Biological variability of albumin excretion rate and albumin-to-creatinine ratio in hypertensive type 2 diabetic patients.

The importance of measuring microalbuminuria is well established. However, only scanty data are available concerning the biological variability of albumin excretion in type 2 diabetic subjects. We report our experience from a large clinical trial of a new antihypertensive drug (Lercanidipine) designed to reduce albumin excretion and blood pressure in type 2 diabetic patients with hypertension and microalbuminuria. Eighty seven patients with persistent microalbuminuria were studied within 1 year of the clinical trial. The measurements were performed on blood and timed urine samples frozen at -80 degrees C and shipped to a central laboratory unit. Preliminary experiments were performed to assess albumin stability in urine under various conditions (4 degrees C, -20 degrees C and -80 degrees C), particularly with regard to the albumin/creatinine ratio. Urine samples can be stored up to 3 weeks at 4 degrees C or up to 2 months at -80 degrees C. The biological variability of the albumin excretion rate was 25.7%, while that of the albumin/creatinine ratio was 13.4%. These data are useful in defining the analytical goals of imprecision for microalbuminuria (CV = 13% for albumin, and CV = 6% for albumin/creatinine ratio). No correlation between albumin/creatinine ratio and HbA1c was found in the cohort of 61 microalbuminuric patients who completed the trial. The results of this study confirm that the albumin/ creatinine ratio is much more suitable for monitoring albumin excretion in longitudinal studies than the albumin excretion rate.     

Microalbuminuria and cardiovascular risk

The term 'microalbuminuria' has been introduced to describe a measurable increase in urine albumin excretion, which is still within normal total urine protein excretion levels. Many data suggest that microalbuminuria is of value as an index of vascular damage, especially in hypertension and diabetes, and there is increasing information on its associations with traditional cardiovascular risk factors and its prognostic value. The association between microalbuminuria and peripheral markers of endothelial damage or dysfunction, such as von Willebrand factor, suggests the possibility that microalbuminuria may be a simple, cheap and easy index of endothelial abnormalities in cardiovascular disease. Nevertheless, further information on the value of microalbuminuria in other atherosclerotic vascular complications, such as ischaemic heart disease, stroke and peripheral artery disease is still needed.      

Validation of albumin determined in urine with the HemoCue point-of-care analyser

Albumin concentrations persistently between 20 and 200 mg/L in first morning spot urine or urine collected overnight, referred to as microalbuminuria, indicate incipient nephropathy in diabetes mellitus. This study validates a new point-of-care device, the HemoCue Urine Albumin analyser, for handling, accuracy precision and predictive values (PV+/-) at 20 mg/L. Over a period of 2 months, 200 microalbuminuria samples were selected at the Department of Clinical Chemistry according to the results from the Integra 700 instrument (Roche, R) and analysed on the same day using the HemoCue analyser (HemoCue, H) and the Immage instrument (Beckman, B), in all cases closely following the manufacturers' instructions. Only 137 results were within the measuring range of H, 10-150 mg/L. Comparisons yielded regression lines H=1.06R-7.2 (r2=0.94), H=1.08B-3.1 (r2=0.94) and R=1.00B+4.3 (r2=0.99). Inter-assay (n=24) CV% at 12 mg/L was H=18.2, R=4.2 and B=2.9 and at 65 mg/L: H=6.1, R=1.8 and B=2.6. Intra-assay duplicate CV% for H at 21-40 mg/L was 13.2, at 41-80 mg/L 10.8 and at 81-150 mg/L 9.2. Intra-assay repeatability (n=8) CV% at 28 mg/L was 7.2-13.8, at 57 mg/L 6.4-8.4 and at 105 mg/L 4.3-7.1. External quality assurance urine albumin (B) was +5.7% cf. nephelometry and (R) +1.0% cf. turbidimetry (n=6) method-group means. PV+/- values were (H versus R) 0.98/0.37 and (H versus B) 0.95/0.65. HemoCue is easy to handle. Results below 20 mg/L need to be confirmed at the central laboratory to exclude microalbuminuria. Values above 20 mg/L can be used to follow microalbuminuria, as precision allows discerning steps of 10 mg/L.     

