Detection and measurement of urinary protein

PURPOSE OF REVIEW: The measurement of urine total protein and albumin is central to the diagnosis and management of subjects with kidney disease and in assessing cardiovascular risk. Accurate assessment is vital to enable detection and management of the patient with proteinuria. RECENT FINDINGS: The spot urine protein has been suggested as an acceptable alternative to 24-h urine collections. Recent studies suggest that this holds true for screening to exclude significant proteinuria (>1 g/day) but data are lacking for the quantification of proteinuria and in assessing response to therapy. For albuminuria, while 24-h urinary albumin excretion remains the gold standard, spot urine samples are appropriate for screening. The optimal technique for the laboratory determination of urinary albumin has been questioned with the high-performance liquid chromatography-based method demonstrating significantly more albumin in the urine. Population-based studies have found dramatic increases in the prevalence of microalbuminuria with the new high-performance liquid chromatography assay. Whether this extra immunounreactive albumin detected by high-performance liquid chromatography is clinically important remains to be established. SUMMARY: Twenty-four-hour urine collection remains the gold standard for the accurate determination of both total urinary protein and albumin. Spot urine samples can be used for screening patients for albuminuria and proteinuria. The optimal method for measuring urinary albumin concentration remains to be established.     

Prevalence of microalbuminuria and relationship to the risk of cardiovascular disease in the Japanese population

The prevalence of microalbuminuria and its relationship to cardiovascular disease risk factors were examined in subjects participating in an annual physical and laboratory examination program. The urinary albumin concentration and the urinary albumin/creatinine ratio were determined in morning urine specimens. A turbidimetric immunoassay was used for the measurement of urinary albumin. Of the 731 subjects, 41 (5.6%) who were weakly positive or positive on a routine dipstick test for protein were excluded from the final analysis of data. Microalbuminuria was present in 14.5% of the men, in 12.4% of the women, and in 13.2% of the entire subject population when defined as a urinary albumin concentration of 30-299 microgram/ml. The prevalence of microalbuminuria was significantly higher in subjects with a high normal blood pressure (15.0%) or hypertension (26.2%) as compared with normotensive subjects (6.5%). Subjects with impaired glucose tolerance (24.3%) or hyperglycemic subjects (50.0%) had a significantly higher prevalence of microalbuminuria than normoglycemic subjects (11.3%). The prevalence of microalbuminuria was significantly higher in subjects with left ventricular hypertrophy (47.1%) as compared with those with normal electrocardiograms (11.3%). A good correlation was observed between urinary albumin concentration and albumin/creatinine ratio, and both showed a significant positive correlation with age, systolic and diastolic blood pressures, and fasting plasma glucose, total serum protein, albumin, and triglyceride levels, but not with angiotensin-converting enzyme activity. Multiple regression analysis demonstrated that both the urinary albumin concentration and the albumin/creatinine ratio show a significant positive correlation with systolic blood pressure and fasting plasma glucose. The prevalence of microalbuminuria was about 13% in this Japanese cohort, and the systolic blood pressure and the fasting plasma glucose level were demonstrated as independent risk indicators for both urinary microalbumin level and urinary microalbumin/creatinine ratio.     

Assessment of proteinuria

Proteinuria is a strong predictor of adverse cardiovascular and kidney events, and an accurate assessment of proteinuria is important for the evaluation and management of CKD. Total urinary protein can be assessed using dipstick, precipitation, and electrophoresis methods. Urinary albumin, the predominant urinary protein in most proteinuric kidney diseases, can be assessed using an albumin-specific dipstick, immunochemical techniques, and size-exclusion high-performance liquid chromatography. Urine albumin may be immune-reactive, immune-unreactive, fragmented, and biochemically modified, and laboratory techniques have variable abilities to detect different types of albumin. Urine specimen for proteinuria assessment can either be obtained from a timed-collection or a spot urine sample. Spot urine protein- or albumin-to-creatinine ratios are preferred to a 24-hour urine sample in routine practice. Assessment of albuminuria rather than proteinuria is more clinically meaningful in patients with diabetic kidney disease, and proteinuria and albuminuria assessments both have a role in nondiabetic kidney disease and in general population screening. As measurement and sampling procedures for proteinuria assessment have yet not been standardized, it is important for physicians to be aware of different types of urinary proteins, albumins, laboratory techniques, and urine sampling methods.     

