clearance, with corresponding reduction of albuminuria/proteinuria suggesting improved renal function in hemin-treated ZFs. Importantly, the concomitant potentiation regeneration proteins and podocyte cytoskeletal proteins are novel mechanisms by which hemin rescue nephropathy in obesity.
Conclusiones: Uno de cada 5 hipertensos sin enfermedad cardiovascular ≥60 años en atención primaria presentó disminución moderada del FGe. Además de la edad y el sexo, la albuminuria y la insuficiencia cardiaca fueron los principales factores asociados. A pesar de la mayor exposición a fármacos, el control de la PA fue inferior en ERC.
Bouchi, R; Babazono, T; Yoshida, N; Nyumura, I; Toya, K; Hayashi, T; Hanai, K; Tanaka, N; Ishii, A; Iwamoto, Y
Silent cerebral infarction (SCI) is an independent risk factor for future symptomatic stroke. Although the prevalence of SCI is closely related to kidney function in non-diabetic individuals, evidence is lacking whether albuminuria and/or reduced estimated glomerular filtration rate (eGFR) independently increase the risk of SCI in diabetic patients. We therefore examined the relationships between albuminuria, eGFR and SCI in patients with Type 2 diabetes mellitus (T2DM). We studied 786 T2DM patients with an eGFR > or = 15 ml/min 1.73/m(2), including 337 women and 449 men [mean (+/- sd), age 65 +/- 11 years]. All patients underwent cranial magnetic resonance imaging (MRI) to detect SCI. GFR was estimated using the modified three-variable equation for Japanese subjects. Albuminuria was defined as a first morning urinary albumin-to-creatinine ratio (ACR) > or = 30 mg/g. SCI was detected in 415 (52.8%) of the subjects. The prevalence of SCI was significantly associated with both elevated ACR and decreased eGFR in univariate analysis. In multivariate logistic regression analysis, urinary ACR remained independently associated with SCI after adjusting for conventional cardiovascular risk factors [odds ratio (OR) of urinary ACR per logarithmical value: 1.89, 95% confidence interval (CI) = 1.41-2.51, P < 0.001]; however, eGFR was no longer significantly associated with SCI (OR per ml/min 1.73/m(2) = 0.99, 95% CI = 0.98-1.00, P = 0.095). In conclusion, albuminuria but not decreased eGFR may be an independent predictor of prevalent SCI in patients with T2DM.
Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small arter...
Parving, H H; Smidt, U M; Hommel, E
of antihypertensive treatment with metoprolol, hydralazine, and furosemide, the arterial blood pressure decreased from 143/96 mm Hg to 130/84 mm Hg and albuminuria decreased from 1,038 micrograms/min to 547 micrograms/min. The rate of decline in GFR decreased from 10.7 mL/min/yr (range, 5.3 to 17.5 mL/min/yr) before...
Pontillo, Claudia; Zhang, Zhen-Yu; Schanstra, Joost P
Introduction: CKD273 is a urinary biomarker, which in advanced chronic kidney disease predicts further deterioration. We investigated whether CKD273 can also predict a decline of estimated glomerular filtration rate (eGFR) to ... threshold (P = 0.086). Discussion: In conclusion, while accounting for baseline eGFR, albuminuria, and covariables, CKD273 adds to the prediction of stage 3 chronic kidney disease, at which point intervention remains an achievable therapeutic target....
El-Nahas, Ahmed R; Elsaadany, Mohamed M; Taha, Diaa-Eldin; Elshal, Ahmed M; El-Ghar, Mohamed Abo; Ismail, Amani M; Elsawy, Essam A; Saleh, Hazem H; Wafa, Ehab W; Awadalla, Amira; Barakat, Tamer S; Sheir, Khaled Z
To evaluate the protective effects of selenium with vitamins A, C and E (selenium ACE, i.e. antioxidants), verapamil (calcium channel blocker), and losartan (angiotensin receptor blocker) against extracorporeal shockwave lithotripsy (ESWL)-induced renal injury. A randomised controlled trial was conducted between August 2012 and February 2015. Inclusion criteria were adult patients with a single renal stone (300 mg/L) were excluded. ESWL was performed using the electromagnetic DoLiS lithotripter. Eligible patients were randomised into one of four groups using sealed closed envelopes: Group1, control; Group 2, selenium ACE; Group 3, losartan; and Group 4, verapamil. Albuminuria and urinary neutrophil gelatinase-associated lipocalin (uNGAL) were estimated after 2-4 h and 1 week after ESWL. The primary outcome was differences between albuminuria and uNGAL. Dynamic contrast-enhanced magnetic resonance imaging was performed before ESWL, and at 2-4 h and 1 week after ESWL to compare changes in renal perfusion. Of 329 patients assessed for eligibility, the final analysis comprised 160 patients (40 in each group). Losartan was the only medication that showed significantly lower levels of albuminuria after 1 week (P < 0.001). For perfusion changes, there was a statistically significant decrease in the renal perfusion in patients with obstructed kidneys in comparison to before ESWL (P = 0.003). These significant changes were present in the control or antioxidant group, whilst in the losartan and verapamil groups renal perfusion was not significantly decreased. Losartan was found to protect the kidney against ESWL-induced renal injury by significantly decreasing post-ESWL albuminuria. Verapamil and losartan maintained renal perfusion in patients with post-ESWL renal obstruction. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.
Pazit Beckerman; Chengxiang Qiu; Jihwan Park; Nora Ledo; Yi-An Ko; Ae-Seo Deok Park; Sang-Youb Han; Peter Choi; Matthew Palmer; Katalin Susztak
Chronic kidney disease (CKD) has diverse phenotypic manifestations including structural (such as fibrosis) and functional (such as glomerular filtration rate and albuminuria) alterations. Gene expression profiling has recently gained popularity as an important new tool for precision medicine approaches. Here we used unbiased and directed approaches to understand how gene expression captures different CKD manifestations in patients with diabetic and hypertensive CKD. Transcriptome data from ni...
De Cosmo, Salvatore; Viazzi, Francesca; Pacilli, Antonio; Giorda, Carlo; Ceriello, Antonio; Gentile, Sandro; Russo, Giuseppina; Rossi, Maria Chiara; Nicolucci, Antonio; Guida, Pietro; Di Bartolo, Paolo; Pontremoli, Roberto
Chronic kidney disease (CKD) entails a worse cardiovascular outcome. The aim of our work was to study the relationship between CKD and the achievement of recommended targets for glycated haemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-c) and blood pressure (BP) in a real-life sample of patients with type 2 diabetes mellitus (T2DM). We analysed a sample of 116 777 outpatients from the Network of the Italian Association of Clinical Diabetologists; all patients had T2DM and at least one measurement of HbA1c, LDL-c, BP, serum creatinine and albuminuria in the year 2010. The outcome was the achievement of HbA1c, LDL-c and BP values as recommended by International Guidelines. In the entire sample, the mean value of HbA1c was 7.2 ± 1.2%, of LDL-c was 102 ± 33 mg/dL and of BP was 138/78 ± 19/9 mmHg. CKD and its components were associated with poor glycaemic and BP control, notwithstanding greater use of glucose and BP-lowering drugs, while no association was found with LDL-c values. Factors independently related to unsatisfactory glycaemic control included female gender, body mass index, duration of disease and high albuminuria. Men, older people and those taking statins were more likely to reach LDL-c target levels. Male gender, age and high albuminuria strongly affected the achievement of BP targets. CKD or its components, mainly high albuminuria, are associated with failure to reach therapeutic targets, especially for HbA1c and BP, despite a greater use of drugs in patients with T2DM. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Objective: To investigate the correlation between plasma tenofovir (TFV concentration and certain renal function markers in HIV-infected women on TDF antiretroviral therapy (ART.These markers were also compared to a HIV-uninfected control group. Methods: HIV-infected women (n = 30 on TDF-based ART were matched with 30 controls forage and body mass index. Renal markers analysed were estimated glomerular filtration rate (eGFR, creatinine clearance (CrCl, serum creatinine, albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained retrospectively for the HIV-infected women. Plasma TFV was assayed using a validated HPLC-MS/MS method. Step wise regression, Mann–Whitney test, unpaired and paired t-tests were applied in the statistical analyses. Results: TFV concentration was independently associated with albuminuria (adjusted r2 = 0.339; p = 0.001 in HIV-infected women. In the adjusted (weight analysis, eGFR (p = 0.038,CrCl (p = 0.032 and albuminuria (p = 0.048 were significantly higher in HIV-infected compared to the uninfected women, but eGFR was abnormally high in HIV-infected women. Both eGFR (p < 0.001 and CrCl (p = 0.008 increased from baseline to follow-up in HIV-infected women. Conclusion: Plasma TFV concentration was associated with increased albuminuria in HIV infected women in this sub-study. Both eGFR and CrCl were increased in HIV-infected women from baseline. These findings should be confirmed in larger studies, and hyperfiltration in HIV-infected women warrants further investigation.
