Twenty-four hour urinary albumin excretion (UAE) is considered as gold standard method for albuminuria measurement, but collection of 24-h urine is inconvenient. The aim of present study was to evaluate whether albumin: creatinine ratio (ACR) and urinary albumin concentration (UAC) in different spot urine samples correlate or not with 24-h UAE for screening of microalbuminuria in type 2 diabetic patients. We collected first morning void (FMV), random urine sample (RUS) and 24-h urine, separately on consecutive days from 104 type 2 diabetic patients. ACR and UAC in each spot urine sample compared with 24-h UAE with regard to Pearson correlation coefficient. Pearson’s correlation of albumin: creatinine ratio (ACR) with 24-h UAE was (r = 0.802 and 0.623) in first morning void (FMV) and random urine sample (RUS), respectively. Pearson’s correlation coefficient of urinary albumin concentration (UAC) compared with 24-h UAE was (r = 0.943 and 0.920), in FMV and RUS, respectively, P < 0.01. Results revealed that values in first morning void (FMV) were better correlated with 24-h urinary albumin excretion (UAE), than the values in random urine sample (RUS). We conclude that the first morning void (FMV) may be able to replace 24-h urine collection, preferably urinary albumin concentration (UAC) in the initial screening of microalbuminuria in diabetic patients.
Electronic supplementary material
The online version of this article (doi:10.1007/s12291-011-0136-0) contains supplementary material, which is available to authorized users.
Diabetes mellitus; Microalbuminuria; Screening; Spot urine sample; Urinary albumin concentration
OBJECTIVE--To ascertain which factors determine the progression from very low rates of albumin excretion to persistent microalbuminuria in patients with insulin dependent diabetes mellitus. DESIGN--A 10 year prospective study of a cohort of diabetic patients. SETTING--Outpatient department of the Portsmouth District Hospitals. SUBJECTS--97 patients with insulin dependent diabetes mellitus who were initially free of microalbuminuria and hypertension. MAIN OUTCOME MEASURE--Urinary albumin: creatinine ratio. RESULTS--Eight of the 97 patients had developed microalbuminuria (urinary albumin:creatinine ratio > 3 mg/mmol in three consecutive early morning samples) by the 10 year follow up. The group who developed microalbuminuria had higher baseline log10 plasma glucose concentrations (mean (SD), 1.210 (0.122) v 0.984 (0.196) mmol/l, P < 0.001) and glycated haemoglobin concentrations (1.112% (0.069%) v 0.997% (0.076%), P < 0.001) and a younger age at onset of diabetes (10.0 (5.5) v 15.6 (7.8) years, P < 0.05). There was no difference in baseline duration of diabetes, smoking, sex, insulin dose, body mass index, serum creatinine concentration, or systolic, diastolic, or mean arterial blood pressure between the two groups. Multiple linear regression analysis showed that urinary albumin:creatinine ratio at 10 years was influenced by initial albumin:creatinine ratio (P = 0.006), initial glycated haemoglobin concentration (P = 0.002), and duration of diabetes (P = 0.045). Genotype for angiotensin converting enzyme was not related to the development of microalbuminuria nor, in a larger group of patients, the presence of any degree of diabetic nephropathy. CONCLUSION--In patients with insulin dependent diabetes mellitus the progression of minimal albuminuria and the development of microalbuminuria is determined primarily by poor long term glycaemic control. There is a weaker relation with longer duration of disease and younger age at onset of diabetes, but blood pressure does not seem to be implicated. Gene polymorphism for angiotensin converting enzyme is not linked to the development of microalbuminuria or established diabetic nephropathy.
Microalbuminuria (defined as urinary albumin excretion of 30-300 mg/day, or 20-200 µg/min) is an earlier sign of vascular damage. It is a marker of general vascular dysfunction and nowadays is considered a predictor of worse outcomes for both kidney and heart patients. There is a significant correlation between blood pressure and microalbuminuria. Even high normal blood pressure is associated with significant higher frequency of microalbuminuria and this way may be a biomarker of increased cardiovascular risk. Microalbuminuria could be taken also, as an indicator of insulin resistance and of the increased renal and cardiovascular risk associated with metabolic syndrome. Renal involvement is a pivotal development in diabetes and microalbuminuria is generally the first clinical sign of renal dysfunction in diabetics. It is demonstrated that cardiovascular and renal risk is elevated even in the high normal range of microalbuminuria (below 30 mg/day). There is no doubt that therapies that prevent or delay the development of microalbuminuria and all measures that reduce it, may help to prevent or delay end organ damage.
