Validation of an Albuminuria Self-assessment Tool in the Multi-Ethnic Study of Atherosclerosis.

Science.gov (United States)

Tanner, Rikki M; Woodward, Mark; Peralta, Carmen; Warnock, David G; Gutiérrez, Orlando; Shimbo, Daichi; Kramer, Holly; Katz, Ronit; Muntner, Paul

2015-11-05

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.

Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers

NARCIS (Netherlands)

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

Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells.

Directory of Open Access Journals (Sweden)

Li Fang

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.

Urinary adiponectin and albuminuria in non-diabetic hypertensive patients: an analysis of the ESPECIAL trial.

Science.gov (United States)

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

2015-08-01

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.

YKL-40 levels are independently associated with albuminuria in type 2 diabetes

DEFF Research Database (Denmark)

Røndbjerg, Anne K; Omerovic, Emina; Vestergaard, Henrik

2011-01-01

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 morta...... 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.......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...

Albuminuria and associated risk factors in type II diabetics

International Nuclear Information System (INIS)

Hashim, R.; Ahmed, T.A.; Mushtaq, S.; Zafar, L.; Attique, M.; Khalil-ur-Rehman

2004-01-01

Objective: To determine the frequency of microalbuminuria (MA) and its associated medical risk factors in type II diabetic patients. Materials and Methods: Study population included 150 type II diabetic patients (70 women, 80 men) attending outpatient department of the hospital. Patients having clinical albuminuria and with other causes of proteinuria were excluded. Results: Women and men were of comparable ages. Women (26.4 kg/m/sup 2/) had higher body mass index (BMI) than men 24.3 kg/m/sup 2/). The frequency of MA was 46.7%, higher in males (50.6%) than females (41.5%). Fasting plasma glucose HbA/sub 1c/ levels were significantly higher in patients with MA compared to those with normo albuminuria (p < 0.001). The microalbuminuria patients had significantly decreased HDL-c levels compared to normoalbuminuric subjects (p< 0.001). However, no relation of MA with age, gender, known duration of diabetes, BMI, history of smoking, hypertension and serum: total cholesterol, LDL-c, triglyceride, urea and creatinine was found. Conclusion: There is a strong association of poor glycaemic control and decreased HDL-c levels with the presence of micro albuminuria. (author)

Determining the Optimal Protocol for Measuring an Albuminuria Class Transition in Clinical Trials in Diabetic Kidney Disease

DEFF Research Database (Denmark)

Kröpelin, Tobias F; de Zeeuw, Dick; Remuzzi, Giuseppe

2016-01-01

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...... 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...... 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...

Prevalence and determinants of albuminuria in a cohort of diabeticpatients in Lebanon

International Nuclear Information System (INIS)

Taleb, N.; Al-Mokadda, M.; Merheb, M.; Salti, I.; Nasrallah, M.; Salti, H.

2008-01-01

Few data are available on the extent of albuminuria in diabeticpopulations in the Middle East generally and in Lebanon specifically. Weconducted this study to determine the prevalence of albuminuria and its majorrisk factors in cohort of diabetic patients in Lebanon. Diabetic patientsfollowed in the outpatient department at the American University of BeirutMedical Center (AUBMC) were included in prospective observational study.AUBMC is a tertiary referral center and the outpatient department typicallyhandles patients of low socioeconomic status with advanced disease. Patientswere classified according to their urinary albumin-to-creatinine ratio (ACR)as having normoalbuminuria (ACR -300mg/g creatinine). Thethree groups were compared to analyze the association between albuminuria andits risk factors. In addition, independent predictors of albuminuria weredetermined using multivariate logistic regression and presented as an oddsratio. Microalbuminuria and macroalbuminuira 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 associatedwith microalbuminuria included glycemic control, insulin use and total andLDL cholesterol. Those associated with macroalbuminuria included in additionto glycemic control and insulin use, duration of diabetes, hypertension,elevated mean arterial pressure (MAP) and presence of neuropathy, retinopathyand peripheral vascular disease by bivariate analysis. Only glycemic controlwas an independent risk factor for both in addition to MAP and retinopathyfor macroalbuminuria by multivariate analysis. Albuminuria is highlyprevalent among this cohort of diabetic patients in Lebanon. Both glycemiccontrol and blood pressure need to be better targeted in its management.(author)

Prevalence and determinants of albuminuria in a cohort of diabetic patients in Lebanon

International Nuclear Information System (INIS)

Nadine, Taleb

2010-01-01

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).

Predictors of Atrasentan-Associated Fluid Retention and Change in Albuminuria in Patients with Diabetic Nephropathy

DEFF Research Database (Denmark)

Kohan, Donald E; Lambers Heerspink, Hiddo J; Coll, Blai

2015-01-01

. CONCLUSIONS: 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......BACKGROUND AND OBJECTIVES: 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A post hoc analysis...

Extracellular ATP induces albuminuria in pregnant rats

NARCIS (Netherlands)

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.

Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients with left ventricular hypertrophy and diabetes

DEFF Research Database (Denmark)

Ibsen, H.; Olsen, M.H.; Wachtell, K.

2008-01-01

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......, 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...... baseline values of albuminuria had the greatest benefit in terms of reduction in cardiovascular morbidity and mortality on losartan as compared with atenolol. The level of albuminuria during treatment was closely related to the risk for cardiovascular events. We conclude that tiny amounts of albuminuria...

ABNORMAL PLASMA NORADRENALINE RESPONSE AND EXERCISE INDUCED ALBUMINURIA IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

NARCIS (Netherlands)

HOOGENBERG, K; DULLAART, RPF

1992-01-01

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

Micro-Albuminuria In Adolescent/Young Adult Offsprings Of ...

African Journals Online (AJOL)

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, ...

Epitope mapping of monoclonal antibodies directed to aminopeptidase A and their relevance for albuminuria in mice.

Science.gov (United States)

Gerlofs-Nijland, Miriam E; Assmann, Karel J M; van Son, Jacco P H F; Dijkman, Henry B P M; te Loeke, Nathalie A J M; van der Zee, Ruurd; Wetzels, Jack F M; Groenen, Patricia J T A

2003-01-01

We have shown previously that injection of specific combinations of anti-aminopeptidase A monoclonal antibodies induces an acute massive albuminuria in mice. This albuminuria is neither dependent on systemic mediators of inflammation nor angiotensin II. In this study, we examined the contribution of two individual antibodies, the enzyme-inhibiting antibody ASD-37 and the non-enzyme-inhibiting antibody ASD-41, in the induction of albuminuria as well as the interactions between these two monoclonals. In addition, we have mapped the epitopes of both antibodies using in vitro coupled transcription/translation of specifically designed cDNA fragments followed by immunoprecipitation, and using peptide enzyme-linked immunosorbent assay in case of a continuous epitope. A single intravenous injection of 4 mg of either ASD-37 or ASD-41 did not induce albuminuria. This dose of ASD-37 did not completely inhibit enzyme activity. The combination of 4 mg ASD-37/41 (1:1 weight ratio) induced albuminuria and almost completely inhibited enzyme activity. Similar results were obtained with a combination of ASD-37/41 in a 1:39 or 39:1 weight ratio. Administration of 2 mg ASD-41 24 h before injection of 2 mg ASD-37 significantly enhanced albuminuria. The epitope of ASD-37 is located at the C-terminal end of aminopeptidase A, whereas the ASD-41 epitope is mapped near the enzyme active site. Our data suggest that ASD-41 modulates the binding of ASD-37 to its epitope and/or vice versa. As a consequence, ASD-37 and ASD-41 act synergistically, not only in inhibiting enzyme activity but also in inducing albuminuria. Copyright 2003 S. Karger AG, Basel

Prevalence, risk factors and awareness of albuminuria on a Canadian First Nation: A community-based screening study

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Zacharias James

2012-04-01

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.

Prevalence of Albuminuria in Children Living in a Rural Agricultural and Fishing Subsistence Community in Lake Chapala, Mexico

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Felipe Lozano-Kasten

2017-12-01

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.

Nickel exposure and prevalent albuminuria and β2-microglobulinuria: evidence from a population-based study.

Science.gov (United States)

Liu, Gang; Sun, Qi; Zhu, Mingjiang; Sun, Liang; Wang, Zhenzhen; Li, Huaixing; Li, Zi; Chen, Yan; Yin, Huiyong; Lin, Xu

2016-05-01

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/

Effects of liraglutide on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria

DEFF Research Database (Denmark)

von Scholten, Bernt Johan; Persson, Frederik; Rosenlund, Signe

2017-01-01

-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...

The Association of Albuminuria With Tubular Reabsorption of Uric Acid : Results From a General Population Cohort

NARCIS (Netherlands)

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

Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability.

Science.gov (United States)

Salmon, Andrew H J; Satchell, Simon C

2012-03-01

Appreciation of the glomerular microcirculation as a specialized microcirculatory bed, rather than as an entirely separate entity, affords important insights into both glomerular and systemic microvascular pathophysiology. In this review we compare regulation of permeability in systemic and glomerular microcirculations, focusing particularly on the role of the endothelial glycocalyx, and consider the implications for disease processes. The luminal surface of vascular endothelium throughout the body is covered with endothelial glycocalyx, comprising surface-anchored proteoglycans, supplemented with adsorbed soluble proteoglycans, glycosaminoglycans and plasma constituents. In both continuous and fenestrated microvessels, this endothelial glycocalyx provides resistance to the transcapillary escape of water and macromolecules, acting as an integral component of the multilayered barrier provided by the walls of these microvessels (ie acting in concert with clefts or fenestrae across endothelial cell layers, basement membranes and pericytes). Dysfunction of any of these capillary wall components, including the endothelial glycocalyx, can disrupt normal microvascular permeability. Because of its ubiquitous nature, damage to the endothelial glycocalyx alters the permeability of multiple capillary beds: in the glomerulus this is clinically apparent as albuminuria. Generalized damage to the endothelial glycocalyx can therefore manifest as both albuminuria and increased systemic microvascular permeability. This triad of altered endothelial glycocalyx, albuminuria and increased systemic microvascular permeability occurs in a number of important diseases, such as diabetes, with accumulating evidence for a similar phenomenon in ischaemia-reperfusion injury and infectious disease. The detection of albuminuria therefore has implications for the function of the microcirculation as a whole. The importance of the endothelial glycocalyx for other aspects of vascular function

Prevalence and determinants of albuminuria in a cohort of diabetic patients in Lebanon.

Science.gov (United States)

Taleb, Nadine; Salti, Haytham; Al-Mokaddam, Mona; Merheb, Marie; Salti, Ibrahim; Nasrallah, Mona

2008-01-01

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. 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 or =300 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 glycemic control and blood pressure need to be better targeted in its management.

[The effect of trandolapril, in monotherapy and associated with verapamil, on arterial pressure, albuminuria, and metabolic control in hypertensive patients with type 2 diabetes and albuminuria].

Science.gov (United States)

Fernández González, R; García Robles, R; Rodríguez Pérez, J C; Gómez Pajuelo, C; Moreno Carretero, E

2001-01-01

The aim of this study was to analyse the effect of the ACE-1, Trandolapril, alone or with Verapamil on blood pressure, albuminuria and metabolic profile in type 2 diabetic patients with hypertension and albuminuria. It was an open multicenter, consecutive and prospective study conducted in 281 patients. There was a four-week wash-out period of antihypertensive drugs, after which we carried out a measurement over a 24-h period of the urinary excretion of albumina (UEA). Blood pressure was recorded after at least 5 minutes of rest in the sitting position at 1 to 3 minute intervals with a mercury sphygmomanometer in good condition. Average BP was obtained from three consecutive readings. Within treatment changes were analysed using descriptive statistics and t-tests on the change from baseline. Analysis of variance, chi-square and Mc Nemar tests were also used. If after 8 weeks of treatment with Trandolapril 2 mg o.q.d. the patients were non-responders (mean blood pressure reduction of 5 mmHg or less) or their blood pressure remained uncontrolled (blood pressure > or = 140/90 mmHg), Verapamil 180 mg o.q.d. was added. Two hundred and thirty patients completed the 12 weeks study. Population included 157 (55.9%) males with an average of 61.7 +/- 9.2 years. Baseline measurements were systolic 165.4 +/- 14.6 and diastolic 94.8 +/- 8.5 mmHg blood pressures, fasting glucose 162.7 +/- 43.9 mg/dL, glycosylated hemoglobin (HbAlc) 6.8 +/- 1.2%, and albuminuria 520.9 +/- 602 mg/day. UEA fell significantly (p < 0.001) after treatment to 177.9 +/- 24.3 mg/day (CI 95%, 129.9 to 225.8). The percent reduction reached 29.6%. Albuminuria was lower than 30 mg/day in 47 patients. Blood pressure was completely controlled in 125 (54%) patients. Glucemia fell significantly (p < 0.001) to 153.2 +/- 42.7 mg/dL, and the HbAlc to 6.5 +/- 1.3% (p = 0.012). In summary, in those diabetic type 2 patients with arterial hypertension and proteinuria, Trandolapril alone or associated with Verapamil

The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy

DEFF Research Database (Denmark)

de Zeeuw, Dick; Coll, Blai; Andress, Dennis

2014-01-01

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...... reduces albuminuria when administered concomitantly with maximum tolerated labeled doses of RAS inhibitors. We enrolled 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) in two identically designed, parallel, multinational, double...... parameters returned to pretreatment levels. In conclusion, atrasentan reduced albuminuria and improved BP and lipid spectrum with manageable fluid overload-related adverse events in patients with type 2 diabetic nephropathy receiving RAS inhibitors....

Xanthine oxidase and uric acid as independent predictors of albuminuria in patients with diabetes mellitus type 2.

Science.gov (United States)

Klisic, Aleksandra; Kocic, Gordana; Kavaric, Nebojsa; Jovanovic, Milovan; Stanisic, Verica; Ninic, Ana

2018-05-01

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.

Urinary excretion of uric acid is negatively associated with albuminuria in patients with chronic kidney disease: a cross-sectional study.

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Li, Fengqin; Guo, Hui; Zou, Jianan; Chen, Weijun; Lu, Yijun; Zhang, Xiaoli; Fu, Chensheng; Xiao, Jing; Ye, Zhibin

2018-04-24

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.

The effects of protein intake on albuminuria in different estimated glomerular filtration rate: A population-based study.

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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

2018-02-01

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.

Second measurement of morning systolic blood pressure is more closely associated with albuminuria.

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Sakabe, Kazumi; Fukui, Michiaki; Ushigome, Emi; Hamaguchi, Masahide; Tanaka, Toru; Atsuta, Haruhiko; Ohnishi, Masayoshi; Oda, Yohei; Hasegawa, Goji; Nakamura, Naoto

2012-08-01

It is important to control blood pressure as well as to control blood glucose for the prevention of diabetic nephropathy. However, to our knowledge, there are no reports investigating which blood pressure, including morning, evening and clinic, is more closely associated with albuminuria and whether one measurement is sufficient or not in patients with Type 2 diabetes. We measured morning, evening and clinic blood pressure and compared the area under the curve (AUC) of blood pressure for urinary albumin excretion equal to or more than 30 mg/g creatinine using receiver-operating characteristic curve analyses and odds ratio for albuminuria defined as urinary albumin excretion equal to or more than 30 mg/g creatinine in 858 patients with Type 2 diabetes. Odds ratio (95% confidence interval (CI)) of morning, evening and clinic systolic blood pressure for albuminuria was 1.034 (1.024 - 1.044), 1.033 (1.023 - 1.043) and 1.013 (1.055 - 1.021), respectively (p AUC of morning, evening and clinic systolic blood pressure was 0.644 (0.628 - 0.700) (p AUC of the second morning systolic blood pressure was greater than the first (p = 0.033). The second measurement of morning systolic blood pressure is more closely associated with albuminuria than the first measurement of the morning in addition to clinic systolic blood pressure.

Changes in albuminuria and renal outcome in patients with type 2 diabetes and hypertension: a real-life observational study.

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Viazzi, Francesca; Ceriello, Antonio; Fioretto, Paola; Giorda, Carlo; Guida, Pietro; Russo, Giuseppina; Greco, Eulalia; De Cosmo, Salvatore; Pontremoli, Roberto

2018-04-19

To assess the predictive role of changes in albuminuria on the loss of renal function under antihypertensive treatment in patients with type 2 diabetes (T2D). Clinical records from a total of 12 611 patients with hypertension and T2D, attending 100 antidiabetic centers in Italy, with normal estimated glomerular filtration rate (eGFR) at baseline and regular visits during a 4-year period were retrieved and analyzed. We assessed the association between changes in albuminuria status during a 1-year baseline period and time updated blood pressure (BP) and eGFR loss over the subsequent 4-year follow-up. Mean age at baseline was 65 ± 9 years, known duration of diabetes11 ± 8 years, eGFR 85 ± 13 ml/min and BP 142 ± 17/81 ± 9 mmHg. Patients with persistent albuminuria showed the highest 4-year risk of eGFR loss more than 30% from baseline or onset of stage 3 chronic kidney disease (eGFR < 60 ml/min) as compared with those with persistent normal albuminuria (odds ratio 2.00, confidence interval 1.71-2.34; P < 0.001). Female sex, age, disease duration, BMI, low baseline eGFR, lipid profile, the number of antihypertensive drugs and variations in albuminuria status were associated with renal risk in the whole study population. Furthermore, lower time updated BP values and the use of renin-angiotensin-aldosterone-system-inhibitors were related to the occurrence of renal endpoints only in the subgroup of patients without albuminuria. In patients with hypertension and T2D under real-life clinical conditions, changes in albuminuria parallel changes of renal risk. Albuminuria status could be a guide to optimize therapeutic strategy.

Global Longitudinal Strain Is Not Impaired in Type 1 Diabetes Patients Without Albuminuria

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Jensen, Magnus Thorsten; Sogaard, Peter; Andersen, Henrik Ullits

2015-01-01

suggested. It is not known whether myocardial dysfunction is a feature of T1DM per se or primarily associated with diabetes with albuminuria. METHODS: This cross-sectional study compared 1,065 T1DM patients without known heart disease from the outpatient clinic at the Steno Diabetes Center with 198 healthy......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...... mass index 25.5 kg/m(2), and mean diabetes duration 26.1 years. In unadjusted analyses, GLS differed significantly between T1DM patients and control subjects (p = 0.02). When stratified by degrees of albuminuria, the difference in GLS compared with control subjects was -18.8 ± 2.5% versus -18.5 ± 2...

Albuminuria, Proteinuria, and Novel Urine Biomarkers as Predictors of Long-term Allograft Outcomes in Kidney Transplant Recipients

NARCIS (Netherlands)

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

Albuminuria, proteinuria, and novel urine biomarkers as predictors of long-term allograft outcomes in kidney transplant recipients

NARCIS (Netherlands)

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.

2011-01-01

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

Cost-effectiveness of aliskiren in type 2 diabetes, hypertension, and albuminuria

DEFF Research Database (Denmark)

Delea, Thomas E; Sofrygin, Oleg; Palmer, James L

2009-01-01

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...... health care costs increased by $2952, reflecting the higher pharmacy costs of aliskiren and losartan ($7769), which were partially offset by savings in costs of ESRD ($4860). We estimated the cost-effectiveness of aliskiren to be $30,500 per quality-adjusted life year gained. In conclusion, adding...... 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....

Induction of albuminuria in mice: synergistic effect of two monoclonal antibodies directed to different domains of aminopeptidase A.

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Mentzel, S; van Son, J P; Dijkman, H B; Wetzels, J F; Assmann, K J

1999-04-01

Aminopeptidase A is an enzyme that is present on podocytes and is involved in the degradation of angiotensin II. In previous studies in mice, we administered single monoclonal antibodies directed against aminopeptidase A. We observed that only monoclonal antibodies that inhibited aminopeptidase A enzyme activity caused albuminuria. In this study, the effects of the combined injections of two monoclonal anti-aminopeptidase A antibodies (mAbs) were studied, using a combination of anti-aminopeptidase A mAbs that were directed against two different domains involved in the aminopeptidase A enzyme activity (ASD-3 or ASD-37) and an anti-aminopeptidase A mAb not related to the enzyme active site (ASD-41). An injection of the combinations ASD-3/37 (total 4 mg, 1:1 ratio) and ASD-37/41 (total 4 mg, 1:1 ratio) in doses that do not cause albuminuria when given alone (4 mg) induced massive albuminuria at day 1 after injection. The combination ASD-3/41 had no effect. This albuminuria was not dependent on systemic immune mediators of inflammation and could not merely be related to a blockade of aminopeptidase A enzyme activity. However, a correlation was observed between the induction of albuminuria and the aggregation of the mAbs injected and aminopeptidase A on the podocytes. An injection of the combinations ASD-3/37 or ASD-37/41 did not cause an increase in systemic blood pressure. The treatment with a combination of enalapril and losartan lowered blood pressure (53 +/- 10 vs. 90 +/- 3 mm Hg in untreated mice) and reduced the acute albuminuria by 55% (11,145 +/- 864 vs. 24,517 +/- 2448 micrograms albumin/18 hr in untreated mice). However, similar effects were observed using triple therapy. Therefore, the reduction of albuminuria by the combined treatment of enalapril/losartan seems to be the consequence of the reduction in the systemic blood pressure. These findings argue against a specific role for angiotensin II in this model. The combined injection of two mAbs directed

A gene variant in CERS2 is associated with rate of increase in albuminuria in patients with diabetes from ONTARGET and TRANSCEND.

Directory of Open Access Journals (Sweden)

Dov Shiffman

Full Text Available Although albuminuria and subsequent advanced stage chronic kidney disease are common among patients with diabetes, the rate of increase in albuminuria varies among patients. Since genetic variants associated with estimated glomerular filtration rate (eGFR were identified in cross sectional studies, we asked whether these variants were also associated with rate of increase in albuminuria among patients with diabetes from ONTARGET and TRANSCEND-randomized controlled trials of ramipril, telmisartan, both, or placebo. For 16 genetic variants associated with eGFR at a genome-wide level, we evaluated the association with annual rate of increase in albuminuria estimated from urine albumin:creatinine ratio (uACR. One of the variants (rs267734 was associated with rate of increase in albuminuria. The annual rate of increase in albuminuria among risk homozygotes (69% of the study population was 11.3% (95%CI; 7.5% to 15.3%, compared with 5.0% (95%CI; 3.3% to 6.8% for heterozygotes (27% of the population, and 1.7% (95%CI; -1.7% to 5.3% for non-risk homozygotes (4% of the population; P = 0.0015 for the difference between annual rates in the three genotype groups. These estimates were adjusted for age, sex, ethnicity, and principal component of genetic heterogeneity. Among patients without albuminuria at baseline (uACR<30 mg/g, each risk allele was associated with 50% increased risk of incident albuminuria (OR = 1.50; 95%CI 1.15 to 1.95; P = 0.003 after further adjustment for traditional risk factors including baseline uACR and eGFR. The rs267734 variant is in almost perfect linkage-disequilibrium (r2 = 0.94 with rs267738, a single nucleotide polymorphism encoding a glutamic acid to alanine change at position 115 of the ceramide synthase 2 (CERS2 encoded protein. However, it is unknown whether CERS2 function influences albuminuria. In conclusion, we found that rs267734 in CERS2 is associated with rate of increase in albuminuria among patients

TLR-mediated albuminuria needs TNFα-mediated cooperativity between TLRs present in hematopoietic tissues and CD80 present on non-hematopoietic tissues in mice

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Nidhi Jain

2016-06-01

Full Text Available 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.

Reduction in albuminuria predicts diminished progression in diabetic nephropathy

DEFF Research Database (Denmark)

Rossing, P; Hommel, E; Smidt, U M

1994-01-01

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...

Albuminuria in heart failure : what do we really know?

NARCIS (Netherlands)

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

HbA1c variability in type 2 diabetes is associated with the occurrence of new-onset albuminuria within three years.

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Dorajoo, Sreemanee Raaj; Ng, Joceline Shi Ling; Goh, Jessica Hui Fen; Lim, Su Chi; Yap, Chun Wei; Chan, Alexandre; Lee, Joyce Yu Chia

2017-06-01

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, pHbA1c-CV improves 3-year prediction of new-onset albuminuria. 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.

High rates of albuminuria but not of low eGFR in Urban Indigenous Australians: the DRUID Study

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Zimmet Paul Z

2011-05-01

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

TRPC6 enhances angiotensin II-induced albuminuria.

LENUS (Irish Health Repository)

Eckel, Jason

2011-03-01

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.

Albuminuria and masked uncontrolled hypertension in chronic kidney disease.

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Agarwal, Rajiv

2017-12-01

Masked uncontrolled hypertension (MUCH) is associated with greater target organ damage such as left ventricular hypertrophy, increased arterial stiffness and albuminuria. Whether MUCH independently associates with greater cardiovascular end-organ damage or kidney damage is unclear. The objective of this study was to assess the strength of the relationship of MUCH (awake ambulatory blood pressure ≥135/85 mmHg and clinic blood pressure <140/90 mmHg) with target organ damage. In a cross-sectional study at a veterans' administration medical center, clinically normotensive veterans without chronic kidney disease (CKD) (n = 29) and 287 patients with CKD and controlled hypertension (CH, n = 193), MUCH (n = 67) and uncontrolled hypertension (UCH, n = 27) had evaluation of target organ damage. Target organ damage was measured by echocardiography [left ventricular mass index (LVMI)], arterial ultrasonography [aortic pulse wave velocity (PWV)] and 24-h urine collection [albuminuria (urine albumin to creatinine ratio)] in all participants. Compared to that of controls, LVMI was higher by 21.8 g/m2 (CI, 4.0-39.7 g/m2) in CH, 27.9 (CI, 8-47.8) in MUCH and 39.5 (CI, 15.7-63.2) in UCH (P < 0.01 for group differences, P < 0.01 for linear trend). Although differences persisted after adjustment for age, sex and race, they lost significance after adjustments for cardiovascular risk factors and their treatment. Compared to that of controls, PWV was different among CH, MUCH and UCH (P = 0.04 for group differences, P = 0.02 for linear trend). However, differences lost significance after adjustments for age, sex and race. Compared to that of controls, log2 UACR was higher by 2.40 mg/mg (CI, 1.28-3.52) in CH, 4.94 (CI, 3.70-6.18) in MUCH and 6.01 (CI, 4.49-7.53) in UCH (P < 0.0001 for group difference, P < 0.0001 for linear trend). Differences persisted after adjustment for age, sex and race, cardiovascular risk factors and their treatment and cardiovascular disease (P < 0.0001 for group

Which Measurement of Blood Pressure Is More Associated With Albuminuria in Patients With Type 2 Diabetes: Central Blood Pressure or Peripheral Blood Pressure?

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Kitagawa, Noriyuki; Okada, Hiroshi; Tanaka, Muhei; Hashimoto, Yoshitaka; Kimura, Toshihiro; Nakano, Koji; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto; Fukui, Michiaki

2016-08-01

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, PAUC 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.

Predicting albuminuria response to spironolactone treatment with urinary proteomics in patients with type 2 diabetes and hypertension

DEFF Research Database (Denmark)

Lindhardt, Morten; Persson, Frederik; Oxlund, Christina

2018-01-01

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......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...... 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 proteomics may be a valuable tool to tailor therapy, but confirmation in a larger clinical trial is required....

Development and Validation of a Self-Assessment Tool for Albuminuria: Results From the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Science.gov (United States)

Muntner, Paul; Woodward, Mark; Carson, April P; Judd, Suzanne E; Levitan, Emily B; Mann, Devin; McClellan, William; Warnock, David G

2011-01-01

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

LONG-TERM EFFECTS OF PROTEIN-RESTRICTED DIET ON ALBUMINURIA AND RENAL-FUNCTION IN IDDM PATIENTS WITHOUT CLINICAL NEPHROPATHY AND HYPERTENSION

NARCIS (Netherlands)

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

GlycA, a marker of protein glycosylation, is related to albuminuria and estimated glomerular filtration rate: the ELSA-Brasil study.

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Titan, Silvia M; Pecoits-Filho, Roberto; Barreto, Sandhi M; Lopes, Antônio Alberto; Bensenor, Isabela J; Lotufo, Paulo A

2017-12-20

Systemic inflammation has been implicated in several chronic diseases. GlycA is a new nuclear mass resonance (NMR) spectroscopy-derived biomarker of systemic inflammation that reflects protein glycosylation. We evaluated the association of GlycA with albuminuria and eGFR in the ELSA-Brasil Study. The cross-sectional association between GlycA (automated NMR LipoProfile(®) test spectra, LabCorp, Raleigh, NC), and overnight 12 h-albuminuria and CKD-EPI eGFR was evaluated among 5050 participants. GlycA was higher among older, women, smokers, alcohol abstemious, obese and in those with diabetes, hypertension or dyslipidemia. In addition, both eGFR and albuminuria were associated to GlycA. In linear regression, GlycA was independently associated with log albuminuria (B 0.03; 95%CI 0.02-0.04, P < 0.0001, per 1sd increase) and inversely related to eGFR (B -0.53; 95%CI -0.99 - -0.07, P < 0.02), even after adjustments including hsCRP. In logistic regression, GlycA was independently related to the risk of A2 or A3 albuminuria (OR 1.42, 95%CI 1.27-1.57, p < 0.0001, per 1sd increase), of having an eGFR < 60 ml/min/1.73m 2 (OR 1.26, 95%CI 1.12-1.41, p = 0.0003, per 1 sd) or of a combined diagnosis of both conditions (OR 1.35, 95%CI 1.23-1.46, p < 0.0001, per 1 sd). In the ROC curve, GlycA had a higher AUC in comparison to hsCRP (AUC 0.67 vs. 0.62, p = 0.06) for the association with albuminuria A2 or A3. The present study demonstrates that GlycA is associated with albuminuria and eGFR, independently of major risk factors for CKD progression, including (and with a stronger association than) hsCRP. GlycA should be further evaluated in CKD progression.

Albuminuria : what can we expect from the determination of nonimmunoreactive albumin?

NARCIS (Netherlands)

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

Albuminuria : What can we expect from the determination of nonimmunoreactive albumin?

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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

Circadian rhythm of arterial blood pressure and albuminuria in diabetic nephropathy

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Hansen, H P; Rossing, P; Tarnow, L

1996-01-01

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 p...

Is albuminuria screening and treatment optimal in patients with type 2 diabetes in primary care? Observational data of the GIANTT cohort

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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

Cardiovascular risk factors and incident albuminuria in screen-detected type 2 diabetes

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Webb, D. R.; Zaccardi, F.; Davies, M. J.; Griffin, S. J.; Wareham, N. J.; Simmons, R. K.; Rutten, G. E.; Sandbaek, A.; Lauritzen, T.; Borch-Johnsen, K.; Khunti, K.

2017-01-01

Background: It is unclear whether cardiovascular risk factor modification influences the development of renal disease in people with type 2 diabetes identified through screening. We determined predictors of albuminuria 5 years after a diagnosis of screen-detected diabetes within the ADDITION-Europe

Diabetes mellitus, hypertension and albuminuria in rural Zambia: a hospital-based survey.

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Rasmussen, Jon B; Thomsen, Jakúp A; Rossing, Peter; Parkinson, Shelagh; Christensen, Dirk L; Bygbjerg, Ib C

2013-09-01

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). A cross-sectional survey was conducted at St. Francis Hospital in the Eastern province of Zambia. Albumin-creatinine ratio in one urine sample was used to assess albuminuria. Other information obtained included age, sex, body mass index (BMI), waist circumference (WC), blood pressure (BP), glycosylated haemoglobin (HbA1c ), random capillary glucose, time since diagnosis, medication and family history of DM or HTN. A total of 193 participants were included (DM group: n = 33; HTN group: n = 92; DM/HTN group: n = 68). The participants in the DM group used insulin more frequently as diabetes medication than the DM/HTN group (P < 0.05). Furthermore, the DM group was younger and had lower BMI, WC and BP than the two other groups. In the DM group, HTN group and DM/HTN group, microalbuminuria was found in 12.1%, 19.6% and 29.4% (P = 0.11), and macroalbuminuria was found in 0.0%, 3.3% and 13.2% (P = 0.014), respectively. The urine albumin (P = 0.014) and albumin-creatinine ratio (P = 0.0006) differed between the three groups. 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. © 2013 John Wiley & Sons Ltd.

Exercise-induced albuminuria is related to metabolic syndrome.

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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

2016-06-01

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.

Renal effects of aliskiren compared with and in combination with irbesartan in patients with type 2 diabetes, hypertension, and albuminuria

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Persson, Frederik; Rossing, Peter; Reinhard, Henrik

2009-01-01

throughout the study. The primary end point was a change in albuminuria. Secondary measures included change in 24-h blood pressure and glomerular filtration rate (GFR). RESULTS: Placebo geometric mean albuminuria was 258 mg/day (range 84-2,361), mean +/- SD 24-h blood pressure was 140/73 +/- 15/8 mm...... 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......-79), more than either monotherapy (P blood pressure was reduced 3/4 mmHg by aliskiren (NS/P = 0.009), 12/5 mmHg by irbesartan (P

Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial

DEFF Research Database (Denmark)

de Zeeuw, Dick; Agarwal, Rajiv; Amdahl, Michael

2010-01-01

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....

Diabetes mellitus, hypertension and albuminuria in rural Zambia

DEFF Research Database (Denmark)

Rasmussen, Jon B; Thomsen, Jakúp A; Rossing, Peter

2013-01-01

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...... of DM or HTN. RESULTS: A total of 193 participants were included (DM group: n = 33; HTN group: n = 92; DM/HTN group: n = 68). The participants in the DM group used insulin more frequently as diabetes medication than the DM/HTN group (P

Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD : The Pro View

NARCIS (Netherlands)

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

Additive Effect of Qidan Dihuang Grain, a Traditional Chinese Medicine, and Angiotensin Receptor Blockers on Albuminuria Levels in Patients with Diabetic Nephropathy: A Randomized, Parallel-Controlled Trial

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Xiang, Lei; Jiang, Pingping; Zhou, Lin; Sun, Xiaomin; Bi, Jianlu; Cui, Lijuan; Nie, Xiaoli; Luo, Ren; Liu, Yanyan

2016-01-01

Albuminuria is characteristic of early-stage diabetic nephropathy (DN). The conventional treatments with angiotensin receptor blockers (ARB) are unable to prevent the development of albuminuria in normotensive individuals with type 2 diabetes mellitus (T2DM). Purpose. The present study aimed to evaluate the effect of ARB combined with a Chinese formula Qidan Dihuang grain (QDDHG) in improving albuminuria and Traditional Chinese Medicine Symptom (TCMS) scores in normotensive individuals with T2DM. Methods. Eligible patients were randomized to the treatment group and the control group. Results. Compared with baseline (week 0), both treatment and control groups markedly improved the 24-hour albuminuria, total proteinuria (TPU), and urinary albumin to creatinine ratio (A/C) at 4, 8, and 12 weeks. Between treatment and the control group, the levels of albuminuria in the treatment group were significantly lower than in the control group at 8 and 12 weeks (p < 0.05). In addition, treatment group markedly decreased the scores of TCMS after treatment. Conclusion. This trial suggests that QDDHG combined with ARB administration decreases the levels of albuminuria and the scores for TCMS in normotensive individuals with T2DM. PMID:27375762

Albuminuria and neck circumference are determinate factors of successful accurate estimation of glomerular filtration rate in high cardiovascular risk patients.

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Po-Jen Hsiao

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.

Association of high blood pressure with renal insufficiency: role of albuminuria, from NHANES, 1999-2006.

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Yan, Ping; Zhu, Xiangzhu; Li, Haiming; Shrubsole, Martha J; Shi, Haiming; Zhang, Ming-zhi; Harris, Raymond C; Hao, Chuan-Ming; Dai, Qi

2012-01-01

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.

DIETARTY EDUCATOIN IN TYPE 1 DIABETES EDUCATION (DAFNE AND ALBUMINURIA CHANGE: KUWAIT’S EXPERIENCE

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Ebaa Al Ozairi

2012-06-01

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.

Serum homocysteine levels are associated with the development of (micro)albuminuria : the Hoorn study

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Jager, A; Kostense, P J; Nijpels, G; Dekker, J M; Heine, R J; Bouter, L M; Donker, A J; Stehouwer, C D

Microalbuminuria is a strong indicator of the risk of future cardiovascular disease and renal dysfunction. Slightly increased levels of homocysteine, an independent risk factor for atherothrombotic disease, have recently been found to be associated with the presence of (micro)albuminuria. However,

Sugary soda consumption and albuminuria: results from the National Health and Nutrition Examination Survey, 1999-2004.

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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

Inhibition of the soluble epoxide hydrolase promotes albuminuria in mice with progressive renal disease.

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Oliver Jung

2010-08-01

Full Text Available Epoxyeicotrienoic acids (EETs are cytochrome P450-dependent anti-hypertensive and anti-inflammatory derivatives of arachidonic acid, which are highly abundant in the kidney and considered reno-protective. EETs are degraded by the enzyme soluble epoxide hydrolase (sEH and sEH inhibitors are considered treatment for chronic renal failure (CRF. We determined whether sEH inhibition attenuates the progression of CRF in the 5/6-nephrectomy model (5/6-Nx in mice. 5/6-Nx mice were treated with a placebo, an ACE-inhibitor (Ramipril, 40 mg/kg, the sEH-inhibitor cAUCB or the CYP-inhibitor fenbendazole for 8 weeks. 5/6-Nx induced hypertension, albuminuria, glomerulosclerosis and tubulo-interstitial damage and these effects were attenuated by Ramipril. In contrast, cAUCB failed to lower the blood pressure and albuminuria was more severe as compared to placebo. Plasma EET-levels were doubled in 5/6 Nx-mice as compared to sham mice receiving placebo. Renal sEH expression was attenuated in 5/6-Nx mice but cAUCB in these animals still further increased the EET-level. cAUCB also increased 5-HETE and 15-HETE, which derive from peroxidation or lipoxygenases. Similar to cAUCB, CYP450 inhibition increased HETEs and promoted albuminuria. Thus, sEH-inhibition failed to elicit protective effects in the 5/6-Nx model and showed a tendency to aggravate the disease. These effects might be consequence of a shift of arachidonic acid metabolism into the lipoxygenase pathway.

Hyperuricemia is an independent risk factor for new onset micro-albuminuria in a middle-aged and elderly population: a prospective cohort study in taiwan.

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Hung-Yu Chang

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.

Low-Grade Albuminuria Is Associated with Metabolic Syndrome and Its Components in Middle-Aged and Elderly Chinese Population.

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Jie Zhang

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

The prevalence of hypertension in relation with the normal albuminuria range in type 2 diabetes mellitus within the South Korean population: The Korean National Health and Nutrition Examination Survey, 2011-2012.

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Shin, Koh-Eun; Roh, Yong-Kyun; Cho, Kyung-Hwan; Han, Kyung-Do; Park, Yong-Gyu; Kim, Do-Hoon; Kim, Yang-Hyun

2017-06-01

The coexistence of hypertension (HTN) and diabetes mellitus (DM) increases the risk of cardiovascular disease. In some studies, normal albuminuria has also been associated with cardiovascular disease and HTN. Therefore, we examined the relationships between albuminuria and the prevalence of HTN and its control rate in type 2 DM patients. We analyzed data from the 2011-2012 Korea National Health and Nutrition Examination Survey, and 1188 subjects with type 2 DM were included in the study. We divided albuminuria into 3 albuminuria tertiles (T): T1: hypertension had more ACR T3 (odds ratio=2.018, 95% confidence interval=1.445-2.818) than subjects without HTN. Subjects with controlled HTN had less ACR T3 than subjects without controlled HTN (odds ratio=0.566, 95% confidence interval=0.384-0.836). When, we redivided albuminuria by Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Normal range albuminuria and metabolic syndrome in South Korea: the 2011-2012 Korean National Health and Nutrition Examination Survey.

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Si-Young Park

Full Text Available It is well-known that there is a close relationship between metabolic syndrome (MetS and microalbuminuria. However, some recent studies have found that even normal range albuminuria was associated with MetS and cardiometabolic risk factors. The purpose of this study is to analyze the relationship between MetS and normal range albuminuria and to calculate the cutoff value for albuminuria that correlates with MetS in the representative fraction of Korean population.Data were obtained from the 2011-2012 Korea National Health and Nutrition Examination Survey and included 9,650 subjects aged ≥ 19 years. We measured metabolic parameters: fasting blood glucose, waist circumference, blood pressure, and lipids, and albumin-to-creatinine ratio (ACR. The optimal ACR cutoff points for MetS were examined by the receiver operating characteristic curve. Multivariate logistic regression was used to obtain the prevalence of MetS and its components according to the ACR levels.The first cutoff value of ACR were 4.8 mg/g for subjects with ≥ 3 components of MetS. There was a graded association between ACR and prevalence of MetS and its components. If ACR was <4 mg/g, there was no significant increase in the prevalence of MetS or its components. From the ACR level of 4-5 mg/g, the prevalence of MetS significantly increased after adjusting for age, sex, body mass index, smoking, alcohol intake, exercise, and medications for diabetes mellitus and hypertension (odds ratio; 95% confidence intervals = 1.416; 1.041-1.926.Albuminuria within the normal range (around 5 mg/g was associated with prevalence of MetS in the Korean population.

The selective vitamin D receptor activator for albuminuria lowering (VITAL) study: study design and baseline characteristics

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Lambers Heerspink, H J; Agarwal, R; Coyne, D W

2009-01-01

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 ...

Exercise excess pressure and exercise-induced albuminuria in patients with type 2 diabetes mellitus.

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Climie, Rachel E D; Srikanth, Velandai; Keith, Laura J; Davies, Justin E; Sharman, James E

2015-05-01

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.

Albuminuria in Australian Aboriginal people: prevalence and associations with components of the metabolic syndrome.

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Rowley, K G; Iser, D M; Best, J D; O'Dea, K; Leonard, D; McDermott, R

2000-11-01

To examine the prevalence and associations with the metabolic syndrome of albuminuria among Australian Aboriginal people. Early-morning urine specimens were collected as part of community-based risk factor surveys assessing the prevalence of diabetes and cardiovascular disease in eight remote communities, with a sample size of 1,075 people. Microalbuminuria was defined as urinary albumin : creatinine ratio 3.4-33.9 mg/mmol, macroalbuminuria as albumin: creatinine ratio equal to or greater than 34 mg/mmol. There were high prevalences of microalbuminuria (men 22.2 %, women 26.9 %) and of macroalbuminuria (men 10.4%, women 13.5%). There were highly statistically significant linear associations of microalbuminuria and macroalbuminuria with increasing number of coexisting components of the metabolic syndrome (hypertension, glucose intolerance, dyslipidaemia, insulin resistance, abdominal obesity): among people with zero, one, two and three to five of these conditions, respectively, prevalence of microalbuminuria was 16%, 20%, 36% and 32% (p < 0.001); prevalence of macroalbuminuria was 2%, 6%, 12% and 32% (p < 0.001). There were independent associations of microalbuminuria with hypertension (odds ratio, 95% confidence interval = 2.36, 1.63-3.42) and diabetes (2.10, 1.28-3.45): macroalbuminuria was independently associated with hypertension (6.39, 3.93-10.4), diabetes (3.49, 1.93-6.28) and abdominal obesity (4.56, 2.40-8.64) and had a weaker association with insulin resistance (1.99, 1.12-3.54). Dyslipidaemia and impaired glucose tolerance were neither independently associated with microalbuminuria or macroalbuminuria, nor was insulin resistance or abdominal obesity independently associated with microalbuminuria. There was a strong clustering of albuminuria with components of the metabolic syndrome. Diabetes, hypertension and abdominal obesity are major contributors to high rates of albuminuria among Australian Aboriginal people.

Kalirin and CHD7: novel endothelial dysfunction indicators in circulating extracellular vesicles from hypertensive patients with albuminuria

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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.

2017-01-01

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

Skin Autofluorescence Relates to Soluble Receptor for Advanced Glycation End-Products and Albuminuria in Diabetes Mellitus

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J. Škrha

2013-01-01

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.

DHEA supplementation to dexamethasone-treated rabbits alleviates oxidative stress in kidney-cortex and attenuates albuminuria.

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Kiersztan, Anna; Trojan, Nina; Tempes, Aleksandra; Nalepa, Paweł; Sitek, Joanna; Winiarska, Katarzyna; Usarek, Michał

2017-11-01

Our recent study has shown that dehydroepiandrosterone (DHEA) administered to rabbits partially ameliorated several dexamethasone (dexP) effects on hepatic and renal gluconeogenesis, insulin resistance and plasma lipid disorders. In the current investigation, we present the data on DHEA protective action against dexP-induced oxidative stress and albuminuria in rabbits. Four groups of adult male rabbits were used in the in vivo experiment: (1) control, (2) dexP-treated, (3) DHEA-treated and (4) both dexP- and DHEA-treated. Administration of dexP resulted in accelerated generation of renal hydroxyl free radicals (HFR) and malondialdehyde (MDA), accompanied by diminished superoxide dismutase (SOD) and catalase activities and a dramatic rise in urinary albumin/creatinine ratio. Treatment with DHEA markedly reduced dexP-induced oxidative stress in kidney-cortex due to a decline in NADPH oxidase activity and enhancement of catalase activity. Moreover, DHEA effectively attenuated dexP-evoked albuminuria. Surprisingly, dexP-treated rabbits exhibited elevation of GSH/GSSG ratio, accompanied by a decrease in glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities as well as an increase in glucose-6-phosphate dehydrogenase (G6PDH) activity. Treatment with DHEA resulted in a decline in GSH/GSSG ratio and glutathione reductase (GR) activity, accompanied by an elevation of GPx activity. Interestingly, rabbits treated with both dexP and DHEA remained the control values of GSH/GSSG ratio. As the co-administration of DHEA with dexP resulted in (i) reduction of oxidative stress in kidney-cortex, (ii) attenuation of albuminuria and (iii) normalization of glutathione redox state, DHEA might limit several undesirable renal side effects during chronic GC treatment of patients suffering from allergies, asthma, rheumatoid arthritis and lupus. Moreover, its supplementation might be particularly beneficial for the therapy of patients with glucocorticoid-induced diabetes

Urine Albumin-Creatinine Ratio Versus Albumin Excretion for Albuminuria Staging: A Prospective Longitudinal Cohort Study.

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Vart, Priya; Scheven, Lieneke; Lambers Heerspink, Hiddo J; de Jong, Paul E; de Zeeuw, Dick; Gansevoort, Ron T

2016-01-01

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 (Phigh 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 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Joint effects of hypertension, smoking, dyslipidemia and obesity and angiotensin-converting enzyme DD genotype on albuminuria in Taiwanese patients with type 2 diabetes mellitus.

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Tseng, Chin-Hsiao; Tseng, Ching-Ping; Chong, Choon-Khim

2010-05-01

We investigated the individual and joint effects of hypertension, smoking, dyslipidemia, and obesity and angiotensin-converting enzyme (ACE) DD genotype on albuminuria in Taiwanese type 2 diabetic patients. ACE genotypes were determined in 519 (287 men and 232 women) patients aged 58.5 (SD: 9.0) years. Among them, 240 had albuminuria (urinary albumin-to-creatinine ratio > or =30 microg/mg). Logistic regression was used to evaluate the individual and joint effects of risk factors and DD classified by two-by-four table. The adjusted odds ratios were significant for hypertension, smoking and obesity but not for DD and dyslipidemia in models evaluating individual effects. However, while analyzing the joint effects of DD and hypertension, smoking, dyslipidemia and obesity, the respective adjusted odds ratios were 3.253 (1.261-8.391), 3.016 (1.086-8.376), 2.385 (1.010-5.630) and 2.508 (1.117-5.631). Hypertension, smoking, dyslipidemia and obesity jointly play an important role with DD genotype in mediating albuminuria. 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Tissue factor pathway inhibitor (TFPI) release after heparin stimulation is increased in Type 1 diabetic patients with albuminuria

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Leurs, PB; van Oerle, R; Hamulyak, K; Wolffenbuttel, BHR

Aims To study heparin-stimulated TFPI release in relation to complications in Type 1 diabetic patients. Subjects and methods Nineteen uncomplicated Type 1 diabetic patients (group I) were compared with 18 patients with retinopathy (group II), and nine patients with retinopathy and albuminuria (group

Impacts of chronic kidney disease and albuminuria on associations between coronary heart disease and its traditional risk factors in type 2 diabetic patients – the Hong Kong diabetes registry

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Cockram Clive S

2007-12-01

Full Text Available Abstract Background Glycated haemoglobin (HbA1c, blood pressure and body mass index (BMI are risk factors for albuminuria, the latter in turn can lead to hyperlipidaemia. We used novel statistical analyses to examine how albuminuria and chronic kidney disease (CKD may influence the effects of other risk factors on coronary heart disease (CHD. Methods A prospective cohort of 7067 Chinese type 2 diabetic patients without history of CHD enrolled since 1995 were censored on July 30th, 2005. Cox proportional hazard regression with restricted cubic spline was used to auto-select predictors. Hazard ratio plots were used to examine the risk of CHD. Based on these plots, non-linear risk factors were categorised and the categorised variables were refitted into various Cox models in a stepwise manner to confirm the findings. Results Age, male gender, duration of diabetes, spot urinary albumin: creatinine ratio, estimated glomerular filtration rate, total cholesterol (TC, high density lipoprotein cholesterol (HDL-C and current smoking status were risk factors of CHD. Linear association between TC and CHD was observed only in patients with albuminuria. Although in general, increased HDL-C was associated with decreased risk of CHD, full-range HDL-C was associated with CHD in an A-shaped manner with a zenith at 1.1 mmol/L. Albuminuria and CKD were the main contributors for the paradoxically positive association between HDL-C and CHD for HDL-C values less than 1.1 mmol/L. Conclusion In type 2 diabetes, albuminuria plays a linking role between conventional risk factors and CHD. The onset of CKD changes risk associations between lipids and CHD.

Tiaolipiwei Acupuncture Reduces Albuminuria by Alleviating Podocyte Lesions in a Rat Model of Diabetic Nephropathy

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Zhilong Zhang

2018-01-01

Full Text Available Background. Diabetic nephropathy is a common and serious complication of diabetes and a major cause of end-stage renal disease. Tiaolipiwei acupuncture is a safe treatment approach that may be effective for lowering albuminuria in diabetic nephropathy. Yet, the exact mechanisms of this therapeutic effect are unclear. Methods. A rodent model of type 2 diabetic nephropathy (T2DN was induced by a high-fat diet combined with low-dose streptozotocin. T2DN rats were treated with Tiaolipiwei acupuncture (ACU for 4, 8, or 12 weeks. At the end of treatment, urinary and blood samples were collected for analysis. Transmission electron microscopy was used to observe morphological changes, and protein expression levels of nephrin, CD2AP, podocalyxin, and desmin were quantified in renal tissue. Results. Compared to the T2DN groups, the T2DN + ACU groups showed significant improvements in 24-hour urinary protein, serum urea, cholesterol, and triglycerides at all time points. ACU treatment also improved the density of slit diaphragms. Simultaneously, ACU promoted the renal expression of nephrin, CD2AP, and podocalyxin and decreased the expression of desmin. Conclusion. Our study suggests that Tiaolipiwei acupuncture ameliorates podocyte lesions to reduce albuminuria and prevent the progression of T2DN in a rat model.

Albuminuria and Glomerular Filtration Rate in Individuals with Type 1 Diabetes Mellitus: Contribution of Metabolic Syndrome.