Full Text Available Even within accepted normal ranges, higher serum phosphorus, dietary phosphorus density, parathyroid hormone (PTH and alkaline phosphatase (ALP are independent predictors of cardiovascular mortality. Lower serum 25-hydroxy vitamin D (25(OHD also predicts adverse cardiovascular outcomes. We hypothesized that vascular dysfunction accompanying subtle disturbances of these bone metabolism parameters would result in associations with increased low grade albuminuria.We examined participants in the National Health and Nutrition Examination Surveys 1999-2010 (N = 19,383 with estimated glomerular filtration rate (eGFR ≥60 ml/min/1.73 m² and without severe albuminuria (urine albumin:creatinine ratio (ACR <300 mg/g. Albuminuria was quantified as ACR and fractional albumin excretion (FE(alb.Increasing quintiles of dietary phosphorus density, serum phosphorus and ALP were not associated with higher ACR or FE(alb. The lowest versus highest quintile of 25(OHD was associated with greater albuminuria, but not after adjustment for other covariates including cardiovascular risk factors. An association between the highest versus lowest quintile of bone-specific ALP and greater ACR persisted after covariate adjustment, but was not accompanied by an independent association with FE(alb. Increasing quintiles of PTH demonstrated associations with both higher ACR and FE(alb that were not abolished by adjusting for covariates including age, gender, race, body mass index, diabetes, blood pressure, history of cardiovascular disease, smoking, eGFR, 25(OHD, season of measurement, lipids, hemoglobin and C-reactive protein. Adjusted increases in ACR and FE(alb associated with the highest versus lowest quintile of PTH were 19% (95% confidence interval 7-28% p<0.001 and 17% (8-31% p = 0.001 respectively.In this population, of the bone mineral parameters associated with cardiovascular outcomes, only PTH is independently associated with ACR and FE(alb.
Parving, Hans-Henrik; Brenner, Barry M; McMurray, John J V
Patients with type 2 diabetes are at enhanced risk for macro- and microvascular complications. Albuminuria and/or reduced kidney function further enhances the vascular risk. We initiated the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Aliskiren, a novel direct renin...... inhibitor, which lowers plasma renin activity, may thereby provide greater cardio-renal protection compared with angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) alone....
Mbodj, M.; Seck Gassama, S.; Ndong, B.; Ndoye, O.; Toure Sow, H.; Senghor, S.R. [Universite Cheikh Anta Diop, Lab. Biophysique et Service de Medecine Nucleaire, Faculte de Medecine, de Pharmacie et d' Odontostomatologie, Dakar (UCAD) (Senegal); Diop, S.N. [Centre Antidiabetique Marc Sankale, Hopital Abass Ndao, Dakar (Senegal); Solanki, K.K. [International Atomic Energy Agency, Dept. de la Cooperation Technique, Section Medecine Nucleaire, Vienna (Austria)
Aim: to sensitize at the same time experts and public authorities on the interest of the establishment of nuclear cardiology in Senegal. Material and method: the radioimmunoassay of micro-albuminuria, early marker of cardiovascular morbid-mortality was carried out in the nuclear medicine department of Dakar on a population of 100 diabetic patients (74 of type 1 and 26 of type 2) presenting one or more traditional cardiovascular risk factors. Out of these patients, 39% had abnormal rest ECG, asymptomatic in half of the cases. Results: prevalence of micro-albuminuria is high (24%). There is no significant difference in distribution between type I and type 2. Micro-albuminuria > 30 mg/24 h exists in 16,3% of patients with lipid abnormalities (ratio: total cholesterol/HDL cholesterol > 5), 30% of obese, 75% of hypertensive patients and 43,6% of patients with abnormal rest ECG, who would benefit from myocardial perfusion imaging (MPI): about 17% of patients involved in this study. No or weak correlation is found between micro-albuminuria and traditional risk factors. Conclusion: From these results and available epidemiological data in 2005, the estimate of the requirements in nuclear cardiology for the Senegalese diabetic population, indicates that 3740 patients should have benefited that year from it. Considering that this figure underestimates the real needs, taking into account the needs brought back to a population of 10 million inhabitants and the expect expansion of the diabetic disease, it appears justified to include the nuclear cardiology in the national programmes of prevention of the public health in Senegal. (author)
Dell'Omo, Giulia; Penno, Giuseppe; Pucci, Laura; Lucchesi, Daniela; Del Prato, Stefano; Pedrinelli, Roberto
Polymorphisms within the gene for transforming growth factor (TGF)-beta-1, a pro-fibrogenic cytokine pathophysiologically involved in hypertension and hypertensive target damage, might modulate the biological activity of the encoded protein. Through that mechanism, they might contribute to microalbuminuria, a marker of subclinical renal damage and a correlate of systemic inflammation and endothelial dysfunction in hypertension, a possibility never before tested. For this reason, we assessed the association of four TGF-beta-1 polymorphic variants (C-509T, Leu(10)-->Pro, Arg(25)-->Pro, Thr(263)-->Ile) with albuminuria in uncomplicated essential hypertensive men, using (circulating active + acid-activatable latent) TGF-beta-1 levels as an indirect index of their in vivo biological activity. Because of the close pathophysiological link of TGF-beta-1 with the renin-angiotensin system, we also tested the behaviour of the angiotensin converting enzyme (ACE) deletion/insertion (D/I) polymorphism. Albuminuria (three overnight collections), office and 24-h BP, left ventricular mass index (LVMI), BMI, renal function, glucose, lipids, plasma TGF-beta-1 (n = 162, ELISA) were measured in 222 genetically unrelated, never-treated, uncomplicated Caucasian hypertensive men. ACE D/I polymorphisms were analysed by the polymerase chain reaction technique or a 5' nuclease assay with further restriction analysis when required. Urine albumin levels or microalbuminuria (albuminuria > or =15 microg/min) did not differ by TGF-beta-1 genotypes, but both parameters were more frequent in ACE D/D homozygotes. Plasma TGF-beta-1 was similar across genetic backgrounds and was unrelated to albuminuria. Cardiovascular, renal, metabolic parameters were homogeneously distributed across genotypes. In contrast to its link with the ACE D/I genotype, microalbuminuria was independent of TGF-beta-1 polymorphism in this group of never-treated, uncomplicated essential hypertensive men.
Parving, Hans-Henrik; Persson, Frederik; Rossing, Peter
Diabetic nephropathy is characterised by persistent albuminuria, elevated blood pressure, relentless decline in GFR and enhanced fatal and nonfatal cardiovascular diseases. Microalbuminuria has been central to the development of clinical practise in prevention and treatment of diabetic nephropathy...... from urinary proteomics, none has yet outperformed Harry Keen's discovery of microalbuminuria as the best screening tool for diabetic nephropathy. Remission of microalbuminuria preserves renal function. Microalbuminuria has also stood the test of time as a valid powerful independent predictor for fatal...
Pena, Michelle J; Heinzel, Andreas; Rossing, Peter; Parving, Hans-Henrik; Dallmann, Guido; Rossing, Kasper; Andersen, Steen; Mayer, Bernd; Heerspink, Hiddo J L
Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response to ARBs in patients with diabetes mellitus and micro- or macroalbuminuria. Liquid chromatography-tandem mass spectrometry metabolomics was performed on serum samples. Data from patients with type 2 diabetes and microalbuminuria (n = 49) treated with irbesartan 300 mg/day were used for discovery. LASSO and ridge regression were performed to develop the classifier. Improvement in albuminuria response prediction was assessed by calculating differences in R(2) between a reference model of clinical parameters and a model with clinical parameters and the classifier. The classifier was externally validated in patients with type 1 diabetes and macroalbuminuria (n = 50) treated with losartan 100 mg/day. Molecular process analysis was performed to link metabolites to molecular mechanisms contributing to ARB response. In discovery, median change in urinary albumin excretion (UAE) was -42 % [Q1-Q3: -69 to -8]. The classifier, consisting of 21 metabolites, was significantly associated with UAE response to irbesartan (p R(2) increase from 0.10 to 0.70; p R(2) increase from 0.20 to 0.59; p < 0.001). Specifically ADMA impacting eNOS activity appears to be a relevant factor in ARB response. A serum metabolite classifier was discovered and externally validated to significantly improve prediction of albuminuria response to ARBs in diabetes mellitus.
