A study of exercise-induced microalbuminuria in type I (insulin-dependent) diabetes mellitus

Microalbuminuria is thought to be an important prognostic factor in diabetes mellitus. To study the influence of changes in blood pressure on the development of microalbuminuria during exercise, two exercise tests were carried out. A total of 32 insulin dependent diabetic men whose age at onset was less than 30 years, mean duration of diabetes 14 years (range 7 to 21) and mean age 29 years (range 21 to 40), and who did not have albuminuria (N-labstix negative) were studied. The diabetic patients were compared with a total of 29 age-matched male control subjects. Urinary albumin excretion was measured during two exercise tests: at a standardised workload (150 W) for 30 min, and at a standardised heart rate for 25 min. The diabetic patients had higher albumin excretion rates during both exercise tests compared with the control subjects. Blood pressure and heart rate during exercise were significantly higher in diabetic patients compared with control subjects in the standardised workload test. If the test was individualised to achieve the same standardised heart rate there was no significant difference in blood pressure between the diabetic patients and the control subjects. These results indicate that the diabetic kidneys were more sensitive than the healthy kidneys to similar degrees of haemodynamic stress induced by exercise.     

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.     

Urinary albumin excretion rate and glomerular filtration rate in the prediction of diabetic nephropathy; a long-term follow-up study of childhood onset type-1 diabetic patients.

BACKGROUND: Predictors of diabetic nephropathy are only partly known. The role of glomerular hyperfiltration is much discussed. We have studied the cumulative incidence of micro and macroalbuminuria and the predictive value of glomerular filtration rate (GFR) and screening value of albumin excretion rate (AER) in type-1 diabetes. METHODS: A cohort of diabetic children was followed up at a mean duration of 29+/-3 years. All 75 children treated in one hospital with diabetes duration > or =8 years were prospectively followed for 8 years examining GFR, AER, blood pressure and HbA1c. After another 8-10 years, 60 of them were traced for endpoint follow-up. RESULTS: Seven patients (12%) developed macroalbuminuria, i.e. persistent overnight AER>200 mg/min, 12 (20%) developed persistent microalbuminuria (AER 15-200 mg/min) and 17 (28%) transient microalbuminuria (>15 mg/min on two consecutive occasions, normalized at endpoint). One baseline screening value of 24-h AER>15 mg/min predicted 93% of patients with persistent micro or macroalbuminuria. The negative predictive value was 78%. Six of seven macroalbuminuric and 10 of 12 microalbuminuric patients had a baseline GFR above the normal limit of the method (> or =125 ml/min/1.73 m(2)). When adjusted for diabetes duration, increased GFR predicted macro or microalbuminuria (odds ratios=5.44, P=0.04). The positive predictive value for having an increased baseline GFR was 53%.The negative predictive value was 77%. Stratification for HbA1c did not change the effect of an increased GFR. CONCLUSIONS: At a mean diabetes duration of 29 years the cumulative incidence of macroalbuminuria was 12%; however, another 20% had persistent microalbuminuria. A screening value of 24-h AER >15 mg/min was a strong predictor, whereas increased GFR was a weaker but significant predictor for micro and macroalbuminuria.     

Mannose-binding lectin as a predictor of microalbuminuria in type 1 diabetes: an inception cohort study

Inflammation and complement activation via the mannose-binding lectin (MBL) pathway have been suggested to play a role in the pathogenesis of diabetic microvascular complications. The association between the complement-activating protein MBL and the development of persistent microalbuminuria was evaluated in an inception cohort of 286 newly diagnosed type 1 diabetic patients consecutively admitted to the Steno Diabetes Center between 1 September 1979 and 31 August 1984. Serum MBL was measured with an immunofluorometric assay in 270 of the patients (159 men) after 3 years of diabetes duration. During the median (range) follow-up period of 18.0 (1.0-21.8) years, 75 patients subsequently progressed to persistent micro- or macroalbuminuria (urinary albumin excretion rate >30 mg/24 h). In patients with MBL levels above the median (1,597 microg/l), the cumulative incidence of persistent micro- or macroalbuminuria was 41% (CI 31-50) as compared with 26% (CI 17-34) in patients with MBL levels below the median (log-rank test, P = 0.003). In a Cox proportional hazard model with sex and age as fixed covariates, MBL was independently associated with later development of persistent micro- or macroalbuminuria (hazard ratio 1.21 [CI 1.02-1.42] per 1,000 microg/l increase in MBL; P = 0.03) after adjusting for possible confounders. In our study, high levels of MBL early in the course of type 1 diabetes was significantly associated with later development of persistent micro- or macroalbuminuria, suggesting that complement activation initiated by MBL may be involved in the pathogenesis of diabetic microvascular complications.     