Screening for microalbuminuria simplified by urine specific gravity

BACKGROUND: The albumin-to-creatinine ratio and the 24-hour urine collection to measure microalbuminuria are inconvenient and expensive. The newer rapid and less expensive dipstick methods for screening of microalbuminuria estimate only albumin and are subject to errors caused by variation in volume. We determined the relation between urine-specific gravity (Usg) and urine creatinine (Ucr) so that Ucr can be derived from Usg to correct for albumin concentration in the urine which is influenced by urine volume. METHODS: We randomly included 42 consecutive patients from the primary care clinic, and 34 patients from the diabetic clinic. RESULTS: We found that a very good correlation existed between Usg and Ucr in the 42 patients from the primary care clinic (Ucr = 11.4 x Usg -11,509, r = 0.83, p < 0.001). Patients from the diabetic clinic who had well-controlled blood sugar (n = 21) showed a similar trend (Ucr = 10.82 x Usg -10,882, r = 0.87, p < 0.001). However, this was not the case with uncontrolled diabetics (Ucr = 2.53 x Usg -2,513, r = 0.26, NS). Using simple arithmetic, we derived a simplified formula where Ucr can be predicted from Usg. Using multiple regression to incorporate the urinary glucose level by dipstick, a more generic formula was obtained for estimating urinary creatinine. CONCLUSION: Usg can be used instead of Ucr to normalize for the varied urine concentration while screening for microalbuminuria. Poorly controlled diabetics should be screened after their blood sugars are well controlled or use the more generic formula that incorporates urinary glucose. Thus, by measuring spot urine albumin and specific gravity by dipsticks one gets an easy, immediate and accurate estimation of microalbuminuria in an office setting.     

Urinary albumin and cardiovascular profile in the middle-aged population

The moderate increase in urinary albumin excretion defined as microalbuminuria is not rare and is associated with cardiovascular risk factors. Microalbuminuria prevalence is low in the absence of cardiovascular risk factors and progressively increases with the number cardiovascular risk factors. The main correlate of microalbuminuria is blood pressure, either systolic or diastolic pressure. The relation between blood pressure and microalbuminuria is continuous and graded because the microalbuminuria prevalence increases with the severity of hypertension. Among hypertensive patients on drug treatment, blood pressure control is associated with a low prevalence of microalbuminuria. Thus, blood pressure appears as a determinant of microalbuminuria rather than a mere correlate. For hypercholesterolemia, smoking, and diabetes, data are less strong but point to an independent positive association with microalbuminuria. Altogether, data indicate that microalbuminuria in the population reflects the presence of cardiovascular risk factors. Data on microalbuminuria and coronary heart disease support this idea. There is a continuous and graded relation between urinary albumin excretion and coronary heart disease prevalence. High urinary albumin excretion is likely a sign of vascular damage existing both at the renal and cardiac levels and induced by 1 or more uncontrolled cardiovascular risk factors.     

Proteinuria--what value is the dipstick?

The value of the urinary dipstick in the assessment of proteinuria was investigated in a study correlating laboratory measurements of protein and albumin against the dipstick protein in the same samples of urine; 94 patients (100 admissions) were studied at the Royal Air Force Renal Unit, each patient collecting two 24-h urine samples. Along with each 24-h sample, 10-ml aliquots of urine were obtained at 3 designated times during the day for both ward dipstick testing and laboratory assay; + or more on the dipstick correlated with abnormal proteinuria (greater than or equal to 150 mg/24 h) in 88% of cases, whilst trace values straddled the level of significant proteinuria. Further differentiation of trace was possible by repeat testing during the day. The subsequent presence of a dipstick negative during that day correlated with normality in all but 5% of cases. In order to ensure detection of renal disease presenting as isolated orthostatic proteinuria, assay of the mid-morning sample is recommended.     

Rapid microalbuminuria screening in type 2 diabetes mellitus: simplified approach with Micral test strips and specific gravity.