Full Text Available Aims: No long-term studies of renal function evolution in morbidly obese (MO patients after weight loss are available. The aim of our work was to ascertain the long-term influence of drastic weight reduction on renal function in MO patients with obesity-related glomerular lesions. Methods: 92 MO patients with normal renal function and biopsy evidence of mild obesity-related glomerulopathy underwent bariatric surgery (BS and subsequent drastic weight loss. A long-term prospective follow-up (mean duration: 76 ± 42 months was carried out. Basal renal biopsies and basal and long-term metabolic and renal function studies were performed in all cases. Linear mixed models were applied. Results: Blood pressure dropped early after BS and remained stable thereafter. Creatinine clearance and BMI fell in the first 2 years, rose slightly after 5 years and then remained stable. Serum creatinine and albuminuria decreased throughout the follow-up period. Renal function and albuminuria evolution showed non-significant differences in relation to the number of glomerular lesions. Conclusions: Drastic weight loss in BS-treated MO patients with pre-surgical normal renal function and mild obesity-related glomerular lesions is associated with short- and long-term maintenance of normal renal function and improvement in both arterial hypertension and albuminuria.
Full Text Available Although the pathogenetic mechanism of DN has not been elucidated, an inflammatory mechanism has been suggested as a potential contributor. This study was designed to explore the relationship between low-grade inflammation and renal microangiopathy in T2DM. A total of 261 diabetic subjects were divided into three groups according to UAE: a normal albuminuria group, a microalbuminuria group, and a macroalbuminuria group. A control group was also chosen. Levels of hs-CRP, TNF-α, uMCP-1, SAA, SCr, BUN, serum lipid, blood pressure, and HbA1c were measured in all subjects. Compared with the normal controls, levels of hs-CRP, TNF-α, uMCP-1, and SAA in T2DM patients were significantly higher. They were also elevated in the normal albuminuria group, P<0.05. Compared with the normal albuminuria group, levels of these inflammatory cytokines were significantly higher in the microalbuminuria and macroalbuminuria group, P<0.01. The macroalbuminuria group also showed higher levels than the microalbuminuria group, P<0.01. Also they were positively correlated with UAE, SBP, DBP, LDL-C, and TC. We noted no significance correlated with course, TG, or HDL-C. Only TNF-α; was positively correlated with HbA1c. This study revealed the importance of these inflammatory cytokines in DN pathogenesis. Further studies are needed to fully establish the potential of these cytokines as additional biomarkers for the development of DN.
Full Text Available Background/Aims: In recent years, the relationship between chronic kidney disease (CKD and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods: Seventy-nine type 2 diabetic patients (mean age, 76.0 years were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR 2. SVD was evaluated by the presence and severity of silent brain infarcts (SBIs and white matter lesions (WMLs on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. Results: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (β = 0.284, p = 0.017 and low eGFR was associated with reduced Digit Symbol Substitution scores (β = -0.224, p = 0.026 after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. Conclusion: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.
Full Text Available Vitamin D deficiency is fequently observed in chronic kidney disease. We conducted this study to determine the concentration of the above-mentioned parameters and the correlation between them in order to optimize therapy with vitamin D in patients with end-stage renal disease (ESRD on hemodialysis. In 53 patients on hemodialysis due to ESRD, vitamin D [Calcidiol (25(OHD], parathyroid hormone (PTH, calcium, phosphorus, albuminuria, albumin:creatinine ratio (ACR and other parameters have been followed up. Analysis of the levels of vitamin D has been carried out by High Performance Liquid Chromatography (HPLC, the PTH is determined by the system Centaur XP, Siemens Diagnostic, Electro-chemiluminescence immunoassay (ECLIA, and for albumin in urine we used immunological method [Miltigent microalbumin assay (Abbott Laboratories Diagnostics. We found out deficiency and insufficiency of vitamin D in 56.6% and 37.7%, as well as average 4.5 times increase in the PTH, hyperphosphatemia, hypocalcemia, albuminuria (A2 or A3, over 10 times increase in the ACR, secondary hyperparathyroidism. We registered a negative correlation between vitamin D and PTH. We confirmed the increase in creatinine and cystatin C in the patients on hemodialysis. There are few literature data for patients on hemodialysis, however, regarding the extent of the vitamin deficiency and its relationship with PTH, albuminuria, calcium, phosphorus, etc. Our data have indicated that patients on hemodialysis due to ESRD are associated with high incidence of vitamin D insufficiency or deficiency.
Hermida, Fernando J; Soto, Sonia; Benitez, Alfonso J
Screening for urine proteins is recommended for the detection of albuminuria in high risk groups. The aim of this study was to compare the Clinitek Atlas PRO12 reagent urine strip with quantitative methods for the determination of protein/creatinine ratio and to evaluate the usefulness of the semi-quantitative Clinitek Atlas PRO12 reagent urine strip as a tool in the early detection of albuminuria among the general population. Six hundred first morning urine specimens were collected from outpatients with various clinical conditions. The results showed that the test data for the urine dipstick Clinitek Atlas PRO12 show good agreement with the quantitative measurement of protein, creatinine and protein/creatinine ratio. In addition, this study shows that 97.2% of the samples which gave "normal" protein/creatinine ratios by the semi-quantitative method, showed albumin/creatinine ratio < 30 mg/g by the quantitative methods. Our results show that Clinitek Atlas PRO12 reagent strips can be used for the purposes of albuminuria screening in the general population.
Full Text Available BackgroundTo determine the frequency of chronic kidney disease (CKD and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009.MethodsPatients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g.ResultsWe recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9±12.0 years. The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval being 1.93 (1.28 to 2.93, 1.70 (1.09 to 2.64, and 1.03 (1.00 to 1.06, respectively.ConclusionIn conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.
Full Text Available Despite optimal control of hyperglycaemia, hypertension, and dyslipidaemia, the number of patients with diabetic nephropathy (DN continues to grow. Strategies to target various signaling pathways to prevent DN have been intensively investigated in animal models and many have been proved to be promising. However, targeting these pathways once kidney disease is established, remain unsatisfactory. The clinical scenario is that patients with diabetes mellitus often present with established kidney damage and need effective treatments to repair and reverse the kidney damage. In this studies, eNOS-/- mice were administered with streptozotocin to induce diabetes. At 24 weeks, at which time we have previously demonstrated albuminuria and pathological changes of diabetic nephropathy, mice were randomised to receive TRAM34 subcutaneously, a highly selective inhibitor of potassium channel KCa3.1 or DMSO (vehicle for a further 14 weeks. Albuminuria was assessed, inflammatory markers (CD68, F4/80 and extracellular matrix deposition (type I collagen and fibronectin in the kidneys were examined. The results clearly demonstrate that TRAM34 reduced albuminuria, decreased inflammatory markers and reversed extracellular matrix deposition in kidneys via inhibition of the TGF-β1 signaling pathway. These results indicate that KCa3.1 blockade effectively reverses established diabetic nephropathy in this rodent model and provides a basis for progressing to human studies.
