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.     

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     

Prevalence of microalbuminuria in children with sickle cell disease

Renal involvement is common in homozygous sickle cell disease (HbSS), including glomerular hypertension and hypertrophy similar to that seen in rodent models of ablative nephrectomy and stage I diabetic nephropathy (DN). The proteinuria in the rodent models is attenuated by angiotensin converting enzyme inhibition (ACEI). Microalbuminuria (MA) is a sensitive marker for renal involvement in DN prior to the development of proteinuria, and is also attenuated with ACEI. Elevated urinary microalbumin/creatinine ratios (U Alb/Cr) >20 mg/g Cr are reported in 39%–43% of adults with HbSS, and studies are ongoing in this age group to assess the effect of attenuated proteinuria by ACEI on long-term renal function. The purpose of this study was to prospectively investigate the prevalence of MA in children with HbSS and determine factors which affect its expression. U Alb/Cr values were measured on spot urine samples in 102 children (aged 2–18 years, mean 9.47±4.62, M:F=53:49) by rate nephelometry. Children with prior known proteinuria, hypertension, or fever/pain episode in the last 15 days were excluded. MA was present in 26.5% of all children with HbSS. However, in children between the ages of 10 and 18 years, the prevalence was 46% (similar to the prevalence in adults). There was a strong correlation between patient age and prevalence of MA (P<0.0001) by both univariate and multivariate analysis. However, pain frequency, hospitalization, transfusion program, ferritin levels, and Cr clearance (C _Cr) did not correlate with prevalence, although C _Cr (as estimated by Schwartz formula) was elevated in all. We conclude that the prevalence of MA in the 2nd decade of life is similar to that in adults. Received April 11, 1998; received in revised form and accepted March 6, 1998     

Glomerular volume and renal function in children with different types of the nephrotic syndrome

Glomerular hypertrophy has been suggested to be an important factor in the pathogenesis of focal glomerular sclerosis. The aim of the present study was to analyse retrospectively the renal biopsies of 58 children (0.2–16.1 years of age) with different types of the nephrotic syndrome, minimal change nephrotic syndrome (MCNS), diffuse mesangial proliferation (DMP) and focal segmental glomerulosclerosis (FSGS). Glomerular surface area was measured and glomerular volume was calculated and related to steroid responsiveness and to renal function, measured by clearances of inulin and para-aminohippuric acid. Glomerular volume correlated with body surface area (BSA) and age. Because of this, patients with FSGS and DMP were matched according to BSA and age, with corresponding MCNS patients. Glomerular volumes of FSGS and DMP patients were significantly larger than those of MCNS patients. In the MCNS patients, significant correlations were found between glomerular volumes and glomerular filtration rate and effective renal plasma flow. Steroid-dependent and steroid-resistant patients showed larger glomeruli than the steroid-responsive children. We suggest that hyperfiltration and hyperperfusion, among other factors, may contribute to glomerular hypertrophy, mesangial proliferation and glomerulosclerosis.     

Urinary protein excretion and renal function in children with IgA nephropathy

Renal haemodynamics and the pattern of urinary protein excretion were studied in 38 children (21 boys, 17 girls) with biopsy-proven IgA nephropathy (IgAN), 0.4–16.8 (median 5.3) years after onset of the disease. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were evaluated by clearances of inulin and para-aminohippuric acid. Serum and urinary albumin, IgG and beta₂-microglobulin (2) were determined and the excretion rates, clearances, and fractional clearances were calculated. The patients were grouped according to the type and the amount of proteinuria. Mean GFR and ERPF were significantly decreased (107±3 and 580±17 ml/min per 1.73 m², respectively) versus controls (119±2 and 627±14 ml/min per 1.73 m², respectively). Grouped according to albumin excretion rates, non-albuminuric patients had normal GFR, while mean GFR was reduced in patients with micro-albuminuria (106±3 ml/min per 1.73 m²) and albuminuric patients (92±7 ml/min per 1.73 m²). IgG excretion increased with increasing albuminuria, but the selectivity index was lower in albuminuric patients than in patients with micro-albuminuria. Albuminuric patients had also higher blood pressure than those with micro-albuminuria. 2 excretion did not discriminate between patients with impaired renal function. The results suggest that childhood IgAN is not a benign kidney disease. After a median duration of 5 years of the disease a number of children had impaired renal function. Mean GFR was reduced most in the albuminuric patients but was also decreased in micro-albuminuric patients, indicating that micro-albuminuria may be a predictor of more severe disease.     