Risk factors for development of incipient and overt diabetic nephropathy in type 1 diabetic patients: a 10-year prospective observational study

OBJECTIVE: To evaluate prospectively putative risk factors for development of microalbuminuria and macroalbuminuria in type 1 diabetes. RESEARCH DESIGN AND METHODS: Prospective observational study of a cohort of type 1 diabetic patients followed in the outpatient clinic at Steno Diabetes Center for < or =10 years (median 9 years). We followed 537 patients aged > or =18 years with type 1 diabetes, with duration of diabetes > or =5 years, with normoalbuminuria (urinary albumin excretion rate < or =30 mg/24 h), and who were not taking antihypertensive medication. Risk factors for development of microalbuminuria and macroalbuminuria were evaluated. RESULTS: The mean progression of urinary albumin excretion rate was 7.6% (SE 0.8) per year. During follow-up, 134 patients (25%) progressed to persistent microalbuminuria or macroalbuminuria (>30 mg/24 h in two of three consecutive urine samples). Cox multiple regression analysis using baseline values of putative predictors of progression showed the following significant predictors of progression from normoalbuminuria to microalbuminuria or macroalbuminuria: baseline log urinary albumin excretion rate 2.63 (relative risk; 95% CI 1.65-4.19), HbA(1c) 1.13% (1.04-1.23), presence of any retinopathy 1.90 (1.26-2.88), and smoking 1.61 (1.11-2.33). Sex, duration of diabetes, arterial blood pressure, serum creatinine, height, and social class were not risk factors. CONCLUSIONS: Our study suggests that several potentially modifiable risk factors predict the development of microalbuminuria and macroalbuminuria in type 1 diabetic patients.     

The relationship between long-term glycaemic control and diabetic nephropathy.

Urine albumin excretion was studied by two widely accepted methods in 210 patients with insulin-dependent diabetes mellitus and related to the mean of serial glycosylated haemoglobin (HbA1) measurements made every 3 months during the previous 6 years. Microalbuminuria (albumin excretion rate > 20 micrograms/min) was present in 9.5 per cent of patients when defined by a 24-hour collection and 8.1 per cent of patients when defined by a timed overnight urine sample. Those with microalbuminuria, as estimated from a timed overnight urine sample, had a longer duration of diabetes but otherwise did not differ in age, duration of diabetes or arterial blood pressure from patients whose albumin excretion rate was 20 micrograms/min or less irrespective of the method of urine collection. The mean and the most recent HbA1 levels differed significantly between the normal and the microalbuminuric groups when defined by the 24-hour albumin excretion rate (p < 0.001, p < 0.01), but no significant difference between these groups was found when albumin excretion rates were calculated from the timed overnight urine sample. Albumin excretion rate, examined in relation to mean HbA1, increased significantly with worsening glycaemic control whether measured over 24 hours or overnight (p < 0.05, p < 0.01). These findings support an association between glycaemic control and microalbuminuria, but the correlation is weak, dependent on the method of urine collection and is just as good for a relatively short-term as for a long-term measure of average blood glucose.     

Rhythmic pattern of PCA opioid demand in adults with cancer pain

Introduction: Patient‐controlled analgesia (PCA) has an established role in managing postoperative pain and has been successfully used in‐patients with cancer pain. The variation of opioid requirement over a 24h period for patients with cancer pain is debated with suggestions of reduced need over night. Methods: Retrospective review of 10years (1997–2006) data of all in‐patients with cancer pain treated with strong opioids delivered by PCA. Results: 141 patients with cancer pain had a mean cumulative 10day morphine equivalent dose per patient of 671mg (median 470mg; range 10–2170mg). At night (10:01pm to 06:00am) the patient's self administered less bolus doses (69mg, (25%)) than during the other two 8h periods (06:01am to 02:00pm, 91mg (33%) and 02:01pm to 10:00pm, 116mg (42%)). In 8 out of 10days a significant variation in bolus requests was observed with significantly less bolus requests during the night (Friedman test, p<0.05). Furthermore, the median number of delivered bolus requests per patient, at night, was 2–3 compared to the morning and afternoon periods of 3–7 and 3.5–6, respectively. Conclusion: PCA met individual patient's opioid needs in a safe and effective manner despite a large inter‐individual variability in opioid consumption. Moreover, the study indicated a pattern of less opioid requirement at night.     