Schievink, Bauke; de Zeeuw, Dick; Smink, Paul A; Andress, Dennis; Brennan, John J; Coll, Blai; Correa-Rotter, Ricardo; Hou, Fan Fan; Kohan, Donald; Kitzman, Dalane W; Makino, Hirofumi; Parving, Hans-Henrik; Perkovic, Vlado; Remuzzi, Giuseppe; Tobe, Sheldon; Toto, Robert; Hoekman, Jarno; Lambers Heerspink, Hiddo J
A recent phase II clinical trial (Reducing Residual Albuminuria in Subjects with Diabetes and Nephropathy with AtRasentan trial and an identical trial in Japan (RADAR/JAPAN)) showed that the endothelin A receptor antagonist atrasentan lowers albuminuria, blood pressure, cholesterol, hemoglobin, and increases body weight in patients with type 2 diabetes and nephropathy. We previously developed an algorithm, the Parameter Response Efficacy (PRE) score, which translates short-term drug effects into predictions of long-term effects on clinical outcomes. We used the PRE score on data from the RADAR/JAPAN study to predict the effect of atrasentan on renal and heart failure outcomes. We performed a post-hoc analysis of the RADAR/JAPAN randomized clinical trials in which 211 patients with type-2 diabetes and nephropathy were randomly assigned to atrasentan 0.75 mg/day, 1.25 mg/day, or placebo. A PRE score was developed in a background set of completed clinical trials using multivariate Cox models. The score was applied to baseline and week-12 risk marker levels of RADAR/JAPAN participants, to predict atrasentan effects on clinical outcomes. Outcomes were defined as doubling serum creatinine or end-stage renal disease and hospitalization for heart failure. The PRE score predicted renal risk changes of -23% and -30% for atrasentan 0.75 and 1.25 mg/day, respectively. PRE scores also predicted a small non-significant increase in heart failure risk for atrasentan 0.75 and 1.25 mg/day (+2% vs. +7%). Selecting patients with >30% albuminuria reduction from baseline (responders) improved renal outcome to almost 50% risk reduction, whereas non-responders showed no renal benefit. Based on the RADAR/JAPAN study, with short-term changes in risk markers, atrasentan is expected to decrease renal risk without increased risk of heart failure. Within this population albuminuria responders appear to contribute to the predicted improvements, whereas non-responders showed no benefit
Full Text Available AIM To study the changes in phosphate metabolism in kidney donors, to study the correlation of albuminuria, fractional excretion of phosphorus [FE Pi] and estimated glomerular filtration rate [eGFR] with fibroblast growth factor 23 [FGF 23] in kidney donors, to study the early tubule interstitial injury in the remnant kidney of donors by measuring urine transforming growth factor beta [TGF beta] levels. MATERIALS AND METHODS A cross-sectional study in which kidney donors with 1 year or more after donation were included. 69 kidney donors with a mean duration of 5.86 years after kidney donation were studied. Serum phosphate level, fractional excretion of phosphorus [FE Pi] and serum levels of parathyroid hormone were measured. Plasma levels of FGF 23 were measured by a second generation enzyme linked immune sorbent assay [ELISA]. Renal function was assessed by estimated glomerular filtration rate [eGFR] and degree of albuminuria. Urine levels of transforming growth factor beta [TGF beta] were measured by ELISA. A hypothesis that in kidney donors with reduced nephron number, the single nephron excretion of phosphorus will be increased to maintain normal phosphorus homeostasis and that this increase in single nephron phosphorus excretion may be mediated by FGF 23 was proposed. Testing of this hypothesis was done by studying the correlation between parameters of phosphorus metabolism, FGF 23 and the renal function of the donors. RESULTS The mean eGFR was 70.36 mL/min/1.73 m2 . 52.2% of donors had moderate increase in albuminuria [microalbuminuria], Serum phosphorus, fractional excretion of phosphorus and serum PTH levels were in the normal range. FGF 23 levels were in the normal reference range and showed no correlation with FE pi, eGFR or albuminuria, Urine TGF-beta levels were undetectable in all the donors. DISCUSSION Normal phosphorus homeostasis is maintained in kidney donors. There was no correlation between FE pi and FGF 23 levels. Kidney
Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial.
Cherney, David Z I; Zinman, Bernard; Inzucchi, Silvio E; Koitka-Weber, Audrey; Mattheus, Michaela; von Eynatten, Maximilian; Wanner, Christoph
In a pooled analysis of short-term trials, short-term treatment with the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin reduced albuminuria in patients with type 2 diabetes and prevalent albuminuria. In this exploratory analysis of the EMPA-REG OUTCOME trial, we report the short-term and long-term effects of empagliflozin on albuminuria in patients with type 2 diabetes and established cardiovascular disease, according to patients' baseline albuminuria status. In this randomised, double-blind, placebo-controlled trial at 590 sites in 42 countries, we randomly assigned patients aged 18 years and older with type 2 diabetes and established cardiovascular disease (1:1:1) to empagliflozin 10 mg, empagliflozin 25 mg, or placebo in addition to standard of care until at least 691 patients experienced an adjudicated event included in the primary outcome. We did the randomisation with a computer-generated random-sequence and interactive voice-response and web-response system, stratified by HbA 1c , BMI, region, and estimated glomerular filtration rate. Patients, investigators, and individuals involved in analysis of trial data were masked to treatment assignment. The primary and secondary efficacy and safety endpoints of this trial have been reported previously. Here, we report urinary albumin-to-creatinine ratio (UACR) data for the pooled empagliflozin group versus placebo according to albuminuria status at baseline (normoalbuminuria: UACR 300 mg/g). We did the analysis with mixed-model repeated measures including prespecified and post-hoc tests. This study is completed and registered with ClinicalTrials.gov, number NCT01131676. Between Sept 1, 2010, and April 22, 2013, we randomly assigned 7028 patients to treatment groups and 7020 patients received treatment. At baseline, we had UACR data for 6953 patients: 4171 (59% of treated patients; 1382 assigned to placebo and 2789 assigned to empagliflozin) had normoalbuminuria, 2013 (29%; 675 assigned to placebo
De Cosmo, Salvatore; Viazzi, Francesca; Pacilli, Antonio; Giorda, Carlo; Ceriello, Antonio; Gentile, Sandro; Russo, Giuseppina; Rossi, Maria C; Nicolucci, Antonio; Guida, Pietro; Pontremoli, Roberto
The identification of clinical predictors for the development of chronic kidney disease is a critical issue in the management of patients with type 2 diabetes mellitus.We evaluated 27,029 patients with type 2 diabetes mellitus and estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m and normoalbuminuria from the database of the Italian Association of Clinical Diabetologists network. Primary outcomes were eGFR <60 mL/min/1.73 m and normoalbuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m; and eGFR <60 mL/min/1.73 m and albuminuria. Secondary outcomes were eGFR <60 mL/min/1.73 m and albuminuria. eGFR from serum creatinine by chronic kidney disease epidemiology collaboration equation (CKD-EPI), urinary albumin excretion, HbA1c, triglycerides, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c), blood pressure, and body mass index.Over a 4-year period, 33.2% of patients (n = 8973) developed chronic kidney disease, 10.3% (n = 2788) showed a decline in eGFR <60 mL/min/1.73 m, 18.4% (n = 4978) developed albuminuria, and 4.5% (n = 1207) developed both features. Relative risk ratios (RRRs) for age (1.37, P < 0.001 by 5 years), sex (0.77, P < 0.001 for being male), body mass index (1.03, P < 0.001 by 1 kg/m), triglycerides (1.02, P < 0.001 by 10 mg/dL), and LDL-c (0.97, P = 0.004 by 10 mg/dL) were independently related to the onset of eGFR reduction. Age (1.08, P < 0.001 by 5 years), sex (1.36, P < 0.001 for being male), body mass index (1.02, P < 0.001 by 1 kg/m), triglycerides (1.01, P = 0.02 by 10 mg/dL), HDL-c, and LDL-c (0.97, P = 0.008 and 0.99, P = 0.003 by 5 and 10 mg/dL, respectively) were related to the onset of albuminuria. HbA1c and the intensity of antihypertensive treatment showed a weaker association with renal outcome.Reduction in eGFR and albuminuria showed distinct sets of risk factors, suggesting that different mechanisms are involved in
Aguiar, Patrício; Azevedo, Olga; Pinto, Rui; Marino, Jacira; Baker, Robert; Cardoso, Carlos; Ducla Soares, José Luís; Hughes, Derralynn
Renal involvement in Fabry disease is a major determinant of overall disease prognosis and early enzyme replacement therapy seems effective in preventing progression of kidney injury. Gb3 storage, glomerular sclerosis and tubulo-interstitial fibrosis may occur with minimal or no changes on standard renal tests, hence alternative markers of renal dysfunction are crucial. In this study we compared several biomarkers with albuminuria in the identification of incipient Fabry nephropathy and their diagnostic accuracy to identify chronic kidney disease (CKD) stage≥2. In this multicentre, prospective, cross-sectional and diagnostic test study, a cohort of 78 Fabry patients and 25 healthy controls was consecutively recruited. Patients were grouped by severity of nephropathy: 1) albuminuria300mg/g; 4) glomerular filtration rate (GFR)Fabry patients, even in the subgroup of patients without evidence of nephropathy. We also found inverse significant correlations between estimated GFR and collagen type IV (ρ=-0.289; p=0.003) or N-acetyl-β-glucosaminidase (ρ=-0.448; p<0.001), which were stronger than with albumin (ρ=-0.274; p=0.019). There was also better diagnostic accuracy of N-acetyl-β-glucosaminidase to predict CKD stage≥2. These results suggest that studied biomarkers may overcome the limitations of albuminuria as sensitive marker of early renal dysfunction and as marker for CKD progression risk. These biomarkers may also define novel early stages of nephropathy characterized by mesangial expansion and/or tubular damage. Copyright © 2017 Elsevier Inc. All rights reserved.