Oxidant/antioxidant status and hyperfiltration in young patients with type 1 diabetes mellitus

Diabetic nephropathy (DN), a major cause of morbidity and mortality in diabetes, will develop within a subset of type 1 diabetes mellitus (T1DM) patients, and oxidative stress has been implicated in its pathogenesis. To investigate the relationship between indicators of early DN stages (hyperfiltration estimated by creatinine clearance ≥150 ml/min per 1.73 m², microalbuminuria) and oxidative stress, a prospective study was conducted in 29 T1DM patients (age 13.89 ± 4.61 years) and 18 control subjects (age 13.23 ± 3.99 years). Blood samples were collected to assay for biomarkers of oxidative stress (malondialdehyde and carbonyl groups) and antioxidants (glutathione peroxidase, reduced glutathione, α-tocopherol, and β-carotene). With respect to control subjects, in T1DM patients, an increase was found in biomarkers of oxidative stress (p < 0.05), mainly due to the group of subjects with hyperfiltration, and a decrease in the ratio α-tocopherol/lipids (p < 0.05). In multiple regression analyses, age at disease onset, glycated hemoglobin, microalbuminuria, and oxidative stress biomarkers remained as explicative variables of hyperfiltration (R ² adjusted = 0.731, p = 0.000). These findings support the importance of the oxidative damage to lipids and proteins, which is linked to hyperfiltration and which could contribute to the development of DN in patients with T1DM.     

Diabetic nephropathy-pathophysiology and management

Diabetes mellitus is the leading cause ofend-stage renal disease in the United States. Between 1996 and 2001, the prevalence ofdiabetes in the Medicare population increasedby 31%. Patients with diabetes account forapproximately one-third of all cases ofend-stage renal disease (ESRD). This number isexpected to rise dramatically as a result ofthe growing incidence of diabetes and the agingpopulation. A major complication of diabetesincludes end-stage renal disease as a resultfrom diabetic nephropathy. The earliestclinical evidence that nephropathy exists isthe appearance of low, yet abnormal, levels ofalbumin in the urine, referred to asmicroalbuminuria. This can progress toproteinuria representing overt diabeticnephropathy. Prevention remains the best way toreduce mortality and maintain a high quality oflife in these individuals as recent clinicaltrials confirm that it is possible to not onlyslow down the progression of diabeticnephropathy, but even prevent it from becominga significant problem. This article reviewsthe pathogenesis, diagnostic screening, andtreatment strategies of diabetic nephropathy.     

糖尿病早期肾损害的彩色多普勒超声研究

目的：探讨彩色多普勒超声肾血流测定对诊断糖尿病早期肾损害的价值。方法：以尿白蛋白排泄率（UAER）作为早期肾损害指标,对60例糖尿病患在26例正常人行彩色多普勒超声肾血流检查,结果：小叶间动脉收缩期峰值流速（Vs),弓状动脉及小叶间动脉舒张末期流速（Vd)的减慢是糖尿病患最早出现的肾内血流动力学改变;有肾脏早期损害的糖尿病患肾血流频谱参数特点是肾内弓状动脉,小叶间动脉的Vs和肾内各分支动脉的Vd明显减低,肾内各分支动脉的阻力指数（RI）明显增高,RI与糖尿病患肾功能损害程度相关。结论：彩色多普勒超声肾血流检测是早期诊断糖悄病肾损害的简便,可靠的方法。     

Effect of glycemic control on microalbuminuria development among type 2 diabetes with high-normal albuminuria