Prevalence and risk factors for micro- and macroalbuminuria in diabetic subjects and entire population of Nauru

Rates of elevated urinary albumin concentration, defined as microalbuminuria (30-299 micrograms/ml) and macroalbuminuria (greater than or equal to 300 micrograms/ml), were determined on random morning urine specimens in the population of Nauru, which has a high prevalence of non-insulin-dependent diabetes mellitus. The prevalence of elevated urinary albumin levels in the total Nauruan population was very high: 26 and 30% of men and women, respectively, had microalbuminuria, whereas 13% of both sexes had macroalbuminuria. Of the subjects with macroalbuminuria, 66% had diabetes. The prevalence increased with worsening glucose tolerance; 26% of subjects with normal glucose tolerance had either micro- or macroalbuminuria, increasing to 43% of subjects with impaired glucose tolerance, 63% of newly diagnosed diabetic subjects, and 75% of previously diagnosed diabetic subjects. Associations between elevated urinary albumin concentration and putative risk factors were assessed for both the total population (n = 1184) and the diabetic subgroup alone (n = 318). Fasting plasma glucose and hypertension were the most important independent correlates for the whole population, whereas plasma creatinine was also important in diabetic subjects. Age at onset and duration of diabetes were not found to be significantly associated with elevated albumin concentration. In subjects with normal glucose tolerance, hypertension and hyperuricemia were the most important associated factors. These results suggest that blood glucose, blood pressure, and possibly obesity and plasma uric acid are important modifiable risk factors for both micro- and macroalbuminuria in this population.     

Asymmetric Dimethylarginine (ADMA) and Progression of Nephropathy in Patients with Type 2 Diabetes

Diabetic nephropathy is the leading cause of kidney failure all over the world. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase. ADMA is in part eliminated via urinary excretion. It is found to be elevated in end stage renal disease. Identification of the plasma concentrations of ADMA in patients with different stages of diabetic nephropathy compared with healthy age-matched control subjects for estimation of the role of ADMA as a marker of progression of kidney disease in diabetic patients. Seventy-five diabetic patients were divided into five groups: Group I: patients with normoalbuminuria (urinary albumin excretion UAE < 30 mg/d), Group II: patients with microalbuminuria (UAE: 30–300 mg/d), Group III: patients with macroalbuminuria (UAE > 300 mg/d), Group IV: patients one month after renal transplantation and Group V: patients on haemodialysis. Patients were compared to 15 healthy control subjects matched for age and sex. All subjects subjected to thorough clinical examination and laboratory investigations including: serum albumin, urea, creatinine, fasting and postprandial blood glucose, UAE, urinary albumin/creatinine ratio and serum ADMA level. All patients groups had significantly higher levels of ADMA when compared to control group P < 0.01. The levels of ADMA were positively correlated with disease progression and degree of proteinuria. ADMA can be used as a marker of progression of kidney disease among diabetic patients.     

Influence of renal involvement on peripheral blood mononuclear cell expression behaviour of tumour necrosis factor-alpha and interleukin-6 in type 2 diabetic patients.

