Microalbuminuria: associations with height and sex in non-diabetic subjects.

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.     

Role of glycaemic control in development of microalbuminuria in patients with insulin dependent diabetes.

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.     

Predictive value of microalbuminuria in patients with insulin-dependent diabetes of long duration.

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.     

Microtransferrinuria and microalbuminuria. I. In the diabetic human

We studied albumin, transferrin and total protein excretion in the urine of 110 diabetics visiting a family practice department. Of these patients 18.2% had an elevated total urinary protein above the reference range (greater than 200 mg/g creatinine). Of the remaining patients (normoproteinuria), 25.5% have elevated transferrin (greater than 0.9 mg/g creatinine) while 18.8% have elevated albumin (greater than 32 mg/g creatinine). The correlation coefficient between transferrin and albumin in urine when total urinary protein is normal was 0.77. Moderate exercise increased urinary transferrin in normal subjects 950%, while for albumin the increase was 440%. These data demonstrate the usefulness of microtransferrinuria, a potentially more sensitive indicator than microalbuminuria for diabetic nephropathy.     

Long term renal outcome of childhood haemolytic uraemic syndrome.

OBJECTIVE--To evaluate the long term outcome of renal function in infants and children after diarrhoea associated haemolytic uraemic syndrome. SETTING--The Hospital for Sick Children, Great Ormond Street, and the Royal Free Hospital, London. SUBJECTS--103 children with the syndrome who presented between 1966 and 1985; 88 attended for follow up investigations (40 male, 48 female) with a mean age 11.6 (range 5.2-22.6) years and a mean duration of follow up of 8.5 (range 5.1-21.3) years. MAIN OUTCOME MEASURES--Blood pressure, ratio of early morning urine albumin to creatinine concentration, glomerular filtration rate, and plasma renin activity. RESULTS--The mean (SD) systolic blood pressure standard deviation score was 0.38 (0.67) and diastolic blood pressure SD score was 0.10 (0.76). The geometric mean ratio of overnight urine albumin to creatinine concentration was 1.27 (range 0.03-48.2), significantly higher than the value observed in 77 normal children (0.32 (0.05-1.95), p less than 0.0001). Glomerular filtration rate estimated from the plasma clearance of chromium-51 EDTA was 95.1 (22.7) ml/min/1.73 m2 surface area, and 16 children had a rate of less than or equal to 80 ml/min/1.73 m2. Significant negative correlations were found between glomerular filtration rate and urinary albumin to creatinine ratio (r = -0.41, p less than 0.0001) and glomerular filtration rate and systolic blood pressure SD score (r = -0.48, p less than 0.0001). A significant positive correlation was found between urinary albumin to creatinine ratio and systolic blood pressure SD score (r = 0.25, p = 0.02). CONCLUSIONS--After an acute episode of diarrhoea associated haemolytic uraemic syndrome 31% (27/88) of children had an increased albumin excretion, 18% (16/88) had a reduced glomerular filtration rate and 10% (9/88) had both, in association with a higher systolic blood pressure, indicating considerable residual nephropathy in this group.     

Predictors of mortality in insulin dependent diabetes: 10 year observational follow up study.