microalbuminuria; cardiovascular risk; high blood pressure; diabetic nephropathy
OBJECTIVES--To study the association(s) between microalbuminuria and cardiovascular risk factors in non-diabetic subjects. DESIGN--Patients aged 40-75 years were randomly selected from a general practice list and invited to participate. SETTING--Health centre in inner city London. SUBJECTS--Of those invited, 1046 out of 1671 (62.6%) attended. Subjects were excluded for the following reasons: not being white (44); urinary albumin excretion rate > 200 micrograms/min (3); having a urinary infection (5); taking penicillamine or angiotensin converting enzyme inhibitors (7); older than 75 (2); having diabetes (25); missing data on glucose concentration (1). MAIN OUTCOME MEASURES--Glucose tolerance test results, albumin excretion rate from overnight and timed morning collections of urine; blood pressure; height. RESULTS--Mean albumin excretion rate was significantly lower in women than men (mean ratio 0.8, 95% confidence interval (0.69 to 0.91)). Mean albumin excretion rate was significantly associated with age, blood pressure, and blood glucose concentration (fasting, 1 hour, and 2 hour) in men and inversely with height. Men who had microalbuminuria in both samples were significantly shorter (by 5 cm (1.3 to 9.3 cm)) than those who had no microalbuminuria in either sample when age was taken into account. In the case of women only systolic pressure was significantly associated with albumin excretion rate. CONCLUSIONS--Microalbuminuria and short stature in men are associated. Cardiovascular risk has been associated with both of these factors and with lower birth weight. The inverse association of microalbuminuria with height is compatible with the suggestion that factors operating in utero or early childhood are implicated in cardiovascular disease. The higher prevalence of microalbuminuria in men compared with women may indicate that sex differences in cardiovascular risk are reflected in differences in albumin excretion rate.
Objective To investigate whether a low dose of the angiotensin converting enzyme (ACE) inhibitor ramipril lowers cardiovascular and renal events in patients with type 2 diabetes who have microalbuminuria or proteinuria.
Design Randomised, double blind, parallel group trial comparing ramipril (1.25 mg/day) with placebo (on top of usual treatment) for cardiovascular and renal outcomes for at least three years.
Setting Multicentre, primary care study conducted mostly by general practitioners in 16 European and north African countries.
Participants 4912 patients with type 2 diabetes aged >50 years who use oral antidiabetic drugs and have persistent microalbuminuria or proteinuria (urinary albumin excretion ≥ 20 mg/l in two consecutive samples), and serum creatinine ≤ 150 μmol/l.
Main outcome measures The primary outcome measure was the combined incidence of cardiovascular death, non-fatal myocardial infarction, stroke, heart failure leading to hospital admission, and end stage renal failure.
Results Participants were followed for 3 to 6 (median 4) years. There were 362 primary events among the 2443 participants taking ramipril (37.8 per 1000 patient years) and 377 events among the 2469 participants taking placebo (38.8 per 1000 patient years; hazard ratio 1.03 (95% confidence interval 0.89 to 1.20, P = 0.65)). None of the components of the primary outcome was reduced. Ramipril lowered systolic and diastolic blood pressures (by 2.43 and 1.06 mm Hg respectively after two years) and favoured regression from microalbuminuria (20-200 mg/l) or proteinuria (> 200mg/l) to normal level (< 20 mg/l) or microalbuminuria (P < 0.07) in 1868 participants who completed the study.
Conclusions Low dose (1.25 mg) ramipril once daily has no effect on cardiovascular and renal outcomes of patients with type 2 diabetes and albuminuria, despite a slight decrease in blood pressure and urinary albumin. The cardiovascular benefits of a daily higher dose (10 mg) ramipril observed elsewhere are not found with an eightfold lower daily dose.