BACKGROUND: Type 2 diabetes is associated with a high cardiovascular risk, which is even increased if renal damage is superimposed. Peripheral blood mononuclear cells (PBMCs) and pro-inflammatory cytokines are key factors linking type 2 diabetes and atherosclerosis. We investigated the influence of renal damage on serum, urinary and PBMCs expression behavior of TNF-alpha and IL-6 in these patients. METHODS: PBMCs were isolated by density gradient centrifugation (Ficoll-Paque method) from fasting blood samples of 22 non-diabetic control subjects and 78 diabetic patients with normal renal function and different stages of diabetic nephropathy (18 with normoalbuminuria, 29 with microalbuminuria and 31 with macroalbuminuria). Expression levels of TNF-alpha and IL-6 were analyzed by real-time quantitative RT-PCR. Serum and urinary TNF-alpha and IL-6 concentrations were measured by a solid-phase, chemiluminescent immunometric assay. RESULTS: The mean percent increases in the serum and urinary levels of TNF-alpha and IL-6 in diabetic patients with respect to control subjects were 176% (P < 0.0001), 250% (P < 0.0001), 114% (P < 0.0001) and 39.6% (P = 0.01), respectively. The mRNA expression level of TNF-alpha was higher by 68.8% (P < 0.001) and IL-6 mRNA levels were higher by 64.1% (P < 0.001) with respect to non-diabetic controls. TNF-alpha mRNA expression in patients with macroalbuminuria was higher by 84.8% with respect to subjects with normalbuminuria (P < 0.001) and by 29% with respect to individuals with microalbuminuria (P < 0.05). Likewise, microalbuminuric patients showed a 44.5% increase in TNF-alpha mRNA expression compared to subjects with normoalbuminuria (P < 0.05). Concerning IL-6, the mRNA expression levels of this cytokine was higher by 63.1% with respect to normoalbuminuric subjects (P < 0.01), and by 23.1% with respect to patients with microalbuminuria (P < 0.05). However, with respect to controls, diabetic patients with normoalbuminuria had similar serum TNF-alpha and urinary excretion of IL-6, without any differences in the mRNA expression levels of these cytokines in PBMCs. Partial correlation and multiple regression analysis using TNF-alpha and IL-6 mRNA levels as the dependent variables showed that urinary albumin excretion (UAE) was direct and independently associated with the expression profile of these pro-inflammatory cytokines in PBMCs. CONCLUSIONS: These data show for the first time the relationship between inflammatory activation of PBMCs (reflected by enhanced mRNA expression of TNF-alpha and IL-6) and renal involvement (reflected by increased UAE) in type 2 diabetic patients. These results provide potential insights for the increased inflammation, accelerated atherosclerosis and cardiovascular risk associated with nephropathy in type 2 diabetes.     

Relationship between urinary albumin excretion and glomerular filtration rate in normotensive, nonproteinuric patients with type 2 diabetes mellitus

BACKGROUND/AIM: In patients with type 2 diabetes mellitus, the relationship between glomerular filtration rate (GFR) and urinary albumin excretion remains an unresolved issue. In order to investigate the early renal function abnormalities, GFR and urinary albumin excretion were assessed, and their relationship was examined in normotensive patients with type 2 diabetes mellitus. METHODS: In a cross-sectional study of 85 nonhypertensive Japanese patients with type 2 diabetes mellitus not showing overt proteinuria, the GFR was measured using (99m)Tc-diethylenetriamine pentaacetate renography. Fifty-one diabetic patients lacked microalbuminuria (albumin excretion <30 mg/day), while 34 patients showed microalbuminuria (between 30 and 300 mg/day). Fifteen healthy subjects served as controls. RESULTS: The three groups were well matched with regard to gender, age, and body mass index. The GFR in microalbuminuric patients (134 +/- 23 ml/min/1.48 m(2)) was significantly higher than in patients without microalbuminuria (108 +/- 21 ml/min/1.48 m(2)) and in controls (109 +/- 18 ml/min/1.48 m(2); p < 0.0001). In type 2 diabetic patients, the GFR positively correlated with the logarithmically transformed urinary albumin excretion. Multiple regression analysis showed that the urinary albumin excretion was significantly and independently affected by GFR (beta = 0.548), duration of diabetes (beta = 0.297), and systolic blood pressure (beta = 0.232; R(2) = 0.409; p < 0.0001). CONCLUSION: It is suggested that one of the mechanisms underlying increased urinary albumin excretion in early nephropathy in normotensive type 2 diabetes is glomerular hyperfiltration.     