BACKGROUND: Microalbuminuria is known to be a harbinger of serious complications in type 2 diabetes mellitus. Since medical intervention at the onset of microalbuminuria can be critical in reducing these adverse outcomes, it is widely agreed that type 2 diabetic patients should be screened for microalbuminuria. The purpose of the present study is to evaluate Micral test strips in conjunction with a urine specific gravity determination as a rapid and accurate method for detecting microalbuminuria in type 2 diabetic patients. METHODS: In this prospective study, a total of 444 urine samples of type 2 diabetic patients were obtained from the ABCD study cohort for analysis. Urinary albumin concentrations were determined using Micral test strips and compared to results measuring albumin by the immunoturbidimetry method of timed collections. Urine specific gravity was measured by a standard urine dipstick. RESULTS: The performance characteristics of the Micral test strips for detecting microalbuminuria (30-300 mg albumin/24 h) were adequate but not optimal: sensitivity 88%, specificity 80%, positive predictive value 69%, negative predictive value 92%. A concomitant specific gravity determination was useful in indexing the magnitude of false negative and false positive readings by the Micral test strips. CONCLUSIONS: While the use of Micral test strips provides a rapid approach to detecting microalbuminuria in type 2 diabetic patients, this method has limitations. The simultaneous measurement of specific gravity is helpful in addressing some of the shortcomings of this screening test.     

Physical Activity Alters Urinary Albumin/ Creatinine Ratio in Type 1 Diabetic Patient

While the best way to identify microalbuminuria is to determine albumin excretion rate (AER) in a 24 h urine sample. Published data have shown that calculation of an albumin/creatinine ratio (ACR) in a spot urine sample has reasonable rate of sensitivity and specificity. We aimed to evaluate the effect of daily exercise on ACR and estimate the best time for the examination of the ACR in a spot urine sample. Sixteen eligible patients with Type 1 diabetes mellitus were asked to perform varying degree of exercise periods. Urinary albumin and creatinine excretion rates during each period were determined. ACR and AER of timed urinary samples were compared with the 24 hour urinary AER. We found significant correlations between timed and 24 hour urinary AER. According to diagnostic performance tests, ACR and AER of timed urine samples were both found to be significantly more sensitive during resting period when compared with mild or moderate active periods. It is concluded that ACR and AER of a timed urine sample are sensitive and specific methods for determining microalbuminuria, while overnight resting samples give the impression of being more diagnostic.

Key Points

• Timed urine samples can predict microalbuminuria but because of the erroneous urine collections, microalbuminuria measurement should be calculated with creatiniuria measurement.
• With increasing physical activity during urine collection diagnostic performances of the cut-off values go downhill.
• For detecting microalbuminuria best results are reached with the early-morning urine samples.

Key Words: Microalbuminuria, albumin/creatinine ratio, type 1 diabetes mellitus, exercise, nephropathy     

Albumin-like material in urine

Recent studies have demonstrated the presence, in both rat and human urine, of a modified form of albumin not detected by conventional antibodies. This modified albumin behaves physicochemically as intact albumin under nondenaturing conditions. We have demonstrated this form of albumin to be disproportionately excreted in microalbuminuric states in diabetes. Quantitation of this modified form of albumin leads to the prediction of the onset of microalbuminuria in diabetic patients on average 3 to 4 years earlier than when measured by conventional immunoassays.     

First Morning Voids Are More Reliable Than Spot Urine Samples to Assess Microalbuminuria