OBJECTIVE: To evaluate the prognostic significance of microalbuminuria and overt diabetic nephropathy and other putative risk factors for cardiovascular and all cause mortality in insulin dependent diabetes. DESIGN: Ten year observational follow up study. SETTING: Outpatient diabetic clinic in a tertiary referral centre. SUBJECTS: All 939 adults with insulin dependent diabetes (duration of diabetes five years or more) attending the clinic in 1984; 593 had normal urinary albumin excretion (< or = 30 mg/24 h), 181 persistent microalbuminuria (31-299 mg/24 h), and 165 overt nephropathy (> or = 300 mg/24 h). MAIN OUTCOME MEASURE: All cause and cardiovascular mortality. RESULTS: Fifteen per cent of patients (90/593) with normoalbuminuria, 25% (45/181) with microalbuminuria, and 44% (72/165) with overt nephropathy at baseline died during follow up. Cox multiple regression analysis identified the following significant predictors of all cause mortality: male sex (relative risk 2.03; 95% confidence interval 1.37 to 3.02), age (1.07; 1.06 to 1.08), height (0.96; 0.94 to 0.98), smoking (1.51; 1.09 to 2.08), social class V versus social class IV (1.70; 1.25 to 2.31), log10 urinary albumin excretion (1.45; 1.18 to 1.77), hypertension (1.63; 1.18 to 2.25), log10 serum creatinine concentration (8.96; 3.34 to 24.08), and haemoglobin A1c concentration (1.11; 1.03 to 1.20). Age, smoking, microalbuminuria, overt nephropathy, and hypertension were significant predictors of cardiovascular mortality. Mortality in patients with microalbuminuria was only slightly increased compared with that in patients with normoalbuminuria. Median survival time after the onset of overt diabetic nephropathy was 13.9 years (95% confidence interval 11.8 to 17.2 years). CONCLUSIONS: Abnormally increased urinary albumin excretion and other potentially modifiable risk factors such as hypertension, smoking, poor glycaemic control, and social class predict increased mortality in insulin dependent diabetes. Microalbuminuria by itself confers only a small increase in mortality. The prognosis of patients with overt diabetic nephropathy has improved, probably owing to effective antihypertensive treatment.     

The influence of urinary flow rate on mercury excretion in children

ProjectThere is limited literature concerning the effect of urinary flow rate on mercury excretion at low-level exposure. The aim of the present study is to examine the influence of urinary flow rate on mercury excretion in children. Also of interest is the influence of flow rate on creatinine excretion and creatinine-corrected mercury, which arisearises with spot urine samples.ProcedureA substudy of the New England Children's Amalgam Trial collected pairs of urine samples from children aged 10–16 years: a timed overnight collection and a spot daytime sample collected the following day. These samples were analyzed for mercury and creatinine concentration. Regression analysis was used to model the effect of urinary flow rate in the timed overnight samples. A paired t-test compared concentrations and creatinine-corrected mercury between overnight and daytime samples.ResultsCreatinine excretion rate (mg/h) increased significantly with urinary flow rate (mL/h), whereas creatinine concentration (g/L) decreased with flow rate. We found a non-significant increase in mercury excretion rate (ng/h) with flow rate, and mercury concentration decreased with flow rate. Mercury and creatinine concentrations were significantly higher in the overnight compared to daytime samples. For creatinine-corrected mercury, no significant impact of urinary flow rate was found.ConclusionsAlthough the creatinine excretion rate, and probably the mercury excretion rate, increased with urinary flow rate, the mercury/creatinine ratio seemed relatively unaffected by urinary flow rate.     

Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin dependent diabetes mellitus: prospective,observational study.

OBJECTIVE: To evaluate putative risk factors for the development of incipient diabetic nephropathy (persistent microalbuminuria) and overt diabetic nephropathy (persistent macroalbuminuria) in patients with non-insulin dependent diabetes. DESIGN: Prospective, observational study of a cohort of white, non-insulin dependent diabetic patients followed for a median period of 5.8 years. SETTING: Outpatient clinic in tertiary referral centre. SUBJECTS: 191 patients aged under 66 years with non-insulin dependent diabetes and normoalbuminuria (urinary albumin excretion rate < 30 mg/24 h) who attended the clinic during 1987. MAIN OUTCOME MEASURES: Incipient and overt diabetic nephropathy. RESULTS: Fifteen patients were lost to follow up. Thirty six of the 176 remaining developed persistent microalbuminuria (30-299 mg/24 h in two out of three consecutive 24 hour urine collections) and five developed persistent macroalbuminuria (> or = mg/24 h in two out of three consecutive collections) during follow up. The five year cumulative incidence of incipient diabetic nephropathy was 23% (95% confidence interval 17% to 30%). Cox''s multiple stepwise regression analysis revealed the following risk factors for the development of incipient or overt diabetic nephropathy: increased baseline log urinary albumin excretion rate (relative risk 11.1 (3.4 to 35.9); P < 0.0001); male sex (2.6 (1.2 to 5.4); P < 0.02); presence of retinopathy (2.4 (1.3 to 4.7); P < 0.01); increased serum cholesterol concentration (1.4 (1.1 to 1.7); P < 0.01); haemoglobin A1c concentration (1.2 (1.0 to 1.4); P < 0.05); and age (1.07 (1.02 to 1.12); P < 0.01). Known duration of diabetes, body mass index, arterial blood pressure, serum creatinine concentration, pre-existing coronary heart disease, and history of smoking were not risk factors. CONCLUSION: Several potentially modifiable risk factors predict the development of incipient and overt diabetic nephropathy in normoalbuminuric patients with non-insulin dependent diabetes.     