Effects of the angiotensin II type 1 receptor antagonist candesartan,compared with angiotensin-converting enzyme inhibitors,on the urinary excretion of albumin and type IV collagen in patients with diabetic nephropathy

Background. We previously reported that the angiotensin II type 1 receptor antagonist candesartan was effective in reducing blood pressure and microalbuminuria in hypertensive patients with diabetic nephropathy after angiotensin-converting enzyme (ACE) inhibitors were replaced due to side effects. In the present study, the clinical effects of candesartan were investigated and compared with ACE inhibitors in patients with stage 2 or 3A diabetic nephropathy, mainly with respect to the effects on the urinary excretion of albumin and type IV collagen. Methods. Forty-nine patients (26 males/23 females) with diabetic nephropathy (stage 2 or 3A), including normotensive patients, were the study subjects. The patients were treated with either an ACE inhibitor (23 patients) or candesartan (26 patients) for 11 ± 3 months. The urinary excretion of albumin and urinary type IV collagen was measured. Results. Posttreatment blood pressure tended to decrease, but such a decrease did not reach a statistically significant level, nor did it show any intergroup difference. The urinary albumin excretion was positively correlated with pretreatment mean blood pressure and left ventricular mass index, but the urinary type IV collagen excretion did not show such correlations. The urinary albumin excretion decreased significantly after treatment to a similar extent in both groups, whereas the urinary type IV collagen excretion decreased significantly only in the candesartan group. Conclusion. It was revealed that ACE inhibitors and candesartan reduced urinary albumin excretion to a similar extent in patients with diabetic nephropathy. From the results of the present study, it is inferred that the renoprotective effect of candesartan in diabetic nephropathy may partially differ from that of ACE inhibitors.     

A study of Tamm-Horsfall protein excretion in hypertensive patients and type 1 diabetic patients.

OBJECTIVE: The study was performed in order to evaluate to what extent hypertension or diabetes mellitus may affect the urinary excretion rate of Tamm-Horsfall protein. MATERIALS AND METHOD: The urinary excretion rates of albumin and Tamm-Horsfall protein, a measure of glomerular and distal tubular function, respectively were measured in patients with essential hypertension (n = 17) and in type 1 diabetes with (n = 20) or without nephropathy (n = 8) and in apparently healthy subjects (n = 10). RESULTS: Mean 24-h ambulatory blood pressure measurements showed higher blood pressure levels in the hypertensive (167/ 106 mmHg, p < 0.001) than in the diabetic patients with (136/84 mmHg) and without nephropathy (121/74 mmHg) and in healthy subjects (122/76 mmHg). Day and night ratios of systolic and diastolic blood pressure levels were not different among the four groups. Urinary albumin excretion rate was increased in patients with hypertension (30.8 x/ 3.4 microg/min; geometric mean x/tolerance factor; p < 0.001) and diabetes with nephropathy (462 x/ 3.5 microg/min; p < 0.001) compared with diabetic patients without nephropathy and healthy subjects (4.6 x/ 1.9 and 3.7 x/ 1.5 microg/min, respectively). The Tamm-Horsfall protein excretion rate was decreased in patients with diabetic nephropathy (11.6 x/ 3.5 microg/min) compared to patients with hypertension (36.3 x/2.1 1g/min; p < 0.01), diabetes without nephropathy (39.2 x/ 2.0 microg/min; p < 0.05) and healthy subjects (63.0 x/ 1.4 microg/min; p < 0.001), whereas no differences were found among the latter three groups. CONCLUSION: These data indicate that high blood pressure may be associated with albuminuria, while a decrease in excretion rate of Tamm-Horsfall protein may be associated with diabetic nephropathy. These associations need to be studied in a larger population.     

Combination of Pentoxifylline with Angiotensin Converting Enzyme Inhibitors Produces an Additional Reduction in Microalbuminuria in Hypertensive Type 2 Diabetic Patients

Objective.?To investigate the anti proteinuric effect of pentoxifylline in diabetic patients, we prospectively studied in 25 hypertensive type 2 diabetic patients with persistent microalbuminuria and normal renal function the impact of combining pentoxifylline with an angiotensin converting enzyme inhibitor, lisinopril, on urinary albumin excretion and compared the results with those obtained in a control group of 25 type 2 diabetic patients treated with lisinopril only. Material and Methods.?Fifty hypertensive type 2 diabetic patients with persistent microalbuminuria (31 males and 19 females, aged between 47–73 years) were randomly assigned to two groups. Group A received lisinopril 10 mg/day, while group B was given lisinopril 10 mg/day and pentoxifylline 600 mg/day for nine months. There were no significant differences between serum creatinine, HbA1c, blood pressure and urinary albumin excretion in both groups (p>0.05). Results.?Serum creatinine, creatinine clearance, blood pressure, HbA1c levels did not change significantly during the study. Urinary albumin excretion decreased from 228 ± 28 to 148 ± 15 mg/day in group A (p<0.05). In group B urinary albumin excretion decreased from 219 ± 26 to 128 ± 12 mg/day (p<0.05). Pentoxifylline and lisinopril combination caused a significant additional reduction in urinary albumin excretion when compared to lisinopril regimen (p<0.05).