Elevated urinary albumin excretion in patients with type 1 diabetes reverts to normoalbuminuria in a majority of patients but advances toward proteinuria in some. In order to gain valuable insights into the early pathophysiology of diabetic nephropathy we evaluated the association of kidney tubular injury biomarkers with changes in albuminuria in patients with type 1 diabetes mellitus. Urine levels of kidney injury molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), and some inflammatory markers were determined in 38 healthy individuals and 659 patients with type 1 diabetes mellitus having varying degrees of albuminuria. Urinary interleukin-6, CXCL10/IP-10, NAG, and KIM-1 levels were very low in healthy individuals, increased in type 1 patients with normoalbuminuria, and were highest in diabetic patients that had microalbuminuria. Low baseline concentrations of urinary KIM-1 and NAG both individually and collectively were significantly associated with the regression of microalbuminuria over the subsequent 2 years; an effect independent of clinical characteristics. Progression and regression of microalbuminuria were unrelated to urinary levels of interleukins 6 and 8, CXCL10/IP-10, and monocyte chemoattractant protein-1. Thus our results show that lower urinary KIM-1 and NAG levels were associated with the regression of microalbuminuria in type 1 diabetes mellitus. Hence, tubular dysfunction is a critical component of the early course of diabetic nephropathy.
chronic kidney disease; diabetic nephropathy; renal proximal tubule cell; tubular epithelium
Microalbuminuria (MA) represents the earliest clinical evidence of diabetic nephropathy and is a predictor of increased cardiovascular morbidity and mortality. The aim of this study was to determine the prevalence of MA among diabetic patients in the Al-Ain district of the United Arab Emirates (UAE).
The study was part of a general cross-sectional survey carried out to assess the prevalence of diabetes mellitus (DM) complications in Al-Ain district, UAE and was the first to assess the prevalence of MA among diabetic patients. A sample of 513 diabetic patients with a mean age of 53 years (SD: ± 13) was randomly selected during 2003/2004. All patients completed an interviewer-administered questionnaire and underwent medical assessment. First morning urine collections were obtained and were tested for clinical proteinuria using urine dipsticks and for MA using the single Micral-Test II strips.
MA was found in 61% (95% CI: 56.7–65.7) of the sample and the rate was significantly higher among males, positively related to body mass index (BMI), type 2 DM and presence of other DM complications such as diabetic retinopathy and neuropathy. Of the total sample population, 12.5% (95% CI: 8.1-14.1) had clinical proteinuria.
The prevalence rate of MA was considerably high ( 61%) among diabetic patients in the UAE. Therefore, regular screening for MA is recommended for all diabetic patients, as early treatment is critical for reducing cardiovascular risks and slowing the progression to late stages of diabetic nephropathy (overt proteinuria and end-stage renal disease).
Microalbuminuria is associated with diabetes and is an independent risk factor for developing diabetic nephropathy. We have previously reported the overall prevalence of normoalbuminuria, microalbuminuria, and macroalbuminuria to be 51, 39, and 9.8%, respectively, in an unselected 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.
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 <30 mg/g, microalbuminuria as 30–299 mg/g, and macroalbuminuria as >300 mg/g.
Among the patients with estimated kidney function determined, chronic kidney disease was noted in 17% of those with normoalbuminuria (stage 3–5), and significant kidney dysfunction was found in 27% of those with microalbuminuria and 31% of those with overt proteinuria. CrCl was <60 ml/min in 20.5% of normoalbuminurics, 30.7% of microalbuminurics, and 35.0% of macroalbuminurics (p < 0.0001).
A large proportion of diabetic patients with completely normal urinary albumin excretion or microalbuminuria presented with significant kidney dysfunction. Therefore, further investigation is warranted.
Albuminuria; Chronic kidney disease; Diabetes; Diabetic nephropathy; Normoalbuminuria; Proteinuria
Twenty-four hour urinary albumin concentrations were measured in 113 (mean age 51.1 years) non-insulin-dependent (NIDDM) Nigerian diabetics (50 males, 63 females). A high prevalence of microalbuminuria (> or = 30 mg/24 hour) was observed in male (54%) as well as female diabetics (59%). Microalbuminuria was also observed in a high proportion of diabetics (52%) with a short duration (< 5 years) of disease. Elevated blood pressure and retinopathy were present in 41% and 16% of patients respectively. Among the 49 patients with normoalbuminuria (< 30 mg/24 hour), six (12%) had retinopathy compared with 12 (18%) in the microalbuminuria group. Diastolic blood pressure levels were significantly higher (P < 0.01) in male diabetics with retinopathy but this was not associated with higher albuminuria. Urinary albumin concentrations were not influenced by elevated blood pressure. There were no significant differences in age, duration of diabetes, blood pressure or serum creatinine between diabetics with and without microalbuminuria. These results suggest that though there is a high prevalence of microalbuminuria amongst NIDDM Nigerian diabetics it may not predict retinopathy and occurs independently of either glycaemic control or elevated blood pressure levels.