Jin, S-M; Kim, T-H; Oh, S; Baek, J; Joung, J Y; Park, S-M; Cho, Y Y; Sohn, S Y; Hur, K Y; Lee, M-S; Lee, M-K; Kim, J H
The contribution of glycaemic variability to the microvascular complication of diabetes has not been established. We examined whether there is an independent association between indices of glycaemic variability in continuous glucose monitoring and extent of albuminuria. A total of 173 patients with Type 2 diabetes (without insulin therapy, n = 96; with insulin therapy, n = 77) who had unexplained large fluctuations in blood glucose values underwent three-day continuous glucose monitoring. We used a multinomial logistic regression model to determine whether the indices of glycaemic variability independently affected the odds of having a spot urine albumin/creatinine ratio of 30-299 mg/g and ≥ 300 mg/g. Higher standard deviation (P = 0.002), mean of daily differences (P = 0.023) and mean amplitude of glycaemic excursion (P = 0.043) significantly increased the odds of having a urine albumin/creatinine ratio of ≥ 300 mg/g. In multivariable analysis, only higher standard deviation, but not mean amplitude of glycaemic excursion and mean of daily differences, independently increased the odds of having a urine albumin/creatinine ratio of ≥ 300 mg/g (P = 0.025). Coefficient of variation (sd/mean) was not associated with the odds of having a urine albumin/creatinine ratio of 30-299 or ≥ 300 mg/g. The independent association between standard deviation and the extent of albuminuria was lost when the measures were normalized by mean glucose level. At least in terms of relative measures of glycaemic variability, we failed to demonstrate an independent association between glycaemic variability and albuminuria extent in patients with inadequately controlled Type 2 diabetes. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.
Taskin, Fuesun [Adnan Menderes University, Faculty of Medicine, Department of Radiology, 09100 Aydin (Turkey)]. E-mail: email@example.com; Akdilli, Alev [Adnan Menderes University, Faculty of Medicine, Department of Radiology, 09100 Aydin (Turkey); Karaman, Can [Adnan Menderes University, Faculty of Medicine, Department of Radiology, 09100 Aydin (Turkey); Unsal, Alparslan [Adnan Menderes University, Faculty of Medicine, Department of Radiology, 09100 Aydin (Turkey); Koeseoglu, Kutsi [Adnan Menderes University, Faculty of Medicine, Department of Radiology, 09100 Aydin (Turkey); Ergin, Filiz [Adnan Menderes University, Faculty of Medicine, Department of Public Health, Aydin (Turkey)
Purpose: To determine the prevalence of breast arterial calcifications (BAC) detected on mammography and search for conditions that may influence their existence. Materials and methods: The mammograms of 6156 consecutive patients were reevaluated for the presence of BAC. Four hundred eighty-five women having BAC were enrolled in the patient group. Additionally, randomly selected 500 women, without BAC constituted the control group. Hospital records of the participants were reviewed for parity, menopausal status, oral contraceptive agent (OCA) usage, hormone replacement therapy (HRT) usage, presence of diabetes, hypertension, hyperlipidemia, albuminuria and history of myocardial infarction (MI). Results: Prevalence of BAC was 7.9% on mammograms. Ninety-four women were aged between 40 and 49 years, 165 were aged between 50 and 59 years and 226 were over 60 years among BAC positive 485 women. A significant relationship was found for the frequency of BAC versus age and HRT usage in all age groups (p < 0.05). Similarly, significant relationships were also found for the frequency of BAC versus OCA usage, HRT usage, hyperlipidemia and diabetes in age group of 40-49 and in age group of 50-59, and for the frequency of BAC versus albuminuria in age group of 40-49, BAC versus history of myocardial infarction in age group of 59-59 and over 60 years (p < 0.05). The correlations were not significant for the relationships of BAC with OCA usage, hyperlipidemia, diabetes and albuminuria in women over 60 years (p > 0.05). Conclusion: Most benign findings like BAC are not routinely reported during mammographic evaluation. Our study showed that, presence of BAC on mammography was strongly related to advancing age. However, these findings may signify a systemic risk and can be used as precautious indicators for undocumented systemic diseases, especially in premenopausal women.
Hye Won Lee
Full Text Available BackgroundNonalbuminuric renal insufficiency is a unique category of diabetic kidney diseases. The objectives of the study were to evaluate prevalent rate of nonalbuminuric renal insufficiency and to investigate its relationship with previous cardiovascular disease (CVD event in Korean patients with type 2 diabetes mellitus (T2DM.MethodsLaboratory and clinical data of 1,067 subjects with T2DM were obtained and reviewed. Study subjects were allocated into four subgroups according to the CKD classification. Major CVD events were included with coronary, cerebrovascular, and peripheral vascular events.ResultsNonalbuminuric stage ≥3 CKD group, when compared with albuminuric stage ≥3 CKD group, had shorter diabetic duration, lower concentrations of glycated hemoglobin, high density lipoprotein cholesterol, and high-sensitivity C-reactive protein, lower prevalent rates of retinopathy and previous CVD, and higher rate of treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Nonalbuminuric stage ≥3 CKD group showed a greater association with prior CVD events than no CKD group; however, albuminuric stage ≥3 CKD group made addition to increase prevalence of prior CVD events significantly when CKD categories were applied as covariates. Association of prior CVD events, when compared with normal estimated glomerular filtration rate (eGFR and nonalbuminuria categories, became significant for declined eGFR, which was higher for eGFR of <30 mL/min/1.73 m2, and albuminuria.ConclusionThe results show that subjects with nonalbuminuric stage ≥3 CKD is significantly interrelated with occurrence of prior CVD events than those with normal eGFR with or without albuminuria. Comparing with normal eGFR and nonalbuminuria categories, the combination of increased degree of albuminuria and declined eGFR is becoming significant for the association of prior CVD events.