Measurement of urinary albumin excretion (UAE) in a 24-h collection is the gold standard method to determine the presence of microalbuminuria. We sought to compare more practical alternatives—measurement of urinary albumin concentration (UAC) or albumin:creatinine ratio (ACR)—in a first morning void or in a spot urine sample with this gold standard. We asked 241 participants of a prospective cohort study to make three 24-h urine collections, a first morning void, and a spot urine sample. Regression analysis showed that the ACR in a first morning void best agreed with 24-h UAE. The prevalence of microalbuminuria determined by data from a first morning void (7.5%, whether by UAC or ACR) nearly equaled the prevalence of microalbuminuria determined by 24-h UAE (10.0%), whereas the prevalence was higher when determined by spot urine samples (25.4% for UAC and 22.4% for ACR; both P < 0.001 versus 24-h UAE). The intraindividual coefficients of variation of the ACR in a first morning void and 24-h UAE were similar (19%). Intraindividual coefficients of variations of all other measurements of albuminuria were significantly greater. In conclusion, measurement of albuminuria in a first morning void, preferably as the ACR, is more reliable than a spot urine sample to diagnose and monitor microalbuminuria.Microalbuminuria has been established as a valuable risk marker for renal and cardiovascular complications. Consequently, treatment guidelines from various medical societies have recommended assessment of urinary albumin in patients with hypertension or diabetes and even in the general population to identify individuals at increased risk for renal and cardiovascular disease.^1–4Various methods for urine collection are used in clinical practice to determine presence of microalbuminuria. Because urinary albumin excretion (UAE) follows a circadian rhythm, the amount of albumin excreted in urine during a 24-h period has been considered the “gold standard”; however, 24-h urine collection is a cumbersome procedure. More practical and easier alternatives are collection of a first morning void or a spot (random) urine sample. It has been suggested that a first morning void (collection of the first urine void after the individual awakes from sleep) is to be preferred over a spot urine sample (daytime random sample), because the former is less influenced by factors such as hydration status and physical activity, reducing the variability that is caused by these factors.⁵ From a practical point of view, however, spot urine samples are preferred because they can be collected during consultation at the doctor''s office and therefore pose the least inconvenience for individuals.As yet, only one study has compared the validity of using a first morning void or a spot urine sample as a substitute for a 24-h urine collection to diagnose microalbuminuria and to monitor albuminuria over time⁶; however, this study included only 11 patients, limiting the validity of the results. The aim of this study, therefore, was to investigate whether albuminuria measures derived from a first morning void or a spot urine sample could be used as an alternative to a 24-h UAE to diagnose microalbuminuria and to monitor albuminuria over time.     

Clinical utility of trace proteinuria for microalbuminuria screening in the general population

Background The urine dipstick test that regards > 1+ proteinuria as positive is unsuitable for microalbuminuria screening owing to its low sensitivity in the general population. We conducted a cross-sectional survey to examine whether trace proteinuria could be an indicator of microalbuminuria. Methods The subjects were 2321 participants in a community-based health check-up in Takahata, Japan. Dipstick tests for proteinuria and the urine albumin–creatinine ratio (UACR) measurement were performed with single-spot urine specimens collected early in the morning. The results of the dipstick tests were recorded as (−), trace, (1+), (2+), and (3+). Micro- and macroalbuminuria were defined as UACR 30–300 mg/g and > 300 mg/g, respectively. Results Overall, the prevalence and median UACR levels of urine protein (−), trace, (1+), (2+), and (3+) were 92.0% (8.8 mg/g), 3.5% (43 mg/g), 2.6% (81 mg/g), 1.4% (315 mg/g), and 0.5% (1073 mg/g), respectively. Within the trace proteinuria category, the prevalence of microalbuminuria in all subjects, men, subjects ≥60 years, diabetic subjects, and hypertensive subjects was 59.3%, 73.8%, 71.2%, 88.9%, and 68.0%, respectively. By regarding trace proteinuria as positive, the sensitivity of the urine protein dipstick test for micro- and macroalbuminuria was improved (from 23.3% to 37.1%), while its specificity was not significantly changed (from 98.9% to 97.3%). Conclusion Trace proteinuria could be a useful indicator of microalbuminuria in the general population, and especially in subjects at high risk of cardiovascular disease.     

Microalbuminuria as an early marker for cardiovascular disease

Excretion of albumin in the urine is highly variable, ranging from nondetectable quantities to milligrams of albumin and even grams of albumin. Microalbuminuria is defined as low levels of urinary albumin excretion of 30 to 300 mg/d. Microalbuminuria is highly prevalent; in hypertensive and diabetic populations, its prevalence varies from 10 to 40%. It is interesting that microalbuminuria also is found frequently in seemingly healthy individuals (5 to 7%). The variable excretion of albumin in the urine is related to the risk for the individual to develop cardiovascular (CV) disease: Absence or very low levels of albuminuria is associated with low CV risk, whereas the CV risk increases markedly with increasing amount of albumin in the urine (even within the now considered normal range). The predictive power of urinary albumin levels for CV risk is independent of other CV risk factors and not only is present in individual with diabetes and/or hypertension but also in healthy individuals. Treatments that lower albuminuria are associated with CV protection, as demonstrated in randomized, controlled trials of patients with diabetes as well as in patients with hypertension. There is preliminary evidence that albuminuria lowering is CV protective in healthy individuals with an elevated albumin excretion rate. Differences between individuals in their level of albumin excretion are already observed at a very early age (just after birth). In fact, the interindividual variability seems to be relatively constant in the first 5 decades of life, indicating that microalbuminuria is not necessarily a consequence of vascular damage at later age. Higher levels of urinary albumin seem to reflect the ordinary interindividual variability in (renal and systemic) endothelial function. Experimental data show that between strains and even within strains, rats at young age show a remarkable difference in individual endothelial function, and this is strongly related to the susceptibility of that rat to organ damage. In conclusion, albuminuria seems to be a sensitive marker very early in life for the susceptibility of an individual to CV disease. It therefore may be an ideal target for early primary prevention using CV-protective therapy regimens.     