Microalbuminuria in non-insulin-dependent diabetes: its prevalence in Indian compared with Europid patients

Non-insulin-dependent diabetes mellitus is strikingly common in British Indians, but their susceptibility to diabetic complications is unknown. The ratio of albumin to creatinine concentrations was measured in samples of the first urine voided in the morning in 154 Indian and 82 Europid patients with non-insulin-dependent diabetes and in a control group of 129 non-diabetic Indians. The ratio was significantly higher in the Indian patients than in the Europid patients and the Indian controls. There were no significant correlations between the logarithm of the albumin: creatinine ratio and age, known duration of diabetes, haemoglobin A₁ concentration, or body mass index within either diabetic group. Hypertension and raised albumin:creatinine ratio were significantly associated, and significant correlations were seen between the logarithm of the albumin:creatinine ratio and systolic and diastolic blood pressures in the Indian but not the Europid diabetics.Because of the high prevalence of diabetes at a relatively early age in Indians, nephropathy may emerge as an important clinical problem.     

Laboratory measurement of urine albumin and urine total protein in screening for proteinuria in chronic kidney disease

Laboratory measurement of urine total protein has been important for the diagnosis and monitoring of renal disease for decades, and since the late 1990s, urine albumin has been measured to determine whether a diabetic patient has incipient nephropathy. Evolving understanding of chronic kidney disease (CKD) and, in particular, the cardiovascular risks that CKD confers, demands more sensitive detection of protein in urine. As well, evidence is now emerging that cardiovascular and all-cause mortality risks are increased at levels within the current 'normal' range for urine albumin. Standardisation is essential to permit valid application of universal decision points, and a National Kidney Disease Education Program/International Federation of Clinical Chemistry and Laboratory Medicine (NKDEP/IFCC) Working Party is making progress towards a reference system for urine albumin. In the meantime, available data suggest that Australasian laboratory performance is adequate in terms of precision and accuracy above current decision limits for urine albumin. In contrast, the complexity of proteins in urine makes standardisation of urine total protein measurement impossible. As well, urine total protein measurement is insufficiently sensitive to detect clinically important concentrations of urine albumin. An Australasian Expert Group, the Proteinuria Albuminuria Working Group (PAWG) has proposed that urine albumin/creatinine ratio is measured in a fresh, first morning, spot sample to screen for proteinuria in CKD. Both NKDEP/IFCC and PAWG emphasise the need for standardisation of sample collection and handling.     

A correlation between microalbuminuria and anti-insulin antibodies in type I diabetics

A link between circulating anti-insulin antibodies and diabetic glomerulopathy has been suggested. This paper presents two different studies aiming to detect a relationship between incipient nephropathy (indicated by microalbuminuria) and anti-insulin antibodies. In 64 type I diabetics, overnight urinary albumin excretion during an exercise-test was found to be correlated with systolic blood pressure (r = 0.258 p less than 0.05), anti-insulin antibodies (r = 0.258 p less than 0.05), and glycosylated hemoglobin (r = 0.258 p less than 0.05) whereas no correlation was found among these three parameters. In another group of 80 type I diabetics, urinary albumin excretion during a standardized exercise-test was also correlated with anti-insulin antibodies (r = 0.360 p less than 0.001). In this latter group, diabetics with elevated (greater than 200 microU/ml) levels of anti-insulin antibodies had higher values of microalbuminuria after exercise (p less than 0.001) when compared to those with lower or undetectable levels, although they did not differ with respect to blood pressure and glycemic control. Therefore, we confirm preliminary reports indicating a statistical relationship between anti-insulin antibodies and microalbuminuria. We hypothesize that anti-insulin antibodies may be an additional factor of risk in the pathogenesis of early (reversible) stages of diabetic nephropathy.     