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Uribe-Wiechers, Ana Cecilia; Janka-Zires, Marcela; Almeda-Valdés, Paloma; López-Gutiérrez, Joel; Gómez-Pérez, Francisco J

2015-01-01

The development of metabolic syndrome has been described in patients with type 1 diabetes mellitus as the disease progresses over time. The purpose of this study is to assess the relationship between metabolic syndrome, albuminuria, and glomerular filtration rate, as well as to determine the prevalence of metabolic syndrome, in a group of Mexican patients with type 1 diabetes mellitus. We conducted a cross-sectional study that included patients with type 1 diabetes mellitus who were diagnosed over 10 years ago and who are seen at the Diabetes Intensive Control Clinic of the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran in Mexico City. The presence of metabolic syndrome was determined by using the National Cholesterol Education Program-Adult Treatment Panel III (ATP III) criteria. A total of 81 individuals were studied. The prevalence of metabolic syndrome was 18.5% (n = 15). A higher albuminuria was found in subjects with metabolic syndrome (34.9 mg/24 hours; 8.3-169.3) than in those without metabolic syndrome (9.0 mg/24 hours; 5.0-27.0; p = 0.02). Glomerular filtration rate was lower in patients with metabolic syndrome (95.3 ml/minute; [64.9-107.2] vs. 110.2 ml/minute [88.1-120.3]; p = 0.04). After classifying the population according to the number of metabolic syndrome criteria, a progressive increase in albuminuria and a progressive decrease in glomerular filtration rate were found with each additional metabolic syndrome criterion (p = 0.008 and p = 0.032, respectively). After adjusting for age, time from diagnosis, systolic blood pressure, triglycerides, HDL-cholesterol, and treatment with angiotensin receptor blockers or angiotensin converting enzyme inhibitors, we found that age, time from diagnosis, triglycerides, and HDL-cholesterol were independent factors associated with glomerular filtration rate (R2 = 0.286; p diabetes mellitus. Metabolic syndrome was present in 18.5% of this group of Mexican individuals with type 1 diabetes

Inhibition of the Metabolic Degradation of Filtered Albumin Is a Major Determinant of Albuminuria

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Vuchkova, Julijana; Comper, Wayne D.

2015-01-01

Inhibition of the degradation of filtered albumin has been proposed as a widespread, benign form of albuminuria. There have however been recent reports that radiolabeled albumin fragments in urine are not exclusively generated by the kidney and that in albuminuric states albumin fragment excretion is not inhibited. In order to resolve this controversy we have examined the fate of various radiolabeled low molecular weight protein degradation products (LMWDPs) introduced into the circulation in rats. The influence of puromycin aminonucleoside nephrosis on the processing and excretion of LMWDPs is also examined. The status and destinies of radiolabeled LMWDPs in the circulation are complex. A major finding is that LMWDPs are rapidly eliminated from the circulation (>97% in 2 h) but only small quantities (24 h) due to binding to high molecular weight components in the circulation. If LMWDPs of albumin seen in the urine are produced by extra renal degradation it would require the degradation to far exceed the known catabolic rate of albumin. Alternatively, if an estimate of the role of extra renal degradation is made from the limit of detection of LMWDPs in plasma, then extra renal degradation would only contribute albumin. We confirm that the degradation process for albumin is specifically associated with filtered albumin and this is inhibited in albuminuric states. This inhibition is also the primary determinant of the massive change in intact albuminuria in nephrotic states. PMID:26010895

Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

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Mervi E. Hyvönen

2015-01-01

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.

Morning pulse pressure is associated more strongly with elevated albuminuria than systolic blood pressure in patients with type 2 diabetes mellitus: post hoc analysis of a cross-sectional multicenter study.

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Ushigome, Emi; Fukui, Michiaki; Hamaguchi, Masahide; Matsumoto, Shinobu; Mineoka, Yusuke; Nakanishi, Naoko; Senmaru, Takafumi; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto

2013-09-01

Recently, focus has been directed toward pulse pressure as a potentially independent risk factor for micro- and macrovascular disease. This study was designed to examine the relationship between pulse pressure taken at home and elevated albuminuria in patients with type 2 diabetes. This study is a post hoc analysis of a cross-sectional multicenter study. Home blood pressure measurements were performed for 14 consecutive days in 858 patients with type 2 diabetes. We investigated the relationship between systolic blood pressure or pulse pressure in the morning or in the evening and urinary albumin excretion using univariate and multivariate analyses. Furthermore, we measured area under the receiver-operating characteristic curve (AUC) to compare the ability to identify elevated albuminuria, defined as urinary albumin excretion equal to or more than 30 mg/g creatinine, of systolic blood pressure or pulse pressure. Morning systolic blood pressure (β=0.339, Ppressure (β=0.378, PAUC for elevated albuminuria in morning systolic blood pressure and morning pulse pressure were 0.668 (0.632-0.705; PAUC of morning pulse pressure was significantly greater than that of morning systolic blood pressure (P=0.040). Our findings implicate that morning pulse pressure is associated with elevated albuminuria in patients with type 2 diabetes, which suggests that lowering morning pulse pressure could prevent the development and progression of diabetic nephropathy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Blood pressure-lowering effects of sulodexide depend on albuminuria severity: post hoc analysis of the sulodexide microalbuminuria and macroalbuminuria studies

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Olde Engberink, Rik H. G.; Heerspink, Hiddo J. L.; de Zeeuw, Dick; Vogt, Liffert

2016-01-01

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,

Blood pressure-lowering effects of sulodexide depend on albuminuria severity : post hoc analysis of the sulodexide microalbuminuria and macroalbuminuria studies

NARCIS (Netherlands)

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

Striking association between urinary cadmium level and albuminuria among Torres Strait Islander people with diabetes

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Haswell-Elkins, Melissa; Satarug, Soisungwan; O'Rourke, Peter; Moore, Michael; Ng, Jack; McGrath, Victor; Walmby, Maria

2008-01-01

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

Inflammation gene variants and susceptibility to albuminuria in the U.S. population: analysis in the Third National Health and Nutrition Examination Survey (NHANES III, 1991-1994

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Chang Man-huei

2010-11-01

Full Text Available Abstract Background Albuminuria, a common marker of kidney damage, serves as an important predictive factor for the progression of kidney disease and for the development of cardiovascular disease. While the underlying etiology is unclear, chronic, low-grade inflammation is a suspected key factor. Genetic variants within genes involved in inflammatory processes may, therefore, contribute to the development of albuminuria. Methods We evaluated 60 polymorphisms within 27 inflammatory response genes in participants from the second phase (1991-1994 of the Third National Health and Nutrition Examination Survey (NHANES III, a population-based and nationally representative survey of the United States. Albuminuria was evaluated as logarithm-transformed albumin-to-creatinine ratio (ACR, as ACR ≥ 30 mg/g, and as ACR above sex-specific thresholds. Multivariable linear regression and haplotype trend analyses were conducted to test for genetic associations in 5321 participants aged 20 years or older. Differences in allele and genotype distributions among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans were tested in additive and codominant genetic models. Results Variants in several genes were found to be marginally associated (uncorrected P value IL1B (rs1143623 among Mexican Americans remained significantly associated with increased odds, while IL1B (rs1143623, CRP (rs1800947 and NOS3 (rs2070744 were significantly associated with ACR ≥ 30 mg/g in this population (additive models, FDR-P TNF rs1800750, which failed the test for Hardy-Weinberg proportions in this population. Haplotypes within MBL2, CRP, ADRB2, IL4R, NOS3, and VDR were significantly associated (FDR-P Conclusions Our findings suggest a small role for genetic variation within inflammation-related genes to the susceptibility to albuminuria. Additional studies are needed to further assess whether genetic variation in these, and untested, inflammation genes alter the

Several Conventional Risk Markers Suggesting Presence of Albuminuria Are Weak Among Rural Africans With Hypertension

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Rasmussen, Jon Bjarke Jarløv; Nordin, Lovisa S.; Thomsen, Jakup Andreas

2016-01-01

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...

Albuminuria and Diabetic Retinopathy in Type 2 Diabetes Mellitus Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular Genetic Study (SN-DREAMS, report 12

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Rani Padmaja K

2011-05-01

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.

Differences between nisoldipine and lisinopril on glomerular filtration rates and albuminuria in hypertensive IDDM patients with diabetic nephropathy during the first year of treatment

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Rossing, P; Tarnow, L; Boelskifte, S

1997-01-01

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......-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...... pressure (24 h) was reduced from (mean +/- SE) 108 +/- 3 mmHg at baseline to 101 +/- 2 in average during treatment in the lisinopril group and from 105 +/- 2 to 103 +/- 2 in the nisoldipine group (P = 0.06 comparing changes in the two groups). Albuminuria was reduced 47% (95% CI 21-65) in the lisinopril...

Evaluation of Urinary Indices for Albuminuria and Proteinuria in Patients with Chronic Kidney Disease

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Dennis Sung Chul Hong

2016-04-01

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.

Prediction of Declining Renal Function and Albuminuria in Patients With Type 2 Diabetes by Metabolomics.

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Solini, Anna; Manca, Maria Laura; Penno, Giuseppe; Pugliese, Giuseppe; Cobb, Jeff E; Ferrannini, Ele

2016-02-01

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.

Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts

NARCIS (Netherlands)

van der Velde, Marije; Matsushita, Kunihiro; Coresh, Josef; Astor, Brad C.; Woodward, Mark; Levey, Andrew S.; de Jong, Paul E.; Gansevoort, Ron T.

Screening for chronic kidney disease is recommended in people at high risk, but data on the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with all-cause and cardiovascular mortality are limited. To clarify this, we performed a collaborative

Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts

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Astor, Brad C; Matsushita, Kunihiro; Gansevoort, Ron T

2011-01-01

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...

Exercise-induced albuminuria vs circadian variations in blood pressure in type 1 diabetes.

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Tadida Meli, Isabelle Hota; Tankeu, Aurel T; Dehayem, Mesmin Y; Chelo, David; Noubiap, Jean Jacques N; Sobngwi, Eugene

2017-02-15

To investigated the relationship between exercise-induced ambulatory blood pressure measurement (ABPM) abnormalities in type 1 diabetes mellitus (T1DM) adolescents. We conducted a case-control at the National Obesity Center of the Yaoundé Central Hospital, Cameroon. We compared 24 h ABPM and urinary albumin-to-creatinine ratio (ACR) at rest and after a standardized treadmill exercise between 20 Cameroonian T1DM patients and 20 matched controls. T1DM adolescents were aged 12-18 years, with diabetes for at least one year, without proteinuria, with normal office blood pressure (BP) and renal function according to the general reference population. Non-diabetic controls were adolescents of general population matched for sex, age and BMI. Mean duration of diabetes was 4.2 ± 2.8 years. The mean 24 h systolic blood pressure (SBP) and diastolic blood pressure (DBP) were respectively 116 ± 9 mmHg in the diabetic group vs 111 ± 8 mmHg in the non-diabetic ( P = 0.06), and 69 ± 7 mm Hg vs 66 ± 5 mm Hg ( P = 0.19). There was no difference in the diurnal pattern of BP in diabetes patients and non-diabetic controls (SBP: 118 ± 10 mmHg vs 114 ± 10 mmHg, P = 0.11; DBP: 71 ± 7 mmHg vs 68 ± 6 mmHg, P = 0.22). Nighttime BP was higher in the diabetic group with respect to SBP (112 ± 11 mmHg vs 106 ± 7 mmHg, P = 0.06) and to the mean arterial pressure (MAP) (89 ± 9 mmHg vs 81 ± 6 mmHg, P = 0.06). ACR at rest was similar in both groups (5.5 mg/g vs 5.5 mg/g, P = 0.74), but significantly higher in diabetes patients after exercise (10.5 mg/g vs 5.5 mg/g, P = 0.03). SBP was higher in patients having exercise-induced albuminuria (116 ± 10 mmHg vs 108 ± 10 mmHg, P = 0.09). Exercise-induced albuminuria could be useful for early diagnosis of kidney damage in adolescents with T1DM.

Comparison of renal function assessment by cystatin c and creatinine based equations for e-gfr in type 2 diabetics in different stages of albuminuria

International Nuclear Information System (INIS)

Qamar, A.; Ahmad, T.M.; Hayat, A.; Khan, M.A.; Rehman, S. Z.

2017-01-01

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

Analysis of the Associations between Vitamin D and Albuminuria or β-Cell Function in Chinese Type 2 Diabetes

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Xiaoling Cai

2014-01-01

Full Text Available Objective. To investigate the associations of 25-(OHD and β-cell function or insulin resistance or albuminuria in Chinese type 2 diabetic patients. Methods. In total, 1408 type 2 diabetic patients without vitamin D supplement were included in this retrospective study. Results. Comparison between patients with and without 25-(OHD deficiency indicated that, compared with patients with 25-(OHD ≥ 50 nmol/L, patients with 25-(OHD < 50 nmol/L showed a higher level of urine albumin-creatinine ratio (ACR (90.15±10.30 mg/g versus 52.79±14.97 mg/g. Multiple regression analysis indicated that 25-(OHD was independently and negatively correlated with urine ACR (OR=0.985, 95%CI 0.972–0.999, P=0.03, adjusted by age, diabetic duration, HBP duration, SBP, HbA1c, creatinine, LDL-C, triglyceride, total cholesterol, and HDL-C. Compared with patients with normal level of urine ACR, patients with higher level of urine ACR showed a significant lower level of 25-(OHD (34.49±13.52 nmol/L versus 37.46±13.6 nmol/L, P=0.00. Analysis of the associations of 25-(OHD and β-cell function or insulin resistance showed that 25-(OHD may not correlate with β-cell function or insulin resistance. Conclusion. 25-(OHD was independently associated with albuminuria in Chinese type 2 diabetic patients but was not associated with β-cell function or insulin resistance.

Association between albuminuria, atherosclerotic plaques, elevated pulse wave velocity, age, risk category and prognosis in apparently healthy individuals

DEFF Research Database (Denmark)

Greve, Sara V; Blicher, Marie K; Blyme, Adam

2014-01-01

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.......4, 20.6% or 7.9, 8.2, 16.6, 19.5% or 6.6, 7.6, 9.8, 20.0%) increased, all P high SCORE or intermediate or high FRS (all P ..., with moderate SCORE or with high-intermediate or high FRS (all P high FRS (P 

Size- and charge selectivity of glomerular filtration in Type 1 (insulin-dependent) diabetic patients with and without albuminuria

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Deckert, T; Kofoed-Enevoldsen, A; Vidal, P

1993-01-01

Albuminuria is the first clinical event in the development of diabetic nephropathy. We assessed glomerular charge- and size selectivity in 51 patients with Type 1 (insulin-dependent) diabetes mellitus of juvenile onset and 11 healthy individuals. Patients were allocated to five groups. The urinary...... techniques and tubular protein reabsorption by excretion of beta 2-microglobulin. Charge selectivity was estimated from the IgG/IgG4 selectivity index. Size selectivity was measured by dextran clearance. Dextran was measured by refractive index detection after fractionation (2 A fractions in the range 26...... macromolecular pathways in the development of diabetic nephropathy....

Validation of an electrophoretic method to detect albuminuria in cats.

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Ferlizza, Enea; Dondi, Francesco; Andreani, Giulia; Bucci, Diego; Archer, Joy; Isani, Gloria

2017-08-01

Objectives The aims of this study were to validate a semi-automated high-resolution electrophoretic technique to quantify urinary albumin in healthy and diseased cats, and to evaluate its diagnostic performance in cases of proteinuria and renal diseases. Methods Urine samples were collected from 88 cats (healthy; chronic kidney disease [CKD]; lower urinary tract disease [LUTD]; non-urinary tract diseases [OTHER]). Urine samples were routinely analysed and high-resolution electrophoresis (HRE) was performed. Within-assay and between-assay variability, linearity, accuracy, recovery and the lowest detectable and quantifiable bands were calculated. Receiver operating curve (ROC) analysis was also performed. Results All coefficients of variation were HRE allowed the visualisation of a faint band of albumin and a diffused band between alpha and beta zones in healthy cats, while profiles from diseased cats were variable. Albumin (mg/dl) and urine albumin:creatinine ratio (UAC) were significantly ( P HRE is an accurate and precise method that could be used to measure albuminuria in cats. UAC was useful to correctly classify proteinuria and to discriminate between healthy and diseased cats. HRE might also provide additional information on urine proteins with a profile of all proteins (albumin and globulins) to aid clinicians in the diagnosis of diseases characterised by proteinuria.

Despite similar reduction of blood pressure and renal ANG II and ET-1 levels aliskiren but not losartan normalizes albuminuria in hypertensive Ren-2 rats

Czech Academy of Sciences Publication Activity Database

Vaňourková, Z.; Kramer, H. J.; Husková, Z.; Červenka, L.; Vaněčková, Ivana

2010-01-01

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

Plasma lipoprotein(a levels are associated with mild renal impairment in type 2 diabetics independent of albuminuria.

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Jennie Lin

Full Text Available CKD, an independent risk factor for CV disease, increases mortality in T2DM. Treating modifiable CV risk factors decreases mortality in diabetics with microalbuminuria, but the role of early CV prevention in diabetics with mild CKD by GFR criteria alone remains unclear. The purpose of this study was to probe whether T2DM patients with mild GFR impairment have atherogenic lipid profiles compared to diabetic counterparts with normal renal function.In the Penn Diabetes Heart Study (PDHS, a single-center observational cohort of T2DM patients without clinical CVD, cross-sectional analyses were performed for directly measured lipid fractions in 1852 subjects with eGFR>60 mL/min/1.73 m² determined by the CKD-EPI equation (n = 1852. Unadjusted and multivariable analyses of eGFR association with log-transformed lipid parameters in incremental linear and logistic regression models (with eGFR 90 mL/min/1.73 m² as a cut-point were performed.Mild GFR impairment (eGFR 60-90 mL/min/1.73 m², median urinary ACR 5.25 mg/g was associated with higher log-transformed Lp(a values (OR 1.17, p = 0.005 and with clinically atherogenic Lp(a levels above 30 mg/dL (OR 1.35, p = 0.013 even after full adjustment for demographics, medications, metabolic parameters, and albuminuria. Logistic regression demonstrated a trend towards significance between worse kidney function and apoB (p = 0.17 as well as apoC-III (p = 0.067 in the fully adjusted model.Elevated Lp(a levels have a robust association with mild GFR impairment in type 2 diabetics independent of race, insulin resistance, and albuminuria.

Eicosapentaenoic and Docosahexaenoic Acids Attenuate Progression of Albuminuria in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease.

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Elajami, Tarec K; Alfaddagh, Abdulhamied; Lakshminarayan, Dharshan; Soliman, Michael; Chandnani, Madhuri; Welty, Francine K

2017-07-14

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.

Association Between Obesity and Chronic Kidney Disease, Defined by Both Glomerular Filtration Rate and Albuminuria, in Korean Adults.

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Kim, Yoon Ji; Hwang, Seun Deuk; Oh, Tae Jung; Kim, Kyoung Min; Jang, Hak Chul; Kimm, Heejin; Kim, Hyeon Chang; Jee, Sun Ha; Lim, Soo

2017-10-01

Chronic kidney disease (CKD) has often been defined based on glomerular filtration rate (GFR) alone. The Kidney Disease: Improving Global Outcomes guideline highlights albuminuria in the CKD definition. Thus, we investigated the association between obesity and CKD, as defined by both GFR and albuminuria, in Korean adults. We used Korea National Health and Nutrition Examination Survey 2011-2014 data (N = 19,331, ≥19 years old) representing the national Korean population. CKD was classified by (1) estimated GFR (eGFR) obesity and each CKD category were evaluated using multivariate logistic regression analysis. The prevalence rates of CKD GFR , CKD ACR , and CKD Risk were 2.2%, 6.7%, and 8.1%, respectively. Compared with the normal body mass index (BMI; 18.5-22.9 kg/m 2 ) group, men with BMI ≥ 25 kg/m 2 had 1.88 times greater risk of CKD GFR in the adjusted model [95% confidence interval (CI), 1.26-2.80; P = 0.002]; BMI was not significantly associated with CKD GFR in women. In contrast, both men and women with BMI ≥ 25 kg/m 2 had 1.58 and 1.40 times higher risk of CKD ACR (95% CI, 1.21-2.07 and 1.08-1.81, respectively, both P Obese men and women had 1.65 and 1.38 times higher risk of CKD Risk (95% CI, 1.29-2.12 and 1.09-1.75, respectively, both P Obesity was significantly associated with an increased ACR-based CKD risk. Longitudinal studies are needed to investigate the role of overweight and obesity in the development and progression of CKD.

DBA2J db/db mice are susceptible to early albuminuria and glomerulosclerosis that correlate with systemic insulin resistance.

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Østergaard, Mette V; Pinto, Vanda; Stevenson, Kirsty; Worm, Jesper; Fink, Lisbeth N; Coward, Richard J M

2017-02-01

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.

Effect of exercise intensity on albuminuria in adolescents with Type 1 diabetes mellitus.

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Kornhauser, C; Malacara, J-M; Macías-Cervantes, M-H; Rivera-Cisneros, A-E

2012-01-01

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.

SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice

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Gerasimova, Maria; Rose, Michael A.; Masuda, Takahiro; Satriano, Joseph; Mayoux, Eric; Koepsell, Hermann; Thomson, Scott C.; Rieg, Timo

2013-01-01

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

Benefits of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise on albuminuria in diabetic and non-diabetic Japanese populations.

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Yamamoto-Kabasawa, Keiko; Hosojima, Michihiro; Yata, Yusuke; Saito, Mariko; Tanaka, Noriko; Tanaka, Junta; Tanabe, Naohito; Narita, Ichiei; Arakawa, Masaaki; Saito, Akihiko

2015-12-01

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.

A study of the relationship between albuminuria, proteinuria and urinary reagent strips.

LENUS (Irish Health Repository)

Collier, Geraldine

2012-02-01

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.

Albuminuria as a Risk Factor for Anemia in Chronic Kidney Disease: Result from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD.

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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.

Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients

DEFF Research Database (Denmark)

Gaede, P; Poulsen, H E; Parving, H H

2001-01-01

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...

Effects of sodium-glucose co-transporter 2 (SGLT2 inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis

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Lubin Xu

2017-06-01

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.

Urinary excretion of fatty acid-binding protein 4 is associated with albuminuria and renal dysfunction.

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Yusuke Okazaki

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.

Blood pressure control is similar in treated hypertensive patients with optimal or with high-normal albuminuria.

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Oliveras, Anna; Armario, Pedro; Lucas, Silvia; de la Sierra, Alejandro

2014-09-01

Although elevated urinary albumin excretion (UAE) is associated with cardiovascular prognosis and high blood pressure (BP), it is unknown whether differences in BP control could also exist between patients with different grades of UAE, even in the normal range. We sought to explore the association between different levels of UAE and BP control in treated hypertensive patients. A cohort of 1,200 treated hypertensive patients was evaluated. Clinical data, including 2 office BP measurements and UAE averaged from 2 samples, were recorded. Albuminuria was categorized into 4 groups: G0 (UAE <10mg/g), G1 (UAE 10-29 mg/g), G2 (UAE 30-299 mg/g), and G3 (UAE ≥300 mg/g). Forty-three percent of patients had systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg. Median UAE was significantly higher (20.3 vs. 11.7 mg/g; P < 0.001) in these patients than in controlled hypertensive patients (BP<140/90 mm Hg). When UAE was categorized into the 4 groups, there were differences in BP control among groups (P < 0.001).The proportion of noncontrolled patients in G2 (52.3%) was significantly higher than in G0 (36.8%) and G1 (41.5%) (P < 0.01 and P < 0.05, respectively). Importantly, no significant differences were observed between G0 and G1 (P = 0.18) or between G2 and G3 (P = 0.48). With G0 as the reference group, the odds ratio of lack of BP control for the G2 group after adjustment for confounders was 1.40 (95% confidence interval =1.16-1.68; P < 0.001). Lack of BP control is more prevalent among patients with microalbuminuria than in patients with normoalbuminuria. No significant difference was seen between patients with optimal or high-normal UAE. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prevalence and Determinants of Diabetic Nephropathy in Korea: Korea National Health and Nutrition Examination Survey

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Jae Hee Ahn

2014-04-01

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.

The correlates of urinary albumin to creatinine ratio (ACR) in a high risk Australian aboriginal community.

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Wang, Zaimin; Hoy, Wendy E; Wang, Zhiqiang

2013-08-16

Albuminuria marks renal disease and cardiovascular risk. It was estimated to contribute 75% of the risk of all-cause natural death in one Aboriginal group. The urine albumin/creatinine ratio (ACR) is commonly used as an index of albuminuria. This study aims to examine the associations between demographic factors, anthropometric index, blood pressure, lipid-protein measurements and other biomarkers and albuminuria in a cross-sectional study in a high-risk Australian Aboriginal population. The models will be evaluated for albuminuria at or above the microalbuminuria threshold, and at or above the "overt albuminuria" threshold with the potential to distinguish associations they have in common and those that differ. This was a cross-sectional study of 598 adults aged 18-76 years. All participants were grouped into quartiles by age. Logistic regression models were used to explore the correlates of ACR categories. The significant correlates were systolic blood pressure (SBP), C-reactive protein (CRP), uric acid, diabetes, gamma-glutamyl transferase (GGT) (marginally significant, p=0.054) and serum albumin (negative association) for ACR 17+ (mg/g) for men and 25+ for women. Independent correlates were SBP, uric acid, diabetes, total cholesterol, alanine amino transferase (ALT), Cystatin C and serum albumin (negative association) for overt albuminuria; and SBP, CRP and serum albumin only for microalbuminuria. This is the most detailed modelling of pathologic albuminuria in this setting to date. The somewhat variable association with risk factors suggests that microalbuminuria and overt albuminuria might reflect different as well as shared phenomena.

Changes in urine albumin to creatinine ratio with the initiation of hydroxyurea therapy among children and adolescents with sickle cell disease.

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Tehseen, Sarah; Joiner, Clinton H; Lane, Peter A; Yee, Marianne E

2017-12-01

Renal damage is a progressive complication of sickle cell disease (SCD) that begins in childhood and may progress to renal failure and early mortality in 12% of adults with hemoglobin SS (HbSS) SCD. Early sickle nephropathy is characterized by hyperfiltration and microalbuminuria; therefore, urine albumin to creatinine ratio (ACR) is an effective screening tool for its detection. This study investigated the effect of hydroxyurea (HU) therapy on urine ACR levels among children with SCD. A retrospective review was conducted to identify all patients with HbSS or HbSβ 0 thalassemia of age 7-18 years who began HU therapy in 2011-2013; a control group of patients not on HU were matched by age and baseline hemoglobin. All urine ACR measurements ≤24 months prior to and ≥24 months after HU initiation were recorded. There were 63 eligible patients on HU and 13 (25%) with albuminuria prior to HU initiation. Among those with baseline albuminuria, the median ACR was 96 mg/g prior to HU, 39 mg/g at 1 year (P = 0.02), and 25 mg/g at 2 years (P = 0.03). Albuminuria normalized in 37.5% (6/16) after 1 year and 61% (8/13) after 2 years of HU therapy. Among those without albuminuria prior to HU, 13% (6/47) developed albuminuria during HU therapy. Sixteen percent (13/80) of control patients had albuminuria in the beginning of study period, which normalized in 15% (two of 13) of patients at 1-year follow up. Introduction of HU is associated with significant decreases in urine ACR in children with SCD and albuminuria. © 2017 Wiley Periodicals, Inc.

Angiotensin converting enzyme gene polymorphism and ACE inhibition in diabetic nephropathy

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Jacobsen, P; Rossing, K; Rossing, P

1998-01-01

induced a significant reduction in MABP, albuminuria and kidney function in all three groups (II/ID/DD; P ANOVA, P = 0.02); (2) albuminuria [mean (95% CI)] 61 (34 to 77)/22 (3 to 37)/31 (13 to 46) %, (ANOVA, 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

Metabolic Syndrome and Chronic Renal Disease

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Vaia D. Raikou

2018-01-01

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.

Renal disease in adult Nigerians with sickle cell anemia: A report of prevalence, clinical features and risk factors

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R A Bolarinwa

2012-01-01

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.

Increased transvascular lipoprotein transport in diabetes

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Jensen, Jan Skov; Feldt-Rasmussen, Bo; Borch-Johnsen, Knut

2005-01-01

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...... 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...... likely were not caused by altered hepatic LDL receptor expression, glycosylation of LDL, small LDL size, or medicine use. CONCLUSIONS: Transvascular LDL transport is increased in patients with diabetes mellitus, especially if systolic hypertension or albuminuria is present. Accordingly, lipoprotein flux...

Effect of LDL cholesterol and treatment with losartan on end-stage renal disease in the RENAAL study

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Tershakovec, A.M.; Keane, W.F.; Zhang, Z.

2008-01-01

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...

Early myocardial impairment in type 1 diabetes patients without known heart disease assessed with tissue Doppler echocardiography

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Jensen, Magnus Thorsten; Søgaard, Peter; Andersen, Henrik Ullits

2016-01-01

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:...

Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance to RAAS inhibition?

NARCIS (Netherlands)

Petrykiv, Sergei; Laverman, Gozewijn D.; de Zeeuw, Dick; Heerspink, Hiddo J. L.

Individual patients show a large variation in their response to renin-angiotensin-aldosteron system (RAAS) inhibition (RAASi), both in surrogates such as albuminuria and in hard renal outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2) have been shown to lower albuminuria and to confer

Evaluation of measures of urinary albumin excretion

NARCIS (Netherlands)

Gansevoort, Ronald T.; Brinkman, Jacoline; Bakker, Stephan J. L.; De Jong, Paul E.; de Zeeuw, Dick

2006-01-01

Albuminuria has recently drawn much attention as a valuable risk marker for cardiovascular and renal disease progression. Albuminuria can be measured and expressed in several ways: 1) in a spot morning urine sample as urinary albumin concentration (mg/liter) or albumin:creatinine ratio (mg/mmol) and

Sodium-glucose co-transporter type 2 inhibitors reduce evening home blood pressure in type 2 diabetes with nephropathy.

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Takenaka, Tsuneo; Kishimoto, Miyako; Ohta, Mari; Tomonaga, Osamu; Suzuki, Hiromichi

2017-05-01

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.

Association between dyslipidemia and chronic kidney disease: a cross-sectional study in the middle-aged and elderly Chinese population.

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Liu, Dong-Wei; Wan, Jia; Liu, Zhang-Suo; Wang, Pei; Cheng, Gen-Yang; Shi, Xue-Zhong

2013-04-01

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.

Mannanbindende lektin og mortalitet hos patienter med type 2-diabetes--sekundaerpublikation

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Hansen, Troels Krarup; Gall, Mari-Anne; Tarnow, Lise

2009-01-01

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...... and the development of albuminuria in T2DM Udgivelsesdato: 2009-Feb-2...

Stirring the Pot: Can Dietary Modification Alleviate the Burden of CKD?

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Matthew Snelson

2017-03-01

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.

Treatment-Induced Changes in Plasma Adiponectin Do Not Reduce Urinary Albumin Excretion in the Diabetes Prevention Program Cohort.

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Kieren J Mather

Full Text Available Molecular data suggests that adiponectin may directly regulate urinary albumin excretion. In the Diabetes Prevention Program (DPP we measured adiponectin and albuminuria before and after intervention, and we previously reported increases in adiponectin with interventions. Here we have used the DPP dataset to test the hypothesis that treatment-related increases in adiponectin may reduce albuminuria in obesity.We evaluated cross-sectional correlations between plasma adiponectin and urinary albumin excretion at baseline, and the relationship of treatment-related changes in adiponectin and albuminuria. Baseline and follow-up urine albumin to creatinine ratios (ACR (albumin to creatinine ratio and plasma adiponectin concentration were available in 2553 subjects.Adjusting for age, sex and race/ethnicity, we observed a statistically significant but weak inverse relationship between adiponectin and ACR at baseline (conditional Spearman's rho = (- 0.04, p = 0.04. Although DPP treatments significantly increased plasma adiponectin, there were no treatment effects on ACR and no differences in ACR across treatment groups. There was a weak direct (not inverse association between change in adiponectin and change in albuminuria (adjusted Spearman's rho = (+ 0.04, p = 0.03.In a large, well-characterized cohort of obese dysglycemic subjects we observed a weak inverse association between circulating adiponectin concentrations and urinary albumin excretion at baseline. Contrary to the hypothesized effect, treatment-related increases in plasma adiponectin were not associated with a reduction in ACR. The association of change in adiponectin with change in ACR should be assessed in populations with overt albuminuria before excluding a beneficial effect of increasing adiponectin to reduce ACR in obesity.

Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010.

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Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K; Kramer, Holly; Rosas, Sylvia E; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L

2016-01-01

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.

Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010.

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Harini Sarathy

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.

ACEI/ARB underused in patients with type 2 diabetes in Chinese population (CCMR-3B study.

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Qionghong Xie

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.

Is it time to change the definition of normal urinary albumin excretion?

DEFF Research Database (Denmark)

Wachtell, K.; Olsen, M.H.

2008-01-01

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...

Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease

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Prabakaran, Thaneas; Birn, Henrik; Bibby, Bo M

2014-01-01

dysfunction in women with Fabry disease treated with ERT. METHODS: A retrospective, single centre, cohort study evaluated the long-term association between ERT, albuminuria and eGFR in 13 women with Fabry disease and mild renal involvement. In particular, we analysed the changes in the proteinuric profile...... to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes...... in albuminuria was paralleled by a decrease in both glomerular and tubular urine protein markers. CONCLUSIONS: The data indicate that long-term ERT is associated with a reduction in albuminuria and glomerular and tubular urinary protein markers in women with Fabry disease and mild renal manifestations....

Aliskiren suppresses the renin–angiotensin–aldosterone system and reduces blood pressure and albuminuria in elderly chronic kidney disease patients with hypertension

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Morishita Y

2012-09-01

patients with hypertension.Keywords: aliskiren, renin–angiotensin–aldosterone system, blood pressure, albuminuria, elderly chronic kidney disease

Fish Oil in Diabetic Nephropathy

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Rossing, Peter; Hansen, Birgitte V.; Nielsen, Flemming S.

1996-01-01

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...... in the fish oil compared with the placebo group. CONCLUSIONS: Our study does not suggest that fish oil has beneficial effects on albuminuria, kidney function, blood pressure, and dyslipidemia in normotensive IDDM patients suffering from diabetic nephropathy....

Comparison of exposure response relationship of atrasentan between North American and Asian populations

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Heerspink, Hiddo J L; Makino, Hirofumi; Andress, Dennis

2017-01-01

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...

Prevalence of chronic kidney disease after preeclampsia.

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Lopes van Balen, Veronica Agatha; Spaan, Julia Jeltje; Cornelis, Tom; Spaanderman, Marc Erich August

2017-06-01

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.

Underestimation of urinary albumin to creatinine ratio in morbidly obese subjects due to high urinary creatinine excretion.

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Guidone, Caterina; Gniuli, Donatella; Castagneto-Gissey, Lidia; Leccesi, Laura; Arrighi, Eugenio; Iaconelli, Amerigo; Mingrone, Geltrude

2012-04-01

Albuminuria, a chronic kidney and/or cardiovascular disease biomarker, is currently measured as albumin-to-creatinine ratio (ACR). We hypothesize that in severely obese individuals ACR might be abnormally low in spite of relatively high levels of urinary albumin due to increased creatininuria. One-hundred-eighty-four subjects were divided into tertiles based on their BMI. Fat-free mass (FFM) and fat-mass were assessed by DEXA; 24-h creatinine and albumin excretion, ACR, lipid profile and blood pressure were measured. Twenty-four-hour creatinine highly correlated (R = 0.75) with FFM. Since both creatininuria and albuminuria increased with the BMI, being the increase in creatininuria preponderant in subjects with BMI>35, their ratio (AC-ratio) did not change significantly from that of subjects in the lower BMI tertile. ACR only correlated with the systolic blood pressure, while both albuminuria and cretininuria correlated (P = 0.01) with the absolute 10-year CHD risk. In subjects with BMI>35, 100 mg of albumin excreted with urine increased the CHD risk of 2%. Albumin-to-creatinine ratio is underestimated in severely obese individuals as a consequence of the large creatininuria, which is proportional to the increased FFM. Therefore, at least in this population 24-h albuminuria should be more reliable than ACR. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

DD genotype of angiotensin-converting enzyme in type 2 diabetes mellitus with renal disease in Mexican Mestizos.

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Palomo-Piñón, Silvia; Gutiérrez-Rodríguez, Margarita E; Díaz-Flores, Margarita; Sánchez-Barrera, Reyna; Valladares-Salgado, Adán; Utrera-Barillas, Dolores; Durán-Reyes, Genoveva; Galván-Duarte, Rosa E; Trinidad-Ramos, Pedro; Cruz, Miguel

2009-04-01

The DD genotype of angiotensin-converting enzyme (ACE) has been suggested as a major contributor of diabetic nephropathy in several populations. The purpose of the present study was to determine whether micro/macroalbuminuria is associated with ACE insertion/deletion (I/D) polymorphism in Mexican Mestizos with type 2 diabetes mellitus. A total of 435 patients with type 2 diabetes mellitus, of whom 233 had albuminuria, were characterized for the ACE I/D polymorphism by the polymerase chain reaction method. Clinical and biochemical characteristics and frequencies according to DD, ID and II genotypes in patients with and without albuminuria showed no significant differences. However, only females with micro/macroalbuminuria showed higher frequency of a DD genotype than those without albuminuria (27.9%, 21.2% and 10.5%, respectively; P DD genotype is a risk factor for the development of renal disease in Mexican Mestizo females with type 2 diabetes, indicating a possible DD genotype-associated sex effect in renal disease.

Remission and regression in the nephropathy of type 1 diabetes when blood pressure is controlled aggressively

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Hovind, P; Rossing, P; Tarnow, L

2001-01-01

BACKGROUND: Diabetic nephropathy is a chronic, progressive kidney disease with a mean rate of decline of in glomerular filtration rate (GFR) of 10 to 12 mL/min/year (natural history). The introduction of aggressive antihypertensive treatment has improved the renal prognosis during the last decades...... pressure, albuminuria, glycosylated hemoglobin A1c, and serum cholesterol were measured every three to four months during the study. In total, 271 patients received antihypertensive treatment, 179 patients predominantly with angiotensin-converting enzyme inhibitors. Remission was defined as albuminuria...

The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system.

Science.gov (United States)

Schernthaner, Guntram; Mogensen, Carl Erik; Schernthaner, Gerit-Holger

2014-09-01

Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. © The Author(s) 2014.

Evaluation of the Urine Protein/Creatinine Ratio Measured with the Dipsticks Clinitek Atlas PRO 12.

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Hermida, Fernando J; Soto, Sonia; Benitez, Alfonso J

2016-01-01

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.

Effectiveness of angiotensin II receptor antagonists in a cohort of Dutch patients with type 2 diabetes mellitus (ZODIAC-14).

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van Hateren, Kornelis J J; Landman, Gijs W D; Groenier, Klaas H; Bilo, Henk J G; Kleefstra, Nanne

2015-04-01

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.

Nuclear cardiology in Senegal: a luxury or a need?

International Nuclear Information System (INIS)

Mbodj, M.; Seck Gassama, S.; Ndong, B.; Ndoye, O.; Toure Sow, H.; Senghor, S.R.; Diop, S.N.; Solanki, K.K.

2006-01-01

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)

Associations between plasma tenofovir concentration and renal function markers in HIV-infected women

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Mwila Mulubwa

2016-07-01

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.

Renoprotection with and without blood pressure reduction

DEFF Research Database (Denmark)

Laverman, Gozewijn Dirk; Andersen, Steen; Rossing, Peter

2005-01-01

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...

PHOSPHATE METABOLISM IN KIDNEY DONORS: A CROSS-SECTIONAL STUDY

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Jayakumar Edathedathe

2016-05-01

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

A difference in systolic blood pressure between arms is a novel predictor of the development and progression of diabetic nephropathy in patients with type 2 diabetes.

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Okada, Hiroshi; Fukui, Michiaki; Tanaka, Muhei; Matsumoto, Shinobu; Iwase, Hiroya; Kobayashi, Kanae; Asano, Mai; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto

2013-10-01

Recent studies have suggested that a difference in systolic blood pressure (SBP) between arms is associated with both vascular disease and mortality. The aim of this study was to investigate the relationship between a difference in SBP between arms and change in urinary albumin excretion or development of albuminuria in patients with type 2 diabetes. We measured SBP in 408 consecutive patients with type 2 diabetes, and calculated a difference in SBP between arms. We performed follow-up study to assess change in urinary albumin excretion or development of albuminuria, mean interval of which was 4.6 ± 1.7 years. We then evaluated the relationship of a difference in SBP between arms to diabetic nephropathy using multiple regression analysis and multiple Cox regression model. Multiple regression analyses demonstrated that a difference in SBP between arms was independently associated with change in urinary albumin excretion (β = 0.1869, P = 0.0010). Adjusted Cox regression analyses demonstrated that a difference in SBP between arms was associated with an increased hazard of development of albuminuria; hazard ratio was 1.215 (95% confidence interval 1.077-1.376). Moreover, the risk of development of albuminuria was increased in patients with a difference in SBP of equal to or more than 10 mmHg between arms; hazard ratio was 4.168 (95% confidence interval 1.478-11.70). A difference in SBP between arms could be a novel predictor of the development and progression of diabetic nephropathy in patients with type 2 diabetes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Optimal dose of losartan for renoprotection in diabetic nephropathy

DEFF Research Database (Denmark)

Andersen, Steen; Rossing, Peter; Juhl, Tina R

2002-01-01

filtration rate (GFR) ([(51)Cr]EDTA plasma clearance) were determined. RESULTS: Baseline values of albuminuria (geometric mean (95% CI)) and GFR (means+/-SEM) were 1138 (904-1432) mg/24 h and 91+/-3 ml/min/1.73 m(2), respectively. The blood pressure at baseline was 155/81+/-3/2 mmHg. All doses of losartan...... consecutive hypertensive type 1 diabetic patients with diabetic nephropathy received increasing doses of losartan, 50, 100, and 150 mg once daily in three periods each lasting 2 months. At baseline and at the end of each treatment period, albuminuria, 24-h blood pressure (TM2420 A&D), and glomerular...

Hypertension og diabetes mellitus

DEFF Research Database (Denmark)

Poulsen, Per Løgstrup; Hansen, Klavs Würgler; Gaede, Peter Haulund

2009-01-01

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....

Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes

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Qing-Lin Lou

2012-12-01

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.

Association of Chronic Kidney Disease and Cerebral Small Vessel Disease with Cognitive Impairment in Elderly Patients with Type 2 Diabetes

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Toshitaka Umemura

2013-07-01

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.

The KCa3.1 blocker TRAM34 reverses renal damage in a mouse model of established diabetic nephropathy.

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Chunling Huang

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.

Cardiovascular risk management of different ethnic groups with type 2 diabetes in primary care in New Zealand.

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Elley, C Raina; Kenealy, Tim; Robinson, Elizabeth; Bramley, Dale; Selak, Vanessa; Drury, Paul L; Kerse, Ngaire; Pearson, Janet; Lay-Yee, Roy; Arroll, Bruce

2008-03-01

To examine cardiovascular preventive and renal protective treatment for different ethnic groups with diabetes in primary care. The study population included patients with type 2 diabetes attending an annual review in New Zealand primary care during 2004. Primary care data were linked to hospital admission data to identify previous cardiovascular disease (CVD). For those without previous CVD, 5-year cardiovascular risk was calculated. Proportions on, and predictors of appropriate treatment according to guidelines were investigated. Data were available on 29,179 patients. Maori and Pacific participants had high rates of obesity, poor glycaemic control and albuminuria. Two thirds of all participants with previous CVD (68% of Maori and 70% of Pacific) and 44% with high CVD risk received appropriate CVD treatment; 73% of Maori, 62% of Pacific and 65% of European patients with albuminuria received ACE-inhibitors. Those with high CVD risk were more likely, and those that were young were less likely, to receive anti-hypertensive and lipid-lowering treatment after controlling for other factors. Maori and Pacific people were receiving similar high rates of appropriate CVD and renal preventive drug therapy to Europeans, but their prevalence of smoking, obesity, raised HbA1c and albuminuria were substantially higher. Non-drug components of preventive care also need to be addressed to reduce major ethnic disparities in diabetes-related morbidity and mortality in New Zealand.

Cardiovascular risk prediction in chronic kidney disease patients

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Santiago Cedeño Mora

2017-05-01

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.

PTH levels and not serum phosphorus levels are a predictor of the progression of kidney disease in elderly patients with advanced chronic kidney disease

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Néstor Gabriel Toapanta Gaibor

2017-03-01

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.

Utility of Urinary Biomarkers in Predicting Loss of Residual Renal Function: The balANZ Trial

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Cho, Yeoungjee; Johnson, David W.; Vesey, David A.; Hawley, Carmel M.; Clarke, Margaret; Topley, Nicholas

2015-01-01

♦ Background: The ability of urinary biomarkers to predict residual renal function (RRF) decline in peritoneal dialysis (PD) patients has not been defined. The present study aimed to explore the utility of established biomarkers from kidney injury models for predicting loss of RRF in incident PD patients, and to evaluate the impact on RRF of using neutral-pH PD solution low in glucose degradation products. ♦ Methods: The study included 50 randomly selected participants from the balANZ trial who had completed 24 months of follow-up. A change in glomerular filtration rate (GFR) was used as the primary clinical outcome measure. In a mixed-effects general linear model, baseline measurements of 18 novel urinary biomarkers and albumin were used to predict GFR change. The model was further used to evaluate the impact of biocompatible PD solution on RRF, adjusted for each biomarker. ♦ Results: Baseline albuminuria was not a useful predictor of change in RRF in PD patients (p = 0.84). Only clusterin was a significant predictor of GFR decline in the whole population (p = 0.04, adjusted for baseline GFR and albuminuria). However, the relationship was no longer apparent when albuminuria was removed from the model (p = 0.31). When the effect of the administered PD solutions was examined using a model adjusted for PD solution type, baseline albuminuria, and GFR, higher baseline urinary concentrations of trefoil factor 3 (TFF3, p = 0.02), kidney injury molecule 1 (KIM-1, p = 0.04), and interferon γ-induced protein 10 (IP-10, p = 0.03) were associated with more rapid decline of RRF in patients receiving conventional PD solution compared with biocompatible PD solution. ♦ Conclusions: Higher urinary levels of kidney injury biomarkers (TFF3, KIM-1, IP-10) at baseline predicted significantly slower RRF decline in patients receiving biocompatible PD solutions. Findings from the present investigation should help to guide future studies to validate the utility of urinary

Do treatment quality indicators predict cardiovascular outcomes in patients with diabetes?

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Grigory Sidorenkov

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

I Yes ~Still MA ----I

African Journals Online (AJOL)

significance of micro-albuminuria in diabetes mellitus.1 Micro- ... Prospective Diabetes Study (UKPDS), has confirmed that intensive blood .... L Motala AA. ... on the progresSion of diabetic and non-diabetic renal disease: a meta-analysis.

Presence of micro- and macroalbuminuria and the association with cardiac mechanics in patients with type 2 diabetes

DEFF Research Database (Denmark)

Jørgensen, Peter Godsk; Biering-Sørensen, Tor; Mogelvang, Rasmus

2017-01-01

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...

Add-On Aliskiren Elicits Stronger Renoprotection Than High-Dose Valsartan in Type 2 Diabetic KKAy Mice That Do Not Respond to Low-Dose Valsartan

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Lei, Bai; Nakano, Daisuke; Fan, Yu-Yan; Kitada, Kento; Hitomi, Hirofumi; Kobori, Hiroyuki; Mori, Hirohito; Masaki, Tsutomu; Nishiyama, Akira

2012-01-01

We hypothesized that aliskiren provides renoprotection in diabetic animals that did not receive sufficient renoprotection by AT1-receptor antagonist treatment. Type 2 diabetic KKAy mice were treated with group 1: vehicle or group 2: valsartan (15 mg/kg per day) from 12 to 16 weeks of age. The mice were subsequently divided into 4 groups and treated with the following combinations of drugs for another 6 weeks: 1: group 1 kept receiving vehicle, 2: group 2 continuously received 15 mg/kg per day of valsartan (Val-Val15), 3: group 2 received 50 mg/kg per day of valsartan (Val-Val50), 4: group 2 continuously received 15 mg/kg per day of valsartan with 25 mg/kg per day of aliskiren (Val-Val+Ali). Aliskiren exerted significant anti-albuminuric effects, whereas valsartan failed to ameliorate the albuminuria in the first four weeks. Surprisingly, the increasing dosage of valsartan in the Val-Val50 group showed non-significant tendencies to attenuate the albuminuria compared with vehicle infusion. Val-Val+Ali significantly suppressed the development of albuminuria and podocyte injury. Val-Val50 and Val-Val+Ali showed similar suppression of angiotensin II contents in the kidney of KKAy mice. In conclusion, the anti-albuminuric effect that was observed in the type 2 diabetic mice showing no anti-albuminuric effect by valsartan can be attributed to the add-on aliskiren. PMID:22673148

Determining the Levels of Vitamin D and Parathyroid Hormone in Patients on Hemodialysis

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Mihaylov R.

2016-03-01

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.

Relation of serum magnesium level to microvascular complications and the components of metabolic syndrome in patients with type 2 diabetes mellitus

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Heba M Yossef

2017-01-01

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.

Predictors of angiotensin-converting enzyme inhibitor - Induced reduction of urinary albumin excretion in nondiabetic patients

NARCIS (Netherlands)

van de Wal, Ruud M. A.; Gansevoort, Ron T.; van der Harst, Pim; Boomsma, Frans; Thijs Plokker, H. W.; van Veldhuisen, Dirk J.; de Jong, Paul E.; van Gilst, Wiek H.; Voors, Adriaan A.

2006-01-01

Urinary albumin excretion is a predictor for cardiovascular mortality and morbidity. We investigated which parameters determine baseline urinary albumin excretion in nondiabetic subjects, without renal disease. In addition, we evaluated the parameters that predict the albuminuria-lowering efficacy

Association between probiotic and yogurt consumption and kidney disease: insights from NHANES.

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Yacoub, Rabi; Kaji, Deepak; Patel, Shanti N; Simoes, Priya K; Busayavalasa, Deepthi; Nadkarni, Girish N; He, John C; Coca, Steven G; Uribarri, Jaime

2016-01-27

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.

Angiotensin-converting enzyme inhibition in diabetic nephropathy

DEFF Research Database (Denmark)

Parving, H H; Rossing, P; Hommel, E

1995-01-01

The aim of our prospective study was to evaluate putative progression promoters, kidney function, and prognosis during long-term treatment with angiotensin-converting enzyme inhibition in insulin-dependent diabetes mellitus patients suffering from diabetic nephropathy. Eighteen consecutive......, albuminuria (geometric mean +/- antilog SE) 982 +/- 1.2 micrograms/min, and GFR 98 +/- 5 mL/min/1.73 m2. Angiotensin-converting enzyme inhibition induced a significant reduction during the whole treatment period of blood pressure (137/85 +/- 3/1 mm Hg; P ....01), and the rate of decline in GFR was 4.4 +/- 0.7 mL/min/yr, in contrast to previous reports of 10 to 14 mL/min/yr (natural history). Univariate analysis revealed a significant correlation between the rate of decline in GFR and mean arterial blood pressure (r = 0.58, P = 0.01), albuminuria (r = 0.67, P

Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials

DEFF Research Database (Denmark)

Bilous, Rudy; Chaturvedi, Nish; Sjølie, Anne Katrin

2009-01-01

candesartan compared with placebo affects microalbuminuria incidence or rate of change in albuminuria in type 1 and type 2 diabetes. DESIGN: 3 randomized trials of the DIRECT (Diabetic Retinopathy Candesartan Trials) Program. SETTING: 309 secondary care centers. PATIENTS: 3326 and 1905 patients with type 1...... further collections were done. The primary end point was new microalbuminuria (3 or 4 collections of urinary albumin excretion rate >or=20 microg/min). The secondary end point was rate of change in albuminuria. RESULTS: Individual and pooled results of the 3 trials showed that candesartan had little...... normotensive patients or patients with well-controlled hypertension who were at low overall vascular risk, which resulted in a low rate of microalbuminuria. Studies were powered for retinal and not renal end points. CONCLUSION: Candesartan, 32 mg/d, for 4.7 years did not prevent microalbuminuria in mainly...