Revised criteria for the early diagnosis of diabetic nephropathy

The Diabetic Nephropathy Committee recommends the use of revised criteria for the early diagnosis of diabetic nephropathy in Japan. The new criteria are as follows: 1) Urinary albumin should be determined by immunoassay using a morning spot urine sample in diabetic patients without proteinuria or with dipstick-positive(+ 1) proteinuria. 2) A urinary albumin-to-creatinine ratio ranging from 30 to 299 mg/ gCr in 2 or more of 3 specimens may be diagnosed as microalbuminuria. 3) Two alternatives, i.e. the urinary albumin excretion rate of 30-299 mg/24hr in 24hr urine collection or 20-199 microg/min in timed urine collection can be used to detect microalbuminuria. 4) Renal hypertrophy and elevated urinary type IV collagen may indicate the existence of diabetic renal disease. 5) Microalbuminuria originating in non-diabetic diseases should be excluded.     

Urinary excretion of podocytes in patients with diabetic nephropathy.

BACKGROUND: Detection of podocytes in the urinary sediments of children with glomerulonephritis has been shown to indicate severe injury to the podocytes. The aim of the present study was to determine whether podocytes are present in the urine sediments of adult patients with diabetes with and without nephropathy and whether trandolapril is effective for podocyte injury. METHODS: Fifty diabetic patients (10 with normoalbuminuria, 15 with microalbuminuria, 15 with macroalbuminuria and 10 with chronic renal failure) and 10 healthy controls were studied. Urinary podocytes were examined by immunofluorescence using monoclonal antibodies against podocalyxin, which is present on the surface of podocytes. In addition, we studied plasma metalloproteinase (MMP)-9 concentrations in all patients. RESULTS: Urinary podocytes were absent in healthy controls, diabetic patients with normoalbuminuria and diabetic patients with chronic renal failure. Podocytes were detected in the urine of eight diabetic patients with microalbuminuria (53%) and of 12 patients with macroalbuminuria (80%). The number of podocytes in the urine of patients with macroalbuminuria was significantly greater than in patients with microalbuminuria (P:<0.01). However, there was no relationship between urinary albumin excretion and urinary podocytes. In addition, plasma MMP-9 concentrations were significantly correlated with the number of urinary podocytes (P:<0.01). Twelve diabetic patients with macroalbuminuria and eight patients with microalbuminuria who had urinary podocytes were treated with the angiotensin-converting enzyme inhibitor trandolapril. Urinary albumin excretion, the number of podocytes and plasma MMP-9 concentrations were reduced by the trandolapril treatment. CONCLUSIONS: Podocytes in the urine may be a useful marker of disease activity in diabetic nephropathy. Trandolapril may be effective for podocyte injury.     

The validity of screening based on spot morning urine samples to detect subjects with microalbuminuria in the general population