This study was aimed at revealing the factors and the interrelationships between factors on microalbuminuria development among type 2 diabetes (T2D) patients. Between 2004 and 2011, 461 T2D patients with a baseline urine albumin-to-creatinine ratio (UACR) of <30?mg/g, and an estimated glomerular filtration rate (eGFR) of >60?mL/min were evaluated retrospectively. Sixty-eight (14.8%) subjects had developed microalbuminuria in a mean follow-up of 6.82 years. Statistical analysis had revealed that the higher baseline UACR (10?mg/g; sensitivity, 80.9%, specificity, 63.6%; AUC?=?0.774) and glycohemoglobin level (HbA1c) (8%; sensitivity, 72.1%, specificity, 61.6%; AUC?=?0.698) were the two independent microalbuminuria risk factors. When considering the risk of microalbuminuria, the data were normalized with respect to subjects with low-normal UACR (<10?mg/g) and HbA1c??8%, high-normal UACR/HbA1c?8% were 2.59 (p?=?0.107), 6.15 (p?=?0.001), and 16.96 (p?10%) showed a progressively increase of the hazard risk in baseline high-normal UACR group. But the same correlation was not shown in the low-normal UACR group. This study identified the relationships of high-normal albuminuria and glycemic control on microalbuminuria development among T2D patients. Glycemic control is especially beneficial for T2D patients with baseline high-normal UACR in preventing microalbuminuria development.     

Insulin resistance precedes microalbuminuria in patients with insulin-dependent diabetes mellitus

Background. Insulin resistance has been associated with hypertension and with renal complications in patients with type 1 diabetes mellitus. Causal relationships have not been fully explained. Methods. We investigated whether insulin resistance precedes microalbuminuria by measuring insulin resistance with a euglycaemic clamp in combination with indirect calorimetry in 16 uncomplicated type 1 diabetic patients and in six healthy control subjects. The patients had over 10 year duration of diabetes, and were expected to experience either a complication-free or complicated disease course within the next few years. They have thereafter been followed for the development of microalbuminuria for 3 years. Results. In a euglycaemic insulin clamp glucose disposal was lower in diabetic patients compared with control subjects (7.5±2.9 and 12.6±2.0 mg/kg LBM/min; P<0.002), mainly due to impaired glucose storage (4.3±2.3 vs 8.6±1.6 mg/kg LBM/min; P<0.001). Three years later seven IDDM patients had albumin excretion rate over 30 mg/24 h; glucose disposal (5.5±2.1 vs 9.0±2.2 mg/kg LBM/min; P<0.01) had been lower in patients who developed microalbuminuria compared with those who remained normoalbuminuric. Conclusions. Insulin resistance predicts the increment in urinary albumin excretion. Insulin resistance depends mainly on impaired glucose storage in uncomplicated IDDM.     

Diabetic nephropathy in children and adolescents

Type 1 diabetes mellitus (T1DM) commonly occurs in childhood or adolescence, although the rising prevalence of type 2 diabetes mellitus (T2DM) in these age groups is now being seen worldwide. Diabetic nephropathy (DN) develops in 15–20% of subjects with T1DM and in similar or higher percentage of T2DM patients, causing increased morbidity and premature mortality. Although overt DN or kidney failure caused by either type of diabetes are very uncommon during childhood or adolescence, diabetic kidney disease in susceptible patients almost certainly begins soon after disease onset and may accelerate during adolescence, leading to microalbuminuria or incipient DN. Therefore, all diabetics warrant ongoing assessment of kidney function and screening for the earliest manifestations of renal injury. Pediatric health care professionals ought to understand about risk factors, strategy for prevention, method for screening, and treatment of early DN. This review considers each form of diabetes separately, including natural history, risk factors for development, screening for early manifestations, and strategy recommended for prevention and treatment of DN in children and adolescents.     

2型糖尿病患者不同蛋白尿期肾小球滤过率的变化及影响因素

目的 研究2型糖尿病（DM）患者不同蛋白尿期的肾小球滤过率并探讨其影响因素。 方法 根据尿白蛋白量（24 h）把630例2型糖尿病住院患者分成正常白蛋白尿组（A组）、微量白蛋白尿组（B组）及大量白蛋白尿组（C组），用放射性核素(99m Tc-DTPA)肾动态显像测定肾小球滤过率(GFR), 同时测定其体质量指数、血压、血糖、糖化血红蛋白、肾功能、血脂及尿白蛋白量（24 h）。 结果 （1）A组GFR值平均为（99.8±26.3） ml/min；B组为（96.1±31.2） ml/min；C组为（69.7±29.8） ml/min。C组的GFR显著低于A组和B组（P < 0.01）。（2）3组患者的GFR均与年龄呈负相关（A组r = -0.533，B组r = -0.612，C组r = -0.412，均P < 0.01）。（3）有高血压史者的GFR平均值均低于同组无高血压史者（P均< 0.05）。（4）控制年龄后的偏相关分析结果显示，在B组及C组，GFR与尿白蛋白量（24 h）呈负相关（r = -0.283 及-0.240，均P < 0.05）。多元逐步回归分析结果显示，尿白蛋白量（24 h）是影响异常蛋白尿组患者GFR的主要因素。 结论 放射性核素肾动态显像法测定GFR，同时联合尿白蛋白量检测，能更全面准确地评估糖尿病肾病的进展。应积极控制蛋白尿，尤其在微量白蛋白尿期。     