Prediction of the effect of atrasentan on renal and heart failure outcomes based on short-term changes in multiple risk markers

DEFF Research Database (Denmark)

Schievink, Bauke; de Zeeuw, Dick; Smink, Paul A

2016-01-01

from the RADAR/JAPAN study to predict the effect of atrasentan on renal and heart failure outcomes. METHODS: 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......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......, 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. DESIGN: We used the PRE score on data...

Management of hyperkalaemia consequent to mineralocorticoid-receptor antagonist therapy

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Roscioni, Sara S.; de Zeeuw, Dick; Bakker, Stephan J. L.; Lambers Heerspink, Hiddo J.

2012-01-01

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

History of preeclampsia is more predictive of cardiometabolic and cardiovascular risk factors than obesity

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Heidema, W.M.; Scholten, R.R.; Lotgering, F.K.; Spaanderman, M.E.A.

2015-01-01

OBJECTIVE: To determine to what extent a history of preeclampsia affects traditional cardiometabolic (insulin resistance and dyslipidemia) and cardiovascular (hypertension and micro-albuminuria) risk factors of the metabolic syndrome irrespective of BMI. STUDY DESIGN: In a retrospective case-control

Urinary albumin excretion is associated with renal functional abnormalities in a nondiabetic population

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Pinto-Sietsma, SJ; Janssen, WMT; Hillege, HL; Navis, G; De Zeeuw, D; De Jong, PE

2000-01-01

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

Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial

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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

2016-01-01

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

Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade : A Randomized Clinical Trial

NARCIS (Netherlands)

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.

The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial

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Vogt, Liffert; Navis, Gerjan; Koester, Juergen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick

2005-01-01

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

Reducing cardiovascular risk : protecting the kidney

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Dobre, Daniela; Lambers Heerspink, Hiddo J.; de Zeeuw, Dick

2009-01-01

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

Profiling of Plasma Metabolites Suggests Altered Mitochondrial Fuel Usage and Remodeling of Sphingolipid Metabolism in Individuals With Type 2 Diabetes and Kidney Disease

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Jian-Jun Liu

2017-05-01

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.

Rationale, Design, and Baseline Characteristics of ARTS-DN : A Randomized Study to Assess the Safety and Efficacy of Finerenone in Patients with Type 2 Diabetes Mellitus and a Clinical Diagnosis of Diabetic Nephropathy

NARCIS (Netherlands)

Ruilope, Luis M.; Agarwal, Rajiv; Chan, Juliana C.; Cooper, Mark E.; Gansevoort, Ron T.; Haller, Hermann; Remuzzi, Giuseppe; Rossing, Peter; Schmieder, Roland E.; Nowack, Christina; Ferreira, Anna C.; Pieper, Alexander; Kimmeskamp-Kirschbaum, Nina; Bakris, George L.

2014-01-01

Background/Aims: Finerenone decreases albuminuria in patients having heart failure with reduced ejection fraction and mild-to-moderate (stage 2-3) chronic kidney disease. The MinerAlocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN; NCT01874431) is a multicenter,

The effect of liraglutide on renal function

DEFF Research Database (Denmark)

von Scholten, Bernt J; Persson, Frederik; Rosenlund, Signe

2017-01-01

(GLP-1) receptor agonist liraglutide on top of multifactorial care, including renin-angiotensin-system (RAS)-inhibition. MATERIALS AND METHODS: Randomized, double-blind, placebo-controlled, cross-over trial including patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine...

Differential Effects of Dapagliflozin on Cardiovascular Risk Factors at Varying Degrees of Renal Function

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Petrykiv, Sergei; Sjostrom, C. David; Greasley, Peter J.; Xu, John; Persson, Frederik; Heerspink, Hiddo J. L.

2017-01-01

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

Disparate effects of eplerenone, amlodipine and telmisartan on podocyte injury in aldosterone-infused rats

NARCIS (Netherlands)

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

The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial

NARCIS (Netherlands)

Vogt, Liffert; Navis, Gerjan; Köster, Jürgen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick

2005-01-01

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

Excretion of amine nitrogen and ammonia in urine of pregnant women with type 1 diabetes mellitus

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Zulfiya Raisovna Alimetova

2010-12-01

Full Text Available Aim. To study excretion of amine nitrogen and ammonia in urine of pregnant women with type 1 diabetes mellitus depending on gestational ageand albuminuria level. Materials and methods. A total of 60 pregnant women with type 1 diabetes mellitus were examined. Proximal and distal tubular function was estimatedfrom daily excretion of amine nitrogen and ammonia respectively. Results. Daily excretion of amine nitrogen and ammonia in urine of pregnant women with type 1 diabetes mellitus was lower than in healthycontrols in the 2nd trimester regardless of albuminuria and in the 3rd trimester in patients with microalbuminuria (MAU and proteinuria (PU.Ammonia excretion was twice lower than normal in the 2nd trimester in women with MAU and PU, and in the 3rd trimester in patients with PU.Healthy pregnant women showed significant correlation between ammonia and amine nitrogen excretion throughout pregnancy (r?0.833,p

Thyrotropin levels are associated with chronic kidney disease among healthy subjects in cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

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Peixoto de Miranda, Érique José F; Bittencourt, Márcio Sommer; Goulart, Alessandra C; Santos, Itamar S; de Oliveira Titan, Silvia Maria; Ladeira, Roberto Marini; Barreto, Sandhi Maria; Lotufo, Paulo A; Benseñor, Isabela Judith Martins

2017-12-01

Few studies have evaluated a possible relationship between thyrotropin levels and glomerular filtration rate (GFR) and albumin/creatinine ratio in euthyroid subjects. We aimed to analyze this association using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Cross-sectionally, we included subjects with normal thyroid function and with subclinical hypothyroidism (SCH). We excluded individuals using medications that affect thyroid function. Linear and logistic regression models evaluated GFR estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) and albuminuria/creatinine ratio as dependent variables and thyrotropin quartiles in individuals with euthyroidism and SCH as independent variables, adjusted for demographical characteristics and diseases related to CKD. We included 13,193 subjects with a median age of 51 years [interquartile range, (IQR): 45-58], 6840 (51.8%) women, 12,416 (94.1%) euthyroid, and 777 (5.9%) with SCH. SCH subjects were characterized by higher age, triglycerides, frequency of white race, cardiovascular disease, CKD, and former smokers. In adjusted models, log-transformed TSH in euthyroid subjects was inversely and strongly associated with CKD (β = -2.181, 95% CI -2.714 to -1.648), P < 0.0001 for glomerular filtration rate and 4.528 (1.190-7.865) for albuminuria/creatinine ratio. Multivariate logistic models for euthyroid subjects showed an OR of 1.45 (95% CI 1.15-1.83) for GFR and of 1.95 (95% CI 1.08-3.54) for albuminuria/creatinine ratio in the fourth quartile of TSH using the first as the reference. Thyrotropin levels are independently associated with CKD in euthyroid subjects.

Renoprotective effects of topiroxostat for hyperuremic patients with overt diabetic nephropathy study (ETUDE Study): A prospective, randomized, multicenter clinical trial.

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Mizukoshi, Toshihiro; Kato, Sawako; Ando, Masahiko; Sobajima, Hiroshi; Ohashi, Norimi; Naruse, Tomohiko; Saka, Yosuke; Shimizu, Hideaki; Nagata, Takanobu; Maruyama, Shoichi

2017-10-09

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.

History of preeclampsia is more predictive of cardiometabolic and cardiovascular risk factors than obesity.

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Heidema, Wieteke M; Scholten, Ralph R; Lotgering, Fred K; Spaanderman, Marc E A

2015-11-01

To determine to what extent a history of preeclampsia affects traditional cardiometabolic (insulin resistance and dyslipidemia) and cardiovascular (hypertension and micro-albuminuria) risk factors of the metabolic syndrome irrespective of BMI. In a retrospective case-control study we compared 90 formerly preeclamptic women, divided in 3 BMI-classes (BMI 19.5-24.9, 25.0-29.9, ≥30.0kg/m(2)) to 30 controls, matched for BMI, age and parity. Cardiometabolic and cardiovascular risk factors (WHO-criteria) were tested 6-18 months post partum. Statistical analysis included unpaired t-tests, Mann-Whitney U test, or Chi square test and two-way ANOVA. Constituents of the metabolic syndrome (glucose, insulin, HOMAIR, HDL-cholesterol, triglycerides, blood pressure, micro-albuminuria) were higher in formerly preeclamptic women than in BMI-matched controls. Resultantly, traditional risk factors were more prevalent in formerly preeclamptic women than in controls (insulin resistance 80% vs 30%, dyslipidemia 52% vs 3%, hypertension 24% vs 0%, micro-albuminuria 30% vs 0%). Cardiometabolic risk factors increased with BMI, to the same extent in both groups. Formerly preeclamptic women had metabolic syndrome more often than their BMI-matched controls (38% vs 3%, p<0.001). Traditional risk factors of the metabolic syndrome are more prevalent in formerly preeclamptic women than in BMI-matched controls and increase with BMI to the same extent in both groups. A history of preeclampsia seems to be a stronger indicator of cardiovascular risk than obesity per se. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Risk Factors for Heart Failure in Patients With Chronic Kidney Disease: The CRIC (Chronic Renal Insufficiency Cohort) Study.

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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

2017-05-17

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 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 failure. Our study indicates that cystatin C-based eGFR and albuminuria are better predictors for risk of heart failure compared to creatinine-based eGFR. Furthermore, anemia, insulin resistance, inflammation, and poor glycemic control are independent risk factors for the development of heart failure among patients with chronic kidney disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Renal albumin absorption in physiology and pathology.

Science.gov (United States)

Birn, H; Christensen, E I

2006-02-01

Albumin is the most abundant plasmaprotein serving multiple functions as a carrier of metabolites, hormones, vitamins, and drugs, as an acid/base buffer, as antioxidant and by supporting the oncotic pressure and volume of the blood. The presence of albumin in urine is considered to be the result of the balance between glomerular filtration and tubular reabsorption. Albuminuria has been accepted as an independent risk factor and a marker for renal as well as cardiovascular disease, and during the past decade, evidence has suggested that albumin itself may cause progression of renal disease. Thus, the reduction of proteinuria and, in particular, albuminuria has become a target in itself to prevent deterioration of renal function. Studies have shown albumin and its ligands to induce expression of inflammatory and fibrogenic mediators, and it has been hypothesized that increased filtration of albumin causes excessive tubular reabsorption, resulting in inflammation and fibrosis, resulting in the loss of renal function. In addition, it is known that tubular dysfunction in itself may cause albuminuria owing to decreased reabsorption of filtered albumin, and, recently, it has been suggested that significant amounts of albumin fragments are excreted in the urine as a result of tubular degradation. Thus, although both tubular and glomerular dysfunction influences renal handling of albumin, it appears that tubular reabsorption plays a central role in mediating the effects of albumin on renal function. The present paper will review the mechanisms for tubular albumin uptake and the possible implications for the development of renal disease.

Prevalencia y características de los pacientes con hipertensión arterial resistente y enfermedad renal crónica

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Úrsula Verdalles

2016-09-01

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.

Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

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Parving, Hans-Henrik; Brenner, Barry M; McMurray, John J V

2012-01-01

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...

CARDIOVASCULAR ENDOCRINOLOGY Dual RAAS blockade has dual effects on outcome

NARCIS (Netherlands)

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

Albuminuria as a laboratory risk marker : Methods evaluated

NARCIS (Netherlands)

Brinkman, Jacoline Willijanne

2007-01-01

Albumin is the most abundant protein (65 kDalton) in human blood plasma. After being produced by the liver, albumin circulates as a polypeptide chain of 585 amino acids which is cross-linked by 17 disulphide bonds. Albumin contributes to about 80% of the colloid osmotic pressure, and it binds a

Insulinoma in a third-trimester pregnant woman combined with pre-eclampsia

DEFF Research Database (Denmark)

Christiansen, Poul Erik; Vestergaard, Henrik

2008-01-01

week due to slurred speech, weakness and slow reaction patterns. An electroencephalogram and computed tomography scan of the brain and blood samples were normal. Blood pressure was 170-145/110-95 mmHg, albuminuria was moderate and there was moderate edema of the ankles. Labor started spontaneously...

Comparison of exposure response relationship of atrasentan between North American and Asian populations

NARCIS (Netherlands)

Heerspink, Hiddo J. L.; Makino, Hirofumi; Andress, Dennis; Brennan, John J.; Correa-Rotter, Ricardo; Coll, Blai; Davis, Justin W.; Idler, Ken; Kohan, Donald E.; Liu, Mohan; Perkovic, Vlado; Remuzzi, Giuseppe; Tobe, Sheldon W.; Toto, Robert; Parving, Hans-Henrik; de Zeeuw, Dick

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 of

38 CFR 4.115a - Ratings of the genitourinary system-dysfunctions.

Science.gov (United States)

2010-07-01

..., 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...

Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers

DEFF Research Database (Denmark)

Lambers Heerspink, Hiddo J; Holtkamp, Frank A; Parving, Hans-Henrik

2012-01-01

Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis of...

Antialbuminuric effect of eplerenone in comparison to thiazide diuretics in patients with hypertension.

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Sawai, Toshiki; Dohi, Kaoru; Fujimoto, Naoki; Okubo, Setsuya; Isaka, Naoki; Ichikawa, Takehiko; Makino, Katsutoshi; Okamoto, Shinya; Koyabu, Sukenari; Kitamura, Tetsuya; Ogura, Toru; Yamada, Tomomi; Tamaru, Satoshi; Nishikawa, Masakatsu; Nakamura, Mashio; Ito, Masaaki

2017-10-01

This study investigated the effects and safety of eplerenone or thiazide diuretics in patients with hypertension and albuminuria (pretreatment urinary albumin/creatinine ratio ≥10 mg/gCr) treated with an angiotensin II receptor blocker. The primary end point was the mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks. An efficacy analysis was performed in 195 patients (98 in the eplerenone group and 97 in the thiazide group). Systolic and diastolic blood pressures at 48 weeks were similar in the two groups. The mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks was similar in the two groups (P=.804). In the safety analysis, the withdrawal rates for adverse events were similar in both groups. The antialbuminuric effects and safety of eplerenone therapy were similar to those of thiazide diuretics when combined with an angiotensin II receptor blocker in patients with hypertension and albuminuria. ©2017 Wiley Periodicals, Inc.

Role of albumin and its modifications in glomerular injury.

Science.gov (United States)

Agrawal, Shipra; Smoyer, William E

2017-08-01

Albuminuria is both a characteristic hallmark and a known risk factor for progressive glomerular disease. Although the molecular basis for a potential causative role for albuminuria in progressive chronic kidney disease remains poorly understood, there have been several recent advances in our understanding of the role of albumin, and its molecular modifications, in the development and progression of glomerular disease. This review discusses recent findings related to the ability of albumin and its associated factors to directly induce podocyte and glomerular injury. Additional recent studies confirming the ability and mechanisms by which podocytes endocytose albumin are also discussed. Lastly, we present several known molecular modifications in the albumin molecule itself, as well as substances bound to it, which may be important and potentially clinically relevant mediators of albumin-induced glomerular injury. These recent findings may create entirely new opportunities to develop novel future therapies directed at albumin that could potentially help reduce podocyte and renal tubular injury and slow the progression of chronic glomerular disease.

Chronic kidney disease : Defining clinical cut-offs for albumin:creatinine ratio

NARCIS (Netherlands)

Bakker, Stephan J L

2013-01-01

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

Rationale and design of ARTS

DEFF Research Database (Denmark)

Pitt, Bertram; Filippatos, Gerasimos; Gheorghiade, Mihai

2012-01-01

. placebo (primary endpoint) and vs. spironolactone, safety and tolerability, biomarkers of cardiac and renal function or injury, eGFR, and albuminuria. BAY 94-8862 pharmacokinetics are also assessed. Perspectives ARTS is the first phase II clinical trial of BAY 94-8862 and is expected to provide a wealth...

Indirect assessment of eosinophiluria in urinary schistosomiasis using eosinophil cationic protein (ECP) and eosinophil protein X (EPX)

DEFF Research Database (Denmark)

Reimert, C M; Ouma, J H; Mwanje, M T

1993-01-01

of infection (eggs/10 ml of urine), albuminuria and pathological changes as detected by ultrasonography. ECP and EPX were determined by means of specific ELISA methods and levels were determined in both urine supernatants and extracted urine deposits (cells and cell debris). The level of ECP was significantly...

Predictive properties of plasma amino acid profile for cardiovascular disease in patients with type 2 diabetes.

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Shinji Kume

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.

Comparison of Urine Albumin-to-Creatinine Ratio (ACR) Between ACR Strip Test and Quantitative Test in Prediabetes and Diabetes

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Cho, Seon; Kim, Suyoung; Cho, Han-Ik

2017-01-01

Background Albuminuria is generally known as a sensitive marker of renal and cardiovascular dysfunction. It can be used to help predict the occurrence of nephropathy and cardiovascular disorders in diabetes. Individuals with prediabetes have a tendency to develop macrovascular and microvascular pathology, resulting in an increased risk of retinopathy, cardiovascular diseases, and chronic renal diseases. We evaluated the clinical value of a strip test for measuring the urinary albumin-to-creatinine ratio (ACR) in prediabetes and diabetes. Methods Spot urine samples were obtained from 226 prediabetic and 275 diabetic subjects during regular health checkups. Urinary ACR was measured by using strip and laboratory quantitative tests. Results The positive rates of albuminuria measured by using the ACR strip test were 15.5% (microalbuminuria, 14.6%; macroalbuminuria, 0.9%) and 30.5% (microalbuminuria, 25.1%; macroalbuminuria, 5.5%) in prediabetes and diabetes, respectively. In the prediabetic population, the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the ACR strip method were 92.0%, 94.0%, 65.7%, 99.0%, and 93.8%, respectively; the corresponding values in the diabetic population were 80.0%, 91.6%, 81.0%, 91.1%, and 88.0%, respectively. The median [interquartile range] ACR values in the strip tests for measurement ranges of 300 mg/g were 9.4 [6.3-15.4], 46.9 [26.5-87.7], and 368.8 [296.2-575.2] mg/g, respectively, using the laboratory method. Conclusions The ACR strip test showed high sensitivity, specificity, and negative predictive value, suggesting that the test can be used to screen for albuminuria in cases of prediabetes and diabetes. PMID:27834062

Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury.

Science.gov (United States)

Hong, Quan; Zhang, Lu; Das, Bhaskar; Li, Zhengzhe; Liu, Bohan; Cai, Guangyan; Chen, Xiangmei; Chuang, Peter Y; He, John Cijiang; Lee, Kyung

2018-06-01

Podocyte injury and loss contribute to the progression of glomerular diseases, including diabetic kidney disease. We previously found that the glomerular expression of Sirtuin-1 (SIRT1) is reduced in human diabetic glomeruli and that the podocyte-specific loss of SIRT1 aggravated albuminuria and worsened kidney disease progression in diabetic mice. SIRT1 encodes an NAD-dependent deacetylase that modifies the activity of key transcriptional regulators affected in diabetic kidneys, including NF-κB, STAT3, p53, FOXO4, and PGC1-α. However, whether the increased glomerular SIRT1 activity is sufficient to ameliorate the pathogenesis of diabetic kidney disease has not been explored. We addressed this by inducible podocyte-specific SIRT1 overexpression in diabetic OVE26 mice. The induction of SIRT1 overexpression in podocytes for six weeks in OVE26 mice with established albuminuria attenuated the progression of diabetic glomerulopathy. To further validate the therapeutic potential of increased SIRT1 activity against diabetic kidney disease, we developed a new, potent and selective SIRT1 agonist, BF175. In cultured podocytes BF175 increased SIRT1-mediated activation of PGC1-α and protected against high glucose-mediated mitochondrial injury. In vivo, administration of BF175 for six weeks in OVE26 mice resulted in a marked reduction in albuminuria and in glomerular injury in a manner similar to podocyte-specific SIRT1 overexpression. Both podocyte-specific SIRT1 overexpression and BT175 treatment attenuated diabetes-induced podocyte loss and reduced oxidative stress in glomeruli of OVE26 mice. Thus, increased SIRT1 activity protects against diabetes-induced podocyte injury and effectively mitigates the progression of diabetic kidney disease. Published by Elsevier Inc.

Association between the extent of urinary albumin excretion and glycaemic variability indices measured by continuous glucose monitoring.

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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

2015-02-01

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.

Predictive Properties of Plasma Amino Acid Profile for Cardiovascular Disease in Patients with Type 2 Diabetes

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Kume, Shinji; Araki, Shin-ichi; Ono, Nobukazu; Shinhara, Atsuko; Muramatsu, Takahiko; Araki, Hisazumi; Isshiki, Keiji; Nakamura, Kazuki; Miyano, Hiroshi; Koya, Daisuke; Haneda, Masakazu; Ugi, Satoshi; Kawai, Hiromichi; Kashiwagi, Atsunori; Uzu, Takashi; Maegawa, Hiroshi

2014-01-01

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. PMID:24971671

High urinary albumin/creatinine ratio at admission predicts poor functional outcome in patients with acute ischaemic stroke.

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Watanabe, Yoko; Suda, Satoshi; Kanamaru, Takuya; Katsumata, Toshiya; Okubo, Seiji; Kaneko, Tomohiro; Mii, Akiko; Sakai, Yukinao; Katayama, Yasuo; Kimura, Kazumi; Tsuruoka, Shuichi

2017-03-01

Albuminuria and a low estimated glomerular filtration rate (eGFR) are widely recognized indices of kidney dysfunction and have been linked to cardiovascular events, including stroke. We evaluated albuminuria, measured using the urinary albumin/creatinine ratio (UACR), and the eGFR in the acute phase of ischaemic stroke, and investigated the clinical characteristics of ischaemic stroke patients with and those without kidney dysfunction. The study included 422 consecutive patients admitted between June 2010 and May 2012. General blood and urine examinations were performed at admission. Kidney dysfunction was defined as a low eGFR (high albuminuria (≥30 mg/g creatinine), or both. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and the modified Rankin scale (mRS) at discharge. A poor outcome was defined as a mRS score of 3-5 or death. The impacts of the eGFR and UACR on outcomes at discharge were evaluated using multiple logistic regression analysis. Kidney dysfunction was diagnosed in 278 of the 422 patients (65.9%). The eGFR was significantly lower and UACR was significantly higher in patients with a poor outcome than in those with a good outcome. In multivariate analyses performed after adjusting for confounding factors, UACR >31.2 mg/g creatinine (OR, 2.58; 95% CI, 1.52-4.43; P = 0.0005) was independently associated with a poor outcome, while a low eGFR was not associated. A high UACR at admission may predict a poor outcome at discharge in patients with acute ischaemic stroke. © 2016 Asian Pacific Society of Nephrology.

Endocytosis of Albumin by Podocytes Elicits an Inflammatory Response and Induces Apoptotic Cell Death

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Okamura, Kayo; Dummer, Patrick; Kopp, Jeffrey; Qiu, Liru; Levi, Moshe; Faubel, Sarah; Blaine, Judith

2013-01-01

The presence of albuminuria is strongly associated with progression of chronic kidney disease. While albuminuria has been shown to injure renal proximal tubular cells, the effects of albumin on podocytes have been less well studied. We have addressed the hypothesis that exposure of podocytes to albumin initiates an injury response. We studied transformed human-urine derived podocytes-like epithelial cells (HUPECS, or podocytes). Upon differentiation, these cells retain certain characteristics of differentiated podocytes, including expression of synaptopodin, CD2AP, and nestin. We exposed podocytes to recombinant human albumin, which lacks lipids and proteins that bind serum albumin; this reagent allowed a direct examination of the effects of albumin. Podocytes endocytosed fluoresceinated albumin and this process was inhibited at 4°C, suggesting an energy-dependent process. Exposure to albumin at concentrations of 5 and 10 mg/ml was associated with increased cell death in a dose-dependent manner. The mechanism of cell death may involve apoptosis, as caspase 3/7 were activated and the pan-caspase inhibitor z-VAD reduced cell death. Albumin exposure also increased nuclear factor (NF)-κB activation and increased transcription and release of interleukin (IL-) 1β, tumor necrosis factor (TNF), and IL-6. We extended these findings to an in vivo model. Glomeruli isolated from mice with nephrotic syndrome also had increased expression of IL-1β and TNF RNA. These data suggest that while podocyte injury begets albuminuria, albumin in the glomerular ultrafiltrate may also beget podocyte injury. Thus, an additional mechanism by which anti-proteinuric therapies are beneficial in the treatment of glomerular diseases may be a reduction in injury to the podocyte by albumin. PMID:23382978

Prevention of diabetic nephropathy by compound 21, selective agonist of angiotensin type 2 receptors, in Zucker diabetic fatty rats

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Castoldi, Giovanna; di Gioia, Cira Rt; Bombardi, Camila

2014-01-01

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 ...

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.

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Cherney, David Z I; Zinman, Bernard; Inzucchi, Silvio E; Koitka-Weber, Audrey; Mattheus, Michaela; von Eynatten, Maximilian; Wanner, Christoph

2017-08-01

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

El nivel de la hormona paratiroidea (PTH y no el de fósforo sérico es predictor de la progresión de la enfermedad renal en pacientes mayores con enfermedad renal crónica avanzada

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Néstor Gabriel Toapanta Gaibor

2017-03-01

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.

High prevalence and associated risk factors for impaired renal function and urinary abnormalities in a rural adult population from southern China.

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Qinghua Liu

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.

Chronic kidney disease and bleeding risk in patients at high cardiovascular risk: a cohort study.

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Ocak, G; Rookmaaker, M B; Algra, A; de Borst, G J; Doevendans, P A; Kappelle, L J; Verhaar, M C; Visseren, F L

2018-01-01

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.

Prevalence estimates of chronic kidney disease in Canada: results of a nationally representative survey

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Arora, Paul; Vasa, Priya; Brenner, Darren; Iglar, Karl; McFarlane, Phil; Morrison, Howard; Badawi, Alaa

2013-01-01

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

Chronic kidney disease screening methods and its implication for Malaysia: an in depth review.

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Almualm, Yasmin; Zaman Huri, Hasniza

2015-01-01

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.

Renal Evaluation in Women with Preeclampsia

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T.A. Facca

2012-05-01

Full Text Available Background/Aims: Preeclampsia (PE is a cause of glomerulopathy worldwide. Urinary retinol-binding protein (RBP is a marker of proximal tubular dysfunction, albuminuria is an endothelial injury marker, urine protein:creatinine ratio (PCR may have a predictive value for renal disease later in life, and, recently, podocyturia has been proposed as a sensitive tool in pregnancy, but it needs to be tested. The aim of this study was to evaluate renal involvement in PE and healthy pregnancy. Methods: Case-control study with 39 pregnant women assessed after 20 weeks of gestation (25 in the control group, CG, and 14 in the PE group by performing urinary tests. Results: Mean (±SD age and gestational age of the CG were 26.9 ± 6.4 years and 37.1 ± 5.0 weeks, and of the PE group 26.4 ± 6.9 years and 30.6 ± 5.6 weeks, respectively (p = 0.001. Mean (±SD urinary RBP (p = 0.017, albuminuria (p = 0.002, and urinary albumin concentration (UAC ratio (p = 0.006 of the CG were 0.4 ± 0.7 mg/l, 7.3 ± 6.9 mg/l, and 8.2 ± 6.7 mg/g and of the PE group 2.0 ± 4.4 mg/l, 2,267.4 ± 2,130.8 mg/l (p = 0.002, and 3,778.9 ± 4,296.6 mg/g (p = 0.006, respectively. Mean (±SD urine PCR in the PE group was 6.7 ± 6.1 g/g (p Conclusions: Urinary RBP, PCR, albuminuria, and UAC ratio were elevated in the PE group in comparison to the CG. Podocyturia did not predict PE.

Prevalent Rate of Nonalbuminuric Renal Insufficiency and Its Association with Cardiovascular Disease Event in Korean Type 2 Diabetes

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Hye Won Lee

2016-12-01

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.

Type 2 diabetes in young adults in Central Auckland: demography and complications.

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Beig, Junaid; Khanolkar, Manish; Cundy, Tim

2018-01-01

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.

Pre-exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Kidney Tubular Dysfunction in HIV-Uninfected Individuals.

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Jotwani, Vasantha; Scherzer, Rebecca; Glidden, David V; Mehrotra, Megha; Defechereux, Patricia; Liu, Albert; Gandhi, Monica; Bennett, Michael; Coca, Steven G; Parikh, Chirag R; Grant, Robert M; Shlipak, Michael G

2018-06-01

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: α1-microglobulin (α1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria. The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC. A cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE. In iPrEx, there were no significant differences in urine α1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine α1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable α1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: -7% to 20%). PrEP with TDF/FTC was associated with a statistically significant rise in urine α1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.

Neutrophil-lymphocyte ratio is a novel reliable predictor of nephropathy, retinopathy, and coronary artery disease in Indians with type-2 diabetes

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Sachin Chittawar

2017-01-01

Full Text Available Background and Aims: Neutrophil-lymphocyte ratio (NLR has been suggested to be a predictor of coronary artery disease (CAD, and end-organ damage in type-2 diabetes mellitus (T2DM. Similar data are lacking from Indians with T2DM. Hence, this study aimed to evaluate the role of NLR as a predictor of microvascular complications and CAD in T2DM. Subjects and Methods: Consecutive T2DM patients attending the outpatient services of 2 different hospitals, who gave consent, underwent clinical, anthropometric evaluation, and evaluation for the occurrence of retinopathy, nephropathy, neuropathy, and CAD. Results: A total of 298 patients were screened of which 265 patients' data were analyzed. Occurrence of hypertension, neuropathy, nephropathy, retinopathy, and CAD was 12.8%, 18.5%, 41.5%, 62.3%, and 3.8%, respectively. Patients in higher NLR quartiles had significantly higher diabetes duration, occurrence of nephropathy, albuminuria, retinopathy, CAD and lpwer glomerular filtration rate. Patients with more microvascular complications had significantly longer diabetes duration, blood pressure, NLR, creatinine, and urine albumin excretion. Binary logistic regression revealed NLR followed by body mass index were best predictors of microvascular complications. NLR had areas under the receiver operating characteristic curve (AUC of 0.888 (95% CI: 0.848–0.929; P < 0.001, 0.708 (95% CI: 0.646–0.771; P < 0.001, and 0.768 (95% CI: 0.599–938; P = 0.004 in predicting albuminuria, retinopathy, and CAD, respectively. NLR of 2.00 had sensitivity and specificity of 86.4% and 69% in predicting albuminuria; sensitivity and specificity of 64.2% and 63% in predicting retinopathy; sensitivity and specificity of 80% and 47.1% in predicting CAD. Conclusion: NLR is inexpensive, easy to use, reliable predictor of nephropathy, retinopathy, and CAD in Indian T2DM.

Dietary Salt Restriction in Chronic Kidney Disease: A Meta-Analysis of Randomized Clinical Trials.

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Garofalo, Carlo; Borrelli, Silvio; Provenzano, Michele; De Stefano, Toni; Vita, Carlo; Chiodini, Paolo; Minutolo, Roberto; Nicola, Luca De; Conte, Giuseppe

2018-06-06

A clear evidence on the benefits of reducing salt in people with chronic kidney disease (CKD) is still lacking. Salt restriction in CKD may allow better control of blood pressure (BP) as shown in a previous systematic review while the effect on proteinuria reduction remains poorly investigated. We performed a meta-analysis of randomized controlled trials (RCTs) evaluating the effects of low versus high salt intake in adult patients with non-dialysis CKD on change in BP, proteinuria and albuminuria. Eleven RCTs were selected and included information about 738 CKD patients (Stage 1⁻4); urinary sodium excretion was 104 mEq/day (95%CI, 76⁻131) and 179 mEq/day (95%CI, 165⁻193) in low- and high-sodium intake subgroups, respectively, with a mean difference of −80 mEq/day (95%CI from −107 to −53; p <0.001). Overall, mean differences in clinic and ambulatory systolic BP were −4.9 mmHg (95%CI from −6.8 to −3.1, p <0.001) and −5.9 mmHg (95%CI from −9.5 to −2.3, p <0.001), respectively, while clinic and ambulatory diastolic BP were −2.3 mmHg (95%CI from −3.5 to −1.2, p <0.001) and −3.0 mmHg (95%CI from −4.3 to −1.7; p <0.001), respectively. Mean differences in proteinuria and albuminuria were −0.39 g/day (95%CI from −0.55 to −0.22, p <0.001) and −0.05 g/day (95%CI from −0.09 to −0.01, p = 0.013). Moderate salt restriction significantly reduces BP and proteinuria/albuminuria in patients with CKD (Stage 1⁻4).

Metabolic syndrome, serum uric acid and renal risk in patients with T2D.

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Francesca Viazzi

Full Text Available Metabolic Syndrome (Mets and increased serum uric acid (SUA, are well known renal risk predictors and often coexist in patients with type 2 diabetes (T2D. Whether they independently contribute to the onset of CKD is at present unclear.Within the AMD Annals database we identified patients with T2D and normal renal function and urine albumin excretion at baseline and regular follow-up visits during a 4-year period. Blood pressure, BMI, HDL, triglycerides, and SUA were available in 14,267 patients. The association between Mets and/or hyperuricemia (HU, top fifth gender specific quintile and the occurrence of renal outcomes were evaluated.At baseline 59% of patients (n = 8,408 showed Mets and 18% (n = 2,584 HU. Over the 4-year follow-up, 14% (n = 1,990 developed low eGFR (i.e. below 60 mL/min/1.73 m2, and 26% (n = 3,740 albuminuria. After adjustment for confounders, BP≥130/85, low HDL, triglycerides ≥150 and HU were independently related to the development of low eGFR (1.57, P<0.001; 1.13, P = 0.056; 1.18, P = 0.008; 1.26, P = 0.001 and of albuminuria (1.35, P<0.001; 1.18, P = 0.001; 1.15, P = 0.002; 1.24, P = 0.001, respectively. The incidence of low eGFR was higher in patients with HU independent of the presence or absence of Mets (21%, OR 1.30, p = 0.009 and 20%, 1.57, p<0.000 respectively, while albuminuria occurred more frequently in those with Mets and HU (32%, OR 1.25, p = 0.005 as compared to the reference group.HU and Mets are independent predictors of CKD and its individual components in patients with T2D.

Natural course of kidney function in Type 2 diabetic patients with diabetic nephropathy

DEFF Research Database (Denmark)

Christensen, P K; Rossing, P; Nielsen, F S

1999-01-01

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...... cholesterol every second year. RESULTS: The patients (12 males/one female), age 56+/-9 (mean +/- SD) years, with a known duration of diabetes of 10+/-6 years, were followed for 55 (24-105) (median (range)) months. GFR decreased from 104 (50-126) to 80 (39-112) ml x min(-1) x 1.73 m(-2) (P = 0.......002) with a median rate of decline of 4.5 (-0.4 to 12) ml x min(-1) x year(-1). During follow-up, albuminuria rose from 494 (301-1868) to 908 (108-2169) mg/24 h (P = 0.25), while BP, HbA1c and serum cholesterol remained essentially unchanged. In univariate analysis the rate of decline in GFR did not correlate...

Chronic Kidney Disease Awareness Among Individuals with Clinical Markers of Kidney Dysfunction

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Plantinga, Laura C.; Hsu, Chi-yuan; Jordan, Regina; Burrows, Nilka Ríos; Hedgeman, Elizabeth; Yee, Jerry; Saran, Rajiv; Powe, Neil R.

2011-01-01

Summary Background and objectives Awareness of chronic kidney disease (CKD) among providers and patients is low. Whether clinical cues prompt recognition of CKD is unknown. We examined whether markers of kidney disease that should trigger CKD recognition among providers are associated with higher individual CKD awareness. Design, setting, participants, & measurements CKD awareness was assessed in 1852 adults with an estimated GFR kidneys?” Participants were grouped by distribution of the following abnormal markers of CKD: hyperkalemia, acidosis, hyperphosphatemia, elevated blood urea nitrogen, anemia, albuminuria, and uncontrolled hypertension. Odds of CKD awareness associated with each abnormal marker and groupings of markers were estimated by multivariable logistic regression. Results Among individuals with kidney disease, only those with albuminuria had greater odds of CKD awareness (adjusted odds ratio, 4.0, P disease. Conclusions Although individuals who manifest many markers of kidney dysfunction are more likely to be aware of their CKD, their CKD awareness remains low. A better understanding of mechanisms of awareness is required to facilitate earlier detection of CKD and implement therapy to minimize associated complications. PMID:21784832

Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

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Temesgen Fiseha

2016-01-01

Full Text Available Diabetic nephropathy (DN is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL, kidney injury molecule-1 (KIM-1, liver-type fatty acid binding protein (L-FABP, N-acetyl-beta-glucosaminidase (NAG, alpha-1 microglobulin (A1M, beta 2-microglobulin (B2-M, and retinol binding protein (RBP associated with early DN.

Monitoring of uranium levels intake in some uranium-miners in egypt. Vol. 4

Energy Technology Data Exchange (ETDEWEB)

Anwar, S M [Nuclear Research Center, Atomic Energy Authority, Cairo (Egypt); Abdelmonem, A A; Aly, M M [Nuclear Materials Authority Cairo (Egypt)

1996-03-01

Uranium extraction results in conditions of intake of amounts of soluble uranium (U) salts and may reflect internal exposure levels. Proteinuria and albuminuria were also determined which reflect effect of U salts on kidney. These parameters can be used for checking the intake conditions and identifying the effect of absorbed U compounds on kidney. The U l eve in urine was evaluated in twenty male volunteers not involved in U mining processes, it ranged from 0.09 to 0.21 g/L. Twenty U miners were subjected to full clinical examination and urine analysis for estimation of U with six month interval. Significant differences were shown between the two groups. The same results were obtained for proteinuria and albuminuria, and only six workers appeared to have the signs of high U dust intake at the beginning of the experiment and decreased after six month by about 50% periodic estimation of the total annual effective dose equivalent in miners is determined to keep it always the annual limit of 20 mSv through improvement of the ventilation system and applying other effective precautions. 3 tabs.

Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

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Junghyun Kim

2012-01-01

Full Text Available Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS, which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c, and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.

SGLT2 inhibitors: a novel choice for the combination therapy in diabetic kidney disease.

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Zou, Honghong; Zhou, Baoqin; Xu, Gaosi

2017-05-16

Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc. Simultaneous use of SGLT-2 inhibitors and renin-angiotensin-aldosterone system (RAAS) blockers are novel strategies to slow the progression of DKD via reducing inflammatory and fibrotic markers induced by hyperglycaemia more than either drug alone. The available population and animal based studies have described SGLT2 inhibitors plus RAAS blockers. The present review was to systematically review the potential renal benefits of SGLT2 inhibitors combined with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and especially the angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.

Role of altered insulin signaling pathways in the pathogenesis of podocyte malfunction and microalbuminuria

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Jauregui, Alexandra; Mintz, Daniel H; Mundel, Peter; Fornoni, Alessia

2010-01-01

Purpose of review In diabetic nephropathy (DN), insulin resistance and hyperinsulinemia correlate with the development of albuminuria. The possibility that altered insulin signaling in glomerular cells and particularly podocytes contributes to the development of DN will be discussed. Recent findings While normal podocytes uptake glucose in response to insulin, diabetic podocytes become insulin resistant in experimental DN prior to the development of significant albuminuria. Both clinical and experimental data suggest that insulin sensitizers may be renoprotective independently of their systemic effects on the metabolic control of diabetes. Summary We will review the clinical and experimental evidence that altered insulin signaling correlates with the development of DN in both type 1 and type 2 diabetes, and that insulin sensitizers may be superior to other hypoglycemic agents in the prevention of DN. We will then review potential mechanisms by which altered podocyte insulin signaling may contribute to the development of DN. Understanding the role of podocyte in glucose metabolism is important because it may lead to the discovery of novel pathogenetic mechanisms of DN, it may affect current strategies for prevention and treatment of DN, and it may allow for the identification of novel therapeutic targets. PMID:19724224

Management of hypertension and diabetes mellitus by cardiovascular and endocrine physicians: a China registry.

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Song, Jie; Sheng, Chang-Sheng; Huang, Qi-Fang; Li, Li-Hua; Ma, Chang-Sheng; Guo, Xiao-Hui; Ji, Li-Nong; Wang, Ji-Guang

2016-08-01

We investigated hypertension and diabetes mellitus in two management settings, namely cardiology and endocrinology, and their associations with albuminuria while accounting for the management of these two diseases. Our multicentre registry included patients (≥20 years) seen for hypertension in cardiology or for diabetes mellitus in endocrinology. We administered a questionnaire and measured blood pressure, glycosylated haemoglobin A1c and albuminuria. Presence of both hypertension and diabetes was observed in 32.9% of hypertensive patients in cardiology (n = 1291) and 58.9% of diabetic patients in endocrinology (n = 1168). When both diseases were present, the use of combination antihypertensive therapy [odds ratio (OR) 0.31, P hypertension and diabetes, however, was not different between the two management settings (P ≥ 0.21), regardless of the therapeutic target (SBP/DBP hypertension (12.6%) or diabetes alone (15.9%). Hypertension and diabetes mellitus were often jointly present, especially in the setting of endocrinology. The management was insufficient on the use of combination antihypertensive therapy and inhibitors of the renin-angiotensin system in endocrinology and for combination antidiabetic therapy in cardiology, indicating a need for more intensive management and better control of both clinical conditions.

Distinct roles of urinary liver-type fatty acid-binding protein in non-diabetic patients with anemia.

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Naohiko Imai

Full Text Available Various stresses including ischemia are known to up-regulate renal L-FABP gene expression and increase the urinary excretion of L-FABP. In diabetic patients with anemia, the urinary excretion of L-FABP is significantly increased. We studied the clinical significance of urinary L-FABP and its relationship with anemia in non-diabetic patients.A total of 156 patients were studied in this retrospective cross-sectional analysis. The associations between anemia and urinary L-FABP levels, and the predictors of urinary L-FABP levels in non-diabetic patients were evaluated.Urinary L-FABP levels were significantly higher in patients with anemia compared to those in patients without anemia. Similarly, the urinary L-FABP levels were significantly higher in patients with albuminuria compared to those in patients without albuminuria. Urinary L-FABP levels correlated with urinary albumin-to-creatinine ratios, estimated glomerular filtration rates, body mass index, and hemoglobin levels. Multivariate linear regression analysis determined that hemoglobin levels (β = -0.249, P = 0.001 and urinary albumin-to-creatinine ratios (β = 0.349, P < 0.001 were significant predictors of urinary L-FABP levels.Urinary L-FABP is strongly associated with anemia in non-diabetic patients.

Monitoring of uranium levels intake in some uranium-miners in egypt. Vol. 4

International Nuclear Information System (INIS)

Anwar, S.M.; Abdelmonem, A.A.; Aly, M.M.

1996-01-01

Uranium extraction results in conditions of intake of amounts of soluble uranium (U) salts and may reflect internal exposure levels. Proteinuria and albuminuria were also determined which reflect effect of U salts on kidney. These parameters can be used for checking the intake conditions and identifying the effect of absorbed U compounds on kidney. The U l eve in urine was evaluated in twenty male volunteers not involved in U mining processes, it ranged from 0.09 to 0.21 g/L. Twenty U miners were subjected to full clinical examination and urine analysis for estimation of U with six month interval. Significant differences were shown between the two groups. The same results were obtained for proteinuria and albuminuria, and only six workers appeared to have the signs of high U dust intake at the beginning of the experiment and decreased after six month by about 50% periodic estimation of the total annual effective dose equivalent in miners is determined to keep it always the annual limit of 20 mSv through improvement of the ventilation system and applying other effective precautions. 3 tabs

Sulodexide for kidney protection in type 2 diabetes patients with microalbuminuria

DEFF Research Database (Denmark)

Lewis, Edmund J; Lewis, Julia B; Greene, Tom

2011-01-01

Sulodexide, a heterogenous group of sulfated glycosaminoglycans, includes low-molecular-weight heparin (~80% ± 8%), high-molecular-weight heparin (~5% ± 3%), and dermatan (~20% ± 8%), with a mean molecular weight of ~9 kDa. The drug is absorbed orally and has no anticoagulant effect in the doses ...... used. Small preliminary studies consistently showed sulodexide to be associated with decreased albuminuria in patients with diabetes....

A low-protein diet restricts albumin synthesis in nephrotic rats.

OpenAIRE

Kaysen, G A; Jones, H; Martin, V; Hutchison, F N

1989-01-01

High-protein diets increase albumin synthesis in rats with Heymann nephritis but albuminuria increases also, causing serum albumin concentration to be suppressed further than in nephrotic animals eating a low-protein diet. Experiments were designed to determine whether dietary protein augmentation directly stimulates albumin synthesis, or whether instead increased albumin synthesis is triggered by the decrease in serum albumin concentration. Evidence is presented that dietary protein augmenta...

Five-Year Incidence of Chronic Kidney Disease (Stage 3-5) and Associated Risk Factors in a Spanish Cohort: The MADIABETES Study

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Salinero-Fort, Miguel A.; San Andrés-Rebollo, Francisco J.; de Burgos-Lunar, Carmen; Gómez-Campelo, Paloma; Chico-Moraleja, Rosa M.; López de Andrés, Ana; Jiménez-García, Rodrigo

2015-01-01

Objective To evaluate the incidence rate of Chronic Kidney Disease (CKD) stage 3-5 (persistent decreased kidney function under 60 mL/min per 1.73 m2) among patients with type 2 diabetes over five years, to identify the risk factors associated with CKD, and develop a risk table to predict five-year CKD stage 3-5 risk stratification for clinical use. Design The MADIABETES Study is a prospective cohort study of 3,443 outpatients with type 2 diabetes mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain). Results The cumulative incidence of CKD stage 3-5 at five-years was 10.23% (95% CI = 9.12–11.44) and the incidence density was 2.07 (95% CI = 1.83–2.33) cases per 1,000 patient-months or 2.48 (95% CI = 2.19–2.79) cases per 100 patient-years. The highest hazard ratio (HR) for developing CKD stage 3-5 was albuminuria ≥300 mg/g (HR = 4.57; 95% CI= 2.46-8.48). Furthermore, other variables with a high HR were age over 74 years (HR = 3.20; 95% CI = 2.13–4.81), a history of Hypertension (HR = 2.02; 95% CI = 1.42–2.89), Myocardial Infarction (HR= 1.72; 95% IC= 1.25–2.37), Dyslipidemia (HR = 1.68; 95% CI 1.30–2.17), duration of diabetes mellitus ≥ 10 years (HR = 1.46; 95% CI = 1.14-1.88) and Systolic Blood Pressure >149 mmHg (HR = 1.52; 95% CI = 1.02–2.24). Conclusions After a five-year follow-up, the cumulative incidence of CKD is concordant with rates described in Spain and other countries. Albuminuria ≥ 300 mg/g and age over 74 years were the risk factors more strongly associated with developing CKD (Stage 3-5). Blood Pressure, lipid and albuminuria control could reduce CKD incidence of CKD in patients with T2DM. PMID:25856231

Prevalence and risk factors of CKD in Chinese patients with periodontal disease.

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Kejin Liu

Full Text Available BACKGROUND: Periodontal disease is common among adults and is associated with an increasing risk of chronic kidney disease (CKD. We aimed to investigate the prevalence and risk factors of CKD in patients with periodontal disease in China. METHODS: In the current cross-sectional study, patients with periodontal disease were included from Guangdong Provincial Stomatological Hospital between March 2011 and August 2011. CKD was defined as estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m(2, the presence of albuminuria, or hematuria. All patients with periodontal disease underwent a periodontal examination, including periodontal probing pocket depth, gingival recession, and clinical attachment level by Florida Probe. They completed a questionnaire and had blood and urine samples taken. The adjusted prevalence of indicators of kidney damage was calculated and risk factors associated with CKD were analyzed. RESULTS: A total of 1392 patients with periodontal disease were invited to participate this study and 1268 completed the survey and examination. After adjusting for age and sex, the prevalence of reduced eGFR, albuminuria, and hematuria was 2.7% (95% CI 1.7-3.7, 6.7% (95% CI 5.5-8.1 and 10.9% (95% CI 9.2-12.5, respectively. The adjusted prevalence of CKD was 18.2% (95% CI 16.2-20.3. Age, male, diabetes, hypertension, history of CKD, hyperuricemia, and interleukin-6 levels (≥7.54 ng/L were independent risk factors for reduced eGFR. Female, diabetes, hypertension, history of CKD, hyperuricemia, high level of cholesterol, and high sensitivity C-reactive protein (hsCRP (≥ 1.03 mg/L and TNF-α levels (≥ 1.12 ng/L were independently associated with an increased risk of albuminuria. Female, lower education (

Five-year incidence of chronic kidney disease (stage 3-5 and associated risk factors in a Spanish cohort: the MADIABETES Study.

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Miguel A Salinero-Fort

Full Text Available To evaluate the incidence rate of Chronic Kidney Disease (CKD stage 3-5 (persistent decreased kidney function under 60 mL/min per 1.73 m2 among patients with type 2 diabetes over five years, to identify the risk factors associated with CKD, and develop a risk table to predict five-year CKD stage 3-5 risk stratification for clinical use.The MADIABETES Study is a prospective cohort study of 3,443 outpatients with type 2 diabetes mellitus, sampled from 56 primary health care centers (131 general practitioners in Madrid (Spain.The cumulative incidence of CKD stage 3-5 at five-years was 10.23% (95% CI = 9.12-11.44 and the incidence density was 2.07 (95% CI = 1.83-2.33 cases per 1,000 patient-months or 2.48 (95% CI = 2.19-2.79 cases per 100 patient-years. The highest hazard ratio (HR for developing CKD stage 3-5 was albuminuria ≥ 300 mg/g (HR = 4.57; 95% CI= 2.46-8.48. Furthermore, other variables with a high HR were age over 74 years (HR = 3.20; 95% CI = 2.13-4.81, a history of Hypertension (HR = 2.02; 95% CI = 1.42-2.89, Myocardial Infarction (HR= 1.72; 95% IC= 1.25-2.37, Dyslipidemia (HR = 1.68; 95% CI 1.30-2.17, duration of diabetes mellitus ≥ 10 years (HR = 1.46; 95% CI = 1.14-1.88 and Systolic Blood Pressure >149 mmHg (HR = 1.52; 95% CI = 1.02-2.24.After a five-year follow-up, the cumulative incidence of CKD is concordant with rates described in Spain and other countries. Albuminuria ≥ 300 mg/g and age over 74 years were the risk factors more strongly associated with developing CKD (Stage 3-5. Blood Pressure, lipid and albuminuria control could reduce CKD incidence of CKD in patients with T2DM.

Urinary Angiotensinogen and Renin Excretion are Associated with Chronic Kidney Disease

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Annett Juretzko

2017-04-01

Full Text Available Background/Aims: Several studies sought to identify new biomarkers for chronic kidney disease (CKD. As the renal renin-angiotensin system is activated in CKD, urinary angiotensinogen or renin excretion may be suitable candidates. We tested whether urinary angiotensinogen or renin excretion is elevated in CKD and whether these parameters are associated with estimated glomerular filtration rate (eGFR. We further tested whether urinary angiotensinogen or renin excretion may convey additional information beyond that provided by albuminuria. Methods: We measured urinary and plasma angiotensinogen, renin, albumin and creatinine in 177 CKD patients from the Greifswald Approach to Individualized Medicine project and in 283 healthy controls from the Study of Health in Pomerania. The urinary excretion of specific proteins is given as protein-to-creatinine ratio. Receiver operating characteristic (ROC curves, spearman correlation coefficients and linear regression models were calculated. Results: Urinary angiotensinogen [2,511 (196-31,909 vs. 18.6 (8.3-44.0 pmol/g, *P<0.01] and renin excretion [0.311 (0.135-1.155 vs. 0.069 (0.045-0.148 pmol/g, *P<0.01] were significantly higher in CKD patients than in healthy controls. The area under the ROC curve was significantly larger when urinary angiotensinogen, renin and albumin excretion were combined than with urinary albumin excretion alone. Urinary angiotensinogen (ß-coefficient -2.405, standard error 0.117, P<0.01 and renin excretion (ß-coefficient -0.793, standard error 0.061, P<0.01 were inversely associated with eGFR. Adjustment for albuminuria, age, sex, systolic blood pressure and body mass index did not significantly affect the results. Conclusion: Urinary angiotensinogen and renin excretion are elevated in CKD patients. Both parameters are negatively associated with eGFR and these associations are independent of urinary albumin excretion. In CKD patients urinary angiotensinogen and renin excretion may

Urinary Angiotensinogen and Renin Excretion are Associated with Chronic Kidney Disease.