Conclusions.?Our findings suggest that the combination of pentoxifylline with an angiotensin converting enzyme inhibitor in hypertensive type 2 diabetic patients with persistent microalbuminuria causes a significant reduction in urinary albumin excretion and this effect seems independent from blood pressure and glycemic control.     

Urinary sulphated glycosaminoglycans and Tamm-Horsfall protein in type 1 diabetic patients

OBJECTIVE: In diabetic nephropathy there is a decrease in glycosaminoglycans (GAG) in basement membranes and in Tamm-Horsfall protein (THP) in the distal tubules of the kidneys. Since GAG is present in both glomerular and tubular basement membranes, and the synthesis of both GAG and THP involves glycosylation, this study was carried out in order to investigate whether urinary excretion of these substances is interrelated. MATERIAL AND METHODS: 24-h urinary collections were analysed. A total of 94 diabetic patients were grouped in accordance with the urinary albumin excretion rate as normo- (<20 microg/min) (n = 35), micro- (20-200 microg/min) (n = 30) and macroalbuminuria (>200 microg/min) (n = 29). RESULTS: In comparison with 26 control subjects, the excretion rate of GAG was decreased in patients with micro- and macroalbuminuria and excretion of Tamm-Horsfall protein in patients with macroalbuminuria. The excretion rates of GAG and THP were associated (r = 0.64, p < 0.001) and correlated with creatinine clearance (r= 0.46 and r= 0.53, p < 0.001; respectively) but not with levels of HbA1c. CONCLUSIONS: In conclusion, albuminuria was associated with decreased urinary excretion of sulphated GAGs, which was associated with the excretion rate of Tamm-Horsfall protein, indicating that excretion of GAG was associated with distal tubular dysfunction in diabetic patients.     

Glomerular hyperfiltration increases the risk of developing microalbuminuria in diabetic children

An elevated glomerular filtration rate (GFR) is frequently detectable in type 1 diabetic children and adolescents and in those without any other evidence of incipient diabetic nephropathy. In 1982 we detected 23 patients with hyperfiltration (GFR>140 ml/min per 1.73 m²), aged 9–15 years, with diabetes for longer than 4 years; 23 age- and sex-matched patients with diabetes of a similar duration and without hyperfiltration served as controls. Both groups were followed until March 1992, by assessing GFR every 12 months, albumin excretion rate every 6 months, blood pressure and glycated haemoglobin (HbA1) every 3 months. Dietary protein intake was similar in patients with hyperfiltration and in controls. No other drug except insulin was used throughout the study. The insulin regimen was similar in the two groups. There was no significant difference between the two groups regarding albumin excretion, blood pressure and HbA1 at the beginning of the study. Of the 23 patients with hyperfiltration, 7 developed persistent microalbuminuria (defined as an overnight albumin excretion rate >30 g/min per 1.73 m² on at least 5 consecutive measurements); 2 of these patients had overt proteinuria. Only 1 of the diabetics with normal GFR developed persistent microalbuminuria. The positive predictive value for microalbuminuria of an initial GFR>140 ml/min per 1.73 m² was 63%; the negative predictive value of an initial GFR<140 ml/min per 1.73 m² was 94%. The increase of albumin excretion rate into the microalbuminuric range precedes the elevation of both systolic and diastolic blood pressure. Persistent glomerular hyperfiltration is a risk factor for the development of microalbuminuria and incipient nephropathy in type 1 diabetic children, adolescents and young adults.     