Glomerular structure in type-1 (insulin-dependent) diabetic patients with normo- and microalbuminuria.

Kidney biopsies from 15 type-1 (insulin-dependent) diabetic patients with a range of albumin excretion (AER) were analyzed. Nine patients had normal AER, and six had microalbuminuria. Basement membrane thickness, BMT, and mesangial matrix volume fraction, Vv(mat/glom), were obtained from at least three glomeruli per biopsy. Mesangial structures were estimated with electron microscopic analysis at three levels in each glomerulus. Glomerulopathy parameters were significantly increased in micro- versus normoalbuminuric patients with the following means and (CV): BMT 571 nm (0.12) and 442 nm (0.25), P = 0.03; Vv(mes/glom) 0.31 (0.20) and 0.22 (0.14), P = 0.002; Vv(matrix/glom) 0.17 (0.25) and 0.11 (0.28), P = 0.006; matrix star volume 56 microns 3 (0.47) and 22 microns 3 (0.43), P = 0.02. A positive correlation obtained between AER and each of the glomerulopathy parameters, BM thickness, Vv(mes/glom) and Vv(matrix/glom), as well as between AER and a structural index expressing the sum of changes in the peripheral BM and in the mesangium (r = 0.62, P = 0.01). The results indicated a parallel course of mesangial and peripheral BM changes: a positive correlation obtained between BM thickness and mesangial parameters [BMT versus Vv(matrix/glom): r = 0.82, P = 0.0001] and the ratio of the two subsets of glomerular BM material (PBM:matrix) did not show significant difference between normo- and microalbuminuric groups. The data give strong support to the contention that the transition from normo- into the microalbuminuric phase is linked to progressing glomerulopathy.     

Renal tubular handling of potassium in children with insulin-dependent diabetes mellitus

To clarify the mechanism by which renal potassium (K) excretion is reduced in children with insulindependent diabetes mellitus, we studied two groups of patients: (A) at diagnosis and (B) after at least 1 year of follow-up. Group A (15 children) was studied twice: on the day of admission and after 1 month of insulin therapy. On admission, urinary K excretion, fractional K excretion, and transtubular K concentration gradient (TTKG) were significantly decreased, but became normal after extended insulin therapy. TTKG was inversely correlated with blood glucose (P<0.001) and hemoglobin A_1c (HbA_1c,P<0.001). Group B (73 children with a mean follow-up of 54±36 months) was subdivided according to the TTKG: 30 patients had a low TTKG<4.0 (median 3.2) and 43 patients had a normal TTKG4.0 (median 5.2). Patients with a low TTKG and those with a normal TTKG had an identical duration of follow-up and similar values for plasma renin activity, aldosterone concentration, calciuria, magnesiuria, albumin excretion rate, and creatinine clearance. However, those with a low TTKG had significantly higher blood HbA_1c levels, urine volume, and glucosuria. Logistic regression analysis showed that the only independent variables predicting a low TTKG were blood HbA_1c and glucosuria (P<0.001). These data confirm that a reduced renal K excretion is a characteristic feature of diabetic children; this is reversible with appropriate insulin therapy, largely depends on the metabolic control of the disease, and, specifically, on the degree of hyperglycemia and/or glucosuria.     