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Juretzko, Annett; Steinbach, Antje; Hannemann, Anke; Endlich, Karlhans; Endlich, Nicole; Friedrich, Nele; Lendeckel, Uwe; Stracke, Sylvia; Rettig, Rainer

2017-01-01

Several studies sought to identify new biomarkers for chronic kidney disease (CKD). As the renal renin-angiotensin system is activated in CKD, urinary angiotensinogen or renin excretion may be suitable candidates. We tested whether urinary angiotensinogen or renin excretion is elevated in CKD and whether these parameters are associated with estimated glomerular filtration rate (eGFR). We further tested whether urinary angiotensinogen or renin excretion may convey additional information beyond that provided by albuminuria. We measured urinary and plasma angiotensinogen, renin, albumin and creatinine in 177 CKD patients from the Greifswald Approach to Individualized Medicine project and in 283 healthy controls from the Study of Health in Pomerania. The urinary excretion of specific proteins is given as protein-to-creatinine ratio. Receiver operating characteristic (ROC) curves, spearman correlation coefficients and linear regression models were calculated. Urinary angiotensinogen [2,511 (196-31,909) vs. 18.6 (8.3-44.0) pmol/g, *P<0.01] and renin excretion [0.311 (0.135-1.155) vs. 0.069 (0.045-0.148) pmol/g, *P<0.01] were significantly higher in CKD patients than in healthy controls. The area under the ROC curve was significantly larger when urinary angiotensinogen, renin and albumin excretion were combined than with urinary albumin excretion alone. Urinary angiotensinogen (ß-coefficient -2.405, standard error 0.117, P<0.01) and renin excretion (ß-coefficient -0.793, standard error 0.061, P<0.01) were inversely associated with eGFR. Adjustment for albuminuria, age, sex, systolic blood pressure and body mass index did not significantly affect the results. Urinary angiotensinogen and renin excretion are elevated in CKD patients. Both parameters are negatively associated with eGFR and these associations are independent of urinary albumin excretion. In CKD patients urinary angiotensinogen and renin excretion may convey additional information beyond that provided by

Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka

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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.

2016-01-01

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

Association of albumin-creatinine ratio and cystatin C with change in ankle-brachial index: the Multi-Ethnic Study of Atherosclerosis (MESA).

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Garimella, Pranav S; Ix, Joachim H; Katz, Ronit; Shlipak, Michael G; Criqui, Michael H; Siscovick, David S; Kramer, Holly; Sibley, Christopher T; Sarnak, Mark J

2015-01-01

Low ankle-brachial index (ABI) is a reflection of atherosclerotic disease, and high ABI is an indicator of calcified vessels. The associations of albuminuria and cystatin C level with incidence of either low or high ABI are unknown. Prospective longitudinal cohort study. MESA (Multi-Ethnic Study of Atherosclerosis) enrolled community-dwelling adults (N=6,814) aged 45-84 years who were free of clinical cardiovascular disease at baseline. Baseline albumin-creatinine ratio (ACR) and serum cystatin C level. Development of low (high (>1.40) ABI using multinomial regression among persons with ABI of 0.90-1.40 at baseline. During 9.8 years of follow-up, 221 and 89 participants progressed to low and high ABIs, respectively. Baseline ACR and cystatin C level were higher among progressors compared with nonprogressors. In multivariable analyses, doubling of ACR was associated with increased risk of progression to low (OR, 1.08; 95% CI, 0.99-1.20) and high (OR, 1.16; 95% CI, 1.01-1.32) ABIs. Compared to the lowest quintile, the highest quintile of ACR had a significantly increased risk of progression to low (OR, 1.79; 95% CI, 1.03-3.12) and high (OR, 2.76; 95% CI, 1.32-5.77) ABIs. Higher cystatin C levels were associated with progression to low (OR per 1-SD greater, 1.12; 95% CI, 1.00-1.26) but not high (OR per 1-SD greater, 1.01; 95% CI, 0.81-1.25) ABI, but the highest quintile of cystatin C was not associated independently with either outcome. Single measure of albuminuria and low number of progressors to high ABI. In adults free of clinical cardiovascular disease, albuminuria was a strong independent risk factor for the development of both high and low ABIs, important and different measures of peripheral artery disease. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu among Agricultural Communities in Sri Lanka.

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Pallagae Mangala C S De Silva

2016-09-01

Full Text Available 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

Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka.

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De Silva, Pallagae Mangala C S; 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

2016-09-01

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

Effect of total glucosides of paeony on the expression of nephrin in the kidneys from diabetic rats.

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Zhang, Pei; Zhang, Jing-Jing; Su, Jing; Qi, Xiang-Ming; Wu, Yong-Gui; Shen, Ji-Jia

2009-01-01

Total glucosides of paeony (TGP), extracted from the traditional Chinese herb root of Paeonia lactiflora pall, have been shown to have a therapeutic role in experimental diabetic nephropathy including albuminuria. Recent investigation has identified nephrin, a podocyte-specific transmembrane protein, as a key regulator in the pathogenesis of diabetic albuminuria. The aim of this study was to investigate whether TGP can attenuate albuminuria through prevention of nephrin loss in the experimental diabetic nephropathy. Fifty male Munich-Wistar rats were obtained from the Experimental Animal Center of Anhui Medical University. These rats were divided into 5 groups (n = 10); normal group, control diabetic group, and 3 TGP treated diabetic groups at different concentrations. Diabetes was induced by streptozotocin, and TGP (50, 100, 200 mg/kg) was orally administered to the 3 TGP treated diabetic groups once a day for 8 weeks, respectively. Blood glucose and 24 hour urinary albumin excretion rate (AER) were measured. The expressions of nephrin, tumor necrosis factor-alpha (TNF-alpha), NF-kappaB p65 and 3-nitrotyrosine (3-NT) protein were determined by immunoinfluorescence or Western blot analysis in the kidneys. Elevated AER was markedly attenuated by TGP treatment in diabetic rats. There was a finely dotted linear epithelial staining of nephrin in normal group glomeruli. In contrast, the staining of glomeruli from untreated diabetic rats was attenuated, more diapersed, and clustered. This diabetic-induced loss of glomerular nephrin expression was prevented in a large degree in TGP-treated diabetic rats. Western blot analysis showed that the expression of nephrin protein was reduced in the kidneys of diabetic rats, but significantly increased in the TGP treatment groups. The expressions of TNF-alpha, NF-kappaB p65 and 3-NT protein were significantly increased in the kidneys of diabetic rats, which were all significantly inhibited by TGP treatment. Our results showed that

PTH levels and not serum phosphorus levels are a predictor of the progression of kidney disease in elderly patients with advanced chronic kidney disease.

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Toapanta Gaibor, Néstor Gabriel; Nava Pérez, Nathasha Carolina; Martínez Echevers, Yeleine; Montes Delgado, Rafael; Guerrero Riscos, María Ángeles

At present, there is a high incidence of elderly patients with advanced chronic kidney disease (CKD) and it is important to know the long term progression and the factors that influence it. To analyse the progression of advanced CKD in elderly patients and the influence of bone-mineral metabolism. Retrospective study of 125 patients ≥70years of age with CKD stages 4-5 who started follow-up from January 1, 2007 to December 31, 2008, showing the progression of CKD (measured by the slope of the regression line of the estimated glomerular filtration rate [eGFR] by MDRD-4) over 5years. Progression in the entire group (median and 25th and 75th percentiles): -1.15 (-2.8/0.17) ml/min/1.73m 2 /year, CKD-4: -1.3 (-2.8/0.03) ml/min/1.73m 2 /year, CKD-5: -1.03 (-3.0/0.8) ml/min/1.73m 2 /year; the slope of the regression line was positive in 35 patients (28%: CKD does not progress) and negative in 90 patients (72%: CKD progresses). Negative correlation (Spearman) (slower progression): PTH, albumin/Cr ratio and daily Na excretion (all baseline measurements). No correlation with eGFR, serum P, urinary P excretion, protein intake and intake of P (all baseline measurements). In the linear regression analysis (dependent variable: slope of progression): albuminuria and PTH (both at baseline measurements) influenced this variable independently. Logistic regression (progresses vs. does not progress): PTH, albuminuria and eGFR (all at baseline measurements) influenced significantly. 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. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Emergence and Progression of Albuminuria in a Cohort of Egyptian ...

African Journals Online (AJOL)

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 ...

Enfermedad renal crónica en individuos hipertensos ≥60 años atendidos en Atención Primaria

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Betlem Salvador-González

2017-07-01

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.

Dehydration as a Cause of Chronic Kidney Disease: Role of Fructokinase

Science.gov (United States)

2016-10-01

hyperfiltration and albuminuria in humans and laboratory animals (2- 4). In this study we sought to examine the role of vasopressin in our heat stress...and Use of Laboratory Animals . The animal protocol was approved by the Animal Care and Use Committee of the University of Colorado. Biochemical...SUPPLEMENTARY NOTES 14. ABSTRACT Our studies evaluate how recurrent dehydration can cause chronic kidney disease, an important question for the

Prediction of Chronic Kidney Disease Stage 3 by CKD273, a Urinary Proteomic Biomarker

DEFF Research Database (Denmark)

Pontillo, Claudia; Zhang, Zhen-Yu; Schanstra, Joost P

2017-01-01

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....

Mechanisms by which heme oxygenase rescue renal dysfunction in obesity

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Joseph Fomusi Ndisang

2014-01-01

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.

Management of hypertension and diabetes mellitus by cardiovascular and endocrine physicians: a China registry

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Song, Jie; Sheng, Chang-Sheng; Huang, Qi-Fang; Li, Li-Hua; Ma, Chang-Sheng; Guo, Xiao-Hui; Ji, Li-Nong; Wang, Ji-Guang

2016-01-01

Objective: We investigated hypertension and diabetes mellitus in two management settings, namely cardiology and endocrinology, and their associations with albuminuria while accounting for the management of these two diseases. Methods: Our multicentre registry included patients (≥20 years) seen for hypertension in cardiology or for diabetes mellitus in endocrinology. We administered a questionnaire and measured blood pressure, glycosylated haemoglobin A1c and albuminuria. Results: Presence of both hypertension and diabetes was observed in 32.9% of hypertensive patients in cardiology (n = 1291) and 58.9% of diabetic patients in endocrinology (n = 1168). When both diseases were present, the use of combination antihypertensive therapy [odds ratio (OR) 0.31, P hypertension and diabetes, however, was not different between the two management settings (P ≥ 0.21), regardless of the therapeutic target (SBP/DBP hypertension (12.6%) or diabetes alone (15.9%). Conclusion: Hypertension and diabetes mellitus were often jointly present, especially in the setting of endocrinology. The management was insufficient on the use of combination antihypertensive therapy and inhibitors of the renin–angiotensin system in endocrinology and for combination antidiabetic therapy in cardiology, indicating a need for more intensive management and better control of both clinical conditions. PMID:27270188

Measurement of the modification and interference rate of urinary albumin detected by size-exclusion HPLC

International Nuclear Information System (INIS)

Markó, Lajos; Molnár, Gergő Attila; Wagner, Zoltán; Szijártó, István; Mérei, Ákos; Wittmann, István; Böddi, Katalin; Szabó, Zoltán; Matus, Zoltán; Kőszegi, Tamás; Nagy, Géza

2009-01-01

The measurement of the excretion of urinary albumin (albuminuria) is an important and well-established method to assess clinical outcomes. A high-performance liquid chromatography (HPLC) method has been introduced to measure albuminuria. Using this method, it was found that commonly used immunological methods do not measure a fraction of urinary albumin. Some authors presumed that the reason of immuno-unreactivity is the modification of urinary albumin; some others presumed that the difference is merely because of interference. In order to decide this question, we established an HPLC method equipped with tandem UV and fluorescent detection to assess the changes in the detectability of albumin with the rate of modification. For this measurement, differently modified forms of albumin were used. Urine samples of diabetic patients were also measured to find a potential connection between the modification rate and clinical parameters. Secondly, we have established a reversed phase HPLC method to assess the interference rate. We conclude that albumin modification does not affect immunoreactivity. The modification rate of urinary albumin in diabetic patients showed a correlation with renal function. The interference rate of the albumin peak was found to be 12.7% on average, which does not explain the difference between the two methods

Delphi consensus on the diagnosis and management of dyslipidaemia in chronic kidney disease patients: A post hoc analysis of the DIANA study

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Aleix Cases Amenós

2016-11-01

Conclusions: The consensus to analyse the lipid profile in CKD patients suggests acknowledgement of the high cardiovascular risk of this condition. However, the lack of consensus in considering renal function or albuminuria, both when selecting a statin and during follow-up, suggests a limited knowledge of the differences between statins in relation to CKD. Thus, it would be advisable to develop a guideline/consensus document on the use of statins in CKD.

Persistent hypertension and progressive renal injury induced by salt overload after short term nitric oxide inhibition Hipertensão persistente e lesão renal progressiva induzidas por sobrecarga de sal após inibição temporária do óxido nítrico

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Ana Lúcia Mattar

2007-01-01

Full Text Available INTRODUCTION: Administration of the NO inhibitor Nwð-nitro-L-arginine methyl ester (NAME and a high-salt diet (HS promotes severe albuminuria and renal injury, which regresses upon discontinuation of treatments. OBJECTIVE: We investigated whether these changes reappear after reinstitution of HS, and whether they are prevented by treatment with the antilymphocyte agent mycophenolate mofetil (MMF or the AT-1 receptor blocker losartan (L. Adult male Munich-Wistar rats received NAME and HS. A control Group (C received only HS. After 20 days, rats receiving HS and NAME exhibited severe hypertension and albuminuria. After a 30-day recovery period, hypertension was attenuated and albuminuria had virtually disappeared. MATERIAL AND METHODS: Rats were then distributed among the following groups: HS, receiving HS; NS, receiving a normal salt (NS diet; HS-MMF, receiving HS and MMF; HS-LOS, receiving HS and L; HS-HDZ, receiving HS and hydralazine (HDZ. Sixty days later, NS rats showed only slight albuminuria and renal damage or inflammation. In contrast, HS rats developed severe hypertension, marked glomerulosclerosis with interstitial expansion and renal infiltration by macrophages and angiotensin II-positive cells. The group treated with losartan had lowered blood pressure and a lack of albuminuria or renal injury. MMF provided similar protection without altering blood pressure, suggesting a nonhemodynamic effect, a hypothesis reinforced by the finding that HDZ lowered blood pressure without preventing renal injury. RESULTS: These results indicate that treatment with HS and NAME predisposes to the development of hypertension and renal injury upon salt overload, characterizing a new model of chronic nephropathy. CONCLUSION: The response to MMF or L, but not HDZ, suggests a key role for inflammatory rather than hemodynamic factors.INTRODUÇÃO: A administração de Nômega-nitro-L-arginina metiléster (NAME, um inibidor da produção de NO, com dieta rica

Food Insecurity, CKD, and Subsequent ESRD in US Adults.

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Banerjee, Tanushree; Crews, Deidra C; Wesson, Donald E; Dharmarajan, Sai; Saran, Rajiv; Ríos Burrows, Nilka; Saydah, Sharon; Powe, Neil R

2017-07-01

Poor access to food among low-income adults has been recognized as a risk factor for chronic kidney disease (CKD), but there are no data for the impact of food insecurity on progression to end-stage renal disease (ESRD). We hypothesized that food insecurity would be independently associated with risk for ESRD among persons with and without earlier stages of CKD. Longitudinal cohort study. 2,320 adults (aged ≥ 20 years) with CKD and 10,448 adults with no CKD enrolled in NHANES III (1988-1994) with household income ≤ 400% of the federal poverty level linked to the Medicare ESRD Registry for a median follow-up of 12 years. Food insecurity, defined as an affirmative response to the food-insecurity screening question. Development of ESRD. Demographics, income, diabetes, hypertension, estimated glomerular filtration rate, and albuminuria. Dietary acid load was estimated from 24-hour dietary recall. We used a Fine-Gray competing-risk model to estimate the relative hazard (RH) for ESRD associated with food insecurity after adjusting for covariates. 4.5% of adults with CKD were food insecure. Food-insecure individuals were more likely to be younger and have diabetes (29.9%), hypertension (73.9%), or albuminuria (90.4%) as compared with their counterparts (Pinsecure group was 51.2 mEq/d versus 55.6 mEq/d, respectively (P=0.05). Food-insecure adults were more likely to develop ESRD (RH, 1.38; 95% CI, 1.08-3.10) compared with food-secure adults after adjustment for demographics, income, diabetes, hypertension, estimated glomerular filtration rate, and albuminuria. In the non-CKD group, 5.7% were food insecure. We did not find a significant association between food insecurity and ESRD (RH, 0.77; 95% CI, 0.40-1.49). Use of single 24-hour diet recall; lack of laboratory follow-up data and measure of changes in food insecurity over time; follow-up of cohort ended 10 years ago. Among adults with CKD, food insecurity was independently associated with a higher likelihood of

Relative risks of Chronic Kidney Disease for mortality and End Stage Renal Disease across races is similar

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Wen, Chi-Pang; Matsushita, Kunihiro; Coresh, Josef; Iseki, Kunitoshi; Islam, Muhammad; Katz, Ronit; McClellan, William; Peralta, Carmen A; Wang, HaiYan; de Zeeuw, Dick; Astor, Brad C; Gansevoort, Ron T; Levey, Andrew S; Levin, Adeera

2014-01-01

Some suggest race-specific cutpoints for kidney measures to define and stage chronic kidney disease (CKD), but evidence for race-specific clinical impact is limited. To address this issue, we compared hazard ratios of estimated glomerular filtration rates (eGFR) and albuminuria across races using meta-regression in 1.1 million adults (75% Asians, 21% whites, and 4% blacks) from 45 cohorts. Results came mainly from 25 general population cohorts comprising 0.9 million individuals. The associations of lower eGFR and higher albuminuria with mortality and end-stage renal disease (ESRD) were largely similar across races. For example, in Asians, whites, and blacks, the adjusted hazard ratios (95% confidence interval) for eGFR 45–59 vs. 90–104 ml/min/1.73m2 were 1.3 (1.2–1.3), 1.1 (1.0–1.2) and 1.3 (1.1–1.7) for all-cause mortality, 1.6 (1.5–1.8), 1.4 (1.2–1.7), and 1.4 (0.7–2.9) for cardiovascular mortality, and 27.6 (11.1–68.7), 11.2 (6.0–20.9), and 4.1 (2.2–7.5) for ESRD, respectively. The corresponding hazard ratios for urine albumin-to-creatinine ratio 30–299 mg/g or dipstick 1-positive vs. an albumin-to-creatinine ratio under 10 or dipstick negative were 1.6 (1.4–1.8), 1.7 (1.5–1.9) and 1.8 (1.7–2.1) for all-cause mortality, 1.7 (1.4–2.0), 1.8 (1.5–2.1), and 2.8 (2.2–3.6) for cardiovascular mortality, and 7.4 (2.0–27.6), 4.0 (2.8–5.9), and 5.6 (3.4–9.2) for ESRD, respectively. Thus, the relative mortality or ESRD risks of lower eGFR and higher albuminuria were largely similar among three major races, supporting similar clinical approach to CKD definition and staging, across races. PMID:24522492

The cost-effectiveness of using chronic kidney disease risk scores to screen for early-stage chronic kidney disease.

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Yarnoff, Benjamin O; Hoerger, Thomas J; Simpson, Siobhan K; Leib, Alyssa; Burrows, Nilka R; Shrestha, Sundar S; Pavkov, Meda E

2017-03-13

Better treatment during early stages of chronic kidney disease (CKD) may slow progression to end-stage renal disease and decrease associated complications and medical costs. Achieving early treatment of CKD is challenging, however, because a large fraction of persons with CKD are unaware of having this disease. Screening for CKD is one important method for increasing awareness. We examined the cost-effectiveness of identifying persons for early-stage CKD screening (i.e., screening for moderate albuminuria) using published CKD risk scores. We used the CKD Health Policy Model, a micro-simulation model, to simulate the cost-effectiveness of using CKD two published risk scores by Bang et al. and Kshirsagar et al. to identify persons in the US for CKD screening with testing for albuminuria. Alternative risk score thresholds were tested (0.20, 0.15, 0.10, 0.05, and 0.02) above which persons were assigned to receive screening at alternative intervals (1-, 2-, and 5-year) for follow-up screening if the first screening was negative. We examined incremental cost-effectiveness ratios (ICERs), incremental lifetime costs divided by incremental lifetime QALYs, relative to the next higher screening threshold to assess cost-effectiveness. Cost-effective scenarios were determined as those with ICERs less than $50,000 per QALY. Among the cost-effective scenarios, the optimal scenario was determined as the one that resulted in the highest lifetime QALYs. ICERs ranged from $8,823 per QALY to $124,626 per QALY for the Bang et al. risk score and $6,342 per QALY to $405,861 per QALY for the Kshirsagar et al. risk score. The Bang et al. risk score with a threshold of 0.02 and 2-year follow-up screening was found to be optimal because it had an ICER less than $50,000 per QALY and resulted in the highest lifetime QALYs. This study indicates that using these CKD risk scores may allow clinicians to cost-effectively identify a broader population for CKD screening with testing for albuminuria

Chronic renal disease in spain: prevalence and related factors in persons with diabetes mellitus older than 64 years.

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Martínez Candela, Juan; Sangrós González, Javier; García Soidán, Francisco Javier; Millaruelo Trillo, José Manuel; Díez Espino, Javier; Bordonaba Bosque, Daniel; Ávila Lachica, Luis

2018-02-07

Type 2 diabetes mellitus and chronic kidney disease (CKD) are conditions which have a high prevalence in individuals ≥ 65 years of age and represent a major public health problem. To determine the prevalence of CKD, its categories and its relationship with various demographic and clinical factors in elderly patients with type 2 diabetes mellitus in Spain. Observational, cross-sectional, multicenter, Spanish epidemiological study. Patients with known type 2 diabetes mellitus, age ≥ 65 years of age treated in Primary Care were included. We collected demographic, anthropometric and analytical variables from the previous 12 months, including the albumin-to-creatinine ratio and estimated glomerular filtration rate to evaluate renal function. The prevalence of CKD was 37.2% (95% CI, 34.1-40.3%), renal failure was 29.7% (95% CI, 26.8-32.6%) and increased albuminuria was 20.6% (95% CI, 17.3-23.9%), moderately increased albuminuria was 17.8% (95% CI, 14.7-20.9%) and severely increased albuminuria was 2.8% (95% CI, 1.4-4.2%). In turn, the prevalence of CKD categories were: G1 1.3% (95% CI, 0.6-2%), G2 6.2% (95% CI, 4.6-7.8%), G3a 17.2% (95% CI, 14.8-19.6%), G3b 9.8% (95% CI, 7.9-11.7%), G4 2% (95% CI, 1.1-2.9%) and G5 0.7% (95% CI, 0.2-1.2%). In the multivariate analysis, after adjusting for the remaining variables, CKD was associated with elderly age (OR 5.13, 95% CI, 3.15-8.35), high comorbidity (OR 3.36. 95% CI, 2.2-5.12) and presence of antihypertensive treatment (OR 2.43. 95% CI, 1.48-4.02). CKD is frequent in the diabetic population ≥ 65 years of age and is associated with elderly age, high comorbidity and with treated hypertension. No relationship has been found with gender and time in years since onset of diabetes. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Effect of urine urea nitrogen and protein intake adjusted by using the estimated urine creatinine excretion rate on the antiproteinuric effect of angiotensin II type I receptor blockers.

Science.gov (United States)

Chin, Ho Jun; Kim, Dong Ki; Park, Jung Hwan; Shin, Sung Joon; Lee, Sang Ho; Choi, Bum Soon; Kim, Suhnggwon; Lim, Chun Soo

2015-01-01

The aim of this study was to determine the role of protein intake on proteinuria in chronic kidney disease (CKD), as it is presently not conclusive. This is a subanalysis of data from an open-label, case-controlled, randomized clinical trial on education about low-salt diets (NCT01552954). We estimated the urine excretion rate of parameters in a day, adjusted by using the equation for estimating urine creatinine excretion, and analyzed the effect of urine urea nitrogen (UUN), as well as estimating protein intake on the level of albuminuria in hypertensive patients with chronic kidney disease. Among 174 participants from whom complete 24-h urine specimens were collected, the estimates from the Tanaka equation resulted in the highest accuracy for the urinary excretion rate of creatinine, sodium, albumin, and UUN. Among 227 participants, the baseline value of estimated urine albumin excretion (eUalb) was positively correlated with the estimated UUN (eUUN) or protein intake according to eUUN (P = 0.012 and P = 0.038, respectively). We were able to calculate the ratios of eUalb and eUUN in 221 participants and grouped them according to the ratio of eUUN during 16-wk trial period. The proportion of patients that achieved a decrement of eUalb ≥25% during 16 wk with an angiotensin II type I receptor blocker (ARB) medication was 80% (24 of 30) in group 1, with eUUN ratio ≤-25%; 82.2% (111 of 135) in group 2, with eUUN ratio between -25% and 25%; and 66.1% (37 and 56) in group 3, with eUUN ratio ≥25% (P = 0.048). The probability of a decrease in albuminuria with ARB treatment was lower in patients with an increase of eUUN or protein intake during the 16 wk of ARB treatment, as observed in multiple logistic regression analysis as well. The estimated urine urea excretion rate showed a positive association with the level of albuminuria in hypertensive patients with chronic kidney disease. The increase of eUUN excretion ameliorated the antiproteinuric effect of ARB

Thiamine deficiency and its correlation with dyslipidaemia in diabetics with microalbuminuria

International Nuclear Information System (INIS)

Waheed, P.; Naveed, A. K.; Ahmed, T.

2013-01-01

Objective: To measure and correlate the levels of thiamine and dyslipidaemia in microalbuminuric diabetics. Methods: Cross-sectional comparative study was conducted at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, from January 2009 to December 2010, and comprised 60 known diabetic patients, who were inducted from diabetic clinics of Rawalpindi. These patients were divided into three equal groups, with group I (n=20) being normal healthy individuals, group II comprised of microalbuminurics type 2 diabetics (n=20) and group III (n=20) were macroalbuminuric type 2 diabetics, based on their albumin excretion rate. The healthy volunteers (n=20) had blood glucose less than 6 mmol/L and were inducted as the comparison group. Fasting blood samples of diabetic and control groups were analysed for glucose, glycosylated haemoglobin, lipid profile, thiamine chloride and thiamine monophosphate. Besides, 24-hour urine samples were analysed for microalbuminuria, thiamine chloride and thiamine monophosphate. Results: Plasma thiamine chloride and thiamine monophosphate levels were found to be significantly (p<0.001) reduced in the diabetics (n=60) compared to the controls (n=20). Furthermore, there was a progressive decline in these levels with increasing albuminuria; the lowest being in the macroalbuminuric group (group IV). Urinary thiamine levels were significantly (p<0.001) higher in the diabetics compared to the controls. These changes were more pronounced as albuminuria level increased; the highest being in group IV. The parameters of lipid profile, including triglycerides, total cholesterol and low-density lipoprotein cholesterol, were significantly (p<0.001) higher in diabetics and showed progressive increase with worsening albuminuria. Whereas, the high-density lipoprotein cholesterol levels were significantly (p<0.001) reduced in diabetics and showed progressive decline as the microalbuminuria status worsened. Furthermore, a

Dose-dependent effects of dihydrotestosterone in the streptozotocin-induced diabetic rat kidney

OpenAIRE

Xu, Qin; Prabhu, Anjali; Xu, Shujing; Manigrasso, Michaele B.; Maric, Christine

2009-01-01

We recently reported that castration exacerbates albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis associated with diabetic renal disease. The aim of the present study was to examine whether these effects of castration can be attenuated with dihydrotestosterone (DHT) supplementation. The study was performed in castrated male Sprague-Dawley, streptozotocin-induced diabetic rats treated with 0 mg/day DHT (DHT0), 0.75 mg/day DHT (DHT0.75), or 2.0 mg/day DHT (DHT2.0) for 14 wk. Tre...

Pathogenesis of diabetic vascular disease: evidence for the role of reduced heparan sulfate proteoglycan

DEFF Research Database (Denmark)

Jensen, Tonny Joran

1997-01-01

that albuminuria is a marker of widespread vascular dysfunction. Increased transport of macromolecules across the vascular wall, elevated plasma levels of von Willebrand factor, and impaired fibrinolytic capacity have been demonstrated in albuminuric patients. The cause of this vascular vulnerability...... problems. What are the mechanisms of action of glycosaminoglycans at the molecular biology level, and how can we select compounds without anticoagulant activity suitable for long-term use in the prevention and treatment of late diabetic complications?...

Albuminuria and overall capillary permeability of albumin in acute altitude hypoxia

DEFF Research Database (Denmark)

Hansen, J M; Olsen, Niels Vidiendal; Feldt-Rasmussen, B

1994-01-01

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 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...... from 2.8 to > 5.0 micrograms/min in both groups (P high altitude significantly increased filtration fraction (P

Higher levels of albuminuria within the normal range predict incident hypertension.

Science.gov (United States)

Forman, John P; Fisher, Naomi D L; Schopick, Emily L; Curhan, Gary C

2008-10-01

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.

Higher Levels of Albuminuria within the Normal Range Predict Incident Hypertension

OpenAIRE

Forman, John P.; Fisher, Naomi D.L.; Schopick, Emily L.; Curhan, Gary C.

2008-01-01

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

Growth hormone replacement does not elevate albuminuria in GH-deficient adults

NARCIS (Netherlands)

Beentjes, JAM; Dullaart, RPF

2002-01-01

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

Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

Energy Technology Data Exchange (ETDEWEB)

Wang, Y.; Mu, J.J.; Liu, F.Q.; Ren, K.Y.; Xiao, H.Y. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Cardiovascular Department, Xi' an, China, Cardiovascular Department, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Ministry of Education, Key Laboratory of Environment and Genes Related to Diseases, Xi' an, China, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi' an (China); Yang, Z. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Department of Pathology, Xi' an, China, Department of Pathology, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Yuan, Z.Y. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Cardiovascular Department, Xi' an, China, Cardiovascular Department, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Ministry of Education, Key Laboratory of Environment and Genes Related to Diseases, Xi' an, China, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi' an (China)

2014-03-03

Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13{sup BN} rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.

The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report.

Science.gov (United States)

Levey, Andrew S; de Jong, Paul E; Coresh, Josef; El Nahas, Meguid; Astor, Brad C; Matsushita, Kunihiro; Gansevoort, Ron T; Kasiske, Bertram L; Eckardt, Kai-Uwe

2011-07-01

The definition and classification for chronic kidney disease was proposed by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) in 2002 and endorsed by the Kidney Disease: Improving Global Outcomes (KDIGO) in 2004. This framework promoted increased attention to chronic kidney disease in clinical practice, research and public health, but has also generated debate. It was the position of KDIGO and KDOQI that the definition and classification should reflect patient prognosis and that an analysis of outcomes would answer key questions underlying the debate. KDIGO initiated a collaborative meta-analysis and sponsored a Controversies Conference in October 2009 to examine the relationship of estimated glomerular filtration rate (GFR) and albuminuria to mortality and kidney outcomes. On the basis of analyses in 45 cohorts that included 1,555,332 participants from general, high-risk, and kidney disease populations, conference attendees agreed to retain the current definition for chronic kidney disease of a GFR 30 mg/g, and to modify the classification by adding albuminuria stage, subdivision of stage 3, and emphasizing clinical diagnosis. Prognosis could then be assigned based on the clinical diagnosis, stage, and other key factors relevant to specific outcomes. KDIGO has now convened a workgroup to develop a global clinical practice guideline for the definition, classification, and prognosis of chronic kidney disease.

Addition of Aliskiren to Angiotensin Receptor Blocker Improves Ambulatory Blood Pressure Profile and Cardiorenal Function Better than Addition of Benazepril in Chronic Kidney Disease

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Satoshi Umemura

2013-07-01

Full Text Available An altered ambulatory blood pressure (BP and heart rate (HR profile is related to chronic kidney disease (CKD and cardiorenal syndrome. In this study, we examined the effects of aliskiren, when added to angiotensin II type 1 receptor blockers, on ambulatory BP and cardiorenal function in CKD. Thirty-six hypertensive CKD patients were randomly assigned to the aliskiren add-on group (n = 18 or the benazepril add-on group (n = 18. Ambulatory BP and cardiorenal function parameters were measured at baseline and 24 weeks after treatment. Compared with the benazepril group, nighttime systolic BP variability in the aliskiren group was lower after treatment. Albuminuria was decreased in the aliskiren group, but not in the benazepril group. In addition, left ventricular mass index (LVMI was significantly lower in the aliskiren group than in the benazepril group after treatment. In the aliskiren group, multivariate linear regression analysis showed an association between changes in albuminuria and changes in nighttime systolic BP. Furthermore, there were associations between changes in LVMI and changes in daytime HR variability, as well as between changes in LVMI and changes in plasma aldosterone concentration. These results suggest that aliskiren add-on therapy may be beneficial for suppression of renal deterioration and pathological cardiac remodeling through an improvement that is effected in ambulatory BP and HR profiles.

Addition of aliskiren to Angiotensin receptor blocker improves ambulatory blood pressure profile and cardiorenal function better than addition of benazepril in chronic kidney disease.

Science.gov (United States)

Ohsawa, Masato; Tamura, Kouichi; Kanaoka, Tomohiko; Wakui, Hiromichi; Maeda, Akinobu; Dejima, Toru; Azushima, Kengo; Uneda, Kazushi; Kobayashi, Ryu; Tsurumi-Ikeya, Yuko; Toya, Yoshiyuki; Fujikawa, Tetsuya; Umemura, Satoshi

2013-07-24

An altered ambulatory blood pressure (BP) and heart rate (HR) profile is related to chronic kidney disease (CKD) and cardiorenal syndrome. In this study, we examined the effects of aliskiren, when added to angiotensin II type 1 receptor blockers, on ambulatory BP and cardiorenal function in CKD. Thirty-six hypertensive CKD patients were randomly assigned to the aliskiren add-on group (n = 18) or the benazepril add-on group (n = 18). Ambulatory BP and cardiorenal function parameters were measured at baseline and 24 weeks after treatment. Compared with the benazepril group, nighttime systolic BP variability in the aliskiren group was lower after treatment. Albuminuria was decreased in the aliskiren group, but not in the benazepril group. In addition, left ventricular mass index (LVMI) was significantly lower in the aliskiren group than in the benazepril group after treatment. In the aliskiren group, multivariate linear regression analysis showed an association between changes in albuminuria and changes in nighttime systolic BP. Furthermore, there were associations between changes in LVMI and changes in daytime HR variability, as well as between changes in LVMI and changes in plasma aldosterone concentration. These results suggest that aliskiren add-on therapy may be beneficial for suppression of renal deterioration and pathological cardiac remodeling through an improvement that is effected in ambulatory BP and HR profiles.

Cyclodextrin Protects Podocytes in Diabetic Kidney Disease

Science.gov (United States)

Merscher-Gomez, Sandra; Guzman, Johanna; Pedigo, Christopher E.; Lehto, Markku; Aguillon-Prada, Robier; Mendez, Armando; Lassenius, Mariann I.; Forsblom, Carol; Yoo, TaeHyun; Villarreal, Rodrigo; Maiguel, Dony; Johnson, Kevin; Goldberg, Ronald; Nair, Viji; Randolph, Ann; Kretzler, Matthias; Nelson, Robert G.; Burke, George W.; Groop, Per-Henrik; Fornoni, Alessia

2013-01-01

Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD+) when compared with diabetic patients with normoalbuminuria (DKD−) and similar duration of diabetes and lipid profile. Glomerular downregulation of ABCA1 was confirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n = 32). Induction of cholesterol efflux with cyclodextrin (CD) but not inhibition of cholesterol synthesis with simvastatin prevented podocyte injury observed in vitro after exposure to patient sera. Subcutaneous administration of CD to diabetic BTBR (black and tan, brachiuric) ob/ob mice was safe and reduced albuminuria, mesangial expansion, kidney weight, and cortical cholesterol content. This was followed by an improvement of fasting insulin, blood glucose, body weight, and glucose tolerance in vivo and improved glucose-stimulated insulin release in human islets in vitro. Our data suggest that impaired reverse cholesterol transport characterizes clinical and experimental DKD and negatively influences podocyte function. Treatment with CD is safe and effective in preserving podocyte function in vitro and in vivo and may improve the metabolic control of diabetes. PMID:23835338

Circulating CXCL16 in Diabetic Kidney Disease

Directory of Open Access Journals (Sweden)

Usama Elewa

2016-09-01

Full Text Available Background/Aims: Chronic kidney disease and, specifically, diabetic kidney disease, is among the fastest increasing causes of death worldwide. A better understanding of the factors contributing to the high mortality may help design novel monitoring and therapeutic approaches. CXCL16 is both a cholesterol receptor and a chemokine with a potential role in vascular injury and inflammation. We aimed at identifying predictors of circulating CXCL16 levels in diabetic patients with chronic kidney disease. Methods: We have now studied plasma CXCL16 in 134 European patients with diabetic kidney disease with estimated glomerular filtration rate (eGFR categories G1-G4 and albuminuria categories A1-A3, in order to identify factors influencing plasma CXCL16 in this population. Results: Plasma CXCL16 levels were 4.0±0.9 ng/ml. Plasma CXCL16 increased with increasing eGFR category from G1 to G4 (that is, with decreasing eGFR values and with increasing albuminuria category. Plasma CXCL16 was higher in patients with prior cardiovascular disease (4.33±1.03 vs 3.88±0.86 ng/ml; p=0.013. In multivariate analysis, eGFR and serum albumin had an independent and significant negative correlation with plasma CXCL16. Conclusion: In diabetic kidney disease patients, GFR and serum albumin independently predicted plasma CXCL16 levels.

Clinical associations of total kidney volume: the Framingham Heart Study.

Science.gov (United States)

Roseman, Daniel A; Hwang, Shih-Jen; Oyama-Manabe, Noriko; Chuang, Michael L; O'Donnell, Christopher J; Manning, Warren J; Fox, Caroline S

2017-08-01

Total kidney volume (TKV) is an imaging biomarker that may have diagnostic and prognostic utility. The relationships between kidney volume, renal function and cardiovascular disease (CVD) have not been characterized in a large community-dwelling population. This information is needed to advance the clinical application of TKV. We measured TKV in 1852 Framingham Heart Study participants (mean age 64.1 ± 9.2 years, 53% women) using magnetic resonance imaging. A healthy sample was used to define reference values. The associations between TKV, renal function and CVD risk factors were determined using multivariable logistic regression analysis. Overall, mean TKV was 278 ± 54 cm3 for women and 365 ± 66 cm3 for men. Risk factors for high TKV (>90% healthy referent size) were body surface area (BSA), diabetes, smoking and albuminuria, while age, female and estimated glomerular filtration rate (eGFR) kidney damage including albuminuria and eGFR <60 mL/min/1.73 m2, while high TKV is associated with diabetes and decreased odds of eGFR <60 mL/min/1.73 m2. Prospective studies are needed to characterize the natural progression and clinical consequences of TKV. Published by Oxford University Press on behalf of ERA-EDTA 2016. This work is written by US Government employees and is in the public domain in the US.

Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

International Nuclear Information System (INIS)

Wang, Y.; Mu, J.J.; Liu, F.Q.; Ren, K.Y.; Xiao, H.Y.; Yang, Z.; Yuan, Z.Y.

2014-01-01

Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13 BN rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure

The Proteoglycan Syndecan 4 Regulates Transient Receptor Potential Canonical 6 Channels via RhoA/ROCK Signaling

DEFF Research Database (Denmark)

Liu, Ying; Echtermeyer, Frank; Thilo, Florian

2012-01-01

OBJECTIVE: Syndecan 4 (Sdc4) modulates signal transduction and regulates activity of protein channels. Sdc4 is essential for the regulation of cellular permeability. We hypothesized that Sdc4 may regulate transient receptor potential canonical 6 (TRPC6) channels, a determinant of glomerular perme...... permeability, in a RhoA/ROCK-dependent manner. METHODS AND RESULTS: Sdc4 knockout (Sdc4(-/-)) mice showed increased glomerular filtration rate and ameliorated albuminuria under baseline conditions and after bovine serum albumin overload (each P...

Incidence of chronic kidney disease among people with diabetes: a systematic review of observational studies.

Science.gov (United States)

Koye, D N; Shaw, J E; Reid, C M; Atkins, R C; Reutens, A T; Magliano, D J

2017-07-01

The aim was to systematically review published articles that reported the incidence of chronic kidney disease among people with diabetes. A systematic literature search was performed using MEDLINE, Embase and CINAHL databases. The titles and abstracts of all publications identified by the search were reviewed and 10 047 studies were retrieved. A total of 71 studies from 30 different countries with sample sizes ranging from 505 to 211 132 met the inclusion criteria. The annual incidence of microalbuminuria and albuminuria ranged from 1.3% to 3.8% for Type 1 diabetes. For Type 2 diabetes and studies combining both diabetes types, the range was from 3.8% to 12.7%, with four of six studies reporting annual rates between 7.4% and 8.6%. In studies reporting the incidence of eGFR Disease (MDRD) equation, apart from one study which reported an annual incidence of 8.9%, the annual incidence ranged from 1.9% to 4.3%. The annual incidence of end-stage renal disease ranged from 0.04% to 1.8%. The annual incidence of microalbuminuria and albuminuria is ~ 2-3% in Type 1 diabetes, and ~ 8% in Type 2 diabetes or mixed diabetes type. The incidence of developing eGFR kidney disease, there was only modest variation in incidence rates. These findings may be useful in clinical settings to help understand the risk of developing kidney disease among those with diabetes. © 2017 Diabetes UK.

Vorapaxar treatment reduces mesangial expansion in streptozotocin-induced diabetic nephropathy in mice.

Science.gov (United States)

Waasdorp, Maaike; Duitman, JanWillem; Florquin, Sandrine; Spek, C Arnold

2018-04-24

Twenty years after the onset of diabetes, up to 40% of patients develop diabetic nephropathy. Protease-activated receptor-1 (PAR-1) has recently been shown to aggravate the development of experimental diabetic nephropathy. PAR-1 deficient mice develop less albuminuria and glomerular lesions and PAR-1 stimulation induces proliferation and fibronectin production in mesangial cells in vitro . Vorapaxar is a clinically available PAR-1 inhibitor which is currently used for secondary prevention of ischemic events. The aim of this study was to investigate in a preclinical setting whether vorapaxar treatment may be a novel strategy to reduce diabetes-induced kidney damage. While control treated diabetic mice developed significant albuminuria, mesangial expansion and glomerular fibronectin deposition, diabetic mice on vorapaxar treatment did not show any signs of kidney damage despite having similar levels of hyperglycemia. These data show that PAR-1 inhibition by vorapaxar prevents the development of diabetic nephropathy in this preclinical animal model for type I diabetes and pinpoint PAR-1 as a novel therapeutic target to pursue in the setting of diabetic nephropathy. 22 C57Bl/6 mice were made diabetic using multiple low-dose streptozotocin injections (50 mg/kg) and 22 littermates served as non-diabetic controls. Four weeks after the induction of diabetes, 11 mice of each group were assigned to control or vorapaxar treatment. Mice were sacrificed after 20 weeks of treatment and kidney damage was evaluated.

Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects.

Directory of Open Access Journals (Sweden)

Keisuke Ishizawa

Full Text Available Diabetic nephropathy (DN is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice, NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.

The Relationship between Metformin and Cancer in Patients with Type 2 Diabetes

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Hyun Hee Chung

2013-04-01

Full Text Available BackgroundRecently, several studies reported that the cancer incidence in type 2 diabetes patients is higher than in the general population. Although a number of risks are shared between cancer and diabetes patients, there have been few studies of its correlation. We evaluated the influences of several factors including low density lipoprotein cholesterol (LDL-C, albuminuria and use of metformin on the risk of cancer in patients with type 2 diabetes.MethodsWe enrolled 1,320 patients with at least 5 years of follow-up and 73 patients were diagnosed with cancer during this period. The associations of the risk factors with cancer incidence were evaluated by multiple regression analysis. The subjects were placed into two subgroups based on metformin dosage (<1,000 mg/day, ≥1,000 mg/day and we compared cancer incidence using analysis of covariance.ResultsLDL-C and albuminuria were not significantly correlated with cancer risk. In contrast, metformin showed a reverse correlation with cancer risk (P=0.006; relative risk, 0.574. In the metformin nonadministration group, smoking, male gender, and high triglyceride levels tended to be contributing factors without statistical significance. Cancer occurence was lower in the low dose metformin group (less than 1,000 mg/day (P=0.00.ConclusionThese results suggest that the administration of low dose metformin in patients with type 2 diabetes may be associated with a reduced risk of cancer.

Ste20-like Kinase, SLK, a Novel Mediator of Podocyte Integrity.

Science.gov (United States)

Cybulsky, Andrey V; Papillon, Joan; Guillemette, Julie; Belkina, Natalya; Patino-Lopez, Genaro; Torban, Elena

2017-11-29

SLK is essential for embryonic development, and may play a key role in wound healing, tumor growth and metastasis. Expression and activation of SLK is increased in kidney development and during recovery from ischemic acute kidney injury. Overexpression of SLK in glomerular epithelial cells/podocytes in vivo induces injury and proteinuria. Conversely, reduced SLK expression leads to abnormalities in cell adhesion, spreading, and motility. Tight regulation of SLK expression thus may be critical for normal renal structure and function. We produced podocyte-specific SLK knockout mice to address the functional role of SLK in podocytes. Mice with podocyte-specific deletion of SLK showed reduced glomerular SLK expression and activity, compared with control. Podocyte-specific deletion of SLK resulted in albuminuria at 4-5 months of age in male mice, and 8-9 months in female mice, which persisted for up to 13 months. At 11-12 months, knockout mice showed ultrastructural changes, including focal foot process effacement and microvillous transformation of podocyte plasma membranes. Mean foot process width was ~2-fold greater in knockout, compared with control. Podocyte number was reduced by 35% in knockout mice, compared with control, and expression of nephrin, synaptopodin and podocalyxin was reduced in knockout mice by 20-30%. In summary, podocyte-specific deletion of SLK leads to albuminuria, loss of podocytes and morphologic evidence of podocyte injury. Thus, SLK is essential to the maintenance of podocyte integrity as mice age.

Effect of Pentoxifylline on Microalbuminuria in Diabetic Patients: A Randomized Controlled Trial

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Shahrzad Shahidi

2015-01-01

Full Text Available Background. Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties. Human studies have proved its antiproteinuric effect in patients with glomerular diseases, but this study was designed to assess the effects of add-on pentoxifylline to available treatment on reduction of microalbuminuria in diabetic patients without glomerular diseases. Methods. In a double-blind placebo-controlled, randomized study we evaluated the influence of pentoxifylline on microalbuminuria in type 2 diabetic patients. 40 diabetic patients with estimated glomerular filtration rate (eGFR of more than 60 mL/min/1.73 m2 in eight weeks and microalbuminuria were randomized to two groups which will receive pentoxifylline 1200 mg/day or placebo added to regular medications for 6 months. albuminuria; eGFR was evaluated at three- and six-month follow-up period. Results. Baseline characteristics were similar between the two groups. At six months, the mean estimated GFR and albuminuria were not different between two groups at 3- and 6-month follow-up. Trend of albumin to creatinine ratio, systolic and diastolic blood pressure, and eGFR in both groups were decreased, but no significant differences were noted between two groups (P value > 0.05. Conclusion. Pentoxifylline has not a significant additive antimicroalbuminuric effect compared with placebo in patients with type 2 diabetes with early stage of kidney disease; however, further clinical investigations are necessary to be done.

Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

Science.gov (United States)

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.

2011-01-01

Background 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. Methods 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. Results 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. Conclusion These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN. PMID:21454968

The Micral-Test as a screening tool to detect micro- albuminuria in ...

African Journals Online (AJOL)

include the 24-hour urine albumin test, the overnight urine albumin test (these are timed .... social strata, both accounting for >80% of either HbSS subjects or. HbAA controls. ... 24-hour urine as the reference standard on the receiver operating.

Podocyte changes upon induction of albuminuria in Thy-1.1 transgenic mice.

NARCIS (Netherlands)

Smeets, B.; Dijkman, H.B.P.M.; Loeke, N. te; Son, J.P.H.F. van; Steenbergen, E.; Assmann, K.J.M.; Wetzels, J.F.M.; Groenen, P.J.T.A.

2003-01-01

BACKGROUND: Thy-1.1 transgenic mice, characterized by ectopic expression of the Thy-1.1 protein on podocytes, spontaneously develop proteinuria and focal glomerulosclerosis (FGS). Injection of a monoclonal antibody (mAb) directed against the Thy-1.1 protein in young transgenic mice induces a massive

Consenso Delphi sobre el diagnóstico y manejo de la dislipidemia en pacientes con enfermedad renal crónica: análisis post-hoc del estudio DIANA

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Aleix Cases Amenós

2016-11-01

Conclusiones: El consenso en analizar el perfil lipídico en los pacientes con ERC indica el reconocimiento del alto riesgo cardiovascular de esta enfermedad. La ausencia de acuerdo en considerar la función renal o la albuminuria, tanto en la elección de la estatina como durante el seguimiento, indica un conocimiento limitado de las diferencias entre estatinas en relación con la ERC, por lo que sería deseable disponer de una guía/documento de consenso sobre uso de estatinas en la ERC.

Impact of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy

DEFF Research Database (Denmark)

Nielsen, F S; Rossing, P; Gall, M A

1994-01-01

. Eight patients dropped out, and the results for the remaining 35 patients (16 lisinopril and 19 atenolol) are presented. Diuretics were required in 10 of 16 lisinopril patients and 12 of 19 atenolol patients. The following variables were measured: 24-hour ambulatory BP (Takeda TM2420), albuminuria...... (enzyme-linked immunosorbent assay), fractional albumin clearance, and glomerular filtration rate (GFR) ([51Cr]EDTA technique). The average reduction in mean arterial BP during the 12 months was identical in the two groups 12 +/- 2 vs. 11 +/- 1 mmHg in the lisinopril and atenolol group, respectively...

Murine nephrotoxic nephritis as a model of chronic kidney disease

DEFF Research Database (Denmark)

Ougaard, M. K.E.; Kvist, P. H.; Jensen, H. E.

2018-01-01

Using the nonaccelerated murine nephrotoxic nephritis (NTN) as a model of chronic kidney disease (CKD) could provide an easily inducible model that enables a rapid test of treatments. Originally, the NTN model was developed as an acute model of glomerulonephritis, but in this study we evaluate...... progressive mesangial expansion and significant renal fibrosis within three weeks suggesting CKD development. CD1 and C57BL/6 females showed a similar disease progression, but female mice seemed more susceptible to NTS compared to male mice. The presence of albuminuria, GFR decline, mesangial expansion...

Comparison of overnight, morning and 24-hour urine collections in the assessment of diabetic microalbuminuria

DEFF Research Database (Denmark)

Eshøj, O; Feldt-Rasmussen, B; Larsen, M L

1987-01-01

With the aim of comparing different urine collection periods in the assessment of micro-albuminuria, urinary albumin excretion rates (AERs) were measured in samples from 24 h, overnight, and morning urine collections in 54 patients aged 17 to 62 years with insulin-dependent diabetes mellitus...... overnight and morning urine samples. These values were slightly improved by relating AER to the excretion of creatinine and it is concluded that overnight as well as morning urine collections can be used when diagnosing microalbuminuria in insulin-dependent diabetics. Furthermore the results show...