Diabetic nephropathy is the main cause of the increased morbidity and mortality in patients with insulin dependent diabetes. The prevalence of microalbuminuria was determined in adults with insulin dependent diabetes of five or more years' duration that had started before the age of 41. All eligible patients (n=982) attending a diabetes clinic were asked to collect a 24 hour urine sample for analysis of albumin excretion by radio-immunoassay; 957 patients complied. Normoalbuminuria was defined as urinary albumin excretion of ≤30 mg/24 h (n=562), microalbuminuria as 31-299 mg/24 h (n=215), and macroalbuminuria as ≥300 mg/24 h (n=180). The prevalence of microalbuminuria and macroalbuminuria was significantly higher in patients whose diabetes had developed before rather than after the age of 20. The prevalence of arterial hypertension increased with increased albuminuria, being 19%, 30%, and 65% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. The prevalence of proliferative retinopathy and blindness rose with increasing albuminuria, being 12% and 1·4%, respectively, in patients with normoalbuminuria, 28% and 5·6% in those with microalbuminuria and 58% and 10·6% in those with macroalbuminuria. An abnormal vibratory perception threshold was more common in patients with microalbuminuria (31%) and macroalbuminuria (50%) than in those with normoalbuminuria (21%).
This study found a high prevalence (22%) of microalbuminuria, which is predictive of the later development of diabetic nephropathy. Microalbuminuria is also characterised by an increased prevalence of arterial hypertension, proliferative retinopathy, blindness, and peripheral neuropathy. Thus, urinary excretion of albumin should be monitored routinely in patients with insulin dependent diabetes.
Proteinuria is the hallmark of diabetic nephropathy; yet, glomerular histology does not fully explain mechanisms contributing to proteinuria. Our objective was to identify proteins in the urine of individuals with type 1 diabetes and microalbuminuria that might implicate a mechanistic pathway operative in proteinuria.
RESEARCH DESIGN AND METHODS
Using a GeLC/MS platform proteomics approach, we compared the urine proteome from 12 healthy nondiabetic individuals, 12 subjects with type 1 diabetes yet normal urinary albumin excretion rates, and 12 subjects with type 1 diabetes and microalbuminuria (type 1 diabetes + microalbuminuria).
The abundance of megalin and cubilin, two multiligand receptors expressed in kidney proximal tubule cells and involved with the reuptake of filtered albumin and megalin/cubilin ligands, was significantly increased in type 1 diabetes + microalbuminuria urine, compared with both nonalbuminuric groups.
Aberrant shedding of megalin and cubilin could contribute to albuminuria in diabetes and to deficiency states of important vitamins and hormones.
Our study evaluates the long-term effect of microalbuminuria on mortality among patients with acute myocardial infarction. We followed 151 patients from 1996 to 2007 to investigate if microalbuminuria is a risk factor in coronary heart disease. All patients admitted with acute myocardial infarction in 1996 were included. At baseline, we recorded urinary albumin/creatinine concentration ratio, body mass index, blood pressure, left ventricle ejection fraction by echocardiography, smoking status, medication, diabetes, age, and gender. Deaths were traced in 2007 by means of the Danish Personal Identification Register. Microalbuminuria, defined as a urinary albumin/creatinine concentration ratio above 0.65 mg/mmoL, occurred in 50% of the patients and was associated with increased all-cause mortality. Thus, 68% of the patients with microalbuminuria versus 48% of the patients without microalbuminuria had died during the 10 years of follow-up (P=0.04). The crude hazard ratio for death associated with microalbuminuria was 1.78 (CI: 1.18–2.68) (P=0.006), whereas the gender- and age-adjusted hazard ratio was 1.71 (CI: 1.03–2.83) (P=0.04). We concluded that microalbuminuria in hospitalized patients with acute myocardial infarction is prognostic for increased long-term mortality. We recommend measurement of microalbuminuria to be included as a baseline risk factor in patients with acute myocardial infarction and in future trials in patients with coronary heart disease.
acute myocardial infarction; microalbuminuria; risk factors; atherosclerosis; cardiovascular disease.
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.
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.
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 < 0.001), and also a greater severity of the disease (60.9% vs. 21.4 vs. 9.9, p < 0.001).
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.