BACKGROUND: No study has yet investigated the validity of prescreening by albumin measurements in a spot morning urine sample to identify in the general population subjects with microalbuminuria. We therefore tested the diagnostic performance of urinary albumin concentration (UAC) and albumin-creatinine ratio (ACR), measured in a spot morning urine sample, in predicting a urinary albumin excretion (UAE) > or =30 mg in subsequent 24-hour urines (microalbuminuria). METHODS: Subjects (2527) participating in the PREVEND study, a representative sample from the general population, collected a spot morning urine sample and, on average, 77 days later, two 24-hour urine collections. RESULTS: The ROC curve of UAC in predicting microalbuminuria has an area-under-the-curve of 0.92 with a discriminator value of 11.2 mg/L. Using this cut-off value for UAC, sensitivity in predicting microalbuminuria is 85.0%, and specificity 85.0%. For ACR these values are, respectively: area-under-the-curve 0.93, discriminator value 9.9 mg/g, sensitivity 87.6%, and specificity 87.5%. Sensitivity for UAC in predicting microalbuminuria does not differ significantly from the sensitivity for ACR, whereas the difference between the specificities of UAC and ACR reaches statistical significance, but is numerically very small. In various subgroups characterized by differences in urinary creatinine excretion, the area-under-the-ROC curve, sensitivity, as well as specificity, do not increase relevantly compared to the results in the overall study population. This holds true for ACR as well as UAC. CONCLUSION: The diagnostic performance of measuring UAC in a spot morning urine sample in predicting microalbuminuria in subsequent 24-hour urine collections is satisfactory, and, moreover, comparable to that of measuring ACR. In order to keep the burden and costs involved in population screening for microalbuminuria as low as possible, we therefore propose prescreening by measuring UAC in a spot morning urine sample. Those subjects with a UAC above a certain predefined level (e.g., 11 mg/L) should be asked to collect timed urine samples.     

Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study

BACKGROUND: Microalbuminuria is a risk factor for cardiovascular disease, but the underlying pathomechanisms are still poorly understood. A relationship between C-reactive protein (CRP), a sensitive marker of inflammation, and atherosclerotic disease has been reported recently. METHODS: We hypothesized that microalbuminuria might be associated with chronic inflammation and investigated the relationship of urinary albumin excretion, as assessed from the albumin-to-creatinine ratio (ACR), in an untimed morning urine specimen, and two inflammatory markers (CRP and fibrinogen) in the large, triethnic population of the Insulin Resistance Atherosclerosis Study (IRAS). After exclusion of subjects with macroalbuminuria, 1481 subjects were studied. RESULTS: Both inflammatory markers were related to urinary ACR (r = 0.17 for CRP and r = 0.14 for fibrinogen, both P = 0.0001), an association that remained significant after adjustment for demographic variables, diabetic status, smoking, and use of angiotensin-converting enzyme inhibitors (P < 0.01). Mean levels of CRP and fibrinogen were elevated in microalbuminuric (N = 262) versus normoalbuminuric (N = 1219) subjects (5.37 +/- 0.47 vs. 3.80 +/- 0.15 mg/L and 295.7 +/- 4. 0 vs. 278.2 +/- 1.6 mg/dL, both P < 0.0001). The associations were consistent among nondiabetic and type 2 diabetic subjects and among the three ethnic groups of the IRAS (non-Hispanic whites, blacks, Hispanics). In a logistic regression model, fibrinogen was independently associated with microalbuminuria (P = 0.047), along with hypertension, female gender, waist circumference, and fasting blood glucose, while CRP was not independently related to microalbuminuria in this model (P = 0.26). CONCLUSION: We have shown an association of CRP and fibrinogen with urinary albumin excretion in the microalbuminuric range in type 2 diabetic and nondiabetic individuals. Chronic inflammation therefore emerges as a potential mediator between microalbuminuria and macrovascular disease.     

Prevalence and risk factor analysis of microalbuminuria in Japanese general population: the Takahata study

Microalbuminuria, an indicator of glomerular injury, is associated with increased risk of progressive renal deterioration, cardiovascular disease, and mortality. However, the prevalence of microalbuminuria in Japanese general population is less certain. Thus, we examined the prevalence of microalbuminuria and its associated risk factors in Japan. Subjects of this cross-sectional study were asymptomatic individuals over 40 years in Takahata, Japan. Urine albumin-creatinine ratio was calculated from a single-spot urine specimen collected in the morning. Creatinine clearance (CCr) was obtained by Cockcroft-Gault equation. Multivariate logistic regression analysis was used to determine which risk factors (i.e., age, hypertension, diabetes, obesity, and salt intake) might predict the presence of microalbuminuria. A total of 2321 subjects (mean age, 64 years; men, 1034; women, 1287) were entered into the final analysis. Among them, the prevalence of microalbuminuria, macroalbuminuria, and proteinuria by dipstick test (> or = 1+) were 317 (13.7%), 39 (1.7%), and 103 (4.4%), respectively. Age, hypertension, and diabetes were independently associated with microalbuminuria in men. In addition to the classical risk factors detected in men, estimated 24-h urinary sodium excretion and uric acid were also independently associated with microalbuminuria in women. Among the 668 subjects with renal insufficiency (CCr <60 ml/min/1.73 m(2)), the prevalence of microalbuminuria and macroalbuminuria were 119 (17.8%) and 18 (2.7%), respectively. In conclusion, microalbuminuria is prevalent across all age groups and is associated with lifestyle-related risk factors in Japanese general population. However, there are a substantial number of subjects with renal insufficiency accompanying no microalbuminuria.     