Single-void urine samples can be used to estimate quantitative microalbuminuria

The excretion of small quantities of urinary albumin (microalbuminuria) may predict renal failure in diabetes. The measurement of microalbuminuria with radioimmunoassays has been based on 24-h, overnight, and 3- to 4-h collections. To determine whether single-void urine samples can be used to estimate 24-h excretion, we compared the results of 24-h outpatient urine collections with single-void samples corrected for creatinine from diabetic and nondiabetic subjects. The overall correlation of single-void sample results expressed as microgram albumin per milligram creatinine with 24-h excretion (mg/24 h) was excellent (r = .82, P less than .001). More important, in the diabetic patients the sensitivity and specificity of detecting 24-h microalbuminuria in the abnormal range were at least 94 and 96%, respectively. Single-void urine specimens adjusted for creatinine discriminate between normal and abnormal levels of microalbuminuria, as determined in 24-h urine collection, with high specificity and sensitivity.     

Albuminuria, intermittent hyperfiltration and salt wasting in patients with stroke: a pilot study

OBJECTIVE: To investigate whether different types of stroke influence renal excretion of albumin, major electrolytes and water. MATERIAL AND METHODS: Timed urine collections were started shortly after admission in 5 patients with haemorrhagic stroke (group A), 5 with ischaemic stroke (group Bx), 6 with presumed ischaemic stroke (groups By/z) and 6 with subarachnoid haemorrhage (group C). Albuminuria was also investigated in four patients undergoing elective abdominal surgery. RESULTS: Increased levels of albuminuria were observed in all patients in groups A and B, but were found to decline with observation time and appeared to be related to outcome in group B. In group C, albuminuria was detected in 4 out of 6 patients. Elective surgery did not affect albumin excretion. In a setting with high urinary osmolality, high excretion rates for creatinine, urea, sodium, potassium and large diuresis were intermittently observed in groups A, B and C. None of these patients was in steady-state condition. CONCLUSIONS: Different types of stroke elicit a complex change in renal function which resembles the response to a hypervolaemic and hyperosmolar signal, possibly mediated by a breakdown of renal autoregulation of blood flow in the presence of high vasopressin activity. Acute changes in excretion of albumin might be an indicator of prognosis in stroke. The findings point to the existence of unrecognized pathways between the central nervous system and the kidneys. Further studies on the mechanisms underlying alterations in renal function in stroke and their implication for treatment and outcome are indicated.     

A comparison of selective microproteinuria with histomorphology of the kidneys in patients with arterial hypertension

Urinary excretion of individual proteins has been examined in 30 patients suffering from arterial hypertension, subjected to renal biopsy. The findings indicate an increased excretion of the proteins associated with the localization of the morphologic shifts in the kidneys. Thus, glomerular abnormalities are characterized by a 10-30-fold increase of albumin and IgG excretion with the urine and normal values of beta-2-microglobulin (beta-2-MG); canalicular abnormalities are associated with normal urine albumin or microalbuminuria and 10-40-fold increased excretion of beta-2-MG, paralleled by increased urine N-acetyl-B-glucosaminidase activity, this latter shift indicating grave tubulointerstitial changes. Hypertensive changes of the vessels involve microalbuminuria. Quantitative and qualitative characteristics of proteinuria may become an additional test in the differential diagnosis of symptomatic arterial hypertension.     