Diabetic Retinopathy; Microalbuminuria; Macroalbuminuria; Risk factor; Type 2 Diabetes
OBJECTIVE--To investigate the predictive value of microalbuminuria (albumin excretion rate 30-300 mg/24 h) as a risk factor for overt diabetic nephropathy in patients with longstanding insulin dependent diabetes. DESIGN--10 year follow up of patients with normoalbuminuria (albumin excretion rate < 30 mg/24 h), microalbuminuria (30-300 mg/24 h), and macroalbuminuria (> 300 mg/24 h) based on two out of three timed overnight urine samples. SETTING--Outpatient clinic of Helsinki University Hospital. SUBJECTS--72 consecutive patients who had had insulin dependent diabetes for over 15 years. MAIN OUTCOME MEASURES--Urinary albumin excretion rate, mortality, and prevalence of diabetic complications after 10 years. RESULTS--56 patients were re-examined at 10 year follow up, 10 had died, five were lost to follow up, and one was excluded because of non-diabetic kidney disease. At initial screening 22 patients had macroalbuminuria, 18 had microalbuminuria, and 26 had normal albumin excretion. Only five (28%, 95% confidence interval 10% to 54%) of the microalbuminuric patients developed macroalbuminuria during the 10 year follow up and none developed end stage renal failure. Two (8%, 1% to 25%) normoalbuminuric patients developed macroalbuminuria and four (15%, 4% to 35%) became microalbuminuric. Seven (32%, 14% to 55%) of the macroalbuminuric patients developed end stage renal failure and six (27%, 11% to 50%) died of cardiovascular complications. CONCLUSION--Microalbuminuria is not a good predictor of progression to overt nephropathy in patients with longstanding insulin dependent diabetes.
the prevalence of microalbuminuria, defined as an albumin to creatinine
ratio (UAC) equal to or greater than 2mg/mmol in at least two of three
early morning urine samples, in adolescents and children with insulin
dependent diabetes mellitus.
coordinated, cross sectional, multicentre study in paediatric diabetes
outpatient clinics in the United Kingdom and Republic of Ireland.
urine samples collected between July 1997 and July 1998 were analysed
at a central reference laboratory for HbA1C using high
performance liquid chromatography, and for urinary albumin and
creatinine concentrations from which the UAC was derived (mg/mmol).
Clinical data were collected locally and coordinated centrally.
aged between 10 and 20 years, with insulin dependent diabetes mellitus
for more than a year, attending diabetes outpatient clinics.
RESULTS—A total of
1007 patients, comprising 69% of the eligible population of 1451, provided three early morning urine samples. Ninety eight (9.7%) had
microalbuminuria using the currently accepted screening cut off of
UAC ⩾ 2 mg/mmol in at least two of three early morning urine
samples. Significantly more girls than boys and significantly more
pubertal and postpubertal patients had abnormal albumin excretion.
Microalbuminuria was not associated with raised blood pressure.
prevalence of 9.7% for abnormal UAC was found in a cohort of 1007 children and adolescents aged 10-20 years. Thus a tenth of this
national sample of young people were identified as being at particular
risk of microvascular and later macrovascular disease.
Continuous increase in the number of patients with end-stage renal disease demands early detection of chronic kidney disease (CKD). The aim of the present study was to diagnose CKD in its earliest stages in a randomly selected population using a diagnostic algorithm developed by the working group.
An algorithm for the diagnostic procedure was created to identify patients with CKD requiring further nephrological care. Randomly chosen adult inhabitants of a city with a population of 60,000 were invited to participate in this study. Screening procedures included a microalbuminuria dipstick test accompanied by blood pressure measurement and medical questionnaire. In further diagnosis of CKD, estimated glomerular filtration rate (eGFR), albumin concentration in urine, urinalysis and ultrasound examination were used according to the algorithm. Multivariate logistic regression was performed to identify associations between participants’ characteristics and albuminuria.
Out of 9,700 invited subjects, 2,471 individuals participated in the PolNef study. Albuminuria was detected in 15.6% of the investigated population using the dipstick test and thereafter confirmed in 11.9% by the turbidimetric method. The modeling of multivariate logistic regression indicated the following independent predictors of albuminuria: male sex, diabetes, nocturia and hypertension. For people without diabetes and without hypertension, nocturia independently predicted detection of albuminuria. 481 people received a consultation with a nephrologist, and 96% of them were recognized as having CKD. At least 9% of patients with CKD had eGFR by MDRD <60 ml/min/1.73 m2. Six persons were referred for further treatment because of newly diagnosed kidney tumor.
CKD in early stages occurs frequently in the studied population. The proposed diagnostic algorithm seems to be a powerful tool to identify subjects at risk of CKD. The role of nocturia as an independent predictor of albuminuria, both in the general population and in people without diabetes or hypertension, should be further examined.