Glomerular size and charge selectivity in insulin-dependent diabetes mellitus

The pathogenesis of clinical nephropathy in Type 1 (insulin-dependent) diabetes was investigated by measuring renal fractional clearances of albumin, total IgG, IgG4 and beta 2-microglobulin, four plasma proteins which differ in size and charge. Seventy patients and eleven control subjects were studied. In diabetic patients with normal urinary albumin excretion (less than 30 mg/24 hr), fractional IgG clearance was two to three times higher than in control subjects, whereas fractional clearance of the anionic plasma proteins IgG4 and albumin was similar to that of control subjects. These alterations indicate an increase in anionic pore charge within the glomerular basement membrane concomitant with an increase in either pore size or impairment of tubular reabsorption. Diabetic patients, whose urinary albumin excretion has started to rise (30 to 100 mg/24 hr), had unchanged fractional IgG compared to patients with normal albumin excretion, while fractional IgG4 and albumin clearances were increased three- to fourfold; indicating unchanged glomerular pore size, but a decrease in anionic pore charge. In patients demonstrating urinary albumin excretion of greater than 100 mg/24 hr fractional IgG clearance increased to the same extent as fractional albumin clearance, indicating an increase in large pore area. Fractional beta 2-microglobulin clearances were similar to that of control subjects in the different patient groups indicating unchanged tubular reabsorption of proteins. Thus, the increase in large pore area seen in patients with clinical nephropathy is preceded by loss of anionic charge in the glomerular basement membrane. It is likely that this loss of anionic charge is due to loss of heparan sulphate-proteoglycan.     

Glomerular filtration rate and its influential factors in type 2 diabetes mellitus at different stages of albuminuria

Objective To study the characteristics of glomerular filtration rate (GFR) and its influential factors in type 2 diabetes mellitus at different stages of albuminuria. Method GFR was measured in 630 cases of type 2 diabetes mellitus between 2002 and 2005 by plasma disappearance of 99m-techmetium-diethylene- triamine- penta-acetic acid (99mTc-DTPA). Body mass index (BMI), blood pressure, plasma glucose, HbA1c, Scr, BUN, uric acid (UA), profile of plasma lipid and 24 h-urinary albumin excretion (24 h-UAE) were also measured. All the patients were divided into 3 groups according to their 24 h-UAE: normoalbuminuric group (group A, 24 h-UAE<30 mg), microalbuminuric group (group B, 24 h-UAE from 30 mg to 300 mg) and macroalbuminuric group (group C, 24 h-UAE>300 mg). Results (1) The mean GFR was (99.8±26.3) ml/min, (96.1±31.2) ml/min and (69.7±29.8) ml/min in A, B and C groups respectively. The GFR in group C was significantly lower than that in group A and group B(P<0.01). (2) Negative correlations were found between GFR and age in all these groups (group A r= -0.533, group B r=-0.612 and group C r=-0.412，respectively, P<0.01）. (3) In each group, GFR of patients with hypertension was significantly lower than that of patients without hypertension（P<0.05）. (4) The Pearson correlation analysis adjusted by age showed that GFR was negatively correlated with 24 h-UAE in group B and group C (r=-0.283 and -0.24 respectively, all P<0.05). The multiple stepwise regression analysis showed that 24 h-UAE was the major influential factor of GFR in these 2 groups. Conclusions Measurement of both GFR performed by non-traumatic plasma disappearance of 99mTc-DTPA method and UAE provides a more precise evaluation on the the development and progression of diabetic nephropathy. Albuminuria should be controlled, especially in microalbuminuric stage.     

彩色多普勒超声对糖尿病患者肾脏大小与肾血流动力学关系的分析

目的:应用彩色多普勒超声观察对糖尿病患者肾脏大小形态、结构及各级肾动脉阻力指数(RI)的改变,分析肾脏大小与阻力指数之间的关系,以期寻找更早期的、无创性的糖尿病肾病(DN)辅助诊断方法.方法:选择120例糖尿病(DM)患者,病程＜5年为DM1组60例,病程＞5年为DM2组60例,排除合并心衰、泌尿系感染、结石、肾血管疾病及其他原因致肾脏原发、继发病变,所有患者尿常规蛋白阴性,血尿素氮、肌酐正常.同时选择120例健康者作为对照组.应用彩色多普勒超声仪检查受试者肾脏大小、各级肾动脉阻力指数.应用SPSS统计软件包进行统计处理.结果:DN2组糖尿病患者肾脏较正常对照组及DM1组者大,两者比较有统计学意义.DM2组RI较DM1组及正常组高.DM2组肾脏大小与肾各级动脉RI之间有线性关系,呈正相关(r=0.85,P＜0.05).结论:彩色多普勒超声(CDFI)检测能提示DM患者肾脏大小和肾血流动力学情况,对早期DN的诊断是有价值的.     