Monitoring urinary orosomucoid in acute inflammation: observations on urinary excretion of orosomucoid, albumin, alpha1-microglobulin, and IgG

BACKGROUND: Inflammation-associated proteinuria in acute, nonrenal disease is a common but poorly understood phenomenon. We performed an observational study of the urinary excretion of orosomucoid (alpha(1)-acid glycoprotein), albumin, alpha(1)-microglobulin (protein HC), and IgG to obtain quantitative and temporal data on these 4 proteins. METHODS: Urine samples were collected at daily intervals for up to 23 days from 6 patients with surgery-induced inflammation and at hourly intervals for a 24-h period from 7 sepsis patients. Urinary protein concentrations were assessed by immunoturbidimetry. RESULTS: During surgery-induced inflammation, the increase and decrease in orosomucoid excretion mirrored changes in plasma C-reactive protein. Values for all 4 urinary proteins were increased in sepsis patients. The observed maximum increases in urinary protein excretion relative to the upper reference values were 280-fold for orosomucoid, 98-fold for alpha(1)-microglobulin, 33-fold for albumin, and 26-fold for IgG. CONCLUSIONS: Orosomucoid, usually present in plasma and urine in much lower concentrations than albumin, is increased in urine to concentrations equal to or higher than albumin in proteinuria associated with acute inflammation. The pathophysiologic mechanisms responsible for this markedly increased excretion are unknown. Monitoring of urinary excretion of orosomucoid and other specific proteins, expressed as protein/creatinine ratios, may provide a window for clinically relevant real-time observation of changes in acute inflammatory processes. Orosomucoid in urine may be a more informative marker than albumin for inflammation.     

The Relationship Between Long-term Glycaemic Control and Diabetic Nephropathy

Urine albumin excretion was studied by two widely accepted methodsin 210 patients with insulin-dependent diabetes mellitus andrelated to the mean of serial glycosylated haemoglobin (HbA₁)measurements made every 3 months during the previous 6 years.Microalbuminuria (albumin excretion rate > 20 µg/min)was present in 9.5 per cent of patients when defined by a 24-hourcollection and 8.1 per cent of patients when defined by a timedovernight urine sample. Those with microalbuminuria, as estimatedfrom a timed overnight urine sample, had a longer duration ofdiabetes but otherwise did not differ in age, duration of diabetesor arterial blood pressure from patients whose albumin excretionrate was 20 µg/min or less irrespective of the methodof urine collection. The mean and the most recent HbA₁ levelsdiffered significantly between the normal and the microalbuminuriagroups when defined by the 24-hour albumin excretion rate (p<0.001,p<0.01), but no significant difference between these groupswas found when albumin excretion rates were calculated fromthe timed overnight urine sample. Albumin excretion rate, examinedin relation to mean HbA₁, increased significantly with worseningglycaemic control whether measured over 24 hours or overnight(p<0.05, p< 0.01). These findings support an associationbetween glycaemic control and microalbuminuria, but the correlationis weak, dependent on the method of urine collection and isjust as good for a relatively short-term as for a long-termmeasure of average blood glucose.     

Antioxidant capacity after acute ischaemic stroke

BACKGROUND:Experimental studies have reported a rapid increase in the production of markers of oxidative damage following acute stroke due to the reperfusion event following ischaemia, and that endogenous antioxidant defences are rapidly depleted, permitting further tissue damage. Aim: To measure changes in antioxidant capacity (individual and total) in stroke disease within a known time period post infarct. DESIGN:Observational cohort study. METHODS:We studied 31 acute ischaemic stroke patients; 26 hospitalized non-stroke patients and 23 community-based healthy controls. Non-fasting venous blood was obtained within 24 h, at 48-72 h and at 7 days after stroke onset (after hospitalization for non-stroke patients) and at baseline for community controls. Vitamins E and C, total plasma glutathione, total antioxidant capacity (TAC), uric acid, thiobarbituric-acid-reactive substances (TBARS), serum albumin, transferrin and C-reactive protein (CRP) were measured. RESULTS:Baseline glutathione concentrations were non-significantly lowest and TBARS significantly highest in ischaemic stroke patients compared with controls. Serum TAC strongly correlated with serum uric acid. Under multivariate analysis, serum uric acid explained most of the variance in TAC during the study period. Despite increased concentrations of uric acid, TAC was reduced in stroke patients compared with controls. Serum vitamin C concentrations deteriorated significantly in stroke patients, and differences between the cumulative changes between strokes and hospital controls were also statistically significant (p=0.013). DISCUSSION:There was some evidence of reduction in TAC, despite increased uric acid concentrations, and deterioration in serum vitamin C levels in ischaemic stroke patients compared with controls.     