Albuminuria; Chronic kidney disease; Diagnostic algorithm; Nocturia
Prevalence of microalbuminuria is increased in patients with HIV. Microalbuminuria is associated with increased mortality in other populations, including diabetics, for whom microalbuminuria testing is standard of care. We investigated whether microalbuminuria is associated with mortality in HIV-infected women not receiving antiretroviral therapy.
Urinalysis for proteinuria and semi-quantitative testing for microalbuminuria were performed in specimens from two consecutive visits in 1,547 HIV-infected women enrolled in the Women’s Interagency HIV Study in 1994–1995. Time to death was modeled using proportional hazards analysis.
Compared to women without albuminuria, the hazard ratio (HR) for all-cause mortality was increased in women with one (HR 3.4; 95% CI 2.2–5.2) or two specimens positive for either proteinuria or microalbuminuria (HR 3.9; 95% CI 2.1–7.0). The highest risk was observed in women with both specimens positive for proteinuria (HR 5.8; 95% CI 3.4–9.8). The association between albuminuria and all-cause mortality risk remained significant after adjustment for demographics, HIV disease severity, and related comorbidities. Similar results were obtained for AIDS death.
We identified a graded relationship between albuminuria and the risk of all-cause and AIDS mortality.
HIV; microalbuminuria; proteinuria; mortality
The formation of advanced glycation end products (AGEs) is accelerated in patients with diabetic nephropathy. The aim of this study was to ascertain if the urinary excretion of proteins modified by advanced glycation can be used as biomarkers for albuminuria in individuals with type 1 or type 2 diabetes.
Community-based patients with type 1 (n = 68) or type 2 diabetes (n = 216) attending a diabetes clinic of a tertiary referral hospital were classified as having normoalbuminuria (Normo, albumin excretion rate (AER) <20 μg/min), microalbuminuria (Micro, AER 20–200 μg/min) or macroalbuminuria (Macro, AER ≥200 μg/min). Serum and urine AGE-modified proteins were measured.
In patients with both type 1 diabetes and type 2 diabetes, there was a clear association between the degree of albuminuria and urinary AGE-modified proteins (p < 0.0001). Exclusive to patients with type 1 diabetes, urinary excretion of the AGE carboxymethyllysine correlated with AER, whereas patients with type 2 diabetes and macroalbuminuria had an increase in urinary methylglyoxal, an AGE intermediate. These changes were independent of isotopic glomerular filtration rate levels. Serum concentrations of AGEs or soluble receptor for AGEs were not consistently associated with albuminuria in either type 1 or type 2 diabetes.
Urinary excretion of proteins modified by AGEs may be useful biomarkers of albuminuria in individuals with type 1 and type 2 diabetes, warranting prospective investigation in larger diabetic cohorts.
Advanced glycation end products; Diabetic nephropathy; Albuminuria; Carboxymethyllysine; Methylglyoxal; Urinary biomarkers
The prevalence of microalbuminuria was assessed in 174 albustix negative hypertensive patients by estimating albumin in the morning random urine samples by immunoturbidimetric method within four hours of voiding of urine. The urine samples were not stored and collected without any preservatives. The urinary albumin was calculated in terms of ratio with respect to urinary creatinine and expressed as albumin creatinine ratio (mg/g). Out of 174 albustix negative hypertensives, 58 (33.3%) patients were found to have microalbuminuria. The prevalence of microalbuminuria in males and females was found to be 34% and 30.7% respectively. No correlation was found between the Body Mass Index (BMI) and albumin excretion (r2 = 0.0271) and between duration of hypertension and urinary albumin excretion (r2 = 0.0042). Prevalence of microalbuminuria in nonsmokers and non-alcoholic hypertensives was 20%. The prevalence in alcoholics, smokers and both smokers and alcoholics was found to be 35%, 42% and 41% respectively. The high prevalence of microalbuminuria than the various reported studies on the subject demands establishment of a screening programme for microalbuminuria, implementation of specific intervention methods and education of hypertensive patients about the consequences of smoking and alcohol on possible involvement of renal system.
