UMLS:C0730345 - FACTA Search

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Query: UMLS:C0730345 (microalbuminuria)
4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative structural studies in native kidneys of IDDM patients have almost all been cross sectional, and little is known regarding the dynamics of progression of structural lesions in relation to clinical progression. It has been suggested that interstitial may be more important than glomerular changes in determining functional outcome. This study evaluated renal structure in sequential biopsies from IDDM patients with established renal lesions to determine whether glomerular, arteriolar and interstitial changes progress together and in concordance with measures of renal function. Eleven long-term IDDM patients [age 29 +/- 10 years, duration 17 +/- 7 years (mean +/- SD)] had renal function studies and kidney biopsies performed at two occasions 5.6 +/- 1.6 years apart. HbA1 as well as creatinine clearance (CCr) did not change over this time; albumin excretion rate (AER) increased from 12 (6 to 280) to 19 (5 to 2462) [median (range)] mg/24 hr (P < 0.03). AER increased in the three patients with abnormal albuminuria at first observation, and two normoalbuminuric patients became microalbuminuric. Blood pressure (BP) did not change; however, the number of patients on antihypertensive therapy increased from 1 to 5. All structural parameters were abnormal at first evaluation. Mesangial fractional volume [Vv(mes/glom)] and mean glomerular volume increased and the surface density of the peripheral glomerular basement membrane (GBM) decreased, while GBM width did not change over the five years of the study. Also, arteriolar hyalinosis lesions progressed, while the fractional volume of cortical interstitium [Vv(interstitium/cortex)] and the percent of globally sclerosed glomeruli did not change. The only structural change that correlated with the increasing AER was the change in Vv(mes/glom). Changes in structural parameters, AER or CCr did not significantly correlate with baseline BP or change in BP over the five years. Although based on a small number of patients, this study suggests that at the stage of disease where renal lesions are established and where some IDDM patients are in transition to microalbuminuria or early clinical nephropathy, continuing mesangial expansion is the central variable. Interstitial changes were not occurring over this time. Progressive interstitial expansion at the later stages of diabetic nephropathy may thus be consequent to advanced diabetic glomerular injury.
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PMID:Sequential renal biopsies in insulin-dependent diabetic patients: structural factors associated with clinical progression. 858 54

Elevated serum sialic acid (SSA) predicts cardiovascular disease in the non-diabetic population and is also associated with the presence of microalbuminuria and clinical proteinuria in patients with insulin-dependent diabetes (IDDM). We have studied 121 patients with IDDM of long duration (mean duration 25.2 years) to investigate the relationship of SSA concentrations to the presence of retinopathy, nephropathy, and neuropathy. SSA levels were elevated in patients with retinopathy (0.578 +/- 0.161 gl-1, n = 98) when compared with those without retinopathy (0.468 +/- 0.145 gl-1, n = 23, p = 0.002). Patients with nephropathy (urinary albumin:creatinine ratio of > 3 mg mmol-1 in all of three early morning specimens of urine) also had raised SSA levels (0.625 +/- 0.169 gl-1, n = 30) compared with those without nephropathy (0.533 +/- 0.160 gl-1, n = 91, p = 0.006). There was a significant correlation of SSA with urinary albumin:creatinine ratio (correlation coefficient 0.33, p < 0.001). SSA levels were not related to the presence or absence of neuropathy (0.567 +/- 0.181 gl-1, n = 28, vs 0.533 +/- 0.160 gl-1, n = 93, p = 0.92, respectively). In conclusion, retinopathy and nephropathy but not neuropathy are associated with increased SSA levels in patients with IDDM. The significance of this is not yet clear but it is possible that sialic acid is involved in the pathophysiology of microvascular disease in IDDM.
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PMID:Serum sialic acid and the long-term complications of insulin-dependent diabetes mellitus. 868 44