Detection of unrecognised nocturnal hypoglycaemia in insulin-treated diabetics.

Cortisol to creatinine ratios in overnight urine samples, urinary glucose excretion, and plasma glucose concentrations were determined in 43 diabetic inpatients. All initially had normal cortisol to creatinine ratios (less than 55 x 10(-6)) and were initially treated by increasing their long-acting insulin component. Nine patients in whom this ratio became raised then had their long-acting insulin component reduced until their fasting plasma glucose concentration was 4-7 mol/l (72-126 mg/100 ml). The 34 patients who had never had a raised ratio were treated by increasing their long-acting insulin component until their fasting plasma glucose concentration was in the range 4-7 mmol/l. All the raised cortisol to creatinine ratios were clearly separate from the other values. A mean reduction in total insulin dose of 23% and in long-acting insulin dose of 53% was achieved, abolishing presumptive nocturnal hypoglycaemia by reducing the ratio to normal and dramatically improving diabetic control. Although there was no definite evidence that the patients who had raised cortisol to creatinine ratios had suffered from nocturnal hypoglycemia, these results strongly support the view that a raised ratio indicates an otherwise unrecognised episode of this condition.     

Diurnal variation of 6beta-hydroxycortisol in cardiac patients

The 24-hour urinary excretion of 6-beta-hydroxycortisol (6beta-OHC) and the urinary ratio of 6beta- hydroxycortisol/cortisol (6beta-OHC/UFC) have been proposed as noninvasive probes for human cytochrome P450 3A4 isoform (CYP3A4). In this study, we evaluated within- and between-day variability of 6beta-OHC excretion and 6beta-OHC/UFC ratio in nine Caucasian men with cardiac disease. Each study participant was asked to collect 24-hour urine specimens during four consecutive days in five standardized time intervals. Concentrations of UFC and 6beta-OHC were determined by immunoassay and the high-performance liquid chromatographic (HPLC) method, respectively. The HPLC method was accurate and precise, as indicated by the recovery rate of 96.5-103.3 % and less than 5.2 % and 6.3 % of the coefficient of variation for within-run and between-run assay, respectively. In patients, diurnal variations in UFC and 6beta-OHC excretion were parallel. Consequently, 6beta-OHC/UFC ratio remained stable during the day. Both, 6beta-OHC excretion and 6beta-OHC/UFC ratio showed significant relationship between 24-hour value and values measured in corresponding collection periods with best correlations obtained from night interval (22.00-06.00, r = 0.86-0.91). These results indicated that urinary 6beta-OHC excretion and 6beta-OHC/UFC ratio measured in overnight/morning urine could precisely reflect 24-hour values even in severely ill patients. In addition, a simple and sensitive HPLC method was described for determination of 6beta-OHC in urine.     

Higher rates of hemolysis are not associated with albuminuria in Jamaicans with sickle cell disease

Background

Albuminuria is a marker of glomerular damage in Sickle Cell Disease (SCD). In this study, we sought to determine the possible predictors of albuminuria in the two more prevalent genotypes of SCD among the Jamaica Sickle Cell Cohort Study participants.

Methods

An age-matched cohort of 122 patients with HbSS or HbSC genotypes had measurements of their morning urine albumin concentration, blood pressure, body mass index, haematology and certain biochemistry parameters done. Associations of albuminuria with possible predictors including hematological parameters, reticulocyte counts, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels were examined using multiple regression models.

Results

A total of 122 participants were recruited (mean age 28.6 years ±2.5 years; 85 HbSS, 37 HbSC). 25.9% with HbSS and 10.8% with HbSC disease had microalbuminuria (urine albumin/creatinine ratio  =  30–300 mg/g of creatinine) whereas 16.5% of HbSS and 2.7% of HbSC disease had macroalbuminuria (urine albumin/creatinine ratio>300 mg/g of creatinine). Mean arterial pressure, hemoglobin levels, serum creatinine, reticulocyte counts and white blood cell counts were statistically significant predictors of albuminuria in HbSS, whereas white blood cell counts and serum creatinine predicted albuminuria in HbSC disease. Both markers of chronic hemolysis, i.e. AST and LDH levels, showed no associations with albuminuria in either genotype.