Diagnosis of diabetic kidney disease

DEFF Research Database (Denmark)

Persson, Frederik; Rossing, Peter

2018-01-01

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...... 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...

Telemedicine compared with standard care in type 2 diabetes mellitus

DEFF Research Database (Denmark)

Rasmussen, O. W.

2015-01-01

Objectives: For patients with T2DM does telemedicine, compared with standard care, provide equivalent clinical outcomes? Methods: Forty patients with type 2 diabetes mellitus allocated from October 2011 until July 2012 randomized to either treatment at home by video conferences only or the standard...... outpatient treatment. Primary outcomes were HbA1c and blood glucose levels and secondary outcomes were 24-h blood pressure, cholesterol levels, and albuminuria. The videotelephone was installed and serviced by the telephone company, TDC, Denmark, as a broadband solution. Results: The improvements in the two...

The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity

Directory of Open Access Journals (Sweden)

Lucia Pacifico

2016-07-01

Full Text Available The association between nonalcoholic fatty liver disease (NAFLD and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m2. Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m2 was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001. The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001. Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16–5.57; p < 0.05 independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease.

Relationship between serum bilirubin concentrations and diabetic nephropathy in Shanghai Han's patients with type 1 diabetes mellitus.

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Li, Xu; Zhang, Lei; Chen, Haibing; Guo, Kaifeng; Yu, Haoyong; Zhou, Jian; Li, Ming; Li, Qing; Li, Lianxi; Yin, Jun; Liu, Fang; Bao, Yuqian; Han, Junfeng; Jia, Weiping

2017-03-31

Recent studies highlight a negative association between total bilirubin concentrations and albuminuria in patients with type 2 diabetes mellitus. Our study evaluated the relationship between bilirubin concentrations and the prevalence of diabetic nephropathy (DN) in Chinese patients with type 1 diabetes mellitus (T1DM). A total of 258 patients with T1DM were recruited and bilirubin concentrations were compared between patients with or without diabetic nephropathy. Multiple stepwise regression analysis was used to examine the relationship between bilirubin concentrations and 24 h urinary microalbumin. Binary logistic regression analysis was performed to assess independent risk factors for diabetic nephropathy. Participants were divided into four groups according to the quartile of total bilirubin concentrations (Q1, 0.20-0.60; Q2, 0.60-0.80; Q3, 0.80-1.00; Q4, 1.00-1.90 mg/dL) and the chi-square test was used to compare the prevalence of DN in patients with T1DM. The median bilirubin level was 0.56 (interquartile: 0.43-0.68 mg/dL) in the DN group, significantly lower than in the non-DN group (0.70 [interquartile: 0.58-0.89 mg/dL], P 1). Spearman's correlational analysis showed bilirubin concentrations were inversely correlated with 24 h urinary microalbumin (r = -0.13, P 1.90% to 2.00%. High bilirubin concentrations are independently and negatively associated with albuminuria and the prevalence of DN in patients with T1DM.

Association between urinary albumin excretion and intraocular pressure in type 2 diabetic patients without renal impairment.

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Jin A Choi

Full Text Available BACKGROUND: To assess the relationship between urinary albumin excretion and intraocular pressure (IOP in type 2 diabetes patients without renal impairment. METHODS: We explored the effects of albuminuria on high IOP in 402 non-glaucomatous type 2 diabetes without renal impairment who participated in the 2011 Korean National Health and Nutrition Examination Survey (KNHANES. Multiple logistic regression analysis was used to assess the relationship between log-transformed albumin/creatinine ratio (ACR tertiles and an IOP of ≥ 18 mmHg after adjusting for age, gender, hypertension, body mass index, triglycerides, area of residence, and education level. RESULTS: Subjects with a high IOP ≥ 18 mmHg were more likely to be current smokers (P = 0.038, heavy drinkers (P = 0.006, and to have high systolic blood pressure (P = 0.016, triglycerides (P = 0.008, and a higher log-transformed ACR (P = 0.022.In multivariate regression analysis, ACR tertile was associated with the prevalence of high IOP significantly (P = 0.022. The associations between ACR tertiles and high IOP were significant in overweight patients and those with abdominal obesity (P = 0.003 and 0.003, respectively. In contrast, there were no associations in the subgroup of patients who were not overweight and those without abdominal obesity (P = 0.291 and 0.561, respectively. CONCLUSIONS: Urinary albumin excretion is associated with high IOP in the type 2 diabetes population without renal insufficiency. The effect of the albuminuria on IOP was evident in a subgroup of patients with components of metabolic syndrome.

Nephroprotective effect of heparanase in experimental nephrotic syndrome.

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Suheir Assady

Full Text Available Heparanase, an endoglycosidase that cleaves heparan sulfate (HS, is involved in various biologic processes. Recently, an association between heparanase and glomerular injury was suggested. The present study examines the involvement of heparanase in the pathogenesis of Adriamycin-induced nephrotic syndrome (ADR-NS in a mouse model.BALB/c wild-type (wt mice and heparanase overexpressing transgenic mice (hpa-TG were tail-vein injected with either Adriamycin (ADR, 10 mg/kg or vehicle. Albuminuria was investigated at days 0, 7, and 14 thereafter. Mice were sacrificed at day 15, and kidneys were harvested for various analyses: structure and ultrastructure alterations, podocyte proteins expression, and heparanase enzymatic activity.ADR-injected wt mice developed severe albuminuria, while ADR-hpa-TG mice showed only a mild elevation in urinary albumin excretion. In parallel, light microscopy of stained cross sections of kidneys from ADR-injected wt mice, but not hpa-TG mice, showed mild to severe glomerular and tubular damage. Western blot and immunofluorescence analyses revealed significant reduction in nephrin and podocin protein expression in ADR-wt mice, but not in ADR-hpa-TG mice. These results were substantiated by electron-microscopy findings showing massive foot process effacement in injected ADR-wt mice, in contrast to largely preserved integrity of podocyte architecture in ADR-hpa-TG mice.Our results suggest that heparanase may play a nephroprotective role in ADR-NS, most likely independently of HS degradation. Moreover, hpa-TG mice comprise an invaluable in vivo platform to investigate the interplay between heparanase and glomerular injury.

Effects of aging and uninephrectomy on renal changes in Tsukuba hypertensive mice.

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Inui, Yosuke; Mochida, Hideki; Yamairi, Fumiko; Okada, Miyoko; Ishida, Junji; Fukamizu, Akiyoshi; Arakawa, Kenji

2013-05-01

Renal dysfunction is accelerated by various factors such as hypertension, aging and diabetes. Glomerular hyper-filtration, considered one of the major risk factors leading to diabetic nephropathy, is often encountered in diabetic patients. However, the interrelationship of these risk factors during the course and development of renal dysfunction has not been fully elucidated. In this study, the effects of aging and uninephrectomy (UNx)-induced hyperfiltration on renal changes were investigated in Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes. In THM, the urinary albumin/creatinine (Alb/Cr) ratio was elevated with age without a concomitant increase in the plasma Cr concentration. Moreover, the urinary neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr) ratio, the renal monocyte chemoattractant protein-1 (MCP-1) mRNA expression and the renal collagen type I α 2 (COL1A2) mRNA expression were also increased with age. Age-related albuminuria in THM is likely caused by renal tubular damage, enhanced inflammatory response and tubulointerstitial fibrosis. Furthermore, following UNx, the urinary Alb/Cr ratio and the plasma Cr concentration were increased in THM. The urinary NGAL/Cr ratio and the renal MCP-1 and COL1A2 mRNA expression were not affected by UNx. These results suggested that UNx-induced albuminuria in THM was caused by glomerular dysfunction, rather than renal tubular injury. In conclusion, this study demonstrated for the first time the effects of aging and UNx on renal changes in THM. These findings strongly reinforce the significance of applying a diversity of therapeutic approaches to the management of renal dysfunction.

The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus.

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Zhuang, Langen; Li, Ming; Yu, Changhua; Li, Can; Zhao, Mingming; Lu, Ming; Zheng, Taishan; Zhang, Rong; Zhao, Weijing; Bao, Yuqian; Xiang, Kunsan; Jia, Weiping; Wang, Niansong; Liu, Limei

2014-02-01

The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case-control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.

Renal structure and function evaluation of rats from dams that received increased sodium intake during pregnancy and lactation submitted or not to 5/6 nephrectomy.

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Marin, Evelyn Cristina Santana; Balbi, Ana Paula Coelho; Francescato, Heloísa Della Coletta; Alves da Silva, Cleonice Giovanini; Costa, Roberto Silva; Coimbra, Terezila M

2008-01-01

Adult rats submitted to perinatal salt overload presented renin-angiotensin system (RAS) functional disturbances. The RAS contributes to the renal development and renal damage in a 5/6 nephrectomy model. The aim of the present study was to analyze the renal structure and function of offspring from dams that received a high-salt intake during pregnancy and lactation. We also evaluated the influence of the prenatal high-salt intake on the evolution of 5/6 nephrectomy in adult rats. A total of 111 sixty-day-old rat pups from dams that received saline or water during pregnancy and lactation were submitted to 5/6 nephrectomy (nephrectomized) or to a sham operation (sham). The animals were killed 120 days after surgery, and the kidneys were removed for immunohistochemical and histological analysis. Systolic blood pressure (SBP), albuminuria, and glomerular filtration rate (GFR) were evaluated. Increased SBP, albuminuria, and decreased GFR were observed in the rats from dams submitted to high-sodium intake before surgery. However, there was no difference in these parameters between the groups after the 5/6 nephrectomy. The scores for tubulointerstitial lesions and glomerulosclerosis were higher in the rats from the sham saline group compared to the same age control rats, but there was no difference in the histological findings between the groups of nephrectomized rats. In conclusion, our data showed that the high-salt intake during pregnancy and lactation in rats leads to structural changes in the kidney of adult offspring. However, the progression of the renal lesions after 5/6 nephrectomy was similar in both groups.

Urinary Analysis of Fluid Retention in the General Population: A Cross-Sectional Study.

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Robert G Hahn

Full Text Available Renal conservation (retention of fluid might affect the outcome of hospital care and can be indicated by increased urinary concentrations of metabolic waste products. We obtained a reference material for further studies by exploring the prevalence of fluid retention in a healthy population.Spot urine sampling was performed in 300 healthy hospital workers. A previously validated algorithm summarized the urine-specific gravity, osmolality, creatinine, and color to a fluid retention index (FRI, where 4.0 is the cut-off for fluid retention consistent with dehydration. In 50 of the volunteers, we also studied the relationships between FRI, plasma osmolality, and water-retaining hormones.The cut-off for fluid retention (FRI ≥ 4.0 was reached by 38% of the population. No correlation was found between the FRI and the time of the day of urine sample collection, and the FRI was only marginally correlated with the time period spent without fluid intake. Volunteers with fluid retention were younger, generally men, and more often had albuminuria (88% vs. 34%, P < 0.001. Plasma osmolality and plasma sodium were somewhat higher in those with a high FRI (mean 294.8 vs. 293.4 mosmol/kg and 140.3 vs. 139.9 mmol/l. Plasma vasopressin was consistently below the limit of detection, and the plasma cortisol, aldosterone, and renin concentrations were similar in subjects with a high or low FRI. The very highest FRI values (≥ 5.0, N = 61 were always accompanied by albuminuria.Fluid retention consistent with moderate dehydration is common in healthy staff working in a Swedish hospital.

Use of Readily Accessible Inflammatory Markers to Predict Diabetic Kidney Disease

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Lauren Winter

2018-05-01

Full Text Available Diabetic kidney disease is a common complication of type 1 and type 2 diabetes and is the primary cause of end-stage renal disease in developed countries. Early detection of diabetic kidney disease will facilitate early intervention aimed at reducing the rate of progression to end-stage renal disease. Diabetic kidney disease has been traditionally classified based on the presence of albuminuria. More recently estimated glomerular filtration rate has also been incorporated into the staging of diabetic kidney disease. While albuminuric diabetic kidney disease is well described, the phenotype of non-albuminuric diabetic kidney disease is now widely accepted. An association between markers of inflammation and diabetic kidney disease has previously been demonstrated. Effector molecules of the innate immune system including C-reactive protein, interleukin-6, and tumor necrosis factor-α are increased in patients with diabetic kidney disease. Furthermore, renal infiltration of neutrophils, macrophages, and lymphocytes are observed in renal biopsies of patients with diabetic kidney disease. Similarly high serum neutrophil and low serum lymphocyte counts have been shown to be associated with diabetic kidney disease. The neutrophil–lymphocyte ratio is considered a robust measure of systemic inflammation and is associated with the presence of inflammatory conditions including the metabolic syndrome and insulin resistance. Cross-sectional studies have demonstrated a link between high levels of the above inflammatory biomarkers and diabetic kidney disease. Further longitudinal studies will be required to determine if these readily available inflammatory biomarkers can accurately predict the presence and prognosis of diabetic kidney disease, above and beyond albuminuria, and estimated glomerular filtration rate.

The Expression of miR-192 and Its Significance in Diabetic Nephropathy Patients with Different Urine Albumin Creatinine Ratio

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Xiaoyu Ma

2016-01-01

Full Text Available Objective. To investigate the expression of miR-192 and its significance in diabetic nephropathy (DN patients. Methods. 464 patients with type 2 diabetes mellitus (T2DM were divided into normal albuminuria group (NA, n=157, microalbuminuria group (MA, n=159, and large amount of albuminuria group (LA, n=148. 127 healthy persons were selected as the control group (NC, n=127. The serum miR-192 levels were detected by Real-Time PCR and transforming growth factor-β1 (TGF-β1 and fibronectin (FN were detected by enzyme-linked immunosorbent assay. The relationships among these parameters were analyzed by Pearson correlation analysis and multiple linear regression analysis. Results. The miR-192 in the LA group was significantly lower than other groups, which was lower in the MA group than in the NA group (P<0.01. The TGF-β1 and FN in the LA group were significantly higher than other groups, which were higher in the MA group than in the NA group (P<0.01. The expression of miR-192 was negatively correlated with TGF-β1, FN, and Ln (UACR and miR-192, TGF-β1, and FN were independent relevant factors affecting Ln (UACR in T2DM (P<0.01. Conclusions. These findings indicate that the levels of miR-192 were lower accompanied by the decrease of urine albumin creatinine ratio (UACR and the association between miR-192 and nephritic fibrosis in DN.

The effects of atrasentan on urinary metabolites in patients with type 2 diabetes and nephropathy

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Pena, Michelle J; de Zeeuw, Dick; Andress, Dennis

2018-01-01

We assessed the effect of atrasentan therapy on a pre-specified panel of 13 urinary metabolites known to reflect mitochondrial function in patients with diabetic kidney disease. This post-hoc analysis was performed using urine samples collected during the RADAR study which was a randomized, double......-blind, placebo-controlled trial that tested the effects of atrasentan on albuminuria reduction in patients with type 2 diabetes and nephropathy. At baseline, four of the 13 metabolites, quantified by gas-chromatography mass spectrometry, were below detectable levels, and six were reduced in patients with e...... diabetes, nephropathy, and eGFR

Telemedicine is cost effective compared with standard care. A randomized controlled project in Type 2 diabetes mellitus in an outpatient clinic

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Rasmussen, Ole Winther; Lauszus, Finn Friis; Lokke, Mette

2017-01-01

the total cost at a reasonable level. Objectives: We evaluated the economic and short-time health effect of two different ways of outpatient treatment in patients with type 2 diabetes (T2DM). A health economist calculated the total cost of replacing the standard care with telemedicine. Methods: Forty......, cholesterol levels and albuminuria were measured. The telephone company, TDC, Denmark delivered and serviced a TandBerg E20 video telephone to the patients in the telemedicine group. The economic analysis was performed with a Danish hospital payer’s cost perspective. Cost data were based on the measured time...

Abnormal albuminuria and blood pressure rise in incipient diabetic nephropathy induced by exercise

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Christensen, Cramer

1984-01-01

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...... diastolic blood pressure was elevated [92.1 mm Hg +/- 6.0 (mean +/- SD)] compared to D2 (80.9 mm Hg +/- 4.8, 2P = 0.003%) and C (79.5 mm Hg +/- 12.4, 2P = 1.2%). Baseline systolic blood pressure was not significantly different in the three groups, but systolic blood pressure was more elevated at 600 kpm...... blood pressure and maximal exercise induced albumin excretion was demonstrable in D3.(ABSTRACT TRUNCATED AT 250 WORDS)...

Antibody mediated albuminuria and focal segmental glomerulosclerosis in Thy- 1.1 transgenic mice.

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Smeets, B.

2006-01-01

Focal segmental glomerulosclerosis (FSGS) is the hallmark of the glomerular lesion that is characteristically observed in failing kidneys. FSGS is one of the leading causes of renal insufficiency. In this thesis the Thy-1.1 transgenic mouse model was used as a model of FSGS. We particularly

Abnormal albuminuria and blood pressure rise in incipient diabetic nephropathy induced by exercise

DEFF Research Database (Denmark)

Christensen, Cramer

1984-01-01

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...

Prediction of cardiovascular and total mortality in Chinese type 2 diabetic patients by the WHO definition for the metabolic syndrome.

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Ko, G T-C; So, W-Y; Chan, N N; Chan, W-B; Tong, P C-Y; Li, J; Yeung, V; Chow, C-C; Ozaki, R; Ma, R C-W; Cockram, C S; Chan, J C-N

2006-01-01

The aim of this study is to investigate the prevalence of metabolic syndrome (MES) in type 2 diabetic patients and the predictive values of the World Health Organization (WHO) and National Cholesterol Education Programme (NCEP) definitions and the individual components of the MES on total and cardiovascular mortality. A prospective analysis of a consecutive cohort of 5202 Chinese type 2 diabetic patients recruited between July 1994 and April 2001. The prevalence of the MES was 49.2-58.1% depending on the use of various criteria. There were 189 deaths (men: 100 and women: 89) in these 5205 patients during a median (interquartile range) follow-up period of 2.1 (0.3-3.6 years). Of these, 164 (87%) were classified as cardiovascular deaths. Using the NCEP criterion, patients with MES had a death rate similar to those without (3.51 vs. 3.85%). By contrast, based on the WHO criteria, patients with MES had a higher mortality rate than those without (4.3 vs. 2.4%, p = 0.002). Compared to patients with neither NCEP- nor WHO-defined MES, only the group with MES defined by the WHO, but not NCEP, criterion had significantly higher mortality rate (2.6 vs. 6.8%, p hypertension, low BMI and albuminuria were the key predictors for these adverse events. In Chinese type 2 diabetic patients, the WHO criterion has a better discriminative power over the NCEP criterion for predicting death. Among the various components of the MES defined either by WHO or NCEP, hypertension, albuminuria and low BMI were the main predictors of cardiovascular and total mortality.

Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

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Ma, Frank Y; Han, Yingjie; Nikolic-Paterson, David J; Kolkhof, Peter; Tesch, Greg H

2015-01-01

Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

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Frank Y Ma

Full Text Available Steroidal mineralocorticoid receptor antagonists (MRAs are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis.Accelerated anti-glomerular basement membrane (GBM glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid from day 0 until being killed on day 15 of disease. Mice were examined for renal injury.Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ and profibrotic molecules (collagen I, fibronectin. In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction.The non-steroidal MRA (BR-4628 provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

Hyperhomocysteinaemia, vascular related pregnancy complications and the response to vitamin supplementation in pregnant women of Pakistan

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Qureshi, S.B.; Ahmad, M.; Qureshi, P.M.A.; Memon, A.; Qazi, R.A.

2010-01-01

To elaborate the relationship between serum homocysteine (hcy) levels and vascular related pregnancy complications in pregnant women as well as to assess the homocysteine lowering effects of folate, vitamin B12 and B6. The secondary objectives were to establish a link between serum homocysteine levels and maternal age, parity, gestational age, foetal birth weight, mean arterial pressure and albuminuria. Methods: A total of 332 pregnant women (gestational age: >24 weeks) attending Liaquat University Hospital Hyderabad, Pakistan, were enrolled. Of these 112 were healthy normal pregnant women; 61 pregnant women had pre-eclampsia, 49 with eclampsia and 110 with placental abruption. A cohort of 30 patients with elevated hcy levels (>8.2 mu mol/liter), were given folate, vitamin B12 and B6 as supplements for 6 weeks. Fasting blood samples were collected, centrifuged and stored at 2 to 8 deg. C. Hcy levels were determined by IMx immunoassay. Results: Higher serum hcy levels, higher mean arterial blood pressure (MAP), pre-term deliveries and low foetal birth weights were noted in women with pregnancies complicated by pre-eclampsia and eclampsia as compared to control and those with placental abruption. Significant hcy lowering effects of folate, vitamin B12 and B6 supplementation were observed. Significant and positive correlation was found between hhcy and MAP (r = 0.001; p<0.001), albuminuria (r = 0.004; p< 0.01) and low birth weights (r= 0.05; p<0.06). Conclusion: Higher hcy levels in pregnancies complicated by pre-eclampsia and eclampsia have been noted. Data support the hypothesis that folate, vitamin B12 and B6 lower hcy levels in hyperhomocysteinaemic women. (author)

Community-based study on CKD subjects and the associated risk factors.

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Chen, Nan; Wang, Weiming; Huang, Yanping; Shen, Pingyan; Pei, Daoling; Yu, Haijin; Shi, Hao; Zhang, Qianying; Xu, Jing; Lv, Yilun; Fan, Qishi

2009-07-01

The study was performed to investigate the prevalence, awareness and the risk factors of chronic kidney disease (CKD) in the community population in Shanghai, China. A total of 2596 residents were randomly recruited from the community population in Shanghai, China. All were screened for albuminuria, haematuria, morning spot urine albumin-to-creatinine ratio and renal function. Serum creatinine, uric acid, cholesterol, triglyceride and haemoglobin were assessed. A simplified MDRD equation was used to estimate the glomerular filtration rate (eGFR). All studied subjects were screened by kidney ultrasound. Haematuria, if present in the morning spot urine dipstick test, was confirmed by microscopy. The associations among the demographic characteristics, health characteristics and indicators of kidney damage were examined. Two thousand five hundred and fifty-four residents (n = 2554), after giving informed consent and with complete data, were entered into this study. Albuminuria and haematuria were detected in 6.3% and 1.2% of all the studied subjects, respectively, whereas decreased kidney function was found in 5.8% of all studied subjects. Approximately 11.8% of subjects had at least one indicator of kidney damage. The rate of awareness of CKD was 8.2%. The logistic regression model showed that age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis each contributed to the development of CKD. This is the first Shanghai community-based epidemiological study data on Chinese CKD patients. The prevalence of CKD in the community population in Shanghai is 11.8%, and the rate of awareness of CKD is 8.2%. All the factors including age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis are positively correlated with the development of CKD in our studied subjects.

Deficiency of the Angiotensinase Aminopeptidase A Increases Susceptibility to Glomerular Injury.

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Velez, Juan Carlos Q; Arif, Ehtesham; Rodgers, Jessalyn; Hicks, Megan P; Arthur, John M; Nihalani, Deepak; Bruner, Evelyn T; Budisavljevic, Milos N; Atkinson, Carl; Fitzgibbon, Wayne R; Janech, Michael G

2017-07-01

Aminopeptidase A (APA) is expressed in glomerular podocytes and tubular epithelia and metabolizes angiotensin II (AngII), a peptide known to promote glomerulosclerosis. In this study, we tested whether APA expression changes in response to progressive nephron loss or whether APA exerts a protective role against glomerular damage and during AngII-mediated hypertensive kidney injury. At advanced stages of FSGS, fawn-hooded hypertensive rat kidneys exhibited distinctly increased APA staining in areas of intact glomerular capillary loops. Moreover, BALB/c APA-knockout (KO) mice injected with a nephrotoxic serum showed persistent glomerular hyalinosis and albuminuria 96 hours after injection, whereas wild-type controls achieved virtually full recovery. We then tested the effect of 4-week infusion of AngII (400 ng/kg per minute) in APA-KO and wild-type mice. Although we observed no significant difference in achieved systolic BP, AngII-treated APA-KO mice developed a significant rise in albuminuria not observed in AngII-treated wild-type mice along with increased segmental and global sclerosis and/or collapse of juxtamedullary glomeruli, microcystic tubular dilation, and tubulointerstitial fibrosis. In parallel, AngII treatment significantly increased the kidney AngII content and attenuated the expression of podocyte nephrin in APA-KO mice but not in wild-type controls. These data show that deficiency of APA increases susceptibility to glomerular injury in BALB/c mice. The augmented AngII-mediated kidney injury observed in association with increased intrarenal AngII accumulation in the absence of APA suggests a protective metabolizing role of APA in AngII-mediated glomerular diseases. Copyright © 2017 by the American Society of Nephrology.

Antioxidant agents for delaying diabetic kidney disease progression: A systematic review and meta-analysis.

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Davide Bolignano

Full Text Available Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD. We aimed at collecting all available information on possible benefits of chronic antioxidant supplementations on DKD progression.Systematic review and meta-analysis.Adults with DKD (either secondary to type 1 or 2 diabetes mellitus.Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs or quasi-RCTs without language or follow-up restriction.Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone alone or in combination.Primary outcome was progression to end-stage kidney disease (ESKD. Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function.From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16 but had apparently no tangible effects on renal function (GFR (3 studies, 85 participants; MD -0.12 ml/min/1.73m2; 95% CI -0.06, 0.01. Evidence of benefits on the other outcomes of interest was inconclusive or lacking.Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD. High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy.In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression.

Environmental exposure to cadmium and renal function of elderly women living in cadmium-polluted areas of the Federal Republic of Germany

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Ewers, U.; Brockhaus, A.; Dolgner, R.; Freier, I.; Jermann, E.; Bernard, A.; Stiller-Winkler, R.; Hahn, R.; Manojlovic, N.

1985-01-01

An epidemiological study was performed to assess whether environmental pollution by cadmium as found in cadmium-polluted areas of the Federal Republic of Germany is associated with an increased prevalence of biological signs of kidney dysfunction in population groups non-occupationally exposed to heavy metals. The study was run in two industrial areas known to be highly contaminated by cadmium, lead and other heavy metals, viz. Stolberg and Duisburg. Duesseldorf was selected as a reference area. As a study population the authors selected 65- and 66-year-old women (n = 286) who had spent the major part of their lives in one of these areas. The average cadmium levels in blood (CdB) and urine (CdU) revealed significant differences in exposure to cadmium in the order Stolberg greater than Duisburg greater than Duesseldorf. Serum creatinine levels were, on average, significantly higher in the Stolberg group than in the Duisburg and Duesseldorf groups. However, with respect to the urinary excretion of low molecular weight proteins (beta 2-microglobulin, retinol-binding protein), albuminuria, total proteinuria, aminoaciduria, phosphaturia and some other biological findings, no significant differences between the study populations were noted. Similarly, the prevalence of clinically-confirmed hypertension as well as the relative frequency of hypertensive subjects (systolic greater than or equal to 160 and/or diastolic greater than or equal to 95 mm Hg) did not differ significantly among the three study groups. There was no exposure-response relationship between CdU and tubular proteinuria in the range of the CdU-levels found (0.1 to 5.2 micrograms/g creatinine). However, albuminuria tended to be increased at CdU levels greater than 2 micrograms/g creatinine.

Association between sleep duration and urinary albumin excretion in patients with type 2 diabetes: the Fukuoka diabetes registry.

Directory of Open Access Journals (Sweden)

Toshiaki Ohkuma

Full Text Available OBJECTIVE: Few studies have so far investigated the impact of sleep duration on chronic kidney disease in diabetic patients. The objective of the present study was to examine the relationship between sleep duration and albuminuria in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 4,870 Japanese type 2 diabetic patients ≥20 years of age were divided into six groups according to self-reported sleep duration: less than 4.5 hours, 4.5-5.4 hours, 5.5-6.4 hours, 6.5-7.4 hours, 7.5-8.4 hours and more than 8.5 hours. The association between sleep duration and urinary albumin-creatinine ratio (UACR was examined cross-sectionally. RESULTS: Both short and long sleep durations were significantly associated with higher UACR levels and higher proportions of patients with albuminuria (≥30 mg/g and macroalbuminuria (≥300 mg/g compared with a sleep duration of 6.5-7.4 hours (P for quadratic trend <0.001. A U-shaped association between sleep duration and UACR remained significant even after adjustment for potential confounders, including age, sex, duration of diabetes, current smoking habits, former smoking habits, current drinking habits, regular exercise habits, total energy intake, total protein intake, hypnotic use and estimated glomerular filtration rate. Furthermore, the association remained substantially unchanged after additional adjustment for body mass index, hemoglobin A1c, systolic blood pressure, renin-angiotensin system inhibitor use and depressive symptoms. CONCLUSIONS: Our findings suggest that sleep duration has a U-shaped association with the UACR levels in type 2 diabetic patients, independent of potential confounders.

Albumin stimulates renal tubular inflammation through an HSP70-TLR4 axis in mice with early diabetic nephropathy

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Jheng, Huei-Fen; Tsai, Pei-Jane; Chuang, Yi-Lun; Shen, Yi-Ting; Tai, Ting-An; Chen, Wen-Chung; Chou, Chuan-Kai; Ho, Li-Chun; Tang, Ming-Jer; Lai, Kuei-Tai A.; Sung, Junne-Ming; Tsai, Yau-Sheng

2015-01-01

ABSTRACT Increased urinary albumin excretion is not simply an aftermath of glomerular injury, but is also involved in the progression of diabetic nephropathy (DN). Whereas Toll-like receptors (TLRs) are incriminated in the renal inflammation of DN, whether and how albumin is involved in the TLR-related renal inflammatory response remains to be clarified. Here, we showed that both TLR2 and TLR4, one of their putative endogenous ligands [heat shock protein 70 (HSP70)] and nuclear factor-κB promoter activity were markedly elevated in the kidneys of diabetic mice. A deficiency of TLR4 but not of TLR2 alleviated albuminuria, tubulointerstitial fibrosis and inflammation induced by diabetes. The protection against renal injury in diabetic Tlr4−/− mice was associated with reduced tubular injuries and preserved cubilin levels, rather than amelioration of glomerular lesions. In vitro studies revealed that albumin, a stronger inducer than high glucose (HG), induced the release of HSP70 from proximal tubular cells. HSP70 blockade ameliorated albumin-induced inflammatory mediators. HSP70 triggered the production of inflammatory mediators in a TLR4-dependent manner. Moreover, HSP70 inhibition in vivo ameliorated diabetes-induced albuminuria, inflammatory response and tubular injury. Finally, we found that individuals with DN had higher levels of TLR4 and HSP70 in the dilated tubules than non-diabetic controls. Thus, activation of the HSP70-TLR4 axis, stimulated at least in part by albumin, in the tubular cell is a newly identified mechanism associated with induction of tubulointerstitial inflammation and aggravation of pre-existing microalbuminuria in the progression of DN. PMID:26398934

Refractory Hypertension: Determination of Prevalence, Risk Factors and Comorbidities in a Large, Population-Based Cohort

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Calhoun, David A.; Booth, John N.; Oparil, Suzanne; Irvin, Marguerite R.; Shimbo, Daichi; Lackland, Daniel T.; Howard, George; Safford, Monika M.; Muntner, Paul

2014-01-01

Refractory hypertension is an extreme phenotype of antihypertensive treatment failure. Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a large (n=30,239), population-based cohort were evaluated to determine the prevalence of refractory hypertension and associated cardiovascular risk factors and comorbidities. Refractory hypertension was defined as uncontrolled blood pressure (systolic/diastolic ≥ 140/90 mm Hg) on ≥ 5 antihypertensive drug classes. Participants with resistant hypertension (systolic/diastolic ≥140/90 mm Hg on ≥ 3 orhypertensive participants served as comparator groups. Of 14,809 REGARDS participants receiving antihypertensive treatment, 78 (0.5%) had refractory hypertension. The prevalence of refractory hypertension was 3.6% among participants with resistant hypertension(n=2,144) and 41.7% among participants on 5 or more antihypertensive drug classes. Among all hypertensive participants, African American race, male gender, living in the stroke belt or buckle, higher body mass index, lower heart rate, reduced estimated glomerular filtration rate, albuminuria, diabetes and history of stroke and coronary heart disease were associated with refractory hypertension. Compared to resistant hypertension, prevalence ratios for refractory hypertension were increased for African Americans (3.00, 95% CI 1.68 – 5.37) and those with albuminuria (2.22, 95% CI 1.40 – 3.52) and diabetes (2.09, 95% CI 1.32 – 3.31). The median 10-year Framingham risk for coronary heart disease and stroke was higher among participants with refractory hypertension compared to either comparator group. These data indicate that while resistant hypertension is relatively common among treated hypertensive patients, true antihypertensive treatment failure is rare. PMID:24324035

Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design

DEFF Research Database (Denmark)

Parving, Hans-Henrik; Brenner, Barry M; McMurray, John J V

2009-01-01

BACKGROUND: Patients with type 2 diabetes are at increased risk of macro- and microvascular disease, and the presence of albuminuria and/or reduced kidney function further enhances macrovascular risk. Angiotensin-converting-enzyme inhibitors reduce both macro- and microvascular events, yet......, which will include three categories of high-risk patients with type 2 diabetes (aged > or =35 years): those with either urinary albumin/creatinine ratio (UACR) > or =200 mg/g; microalbuminuria (UACR) > or =20 or =30 ... whether dual RAAS blockade with the direct renin inhibitor aliskiren in combination with an ACEi or ARB will reduce major morbidity and mortality in a broad range of high-risk patients with type 2 diabetes....

Childhood sarcoidosis in Denmark 1979-1994: incidence, clinical features and laboratory results at presentation in 48 children

DEFF Research Database (Denmark)

Hoffmann, A L; Milman, N; Byg, K E

2004-01-01

AIM: To describe the incidence, clinical presentation and paraclinical findings in childhood sarcoidosis in Denmark, 1979-1994. METHODS: Patients (n = 5536) with a diagnosis of sarcoidosis were drawn from the nationwide Patient Registry; 81 patients were ... examination (glucose, albumin, haemoglobin) was normal in 96% of the patients; the patient with nephrocalcinosis had albuminuria and haematuria. CONCLUSION: The incidence of sarcoidosis in Danish children is low and increases with age. Sarcoidosis in young children may present clinical features...... that are different from the appearance of those in older children and often constitute a diagnostic challenge. In older children, the clinical appearance has many features in common with the presentation in adults....

Childhood sarcoidosis in Denmark 1979-1994: incidence, clinical features and laboratory results at presentation in 48 children

DEFF Research Database (Denmark)

Hoffmann, A L; Milman, N; Byg, K E

2004-01-01

.7-15). In 1979-1994 the incidence was 0.29 per 100000 person-years incidence was 0.06 in children weight loss, abdominal discomfort, respiratory symptoms, lymphadenopathy......AIM: To describe the incidence, clinical presentation and paraclinical findings in childhood sarcoidosis in Denmark, 1979-1994. METHODS: Patients (n = 5536) with a diagnosis of sarcoidosis were drawn from the nationwide Patient Registry; 81 patients were ... examination (glucose, albumin, haemoglobin) was normal in 96% of the patients; the patient with nephrocalcinosis had albuminuria and haematuria. CONCLUSION: The incidence of sarcoidosis in Danish children is low and increases with age. Sarcoidosis in young children may present clinical features...

Impaired aerobic work capacity in insulin dependent diabetics with increased urinary albumin excretion

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Jensen, T; Richter, Erik; Feldt-Rasmussen, Bo

1988-01-01

To assess whether decreased aerobic work capacity was associated with albuminuria in insulin dependent diabetics aerobic capacity was measured in three groups of 10 patients matched for age, sex, duration of diabetes, and degree of physical activity. Group 1 comprised 10 patients with normal...... were not explained by differences in metabolic control or the degree of autonomic neuropathy. Thus the insulin dependent diabetics with only slightly increased urinary albumin excretion had an appreciably impaired aerobic work capacity which could not be explained by autonomic neuropathy...... or the duration of diabetes. Whether the reduced capacity is due to widespread microangiopathy or another pathological process affecting the myocardium remains to be established....

Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data.

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Matsushita, Kunihiro; Ballew, Shoshana H; Coresh, Josef; Arima, Hisatomi; Ärnlöv, Johan; Cirillo, Massimo; Ebert, Natalie; Hiramoto, Jade S; Kimm, Heejin; Shlipak, Michael G; Visseren, Frank L J; Gansevoort, Ron T; Kovesdy, Csaba P; Shalev, Varda; Woodward, Mark; Kronenberg, Florian

2017-09-01

Some evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease. In this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics. We analysed 817 084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18 261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m 2 , adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m 2 and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m 2 . Compared with an ACR of 5 mg/g, the adjusted HR for incident study

Association of Reduced eGFR and Albuminuria with Serious Fall Injuries among Older Adults.

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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

2016-07-07

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.

A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus

NARCIS (Netherlands)

Roscioni, S. S.; de Zeeuw, D.; Hellemons, M. E.; Mischak, H.; Zuerbig, P.; Bakker, S. J. L.; Gansevoort, R. T.; Reinhard, H.; Persson, F.; Lajer, M.; Rossing, P.; Lambers Heerspink, H. J.

Microalbuminuria is considered the first clinical sign of kidney dysfunction and is associated with a poor renal and cardiovascular prognosis in type 2 diabetes. Detection of patients who are prone to develop micro- or macroalbuminuria may represent an effective strategy to start or optimise

Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy : A Randomized Clinical Trial

NARCIS (Netherlands)

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

2015-01-01

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

Endothelial dysfunction, ambulatory pulse pressure and albuminuria are associated in Type 2 diabetic subjects

DEFF Research Database (Denmark)

Knudsen, Søren Tang; Jeppesen, Peter; Frederiksen, Christian Alcaraz

2007-01-01

as three urinary albumin/creatinine ratios. Von Willebrand factor (vWF), fibrinogen, E-selectin and soluble intercellular adhesion molecule 1 (ICAM-1) were measured in plasma. RESULTS: Thirty-four patients had normoalbuminuria (group N) and 12 had micro- or macroalbuminuria (group A). PP levels increased...

Effects of pitavastatin add-on therapy on chronic kidney disease with albuminuria and dyslipidemia.

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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

2015-12-09

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.

Glucose Transporters in Diabetic Kidney Disease-Friends or Foes?

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Wasik, Anita A; Lehtonen, Sanna

2018-01-01

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and a common cause of end-stage renal disease worldwide. DKD manifests as an increased urinary protein excretion (albuminuria). Multiple studies have shown that insulin resistance correlates with the development of albuminuria in non-diabetic and diabetic patients. There is also accumulating evidence that glomerular epithelial cells or podocytes are insulin sensitive and that insulin signaling in podocytes is essential for maintaining normal kidney function. At the cellular level, the mechanisms leading to the development of insulin resistance include mutations in the insulin receptor gene, impairments in the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, or perturbations in the trafficking of glucose transporters (GLUTs), which mediate the uptake of glucose into cells. Podocytes express several GLUTs, including GLUT1, GLUT2, GLUT3, GLUT4, and GLUT8. Of these, the most studied ones are GLUT1 and GLUT4, both shown to be insulin responsive in podocytes. In the basal state, GLUT4 is preferentially located in perinuclear and cytosolic vesicular structures and to a lesser extent at the plasma membrane. After insulin stimulation, GLUT4 is sorted into GLUT4-containing vesicles (GCVs) that translocate to the plasma membrane. GCV trafficking consists of several steps, including approaching of the GCVs to the plasma membrane, tethering, and docking, after which the lipid bilayers of the GCVs and the plasma membrane fuse, delivering GLUT4 to the cell surface for glucose uptake into the cell. Studies have revealed novel molecular regulators of the GLUT trafficking in podocytes and unraveled unexpected roles for GLUT1 and GLUT4 in the development of DKD, summarized in this review. These findings pave the way for better understanding of the mechanistic pathways associated with the development and progression of DKD and aid in the development of new treatments for this devastating disease.

Serum uric acid and renal function in patients with type 1 diabetes: a nationwide study in Brazil.

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Pizarro, Marcela Haas; Santos, Deborah Conte; Barros, Bianca Senger Vasconcelos; de Melo, Laura Gomes Nunes; Gomes, Marilia Brito

2018-01-01

Diabetes nephropathy is a microvascular complication associated with high morbidity and mortality in patients with type 1 diabetes, and its pathogenesis is not fully understood. Our aim was to evaluate the association between levels of serum uric acid and renal function assessed by glomerular filtration rate (GFR) and albuminuria in patients with type 1 diabetes. This is a multicenter, cross-sectional, observational study with 1686 patients, conducted between August 2011 and August 2014 in 14 public clinics from ten Brazilian cities. Renal function was estimated by CKD-EPI (adults) and by Schwartz (adolescents). We analyzed 1686 patients, aged 30.1 ± 12.0, with 15.4 ± 9.3 years of duration of diabetes; 55.8% were female and 54.0% were Caucasians. Serum uric acid was related to renal function, with a mean of 4.8 ± 1.4 (in the normal renal function group) vs 5.2 ± 2.0 (GFR ≥ 60 ml/min and albuminuria) vs 6.5 ± 2.6 mg/dl (GFR uric acid and GFR (r = - 0.316, p uric acid. Considering only patients with normal renal function (n = 1170), a decrease of 2.04 ml/min in the GFR for every increase of 1 mg/dl in Serum uric acid was noted using multivariate analysis. Patients with higher levels of serum uric acid have worse renal function, independently of HbA1c or duration of diabetes, which persisted even in patients with normal renal function. Further prospective studies are necessary to establish if patients with higher serum uric acid may have an elevated risk for developing chronic kidney disease.

Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice.

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Naoto Terami

Full Text Available Inhibition of sodium glucose cotransporter 2 (SGLT2 has been reported as a new therapeutic strategy for treating diabetes. However, the effect of SGLT2 inhibitors on the kidney is unknown. In addition, whether SGLT2 inhibitors have an anti-inflammatory or antioxidative stress effect is still unclear. In this study, to resolve these issues, we evaluated the effects of the SGLT2 inhibitor, dapagliflozin, using a mouse model of type 2 diabetes and cultured proximal tubular epithelial (mProx24 cells. Male db/db mice were administered 0.1 or 1.0 mg/kg of dapagliflozin for 12 weeks. Body weight, blood pressure, blood glucose, hemoglobin A1c, albuminuria and creatinine clearance were measured. Mesangial matrix accumulation and interstitial fibrosis in the kidney and pancreatic β-cell mass were evaluated by histological analysis. Furthermore, gene expression of inflammatory mediators, such as osteopontin, monocyte chemoattractant protein-1 and transforming growth factor-β, was evaluated by quantitative reverse transcriptase-PCR. In addition, oxidative stress was evaluated by dihydroethidium and NADPH oxidase 4 staining. Administration of 0.1 or 1.0 mg/kg of dapagliflozin ameliorated hyperglycemia, β-cell damage and albuminuria in db/db mice. Serum creatinine, creatinine clearance and blood pressure were not affected by administration of dapagliflozin, but glomerular mesangial expansion and interstitial fibrosis were suppressed in a dose-dependent manner. Dapagliflozin treatment markedly decreased macrophage infiltration and the gene expression of inflammation and oxidative stress in the kidney of db/db mice. Moreover, dapagliflozin suppressed the high-glucose-induced gene expression of inflammatory cytokines and oxidative stress in cultured mProx24 cells. These data suggest that dapagliflozin ameliorates diabetic nephropathy by improving hyperglycemia along with inhibiting inflammation and oxidative stress.

Prevalence and risk factors of microalbuminuria in Thai nondiabetic hypertensive patients

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Pongsathorn Gojaseni

2010-03-01

Full Text Available Pongsathorn Gojaseni1, Angkana Phaopha1, Worawon Chailimpamontree1, Thaweepong Pajareya1, Anutra Chittinandana21Division of Nephrology, Department of Medicine, Bhumibol Adulyadej Hospital, Directorate of Medical Services, Royal Thai Air Force, Bangkok, Thailand; 2Department of Education, Directorate of Medical Services, Royal Thai Air Force, Bangkok, ThailandPurpose: To assess the prevalence and risk factors of microalbuminuria in nondiabetic hypertensive patients in Thailand.Patients and methods: A cross-sectional study was performed during January to December 2007 at outpatients departments of Bhumibol Adulyadej hospital. Nondiabetic hypertensive patients without a history of pre-existing kidney diseases participated in this study. A questionnaire was used for collecting information on demographics, lifestyle, and family history of cardiovascular and kidney disease. Spot morning urine samples were collected for albuminuria estimation. Albuminuria thresholds were evaluated and defined using albumin-creatinine ratio (ACR.Results: A total of 559 hypertensive patients (283 males, 276 females, aged 58.0 ± 11.6 years were enrolled in this study. Microalbuminuria (ACR 17 to 299 mg/g in males and 25 to 299 mg/g in females was found in 93 cases (16.6% [15.0%‑18.2%]. The independent determinants of elevated urinary albumin excretion in a multiple logistic regression model were; body mass index ≥30 (odds ratio (OR = 2.24, 95% confidence intervals (CI: 1.33–3.76 and dihydropyridine calcium channel blockers (DCCB use (OR = 1.92, 95% CI: 1.22‑3.02.Conclusion: In Thai nondiabetic hypertensive patients, microalbuminuria was not uncommon. Obesity and use of dihydropyridine calcium channel blocker were found to be the important predictors. Prognostic value of the occurrence of microalbuminuria in this population remains to be determined in prospective cohort studies.Keywords: microalbuminuria, hypertension, obesity, calcium channel blocker, metabolic

The association between C-reactive protein levels and the risk for chronic kidney disease hospitalizations in adults of a remote Indigenous Australian community - A prospective cohort study.

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Arnold, Luke W; Hoy, Wendy E; Wang, Zhiqiang

2017-09-01

Indigenous Australians are significantly burdened by chronic kidney disease (CKD). Elevated levels of C-reactive protein (CRP) have been associated with diabetes and cardiovascular incidence in previous studies. Elevated CRP has been associated with albuminuria and reduced eGFR in cross-sectional studies. This study investigated the long-term predictive association between CRP measured at a baseline exam and the incidence of a CKD-related hospitalization. Health screening examinations were conducted in individuals of a remote indigenous Australian community between 1992 and 1998. The risk of subsequent CKD hospitalisations, documented through Northern Territory hospital records up to 2010, was estimated with Cox proportional hazard models in people aged over 18 years at the baseline screen and who had albumin-creatinine ratios (ACRs) less than 34g/mol. 546 participants were eligible for our study. Individuals in the highest CRP tertile at baseline had increased levels of traditional cardiovascular risk factors. They also had almost 4 times the risk of a CKD-related hospitalisation compared with participants in the lowest CRP tertile (HR=3.91, 95%CI 1.01-15.20, P=0.049) after adjustment for potential confounding factors. Participants with CRP concentrations greater than 3mg/L had almost 3 times the risk of CKD hospitalisations than those ≤3mg/L (HR=2.84, 95%CI 1.00-8.00, P=0.049). Furthermore, risk of CKD hospitalisations increased 34% per doubling of baseline CRP (HR=1.34, 95%CI 1.04-1.74, P=0.024). In individuals in this remote indigenous community without overt albuminuria at baseline the risk for incident CKD related hospitalisations was predicted by elevated C-reactive protein levels almost a decade earlier. Further research is needed to understand the roles that CRP and systemic inflammation play in CKD risk. © 2016 Asian Pacific Society of Nephrology.

Clinical Course and Risk Factors of Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus in Korea

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Jae-Seung Yun

2016-10-01

Full Text Available BackgroundWe investigated clinical course and risk factors for diabetic retinopathy (DR in patients with type 2 diabetes mellitus (T2DM.MethodsA total of 759 patients with T2DM without DR were included from January 2001 to December 2004. Retinopathy evaluation was performed at least annually by ophthalmologists. The severity of the DR was classified into five categories according to the International Clinical Diabetic Retinopathy Severity Scales.ResultsOf the 759 patients, 523 patients (68.9% completed the follow-up evaluation. During the follow-up period, 235 patients (44.9% developed DR, and 32 patients (13.6% progressed to severe nonproliferative DR (NPDR or proliferative DR (PDR. The mean duration of diabetes at the first diagnosis of mild NPDR, moderate NPDR, and severe NPDR or PDR were 14.8, 16.7, and 17.3 years, respectively. After adjusting multiple confounding factors, the significant risk factors for the incidence of DR risk in patients with T2DM were old age, longer duration of diabetes, higher mean glycosylated hemoglobin (HbA1c, and albuminuria. Even in the patients who had been diagnosed with diabetes for longer than 10 years at baseline, a decrease in HbA1c led to a significant reduction in the risk of developing DR (hazard ratio, 0.73 per 1% HbA1c decrement; 95% confidence interval, 0.58 to 0.91; P=0.005.ConclusionThis prospective cohort study demonstrates that glycemic control, diabetes duration, age, and albuminuria are important risk factors for the development of DR. More aggressive retinal screening for T2DM patients diagnosed with DR should be required in order to not miss rapid progression of DR.

Kidney outcomes three years after bariatric surgery in severely obese adolescents.

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Nehus, Edward J; Khoury, Jane C; Inge, Thomas H; Xiao, Nianzhou; Jenkins, Todd M; Moxey-Mims, Marva M; Mitsnefes, Mark M

2017-02-01

A significant number of severely obese adolescents undergoing bariatric surgery have evidence of early kidney damage. To determine if kidney injury is reversible following bariatric surgery, we investigated renal outcomes in the Teen-Longitudinal Assessment of Bariatric Surgery cohort, a prospective multicenter study of 242 severely obese adolescents undergoing bariatric surgery. Primary outcomes of urine albumin-to-creatinine ratio and cystatin C-based estimated glomerular filtration rate (eGFR) were evaluated preoperatively and up to 3 years following bariatric surgery. At surgery, mean age of participants was 17 years and median body mass index (BMI) was 51 kg/m 2 . In those with decreased kidney function at baseline (eGFR under 90 mL/min/1.73m 2 ), mean eGFR significantly improved from 76 to 102 mL/min/1.73m 2 at three-year follow-up. Similarly, participants with albuminuria (albumin-to-creatinine ratio of 30 mg/g and more) at baseline demonstrated significant improvement following surgery: geometric mean of ACR was 74 mg/g at baseline and decreased to 17 mg/g at three years. Those with normal renal function and no albuminuria at baseline remained stable throughout the study period. Among individuals with a BMI of 40 kg/m 2 and more at follow-up, increased BMI was associated with significantly lower eGFR, while no association was observed in those with a BMI under 40 kg/m 2 . In adjusted analysis, eGFR increased by 3.9 mL/min/1.73m 2 for each 10-unit loss of BMI. Early kidney abnormalities improved following bariatric surgery in adolescents with evidence of preoperative kidney disease. Thus, kidney disease should be considered as a selection criteria for bariatric surgery in severely obese adolescents who fail conventional weight management. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Angiotensin converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy

Science.gov (United States)

Wysocki, Jan; Ye, Minghao; Khattab, Ahmed M.; Fogo, Agnes; Martin, Aline; David, Nicolae Valentin; Kanwar, Yashpal; Osborn, Mark; Batlle, Daniel

2016-01-01

Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II(1-8) that could also be effective involves fostering its degradation. Angiotensin converting enzyme 2 (ACE2) is a monocarboxypeptidase than cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity and glomerular size, were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic

Chronic kidney disease, cardiovascular disease and mortality: A prospective cohort study in a multi-ethnic Asian population.