Pulse pressure and isolated systolic hypertension: association with microalbuminuria. The GUBBIO Study Collaborative Research Group

BACKGROUND: The long-term risk of end-stage renal disease is high in persons with isolated systolic hypertension, that is, those with an elevation of pulse pressure and not of diastolic pressure. Other data suggest that pulse pressure is a predictor of the hypertension-induced organ damage. Microalbuminuria is considered an early sign of glomerular damage caused by hypertension. The study shows the relationship of pulse pressure and isolated systolic hypertension to microalbuminuria in nondiabetic subjects. METHODS: This is a cross sectional analysis for a population sample of 677 men and 890 women, aged 45 to 64 years, who were without diabetes mellitus and macroalbuminuria. Data collection included: overnight urinary albumin and creatinine excretion; fasting plasma glucose, cholesterol, and creatinine; creatinine clearance; and blood pressure, weight, height, medical history, and smoking habit. Pulse pressure was calculated as systolic minus diastolic pressure. Isolated systolic hypertension was defined as systolic pressure > or =140 mm Hg in persons not on antihypertensive drugs and with diastolic pressure <90 mm Hg. Microalbuminuria was defined as urinary albumin excretion > or =20 microg/min. RESULTS: Pulse pressure and isolated systolic hypertension were significantly related to urinary albumin excretion and the prevalence of microalbuminuria in univariate and multivariate analyses. Controlling for gender and other variables, the risk of microalbuminuria was 1.71 with a 15 mm Hg higher pulse pressure (95% CI, 1.31 to 2.22) and 4.95 in the presence of isolated systolic hypertension (95% CI, 3.15 to 7.76). CONCLUSIONS: In nondiabetic, middle-aged adults, pulse pressure and isolated systolic hypertension are directly related to microalbuminuria, independent of diastolic pressure and other correlates.     

Glomerular structure in IDDM women with low glomerular filtration rate and normal urinary albumin excretion.

Eight women with insulin-dependent diabetes mellitus (IDDM) with low creatinine clearance rate (CCR) and normal urinary albumin excretion (UAE) were compared with three other groups of diabetic women: 19 with normal creatinine clearance rate (CCR) and UAE, 7 with normal CCR and microalbuminuria, and 7 with low CCR and microalbuminuria. The four groups were similar in age, duration of diabetes, HbA1, incidence of urinary tract infection, prevalence of bladder neuropathy, and urinary urea nitrogen excretion rate. The prevalence of hypertension was similar among the groups, although mean arterial pressure was higher in the low CCR and microalbuminuria group. Renal area index was lower in the low CCR and normal UAE groups than in the other groups of diabetic patients, but was not different from normal. Morphometric measures of mesangial expansion and estimates of arteriolar hyalinosis and global glomerulosclerosis were increased to a similar degree in the low CCR and normal UAE, normal CCR and microalbuminuria, and low CCR and microalbuminuria groups compared with the group without abnormalities of renal function. Therefore, it is likely that diabetic glomerulopathy is, at least in part, responsible for the loss of glomerular filtration rate seen in the low CCR and normal UAE patients. Thus, the definition of incipient nephropathy may have to be expanded beyond the concept of microalbuminuria if longitudinal study of such patients reveals an increased risk of the subsequent development of overt nephropathy. Finally, screening for diabetic kidney disease among IDDM patients should include determination of glomerular filtration rate and measurement of UAE and blood pressure, especially among women.     

微小RNA在糖尿病肾病患者血清中的表达及临床意义

目的 探讨糖尿病肾病发生、进展过程中血清微小RNA (microRNA,miRNA)表达谱及其临床意义.方法 应用miRNA基因芯片检测10例糖尿病肾病患者、10例糖尿病尿蛋白正常患者及10例健康对照者血清miRNA表达谱.实时荧光定量PCR法对66例糖尿病肾病(微量蛋白尿者36例,大量蛋白尿者30例)、40例糖尿病尿蛋白正常者及40例健康对照者进行血清miRNA表达谱验证,分析血清差异表达的miRNA与糖尿病肾病临床参数的关系.结果 实时荧光定量PCR法验证得到miR-150-5p、miR-155-5p、miR-30e-5p及miR-3196在糖尿病微量蛋白尿患者组(n=36)、糖尿病尿蛋白正常者组(n=40)及健康对照组(n=40)血清样本中表达差异有统计学意义(P＜0.05).miR-150-5p (P=0.005)和miR-155-5p (P=0.006)在糖尿病微量蛋白尿组(n=36)及糖尿病大量蛋白尿组(n=30)血清中表达差异有统计学意义.大量蛋白尿组血清miR-150-5p和miR-155-5p表达水平分别是微量蛋白尿组的2.3倍、1.5倍.同时发现,miR-150-5p和miR-155-5p与糖尿病肾病患者的估算肾小球滤过率和尿蛋白排泄率具有明显相关性.结论 miR-150-5p和miR-155-5p可能参与糖尿病肾病发生及发展的病理过程;血清miR-150-5p和miR-155-5p有望成为DN早期诊断及判断预后的潜在分子标志物.     