Effects of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and their combination on microalbuminuria in normotensive patients with type 2 diabetes

The goal of this study was to compare the effects of lisinopril, losartan, and their combination on microalbuminuria in normotensive patients with type 2 diabetes mellitus. Patients were randomly assigned to 3 groups: group 1 (n=9), group 2 (n=9), and group 3 (n=8) received 10 mg lisinopril, 50 mg losartan, and 10 mg lisinopril plus 50 mg losartan, respectively, each day. For 12 mo, the 24-h urine albumin excretion rate was assessed at 3-mo intervals. At study completion, the urine albumin excretion rate had been reduced significantly in each group (P=.001); however, no significant differences were noted among groups (P=.587). Investigators in the present study have concluded that lisinopril, losartan, and their combination have similar effects on microalbuminuria in normotensive patients with type 2 diabetes mellitus, and that combination therapy does not provide additional benefit.     

不同时段尿白蛋白在诊断早期糖尿病肾脏损伤中的应用

目的 研究糖尿病患者不同时段尿白蛋白(urinary albumin)的排泌情况及尿白蛋白在诊断早期糖尿病肾脏损伤中的应用.方法 收集中山医院门诊及住院糖尿病患者及健康对照组3 d内不同时间段的尿液,分析尿白蛋白天内、天间的排泌变化情况;以24 h尿白蛋白为标准判断肾脏早期损伤情况,比较不同时段尿及时间点尿与24 h尿白蛋白的相关性、诊断特异度及敏感度;评估随机尿的诊断特异度及敏感度,推导随机尿最佳诊断水平.结果尿白蛋白天间变异较大,以尿Cr和尿量分别校正后可降低变异.糖尿病组中尿白蛋白使用尿Cr校正后变异系数(CV)小于尿量校正(CV分别为49%±23%vs 64%±30%).尿白蛋白天内排泌呈节律性变化.不同尿液留取方式中夜间尿尿白蛋白/尿Cr(ratio of urinary concentrations of albumin and creatinine,ACR)与24 h尿白蛋白定量相关性最好(R~2=0.976),优于晨尿ACR(R~2=0.900)、午间餐后尿ACR(R~2=0.584)和随机尿ACR(R2=0.791).以24 h尿白蛋白总量作为判断标准进行受试者操作特性曲线(ROC曲线)分析显示,随机尿ACR的判断值为27.7 μg/mg尿Cr(存在男女性别差异:男性12.8μg/mg尿Cr vs性27.0μg/mg尿Cr).最小阴性似然比0.011时推导随机尿ACR的排除判断值为13.0 μg/mg尿Cr;最大阳性似然比481.000时推导随机尿ACR的确诊判断值为87.4 μg/mg尿Cr.结论 尿Cr较尿量能更好地降低尿白蛋白天内变异,但仍无法完全消除变异.夜尿ACR与24 h尿白蛋白定量相关性最好,可替代24 h尿白蛋白定量.随机尿ACR作为最方便留取的尿液标本亦可以较好地替代24 h尿白蛋白定量,但应考虑引入尿Cr后带来的性别间差异.以13.0 μg/mg及87.4 μg/mg作为随机尿ACR的排除判断值及确诊判断值可以便于临床医师基本排除或确定白蛋白尿的出现.     