Conclusions

Renal disease, as evidenced by excretion of increased amounts of albumin in urine due to a glomerulopathy, is a common end-organ complication in SCD. It is shown to be more severe in those with HbSS disease than in HbSC disease. Rising blood pressure, lower hemoglobin levels and higher white blood cell counts are hints to the clinician of impending renal disease, whereas higher rates of hemolysis do not appear to play a role in this complication of SCD.     

Effect of protein restriction in insulin dependent diabetics at risk of nephropathy.

Persistent proteinuria is strongly associated with increased mortality in insulin dependent diabetes, and risk of this condition can be predicted many years in advance by subclinical increases in albumin excretion rate (microalbuminuria). Eight normotensive insulin dependent diabetics with microalbuminuria who had overnight albumin excretion rates of between 15 and 200 micrograms/min underwent a three week randomised crossover study of their normal protein diet (median 92 (range 55-117) g/day) and a low protein diet (47 (38-57) g/day). Both diets were isoenergetic, and the low protein diet was supplemented with calcium and phosphate. Median overnight albumin excretion rate fell from 23.0 (15.0-170.1) micrograms/min during the normal diet to 15.4 (4.1-97.8) micrograms/min during the low protein diet. No consistent change was found in urinary excretion of beta 2 microglobulin during the two diets. The reduction in albumin excretion rate was accompanied by a significant fall in median glomerular filtration rate and fractional renal clearance of albumin. Kidney volume remained unchanged. There were no significant changes in glycaemic control or arterial blood pressure. In these few patients restriction of dietary protein had a beneficial effect on microalbuminuria, independent of changes in glucose concentrations and arterial blood pressure.     

Plasma endothelin-1 levels and albumin excretion rate in normotensive,microalbuminuric type 2 diabetic patients

BACKGROUND: Endothelin-1 (ET-1) is able to determine functional and structural renal alterations and plasma levels of this vasoconstrictor peptide are increased in diabetic patients. In a selected group of type 2 normotensive diabetic patients with microalbuminuria, we investigated circulating ET-1 levels compared to a control group and verified whether there is a relationship between ET-1 levels and albumin excretion rate in diabetics. SUBJECTS AND METHODS: Thirty-two microalbuminuric type 2 diabetic patients (12 males and 20 females; mean age 57 +/- 8 years) without hypertension, renal failure, hypercholesterolemia or atherosclerotic damage were selected. The control group was made up of 28 healthy subjects matched for sex and age. Blood pressure, creatinine clearance, serum cholesterol and plasma ET-1 values were determined in diabetic and control group. In diabetic patients, glycosilated hemoglobin and urinary albumin excretion rate were also assayed. Mean ET-1 values in diabetics and controls were compared using Student's t-test. Linear regression test was done to relate two variables. Statistical significance was set at p<0.05. RESULTS: Mean ET-1 values were significantly higher in the diabetic group than in controls (11.77 +/- 1.16 pg/ml vs 8.9 +/- 2.1 pg/ml; p<0.05). No relationship (p>0.05) was found between circulating ET-1 and blood pressure, creatinine clearance, serum cholesterol and metabolic control in diabetics. There was a significant positive correlation (r=0.403; p=0.03) between plasma ET-1 levels and albumin excretion rate in diabetic patients. CONCLUSIONS: Our results showed that circulating ET-1 values were increased in microalbuminuric, normotensive, type 2 diabetic patients and correlated with albumin excretion rate. These findings confirm that endothelial dysfunction, as expressed by ET-1 levels, occurs early in these patients and support the hypothesis of a potential role for this peptide in development of microalbuminuria in diabetic nephropathy.     

Electronic circular dichroism for the detection of microalbuminuria

Over the past decades, chiroptical spectroscopy has proved its incomparable ability to elucidate the structure and spatial arrangement of chiral molecules. Systematic analysis of biomolecules in the natural environment of biofluids, however, remains challenging. In this study, we used chiroptical spectroscopy to monitor urinary levels of human serum albumin. Not only severe proteinuria but even just a slightly increased urinary excretion of albumin (microalbuminuria) may indicate serious health complications, especially for diabetic individuals. Given the chiral nature of albumin and its typical spectral pattern, it may be easily observable by chiroptical spectroscopy, particularly electronic circular dichroism. The performed chiroptical analysis of urine not only allowed the detection of clinically confirmed microalbuminuria but was also able to reveal this pathological condition in cases beyond the diagnostic capability of common clinical procedures. Thus, our approach suggests that electronic circular dichroism is a useful tool for the fast and reliable qualitative monitoring of microalbuminuria with the potential for a quantitative analysis in the future.     