2型糖尿病患者合并非糖尿病性肾损害的临床病理分析

目的：了解2型糖尿病合并非糖尿病性肾损害的临床病理特点。方法：总结分析29例2型糖尿病合并非糖尿病肾损害的临床资料、病理改变及治疗反应。结果：2型糖尿病或糖尿病肾病可以合并多种非糖尿病肾损害,以各种类型的原发性及继发性肾小球疾病为主。原发性肾小球疾病常见病理类型有轻度系膜增生性肾小球肾炎、膜性肾病、IgA肾病和微小病变。这些患者具有以下不同于典型糖尿病肾病的特点：（1）糖尿病病程短于5年;（2）大量蛋白尿或肾功能不全时血压正常;（3）急性肾功能衰竭;（4）血尿明显。大部分肾病水平蛋白尿患者经糖皮质激素或糖皮质激素联合细胞毒类药物治疗后可完全缓解.结论：（1）2型糖尿病合并肾损害不等于糖尿病肾病;（2）2型糖尿病可以合并各种非糖尿病性肾损害;（3）当2型糖尿病伴肾脏受累者具有上述不符合糖尿病肾病特征时,应尽早行肾活检明确诊断;（4）在充分考虑患者 的临床特点、病理改变、严格控制血糖及血压的情况下,糖皮质激素或糖皮质激素联合细胞毒类药物治疗是安全有效的,可以改变患者的预后。     

Reversible tubular proteinuria precedes microalbuminuria and correlates with the metabolic status in diabetic children

Early tubular alterations were studied in 53 children with insulin-dependent diabetes mellitus (IDDM), 32 of whom were followed at regular 6-monthly intervals for 3 years. The urinary levels of retinol-binding protein (RBP), ₂-microglobulin and brush border antigens and brush border antigens (BBA) (determined by monoclonal enzyme immunoassay) were taken as indices of functional and cellular tubular alterations; urinary albumin was considered an early marker of glomerular alterations. All indices of tubular alterations were higher in IDDM children than in 368 normal children, while albuminuria was unchanged. Urinary levels of BBA, however, varied widely during follow-up, with 25 of the 32 IDDM patients who were followed at regular intervals having pathological values for BBA on at least one occasion, folowed by normalization. Metabolic alteration was found to be the main cause of this variability, since a high statistical correlation was found between urinary BBA and fructosamine (P<0.001) and between RBP and the stable fraction of glycosylated haemoglobin (P<0.001). The data confirm that transient tubular proteinuria occurs in diabetic children before any other marker of renal involvement such as microalbuminuria. The maintenance of good metabolic control is essential to normalize this early abnormality that can be considered a reversible sign of functional renal involvement.     

Postexercise albuminuria in children with different duration of type-1 diabetes mellitus

. About 30% of diabetic patients develop progressive renal failure. We studied albumin, IgG, and transferrin excretion during exercise in diabetic children without signs of nephropathy to investigate proteinuria under these conditions: 39 patients with insulin-dependent diabetes mellitus and 21 healthy children undertook a bicycle exercise test. Albuminuria measured by nephelometry was calculated as the albumin excretion rate (AER) and albumin-to-creatinine ratio before and after exercise. The diabetic group was divided into three subgroups according to disease duration (DI<5 years, DII 5 – 10 years, DIII>10 years). No significant difference in metabolic control (hemoglobin A_1c) was detected between the diabetic groups (median hemoglobin A_1c: DI 7.2%, DII 7.6%, DIII 8.6%). There was no increase in AER in the healthy children after exercise. Before exercise the diabetic groups had an AER similar to controls. No significant increase in albuminuria after exercise was seen in group DI. Both groups with a disease duration of more than 5 years had a significant increase in albuminuria [median before/after: DII 7.8/16.7 (P< 0.05), DIII 0/57.9 (P< 0.05) μg/min per 1.73 m²). Of these patients, 43% also had a measurable urinary excretion of IgG and transferrin, indicating structural glomerular damage. There was no correlation of albuminuria and parameters of metabolic control or renal function. We conclude that in diabetic children an exercise test unveils albuminuria in certain patients, while their AER may be normal at rest. Received September 22, 1995; received in revised form and accepted January 24, 1996