缺血性中风发病与死亡时间探讨--附1 597例病例及90例死亡病例统计学分析

目的:用数学统计法探讨缺血性中风发病及死亡与时间的关系.方法:将1 597例缺血性中风病例的发病时间以及其中90例死亡病例的死亡时间以每日0～24时化为角度坐标,作圆形统计分析,观察缺血性中风的发病与死亡时间的特点.结果:1 597例缺血性中风病例的发病时间在午时11:00～13:00时段有明显的集中趋势,发病高峰时间点在11:32:41(P<0.005);90例死亡病例发病时间在午时11:00～13:00时段有明显的集中趋势,发病高峰时间点在12:03:03(P<0.005),死亡时间在上午4:00～6:00时段有相对的集中趋势(P>0.05);1 507例非死亡病例发病高峰时间点为午时11:31:12(P<0.005).结论:日中午时是缺血性中风的易发病时段,注意日中午时的治疗和护理,可减少缺血性中风的发病率;缺血性中风相对死亡高峰期在上午4:00～6:00时段,该时段应加强治疗和护理,以降低病死率.     

2型糖尿病及糖尿病肾病患者尿脂质运载蛋白-2检测的意义

目的 探讨2型糖尿病(T2DM)及其合并肾病(DN)尿脂质运载蛋白-2(LCN2)浓度变化及临床意义.方法 根据尿清蛋白排泄率(UAER)将115例T2DM患者分为单纯糖尿病(SDM)组46例、早期糖尿病肾病(EDN)组40例和临床糖尿病肾病(CDN)组29例;另选30例健康体检者作为健康对照(NC)组.采用酶联免疫吸附试验双抗体夹心法检测尿LCN2.结果 SDM、EDN、CDN组尿LCN2、超敏C-反应蛋白(hs-CRP)较NC组升高(P<0.05),随病情加重,升高更为明显.尿LCN2与hs-CRP高度相关(r=0.86,P<0.01).T2DM患者尿LCN2水平随着尿清蛋白的增加而升高.结论 T2DM患者尿LCN2水平明显升高,可作为DN早期的敏感的诊断指标.     

Heterogeneity of urinary albumin from diabetic patients

A fundamental cause of diabetic microalbuminuria, heterogeneity of normal and diabetic urinary albumin was shown by affinity chromatography on Cibacron Blue F3GA. By changing the properties of interaction with the matrix, the protein was separated into six fractions. Samples of urinary albumin from proteinuria patients showed the same elution profiles as those of serum albumin, whereas those from controls or normoalbuminuria diabetic patients exhibited different elution patterns. The relative percentage of the resin unbound fraction of urinary albumin was ten or more times higher than that of serum albumin, and the ratio decreased with increasing albumin excretion into urine. More than 6 mol fatty acid/mol albumin combined with the unbound fraction. It is suggested that microalbumin excretion into urine is the result of excessive unesterified fatty acid binding to the protein.     

Urinary excretion of proinflammatory cytokines and transforming growth factor beta at early stages of diabetic nephropathy

AIM: To examine correlations between urine excretion of proinflammatory cytokines, transforming growth factor beta (TGF-b) and changes in renal structure and function, quality of glycemia control in patients with type 1 diabetes mellitus. MATERIAL AND METHODS: Urinary excretion of interleukine 1-beta (IL-1b), monocytic chemoattractive protein-1 (MCP-1), RANTES and TGF-b was measured with enzyme immunoassay in 57 patients including 22 patients with normal albuminuria, 23--with microalbuminuria, 12--with macroalbuminuria. Creatinine clearance was subnormal in 8 patients with macroalbuminuria. The control group consisted of 10 healthy persons. Morphological examination of renal biopsies was performed in 8 patients with normoalbuminuria and 10 patients with microalbuminuria. RESULTS: Patients with normoalbuminuria had excretion of MCP-1 significantly higher than in controls. Microalbuminuria patients showed high excretion of IL-1b, MCP-1 and TGF-b. Excretion of IL-1b, MCP-1, RANTES and TGF-b in patients with macroalbuminuria was higher than in controls and other groups of patients. Excretion of cytokines and TGFb correlated inversely with glomerular filtration rate and hemoglobin level. Positive correlations were detected between excretion of IL-1b, MCP-1, TGFb and glycated hemoglobin A(1c). In patients with normo- and microalbuminuria cytokine and TGFb excretion correlated with thickness of glomerular and glomerular basal membrane. CD68-positive macrophages were detected in the intersticium of 1 patient with normoalbuminuria and 6 patients with microalbuminuria. CONCLUSION: Urinary excretion of proinflammatory cytokines and TGF-b was elevated in patients with DM-1 having micro- and macroalbuminuria suggesting participation of inflammation in development of diabetic nephropathy.     