Science.gov (United States)

Lim, Cynthia C; Teo, Boon Wee; Ong, Peng Guan; Cheung, Carol Y; Lim, Su Chi; Chow, Khuan Yew; Meng, Chan Choon; Lee, Jeannette; Tai, E Shyong; Wong, Tien Y; Sabanayagam, Charumathi

2015-08-01

Few studies have examined the impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes and deaths in Asian populations. We evaluated the associations of CKD with cardiovascular disease (CVD) and all-cause mortality in a multi-ethnic Asian population. Prospective cohort study of 7098 individuals who participated in two independent population-based studies involving Malay adults (n = 3148) and a multi-ethnic cohort of Chinese, Malay and Indian adults (n = 3950). CKD was assessed from CKD-EPI estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Incident CVD (myocardial infarction, stroke and CVD mortality) and all-cause mortality were identified by linkage with national disease/death registries. Over a median follow-up of 4.3 years, 4.6% developed CVD and 6.1% died. Risks of both CVD and all-cause mortality increased with decreasing eGFR and increasing albuminuria (all p-trend <0.05). Adjusted hazard ratios (HR (95% confidence interval)) of CVD and all-cause mortality were: 1.54 (1.05-2.27) and 2.21 (1.67-2.92) comparing eGFR <45 vs ≥60; 2.81 (1.49-5.29) and 2.34 (1.28-4.28) comparing UACR ≥300 vs <30. The association between eGFR <60 and all-cause mortality was stronger among those with diabetes (p-interaction = 0.02). PAR of incident CVD was greater among those with UACR ≥300 (12.9%) and that of all-cause mortality greater among those with eGFR <45 (16.5%). In multi-ethnic Asian adults, lower eGFR and higher albuminuria were independently associated with incident CVD and all-cause mortality. These findings extend previously reported similar associations in Western populations to Asians and emphasize the need for early detection of CKD and intervention to prevent adverse outcomes. © The European Society of Cardiology 2014.

Kidney function after withdrawal of long-term antihypertensive treatment in diabetic nephropathy

DEFF Research Database (Denmark)

Hansen, H P; Nielsen, F S; Rossing, P

1997-01-01

) [median (range)] with diabetic nephropathy receiving antihypertensive treatment (angiotensin converting enzyme inhibition, N = 30) for 5 years (1 to 20 years). The following variables were measured the last day on antihypertensive treatment and one month after withdrawal of treatment; GFR (51Cr-EDTA), 24......-hour arterial blood pressure (24 hr MABP, Takeda TM2420) and albuminuria (ELISA); the mean 24-hour MABP rose from 102 +/- 11 to 111 +/- 10 (P ... +/- 25 to 70 +/- 26 ml.min-1.1.73 m-2, P = 0.21), after withdrawal of antihypertensive treatment. A significant correlation between the relative change in the 24 hour MABP measurement and the relative change in GFR (r = 0.44, P

Plasmin in urine from patients with type 2 diabetes and treatment-resistant hypertension activates ENaC in vitro

DEFF Research Database (Denmark)

Buhl, Kristian B; Stolzenburg Oxlund, Christina; Friis, Ulla G

2014-01-01

diabetes mellitus (T2DM) and treatment-resistant hypertension excrete plasmin(ogen) in urine in proportion to albumin and that plasmin confers to urine the ability to activate ENaC. METHOD:: Patients (n = 113) with T2DM and resistant hypertension, defined as systolic blood pressure (SBP) more than 130 mm...... of plasmin in preurine may inappropriately activate ENaC in patients with type 2 diabetes and microalbuminuria. This may contribute to treatment-resistant hypertension.......BACKGROUND:: Aberrant filtration of plasminogen from plasma and subsequent activation to plasmin in the urinary space may activate proteolytically the epithelial sodium channel, ENaC. In conditions with chronic albuminuria, this may cause hypertension. It was hypothesized that patients with type 2...

GENETICS ASPECTS OF DIABETIC NEPHROPATHY

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Oana-Elena Sauca

2010-09-01

Full Text Available Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, a relentless decline in GFR, raised arterial blood pressure, and increased relative mortality for cardiovascular diseases. The pathogenesis of diabetic nephropathy is multifactorial, with contributions from metabolic abnormalities, hemodynamic alteration, and various growth and genetic factors. The identification of the main genes would allow the detection of those individuals at high risk for diabetic nephropathy and better understanding of its pathophysiologyas well.The present review discusses the main information available in literature regarding some genetic variants (involved in the renin-angiotensin system, glucose and lipid metabolism and some cytoskeleton proteins that reaffirms the importance of genetic factors in diabetic nephropathy.

[Type 2 diabetes mellitus and chronic kidney disease].

Science.gov (United States)

Ponťuch, Peter

The number of type 2 diabetic patients is increasing world-wide and a prediction of prevalence of chronic kidney disease up to 2025 in European diabetic population is alarming. Albuminuria and estimated glomerular filtration rate are cardinal biochemical parameters in diagnostics of diabetic nephropathy. Following diagnostic methods are also used: renal ultrasonography, ophthalmoscopy and in not clarified cases renal biopsy. Long-term optimal glycemic control, efficient antihypertensive treatment by angiotensin converting enzyme inhibitor, or angiotensin receptor blocker and recommended protein intake is a cornerstone of therapy. The research is presently focused on new pathophysiological mechanisms, as analysis of genome, microRNA, kidney injury biomarkers and proteomes.Key words: chronic kidney disease - type 2 diabetes mellitus.

High altitude-induced albuminuria in normal man is enhanced by infusion of low-dose dopamine

DEFF Research Database (Denmark)

Hansen, J M; Kanstrup, I L; Richalet, J P

1996-01-01

-85) (median with quartiles in parentheses) at high altitude. High altitude hypoxia increased Ualb from 3.2 micrograms min-1 (2.7-3.5) to 5.0 micrograms min-1 (3.3-6.6) (p ... flow (ERPF) from 465 ml min-1 (412-503) to 410 ml min-1 (385-451) (p high altitude. Dopamine...... 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 high altitude, but had no effect on Ualb at sea level. In conclusion, high altitude hypoxia per se increases the urinary...

Serum D-dimer concentrations in nephrotic syndrome track with albuminuria, not estimated glomerular filtration rate.

LENUS (Irish Health Repository)

Sexton, D J

2012-01-01

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.

Microalbuminuria. Implications for micro- and macrovascular disease

DEFF Research Database (Denmark)

Deckert, T; Kofoed-Enevoldsen, A; Nørgaard, K

1992-01-01

and cardiovascular morbidity and mortality. Even among nondiabetic individuals, those with microalbuminuria tend to have an increased cardiovascular morbidity. The established cardiovascular risk factors, such as smoking, elevated plasma cholesterol, fibrinogen, and hypertension, are seen more frequently in diabetic...... patients with persistent microalbuminuria than in normoalbuminuric diabetic patients of similar age, sex, and diabetes duration. However, these risk factors cannot by themselves explain the cardiovascular overmortality in these patients. In addition, insulin resistance or genetic disposition...... density of HS in the glomeruli may lead to albuminuria and mesangial proliferation. In the intima of large vessel walls, decreased density and/or sulfation of HS may enhance several of the processes involved in premature atherosclerosis. Diabetes affects the composition and structure of the extracellular...

Genetics of diabetic nephropathy

DEFF Research Database (Denmark)

Parving, H H; Tarnow, L; Rossing, P

1996-01-01

factor for cardiovascular disease in diabetic patients. However, a meta-analysis does not support the suggestion that this factor plays any role for the initiation of diabetic nephropathy. Similar negative results have been obtained in relation to polymorphisms of the genes encoding for angiotensinogen......Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, a relentless decline in GFR, raised arterial blood pressure, and increased relative mortality for cardiovascular diseases. Diabetic nephropathy is a leading cause of end-stage renal failure. The pathogenesis...... of diabetic nephropathy is multifactorial, with contributions from metabolic abnormalities, hemodynamic alterations, and various growth factors and genetic factors. Epidemiologic and family studies have demonstrated that only a subset of the patients develop this complication that family clustering...

Aldosterone-mineralocorticoid receptor promotes urine prostasin through glomerular barrier injury and not tissue abundance

DEFF Research Database (Denmark)

Stolzenburg Oxlund, Christina; Kurt, B.; Schwarzensteiner, I.

2015-01-01

with placebo or the mineralocorticoid antagonist spironolactone. Western immunoblotting of creatinine-normalized urine samples was performed from placebo and spironolactone treated patients with and without albuminuria. Tissue prostasin was measured in membranes from human nephrectomy recieving either ACE......-i/ANGII or no antihypertensive treatment prior to operation. Urine and tissue prostasin was measured in puromycin-induced nephrotic syndrome rats. Results: Plasma prostasin concentration increased significantly with spironolactone but was not changed with placebo. Urine prostasin concentration was below detection limit....... Puromycin-induced nephrotic syndrome in rats was associated with significant increase in u-prostasin while kidney tissue prostasin protein abundance was not changed. Prostasin protein abundance was similar in membranes from human nephrectomy homogenate from patients treated preoperatively with ACE...

Predisposition to essential hypertension and development of diabetic nephropathy in IDDM patients

DEFF Research Database (Denmark)

Fagerudd, J A; Tarnow, L; Jacobsen, P

1998-01-01

Conflicting results have been reported on the relationship between familial predisposition to hypertension and development of diabetic nephropathy in IDDM. In our case-control study, we assessed the prevalence of hypertension among parents of 73 IDDM patients with diabetic nephropathy (DN......+; persistent albuminuria > 200 microg/min or > 300 mg/24 h) and 73 IDDM patients without diabetic nephropathy (DN-; urinary albumin excretion hypertension, defined as antihypertensive therapy or a 24-h ambulatory blood pressure (SpaceLabs 90207) > or = 135/85 mm...... for hypertension than were patients with DN+ and without parental treatment for hypertension (100 vs. 61%; P = 0.034; difference 39% [21-57%]). In conclusion, familial predisposition to essential hypertension increases the risk of diabetic nephropathy and may also contribute to the development of systemic...

Studies on kidney function in workers exposed to uranium contamination

International Nuclear Information System (INIS)

Bugueno, M.C.; Suarez, J.

1983-01-01

The values of some kidney function tests in our workers were studied through the media, range and statistical spread, compared with those used abroad and also in our main hospitals. With that purpose, thirty three personas were selected among those without kidney pathology history of uranium internal contamination as revealed by the permanent control of our clinical and radiotoxicological service. Kidney function was explored through the measurement of uremia, ureic nitrogen, albuminuria, endogenous creatinine clearance and the Addis test. Values determined were normal with respect to those used in the international literature, with the exception of the creatinine clearance test. Also a 6% of our workers were abnormal in at least one or two of the five tests employed. (Author)

Relationship between serum adiponectin concentration and diabetic nephropathy in patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Zhu Wei; Yang Yuzhi; Li Xianhou; Feng Kun; Wang Dan

2007-01-01

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 0.05). 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)

Systems Biology-Derived Biomarkers to Predict Progression of Renal Function Decline in Type 2 Diabetes

DEFF Research Database (Denmark)

Mayer, Gert; Heerspink, Hiddo J L; Aschauer, Constantin

2017-01-01

hormone 1, hepatocyte growth factor, matrix metalloproteinase (MMP) 2, MMP7, MMP8, MMP13, tyrosine kinase, and tumor necrosis factor receptor-1. These biomarkers were measured in baseline serum samples from 1,765 patients recruited into two large clinical trials. eGFR decline was predicted based...... on molecular markers, clinical risk factors (including baseline eGFR and albuminuria), and both combined, and these predictions were evaluated using mixed linear regression models for longitudinal data. RESULTS: The variability of annual eGFR loss explained by the biomarkers, indicated by the adjusted R2 value......, combined with clinical variables, enhances the prediction of renal function loss over a wide range of baseline eGFR values in patients with type 2 diabetes and CKD....

Microalbuminuria

DEFF Research Database (Denmark)

Parving, Hans-Henrik; Persson, Frederik; Rossing, Peter

2015-01-01

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......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...... and cardiovascular disease. Treatment-induced and spontaneous remission of microalbuminuria has been reported both in type 1 and type 2 diabetic patients, underlining the importance of sustained elevation of urinary albumin excretion. Recently many new biomarkers have been evaluated in diabetic patients, and apart...

Alport Syndrome in Women and Girls

Science.gov (United States)

Colville, Deb; Rheault, Michelle; Gear, Susie; Lennon, Rachel; Lagas, Sharon; Finlay, Moira; Flinter, Frances

2016-01-01

Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Inheritance is X-linked (85%) or autosomal recessive (15%). Many renal physicians think of Alport syndrome as primarily affecting men. However, twice as many women are affected by the X-linked diseases. Affected women are commonly undiagnosed, but 15%–30% develop renal failure by 60 years and often hearing loss by middle age. Half of their sons and daughters are also affected. Autosomal recessive Alport syndrome is less common, but is often mistaken for X-linked disease. Recessive inheritance is suspected where women develop early-onset renal failure or lenticonus. Their family may be consanguineous. The prognosis for other family members is very different from X-linked disease. Other generations, including parents and offspring, are not affected, and on average only one in four of their siblings inherit the disease. All women with Alport syndrome should have their diagnosis confirmed with genetic testing, even if their renal function is normal, because of their own risk of renal failure and the risk to their offspring. Their mutations indicate the mode of inheritance and the likelihood of disease transmission to their children, and the mutation type suggests the renal prognosis for both X-linked and recessive disease. Women with X-linked Alport syndrome should be tested at least annually for albuminuria and hypertension. The “Expert guidelines for the diagnosis and management of Alport syndrome” recommend treating those with albuminuria with renin-angiotensin-aldosterone system (RAAS) blockade (and adequate birth control because of the teratogenic risks of angiotensin converting enzyme inhibitors), believing that this will delay renal failure. Current recommendations are that women with autosomal recessive Alport syndrome should be treated with RAAS blockade from the time of diagnosis. In addition, women should be offered genetic

Attenuation of renovascular damage in Zucker diabetic fatty rat by NWT-03, an egg protein hydrolysate with ACE- and DPP4-inhibitory Activity.

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Yumei Wang

Full Text Available BACKGROUND: Dipeptidyl peptidase 4 (DPP4 and angiotensin-converting enzyme (ACE are important target enzymes in glycemic control and renovascular protection. Here, we studied the effect of NWT-03, an egg protein hydrolysate with DPP4- and ACE-inhibitory activity, on renovascular damage in Zucker diabetic fatty (ZDF rats. Comparisons were made to rats treated with vildagliptin (VIL, included as a positive control for the effect of DPP4 inhibition. METHODS: ZDF rats received NWT-03 (1 g/kg/day or VIL (3 mg/kg/day from 10 to 25 weeks of age. Metabolic and renal functions were assessed; the kidney was removed for histological analysis of glomerulosclerosis and expression of pro-inflammatory/fibrotic markers (RT-PCR and Western blotting; and the aorta was removed for studies of endothelium-dependent relaxation (EDR. FINDINGS: Hyperinsulinemic ZDF rats typically developed signs of type-2 diabetes and renovascular damage, as evidenced by albuminuria, glomerulosclerosis, and impaired EDR. Neither NWT-03 nor VIL improved metabolic parameters; for VIL, this was despite a 5-fold increase in glucagon-like peptide (GLP-1 levels. NWT-03 and VIL both reduced renal interleukin (Il-1β/Il-13 mRNA expression and glomerulosclerosis. However, only NWT-03 additionally decreased renal tumor necrosis factor (TNF-α mRNA and P22(phox protein expression, reduced albuminuria, and restored aortic EDR. Indomethacin added to the organ bath instantly improved aortic EDR, indicating a role for cyclooxygenase (COX-derived contractile prostanoids in opposing relaxation in ZDF rats. This indomethacin effect was reduced by NWT-03, but not by VIL, and coincided with decreased renal COX-1/2 protein expression. CONCLUSION AND INTERPRETATION: Long-term supplementation with the egg protein hydrolysate NWT-03 attenuated renovascular damage in this preclinical rat model of type 2 diabetes. A comparison to the DPP4-inhibitor VIL suggests that the effects of NWT-03 were related to both

A low-protein diet exerts a beneficial effect on diabetic status and prevents diabetic nephropathy in Wistar fatty rats, an animal model of type 2 diabetes and obesity.

Science.gov (United States)

Kitada, Munehiro; Ogura, Yoshio; Suzuki, Taeko; Monno, Itaru; Kanasaki, Keizo; Watanabe, Ai; Koya, Daisuke

2018-01-01

The objective of this study is to investigate the effects of a low-protein diet (LPD) starting from a young age on diabetic status and renal injury in a rat model of type 2 diabetes and obesity. Diabetic male Wistar fatty ( fa/fa ) rats (WFRs) were fed a standard diet (23.84% protein) or an LPD (5.77% protein) for 24 weeks beginning at 6 weeks of age. We investigated the effects of the LPD on total body weight (BW); fat weight (FW); lower-limb muscle weight (MW); several measures of diabetic status, including fasting/random glucose levels, HOMA-IR and the IPITT; and renal injuries, including renal hypertrophy, albuminuria and histological changes. Additionally, autophagy and activation of mTORC1 were evaluated in the diabetic renal cortex. Furthermore, plasma FGF21 and high-molecular-weight (HMW) adiponectin levels, as well as UCP1 expression levels in brown adipose tissue (BAT), were evaluated. Increases in BW and FW in WFRs were significantly reduced by the LPD, and the LPD resulted in a significant reduction of lower-limb MW in WFRs. The LPD suppressed the elevation of glucose levels in WFRs through improvement of insulin resistance. The LPD also elevated the plasma FGF21 and HMW adiponectin of WFRs, as well as UCP1 expression in the BAT of the animals. Renal hypertrophy, albuminuria, renal histological changes, and increased expression of p62 and phospho-S6 ribosomal protein (p-S6RP) were observed in WFRs compared with the values from WLRs. The LPD clearly prevented the diabetic kidneys from sustaining any damage. The LPD prevented the progression of diabetic status; this effect may have been associated with the reduction of FW and the elevation of plasma FGF21 and HMW adiponectin, as well as UCP1 expression in BAT, resulting in suppression of diabetic nephropathy. However, MW was decreased in rats by the consumption of an LPD from a young age; therefore, further research is needed to resolve the nutritional issue of LPD on decreasing in MW.

Quality of chronic kidney disease management in primary care: a retrospective study.

Science.gov (United States)

Van Gelder, Vincent A; Scherpbier-De Haan, Nynke D; De Grauw, Wim J C; Vervoort, Gerald M M; Van Weel, Chris; Biermans, Marion C J; Braspenning, Jozé C C; Wetzels, Jack F M

2016-01-01

Early detection and appropriate management of chronic kidney disease (CKD) in primary care are essential to reduce morbidity and mortality. To assess the quality of care (QoC) of CKD in primary healthcare in relation to patient and practice characteristics in order to tailor improvement strategies. Retrospective study using data between 2008 and 2011 from 47 general practices (207 469 patients of whom 162 562 were adults). CKD management of patients under the care of their general practitioner (GP) was qualified using indicators derived from the Dutch interdisciplinary CKD guideline for primary care and nephrology and included (1) monitoring of renal function, albuminuria, blood pressure, and glucose, (2) monitoring of metabolic parameters, and alongside the guideline: (3) recognition of CKD. The outcome indicator was (4) achieving blood pressure targets. Multilevel logistic regression analysis was applied to identify associated patient and practice characteristics. Kidney function or albuminuria data were available for 59 728 adult patients; 9288 patients had CKD, of whom 8794 were under GP care. Monitoring of disease progression was complete in 42% of CKD patients, monitoring of metabolic parameters in 2%, and blood pressure target was reached in 43.1%. GPs documented CKD in 31.4% of CKD patients. High QoC was strongly associated with diabetes, and to a lesser extent with hypertension and male sex. Room for improvement was found in all aspects of CKD management. As QoC was higher in patients who received structured diabetes care, future CKD care may profit from more structured primary care management, e.g. according to the chronic care model. Quality of care for chronic kidney disease patients in primary care can be improved. In comparison with guideline advice, adequate monitoring of disease progression was observed in 42%, of metabolic parameters in 2%, correct recognition of impaired renal function in 31%, and reaching blood pressure targets in 43% of chronic

Associations between renal hyperfiltration and serum alkaline phosphatase.

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Se Won Oh

Full Text Available Renal hyperfiltration, which is associated with renal injury, occurs in diabetic or obese individuals. Serum alkaline phosphatase (ALP level is also elevated in patients with diabetes (DM or metabolic syndrome (MS, and increased urinary excretion of ALP has been demonstrated in patients who have hyperfiltration and tubular damage. However, little was investigated about the association between hyperfiltration and serum ALP level. A retrospective observational study of the 21,308 adults in the Korea National Health and Nutrition Examination Survey IV-V databases (2008-2011 was performed. Renal hyperfiltration was defined as exceeding the age- and sex-specific 97.5th percentile. We divided participants into 4 groups according to their estimated glomerular filtration rate (eGFR: >120, 90-119, 60-89, and 120 mL/min/1.73 m2 showed the highest risk for MS, in the highest ALP quartiles (3.848, 95% CI, 1.876-7.892, compared to the lowest quartile. Similarly, the highest risk for DM, in the highest ALP quartiles, was observed in participants with eGFR >120 ml/min/1.73 m2 (2.166, 95% CI, 1.084-4.329. ALP quartiles were significantly associated with albuminuria in participants with eGFR ≥ 60 ml/min/1.73m2. The highest ALP quartile had a 1.631-fold risk elevation for albuminuria with adjustment of age and sex. (95% CI, 1.158-2.297, P = 0.005. After adjustment, the highest ALP quartile had a 1.624-fold risk elevation, for renal hyperfiltration (95% CI, 1.204-2.192, P = 0.002. In addition, hyperfiltration was significantly associated with hemoglobin, triglyceride, white blood cell count, DM, smoking, and alcohol consumption (P<0.05. The relationship between serum ALP and metabolic disorders is stronger in participants with an upper-normal range of eGFR. Higher ALP levels are significantly associated with renal hyperfiltration in Korean general population.

Manifestation of renal disease in obesity: pathophysiology of obesity-related dysfunction of the kidney

Directory of Open Access Journals (Sweden)

John A D’Elia

2009-11-01

Full Text Available John A D’Elia, Bijan Roshan, Manish Maski, Larry A WeinrauchJoslin Diabetes Center, Renal Unit, Beth Israel Deaconess Medical Center, Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Boston and Cambridge, MassachusettsAbstract: Albuminuria in individuals whose body mass index exceeds 40 kg/m2 is associated with the presence of large glomeruli, thickened basement membrane and epithelial cellular (podocyte distortion. Obstructive sleep apnea magnifies glomerular injury as well, probably through a vasoconstrictive mechanism. Insulin resistance from excess fatty acids is exacerbated by decreased secretion of high molecular weight adiponectin from adipose cells in the obese state. Adiponectin potentiates insulin in its post-receptor signaling resulting in glucose oxidation in mitochondria. Recent studies of podocyte physiology have concentrated on the structural and functional requirements that prevent glomerular albumin leakage. The architecture of the podocyte involves nephrin and podocin, proteins that cooperate to keep slit pores between foot processes competent to retain albumin. Insulin and adiponectin are necessary for high-energy phosphate generation. When fatty acids bind to albumin, the toxicity to proximal renal tubules is magnified. Albumin and fatty acids are elevated in urine of individuals with obesity related nephrotic syndrome. Fatty acid accumulation and resistin inhibit insulin and adiponectin. Study of cytokines produced by adipose tissue (adiponectin and leptin and macrophages (resistin has led to a better understanding of the relationship between weight and hypertension. Leptin, is presumably secreted after food intake to inhibit the midbrain/ hypothalamic appetite centers. Resistance to leptin results in excess signaling to hypothalamic sympathetics leading to hypertension. Demonstration of the existence of a cerebral receptor mutation provide evidence for a role in hypertension of a central nervous

Angiotensin-converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy.

Science.gov (United States)

Wysocki, Jan; Ye, Minghao; Khattab, Ahmed M; Fogo, Agnes; Martin, Aline; David, Nicolae Valentin; Kanwar, Yashpal; Osborn, Mark; Batlle, Daniel

2017-06-01

Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II (1-8) that could also be effective involves fostering its degradation. Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity, and glomerular size were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic

Ethnic disparities in risk of cardiovascular disease, end-stage renal disease and all-cause mortality: a prospective study among Asian people with Type 2 diabetes.

Science.gov (United States)

Liu, J J; Lim, S C; Yeoh, L Y; Su, C; Tai, B C; Low, S; Fun, S; Tavintharan, S; Chia, K S; Tai, E S; Sum, C F

2016-03-01

To study prospectively the ethnic-specific risks of cardiovascular disease, end-stage renal disease and all-cause mortality in patients with Type 2 diabetes mellitus among native Asian subpopulations. A total of 2337 subjects with Type 2 diabetes (70% Chinese, 17% Malay and 13% Asian Indian) were followed for a median of 4.0 years. Time-to-event analysis was used to study the association of ethnicity with adverse outcomes. Age- and gender-adjusted hazard ratios for cardiovascular disease in ethnic Malay and Asian Indian subjects were 2.01 (1.40-2.88; PChinese subjects. Adjustment for conventional cardiovascular disease risk factors, including HbA1c , blood pressure and lipid profile, slightly attenuated the hazards in Malay (1.82, 1.23-2.71; P=0.003) and Asian Indian subjects (1.47, 0.95-2.30; P=0.086); However, further adjustment for baseline renal function (estimated GFR) and albuminuria weakened the cardiovascular disease risks in Malay (1.48, 0.98-2.26; P=0.065) but strengthened that in Asian Indian subjects (1.81, 1.14-2.87; P=0.012). Competing-risk regression showed that the age- and gender-adjusted sub-distribution hazard ratio for end-stage renal disease was 1.87 (1.27-2.73; P=0.001) in Malay and 0.39 (0.18-0.83; P=0.015) in Asian Indian subjects. Notably, the difference in end-stage renal disease risk among the three ethnic groups was abolished after further adjustment for baseline estimated GFR and albuminuria. There was no significant difference in risk of all-cause mortality among the three ethnic groups. Risks of cardiovascular and end-stage renal diseases in native Asian subjects with Type 2 diabetes vary substantially among different ethnic groups. Differences in prevalence of diabetic kidney disease may partially explain the ethnic disparities. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Urinary serine proteases and activation of ENaC in kidney

DEFF Research Database (Denmark)

Svenningsen, Per; Andersen, Henrik; Nielsen, Lise Hald

2015-01-01

with albuminuria compatible with impaired renal Na(+) excretion: hypertension and volume retention is secondary to proteinuria in, e.g., preeclampsia and nephrotic syndrome; plasma concentrations of renin, angiotensin II, and aldosterone are frequently suppressed in proteinuric conditions, e.g., preeclampsia......Serine proteases, both soluble and cell-attached, can activate the epithelial sodium channel (ENaC) proteolytically through release of a putative 43-mer inhibitory tract from the ectodomain of the γ-subunit. ENaC controls renal Na(+) excretion and loss-of-function mutations lead to low blood...... pressure, while gain-of-function mutations lead to impaired Na(+) excretion, hypertension, and hypokalemia. We review an emerging pathophysiological concept that aberrant glomerular filtration of plasma proteases, e.g., plasmin, prostasin, and kallikrein, contributes to proteolytic activation of ENaC, both...

Tubular and glomerular injury in diabetes and the impact of ACE inhibition

DEFF Research Database (Denmark)

Nielsen, Stine E; Sugaya, Takeshi; Tarnow, Lise

2009-01-01

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...... studied Caucasians with type 1 diabetes: 58 with normoalbuminuria (urinary albumin or =300 mg/24 h). A control group consisted of 57 healthy individuals. The groups were matched by sex...... and duration of diabetes. In addition, U-LFABP was measured in 48 type 1 diabetic patients with diabetic nephropathy in a randomized crossover trial consisting of 2 months of treatment with 20, 40, and 60 mg lisinopril once daily in random order. RESULTS: In the cross-sectional study, levels of U-LFABP were...

[Clinical, functional and biochemical characteristics of arterial hypertension in military men under chronic stress].

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Shpagina, L A; Ermakova, M A; Volkova, E A; Iakovleva, S A

2008-01-01

Peculiarities of military occupational activities are repeated stress and high degree of psychoemotional strain. The article deals with results of momentary study covering a select from military men cohort, with thyroid tests, renal functional tests, diurnal monitoring of blood pressure and psychologic state assessment. Course of arterial hypertension in military men subjected to chronic stress presents prevailing systolic-diastolic and diastolic variants with excessive decrease of blood pressure at night, with high values of albuminuria. Psychologic state of the military men examined, whe were subjects to chronic stress, was mostly mixed reactivity type with general overstrain and somatization of inner conflict (psychosomatic variant of dysadaptation). The authors demonstrated close correlation between intrinsic emotional strain degree with arterial hypertension type according to "hyper-dipper" variant and free T3 level.

Plasma proteomics classifiers improve risk prediction for renal disease in patients with hypertension or type 2 diabetes

DEFF Research Database (Denmark)

Pena, Michelle J; Jankowski, Joachim; Heinze, Georg

2015-01-01

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...... proteomics classifiers to predict the development of micro or macroalbuminuria in hypertension or type 2 diabetes. METHODS: Patients with hypertension (n = 125) and type 2 diabetes (n = 82) were selected for this case-control study from the Prevention of REnal and Vascular ENd-stage Disease cohort....... RESULTS: In hypertensive patients, the classifier improved risk prediction for transition in albuminuria stage on top of the reference model (C-index from 0.69 to 0.78; P diabetes, the classifier improved risk prediction for transition from micro to macroalbuminuria (C-index from 0...

Targeting the aldosterone pathway in cardiovascular disease

DEFF Research Database (Denmark)

Gustafsson, Finn; Azizi, Michel; Bauersachs, Johann

2012-01-01

Accumulated evidence has demonstrated that aldosterone is a key player in the pathogenesis of cardiovascular (CV) disease. Multiple clinical trials have documented that intervention in the aldosterone pathway can reduce blood pressure and lower albuminuria and improve outcome in patients with heart...... failure or myocardial infarction. Recent studies have unraveled details about the role of aldosterone at the cellular level in CV disease. The relative importance of glucocorticoids and aldosterone in terms of mineralocorticoid receptor activation is currently being debated. Also, studies are addressing...... which aldosterone modulator to use, which timing of treatment to aim for, and in which population to intervene. This review provides an overview of recent developments in the understanding of the role of aldosterone in CV disease, with particular reference to mechanisms and potential targets...

Danish Registry of Childhood and Adolescent Diabetes

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Svensson, Jannet; Cerqueira, Charlotte; Kjærsgaard, Per

2016-01-01

children diagnosed with diabetes before the age of 15 years since 1996. Since 2015, every child followed up at a pediatric center (years of age) will be included. MAIN VARIABLES: The variables in the registry are the quality indicators, demographic variables, associated conditions, diabetes......, neuropathy, number of severe hypoglycemic events, and hospitalization with ketoacidosis. DESCRIPTIVE DATA: The number of children diagnosed with diabetes is increasing with ∼3% per year mainly for type 1 diabetes (ie, 296 new patients years of age were diagnosed in 2014). The disease management has...... classification, family history of diabetes, growth parameters, self-care, and treatment variables. The quality indicators are selected based on international consensus of measures of good clinical practice. The indicators are metabolic control as assessed by HbA1c, blood pressure, albuminuria, retinopathy...

Elevated vascular endothelial growth factor in type 1 diabetic patients with diabetic nephropathy

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Hovind, P; Tarnow, L; Oestergaard, P B

2000-01-01

patients with and without proliferative retinopathy were detected. CONCLUSIONS: Our data suggest that VEGF is elevated early in the course of diabetic nephropathy in men with type 1 diabetes mellitus. Baseline albuminuria, arterial blood pressure and male gender was predictors of diabetic nephropathy......BACKGROUND: Growth factors have been suggested to play a role in the development and progression of diabetic nephropathy. Vascular endothelial growth factor (VEGF) is a potent cytokine family that induces angiogenesis and markedly increases endothelial permeability. The aim of the present study...... was to investigate plasma levels of VEGF in a large cohort of type 1 diabetic patients with diabetic nephropathy and in long-standing type 1 diabetic patients with persistent normoalbuminuria, and to evaluate VEGF as a predictor of nephropathy progression. METHODS: We measured VEGF with an enzyme...

Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

DEFF Research Database (Denmark)

Alkhalaf, Alaa; Zürbig, Petra; Bakker, Stephan J L

2010-01-01

/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). METHODOLOGY/PRINCIPAL FINDINGS: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously......BACKGROUND: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers...... with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration ≥5 years, cases of DN were defined as albuminuria >300 mg...

Endothelial dysfunction and inflammation predict development of diabetic nephropathy in the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study

DEFF Research Database (Denmark)

Persson, Frederik; Rossing, Peter; Hovind, Peter

2008-01-01

OBJECTIVE: To evaluate risk factors for progression from persistent microalbuminuria to diabetic nephropathy in the Irbesartan in Patients with Type 2 diabetes and Microalbuminuria (IRMA 2) study, including biomarkers of endothelial dysfunction, chronic low-grade inflammation, growth factors...... and advanced glycation end products (AGE peptides). METHODS: IRMA 2 was a 2-year multicentre, randomized, double-blind trial comparing irbesartan (150 and 300 mg once daily) versus placebo. The primary end-point was time to onset of diabetic nephropathy. Samples from a subgroup from the placebo and the 300 mg...... and vWf predicted the end-point. In addition, endothelial Z-score was associated with progression of albuminuria (p = 0.038). CONCLUSION: Endothelial dysfunction and possibly inflammation are novel predictors of progression to diabetic nephropathy in patients with type 2 diabetes and microalbuminuria...

European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy

DEFF Research Database (Denmark)

Tarnow, L.; Groop, P.H.; Hadjadj, S.

2008-01-01

in 541 independent parent-offspring trios with or without diabetic nephropathy was applied for validation of consistency. Candidate genes were selected based on previous linkage studies, knowledge of metabolic pathways, and animal models. A comprehensive SNP discovery in more than 100 candidate genes......BACKGROUND: Diabetic nephropathy is likely to be a complex genetic trait. To date, most diabetic nephropathy candidate gene studies have tested a limited number of genes and variants in small sized populations, or in populations that were poorly matched or phenotyped. The main objective...... of the EURAGEDIC study was to address these problems. METHODS: Single nucleotide polymorphisms (SNPs) in candidate genes were tested for association with overt diabetic nephropathy (persistent albuminuria >300 mg/24 h) in a large (n=2499) Type 1 diabetes case/control study. Testing for transmission disequilibrium...

Impaired aerobic work capacity in insulin dependent diabetics with increased urinary albumin excretion

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Jensen, T; Richter, E A; Feldt-Rasmussen, B

1988-01-01

To assess whether decreased aerobic work capacity was associated with albuminuria in insulin dependent diabetics aerobic capacity was measured in three groups of 10 patients matched for age, sex, duration of diabetes, and degree of physical activity. Group 1 comprised 10 patients with normal...... urinary albumin excretion (less than 30 mg/24 h), group 2 comprised 10 with incipient diabetic nephropathy (urinary albumin excretion 30-300 mg/24 h, and group 3 comprised 10 with clinical diabetic nephropathy (urinary albumin excretion greater than 300 mg/24 h). Ten non-diabetic subjects matched for sex...... were not explained by differences in metabolic control or the degree of autonomic neuropathy. Thus the insulin dependent diabetics with only slightly increased urinary albumin excretion had an appreciably impaired aerobic work capacity which could not be explained by autonomic neuropathy...

A modified RIA for minute albumin in human urine

International Nuclear Information System (INIS)

Chen Panzao; Hao Xiuhua; Xiao Shuqing; Li Zhenjia

1989-01-01

A modified radioimmunoassay for minute albuminuria using a solid phase radioiodination technique (Iodogen), and a precipitating reagent (PR) separation was described. The results of RIA and EIA of albumin are compared with each other (r = 0.925). Aliquots of 100μl diluted urine (1:20-1:100) are incubated at 4 deg C overnight with 100μl 125 I-labelled albumin and 100μl antiserum. Separation with 500 μl PR is very successful. The concentration of standard albumin ranges from 50 to 3200 ng/ml. The sensitivity of detection is 5 ng of albumin. The coefficients of inter-assay and intr-assay variation are 3.2-8.2% and 13.0-14.5% respectively. In 70 normal individuals the range of urinary albumin is 1.2-17.8 mg/24h

Differential Effects of Dapagliflozin on Cardiovascular Risk Factors at Varying Degrees of Renal Function

DEFF Research Database (Denmark)

Petrykiv, Sergei I.; Sjöström, C David; Greasley, Peter J

2017-01-01

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...... changes in HbA1c, body weight, BP, hematocrit, and urinary albumin-to-creatinine ratio with placebo (n=2178) or dapagliflozin 10 mg (n=2226) over 24 weeks in patients with type 2 diabetes according to baseline eGFR (eGFR≥45 to .../min per 1.73 m(2)). RESULTS: Compared with placebo, reductions in HbA1c with dapagliflozin were 0.6%, 0.5%, and 0.3%, respectively, for each consecutive lower eGFR subgroup (P value interaction hematocrit, body weight, and BP were similar regardless of baseline e...

Acute and long-term effect of antihypertensive treatment on exercise-induced albuminuria in incipient diabetic nephropathy

DEFF Research Database (Denmark)

Christensen, Cramer; Mogensen, C E

1986-01-01

. 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...

Effects of isradipine in Type 1 (insulin-dependent) diabetic patients with albuminuria and normal blood pressure

DEFF Research Database (Denmark)

Nørgaard, K; Jensen, T; Feldt-Rasmussen, B

1992-01-01

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...

Reduced albuminuria during early and aggressive antihypertensive treatment of insulin-dependent diabetic patients with diabetic nephropathy

DEFF Research Database (Denmark)

Parving, H H; Andersen, A R; Smidt, U M

1981-01-01

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...

Acute and long-term effect of antihypertensive treatment on exercise-induced albuminuria in incipient diabetic nephropathy

DEFF Research Database (Denmark)

Christensen, Cramer; Mogensen, C E

1986-01-01

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...

Renal Dysfunction in the Presence of Normoalbuminuria in Type 2 Diabetes

DEFF Research Database (Denmark)

Dwyer, Jamie P; Parving, Hans-Henrik; Hunsicker, Lawrence G

2012-01-01

population of patients with type 2 diabetes. Renal dysfunction was present in a large proportion of these patients without proteinuria, assessed by a single random albumin-to-creatinine ratio (ACR). We therefore undertook to characterize the nature of this association of non-proteinuric renal dysfunction...... in type 2 diabetes. METHODS: In the DEMAND (Developing Education on Microalbuminuria for Awareness of Renal and Cardiovascular Risk in Diabetes) study, a global, cross-sectional study which described the prevalence and risk factors for albuminuria in a clinic-based cohort, kidney function was assessed...... in 11,573 patients; ACR was measured using the Bayer reagent strip Multistix® 10SG. Normoalbuminuria was defined as ACR 300 mg/g. RESULTS: Among the patients with estimated kidney function determined, chronic kidney disease was noted in 17% of those with normoalbuminuria (stage 3-5), and significant...

Randomized control trial for the assessment of the anti-albuminuric effects of topiroxostat in hyperuricemic patients with diabetic nephropathy (the ETUDE study).

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Kato, Sawako; Ando, Masahiko; Mizukoshi, Toshihiro; Nagata, Takanobu; Katsuno, Takayuki; Kosugi, Tomoki; Tsuboi, Naotake; Maruyama, Shoichi

2016-05-01

Proteinuria is an established risk factor for diabetic nephropathy. Recent studies indicate that some xanthine oxidase inhibitors have a renoprotective effect. The aim of this study was to assess whether topiroxostat reduces albuminuria in hyperuricemic patients with diabetic nephropathy and overt proteinuria. The ETUDE study is an ongoing 24-week, multicenter, open-label, randomized (1:1), parallel group study involving hyperuricemic patients with diabetic nephropathy (estimated glomerular filtration rate [eGFR] ≥ 20 mL/min/1.73 m(2)) and overt proteinuria (0.3 ≤ urine protein to creatinine ratio (UPCR) ETUDE trial is the first randomized controlled study of topiroxostat in hyperuricemic patients with diabetic nephropathy and overt proteinuria. We will clarify the pleiotropic function of topiroxostat including an anti-albumiuric effect as well as its effects on safely decreasing serum uric acid levels.

Application of serum TGF-β1 determination for early diagnosis of diabetic nephropathy

International Nuclear Information System (INIS)

Jiang Zhonglin; Jiang Guoliang

2005-01-01

Objective: To investigate the feasibility of obtaining early diagnosis of diabetic nephropathy (DN) with determination of serum transforming growth factor-β 1 (TGF- β 1 ). Methods: Serum TGF-β 1 (with ELISA) and β 2 -microglobulin (β 2 -m, with RIA) levels as well as urinany β 2 -m, albumin and mciro-amount of proteins were determined in 35 controls and 84 diabetic patients with different degrees of albuminuria (Group A: urinary albumin excretion UAE 300mg/24h, n=28). Results: The serum TGF-β 1 , β 2 -m and urinary β 2 -m contents were correlated well with UAE in the diabetic patients. Conclusion: TGF-β 1 and β 2 -m were sensitive markers for early renal function injury in diabetic patients and determination of serum TGF-β 1 levels was clinically useful for diagnosis of early DN. (authors)

Clinico-biochemical studies on acute toxic nephropathy in goats due to uranyl nitrate

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Dash, P.K.; Joshi, H.C.

1989-02-01

Acute toxic nephropathy was produced in 6 healthy goats by injecting intravenously 1% uranyl nitrate (UN) (15 mg/kg body weight). The early painful clinical signs simulating shock progressed with subnormal temperature, slow-shallow respiration and arrhythmic pulse followed by death due to respiratory failure within 96 to 120 hr. All the affected goats had normocytic normochromic anemia, leucocytosis, neutrophilia with left shift eosinopenia, decreased monocytes and presence of 1-2% reticulocytes in the peripheral blood smears. On blood chemical analysis, a uniform and continuous rise was seen in serum creatinine with a concomitant daily increase of serum urea and uric acid. Simultaneous analysis of urine indicated polyuria leading to oliguria, acidic pH, albuminuria, glycosuria with presence of neutrophils, RBC's, epithelial and fatty casts, increase of triple phosphate, and cystine crystals reflecting acute damage of kidneys in the affected goats.

Clinico-biochemical studies on acute toxic nephropathy in goats due to uranyl nitrate

International Nuclear Information System (INIS)

Dash, P.K.; Joshi, H.C.

1989-01-01

Acute toxic nephropathy was produced in 6 healthy goats by injecting intravenously 1% uranyl nitrate (UN) (15 mg/kg body weight). The early painful clinical signs simulating shock progressed with subnormal temperature, slow-shallow respiration and arrhythmic pulse followed by death due to respiratory failure within 96 to 120 hr. All the affected goats had normocytic normochromic anemia, leucocytosis, neutrophilia with left shift eosinopenia, decreased monocytes and presence of 1-2% reticulocytes in the peripheral blood smears. On blood chemical analysis, a uniform and continuous rise was seen in serum creatinine with a concomitant daily increase of serum urea and uric acid. Simultaneous analysis of urine indicated polyuria leading to oliguria, acidic pH, albuminuria, glycosuria with presence of neutrophils, RBC's, epithelial and fatty casts, increase of triple phosphate, and cystine crystals reflecting acute damage of kidneys in the affected goats

Divergent functions of the Rho GTPases Rac1 and Cdc42 in podocyte injury

DEFF Research Database (Denmark)

Blattner, Simone M; Hodgin, Jeffrey B; Nishio, Masashi

2013-01-01

-specific deletion of Rac1 prevented foot process effacement. In a long-term model of chronic hypertensive glomerular damage, however, loss of Rac1 led to an exacerbation of albuminuria and glomerulosclerosis. In contrast, mice with podocyte-specific deletion of Cdc42 had severe proteinuria, podocyte foot process...... effacement, and glomerulosclerosis beginning as early as 10 days of age. In addition, slit diaphragm proteins nephrin and podocin were redistributed, and cofilin was dephosphorylated. Cdc42 is necessary for the maintenance of podocyte structure and function, but Rac1 is entirely dispensable in physiological...... steady state. However, Rac1 has either beneficial or deleterious effects depending on the context of podocyte impairment. Thus, our study highlights the divergent roles of Rac1 and Cdc42 function in podocyte maintenance and injury.Kidney International advance online publication, 15 May 2013; doi:10...

Telemedicine compared with standard care in type 2 diabetes mellitus

DEFF Research Database (Denmark)

Rasmussen, O. W.; Lauszus, Finn F; Loekke, M

2016-01-01

Introduction Good metabolic control is important in type 2 diabetes mellitus to improve quality of life, work ability and life expectancy, and the use of telemedicine has proved efficient as an add-on to the usual treatment. However, few studies in type 2 diabetes patients have directly compared...... telemedicine with conventional outpatient treatment, and we wanted to evaluate whether telemedicine, compared with standard care, provides equivalent clinical outcomes. Methods Forty patients with type 2 diabetes mellitus allocated from October 2011-July 2012 were randomized to either treatment at home...... by video conferences only or standard outpatient treatment. Primary outcomes were HbA1c and blood glucose levels and secondary outcomes were 24-hour blood pressure, cholesterol levels and albuminuria. The video-telephone was a broadband solution installed and serviced by the Danish Telephone Company (TDC...

Relationships between serum MCP-1 and subclinical kidney disease: African American-Diabetes Heart Study

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Murea Mariana

2012-11-01

Full Text Available Abstract Background Monocyte chemoattractant protein-1 (MCP-1 plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD were assessed in African Americans (AAs with type 2 diabetes (T2D. Methods Serum MCP-1 concentration, urine albumin:creatinine ratio (ACR, estimated glomerular filtration rate (eGFR, and atherosclerotic calcified plaque (CP in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP. Results Participants were 57% female, with mean ± SD (median age 55.6±9.5 (55.0 years, diabetes duration 10.3±8.2 (8.0 years, urine ACR 149.7±566.7 (14.0 mg/g, CKD-EPI eGFR 92.4±23.3 (92.0 ml/min/1.73m2, MCP-1 262.9±239.1 (224.4 pg/ml, coronary artery CP 280.1±633.8 (13.5, carotid artery CP 47.1±132.9 (0, and aorta CP 1616.0±2864.0 (319.0. Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04 and negatively associated with eGFR (parameter estimate −0.0003, P=0.001. MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes. Conclusions Serum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.

Effect of Processing Delay and Storage Conditions on Urine Albumin-to-Creatinine Ratio.

Science.gov (United States)

Herrington, William; Illingworth, Nicola; Staplin, Natalie; Kumar, Aishwarya; Storey, Ben; Hrusecka, Renata; Judge, Parminder; Mahmood, Maria; Parish, Sarah; Landray, Martin; Haynes, Richard; Baigent, Colin; Hill, Michael; Clark, Sarah

2016-10-07

Because there is substantial biologic intraindividual variation in albumin excretion, randomized trials of albuminuria-reducing therapies may need multiple urine samples to estimate daily urinary albumin excretion. Mailing spot urine samples could offer a convenient and cost-effective method to collect multiple samples, but urine albumin-to-creatinine ratio stability in samples stored at ambient temperatures for several days is unknown. Patients with kidney disease provided fresh urine samples in two tubes (with and without boric acid preservative). Reference aliquots from each participant were analyzed immediately, whereas remaining aliquots were subject to different handling/storage conditions before analysis, including delayed processing for up to 7 days at three different storage temperatures (4°C, 18°C, and 30°C), multiple freeze-thaw cycles, and long-term frozen storage at -80°C, -40°C, and -20°C. We calculated the mean percentage change in urine albumin-to-creatinine ratio for each condition, and we considered samples stable if the 95% confidence interval was within a ±5% threshold. Ninety-three patients provided samples with detectable albuminuria in the reference aliquot. Median (interquartile range) urine albumin-to-creatinine ratio was 87 (20-499) mg/g. The inclusion of preservative had minimal effect on fresh urine albumin-to-creatinine ratio measurements but reduced the changes in albumin and creatinine in samples subject to processing delay and storage conditions. The urine albumin-to-creatinine ratio was stable for 7 days in samples containing preservative at 4°C and 18°C and 2 days when stored at 30°C. It was also stable in samples with preservative after three freeze-thaw cycles and in frozen storage for 6 months at -80°C or -40°C but not at -20°C. Mailed urine samples collected with preservative and received within 7 days if ambient temperature is ≤18°C, or within 2 days if the temperature is higher but does not exceed 30°C, are

Reduction of microalbuminuria by using losartan in normotensive patients with type 2 diabetes mellitus: A randomized controlled trial

International Nuclear Information System (INIS)

Agha, Adnan; Amer, Wasim; Anwar, Eram; Bashir, Kaukab

2009-01-01

Type 2 diabetes mellitus (T2DM) is a worldwide pandemic that may lead to diabetic kidney disease (DKD), a complication which is the single most important and globally prevalent cause of chronic kidney disease. Microalbuminuria has been shown to be an early indicator of DKD and data suggest that angiotensin receptor blockers (ARBs) reduce urinary albumin excretion and retard the progression of renal disease in hypertensive T2DM patients. However, the effects of ARBs on preventing microalbuminuria and ensuing DKD in normotensive patients with T2DM is yet to be fully established. The objective of this study is to assess the anti-microalbuminuric effects of losartan therapy versus placebo in normotensive T2DM patients. This randomized single blinded controlled trial was performed at the Diabetic Clinic, Jinnah Hospital, Lahore over a period of 10 months. A total of 361 normotensive patients with T2DM and microalbuminuria were selected; of them, 171 patients were randomly allocated to the test group and 190 enrolled into the control group. The patients in the test group were started on losartan 50 mg/day for a six month period while those in the control group were put on vitamin B-12 500 mcg/day. The patients as well as the primary attending physicians/lab evaluators were blinded to the study. All study patients were followed up on a monthly basis. Quantitative microalbuminuria was tested at the beginning and at the end of the study. Out of the 171 patients in the test group, 149 (87.1%) had significant reduction of albuminuria by > 30% of their baseline (mean 101.9 +- 21.7 baseline and, 47.5 + - 12.9 post-therapy). The corresponding values for albuminuria in the 190 patients in the control group was mean 104.7 +- 26.3 baseline and post 6-month mean 103.9 +- 22.9, with P< 0.0001. The anti-albuminuric effect of losartan was reversible as seen on re-checking the urinary albumin two months after discontinuation of treatment. Our study shows that losartan was well tolerated

Sources of protein and polyunsaturated fatty acids of the diet and microalbuminuria in type 2 diabetes mellitus.

Science.gov (United States)

Almeida, Jussara C; Zelmanovitz, Themis; Vaz, Juliana S; Steemburgo, Thais; Perassolo, Magda S; Gross, Jorge L; Azevedo, Mirela J

2008-10-01

Albuminuria excretion rate above the reference range and below albustix positive proteinuria (20-199 microg/min) is known as microalbuminuria and has been associated with an increased risk of death and progression to renal failure. Besides hyperglicemia and high blood pressure levels, dietary factors can also influence albuminuria. To evaluate possible associations of dietary components (macronutrients and selected foods) with microalbuminuria in type 2 diabetic patients. In this cross-sectional study, 119 normoalbuminuric [NORMO; 24-h urinary albumin excretion (UAE) protein (20.5 +/- 4.4 vs. 19.0 +/- 3.5% of total energy; p = 0.01) with a higher intake from animal sources (14.5 +/- 4.7 vs. 12.9 +/- 3.8% of total energy; p = 0.015) than NORMO patients. The intakes of PUFAs (8.6 +/- 2.9 vs. 9.7 +/- 3.3% of total energy; p vegetable sources (7.3 +/- 3.4 vs. 8.6 +/- 3.7% of total energy; p = 0.029), plant oils [0.2 (0.1-0.6) vs. 0.3 (0.1-0.9) mg/kg weight; p = 0.02] and margarines [3.3 (0-75.7) vs. 7.0 (0-51.7) g/day; p = 0.01] were lower in MICRO than in NORMO. In multivariate logistic regression models, adjusted for age, gender, presence of hypertension and fasting plasma glucose, intake of total protein (% of total energy; OR 1.104; 95% CI 1.008-1.208; p = 0.032) was positively associated with microalbuminuria. The intakes of total PUFAs (% of total energy; OR 0.855; 95%CI 0.762-0.961; p = 0.008), PUFAs from vegetable sources (% of total energy; OR 0.874; 95%CI 0.787-0.971; p = 0.012) and plant oils (mg/kg weight; OR 0.036; 95% CI 0.003-0.522; p = 0.015) were negatively associated with microalbuminuria. In type 2 diabetic patients, the high intake of protein and the low intake of PUFAs, particularly from plant oils, were associated with the presence of microalbuminuria. Reducing protein intake from animal sources and increasing the intake of lipids from vegetable origin might-reduce the risk of microalbuminuria.