Hypertension; Microalbuminuria; Albumin; Creatinine ratio
A cross-sectional study was performed from November 2005 to July 2007 to determine the prevalence of microalbuminuria and its risk factors among type 2 diabetic patients.. Two hundred and eighty-eight type 2 diabetic patients (141 males and 147 females) referred to Yazd diabetes research center were randomly recruited for the study. Microalbuminuria was detected by measuring the albumin to creatinine ratio in the early morning urine. Microalbuminuria was diagnosed if this ratio was between 30 and 300 mg/g on two occasions during three months. Prevalence of microalbuminuria was 14.2%. Chi-square analysis revealed that microalbuminuria was correlated with the diastolic blood pressure (P = 0.003) and the duration of diabetes (P = 0.000). No statistically significant correlation was found between microalbuminuria and age, sex, body mass index, levels of fasting blood sugar, glycosylated hemoglobin (HbA1c), serum triglyceride, and serum cholesterol, or systolic blood pressure. For 240 patients for whom the duration of diabetes was known from the answers in their questionnaires, logistic regression was used for analysis. Results showed that two variables including the duration of diabetes and Diastolic Blood Pressure (DBP) play a role in this model and the following Logic association was obtained: g^ (x) = -9.233 ± 0.079 DBP ± 0.114 duration according to this model, both DBP and duration of diabetes were directly correlated with microalbuminuria. Determination of the urine albumin to creatinine ratio is an easy method for screening of microalbuminuria that is suggested for all diabetic patients, especially diabetic patients with hypertension and long-term diabetes.
Glycosylated hemoglobin; microalbuminuria; type 2 diabetes mellitus
OBJECTIVE—The aim of this study was to determine the prevalence and risk factors for microalbuminuria among south Indian type 2 diabetic patients attending a diabetes centre.
METHODS—One thousand four hundred and twenty five type 2 diabetic patients attending a diabetes centre in south India were recruited for the study. Urinary albumin concentration was measured by immunoturbodimetric assay. Microalbuminuria was diagnosed if the urinary albumin excretion was >30 mg/g of creatinine.
RESULTS—Overall prevalence of microalbuminuria was 36.3% (95% confidence interval 33.8 to 38.9). The prevalence of microalbuminuria increased with the increase in duration of diabetes. Multivariate regression analysis revealed age, diastolic blood pressure, glycated haemoglobin, fasting plasma glucose, and duration of diabetes to be associated with microalbuminuria.
CONCLUSION—The overall prevalence of microalbuminuria in this south Indian clinic population and its risk factors are similar to that reported in Europeans.
Keywords: microalbuminuria; diabetes; type 2 diabetes; south India
OBJECTIVE--To investigate the risk factors for the development of persistent microalbuminuria in insulin dependent diabetic patients. DESIGN--Four year follow up of a cohort of diabetic patients. SETTING--Outpatient departments of teaching and district general hospitals in England. SUBJECTS--148 non-microalbuminuric, non-hypertensive insulin dependent diabetic patients. MAIN OUTCOME MEASURES--Urinary albumin excretion rate and arterial blood pressure. RESULTS--137 patients completed four year follow up, of whom 11 developed persistent microalbumin-uria (albumin excretion rate > or = 30 micrograms/min on at least two consecutive occasions), giving a cumulative frequency of 8%. 103 remained normoalbuminuric and 23 exhibited intermittent microalbuminuria. At baseline the persistent microalbuminuric group had had significantly raised blood pressure (mean 137.9 (SD 14.9)/82.3 (7.6) v 123.5 (13.2)/72.8 (9.1) mm Hg), glycated haemoglobin concentration 10.4% (2.0%) v 8-9% (2.0%), and albumin excretion rate (median (interquartile range) 17.5 (13.0-22.3) v 4.8 (3.7-6.7) micrograms/min) (p < 0.05 for all) compared with the normo-albuminuric group. Blood pressure and glycated haemoglobin remained significantly higher in the persistent microalbuminuric group throughout the study (p < 0.05). Multiple regression analysis showed initial albumin excretion rate, blood pressure, and smoking to be significant determinants of persistent microalbuminuria (p < 0.02). CONCLUSION--In insulin dependent diabetic patients with poor glucose control, which may initially increase albumin excretion rate, an early rise of arterial pressure and smoking are implicated in the development of persistent microalbuminuria.
We investigated the prevalence of microalbuminuria and its association with the metabolic syndrome and its components in a Chinese population.
The study subjects were recruited from a newly established residential area in the suburb of Shanghai. We measured anthropometry, blood pressure (BP), fasting plasma glucose, and serum lipids, and collected spot urine samples for the determination of albumin-creatinine ratio. We defined microalbuminuria as a urinary albumin-to-creatinine ratio of 30 to 299 mg/g. The metabolic syndrome was defined according to the International Diabetes Federation criteria.