Diagnostic significance of urinary immunoglobulin G in diabetic nephropathy

An early manifestation of diabetic nephropathy, increased excretion of albumin, is now generally believed to be sufficiently specific, particularly in subjects with diabetes mellitus, to predict the subsequent development of clinically overt diabetic nephropathy. However, certain other proteins besides albumin may also be excreted in abnormal amounts during this early phase of diabetic nephropathy. We evaluated the diagnostic utility of urinary immunoglobulin G (IgG) in patients with diabetic nephropathy by comparing the findings with the clinical stage and renal biopsy specimen. Using 24-hour urine samples, IgG was measured by an enzyme-linked immunosorbent assay. In addition, urine samples were assayed for albumin, transferrin, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase. Serum IgG concentration and HbA1c were also evaluated. A total of 197 patients with non-insulin-dependent diabetes mellitus were enrolled in this study. Subjects were grouped according to the rate of urinary albumin excretion (clinical stage). Fifty of these cases were also divided into four groups according to the severity of diffuse glomerular lesions using Gellman's criteria. The urinary excretion of IgG was significantly increased in diabetic patients as compared with the healthy controls. Among diabetic patients, IgG level showed a significant increase with respect to the clinical stage of nephropathy and the progress of glomerular diffuse lesions. In the stage of normoalbuminuria, the urinary excretion of IgG showed a significant increase in parallel with the progress of glomerular diffuse lesions, whereas there was no relationship between the urinary excretion of albumin and the progress of glomerular diffuse lesions. While the excretion of IgG correlated with that of albumin and transferrin, there was no correlation between the excretion of IgG and the other laboratory indices evaluated. These findings indicate that measurement of urinary IgG may be more useful than albuminuria in detecting the early stage of diabetic nephropathy.     

尿干化学分析与尿液沉渣检查对尿路感染诊断价值的比较

目的:探讨尿路感染(UTI)检验的较好方法。方法:以UTI诊断的金标准为参照,对124例UTI住院患者中段尿进行尿干化学分析和尿沉渣WBC计数检验,并作对比分析。结果:尿沉渣镜检的灵敏度、阴性预计值、准确率分别为79.6%、88.5%、81.7%,而尿液干化学分析亚硝酸盐(NIT)或WBC的灵敏度、阴性预计值、准确率分别为63.3%、81.2%、76.8%。结论:在UTI的尿筛查试验中,尿沉渣镜检WBC计数比尿干化学分析NIT、WBC的诊断价值为优。     

Update on microalbuminuria as a biomarker in renal and cardiovascular disease

PURPOSE OF REVIEW: To discuss recently published papers on the potential use of albuminuria as a predictor of cardiovascular and renal disease. RECENT FINDINGS: Recent studies indicate that screening for microalbuminuria may not only be beneficial for detection and prevention of cardiovascular and renal disease in patients with diabetes, but also in the general population. The best method for this, however, is not yet clear. Findings indicate that it is preferable to assess albumin concentration in fresh urine samples rather than in samples that have been frozen. Furthermore, a new assay for albumin assessment has become available, which detects previously undetectable immuno-unreactive albumin above and beyond immunoreactive albumin detected by classic immunochemical assays. The pros and cons of this assay are considered. SUMMARY: Urinary albumin is a cheap, noninvasive, and easily assessable risk marker, that does not per se require a visit to a physician or health center. As such, it is a promising candidate for screening to identify subjects at high risk of cardiovascular and renal disease, even if albuminuria is not shown to be independent of other risk markers.