Urinary-peptide excretion by patients with and volunteers without diabetes

Large quantities of peptides (1-4 g) are excreted in human urine each day. In this study we sought to analyze how peptide excretion varies with increasing albuminuria associated with diabetes, as well as to characterize the size distribution of albumin-derived peptides in urine from volunteers without diabetes and from patients with macroalbuminuria and diabetes. We detected albumin-derived peptides by injecting tritiated albumin intravenously into human volunteers and patients with diabetes. Urine was collected after 24 hours and fractionated on a size-exclusion column. This fractionation revealed peptides with molecular weights ranging from 300 to 500 Da in volunteers without diabetes. The albumin-derived peptides were of higher molecular weight in the urine of a patient with macroalbuminuria and diabetes. The molecular-weight distribution of the peptides derived from tritiated albumin peptides was paralleled by the distribution of all protein peptides (including albumin) as determined with the use of the Biuret protein assay or absorbance at 214 nm. We determined peptide-excretion rates by filtering urine from patients with diabetes through a 10,000 Da molecular-weight-cutoff membrane and then measuring the filtrate with the use of the Biuret assay. This analysis revealed that the peptide-excretion rate increased with increasing total protein excretion, regardless of whether the patient demonstrated normoalbuminuria or microalbuminuria. Among patients with macroalbuminuria, the peptide-excretion rate leveled off and even decreased in the face of an increasing albumin concentration or protein-excretion rate. This study confirms that albumin-derived and protein-derived peptides exist at high concentrations in urine. Although peptide-excretion rates are maintained at similar levels up to macroalbuminuric states, the relative proportion of peptide excretion is significantly reduced compared with total protein.     

Severity of glomerulopathy predicts long-term urinary albumin excretion rate in patients with type 1 diabetes and microalbuminuria.

OBJECTIVE: To investigate whether the degree of glomerular structural lesions in young patients with type 1 diabetes and microalbuminuria was associated with urinary albumin excretion rate (AER) 6 years later and whether the AER level was influenced by blood glucose control, blood pressure, or glomerular filtration rate (GFR). RESEARCH DESIGN AND METHODS: There were 17 young adults with type 1 diabetes and microalbuminuria, 8 men and 9 women with mean age 20 years (95% CI: 18-22) and duration of diabetes of 11 years (10-13), who participated in a 6-year prospective study. Kidney biopsies (measurements of basement membrane thickness [BMT] and mesangial and matrix volume fractions) and GFR were performed at baseline. AER and HbA1c were measured at least three times a year and blood pressure once a year. RESULTS: In a multivariate analysis, baseline BMT and mean 6-year HbA1c contributed significantly to AER at the end of the study (R2 = 0.69, P < 0.01). When mesangial volume fraction replaced BMT as the independent variable, this parameter and AER at baseline predicted the AER at 6 years (R2 = 0.55, P < 0.55). Mesangial volume fraction and BMT (in separate analysis) contributed significantly to change in AER during the study. During the study, neither AER (30 micrograms/min [19-40] to 16 micrograms/min [7-90]) nor blood pressure (96 mmHg [92-102] to 95 mmHg [91-98]) changed significantly in the group. However, HbA1c was reduced from 10.3 (9.6-11.0) to 8.4% (7.8-9.1) (P < 0.01). CONCLUSIONS: In young patients with microalbuminuria, the long-term urinary AER was predicted by the degree of glomerular structural changes and associated with blood glucose control, but not with blood pressure or GFR.