Diabetes mellitus e hipertensión: Estudio en el nivel primario de salud

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Nelson Crespo Mojena

2002-10-01

Full Text Available Se revisaron 11 estudios en pacientes diabéticos del nivel primario de salud para conocer la prevalencia de hipertensión arterial en dicha serie entre los años 1986- 2000, registrándose un total de 1 126 pacientes diabéticos con una prevalencia de hipertensión arterial del 53,2 %. Es importante señalar como factor predictor de daño renal el estudio de la presencia de microalbuminuria en 60 pacientes diabéticos del nivel primario de salud y 60 pacientes diabéticos del nivel secundario, lo que demuestra la relación existente entre la hipertensión arterial y la presencia de microalbuminuria en una fase aún reversible de daño renal. Se discuten los fundamentos del tratamiento antihipertensivo en pacientes diabéticos y se recomienda el uso de los inhibidores del sistema renina angiotensina (SRA. El objetivo del tratamiento es lograr la reducción de la tensión arterial por debajo de 140/90, con un ideal de 120/80 para así reducir la morbimortalidad por enfermedad cardiovascular, cerebrovascular y renal.Diabetes mellitus and hypertension. Study at the primary health care level Eleven studies conducted among diabetic patients at the primary health care level were reviewed to know the prevalence of arterial hypertension in this series from 1986 to 2000. A total of 1 126 diabetic patients with a prevalence of arterial hypertension of 53.2 % were registered. It is important to stress the presence of albuminuria as a predictive factor of renal damage in 60 diabetic patients at the primary health care level and in 60 diabetic patients at the secondary level, which shows the relation existing between arterial hypertension and the presence of albuminuria at a still reversible stage of renal damage. The foundations of the antihypertensive treatment in diabetic patients are discussed and the use of renin-angiotensin system (RAS inhibitors is recommended. The treatment is aimed at reducing arterial hypertension to values under 140 x 90 with an

Incipient and overt diabetic nephropathy in African Americans with NIDDM.

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Dasmahapatra, A; Bale, A; Raghuwanshi, M P; Reddi, A; Byrne, W; Suarez, S; Nash, F; Varagiannis, E; Skurnick, J H

1994-04-01

. CONCLUSIONS--Incipient and overt nephropathy were observed frequently in these African-American subjects with NIDDM. Albuminuria correlated with BP, younger age at diabetes onset, and BMI. Association of albuminuria and increased cardiovascular mortality may place 50% of inner-city African-American patients with NIDDM at risk for developing cardiovascular complications.

An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function

DEFF Research Database (Denmark)

Holtkamp, Frank A; de Zeeuw, Dick; Thomas, Merlin C

2011-01-01

initial fall in eGFR had a significant lower long-term eGFR slope compared to those with a moderate fall or rise. This relationship was independent of other risk markers or change in risk markers for progression of renal disease such as blood pressure and albuminuria. Thus, the greater the acute fall in e......Intervention in the renin-angiotensin-aldosterone-system (RAAS) is associated with slowing the progressive loss of renal function. During initiation of therapy, however, there may be an acute fall in glomerular filtration rate (GFR). We tested whether this initial fall in GFR reflects a renal...... a significantly greater acute fall in estimated (eGFR) during the first 3 months compared to patients assigned to placebo, but a significantly slower long-term mean decline of eGFR thereafter. A large interindividual difference, however, was noticed in the acute eGFR change. When patients were divided...

Calcium antagonists and the diabetic hypertensive patient

DEFF Research Database (Denmark)

Parving, H H; Rossing, P

1993-01-01

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...... nephropathy alone and is rapidly rising. Increased arterial blood pressure is an early and common finding in incipient and overt diabetic nephropathy. Fluid and sodium retention with normal concentrations of active renin, angiotensin I and II, and aldosterone has been demonstrated in diabetic renal disease...

Increased left ventricular mass in normotensive type 1 diabetic patients with diabetic nephropathy

DEFF Research Database (Denmark)

Sato, A; Tarnow, L; Parving, H H

1998-01-01

in normotensive type 1 diabetic patients with and without nephropathy. RESEARCH DESIGN AND METHODS: M-mode and Doppler echocardiography was performed in 17 type 1 diabetic patients with nephropathy (albuminuria [median (range)], 345 (135-2,846) mg/24 h) and compared with 34 normotensive, normoalbuminuric (10 [3......-30] mg/24 h) type 1 diabetic patients matched for arterial blood pressure (mean +/- SD) ([134/77] +/- [13/7] vs. [129/78] +/- [12/7] mmHg), age (40 +/- 11 vs. 42 +/- 10 years), duration of diabetes (28 +/- 7 vs. 28 +/- 6 years), and BMI (24.2 +/- 4.2 vs. 24.6 +/- 2.4 kg/m2). RESULTS: Left ventricular......OBJECTIVE: Diabetic nephropathy increases the risk of premature cardiovascular disease and sudden death, particularly in type 1 diabetic patients. One possible mechanism for this risk may be left ventricular hypertrophy. In our study, we aimed to evaluate left ventricular structure and function...

G/T substitution in intron 1 of the UNC13B gene is associated with increased risk of nephropathy in patients with type 1 diabetes

DEFF Research Database (Denmark)

Tregouet, D.A.; Groop, P.H.; McGinn, S.

2008-01-01

for association with diabetic nephropathy (persistent albuminuria >/=300 mg/24 h) in a large type 1 diabetes case/control (1,176/1,323) study from three European populations. RESULTS: Only one SNP, rs2281999, located in the UNC13B gene, was significantly associated with nephropathy after correction for multiple...... was 1.68 (95% CI 1.29-2.19) (P = 1.0 x 10(-4)). This association was replicated in an independent population of 412 case subjects and 614 control subjects (combined OR of 1.63 [95% CI 1.30-2.05], P = 2.3 x 10(-5)). CONCLUSIONS: We identified a polymorphism in the UNC13B gene associated with nephropathy......OBJECTIVE: Genetic and environmental factors modulate the susceptibility to diabetic nephropathy, as initiating and/or progression factors. The objective of the European Rational Approach for the Genetics of Diabetic Complications (EURAGEDIC) study is to identify nephropathy susceptibility genes...

Arterial-ventricular coupling in type 1 diabetes

DEFF Research Database (Denmark)

Theilade, Simone; Rossing, Peter; Jensen, Jan S

2018-01-01

echocardiography. METHODS: In 305 type 1 diabetes (T1D) patients without known heart disease and with normal left ventricular ejection fraction (LVEF) (biplane LVEF > 45%), we measured arterial stiffness as pulse wave velocity (PWV) and performed conventional and speckle-tracking echocardiography assessing global...... longitudinal strain (GLS) as a measure of systolic myocardial function. Associations between PWV and myocardial function were reported as standardized beta values from adjusted regression models including age, sex, mean arterial pressure, body mass index, HbA1c, diabetes duration, estimated glomerular...... filtration rate, degree of albuminuria, total cholesterol, heart rate and smoking. RESULTS: Patients were 54 (12) years [mean (SD)], 152 (50%) females, diabetes duration 31 (16) years, HbA1c65 (12) mmol/mol, LVEF 58 (5) %, GLS -18.2 (2.6) % and PWV 10.2 (3.4) m/s. There was no association between PWV...

Impact of type 1 diabetes on maternal long-term risk of hospitalisation and mortality

DEFF Research Database (Denmark)

Knorr, Sine; Juul, Svend; Bytoft, Birgitte

2018-01-01

AIMS/HYPOTHESIS: The aims of this study were to examine long-term mortality and morbidity rates in mothers with type 1 diabetes, both overall and according to the level of albuminuria prior to pregnancy, the presence of hypertension, pre-eclampsia and periconceptional HbA1c. METHODS: This study...... was a part of the EPICOM (Environmental Versus Genetic and Epigenetic Influences on Growth, Metabolism and Cognitive Function in Offspring of Mothers with Type 1 Diabetes) study, which is a prospective follow-up study focusing on pregnancies complicated by maternal type 1 diabetes. We carried out...... a nationwide combined clinical and register-based cohort study of mortality rates and hospital admissions in mothers with diabetes (n = 986) who gave birth between 1992 and 2000. Control mothers (n = 91,441) were women from the background population, matched according to age and year of childbirth. Age...

Reduced transcapillary escape of albumin during acute blood pressure-lowering in type 1 (insulin-dependent) diabetic patients with nephropathy

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Parving, H H; Kastrup, J; Smidt, U M

1985-01-01

The effect of acute arterial blood pressure lowering upon albumin extravasation was studied in 10 patients with nephropathy and retinopathy due to long-standing Type 1 (insulin-dependent) diabetes. The following variables were measured: transcapillary escape rate of albumin (initial disappearance....... This may be due to elevated hydrostatic pressure in the microcirculation.......The effect of acute arterial blood pressure lowering upon albumin extravasation was studied in 10 patients with nephropathy and retinopathy due to long-standing Type 1 (insulin-dependent) diabetes. The following variables were measured: transcapillary escape rate of albumin (initial disappearance...... induced the following changes: arterial blood pressure decreased from 134/87 to 107/73 mmHg (p less than 0.01), transcapillary escape rate of albumin declined from 8.1 to 6.7% of the intravascular mass of albumin/h (p less than 0.01), albuminuria diminished from 1434 to 815 micrograms/min (p less than 0...

Soluble receptor for advanced glycation end-product levels are related to albuminuria and arterial stiffness in essential hypertension.

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Dimitriadis, K; Tsioufis, C; Kasiakogias, A; Miliou, A; Poulakis, M; Kintis, K; Bafakis, I; Benardis, E; Tousoulis, D; Stefanadis, C

2013-04-01

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.

Stratifying risk in chronic kidney disease: an observational study of UK guidelines for measuring total proteinuria and albuminuria.

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Methven, S; Traynor, J P; Hair, M D; St J O'Reilly, D; Deighan, C J; MacGregor, M S

2011-08-01

Proteinuria predicts poor renal and cardiovascular outcomes. Some guidelines recommend measuring proteinuria using albumin:creatinine ratio (ACR), while others recommend total protein:creatinine ratio (TPCR). To compare renal outcomes and mortality in the populations identified by these different recommendations. Retrospective longitudinal cohort study. Baseline ACR and TPCR measurements were obtained from 5586 patients with chronic kidney disease (CKD) attending a Scottish hospital nephrology clinic. The cohort was divided into three groups with concordant results by ACR and TPCR (no proteinuria; low proteinuria; significant proteinuria) and one group with discordant results (significant proteinuria with TPCR, but not ACR). Outcomes were assessed using Kaplan-Meier plots and Cox proportional hazards models. Median follow-up was 3.5 years [interquartile range (IQR) 2.1-6.0]; 844 (15%) died at 3.0 years (IQR 1.8-4.7) and 468 (8%) started renal replacement therapy (RRT) at 1.7 years (IQR 0.6-3.4). Proteinuria was associated with a substantially increased risk of RRT and death. Patients with significant proteinuria by TPCR, but not ACR (n = 231) had high renal risk, and the highest all-cause mortality (log-rank P < 0.001). With multivariate analysis the risk fell below those with significant proteinuria with concordant results by ACR and TPCR but remained considerably higher than those without significant proteinuria. Proteinuria screening with TPCR identifies an additional 16% of patients with significant proteinuria, not identified using ACR. This subgroup has high renal risk, and high risk of all-cause mortality and therefore warrant identification. Guideline recommendations on proteinuria screening in CKD should be reconsidered.

A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury.

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James, Matthew T; Grams, Morgan E; Woodward, Mark; Elley, C Raina; Green, Jamie A; Wheeler, David C; de Jong, Paul; Gansevoort, Ron T; Levey, Andrew S; Warnock, David G; Sarnak, Mark J

2015-10-01

Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain. Meta-analysis of cohort studies. 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts. Cohorts participating in the CKD Prognosis Consortium. Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions. Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results. During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension. AKI identified by diagnostic code. Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury

NARCIS (Netherlands)

James, Matthew T.; Grams, Morgan E.; Woodward, Mark; Elley, C. Raina; Green, Jamie A.; Wheeler, David C.; de Jong, Paul; Gansevoort, Ron T.; Levey, Andrew S.; Warnock, David G.; Sarnak, Mark J.; de Zeeuw, Dick; Bakker, Stephan J. L.; van der Harst, Pim; Heerspink, Hiddo J.

2015-01-01

Background: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain. Study Design:

Reduction in albuminuria predicts a beneficial effect on diminishing the progression of human diabetic nephropathy during antihypertensive treatment

DEFF Research Database (Denmark)

Rossing, P; Hommel, E; Smidt, U M

1994-01-01

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...

Effective risk stratification in patients with moderate cardiovascular risk using albuminuria and atherosclerotic plaques in the carotid arteries

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Greve, Sara V; Blicher, Marie K; Sehestedt, Thomas

2015-01-01

, Systematic COronary Risk Evaluation (SCORE), and Framingham risk score (FRS) groups. Subclinical vascular damage was defined as carotid-femoral pulse wave velocity at least 12 m/s, and carotid atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 90th percentile of 0.73/1.06 mg...... risk patients and high-intermediate FRS risk patients with high risk (P = 0.04 and P = 0.001, respectively), whereas elevated carotid-femoral pulse wave velocity did not. Elevated UACR or presence of atherosclerotic plaques reclassified patients from moderate to high SCORE risk [net reclassification...... improvement of 6.4%; P = 0.025), or from high intermediate to high FRS risk (net reclassification improvement 8.8%; P = 0.002). Assuming primary prevention could reduce the relative cardiovascular risk by 24-27%, on the basis of actual levels of blood pressure and cholesterol, one composite endpoint could...

Life after acquired thrombotic thrombocytopenic purpura: morbidity, mortality, and risks during pregnancy.

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Vesely, S K

2015-06-01

Patients who have recovered from their acute episode of acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura (TTP) were once thought to have complete recovery except for risk of relapse. Data from previous publications from the Oklahoma TTP-hemolytic uremic syndrome (HUS) Registry are summarized. Patients have decreased cognitive function and increased prevalence of hypertension, systemic lupus erythematosus, major depression, and albuminuria as compared to the expected values from the US population. The proportion of patients that died during the follow-up period was greater than expected based on the US population reference population. Among women who had a pregnancy following recovery from TTP, relapse during pregnancy or postpartum is uncommon, but the occurrence of preeclampsia may be increased. Thirteen of 16 pregnancies in these women resulted in healthy children. Increased morbidity and mortality in TTP patients following recovery suggest that TTP may be more of a chronic disorder than a disorder with acute episodes and complete recovery. © 2015 International Society on Thrombosis and Haemostasis.

Soluble urokinase plasminogen activator receptor levels are elevated and associated with complications in patients with type 1 diabetes

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Theilade, S; Lyngbaek, S; Hansen, T W

2015-01-01

OBJECTIVES: Soluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation and endothelial dysfunction. We investigated the associations between suPAR and diabetes, including diabetes duration and complications, in patients with type 1 diabetes. DESIGN, SETTING AND SUBJECTS......: From 2009 to 2011, 667 patients with type 1 diabetes and 51 nondiabetic control subjects were included in a cross-sectional study at Steno Diabetes Center, Gentofte, Denmark. suPAR levels were measured with an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: The investigated diabetic......% confidence interval) values per 1 ln unit increase in suPAR were as follows: 2.5 (1.1-5.7) for CVD: 2.7 (1.2-6.2) for autonomic dysfunction; 3.8 (1.3-10.9) for albuminuria and 2.5 (1.1-6.1) for a high degree of arterial stiffness (P ≤ 0.039). CONCLUSION: The suPAR level is higher in patients with type 1...

Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy

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Machado Ubiratan F

2011-04-01

Full Text Available Abstract Background The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored. Methods Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2 in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR ~250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP and heart rate variability (spectral analysis one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting. Results Higher glycemia (p vs. nondiabetics (p vs. SHR. Conclusions Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.

Asymptomatic coronary artery disease in Type-2 diabetes

International Nuclear Information System (INIS)

Ahmed, S.S.F.; Othman, S.; Meo, S.A.

2009-01-01

Objective: To select a subgroup of type-2 diabetics with two additional pre specified risk factors to see that whether there is any benefit of screening such patients. Methodology: Five hundred twenty six patients were sent for treadmill stress test or thallium scan. Those who had abnormal results were advised coronary angiography. The angiographically proven CAD was correlated with various risk factors to find the relationship between the disease and variables. Results: Two hundred thirty five (48%) patients had abnormal results and among them 158 (67%)underwent coronary angiography. Among these 21% had evidence of CAD. Coronary artery bypass grafting (CABG) was performed in 35(33%) patients, catheter based intervention (PCI) in 44(40%) patients and 30(27%) patients were not suitable for intervention. Duration of diabetes, smoking, diabetic retinopathy, albuminuria, and peripheral vascular disease were significant predictor of asymptomatic CAD. Conclusion: This study has demonstrated strong relationship between risk factors and asymptomatic CAD in type 2 diabetics. (author)

Sequential and functional renal scintiscanning in diabetic and hypertensive patients

International Nuclear Information System (INIS)

Wagner, M.

1978-01-01

47 diabetics (94 kidneys), 30 diabetics with concurrent hypertension (60 kidneys), and 23 hypertensives (46 kidneys) were examined by renal serial functional scintiscanning with 131 I-ortho-iodo-hippuric acid. For evaluation, camera nephrographs of the whole kidney, renal hemispheres, and renal cortex were used according to the technique of 'regions of interest', and the parameters of secretory value, maximum secretion, and elimination half-life were determined on this basis. With regard to the extent of hypertension, there are significant differences between all three groups for the elimination half-life; as far as the secretory value was concerned, there was a difference between the group with high hypertension and the two other groups. Significant differences in secretory value and elimination half-life were also observed in hypertensives with and without changes in the fundus of the eye. There was no noticeable difference between the three parameters in groups with and without albuminuria. (orig./AJ) 891 AJ/orig.- 892 MKO [de

[ManNAc, a new therapeutic agent to reduce Angptl4-induced proteinuria in MCD].

Science.gov (United States)

Clément, Lionel; Macé, Camille

2016-01-01

Current therapies used in minimal change disease (MCD) were originally designed to cure other diseases. They are only partially efficient, and present inconvenient side effects. Therefore, understanding the molecular mechanisms implicated in the pathogenesis of proteinuria in MCD could lead to new therapeutic strategies. A new experimental transgenic rat model of human MCD was generated. These NPHS2-Angptl4 transgenic rats over-express two different forms of the glycoprotein Angptl4 from the podocyte. The majority of the protein shows a lack of sialylation that is implicated in the pathogenesis of proteinuria. Supplementation of ManNAc, a precursor of sialic acid, significantly reduces albuminuria in those rats by increasing sialylation of the hyposialylated form of Angptl4. After treatment of the first episode of MCD with glucocorticoids in patients, ManNAc could be used as a maintenance drug, especially to reduce the frequency and intensity of relapse. ManNAc is a promising therapeutic agent for patients with MCD. © 2016 médecine/sciences – Inserm.

Toll-like receptor 2 or toll-like receptor 4 deficiency does not modify lupus in MRLlpr mice.

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Simon J Freeley

Full Text Available Systemic lupus erythematosus is an autoimmune disease with a high morbidity and nephritis is a common manifestation. Previous studies in murine lupus models have suggest a role for Toll-like receptor 2 and 4. We examined the role of these molecules in MRL lpr mice which is one of the most established and robust murine models. We compared disease parameters in Toll-like receptor 2 or Toll-like receptor 4 deficient mice with their littermate controls. We found no difference in the severity of glomerulonephritis as assessed by histology, serum creatinine and albuminuria when Toll-like receptor 2 or Toll-like receptor 4 deficient MRLlpr mice were compared with Toll-like receptor sufficient controls. We also found similar levels of anti-dsDNA and anti-ssDNA antibodies. These results show that Toll-like receptor 2 and Toll-like receptor 4 do not play a significant role in MRLlpr mice, and therefore they may not be important in human lupus.

Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type1) diabetic rats

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Nagai, Ryoji; Nagai, Mime; Shimasaki, Satoko; Baynes, John W.; Fujiwara, Yukio

2010-01-01

Although many fruits such as lemon and orange contain citric acid, little is known about beneficial effects of citric acid on health. Here we measured the effect of citric acid on the pathogenesis of diabetic complications in streptozotocin-induced diabetic rats. Although oral administration of citric acid to diabetic rats did not affect blood glucose concentration, it delayed the development of cataracts, inhibited accumulation of advanced glycation end products (AGEs) such as Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML) in lens proteins, and protected against albuminuria and ketosis . We also show that incubation of protein with acetol, a metabolite formed from acetone by acetone monooxygenase, generate CEL, suggesting that inhibition of ketosis by citric acid may lead to the decrease in CEL in lens proteins. These results demonstrate that the oral administration of citric acid ameliorates ketosis and protects against the development of diabetic complications in an animal model of type 1 diabetes. PMID:20117096

Determinants of Intravascular Resistance in Indian Diabetic Nephropathy Patients: A Hospital-Based Study

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Anubhav Thukral

2011-01-01

Full Text Available Aims and Objectives. Metabolic dysregulation has failed to explain clinical variability of patients with diabetic nephropathy and hence a renewed interest emerged in haemodynamic factors as determinant of progression and development of diabetic nephropathy. We therefore studied for various factors which can correlate with raised renal vascular resistance in diabetic nephropathy. Material and Methods. Renal vascular resistance was measured in patients with established and incipient diabetic nephropathy and compared with controls using noninvasive color Doppler examinations of intrarenal vasculature. Results. Renal vascular resistance correlated with age, duration of disease, GFR, serum creatinine, and stage of retinopathy. Renal vascular resistance was significantly reduced in patients on treatment with RAAS inhibitors and insulin, than those on OHA and antihypertensives other than RAAS inhibitors. Conclusion. The study implies that renal vascular resistance may help identify diabetics at high risk of developing nephropathy, and these set of patients could be candidates for RAAS inhibition and early insulin therapy even in patients without albuminuria.

Effect of Processing Delay and Storage Conditions on Urine Albumin-to-Creatinine Ratio

Science.gov (United States)

Illingworth, Nicola; Staplin, Natalie; Kumar, Aishwarya; Storey, Ben; Hrusecka, Renata; Judge, Parminder; Mahmood, Maria; Parish, Sarah; Landray, Martin; Haynes, Richard; Baigent, Colin; Hill, Michael; Clark, Sarah

2016-01-01

Background and objectives Because there is substantial biologic intraindividual variation in albumin excretion, randomized trials of albuminuria-reducing therapies may need multiple urine samples to estimate daily urinary albumin excretion. Mailing spot urine samples could offer a convenient and cost-effective method to collect multiple samples, but urine albumin-to-creatinine ratio stability in samples stored at ambient temperatures for several days is unknown. Design, setting, participants, & measurements Patients with kidney disease provided fresh urine samples in two tubes (with and without boric acid preservative). Reference aliquots from each participant were analyzed immediately, whereas remaining aliquots were subject to different handling/storage conditions before analysis, including delayed processing for up to 7 days at three different storage temperatures (4°C, 18°C, and 30°C), multiple freeze-thaw cycles, and long–term frozen storage at −80°C, −40°C, and −20°C. We calculated the mean percentage change in urine albumin-to-creatinine ratio for each condition, and we considered samples stable if the 95% confidence interval was within a ±5% threshold. Results Ninety-three patients provided samples with detectable albuminuria in the reference aliquot. Median (interquartile range) urine albumin-to-creatinine ratio was 87 (20–499) mg/g. The inclusion of preservative had minimal effect on fresh urine albumin-to-creatinine ratio measurements but reduced the changes in albumin and creatinine in samples subject to processing delay and storage conditions. The urine albumin-to-creatinine ratio was stable for 7 days in samples containing preservative at 4°C and 18°C and 2 days when stored at 30°C. It was also stable in samples with preservative after three freeze-thaw cycles and in frozen storage for 6 months at −80°C or −40°C but not at −20°C. Conclusions Mailed urine samples collected with preservative and received within 7 days if

Effect of Combination Treatment for Hypothyroidism on Renal Function in Patients with Hypothyroidism

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O.M. Didushko

2016-02-01

Full Text Available Objective. To improve known methods of diagnosing kidney damage in patients suffering from hypothyroidism with elements of metabolic syndrome, to study the effect of combined treatment on renal function. Materials and methods. The study included 240 patients with primary hypothyroidism (among them — 130 patients with primary hypothyroidism with components of the metabolic syndrome. All patients were divided into 2 groups: the I group included 42 patients with hypothyroidism without obesity (age 44.8 ± 5.7 years; body mass index (BMI 21.3 ± 2.6 kg/m2; group II — 45 patients with hypothyroidism and abdominal obesity (age 43.8 ± 6.1 years; BMI 33.4 ± 4.8 kg/m2. The control group included 20 healthy individuals (age 43.5 ± 5.9 years; BMI 22.0 ± 2.4 kg/m2. Kidney damage was detected in violation of glomerular filter permeability — occurrence of albuminuria and parameters of glomerular filtration rate (GFR were determined using CKD-EPI formulas. The concentration of monocyte chemoattractant protein-1 (MCP-1, leptin, insulin was determined by immunoenzyme assay. Results. During the correlation analysis, between GFR in patients of group I we have established: moderate inverse correlation between the level of GFR and thyroid stimulating hormone (TSH (r = 0.571, GFR and vascular endothelial growth factor (r = –0.616, GFR anf interleukin-6 (IL-6 (r = –0.418, total cholesterol (ChS (r = –0.311, GFR and insulin resistance index (IIR (r = –0.606 and weak inverse relationship between level of GFR and MCP-1 (r = –0.2917. In the II group of patients, a strong direct correlation between the level of GFR and IIR (r = 0.819, Caro index (r = 0.793 and a strong inverse correlation between GFR and TSH (r = –0.782, GFR and HOMA index (r = –0.875, moderate inverse correlation between the levels of GFR and ChS (r = –0.577, leptin (r = –0.476, GFR and IL-6 (r = –0.418, GFR and glucose (r = –0.436 and vascular endothelial growth factor (r

Burden of cardiovascular risk factors and disease among patients with type 1 diabetes: results of the Australian National Diabetes Audit (ANDA).

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Pease, Anthony; Earnest, Arul; Ranasinha, Sanjeeva; Nanayakkara, Natalie; Liew, Danny; Wischer, Natalie; Andrikopoulos, Sofianos; Zoungas, Sophia

2018-06-02

Cardiovascular risk stratification is complex in type 1 diabetes. We hypothesised that traditional and diabetes-specific cardiovascular risk factors were prevalent and strongly associated with cardiovascular disease (CVD) among adults with type 1 diabetes attending Australian diabetes centres. De-identified, prospectively collected data from patients with type 1 diabetes aged ≥ 18 years in the 2015 Australian National Diabetes Audit were analysed. The burden of cardiovascular risk factors [age, sex, diabetes duration, glycated haemoglobin (HbA1c), blood pressure, lipid profile, body mass index, smoking status, retinopathy, renal function and albuminuria] and associations with CVD inclusive of stroke, myocardial infarction, coronary artery bypass graft surgery/angioplasty and peripheral vascular disease were assessed. Restricted cubic splines assessed for non-linearity of diabetes duration and likelihood ratio test assessed for interactions between age, diabetes duration, centre type and cardiovascular outcomes of interest. Discriminatory ability of multivariable models were assessed with area under the receiver operating characteristic (ROC) curves. Data from 1169 patients were analysed. Mean (± SD) age and median diabetes duration was 40.0 (± 16.7) and 16.0 (8.0-27.0) years respectively. Cardiovascular risk factors were prevalent including hypertension (21.9%), dyslipidaemia (89.4%), overweight/obesity (56.4%), ever smoking (38.5%), albuminuria (31.1%), estimated glomerular filtration rate  7.0% (53 mmol/mol) (81.0%). Older age, longer diabetes duration, smoking and antihypertensive therapy use were positively associated with CVD, while high density lipoprotein-cholesterol and diastolic blood pressure were negatively associated (p < 0.05). Association with CVD and diabetes duration remained constant until 20 years when a linear increase was noted. Longer diabetes duration also had the highest population attributable risk of 6.5% (95% CI 1

The Effect of Uric Acid Lowering on Albuminuria and Renal Function in Type 1 Diabetes: A Randomized Clinical Trial

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Pilemann-Lyberg, Sascha; Persson, Frederik; Frystyk, Jan

were randomized to: (1) Allopurinol (400 mg daily) + standard therapy; or (2) placebo + standard therapy for 60 days. Participants underwent a 4 week washout period prior to cross-over. Primary end-point was change in UAER (3*24h collections), secondary endpoint was change in GFR (51Cr-EDTA.......8 (1.5) with placebo (p24h UAER (geometric mean (IQR)) was 221 ( 131-367) mg/24h after treatment with allopurinol and 228 (151-344) mg/24h with placebo (p=0.83). Mean (SD) GFR (51Cr-EDTA) was 74 (20) ml/min/1.73m2 after allopurinol treatment compared with 73 (20) ml/min/1.73m2 after...... 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...

[Henoch-Schönlein Purpura with lung abscess].

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Nakazawa, Junji; Watanabe, Atsushi; Nakajima, Tomohiro; Mishina, Taijiro; Miyajima, Masahiro; Higami, Tetsuya

2013-09-01

A 72-year-old man had underwent left lower lobectomy for squamous cell carcinoma in our hospital in 2008. Postoperative stage was I A (T1N0M0). In 2010, follow-up chest computed tomography (CT) images showed similar cavitary nodules in segments 2 and 8 of the right lung with positive uptake on fluorodeoxyglucose-positron emission tomography (FDG-PET) images. Physical examination, blood tests, and levels of serum tumor markers showed no abnormality. Transbronchial lung biopsy revealed the absence of malignant cells. Segment 8 of the right lower lobe with the nodule was partially resected, and pathological examination demonstrated lung abscess. He was discharged but was hospitalized in another hospital for purpuric rash, fever, and arthralgia. Microscopic albuminuria was noted, and renal biopsy revealed nephritis with immunoglobulin A( IgA)deposition. He was made a diagnosis of Henoch-Schönlein purpura. Oral steroid therapy( prednisolone 60 mg/d) was initiated, resulting in the improvement of symptoms and disapearance of the cavitary nodule in the right lung segment 2.

Biomarkers of Renal Disease and Progression in Patients with Diabetes

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Radovan Hojs

2015-05-01

Full Text Available Diabetes prevalence is increasing worldwide, mainly due to the increase in type 2 diabetes. Diabetic nephropathy occurs in up to 40% of people with type 1 or type 2 diabetes. It is important to identify patients at risk of diabetic nephropathy and those who will progress to end stage renal disease. In clinical practice, most commonly used markers of renal disease and progression are serum creatinine, estimated glomerular filtration rate and proteinuria or albuminuria. Unfortunately, they are all insensitive. This review summarizes the evidence regarding the prognostic value and benefits of targeting some novel risk markers for development of diabetic nephropathy and its progression. It is focused mainly on tubular biomarkers (neutrophil-gelatinase associated lipocalin, kidney injury molecule 1, liver-fatty acid-binding protein, N-acetyl-beta-d-glucosaminidase, markers of inflammation (pro-inflammatory cytokines, tumour necrosis factor-α and tumour necrosis factor-α receptors, adhesion molecules, chemokines and markers of oxidative stress. Despite the promise of some of these new biomarkers, further large, multicenter prospective studies are still needed before they can be used in everyday clinical practice.

Hibiscus sabdariffa polyphenols alleviate insulin resistance and renal epithelial to mesenchymal transition: a novel action mechanism mediated by type 4 dipeptidyl peptidase.

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Peng, Chiung-Huei; Yang, Yi-Sun; Chan, Kuei-Chuan; Wang, Chau-Jong; Chen, Mu-Lin; Huang, Chien-Ning

2014-10-08

The epithelial to mesenchymal transition (EMT) is important in renal fibrosis. Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 (S307)) is a hallmark of insulin resistance. We report that polyphenol extracts of Hibiscus sabdariffa (HPE) ameliorate diabetic nephropathy and EMT. Recently it has been observed that type 4 dipeptidyl peptidase (DPP-4) inhibitor linagliptin is effective for treating type 2 diabetes and albuminuria. We investigated if DPP-4 and insulin resistance are involved in renal EMT and explored the role of HPE. In high glucose-stimulated tubular cells, HPE, like linagliptin, inhibited DPP-4 activation, thereby regulating vimentin (EMT marker) and IRS-1 (S307). IRS-1 knockdown revealed its essential role in mediating downstream EMT. In type 2 diabetic rats, pIRS-1 (S307) abundantly surrounds the tubular region, with increased vimentin in kidney. Both the expressions were reduced by HPE. In conclusion, HPE exerts effects similar to those of linagliptin, which improves insulin resistance and EMT, and could be an adjuvant to prevent diabetic nephropathy.

Kidney Disease Measures and Left Ventricular Structure and Function: The Atherosclerosis Risk in Communities Study.

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Matsushita, Kunihiro; Kwak, Lucia; Sang, Yingying; Ballew, Shoshana H; Skali, Hicham; Shah, Amil M; Coresh, Josef; Solomon, Scott

2017-09-22

Heart failure is one of the most important complications of chronic kidney disease (CKD). However, few studies comprehensively investigated left ventricular (LV) structure and function in relation to 2 key CKD measures, estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR). Among 4175 ARIC (Atherosclerosis Risk in Communities) participants (aged 66-90 years during 2011-2013), we quantified the association of eGFR and ACR with echocardiogram parameters of LV mass, size, systolic function, and diastolic function. Adjusting for demographic variables, both CKD measures were significantly associated with most echocardiogram parameters. Additionally accounting for other potential confounders, we observed significantly higher LV mass index according to reduced eGFR (82.3 [95% confidence interval (CI), 77.6-87.0] g/m 2 for eGFR function, significant differences were observed for some parameters, particularly at eGFR function were robustly associated with albuminuria. These results have implications for pathophysiological processes behind cardiorenal syndrome and targeted cardiac assessment in patients with CKD. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Clinico-pathological features of kidney disease in diabetic cases.

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Furuichi, Kengo; Shimizu, Miho; Okada, Hirokazu; Narita, Ichiei; Wada, Takashi

2018-03-21

Diabetic kidney disease is the major cause of end-stage kidney disease in developed countries. However, the onset of kidney disorder and the progression pattern of kidney dysfunction and proteinuria greatly vary cases by cases. Therefore, risk classification with clinical data and pathological findings is important. Recent clinico-pathological study with kidney biopsy samples from diabetic patients revealed that pathological changes of diabetic nephropathy are characteristic and have special impacts on prognosis in each clinical stage. Moreover, comparison of the clinico-pathological findings of diabetic nephropathy with hypertensive nephrosclerosis revealed that there are few differences in their pathological findings in cases with low albuminuria and preserved estimated glomerular filtration rate (eGFR). Because it is so difficult to clearly distinguish pure kidney lesions caused by diabetes and kidney lesions due to effects other than diabetes, it is vital that these overlapped pathological findings be confirmed on kidney biopsy in cases of early stage diabetes. Further research is warranted regarding the pathogenesis of diabetic nephropathy and indication of kidney biopsy in diabetic cases.

Amelioration of renal lesions associated with diabetes by dietary curcumin in streptozotocin diabetic rats.

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Suresh Babu, P; Srinivasan, K

1998-04-01

Curcumin, the coloring principle of the commonly used spice turmeric (Curcuma longa) was fed at 0.5% in the diet to streptozotocin-induced diabetic Wistar rats for 8 weeks. Renal damage was assessed by the amount of proteins excreted in the urine and the extent of leaching of renal tubular enzymes: NAG, LDH, AsAT, AlAT, alkaline and acid phosphatases. The integrity of kidney was assessed by measuring the activities of several key enzymes of the renal tissue: glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and LDH (Carbohydrate metabolism), aldose reductase and sorbitol dehydrogenase (polyol pathway), transaminases, ATPases and membrane PUFA/SFA ratio (membrane integrity). Data on enzymuria, albuminuria, activity of kidney ATPases and fatty acid composition of renal membranes in diabetic condition suggested that dietary curcumin brought about significant beneficial modulation of the progression of renal lesions in diabetes. These findings were also corroborated by histological examination of kidney sections. It is inferred that this beneficial ameliorating influence of dietary curcumin on diabetic nephropathy is possibly mediated through its ability to lower blood cholesterol levels.

Benfotiamine protects against peritoneal and kidney damage in peritoneal dialysis.

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Kihm, Lars P; Müller-Krebs, Sandra; Klein, Julia; Ehrlich, Gregory; Mertes, Laura; Gross, Marie-Luise; Adaikalakoteswari, Antonysunil; Thornalley, Paul J; Hammes, Hans-Peter; Nawroth, Peter P; Zeier, Martin; Schwenger, Vedat

2011-05-01

Residual renal function and the integrity of the peritoneal membrane contribute to morbidity and mortality among patients treated with peritoneal dialysis. Glucose and its degradation products likely contribute to the deterioration of the remnant kidney and damage to the peritoneum. Benfotiamine decreases glucose-induced tissue damage, suggesting the potential for benefit in peritoneal dialysis. Here, in a model of peritoneal dialysis in uremic rats, treatment with benfotiamine decreased peritoneal fibrosis, markers of inflammation, and neovascularization, resulting in improved characteristics of peritoneal transport. Furthermore, rats treated with benfotiamine exhibited lower expression of advanced glycation endproducts and their receptor in the peritoneum and the kidney, reduced glomerular and tubulointerstitial damage, and less albuminuria. Increased activity of transketolase in tissue and blood contributed to the protective effects of benfotiamine. In primary human peritoneal mesothelial cells, the addition of benfotiamine led to enhanced transketolase activity and decreased expression of advanced glycation endproducts and their receptor. Taken together, these data suggest that benfotiamine protects the peritoneal membrane and remnant kidney in a rat model of peritoneal dialysis and uremia. Copyright © 2011 by the American Society of Nephrology

Loss of Kynurenine 3-Mono-oxygenase Causes Proteinuria.

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Korstanje, Ron; Deutsch, Konstantin; Bolanos-Palmieri, Patricia; Hanke, Nils; Schroder, Patricia; Staggs, Lynne; Bräsen, Jan H; Roberts, Ian S D; Sheehan, Susan; Savage, Holly; Haller, Hermann; Schiffer, Mario

2016-11-01

Changes in metabolite levels of the kynurenine pathway have been observed in patients with CKD, suggesting involvement of this pathway in disease pathogenesis. Our recent genetic analysis in the mouse identified the kynurenine 3-mono-oxygenase (KMO) gene (Kmo) as a candidate gene associated with albuminuria. This study investigated this association in more detail. We compared KMO abundance in the glomeruli of mice and humans under normal and diabetic conditions, observing a decrease in glomerular KMO expression with diabetes. Knockdown of kmo expression in zebrafish and genetic deletion of Kmo in mice each led to a proteinuria phenotype. We observed pronounced podocyte foot process effacement on long stretches of the filtration barrier in the zebrafish knockdown model and mild podocyte foot process effacement in the mouse model, whereas all other structures within the kidney remained unremarkable. These data establish the candidacy of KMO as a causal factor for changes in the kidney leading to proteinuria and indicate a functional role for KMO and metabolites of the tryptophan pathway in podocytes. Copyright © 2016 by the American Society of Nephrology.

Epidemiology of diabetic kidney disease.

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Reutens, Anne T

2013-01-01

The increasing prevalence of diabetes has led to DKD becoming the leading cause of ESRD in many regions. The economic cost of DKD will grow to prohibitive amounts unless strategies to prevent its onset or progression are urgently implemented. In type 1 and type 2 diabetes, the presence of microalbuminuria and macroalbuminuria confers increased risk of developing ESRD and of death. Comparison of recent studies with earlier historical studies shows that the incidence of ESRD and death has decreased in DKD. Increased risk of albuminuria has been identified in certain non-European ethnic groups. However, the initial concept of progression of DKD as an albuminuric phenotype involving development of microalbuminuria, macroalbuminuria, and then ESRD has had to be modified. Albumin excretion frequently regresses, and GFR can decline without abnormality in albumin excretion. There is emerging evidence that changes in renal function occurring early in the course of diabetes predict future outcomes. The major challenges are to prevent DKD onset, to detect it early, and to improve DKD outcomes globally. Copyright © 2013 Elsevier Inc. All rights reserved.

Prevalence and biochemical risk factors of diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese adults with type 2 diabetes mellitus.

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Pai, Yen-Wei; Lin, Ching-Heng; Lee, I-Te; Chang, Ming-Hong

To investigate the prevalence and risk factors for diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese. A cross-sectional, hospital-based observational study was conducted. We enrolled 2837 adults with type 2 diabetes mellitus. Diabetic peripheral neuropathy with or without pain were diagnosed using 2 validated screening tools, namely the Michigan Neuropathy Screening Instrument and Douleur Neuropathique 4 questionnaire. In our sample, 2233 participants had no neuropathy, 476 had diabetic peripheral neuropathy without pain, and 128 had diabetic peripheral neuropathy with neuropathic pain, representing an overall diabetic peripheral neuropathy prevalence of 21.3%, and the prevalence of neuropathic pain in diabetic peripheral neuropathy was 21.2%. Multivariate analysis revealed that older age (Pperipheral neuropathy, whereas older age (Pperipheral neuropathy with neuropathic pain. During clinical visits involving biochemical studies, the risk for diabetic peripheral neuropathy with neuropathic pain should be considered for people with older age, elevated glycated haemoglobin, low high-density lipoprotein cholesterol and overt proteinuria, with particular attention given to increased levels of albuminuria while concerning neuropathic pain. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

TGP attenuates endoplasmic reticulum stress and regulates the expression of thioredoxin-interacting protein in the kidneys of diabetic rats.

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Shao, Yunxia; Qi, Xiangming; Xu, Xinxing; Wang, Kun; Wu, Yonggui; Xia, Lingling

2017-01-16

Recent evidence suggests that the endoplasmic reticulum stress (ERS)-thioredoxin-interacting protein (TXNIP)-inflammation chain contributes to diabetic renal injury. The aim of the current study was to investigate whether total glucosides of peony (TGP) could inhibit ERS and attenuate up-regulation of TXNIP in the kidneys of rats with streptozotocin-induced diabetes. TGP was orally administered daily at a dose of 50, 100, or 200 mg/kg for 8 weeks. The expression of glucose-regulated protein 78 (GRP78), phospho-protein kinase RNA-like ER kinase (p-PERK), phosphor- eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), and TXNIP was assessed. Results indicated that TGP significantly decreased diabetes-induced albuminuria and it acted by down-regulating activation of the ERS-TXNIP-inflammation chain in the kidneys of diabetic rats. These findings indicate that renoprotection from TGP in diabetic rats possibly contributed to inhibition of ERS and decreased expression of TXNIP. These findings also offer a new perspective from which to study the molecular mechanisms of diabetic nephropathy and prevent its progression.

Pathogenesis and Novel Treatment from the Mouse Model of Type 2 Diabetic Nephropathy

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Masako Furukawa

2013-01-01

Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage kidney disease worldwide. However, current treatments remain suboptimal. Many factors, such as genetic and nongenetic promoters, hypertension, hyperglycemia, the accumulation of advanced glycation end products (AGEs, dyslipidemia, and albuminuria/proteinuria itself, influence the progression of this disease. It is important to determine the molecular mechanisms and treatment of this disease. The development of diabetes results in the formation of AGEs, oxidative stress, and the activation of the renin-angiotensin-aldosterone system (RAAS within the kidney, which promotes progressive inflammation and fibrosis, leading to DN and declining renal function. A number of novel therapies have also been tested in the experimental diabetic model, including exercise, inhibitors of the RAAS (angiotensin type 1 receptor blockers (ARB, angiotensin-converting enzyme (ACE inhibitors, inhibitors of AGE (pyridoxamine, peroxisome proliferator-activated receptor (PPAR γ agonists (pioglitazone, inhibitors of lipid accumulation (statins and eicosapentaenoic acid (EPA, and the vitamin D analogues. This review summarizes the advances in knowledge gained from our studies and therapeutic interventions that may prevent this disease.

Antihypertensive effects of double the maximum dose of valsartan in African-American patients with type 2 diabetes mellitus and albuminuria

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Weir, Matthew R; Hollenberg, Norman K; Zappe, Dion H

2010-01-01

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...

The effect of uric acid lowering treatment on albuminuria and renal function in Type 1 diabetes:a randomized clinical trial

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Pilemann-Lyberg, S; Persson, F; Frystyk, J

2018-01-01

Significant improvements have been made in the management of Type 1 diabetes over the last three decades [1]. 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...

Aliskiren in combination with losartan reduces albuminuria independent of baseline blood pressure in patients with type 2 diabetes and nephropathy

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Persson, Frederik; Lewis, Julia B; Lewis, Edmund J

2011-01-01

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....

Serum Adiponectin and Glomerular Filtration Rate in Patients with Type 2 Diabetes.

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Lorena Ortega Moreno

Full Text Available High serum adiponectin has been increased in several conditions of kidney disease. Only sparse and conflicting results have been reported in patients with type 2 diabetes (T2D, a subgroup of individuals who are at high risk for renal dysfunction. The aim of this study was to fill up this gap of knowledge by investigating such association in a large sample of Italian diabetic patients. The association between serum adiponectin levels and estimated glomerular filtration rate (eGFR by Chronic Kidney Disease-Epidemiology Collaboration CKD-EPI equation was investigated in 1,243 patients with T2D from two cross-sectional Italian studies: 878 from San Giovanni Rotondo (SGR and 365 from Foggia (FG. Serum adiponectin was inversely associated with eGFR in SGR [β (standard error, SE for 1 standard deviation (SD of adiponectin = -3.26 (0.64] and in FG [β(SE=-5.70(1.28] sample, as well as in the two studies combined [β(SE=-3.99(0.59];(p<0.0001 for all. In this combined analysis, the association was still significant after adjusting for sex, smoking habits, body mass index (BMI, waist circumference, diabetes duration, glycated hemoglobin (HbA1c, albumin creatinine ratio (ACR and anti-hyperglycemic, anti-hypertensive and anti-dyslipidemic treatments [β (SE= -2.19 (0.59, p = 0.0001]. A stronger association between each SD adiponectin increment and low eGFR was observed among patients with micro-/macro-albuminuria, as compared to those with normo-albuminuria [adjusted β(SE=-4.42(1.16 ml/min/1.73m2 vs. -1.50 (0.67 ml/min/1.73m2, respectively; p for adiponectin-by-albuminuric status = 0.022]. For each adiponectin SD increment, the odds of having eGFR < 60 ml/min/1.73m2 increased by 41% (odds ratio, OR = 1.41; 95% confidence interval, CI 1.21-1.64 in SGR sample, 53% (OR = 1.53; 95% CI 1.21-1.94 in FG sample, and 44% (OR = 1.44; 95%CI 1.27-1.64 in the two studies considered together (p<0.0001 for all. In the combined sample, further adjustment for the above

Reversal of diabetic nephropathy by a ketogenic diet.

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Michal M Poplawski

Full Text Available Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita and Type 2 (db/db diabetes, diabetic nephropathy (as indicated by albuminuria was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined.

Ultrasonographic study of common carotid arteries in adolescents with type 1 diabetes mellitus

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Viktoriya Nikolaevna Panfilova

2009-03-01

Full Text Available Aim. To elucidate sonographic characteristics of common carotid arteries in adolescents with type1 diabetes mellitus (DM1 depending on the duration of the disease and thepresence of chronic complications. Materials and methods. A total of 56 adolescents having DM1 of different duration were examined to evaluate conditions of common carotid arteries (CA in the systole anddiastole during at least 3 cardiac cycles. The following parameters were measured: CA diameter, intima-media thickness (IMT, estimated stretch and stiffness coefficients, Youngsmodulus. The control group comprised 16 healthy adolescents. Results. Bilateral increase of IMT was recorded in patients with DM duration over 5 years. Youngs modulus, stretch and stiffness coefficients were virtually unrelated to diseaseduration. In patients having DM for more than 10 years, stretch coefficient was 5.38 (95% DI 4.82-5.8 compared with 5.82 (95% DI 5.63-7.38 in those with DM for less than 3years (p = 0.04. The level of albuminuria correlated with IMT (r=0.32, p=0.03, stiffness coefficient (r = 0.43, p=0.001, stretch coefficient (r= -0.48, p

Relationship between renal hemodynamic status and aging in patients without diabetes evaluated by renal Doppler ultrasonography.

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Kawai, Tatsuo; Kamide, Kei; Onishi, Miyuki; Hongyo, Kazuhiro; Yamamoto-Hanasaki, Hiroko; Oguro, Ryosuke; Maekawa, Yoshihiro; Yamamoto, Koichi; Takeya, Yasushi; Sugimoto, Ken; Ohishi, Mitsuru; Rakugi, Hiromi

2012-10-01

Aging is well known as one of the major causes of a reduced glomerular filtration rate (GFR). The resistive index (RI) measured by renal Doppler ultrasonography (RDU) is thought to be a good indicator of renal vascular resistance induced by arteriosclerosis. In this study, we investigated whether RI could be used to evaluate the pathogenesis of renal damage or the mechanisms of reduction of renal function by aging. We investigated the correlation between RI and multiple clinical parameters and the influence of aging on the renal hemodynamic status of 194 in-patients (mean age 66.2 years) who underwent RDU at our hospital between February 2009 and July 2010. RI was significantly correlated with the age, estimated GFR (eGFR), diastolic blood pressure, pulse pressure, and degree of albuminuria. Subjects aged ≥75 years showed a significantly higher correlation coefficient between eGFR and RI. RI showed a stronger correlation with age in subjects aged ≥75 years compared to eGFR. The present study showed that renal vascular resistance and intra-renal arteriosclerosis had a greater impact on renal function in older than younger subjects, reflecting the possible mechanisms of renal function reduction due to aging.

The effects of environmental chemicals on renal function.

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Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

2015-10-01

The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease.

Alpha-mangostin attenuates diabetic nephropathy in association with suppression of acid sphingomyelianse and endoplasmic reticulum stress.

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Liu, Tingting; Duan, Wang; Nizigiyimana, Paul; Gao, Lin; Liao, Zhouning; Xu, Boya; Liu, Lerong; Lei, Minxiang

2018-02-05

Diabetic nephropathy is a common complication of diabetes, but there are currently few treatment options. The aim of this study was to gain insight into the effect of alpha-mangostin on diabetic nephropathy and possible related mechanisms. Goto-Kakizaki rats were used as a diabetic model and received alpha-mangostin or desipramine treatment with normal saline as a control. Ten age-matched Sprague Dawley rats were used as normal controls and treated with normal saline. At week 12, blood glucose, albuminuria, apoptosis and renal pathologic changes were assessed. Protein levels for acid sphingomyelinase, glucose-regulated protein 78, phosphorylated PKR-like ER-resident kinase, activated transcription factor 4, CCAAT/enhancer-binding protein, homologous protein), and cleaved-caspase12 were measured. The level of acid sphingomyelinase was significantly increased, and ER stress was activated in diabetic rat kidneys when compared to the control animals. When acid sphingomyelinase was inhibited by alpha-mangostin, the expression of ER stress-related proteins was down-regulated in association with decreased levels of diabetic kidney injury. Alpha-mangostin, an acid sphingomyelinase inhibitor plays a protective role in diabetic neuropathy by relieving ER stress induced-renal cell apoptosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Structural and Functional Changes in Human Kidneys with Healthy Aging.