A sensitive routine assay for urinary albumin based on the competitive binding to anti-albumin antibodies in solid phase

The detection of microalbuminuria has a high prognostic value in diabetic patients with no symptoms of clinical nephropathy. Attention has been focused on the development of a simple, reproducible, specific, and, above all, sensitive method to detect albuminuria in the urine. The method is based on the competitive binding between albumin in the urine to be tested and a fixed amount of radiolabelled albumin to anti-albumin immunoglobulins in solid phase. The immunoglobulin C fraction of a rabbit anti-human albumin antiserum was left to coat highly adsorbent polystyrene microtitre tubes. While the aspecific tube binding was overcome by saturation with a solution of gelatine, increasing dilutions of standard albumin or the diluted urine samples to be tested were left to incubate with an equal volume of radiolabelled albumin at room temperature for 1 hour. The cold/hot albumin mixture was added to anti-albumin immunoglobulin-coated tubes, which had been repeatedly washed, and left to incubate. After washing, radioactivity was assessed. This assay has proved to be fast, simple and highly sensitive since it detects up to 25 ng of albumin per ml and is of value in large-scale screening for microalbuminuria in diabetic patients.     

Urinary albumin in head-down bed rest

Previous studies reported low urinary albumin excretion in astronauts during space missions, suggesting an effect of microgravity on renal albumin handling. To test this hypothesis, urinary albumin excretion was investigated with use of head-down bed rest at -6 degrees (HDBR), an experimental model of microgravity. Eight healthy young men underwent two phases. Each phase included 2 days of dietary adaptation (run-in), 4 days of baseline (light activities and bed rest), and 6 days of experiment: HDBR 24h every day for intervention light activities and bed rest for control. The study was done in metabolic ward (DLR, Cologne, Germany). Urine were collected in days 3-4 of baseline and days 4-6 of experiment. Urinary albumin was measured by a double antibody radioimmunoassay, creatininuria by automated colourimetry. Data are expressed as albumin/creatinine ratio to control for timing and completeness of urine collection. Compared to baseline, albumin/creatinine ratio decreased by 9.3% during HDBR and increased by 14.9% during control. The difference in changes over baseline was significant between HDBR and control (p < 0.01 by paired comparison). The data support the hypothesis that low gravity reduces renal albumin excretion.     

Urinary markers of renal inflammation in adolescents with Type 1 diabetes mellitus and normoalbuminuria

Diabet. Med. 29, 1297-1302 (2012) ABSTRACT: Aims Patients with the highest albumin:creatinine ratio within the normal range are at an increased risk for developing microalbuminuria. The mechanistic basis for this is unknown, but may be related to renal inflammation. Our goal was to characterize the urinary excretion of cytokines/chemokines in normoalbuminuric adolescents with Type?1 diabetes to determine whether higher range normoalbuminuria is associated with evidence of renal inflammation. Methods Forty-two urinary cytokines/chemokines were measured in subjects who were screened for the Adolescent Type?1 Diabetes Cardio-Renal Intervention Trial. Urinary cytokines/chemokines were compared across low (n?=?50), middle (n?=?50) or high (n?=?50) albumin:creatinine ratio tertile groups. Results At baseline, participants in the upper tertile were younger and had shorter diabetes duration compared with the other groups. Other clinical characteristics were similar. Urinary levels of interleukin?6, interleukin?8, platelet-derived growth factor-AA and RANTES differed across albumin:creatinine ratio tertiles, with higher values in patients in the middle and high tertiles compared with the lower tertile (ANCOVA P?≤?0.01). Conclusions Within the normal albumin:creatinine ratio range, higher urinary albumin excretion is associated with elevated urinary levels of inflammatory markers. Ultimately, this may provide mechanistic insights into disease pathophysiology and stratify the risk of nephropathy in Type?1 diabetes.