Conrado L R Gomes
Full Text Available Heparanase-1 activation, albuminuria, and a decrease in glomerular heparan sulfate (HS have been described in diabetic nephropathy (DN. Glycosaminoglycan (GAG-based drugs have been shown to have renoprotective effects in this setting, although recent trials have questioned their clinical effectiveness. Here, we describe the effects of fucosylated chondroitin sulfate (FCS, a novel GAG extracted from a marine echinoderm, in experimentally induced DN compared to a widely used GAG, enoxaparin (ENX.Diabetes mellitus (DM was induced by streptozotocin in male Wistar rats divided into three groups: DM (without treatment, FCS (8 mg/kg, and ENX (4 mg/kg, administered subcutaneously. After 12 weeks, we measured blood glucose, blood pressure, albuminuria, and renal function. The kidneys were evaluated for mesangial expansion and collagen content. Immunohistochemical quantifications of macrophages, TGF-β, nestin and immunofluorescence analysis of heparanase-1 and glomerular basement membrane (GBM HS content was also performed. Gene expression of proteoglycan core proteins and enzymes involved in GAG assembly/degradation were analyzed by TaqMan real-time PCR.Treatment with GAGs prevented albuminuria and did not affect the glucose level or other functional aspects. The DM group exhibited increased mesangial matrix deposition and tubulointerstitial expansion, and prevention was observed in both GAG groups. TGF-β expression and macrophage infiltration were prevented by the GAG treatments, and podocyte damage was halted. The diabetic milieu resulted in the down-regulation of agrin, perlecan and collagen XVIII mRNAs, along with the expression of enzymes involved in GAG biosynthesis. Treatment with FCS and ENX positively modulated such changes. Heparanase-1 expression was significantly reduced after GAG treatment without affecting the GBM HS content, which was uniformly reduced in all of the diabetic animals.Our results demonstrate that the administration of FCS
Full Text Available BACKGROUND: The prevalence of chronic kidney disease (CKD has increased and will continue to rise worldwide. However, data regarding the prevalence of CKD in a rural area of China are limited. We therefore investigated the prevalence and associated risk factors of impaired renal function and urinary abnormalities in an adult rural population in southern China. METHODS: Between December 2006 and January 2007, residents older than 20 years from four villages in Zhuhai city were randomly selected using a stratified, multistage sampling technique. All participants were interviewed and tested for hematuria, albuminuria and estimated glomerular filtration rate (eGFR. The associations between age, gender, diabetes mellitus, hypertension, hyperuricemia, education level and indicators of renal damage were examined. RESULTS: Overall, 1,214 subjects were enrolled in this study. After adjustment for age and gender, the prevalence of albuminuria was 7.1% (95% CI: 4.5, 8.1, reduced eGFR was 2.6% (95% CI: 1.7%, 3.3%, and hematuria was 4.6% (95% CI: 3.3%, 6.0%. Approximately 13.6% (95% CI: 12.0%, 15.1% of the patients had at least one indicator of renal damage, but only 8.3% were previously aware. Age, diabetes, hyperlipidemia, hypertension, hyperuricemia, use of nephrotoxic medications, coronary heart disease and history of CKD were independently associated with impaired renal function and urinary abnormalities. Additionally, age, diabetes, and hypertension were independently associated with albuminuria. Age, hypertension, hyperuricemia, central obesity, and coronary heart disease were independently associated with reduced renal function. CONCLUSIONS: The high prevalence and low awareness of impaired renal function and urinary abnormalities in this population illustrates the urgent need to implement a CKD prevention program in the rural areas of southern China.
Almualm, Yasmin; Zaman Huri, Hasniza
Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred. Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia. Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR 60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured.
Mizukoshi, Toshihiro; Kato, Sawako; Ando, Masahiko; Sobajima, Hiroshi; Ohashi, Norimi; Naruse, Tomohiko; Saka, Yosuke; Shimizu, Hideaki; Nagata, Takanobu; Maruyama, Shoichi
We aimed to evaluate the anti-albuminuric effects of topiroxostat in Japanese hyperuricemic patients with diabetic nephropathy. In this 24-week, multicenter, open-label, randomized (1:1) trial, we assigned hyperuricemic patients with diabetic nephropathy (estimated glomerular filtration rate ≥ 20 mL/min/1.73m 2 ) and overt proteinuria (0.3 ≤ urine protein to creatinine ratio (UPCR) <3.5 g/g Cr) to either high dose (160 mg daily) or low dose (40 mg daily) topiroxostat. The primary endpoint was the change in albuminuria indicated by urine albumin-to-creatinine ratio (UACR) from the baseline at the final time point. A total of 80 patients underwent randomization. The changes in UACR after 24 weeks of treatment (or at the final time point if patients failed to reach 24 weeks) relative to the baseline were -122 mg/gCr (95% CI: -5.1 to -240.1, P = 0.041) in patients treated with high dose, while treatment with low dose topiroxostat could not show significant reduction (P = 0.067). In the linear mixed model including baseline albuminuria, eGFR, age, and sex as covariates, the decreases in UACR were still significant from baseline to 12 weeks by 228.7 ± 83.2 mg/gCr (P = 0.0075) in the high dose group. The adverse-event profile during this study was not different between the groups. Topiroxostat 160 mg daily reduced albuminuria in patients with diabetic nephropathy. (Funded by Sanwa Kagaku Kenkyusho; Trial registration, UMIN000015403). This article is protected by copyright. All rights reserved.
Mohammed Abdul, Khaja Shameem; Eakanayake, Eakanayake M. D. V.; Jayasinghe, Sudheera Sammanthi; Jayasumana, Channa; Asanthi, Hewa Bandulage; Perera, Hettiarachigae S. D.; Chaminda, Gamage G. Tushara; Chandana, Ediriweera P. S.; Siribaddana, Sisira H.
Chronic Kidney Disease of uncertain etiology (CKDu) is an emerging epidemic among farming communities in rural Sri Lanka. Victims do not exhibit common causative factors, however, histopathological studies revealed that CKDu is a tubulointerstitial disease. Urine albumin or albumin-creatinine ratio is still being used as a traditional diagnostic tool to identify CKDu, but accuracy and prevalence data generated are questionable. Urinary biomarkers have been used in similar nephropathy and are widely recognised for their sensitivity, specificity and accuracy in determining CKDu and early renal injury. However, these biomarkers have never been used in diagnosing CKDu in Sri Lanka. Male farmers (n = 1734) were recruited from 4 regions in Sri Lanka i.e. Matara and Nuwara Eliya (farming locations with no CKDu prevalence) and two CKDu emerging locations from Hambantota District in Southern Sri Lanka; Angunakolapelessa (EL1) and Bandagiriya (EL2). Albuminuria (ACR ≥ 30mg/g); serum creatinine based estimation of glomerular filtration rate (eGFR); creatinine normalized urinary kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were measured. Fourteen new CKDu cases (18%) from EL1 and nine CKDu cases (9%) from EL2 were recognized for the first time from EL1, EL2 locations, which were previously considered as non-endemic of the disease and associated with persistent albuminuria (ACR ≥ 30mg/g Cr). No CKDu cases were identified in non-endemic study locations in Matara (CM) and Nuwara Eliya (CN). Analysis of urinary biomarkers showed urinary KIM-1 and NGAL were significantly higher in new CKDu cases in EL1 and EL2. However, we also reported significantly higher KIM-1 and NGAL in apparently healthy farmers in EL 1 and EL 2 with comparison to both control groups. These observations may indicate possible early renal damage in absence of persistent albuminuria and potential capabilities of urinary KIM-1 and NGAL in early detection of renal injury
Full Text Available Prevention of cardiovascular disease (CVD is an important therapeutic object of diabetes care. This study assessed whether an index based on plasma free amino acid (PFAA profiles could predict the onset of CVD in diabetic patients. The baseline concentrations of 31 PFAAs were measured with high-performance liquid chromatography-electrospray ionization-mass spectrometry in 385 Japanese patients with type 2 diabetes registered in 2001 for our prospective observational follow-up study. During 10 years of follow-up, 63 patients developed cardiovascular composite endpoints (myocardial infarction, angina pectoris, worsening of heart failure and stroke. Using the PFAA profiles and clinical information, an index (CVD-AI consisting of six amino acids to predict the onset of any endpoints was retrospectively constructed. CVD-AI levels were significantly higher in patients who did than did not develop CVD. The area under the receiver-operator characteristic curve of CVD-AI (0.72 [95% confidence interval (CI: 0.64-0.79] showed equal or slightly better discriminatory capacity than urinary albumin excretion rate (0.69 [95% CI: 0.62-0.77] on predicting endpoints. A multivariate Cox proportional hazards regression analysis showed that the high level of CVD-AI was identified as an independent risk factor for CVD (adjusted hazard ratio: 2.86 [95% CI: 1.57-5.19]. This predictive effect of CVD-AI was observed even in patients with normoalbuminuria, as well as those with albuminuria. In conclusion, these results suggest that CVD-AI based on PFAA profiles is useful for identifying diabetic patients at risk for CVD regardless of the degree of albuminuria, or for improving the discriminative capability by combining it with albuminuria.