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Hommos, Musab S; Glassock, Richard J; Rule, Andrew D

2017-10-01

Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, age-related reduction in GFR with the corresponding increase in CKD (defined by an eGFRage-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria. Copyright © 2017 by the American Society of Nephrology.

The relationship between ACE/AGT gene polymorphisms and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes.

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Qiao, Yong-Chao; Wang, Min; Pan, Yan-Hong; Zhang, Xiao-Xi; Tian, Fang; Chen, Yin-Ling; Zhao, Hai-Lu

2018-01-01

This study aims to investigate the association between renin-angiotensin system gene polymorphism and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes. We consecutively included 1491 patients for the assessment of ACE I/D and AGT M/T gene polymorphisms in 345 DR cases and 1146 patients without retinopathy (DNR). Albuminuria was defined by urine albumin creatinine ratio and albumin excretion rate. Compared with the NDR patients, the DR cases displayed a higher proportion of diabetic nephropathy (32.68% vs. 6.52%, χ 2 = 150.713, p ACE I/D and AGT M/T (all p > 0.05). Intriguingly, DR patients with obesity showed higher frequency of DD (χ 2 = 4.181, p = 0.041), but no significant difference exists in the other stratified BMI and hypertension analyses (all p > 0.05). Binary logistic regression displays that the association of the ACE and AGT gene polymorphisms in DR patients is not significant after adjusting for confounding covariates in all the comparisons. The ACE and AGT gene polymorphisms are not associated with the progress of diabetes developing into retinopathy in Chinese patients with type 2 diabetes. However, more investigations are needed to further prove the association.

Intravenous injection of ioxilan, iohexol and diatrizoate

International Nuclear Information System (INIS)

Thomsen, H.S.; Dorph, S.; Mygind, T.; Sovak, M.; Nielsen, H.; Rygaard, H.; Larsen, S.; Skaarup, P.; Hemmingsen, L.; Holm, J.

1988-01-01

Effects of intravenous ioxilan, a new third generation non-ionic contrast medium, diatrizoate, iohexol and saline on urine profiles were compared. Albumin, glucose, sodium, phosphate, and the enzymes NAG, LDH and GGT were followed in 24 normal rats over 7 days. Diatrizoate significantly affected all profile components during the first two hours. Albuminuria was significantly greater after diatrizoate than after iohexol or ioxilan, and excretion of glucose, LDH and GGT was significantly higher than after ioxilan. Both iohexol and ioxilan increased the excretion of albumin, LDH and GGT, while iohexol also significantly increased excretion of glucose and sodium. There was a greater excretion of glucose and GGT after iohexol than after ioxilan. Saline did not induce any changes. At day 7, serum sodium, urea, creatinine, and albumin were normal for all test substances, and kidney histology revealed no difference between the groups of animals. It is thus concluded that both high osmolar ionic and low osmolar non-ionic contrast media may cause temporary glomerular and tubular dysfunction in rats. In this model, the kidney is affected most by diatrizoate, less by iohexol, and least by ioxilan. (orig.)

Clinical significance of determination of GFR, urinary albumin and UAlb/UCr in patients with type 2 diabetes

International Nuclear Information System (INIS)

Zhang Li; Li Sumei; Zhang Rong; Zhai Fei

2010-01-01

Objective: To study the diagnostic value of determination of glomerular filtration rate (GFR), Urinary albumin (UAlb) and UAlb/UCr for early diabetic nephropathy in patients with type 2 Diabetes. Methods: UAlb, UAlb/UCr were measured with radioimmunoassay (RIA) and GFR measured with Tcm DTPA dynamic renal imaging in 102 DM2 patients with diabetic nephropathy (DN) and 23 DM2 patients without nephropathy. Results: In diabetics with nephropathy with a disease course of less than five years (n=38), the GFR, UAlb/UCr were significantly higher than those in diabetics without nephropathy. With prolongation of the disease, GFR gradually declined and UAlb/UCr rose further and in patients with nephropathy with disease courses over 10 years, the GFR was significantly lower and UAlb/UCr significantly higher than those in diabetics without nephropathy (all P<0.05). The GFR was negatively correlated with course of disease, BMI and UAlb/UCr (r=-0.691, -0.631, -0.698, respectively, P<0.01). Conclusion: GFR can reflect the degree of renal damage of diabetic patients,and may be helpful for evaluation of progression of DN when combined with assay of albuminuria. (authors)

The association of serum leptin levels with metabolic diseases

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Jen-Pi Tsai

2017-01-01

Full Text Available Leptin is a 167-amino-acid protein released by white adipose tissue and encoded by the obese gene. It has a role as a negative regulator of appetite control through sending a satiety signal to act on receptors within the hypothalamus. At normal levels, leptin can exert its effects on weight regulation according to white fat mass, induce sodium excretion, maintain vascular tone, and repair the myocardium. Beyond these effects, elevated serum leptin levels have been implicated in the pathogenesis of metabolic syndrome, diabetes mellitus, hypertension, and multiple cardiovascular diseases. In addition, hyperleptinemia had been reported to contribute to renal diseases through multiple mechanisms resulting in glomerulopathy presenting with a decreased glomerular filtration rate, increased albuminuria, and related clinical symptoms, which are pathophysiological features of chronic kidney disease. Because these cardiovascular and metabolic disorders are great challenges for physicians, understanding the related pathophysiological association with leptin might become a valuable aid in handling patients in daily clinical practice. This review will discuss the roles of leptin in the regulation of biological functions of multiple organs beyond the maintenance of feeding and metabolism.

Reversal of Diabetic Nephropathy by a Ketogenic Diet

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Poplawski, Michal M.; Mastaitis, Jason W.; Isoda, Fumiko; Grosjean, Fabrizio; Zheng, Feng; Mobbs, Charles V.

2011-01-01

Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined. PMID:21533091

Autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury induced by albumin overload.

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Tan, Jin; Wang, Miaohong; Song, Shuling; Miao, Yuyang; Zhang, Qiang

2018-01-10

Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload.

The Prevalence of CKD in Rural Canadian Indigenous Peoples: Results From the First Nations Community Based Screening to Improve Kidney Health and Prevent Dialysis (FINISHED) Screen, Triage, and Treat Program.

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Komenda, Paul; Lavallee, Barry; Ferguson, Thomas W; Tangri, Navdeep; Chartrand, Caroline; McLeod, Lorraine; Gordon, Audrey; Dart, Allison; Rigatto, Claudio

2016-10-01

Indigenous Canadians have high rates of risk factors for chronic kidney disease (CKD), in particular diabetes. Furthermore, they have increased rates of complications associated with CKD, such as kidney failure and vascular disease. Our objective was to describe the prevalence of CKD in this population. Cross-sectional cohort. Indigenous (First Nations) Canadians 18 years or older screened as part of the First Nations Community Based Screening to Improve Kidney Health and Prevent Dialysis (FINISHED) project, an initiative completed in 2015 that accomplished community-wide screening in 11 rural communities in Manitoba, Canada. Indigenous ethnicity and geographic location (communities accessible by road compared with those accessible only by air). Prevalence of CKD, presumed based on a single ascertainment of urine albumin-creatinine ratio (UACR) ≥ 30mg/g and/or estimated glomerular filtration rate (eGFR)indigenous Canadians in comparison to the general population and a prevalence of severely increased albuminuria that was 5-fold higher. This is comparable to patients with diabetes and/or hypertension. Public health strategies to screen, triage, and treat all Canadian indigenous peoples with CKD should be considered. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Pulse Pressure, Instead of Brachium-Ankle Pulse Wave Velocity, is Associated with Reduced Kidney Function in a Chinese Han Population.

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Jia, Linpei; Zhang, Weiguang; Ma, Jie; Chen, Xizhao; Chen, Lei; Li, Zuoxiang; Cai, Guangyan; Huang, Jing; Zhang, Jinping; Bai, Xiaojuan; Feng, Zhe; Sun, Xuefeng; Chen, Xiangmei

2017-01-01

In this study, we aim to investigate the association between renal function and arterial stiffness in a Chinese Han population, and further to discuss the effects of smoking on renal function. We collected the data of the brachium-ankle pulse wave velocity (baPWV), blood pressure, blood chemistry and smoking status. Then, the multiple linear regression was done to explore the relationship between estimated glomerular filtration (eGFR) and baPWV. Further, the parameters were compared among the four groups divided according to the quartiles of baPWV. Finally, the baPWV, eGFR and albuminuria values were compared between smokers and non-smokers. baPWV is associated with eGFR in the correlation analysis and univariate linear regression model. After adjustment, the pulse pressure (PP) instead of baPWV showed a significant association with eGFR. Nevertheless, the eGFR values differed among the four baPWV groups; the baPWV values were significantly higher in the subjects at the CKD (eGFRfunction. Smokers have worse arterial stiffness and worse renal function. © 2017 The Author(s)Published by S. Karger AG, Basel.

[Analysis of microalbuminuria with immunonephelometry and high performance liquid chromatography. Evaluation of new criteria].

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Markó, Lajos; Molnár, Gergo Attila; Wagner, Zoltán; Koszegi, Tamás; Matus, Zoltán; Mohás, Márton; Kuzma, Mónika; Szijártó, István András; Wittmann, István

2008-01-13

Hypertension as well as type 2 diabetes mellitus is a major factor in population mortality. Both diseases damage the endothelium, the early sign of which is microalbuminuria, which can be screened by dipstick and can be diagnosed by using immuno-based and high performance liquid chromatography methods. Using high performance liquid chromatography, the non-immunoreactive albumin can be detected as well. The authors aimed at the examination of albuminuria in the case of immunonephelometrically negative patients with high performance liquid chromatography, in diabetic and hypertensive and non-diabetic hypertensive populations. The authors also wanted to compare the present (albumin-creatinine ratio: male: > or =2.5 mg/mmol, female: > or =3.5 mg/mmol) and a new criteria of the Heart Outcomes Prevention Evaluation study (patients without diabetes: immunological method, > or =0.7 mg/mmol; high performance liquid chromatography, > or =3.1 mg/mmol; individuals with diabetes: immunological method, > or =1.4 mg/mmol; high performance liquid chromatography, > or =5.2 mg/mmol) of microalbuminuria. Examination of fresh urines of 469 microalbuminuria negative patients by dipstick were performed by immunonephelometry. Patients, who were microalbuminuria negative by immunonephelometry as well, were further analyzed by high performance liquid chromatography using the Accumintrade mark Kit, based on size-exclusion chromatography. Three times higher albuminuria were found with high performance liquid chromatography than with immunonephelometry. The intraindividual coefficient of variation did not differ in the two methods (37 +/- 31% vs. 40 +/- 31%, p = 0.869; immunonephelometry vs. high performance liquid chromatography; mean +/- standard deviation). Using the present criteria for microalbuminuria, 43% of immunonephelometrically negative patients proved to be microalbuminuric by high performance liquid chromatography. Using the new criteria of the Heart Outcomes Prevention

Chronic Kidney Disease in Primary Care: Outcomes after Five Years in a Prospective Cohort Study.

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Adam Shardlow

2016-09-01

Full Text Available Chronic kidney disease (CKD is commonly managed in primary care, but most guidelines have a secondary care perspective emphasizing the risk of end-stage kidney disease (ESKD and need for renal replacement therapy. In this prospective cohort study, we sought to study in detail the natural history of CKD in primary care to better inform the appropriate emphasis for future guidance.In this study, 1,741 people with CKD stage 3 were individually recruited from 32 primary care practices in Derbyshire, United Kingdom. Study visits were undertaken at baseline, year 1, and year 5. Binomial logistic regression and Cox proportional hazards models were used to model progression, CKD remission, and all-cause mortality. We used Kidney Disease: Improving Global Outcomes (KDIGO criteria to define CKD progression and defined CKD remission as the absence of diagnostic criteria (estimated glomerular filtration rate [eGFR] >60 ml/min/1.73 m2 and urine albumin-to-creatinine ratio [uACR] <3 mg/mmol at any study visit. Participants were predominantly elderly (mean ± standard deviation (SD age 72.9 ± 9.0 y, with relatively mild reduction in GFR (mean ± SD eGFR 53.5 ± 11.8 mL/min/1,73 m2 and a low prevalence of albuminuria (16.9%. After 5 y, 247 participants (14.2% had died, most of cardiovascular causes. Only 4 (0.2% developed ESKD, but 308 (17.7% evidenced CKD progression by KDIGO criteria. Stable CKD was observed in 593 participants (34.1%, and 336 (19.3% met the criteria for remission. Remission at baseline and year 1 was associated with a high likelihood of remission at year 5 (odds ratio [OR] = 23.6, 95% CI 16.5-33.9 relative to participants with no remission at baseline and year 1 study visits. Multivariable analyses confirmed eGFR and albuminuria as key risk factors for predicting adverse as well as positive outcomes. Limitations of this study include reliance on GFR estimated using the Modification of Diet in Renal Disease study (MDRD equation for

Taurine Alleviates the Progression of Diabetic Nephropathy in Type 2 Diabetic Rat Model

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Jang Hyun Koh

2014-01-01

Full Text Available The overexpression of vascular endothelial growth factor (VEGF is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n=10, OLETF rats as diabetic control group (n=10, and OLETF rats treated with taurine group (n=10. We treated taurine (200 mg/kg/day for 20 weeks and treated high glucose (HG, 30 mM with or without taurine (30 mM in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model.

Glycosylated hemoglobin as a forecast factor of progressing of diabetic nephropathy in patients with diabetes type 1

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Pertseva N.O.

2017-12-01

Full Text Available The aim of the study was to propose a mathematical model for prediction of development of diabetic nephropathy in patients with diabetes mellitus by determining the level of glycosylated hemoglobin - as a factor in the development and progression of diabetic nephropathy. A survey of 136 patients with type 1 diabetes was performed in the endocrinology department of the OSH «Clinic of the Medical Academy», Dnipro in 2016-2017. Clinical laboratory examination included: determination of the level of glycosylated hemoglobin (HbA1c, level of blood creatinine, level of albuminuria. The GFR was calculated by the formula CKD-EPI. The obtained results of the study, using methods of correlation and regression analysis, show a clear correlation between the GFR score in patients with diabetes mellitus and the level of glycosylated hemoglobin. Statistical methods of analysis have shown that the level of glycosylated hemoglobin can be considered as an early predictor of development of diabetic nephropathy. The mathematical equation of prognosis for the onset of diabetic nephropathy can be used to determine the prognosis for the development of diabetic nephropathy in diabetes mellitus patients in clinical practice for the timely inclusion of patients with a high prognostic risk in a group requiring more stringent glycemic control.

Sodium and Its Role in Cardiovascular Disease – The Debate Continues

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Kong, Yee Wen; Baqar, Sara; Jerums, George; Ekinci, Elif I.

2016-01-01

Guidelines have recommended significant reductions in dietary sodium intake to improve cardiovascular health. However, these dietary sodium intake recommendations have been questioned as emerging evidence has shown that there is a higher risk of cardiovascular disease with a low sodium diet, including in individuals with type 2 diabetes. This may be related to the other pleotropic effects of dietary sodium intake. Therefore, despite recent review of dietary sodium intake guidelines by multiple organizations, including the dietary guidelines for Americans, American Diabetes Association, and American Heart Association, concerns about the impact of the degree of sodium restriction on cardiovascular health continue to be raised. This literature review examines the effects of dietary sodium intake on factors contributing to cardiovascular health, including left ventricular hypertrophy, heart rate, albuminuria, rennin–angiotensin–aldosterone system activation, serum lipids, insulin sensitivity, sympathetic nervous system activation, endothelial function, and immune function. In the last part of this review, the association between dietary sodium intake and cardiovascular outcomes, especially in individuals with diabetes, is explored. Given the increased risk of cardiovascular disease in individuals with diabetes and the increasing incidence of diabetes worldwide, this review is important in summarizing the recent evidence regarding the effects of dietary sodium intake on cardiovascular health, especially in this population. PMID:28066329

Cardiorenal syndrome

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Sabry Omar

2013-01-01

Full Text Available Cardiovascular disease is the leading cause of death in patients with chronic kidney disease.  Heart failure may lead to acute kidney injury and vice versa. Chronic kidney disease may affect the clinical outcomes in patients with cardiovascular disorders. Renal impairment with any degree of albuminuria has been increasingly recognized as an independent risk factor for cardiovascular events and heart failure hospitalizations, while chronic heart failure may cause chronic kidney disease. The bidirectional nature of these disorders contributes to the complexity and the composite definitions of cardiorenal syndromes. However, the most important clinical trials in heart failure tend to exclude patients with significant renal dysfunction. The mechanisms whereby renal insufficiency worsens the outcome in heart failure are not known, and several pathways could contribute to the ‘‘vicious heart/kidney circle.’’ Traditionally, renal impairment has been attributed to the renal hypoperfusion due to reduced cardiac output and decreased systemic pressure. The hypovolemia leads to sympathetic activity, increased renin-angiotensin aldosterone pathway, and arginine-vasopressin release. These mechanisms cause fluid and sodium retention, peripheral vasoconstriction, and volume overload. Therapy to improve renal dysfunction, reduce neurohormonal activation and ameliorate renal blood flow could lead to a reduction in mortality and hospitalization in patients with cardiorenal syndrome.

Renoprotective Effects of SGLT2 Inhibitors: Beyond Glucose Reabsorption Inhibition.

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Tsimihodimos, V; Filippatos, T D; Filippas-Ntekouan, S; Elisaf, M

2017-01-01

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that inhibit glucose and sodium reabsorption at proximal tubules. These drugs may exhibit renoprotective properties, since they prevent the deterioration of the glomerular filtration rate and reduce the degree of albuminuria in patients with diabetes-associated kidney disease. In this review we consider the pathophysiologic mechanisms that have been recently implicated in the renoprotective properties of SGLT2 inhibitors. The beneficial effects of SGLT2 inhibitors on the conventional risk factors for kidney disease (such as blood pressure, hyperglycaemia, body weight and serum uric acid levels) may explain, at least in part, the observed renal-protecting properties of these compounds. However, it has been hypothesized that the most important mechanisms for this phenomenon include the reduction in the intraglomerular pressure, the changes in the local and systemic degree of activation of the renin-aldosterone-angiotensin system and a shift in renal fuel consumption towards more efficient energy substrates such as ketone bodies. The beneficial effects of SGLT2 inhibitors on various aspects of renal function make them an attractive choice in patients with (and possibly without) diabetes-associated renal impairment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Proteases and protease inhibitors of urinary extracellular vesicles in diabetic nephropathy.

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Musante, Luca; Tataruch, Dorota; Gu, Dongfeng; Liu, Xinyu; Forsblom, Carol; Groop, Per-Henrik; Holthofer, Harry

2015-01-01

Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM), leads to chronic kidney disease (CKD), and, ultimately, is the main cause for end-stage kidney disease (ESKD). Beyond urinary albumin, no reliable biomarkers are available for accurate early diagnostics. Urinary extracellular vesicles (UEVs) have recently emerged as an interesting source of diagnostic and prognostic disease biomarkers. Here we used a protease and respective protease inhibitor array to profile urines of type 1 diabetes patients at different stages of kidney involvement. Urine samples were divided into groups based on the level of albuminuria and UEVs isolated by hydrostatic dialysis and screened for relative changes of 34 different proteases and 32 protease inhibitors, respectively. Interestingly, myeloblastin and its natural inhibitor elafin showed an increase in the normo- and microalbuminuric groups. Similarly, a characteristic pattern was observed in the array of protease inhibitors, with a marked increase of cystatin B, natural inhibitor of cathepsins L, H, and B as well as of neutrophil gelatinase-associated Lipocalin (NGAL) in the normoalbuminuric group. This study shows for the first time the distinctive alterations in comprehensive protease profiles of UEVs in diabetic nephropathy and uncovers intriguing mechanistic, prognostic, and diagnostic features of kidney damage in diabetes.

Proteases and Protease Inhibitors of Urinary Extracellular Vesicles in Diabetic Nephropathy

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Luca Musante

2015-01-01

Full Text Available Diabetic nephropathy (DN is one of the major complications of diabetes mellitus (DM, leads to chronic kidney disease (CKD, and, ultimately, is the main cause for end-stage kidney disease (ESKD. Beyond urinary albumin, no reliable biomarkers are available for accurate early diagnostics. Urinary extracellular vesicles (UEVs have recently emerged as an interesting source of diagnostic and prognostic disease biomarkers. Here we used a protease and respective protease inhibitor array to profile urines of type 1 diabetes patients at different stages of kidney involvement. Urine samples were divided into groups based on the level of albuminuria and UEVs isolated by hydrostatic dialysis and screened for relative changes of 34 different proteases and 32 protease inhibitors, respectively. Interestingly, myeloblastin and its natural inhibitor elafin showed an increase in the normo- and microalbuminuric groups. Similarly, a characteristic pattern was observed in the array of protease inhibitors, with a marked increase of cystatin B, natural inhibitor of cathepsins L, H, and B as well as of neutrophil gelatinase-associated Lipocalin (NGAL in the normoalbuminuric group. This study shows for the first time the distinctive alterations in comprehensive protease profiles of UEVs in diabetic nephropathy and uncovers intriguing mechanistic, prognostic, and diagnostic features of kidney damage in diabetes.

Establishment of mouse model of MYH9 disorders: heterozygous R702C mutation provokes macrothrombocytopenia with leukocyte inclusion bodies, renal glomerulosclerosis and hearing disability.

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Suzuki, Nobuaki; Kunishima, Shinji; Ikejiri, Makoto; Maruyama, Shoichi; Sone, Michihiko; Takagi, Akira; Ikawa, Masahito; Okabe, Masaru; Kojima, Tetsuhito; Saito, Hidehiko; Naoe, Tomoki; Matsushita, Tadashi

2013-01-01

Nonmuscle myosin heavy chain IIA (NMMHCIIA) encoded by MYH9 is associated with autosomal dominantly inherited diseases called MYH9 disorders. MYH9 disorders are characterized by macrothrombocytopenia and very characteristic inclusion bodies in granulocytes. MYH9 disorders frequently cause nephritis, sensorineural hearing disability and cataracts. One of the most common and deleterious mutations causing these disorders is the R702C missense mutation. We generated knock-in mice expressing the Myh9 R702C mutation. R702C knock-in hetero mice (R702C+/- mice) showed macrothrombocytopenia. We studied megakaryopoiesis of cultured fetal liver cells of R702C+/- mice and found that proplatelet formation was impaired: the number of proplatelet tips was decreased, proplatelet size was increased, and proplatelet shafts were short and enlarged. Although granulocyte inclusion bodies were not visible by May-Grünwald Giemsa staining, immunofluorescence analysis indicated that NMMHCIIA proteins aggregated and accumulated in the granulocyte cytoplasm. In other organs, R702C+/- mice displayed albuminuria which increased with age. Renal pathology examination revealed glomerulosclerosis. Sensory hearing loss was indicated by lowered auditory brainstem response. These findings indicate that Myh9 R702C knock-in mice mirror features of human MYH9 disorders arising from the R702C mutation.

Risk profile, quality of life and care of patients with moderate and advanced CKD : The French CKD-REIN Cohort Study.

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Stengel, Bénédicte; Metzger, Marie; Combe, Christian; Jacquelinet, Christian; Briançon, Serge; Ayav, Carole; Fouque, Denis; Laville, Maurice; Frimat, Luc; Pascal, Christophe; Herpe, Yves-Edouard; Morel, Pascal; Deleuze, Jean-François; Schanstra, Joost P; Lange, Céline; Legrand, Karine; Speyer, Elodie; Liabeuf, Sophie; Robinson, Bruce M; Massy, Ziad A

2018-04-09

The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study was designed to investigate the determinants of prognosis and care of patients referred to nephrologists with moderate and advanced chronic kidney disease (CKD). We examined their baseline risk profile and experience. We collected bioclinical and patient-reported information from 3033 outpatients with CKD and estimated glomerular filtration rates (eGFRs) of 15-60 mL/min/1.73 m2 treated at 40 nationally representative public and private facilities. The patients' median age was 69 (60-76) years, 65% were men, their mean eGFR was 33 mL/min/1.73 m2, 43% had diabetes, 24% had a history of acute kidney injury (AKI) and 57% had uncontrolled blood pressure (BP; >140/90 mmHg). Men had worse risk profiles than women and were more likely to be past or current smokers (73% versus 34%) and have cardiovascular disease (59% versus 42%), albuminuria >30 mg/mmol (or proteinuria > 50) (40% versus 30%) (all P REIN study highlights high-risk profiles of cohort members and identifies several priorities, including improving BP control and dietary counselling and increasing doctors' awareness of AKI, polypharmacy and QoL. ClinicalTrials.gov identifier: NCT03381950.

Relationship of endothelial dysfunction with degree of renal function damage and lipidemic profile in patients with type 2 diabetes mellitus and hypertension

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Pertseva N.O.

2014-09-01

Full Text Available In the article defining relationship between endothelial dysfunction, the degree of renal and lipidemic profile damage in 234 patients with type 2 diabetes mellitus with hypertension was carried depending on the quality of glycemic control. It is shown that the deepening of endothelial dysfunction in patients with insufficient and poor compensation tightly correlates with the degree of renal and lipidemic disorders. In these patients there was a significant increase in the level of albuminuria, reduction in glomerular filtration rate, increase of concentrations of urea and creatinine. Against the background of poor hyperglycemia, compensation total cholesterol, low density lipoprotein content increases by 73,3% (p<0.05, hype¬rtriglyceridemia twice exceeds the control values. In patients with type 2 diabetes mellitus with poor compensation the most significant correlation links were observed between the concentration of endothelin-1 and the level of microalbuminuria (r=+0,79, as well as the content of low density lipoprotein cholesterol (r=+0.81. Thrombomodulin concentration is in direct correlation with microalbuminuria (r=+0.76, hypercholesterolemia (r=+0.80 and hypertriglyceridemia (r=+0.83, indicating to increasing interaction between the pathogenetic mechanisms which cause depression of endothelial dysfunction, renal and dyslipidemic disorders with increasing hyperglycemia.

Mammographically detected breast arterial calcifications: Indicators for arteriosclerotic diseases?

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Taskin, Fuesun; Akdilli, Alev; Karaman, Can; Unsal, Alparslan; Koeseoglu, Kutsi; Ergin, Filiz

2006-01-01

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). 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

Association of HFE gene mutations with nonalcoholic fatty liver disease in the Iranian population.

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Saremi, L; Lotfipanah, S; Mohammadi, M; Hosseinzadeh, H; Sayad, A; Saltanatpour, Z

2016-10-31

To determine whether the HFE gene variants H63D and C282Y are associated with NAFLD in persons with type 2 diabetes, we conducted a case-control study including 145 case of NAFLD patients with a history of type 2 diabetes and 145 matching control. The genomic DNA was extracted from the peripheral venous blood and the genotyping of HFE gene mutations was analyzed using the PCR-RFLP technique. Statistical analysis was performed using SPSS 12.0 software by χ2 test, t test and ANOVA (P<0.05). Data showed no increased frequency of HFE mutations in persons with type 2 diabetes and no association between H63D mutation and NAFLD in the study population. Also, we analyzed index of physiological variables including FBS, lipid profile (TC, TG, LDL-C, and HDL-C), BMI, HbA1c, and micro albuminuria and Cr levels). Data showed there are no relationship between these indexes and HFE gene mutations and either NAFLD as a complication of diabetes. But our results showed a relationship between C282Y mutation and NAFLD in persons with type 2 diabetes. C282Y mutation might be a genetic marker of NAFLD in Iranian population.

Tooth loss strongly associates with malnutrition in chronic kidney disease.

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Ioannidou, E; Swede, H; Fares, G; Himmelfarb, J

2014-07-01

In chronic kidney disease (CKD), inadequate nutritional intake, inflammation, and increased oxidative stress have been the major contributing factors in malnutrition pathogenesis. However, there is still a paucity of evidence assessing the magnitude of the effect of tooth loss on malnutrition in CKD populations. The authors hypothesize that among patients with CKD, tooth loss may affect nutritional status, using the National Health and Nutrition Examination Survey 1988 to 1994 (NHANES III). Glomerular filtration rate (GFR) was estimated based on cystatin C levels using the relevant equation. Urinary albumin-to-creatinine ratio (albuminuria) was calculated in milligrams per gram with a cutoff point of 30 mg/g. CKD was defined based on estimated GFR protein and caloric intake (P = 0.02 and 0.01, respectively). Serum albumin reached a frequency peak in the fully edentulous group without dentures (group 4, 19.2%). In the same group, individuals had lower protein (30.1%) and caloric intake (30.2%) (P = 0.01 and 0.02, respectively). Furthermore, logistic regression analysis confirmed the significant role of tooth loss on serum albumin and protein and energy intake in this population even after adjusting for confounding variables. Tooth loss independently predicts low energy and protein intake, as well as serum albumin levels, biomarkers of malnutrition in CKD.

Early and late scanning electron microscopy findings in diabetic kidney disease.

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Conti, Sara; Perico, Norberto; Novelli, Rubina; Carrara, Camillo; Benigni, Ariela; Remuzzi, Giuseppe

2018-03-20

Diabetic nephropathy (DN), the single strongest predictor of mortality in patients with type 2 diabetes, is characterized by initial glomerular hyperfiltration with subsequent progressive renal function loss with or without albuminuria, greatly accelerated with the onset of overt proteinuria. Experimental and clinical studies have convincingly shown that early interventions retard disease progression, while treatment if started late in the disease course seldom modifies the slope of GFR decline. Here we assessed whether the negligible renoprotection afforded by drugs in patients with proteinuric DN could be due to loss of glomerular structural integrity, explored by scanning electron microscopy (SEM). In diabetic patients with early renal disease, glomerular structural integrity was largely preserved. At variance SEM documented that in the late stage of proteinuric DN, glomerular structure was subverted with nearly complete loss of podocytes and lobular transformation of the glomerular basement membrane. In these circumstances one can reasonably imply that any form of treatment, albeit personalized, is unlikely to reach a given cellular or molecular target. These findings should persuade physicians to start the putative renoprotective therapy soon after the diagnosis of diabetes or in an early phase of the disease before structural integrity of the glomerular filter is irreversibly compromised.

The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet

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Glastras, Sarah J.; Chen, Hui; Tsang, Michael; Teh, Rachel; McGrath, Rachel T.; Zaky, Amgad; Chen, Jason; Wong, Muh Geot; Pollock, Carol A.; Saad, Sonia

2017-01-01

Aims/Hypothesis Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease. Methods Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32. Results HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity. Conclusion Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity. PMID:28225809

Renal Protection by Genetic Deletion of the Atypical Chemokine Receptor ACKR2 in Diabetic OVE Mice

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Shirong Zheng

2016-01-01

Full Text Available In diabetic nephropathy (DN proinflammatory chemokines and leukocyte infiltration correlate with tubulointerstitial injury and declining renal function. The atypical chemokine receptor ACKR2 is a chemokine scavenger receptor which binds and sequesters many inflammatory CC chemokines but does not transduce typical G-protein mediated signaling events. ACKR2 is known to regulate diverse inflammatory diseases but its role in DN has not been tested. In this study, we utilized ACKR2−/− mice to test whether ACKR2 elimination alters progression of diabetic kidney disease. Elimination of ACKR2 greatly reduced DN in OVE26 mice, an established DN model. Albuminuria was significantly lower at 2, 4, and 6 months of age. ACKR2 deletion did not affect diabetic blood glucose levels but significantly decreased parameters of renal inflammation including leukocyte infiltration and fibrosis. Activation of pathways that increase inflammatory gene expression was attenuated. Human biopsies stained with ACKR2 antibody revealed increased staining in diabetic kidney, especially in some tubule and interstitial cells. The results demonstrate a significant interaction between diabetes and ACKR2 protein in the kidney. Unexpectedly, ACKR2 deletion reduced renal inflammation in diabetes and the ultimate response was a high degree of protection from diabetic nephropathy.

Determinants of plasma homocyst(e)ine in patients with nephrotic syndrome.

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Joven, J; Arcelús, R; Camps, J; Ordóñez-Llanos, J; Vilella, E; González-Sastre, F; Blanco-Vaca, F

2000-01-01

Hyperhomocyst(e)inemia is an independent risk factor for atherothrombosis in several clinical settings in which renal function is impaired, but its prevalence in the nephrotic syndrome has not been investigated in detail, even though this syndrome provides an excellent model in which to study a possible link between albuminuria, proteinuria, and hyperhomocyst(e)inemia. We obtained plasma and urine from 27 patients with biopsy-confirmed membranous glomerulonephritis presenting nephrotic syndrome and 27 matched controls and determined the concentrations of homocyst(e)ine and proteins considered putative markers of glomerular and tubular function. Hyperhomocyst(e)inemia, defined as the mean +SD of the plasma homocyst(e)ine concentration of the controls [plasma homocyst(e)ine concentration >10.8 micromol/l] was present in 26% of the patients with nephrotic syndrome but in only 7.4% of the controls. Furthermore, the degree of hyperhomocyst(e)inemia was more severe in the nephrotic patients than in the controls. The existence of renal failure, tubular damage, and, interestingly, relatively well conserved glomerular function barrier were the main predictors of increased levels of plasma homocyst(e)ine. In conclusion, hyperhomocyst(e)inemia is a frequent cardiovascular risk factor present in patients with nephrotic syndrome and renal failure, but it is not directly associated with proteinuria.

Reliability of CKD-EPI predictive equation in estimating chronic kidney disease prevalence in the Croatian endemic nephropathy area.

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Fuček, Mirjana; Dika, Živka; Karanović, Sandra; Vuković Brinar, Ivana; Premužić, Vedran; Kos, Jelena; Cvitković, Ante; Mišić, Maja; Samardžić, Josip; Rogić, Dunja; Jelaković, Bojan

2018-02-15

Chronic kidney disease (CKD) is a significant public health problem and it is not possible to precisely predict its progression to terminal renal failure. According to current guidelines, CKD stages are classified based on the estimated glomerular filtration rate (eGFR) and albuminuria. Aims of this study were to determine the reliability of predictive equation in estimation of CKD prevalence in Croatian areas with endemic nephropathy (EN), compare the results with non-endemic areas, and to determine if the prevalence of CKD stages 3-5 was increased in subjects with EN. A total of 1573 inhabitants of the Croatian Posavina rural area from 6 endemic and 3 non-endemic villages were enrolled. Participants were classified according to the modified criteria of the World Health Organization for EN. Estimated GFR was calculated using Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). The results showed a very high CKD prevalence in the Croatian rural area (19%). CKD prevalence was significantly higher in EN then in non EN villages with the lowest eGFR value in diseased subgroup. eGFR correlated significantly with the diagnosis of EN. Kidney function assessment using CKD-EPI predictive equation proved to be a good marker in differentiating the study subgroups, remained as one of the diagnostic criteria for EN.

The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet.

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Sarah J Glastras

Full Text Available Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease.Female C57BL/6 mice were fed high-fat diet (HFD for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p. or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32.HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity.Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity.

Environmental exposure to cadmium and renal function of elderly women living in cadmium-polluted areas of West-Germany

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Ewers, U.; Brockhaus, A.; Dolgner, R.; Freier, I.; Jermann, E.; Hahn, R.; Schlipkoeter, H.W.; Bernard, A.

1985-12-01

An epidemiological study was carried out to assess whether or not environmental pollution by cadmium as found in cadmium-polluted areas of the Federal Republic auf Germany is associated with an increased prevalence of biological signs of kidney dysfunction in population groups non-occupationally exposed to heavy metals. The study was run in two industrial areas known to be highly polluted by cadmium and other toxic heavy metals, viz. Stolberg and Duisburg. Duesseldorf was selected as a reference area. As a study population we selected 65- and 66-year-old women who had spent the major part of their lives in one of these areas. The average levels of cadmium in blood and urine showed significant differences in exposure to cadmium in the order Stolberg > Duisburg > Duesseldorf. Serum creatinine levels were, on average, significantly higher in the Stolberg group than in the Duisburg and Duesseldorf groups. With respect to other biological findings (total proteinuria, tubular proteinuria, albuminuria, aminoaciduria, phosphaturia, serum complement) no significant differences between the study populations were noted. It cannot be excluded, however, that in the Stolberg group there is a synergism of ageing and cadmium with respect to the age related decline of the glomerular filtration rate.

[Consensus document for the detection and management of chronic kidney disease].

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Martínez-Castelao, Alberto; Górriz, José L; Bover, Jordi; Segura-de la Morena, Julián; Cebollada, Jesús; Escalada, Javier; Esmatjes, Enric; Fácila, Lorenzo; Gamarra, Javier; Gràcia, Silvia; Hernández-Moreno, Julio; Llisterri-Caro, José L; Mazón, Pilar; Montañés, Rosario; Morales-Olivas, Francisco; Muñoz-Torres, Manuel; de Pablos-Velasco, Pedro; de Santiago, Ana; Sánchez-Celaya, Marta; Suárez, Carmen; Tranche, Salvador

2014-11-01

Chronic kidney disease (CKD) is an important global health problem, involving to 10% of the Spanish population, promoting high morbidity and mortality for the patient and an elevate consumption of the total health resources for the National Health System. This is a summary of an executive consensus document of ten scientific societies involved in the care of the renal patient, that actualizes the consensus document published in 2007. The central extended document can be consulted in the web page of each society. The aspects included in the document are: Concept, epidemiology and risk factors for CKD. Diagnostic criteria, evaluation and stages of CKD, albuminuria and glomerular filtration rate estimation. Progression factors for renal damage. Patient remission criteria. Follow-up and objectives of each speciality control. Nephrotoxicity prevention. Cardio-vascular damage detection. Diet, life-style and treatment attitudes: hypertension, dyslipidaemia, hyperglycemia, smoking, obesity, hyperuricemia, anemia, mineral and bone disorders. Multidisciplinary management for Primary Care, other specialities and Nephrology. Integrated management of CKD patient in haemodialysis, peritoneal dialysis and renal transplant patients. Management of the uremic patient in palliative care. We hope that this document may be of help for the multidisciplinary management of CKD patients by summarizing the most updated recommendations. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Albumin-bound fatty acids but not albumin itself alter redox balance in tubular epithelial cells and induce a peroxide-mediated redox-sensitive apoptosis

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Ruggiero, Christine; Elks, Carrie M.; Kruger, Claudia; Cleland, Ellen; Addison, Kaity; Noland, Robert C.

2014-01-01

Albuminuria is associated with metabolic syndrome and diabetes. It correlates with the progression of chronic kidney disease, particularly with tubular atrophy. The fatty acid load on albumin significantly increases in obesity, presenting a proinflammatory environment to the proximal tubules. However, little is known about changes in the redox milieu during fatty acid overload and how redox-sensitive mechanisms mediate cell death. Here, we show that albumin with fatty acid impurities or conjugated with palmitate but not albumin itself compromised mitochondrial and cell viability, membrane potential and respiration. Fatty acid overload led to a redox imbalance which deactivated the antioxidant protein peroxiredoxin 2 and caused a peroxide-mediated apoptosis through the redox-sensitive pJNK/caspase-3 pathway. Transfection of tubular cells with peroxiredoxin 2 was protective and mitigated apoptosis. Mitochondrial fatty acid entry and ceramide synthesis modulators suggested that mitochondrial β oxidation but not ceramide synthesis may modulate lipotoxic effects on tubular cell survival. These results suggest that albumin overloaded with fatty acids but not albumin itself changes the redox environment in the tubules, inducing a peroxide-mediated redox-sensitive apoptosis. Thus, mitigating circulating fatty acid levels may be an important factor in both preserving redox balance and preventing tubular cell damage in proteinuric diseases. PMID:24500687

Nephroprotective action of renin-angiotensin-aldosterone system blockade in chronic kidney disease patients: the landscape after ALTITUDE and VA NEPHRON-D trails.

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Rutkowski, Boleslaw; Tylicki, Leszek

2015-03-01

The intervention in the renin-angiotensin-aldosterone system (RAAS) is currently the most effective strategy that combines blood pressure lowering and renoprotection. Several large, randomized, controlled trials evidenced the renoprotective potential of the angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in nephropathies of almost any etiology. Mineralocorticoid receptor antagonists and direct renin inhibitor, aliskiren, as add-on treatments to standard therapy including the optimal dose of ACEIs or ARBs reduce albuminuria or proteinuria and slow development of renal dysfunction more than placebo. No clinical evidence is available however about whether these strategies may influence on long-term kidney outcome. Three recent trials suggested that aggressive RAAS blockade, that is, combination of 2 RAAS-blocking agents, does not decrease cardiovascular and renal morbidity and may carry an increased risk of serious complications. This article reviews an evidence-based approach on the use of RAAS-inhibiting agents in chronic kidney disease and considers the implementation of dual RAAS blockade with reference to the results of ALTITUDE and VA NEPHRON-D trails aiming to aid clinicians in their treatment decisions for patients with chronic kidney disease. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin

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Stolzenburg Oxlund, Christina; Kurt, Birgül; Schwarzensteiner, Ilona

2017-01-01

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...... spironolactone compared to control. Urinary prostasin and albumin related directly and were reduced by spironolactone. In patients with nephrotic syndrome, urinary prostasin protein was elevated compared to controls. In rat nephrosis, proteinuria coincided with increased urinary prostasin, unchanged kidney...... the result of an improved glomerular filtration barrier function and generally reduced proteinuria....

Effect of 4 years subcutaneous insulin infusion treatment on albuminuria, kidney function and HbA1c compared with multiple daily injections

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Vestergaard Rosenlund, Signe; Hansen, Tine Willum; Andersen, Steen

2015-01-01

injections (MDI) in a single-centre clinical setting. METHODS: All patients initiating CSII treatment from 2004 to 2010 and followed for at least 4 years were included in the study: 193 people with Type 1 diabetes were matched (1 : 2) with 386 patients treated with MDI in the same period. Matching was based...

Neutrophil gelatinase-associated lipocalin and albuminuria as predictors of acute kidney injury in patients treated with goal-directed haemodynamic therapy after major abdominal surgery.

LENUS (Irish Health Repository)

Cullen, Mr

2013-10-11

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.

Treatment and Prevention of Common Complications of Chronic Kidney Disease

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Sheikh Salahuddin Ahmed

2014-01-01

Full Text Available Chronic kidney disease (CKD is a worldwide public health problem with an increasing incidence and prevalence. Outcomes of CKD include not only complications of decreased kidney function and cardiovascular disease but also kidney failure causing increased morbidity and mortality. Unfortunately, CKD is often undetected and undertreated because of its insidious onset, variable progression, and length of time to overt kidney failure. Diabetes is now the leading cause of CKD requiring renal replacement therapy in many parts of the world, and its prevalence is increasing disproportionately in the developing countries. This review article outlines the current recommendations from various clinical guidelines and research studies for treatment, prevention and delaying the progression of both CKD and its common complications such as hypertension, anemia, renal osteodystrophy, electrolyte and acid-base imbalance, and hyperlipidemia. Recommendations for nutrition in CKD and measures adopted for early diabetic kidney disease to prevent further progression have also been reviewed. There is strong evidence that early detection and management of CKD can prevent or reduce disease progression, decrease complications and improve outcomes. Evidence supports that achieving optimal glucose control, blood pressure, reduction in albuminuria with a multifactorial intervention slows the progression of CKD. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists are most effective because of their unique ability to decrease proteinuria, a factor important for the progression of CKD.

Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis.

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Elliot, S J; Berho, M; Korach, K; Doublier, S; Lupia, E; Striker, G E; Karl, M

2007-08-01

Young female mice on a C57Bl/6J (B6) background are considered glomerulosclerosis (GS)-resistant but aging B6 mice develop mild GS. Estrogen deficiency accelerates while estrogen replacement retards GS in young sclerosis-prone oligosyndactyly mutant mice on an ROP background. To explore the effects of sex hormones on glomerular structure and function in the context of gender and genetic background, we studied mice in which the estrogen-receptor (ER) genes alpha- or -beta were deleted (alpha- or betaER knockout (KO)) and crossed into the B6 background. We also studied ovariectomized (Ovx) B6 mice given testosterone. Male and female betaERKO and male alphaERKO mice had no glomerular dysfunction at 9 months of age; however, alphaERKO female mice displayed albuminuria and GS. Ovx prevented glomerular dysfunction in alphaERKO female mice by eliminating endogenous testosterone production while exogenous testosterone induced GS in Ovx B6 mice. Androgen receptor (AR) expression and function was found in microdissected glomeruli and cultured mesangial cells. Testosterone compared to placebo increased both AR expression and TGF-beta1 mRNA levels in glomeruli isolated from female B6 mice. Estrogen deficiency had no deleterious effects on the glomeruli in B6 mice. Our study shows that genetic traits strongly influence the GS-promoting effects of estrogen deficiency while testosterone induces GS in a gender-specific manner.

Comprehensive approach to diabetic nephropathy

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Bancha Satirapoj

2014-09-01

Full Text Available Diabetic nephropathy (DN is a leading cause of mortality and morbidity in patients with diabetes. This complication reflects a complex pathophysiology, whereby various genetic and environmental factors determine susceptibility and progression to end-stage renal disease. DN should be considered in patients with type 1 diabetes for at least 10 years who have microalbuminuria and diabetic retinopathy, as well as in patients with type 1 or type 2 diabetes with macroalbuminuria in whom other causes for proteinuria are absent. DN may also present as a falling estimated glomerular filtration rate with albuminuria as a minor presenting feature, especially in patients taking renin–angiotensin–aldosterone system inhibitors (RAASi. The pathological characteristic features of disease are three major lesions: diffuse mesangial expansion, diffuse thickened glomerular basement membrane, and hyalinosis of arterioles. Functionally, however, the pathophysiology is reflected in dysfunction of the mesangium, the glomerular capillary wall, the tubulointerstitium, and the vasculature. For all diabetic patients, a comprehensive approach to management including glycemic and hypertensive control with RAASi combined with lipid control, dietary salt restriction, lowering of protein intake, increased physical activity, weight reduction, and smoking cessation can reduce the rate of progression of nephropathy and minimize the risk for cardiovascular events. This review focuses on the latest published data dealing with the mechanisms, diagnosis, and current treatment of DN.

The early modern kidney--nephrology in and about the nineteenth century. Part 1.

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Eknoyan, Garabed

2013-01-01

The 19th century was a period of momentous scientific discoveries, technological achievements, and societal changes. A beneficiary of these revolutionary upheavals was medical empiricism that supplanted the rationalism of the past giving rise to early modern scientific medicine. Continued reliance on sensory data now magnified by technical advances generated new medical information that could be quantified with increasing precision, verified by repeated experimentation, and validated by statistical analysis. The institutionalization and integration of these methodologies into medical education were a defining step that assured their progress and perpetuation. Major advances were made in the nosography of diseases of the kidney, notably that of the diagnosis of progressive kidney disease from the presence of albuminuria by Richard Bright (1789-1858); and of renal structure and function, notably the demonstration of the continuity of the glomerular capsule with the tubular basement membrane by William Bowman (1816-1892), and the arguments for hemodynamic physical forces mediated glomerular filtration by Carl Ludwig (1816-1895) and for active tubular transport by Rudolf Heidenhain (1834-1897). Improvements in microscopy and tissue processing were instrumental in describing the cellular ultrastructure of the glomerulus and tubular segments, but their integrated function remained to be elucidated. The kidney continued to be considered a tubular secretory organ and its pathology attributed to injury of the interstitium (interstitial nephritis) or tubules (parenchymatous nephritis). © 2012 Wiley Periodicals, Inc.

The association of ACE gene polymorphism with diabetic kidney disease and renoprotective efficacy of valsartan

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Yuying Wang

2016-09-01

Full Text Available Introduction: To investigate the associations between the insertion/deletion (I/D polymorphisms in the angiotensin converting enzyme (ACE gene and susceptibility to diabetic kidney disease (DKD; and the efficacy of valsartan in reducing the urine protein in Type 2 diabetes mellitus (T2DM patients. Materials and methods: We enrolled 128 T2DM patients in this study, including 54 cases with DKD (DKD+ and 74 controls (DKD–. The ACE polymorphism was assayed by polymerase chain reaction (PCR, and the genotype distribution and allele frequency were analyzed. The DKD+ group was subdivided into the DD, ID and II subgroups, based on their genotypes. In addition, patients with DKD received valsartan treatment for 12 weeks. We determined changes in the urinary albumin to creatinine ratio (ACR and serum creatinine (SCr. Results: The frequencies of the genotypes DD and ID were higher in the DKD+ than in the DKD– group. The frequency of allele D was higher, and of allele I was lower, in the DKD+ than in DKD– group (p < 0.05. Following valsartan treatment, albuminuria was significantly decreased in subgroups DD and ID (p < 0.05. Conclusions: In T2DM patients, the ACE I/D polymorphism was associated with onset of DKD. Furthermore, the ACE I/D polymorphism influenced the renoprotective response to valsartan: Patients with the DD genotype benefitted the most from this treatment.

Optimizing care for Canadians with diabetic nephropathy in 2015.

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Lloyd, Alissa; Komenda, Paul

2015-06-01

Diabetic chronic kidney disease (CKD) is the cause of kidney failure in approximately 35% of Canadian patients requiring dialysis. Traditionally, only a minority of patients with type 2 diabetes and CKD progress to kidney failure because they die of a cardiovascular event first. However, with contemporary therapies for diabetes and cardiovascular disease, this may no longer be true. The classic description of diabetic CKD is the development of albuminuria followed by progressive kidney dysfunction in a patient with longstanding diabetes. Many exciting candidate agents are under study to halt the progression of diabetic CKD; current therapies center on optimizing glycemic control, renin angiotensin system inhibition, blood pressure control and lipid management. Lifestyle modifications, such as salt and protein restriction as well as smoking cessation, may also be of benefit. Unfortunately, these accepted therapies do not entirely halt the progression of diabetic CKD. Also unfortunately, the presence of CKD in general is under-recognized by primary care providers, which can lead to late referral, missed opportunities for preventive care and inadvertent administration of potentially harmful interventions. Not all patients require referral to nephrology for diagnosis and management, but modern risk-prediction algorithms, such as the kidney failure risk equation, may help to guide referral appropriateness and dialysis modality planning in subspecialty nephrology multidisciplinary care clinics. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Andrographolide ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated renal oxidative stress and inflammation via Akt/NF-κB pathway.

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Ji, Xiaoqian; Li, Changzheng; Ou, Yitao; Li, Ning; Yuan, Kai; Yang, Guizhi; Chen, Xiaoyan; Yang, Zhicheng; Liu, Bing; Cheung, Wai W; Wang, Lijing; Huang, Ren; Lan, Tian

2016-12-05

Diabetic nephropathy (DN) is characterized by proliferation of mesangial cells, mesangial hypertrophy and extracellular matrix (ECM) accumulation. Our recent study found that andrographolide inhibited high glucose-induced mesangial cell proliferation and fibronectin expression through inhibition of AP-1 pathway. However, whether andrographolide has reno-protective roles in DN has not been fully elucidated. Here, we studied the pharmacological effects of andrographolide against the progression of DN and high glucose-induced mesangial dysfunction. Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). After 1 weeks after STZ injection, normal diet was substituted with a high-fat diet (HFD). Diabetic mice were intraperitoneal injected with andrographolide (2 mg/kg, twice a week). After 8 weeks, functional and histological analyses were carried out. Parallel experiments uncovering the molecular mechanism by which andrographolide prevents from DN was performed in mesangial cells. Andrographolide inhibited the increases in fasting blood glucose, triglyceride, kidney/body weight ratio, blood urea nitrogen, serum creatinine and 24-h albuminuria in diabetic mice. Andrographolide also prevented renal hypertrophy and ECM accumulation. Furthermore, andrographolide markedly attenuated NOX1 expression, ROS production and pro-inflammatory cytokines as well. Additionally, andrographolide inhibited Akt/NF-κB signaling pathway. These results demonstrate that andrographolide is protective against the progression of experimental DN by inhibiting renal oxidative stress, inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.