The 1079 participants included 410 (38.0%) hypertensive patients, and 66 (6.1%) diabetic patients. The prevalence of microalbuminuria (4.3%) was 3.2 times higher in 167 patients with the metabolic syndrome than 912 subjects without the metabolic syndrome (12.0% vs. 2.9%, P < 0.0001). In multiple regression adjusted for sex, age, body mass index, current smoking, alcohol intake and the use of antihypertensive drugs, and mutually adjusted for the components, microalbuminuria was significantly associated with diastolic BP (odds ratio 1.74 for +10 mmHg; 95% confidence interval [CI] 1.10-2.76; P = 0.02) and fasting plasma glucose (1.18; 95% CI 1.01-1.41; P = 0.04), but not with waist circumference, systolic BP, or serum HDL cholesterol and triglycerides (P > 0.10).
Microalbuminuria is common in the Chinese population, and much more prevalent in the presence of the metabolic syndrome, mainly attributable to elevated diastolic BP and plasma glucose.
To determine the occurrence of microalbuminuria in young people with Type 1 diabetes mellitus followed prospectively for 2 years and to relate the presence of persistent elevations in urinary albumin excretion (UAE) to age, diabetes duration, puberty and other factors.
During a 2 year period, random urine samples were obtained from 471 patients, aged 8–18 years (mean ± SD 12.9 ± 2.3 years) with Type 1 diabetes duration 5.6 ± 3.0 years, as part of routine clinical care. Urine albumin and creatinine concentrations were measured in 1310 samples (median, 3 samples per patient) and the albumin:creatinine ratio was calculated (in micrograms albumin per milligram creatinine). Height, weight, blood pressure (BP), glycated haemoglobin (HbA1c), blood glucose monitoring frequency and Tanner staging were collected from patients’ medical records.
Twenty-three per cent of patients had one or more sample with elevated UAE (≥20 μg/mg) and 9.3% had persistent elevations (≥2 samples ≥20 μg/mg). Those with and without persistent microalbuminuria did not differ significantly in age, diabetes duration, z–score for body mass index, pubertal status or BP percentile. Ten per cent of children <13 years old and 9% of children ≥13 years old had persistent microalbuminuria. Persistent microalbuminuria was significantly associated with diabetes duration only in older children (duration 0.5–3 years, 4%; 4–6 years, 8%; ≥7 years, 14%; P = 0.02, trend test). Mean HbA1c over the 2 years was 8.7 ± 1.2%. In a logistic regression model, mean HbA1c was the only significant predictor of persistent microalbuminuria (odds ratio 1.3, 95% confidence interval 1.0–1.6, P = 0.05).
Microalbuminuria in older children with Type 1 diabetes is likely to be clinically significant. In younger children, it may reflect functional, reversible renal changes. Longitudinal analysis is needed to confirm the probable transient nature of microalbuminuria in young patients with Type 1 diabetes.
children; glycated haemoglobin; microalbuminuria; puberty; Type 1 diabetes mellitus
AIM--To compare the urinary excretion of beta 2-glycoprotein-1 with that of two other markers of early tubular disorder in diabetic patients without clinical proteinuria. METHODS--The urinary excretion of retinol binding protein, beta 2-glycoprotein-1, and N-acetyl-beta-D-glucosaminidase was measured in 90 known diabetic patients who had a negative reagent strip test for proteinuria. RESULTS--Among 43 patients with urinary albumin excretion within the reference range, 23 (53%) had raised urinary N-acetyl-beta-D-glucosaminidase activity, five (12%) increased excretion of beta 2-glycoprotein-1, and five (12%) increased loss of retinol binding protein. Among 47 patients with an albumin excretion of 0.9-7.9 mg/mmol creatinine, 42 (89%) had increased urinary N-acetyl-beta-D-glucosaminidase, 23 (49%) an increased output of beta 2-glycoprotein-1, and 16 (34%) a raised excretion of retinol binding protein. The excretion of these markers of tubular defects seldom exceeded two and a half times the upper reference limit and the differences between the findings in the insulin dependent and non-insulin dependent patients with similar albumin excretion were small and insignificant. CONCLUSIONS--In diabetic patients with a negative dipstick test for proteinuria: (a) assay of urinary beta 2-glycoprotein-1 may be a more sensitive test for the detection of impaired tubular reabsorption of protein than measurement of retinol-binding protein; (b) assay of N-acetyl-beta-D-glucosaminidase can detect tubular injury at a time when protein reabsorption remains normal; and (c) impaired renal tubular function may be present in the absence of evidence of glomerular malfunction.