Ocak, G; Rookmaaker, M B; Algra, A; de Borst, G J; Doevendans, P A; Kappelle, L J; Verhaar, M C; Visseren, F L
Essentials The association between chronic kidney disease and bleeding is unknown. We followed 10 347 subjects at high cardiovascular risk for bleeding events. Chronic kidney disease was associated with a 1.5-fold increased bleeding risk. Especially albuminuria rather than decreased kidney function was associated with bleeding events. Background There are indications that patients with chronic kidney disease have an increased bleeding risk. Objectives To investigate the association between chronic kidney disease and bleeding in patients at high cardiovascular risk. Methods We included 10 347 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2015 for an outpatient visit with classic risk factors for arterial disease or with symptomatic arterial disease (Second Manifestation of Arterial disease [SMART] cohort). Patients were staged according to the KDIGO guidelines, on the basis of estimated glomerular filtration rate (eGFR) and albuminuria, and were followed for the occurrence of major hemorrhagic events until March 2015. Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding were calculated with Cox proportional hazards analyses. Results The incidence rate for bleeding in subjects with chronic kidney disease was 8.0 per 1000 person-years and that for subjects without chronic kidney disease was 3.5 per 1000 person-years. Patients with chronic kidney disease (n = 2443) had a 1.5-fold (95% CI 1.2-1.9) increased risk of bleeding as compared with subjects without chronic kidney disease (n = 7904) after adjustment. Subjects with an eGFR of Chronic kidney disease is a risk factor for bleeding in patients with classic risk factors for arterial disease or with symptomatic arterial disease, especially in the presence of albuminuria. © 2017 University Medical Center Utrecht. Journal of Thrombosis and Haemostasis © 2017 International Society on Thrombosis and Haemostasis.
He, Jiang; Shlipak, Michael; Anderson, Amanda; Roy, Jason A; Feldman, Harold I; Kallem, Radhakrishna Reddy; Kanthety, Radhika; Kusek, John W; Ojo, Akinlolu; Rahman, Mahboob; Ricardo, Ana C; Soliman, Elsayed Z; Wolf, Myles; Zhang, Xiaoming; Raj, Dominic; Hamm, Lee
Heart failure is common in patients with chronic kidney disease. We studied risk factors for incident heart failure among 3557 participants in the CRIC (Chronic Renal Insufficiency Cohort) Study. Kidney function was assessed by estimated glomerular filtration rate (eGFR) using serum creatinine, cystatin C, or both, and 24-hour urine albumin excretion. During an average of 6.3 years of follow-up, 452 participants developed incident heart failure. After adjustment for age, sex, race, and clinical site, hazard ratio (95% CI) for heart failure associated with 1 SD lower creatinine-based eGFR was 1.67 (1.49, 1.89), 1 SD lower cystatin C-based-eGFR was 2.43 (2.10, 2.80), and 1 SD higher log-albuminuria was 1.65 (1.53, 1.78), all P kidney function measures were simultaneously included in the model, lower cystatin C-based eGFR and higher log-albuminuria remained significantly and directly associated with incidence of heart failure. After adjusting for eGFR, albuminuria, and other traditional cardiovascular risk factors, anemia (1.37, 95% CI 1.09, 1.72, P =0.006), insulin resistance (1.16, 95% CI 1.04, 1.28, P =0.006), hemoglobin A1c (1.27, 95% CI 1.14, 1.41, P chronic kidney disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Arora, Paul; Vasa, Priya; Brenner, Darren; Iglar, Karl; McFarlane, Phil; Morrison, Howard; Badawi, Alaa
Background: Chronic kidney disease is an important risk factor for death and cardiovascular-related morbidity, but estimates to date of its prevalence in Canada have generally been extrapolated from the prevalence of end-stage renal disease. We used direct measures of kidney function collected from a nationally representative survey population to estimate the prevalence of chronic kidney disease among Canadian adults. Methods: We examined data for 3689 adult participants of cycle 1 of the Canadian Health Measures Survey (2007–2009) for the presence of chronic kidney disease. We also calculated the age-standardized prevalence of cardiovascular risk factors by chronic kidney disease group. We cross-tabulated the estimated glomerular filtration rate (eGFR) with albuminuria status. Results: The prevalence of chronic kidney disease during the period 2007–2009 was 12.5%, representing about 3 million Canadian adults. The estimated prevalence of stage 3–5 disease was 3.1% (0.73 million adults) and albuminuria 10.3% (2.4 million adults). The prevalence of diabetes, hypertension and hypertriglyceridemia were all significantly higher among adults with chronic kidney disease than among those without it. The prevalence of albuminuria was high, even among those whose eGFR was 90 mL/min per 1.73 m2 or greater (10.1%) and those without diabetes or hypertension (9.3%). Awareness of kidney dysfunction among adults with stage 3–5 chronic kidney disease was low (12.0%). Interpretation: The prevalence of kidney dysfunction was substantial in the survey population, including individuals without hypertension or diabetes, conditions most likely to prompt screening for kidney dysfunction. These findings highlight the potential for missed opportunities for early intervention and secondary prevention of chronic kidney disease. PMID:23649413
Chang, Jae-Hyung; Paik, Seung-Yeol; Mao, Lan; Eisner, William; Flannery, Patrick J; Wang, Liming; Tang, Yuping; Mattocks, Natalie; Hadjadj, Samy; Goujon, Jean-Michel; Ruiz, Phillip; Gurley, Susan B; Spurney, Robert F
Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diabetic controls for functional and structural characteristics of renal and cardiac disease. Podocyte number and apoptosis as well as urinary nephrin excretion were determined in both groups. Male FVB/NJ Akita mice developed sustained hyperglycemia and albuminuria by 4 and 8 weeks of age, respectively. These abnormalities were accompanied by a significant increase in systolic blood pressure in 10-week old Akita mice, which was associated with functional, structural and molecular characteristics of cardiac hypertrophy. By 20 weeks of age, Akita mice developed a 10-fold increase in albuminuria, renal and glomerular hypertrophy and a decrease in the number of podocytes. Mild-to-moderate glomerular mesangial expansion was observed in Akita mice at 30 weeks of age. In 4-week old Akita mice, the onset of hyperglycemia was accompanied by increased podocyte apoptosis and enhanced excretion of nephrin in urine before the development of albuminuria. Urinary nephrin excretion was also significantly increased in albuminuric Akita mice at 16 and 20 weeks of age and correlated with the albumin excretion rate. These data suggest that: 1. FVB/NJ Akita mice have phenotypic characteristics that may be useful for studying the mechanisms of kidney and cardiac injury in diabetes, and 2. Enhanced urinary nephrin excretion is associated with kidney injury in FVB/NJ Akita mice and is detectable early in the disease process.
Arias, Simone Costa Alarcon; Souza, Renata Alves; Malheiros, Denise Maria Avancini Costa; Fanelli, Camilla; Fujihara, Clarice Kazue; Zatz, Roberto
We have previously shown that an association of losartan and hydrochlorothiazide, initiated 1 mo after 5/6 nephrectomy (Nx), reversed hypertension and albuminuria and promoted lasting renoprotection. In this new study, we investigated whether equal or even better protection could be obtained by combining losartan and furosemide. Nx was performed in 58 Munich-Wistar rats. One month later, tail-cuff pressure and albuminuria were markedly elevated. At this time, Nx rats were distributed among the following four groups: untreated Nx rats, Nx rats that received losartan, Nx rats that received losartan + hydrochlorothiazide, and Nx rats that received losartan + furosemide. Seven months later, Nx rats exhibited high mortality, severe hypertension, albuminuria, glomerulosclerosis, and interstitial fibrosis. Losartan treatment limited mortality and attenuated the renal and hemodynamic abnormalities associated with Nx. As previously shown, the losartan + hydrochlorothiazide association normalized tail-cuff pressure and albumin, prevented renal injury, and reduced mortality to zero. The losartan + furosemide treatment failed to reduce tail-cuff pressure or albumin to normal and prevented renal injury less efficiently than the losartan and hydrochlorothiazide regimen. The reasons for the differing efficacies of the losartan + furosemide and losartan + hydrochlorothiazide schemes are unclear and may include beneficial nondiuretic actions of thiazides, such as vasorelaxation and antiproliferative activity. These results refute the established concept that thiazides and thiazide-like diuretics are ineffective at advanced chronic kidney disease stages. Rather, they suggest that, in view of their renoprotective action, these compounds may even be preferable to loop diuretics in the management of hypertension in advanced chronic kidney disease. Copyright © 2016 the American Physiological Society.
Ellam, Timothy; Fotheringham, James; Wilkie, Martin E.; Francis, Sheila E.; Chico, Timothy J. A.