Plasma prorenin levels may predict persistent microalbuminuria in children with diabetes

Diabetic microangiopathy is characterized by increased prorenin concentrations. In the present study, we evaluated plasma prorenin concentrations in a large group of adolescents with onset of diabetes during childhood to determine whether increasing prorenin levels may predict the development of persistent microalbuminuria. Ninety-seven young diabetic patients were studied; they were divided according to the presence of persistent microalbuminuria, at the end of follow-up, into group A and group B (patients who did not develop and who developed persistent microalbuminuria, respectively). One hundred and two healthy subjects, matched for age and sex, were also selected. Patients were followed up for at least 10 years. At the beginning of the study there were no significant differences in prorenin levels between either the two diabetic groups or the healthy controls. During follow-up, an increase in plasma prorenin started at 4 years and became statistically significant (P<0.01) 3 years before the onset of persistent microalbuminuria. No correlation was found between plasma prorenin levels and HbA1c percentages. In conclusion, an increased concentration of prorenin in plasma precedes the elevation of albumin excretion rate (AER) and, therefore, can be useful for identifying patients with onset of diabetes during childhood at risk of developing incipient nephropathy later in life. Received: 16 March 2000 / Revised: 21 September 2000 / Accepted: 23 September 2000     

舒洛地特对糖尿病肾病患者尿蛋白的影响

目的：观察舒洛地特对已应用ACEI/ARB类药物的2型糖尿病肾病患者尿蛋白的影响。方法：据尿白蛋白排泄率将92例2型糖尿病肾病患者分为微量白蛋白尿组和大量白蛋白尿组,患者在入组前至少服用一种ACEI或ARB类降压药6个月,入组后先接受10d舒洛地特注射剂60mg/d静脉滴注,再接受110d舒洛地特软胶囊100mg/d口服。用药前、用药4周、8周、12周及120d分别检测患者血压、空腹血糖、肝肾功能、凝血功能、24h尿蛋白定量等指标。结果：两组患者治疗12周后均出现尿蛋白显著降低（P0.05）。结论：对已应用ACEI/ARB的伴有微量白蛋白尿或大量白蛋白尿的2型DN患者,舒洛地特能有效降低其尿蛋白。     

The predictive value of microalbuminuria

An elevated urinary albumin excretion (termed microalbuminuria) has been proposed as a predictor for later development of clinical diabetic nephropathy (hypertension, falling glomerular filtration rate [GFR], and urinary albumin excretion greater than 300 mg/24 h). However, review of the original reports on the predictability of microalbuminuria revealed a concomitant presence of elevated BP and a propensity to falling GFR. Thus, the predictability of microalbuminuria rests on the added evaluation of BP and GFR. Additional investigation is needed to address the possibility that microalbuminuria and either a rising BP or a falling GFR or both indicates established diabetic nephropathy rather than predicting its development.     

Parental hypertension and 24 h-blood pressure in children prior to diabetic nephropathy

In a search for predictors of nephropathy development, albumin excretion rate (AER), ambulatory blood pressure, and parental hypertension were assessed in 40 type 1 diabetic patients and 27 normal siblings (age<18 years) during a 2-year follow-up period. A double-antibody kit and an automated device were used for measuring 24-h AER and ambulatory blood pressure monitoring (ABPM), respectively. Patients had higher 24-h and daytime diastolic blood pressure (DBP), diastolic load, and daytime heart rate than siblings. Patients with hypertensive parents had higher 24-h DBP and diastolic load than patients with normotensive parents and all siblings. Non-dipping was more frequent in children with hypertensive parents (P<0.05). Both diabetes (P<0.001) and parental hypertension (P<0.05) had independent effects on longitudinal AER (average AER during follow-up). Patients with intermittent or persistent microalbuminuria showed a trend towards higher diastolic load (P<0.05); the latter group had higher 24-h DBP (P<0.01). Longitudinal AER correlated with 24-h DBP (P<0.01) and maternal mean blood pressure (P<0.05). Since changes in blood pressure preceded persistent microalbuminuria, ABPM might help to identify diabetic children prone to nephropathy. Received: 18 June 2001 / Revised: 1 October 2001 / Accepted: 4 October 2001