Background and Hypothesis Even within accepted normal ranges, higher serum phosphorus, dietary phosphorus density, parathyroid hormone (PTH) and alkaline phosphatase (ALP) are independent predictors of cardiovascular mortality. Lower serum 25-hydroxy vitamin D (25(OH)D) also predicts adverse cardiovascular outcomes. We hypothesized that vascular dysfunction accompanying subtle disturbances of these bone metabolism parameters would result in associations with increased low grade albuminuria. Study Population and Measures We examined participants in the National Health and Nutrition Examination Surveys 1999–2010 (N = 19,383) with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 and without severe albuminuria (urine albumin:creatinine ratio (ACR) phosphorus density, serum phosphorus and ALP were not associated with higher ACR or FEalb. The lowest versus highest quintile of 25(OH)D was associated with greater albuminuria, but not after adjustment for other covariates including cardiovascular risk factors. An association between the highest versus lowest quintile of bone-specific ALP and greater ACR persisted after covariate adjustment, but was not accompanied by an independent association with FEalb. Increasing quintiles of PTH demonstrated associations with both higher ACR and FEalb that were not abolished by adjusting for covariates including age, gender, race, body mass index, diabetes, blood pressure, history of cardiovascular disease, smoking, eGFR, 25(OH)D, season of measurement, lipids, hemoglobin and C-reactive protein. Adjusted increases in ACR and FEalb associated with the highest versus lowest quintile of PTH were 19% (95% confidence interval 7–28% p<0.001) and 17% (8–31% p = 0.001) respectively. Conclusion In this population, of the bone mineral parameters associated with cardiovascular outcomes, only PTH is independently associated with ACR and FEalb. PMID:24505486
Ellam, Timothy; Fotheringham, James; Wilkie, Martin E; Francis, Sheila E; Chico, Timothy J A
Even within accepted normal ranges, higher serum phosphorus, dietary phosphorus density, parathyroid hormone (PTH) and alkaline phosphatase (ALP) are independent predictors of cardiovascular mortality. Lower serum 25-hydroxy vitamin D (25(OH)D) also predicts adverse cardiovascular outcomes. We hypothesized that vascular dysfunction accompanying subtle disturbances of these bone metabolism parameters would result in associations with increased low grade albuminuria. We examined participants in the National Health and Nutrition Examination Surveys 1999-2010 (N = 19,383) with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m² and without severe albuminuria (urine albumin:creatinine ratio (ACR) phosphorus density, serum phosphorus and ALP were not associated with higher ACR or FE(alb). The lowest versus highest quintile of 25(OH)D was associated with greater albuminuria, but not after adjustment for other covariates including cardiovascular risk factors. An association between the highest versus lowest quintile of bone-specific ALP and greater ACR persisted after covariate adjustment, but was not accompanied by an independent association with FE(alb). Increasing quintiles of PTH demonstrated associations with both higher ACR and FE(alb) that were not abolished by adjusting for covariates including age, gender, race, body mass index, diabetes, blood pressure, history of cardiovascular disease, smoking, eGFR, 25(OH)D, season of measurement, lipids, hemoglobin and C-reactive protein. Adjusted increases in ACR and FE(alb) associated with the highest versus lowest quintile of PTH were 19% (95% confidence interval 7-28% p<0.001) and 17% (8-31% p = 0.001) respectively. In this population, of the bone mineral parameters associated with cardiovascular outcomes, only PTH is independently associated with ACR and FE(alb).
Beig, Junaid; Khanolkar, Manish; Cundy, Tim
Type 2 diabetes (T2D) in young adults is associated with a high risk of diabetes complications. To investigated the demography and the emergence of complications of young adults with T2D in the central Auckland region where there has been substantial immigration. In total, 310 young adults with T2D (Auckland Diabetes Centre in 2015. We documented demographic, anthropometric and metabolic variables and prevalence and the emergence of complications. Three demographic groups accounted for 243 participants (78%): 135 (44%) were migrants of Asian or Pacific Island origin, diagnosed a median 9 years after migration at a mean age of 28 ± 6 years; 88 (29%) were New Zealand-born Pāsifika descent, with a high prevalence of morbid obesity and 37 (12%) had major mental illness or intellectual disability. At diagnosis, the median HbA1c was 80 mmol/mol, and in 28%, it was ≥100 mmol/mol. A median 6 years after diagnosis, 56% had some degree of retinopathy, with the prevalence related both to the duration of diabetes and glycaemic control (P = 0.001). Forty-four percent of subjects had abnormal albuminuria at diagnosis (12% with macroalbuminuria). Increased albuminuria was strongly associated with obesity (P = 0.002). The development of CKD stages 4-5 was related both to the severity of retinopathy and degree of albuminuria at diagnosis (P = 0.0001). Major cardiovascular events were related to the severity of retinopathy at diagnosis (P = 0.0001). New migrants, New Zealand-born Pāsifika and patients with mental illness or an intellectual disability comprise the bulk of young onset T2D. The disease is aggressive, and by the age of 40, patients are already developing advanced complications. © 2017 Royal Australasian College of Physicians.
Christensen, P K; Rossing, P; Nielsen, F S
AIMS: To determine the natural course of kidney function and to evaluate the impact of putative progression promoters in Caucasian Type 2 diabetes mellitus (DM) patients with diabetic nephropathy who had never received any antihypertensive treatment. METHODS: A long-term observational study of 13...... normotensive to borderline hypertensive Type 2 DM patients with diabetic nephropathy. Glomerular filtration rate (GFR) was measured approximately every year (51Cr-EDTA plasma clearance technique). Albuminuria, blood pressure (BP) and haemoglobin A1c (HbA1c) was determined 2-4 times per year and serum...
Full Text Available BACKGROUND: Landmark clinical trials have led to optimal treatment recommendations for patients with diabetes. Whether optimal treatment is actually delivered in practice is even more important than the efficacy of the drugs tested in trials. To this end, treatment quality indicators have been developed and tested against intermediate outcomes. No studies have tested whether these treatment quality indicators also predict hard patient outcomes. METHODS: A cohort study was conducted using data collected from >10.000 diabetes patients in the Groningen Initiative to Analyze Type 2 Treatment (GIANTT database and Dutch Hospital Data register. Included quality indicators measured glucose-, lipid-, blood pressure- and albuminuria-lowering treatment status and treatment intensification. Hard patient outcome was the composite of cardiovascular events and all-cause death. Associations were tested using Cox regression adjusting for confounding, reporting hazard ratios (HR with 95% confidence intervals. RESULTS: Lipid and albuminuria treatment status, but not blood pressure lowering treatment status, were associated with the composite outcome (HR = 0.77, 0.67-0.88; HR = 0.75, 0.59-0.94. Glucose lowering treatment status was associated with the composite outcome only in patients with an elevated HbA1c level (HR = 0.72, 0.56-0.93. Treatment intensification with glucose-lowering but not with lipid-, blood pressure- and albuminuria-lowering drugs was associated with the outcome (HR = 0.73, 0.60-0.89. CONCLUSION: Treatment quality indicators measuring lipid- and albuminuria-lowering treatment status are valid quality measures, since they predict a lower risk of cardiovascular events and mortality in patients with diabetes. The quality indicators for glucose-lowering treatment should only be used for restricted populations with elevated HbA1c levels. Intriguingly, the tested indicators for blood pressure-lowering treatment did not predict patient
Parving, H H; Jacobsen, P; Tarnow, L
with insulin dependent diabetes and nephropathy who had been treated with captopril for a median of 7 years (range 3-9 years). SETTING: Outpatient diabetic clinic in a tertiary referral centre. PATIENTS: 35 patients with insulin dependent diabetes and nephropathy were investigated during captopril treatment...... blood pressure, and glomerular filtration rate according to insertion/deletion polymorphism. RESULTS: The two groups had comparable glomerular filtration rate, albuminuria, blood pressure, and haemoglobin A1c concentration at baseline. Captopril induced nearly the same reduction in mean blood pressure...
Tarnow, L; Parving, H H; Jacobsen, P
. Patients were investigated during captopril treatment for a median of seven (range three to nine) years. Eleven patients were homozygous for the deletion allele (DD) and 24 were hetero- or homozygous for the insertion allele (ID + II). The two groups had comparable glomerular filtration rate, albuminuria...... and blood pressure at baseline and captopril induced nearly the same mean reduction in blood pressure--to 103 (SD 5) mm Hg in the DD-group and 102 (8) mm Hg in the ID + II-group. The rate of decline in glomerular filtration rate was significantly steeper in the DD group than in the other group (mean 5.7 (SD...