A longitudinal study for six months was conducted to demonstrate the influence of enalapril therapy on microalbuminuria in a group of patients with IDDM without arterial hypertension. An evaluation was also considered of its possible activity on other biochemical parameters, particularly plasma lipid levels. Thirty-four patients with IDDM were selected, with a mean age of 26.1 +/- 7.2 years and a mean clinical course of 11.8 +/- 5.6 years. Arterial blood pressure (ABP) was confirmed lower than 140/85 mmHg in all cases. Patients were administered 5 mg/day of enalapril and if a decrease in microalbuminuria higher than 25% was not achieved at the end of the first month of therapy, the dose was doubled (10 mg/day). No significant differences were found in ABP and in HbA1c throughout the study period. Albumin excretion in the initial period was 125.1 +/- 79.28 mg/24 h, at one month in the follow-up 47.6 +/- 44.1 mg/24 h, at three months 23.8 +/- 18.1 mg/24 h, and at the end of the 6th month 15.33 +/- 6.9 mg/24 h, all differences being significant. Renal function parameters and Na+ and K+ measurements remained unchanged for the follow-up period. No significant changes were detected for lipid and lipoprotein values for the length of the study. We conclude that therapy with enalapril in insulin-dependent diabetic patients without hypertension has an important effect on microalbuminuria during the first month of therapy; a stabilization in the normal range was reached in the third and sixth months of follow-up. No changes in arterial blood pressure nor in renal function were observed. Plasma lipid values were in the normal range throughout the study. Therefore, treatment for microalbuminuria with the ACEI assayed was efficient, in absence of arterial hypertension and irrespective of the metabolic control obtained. Future long-term studies are needed to evaluate the possible delay in the emergence of renal insufficiency.
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PMID:[Effect of enalapril on microalbuminuria and lipid profile of normotensive type I diabetes mellitus patients]. 876 69

Recent studies have suggested that an inherited predisposition to essential hypertension may increase susceptibility to nephropathy for patients with IDDM. Essential hypertension has been linked to the angiotensinogen (AGT) gene in genetic linkage studies in American and European populations. A molecular variant (M235T), which has a functional effect, has been described with highest plasma AGT levels being associated with the TT genotype. In a case-control study, we have evaluated the role of this functional genetic marker in patients with IDDM and nephropathy and in IDDM patients without nephropathy. We studied 195 IDDM patients, of whom 95 had established diabetic nephropathy; the remaining 100 patients, who had no evidence of microalbuminuria, served as control subjects. All patients were whites born in Northern Ireland. The point mutation in the AGT gene was analyzed using restriction typing. The background frequency of the M235T variant was assessed in 80 healthy blood donors, and the TT genotype was present in 9%. This genotype occurred in 8% of control IDDM patients without nephropathy and 19% of IDDM patients with nephropathy (P = 0.025). The odds ratio for diabetic nephropathy associated with the TT genotype was 2.7 (95% CI 1.04-7.52). There was no relationship between blood pressure and AGT genotypes in the control group. We cannot exclude the possibility that the observed association in the nephropathy group is due to an association between AGT genotype and hypertension. This evidence may help to explain the predisposition to diabetic nephropathy afforded by hypertension and merits further investigation.
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PMID:A molecular variant of angiotensinogen is associated with diabetic nephropathy in IDDM. 877 23

An increased activity of Na+/H+ antiport has been reported in leukocytes and fibroblasts from insulin-dependent diabetic (IDDM) patients with nephropathy. To test whether a similar abnormality is present in fibroblasts from non-insulin-dependent diabetic (NIDDM) patients with microalbuminuria and hypertension, we examined intracellular pHi and Na+/H+ antiport activity, using the pH sensitive dye 2', 7'-bis (2-carboxyethyl-5(6)-carboxyfluorescein (BCECF), in cultured skin fibroblasts obtained from 34 NIDDM patients, divided into four groups based upon whether they had microalbuminuria or hypertension, or both: Group 1, nine NIDDM patients with microalbuminuria and hypertension. Group 2, nine NIDDM patients with hypertension and normal albumin excretion rate. Group 3, seven NIDDM patients with microalbuminuria and normal blood pressure. Group 4, nine NIDDM patients with normal blood pressure and normal albumin excretion rate. Nine normal subjects served as control group. Resting pHi was more alkaline in fibroblasts from Group 1 (7.22 +/- 0.03; p < 0.05), Group 2 (7.21 +/- 0.02; p < 0.05) and Group 3 (7.19 +/- 0.02, p = 0.17) than in Group 4 and normal subjects. This was due to higher Vmax values of Na+/H+ antiport activity in cultured fibroblasts from Group 1 (52.1 +/- 5.3 mmol H+/min; p < 0.05), Group 2 (57.7 +/- 8.3; p < 0.05) and Group 3 (60.6 +/- 7.4, p < 0.05) than those from Group 4 (31.2 +/- 3.6) or control subjects (31.3 +/- 3.5). The intracellular pH for half-maximal activation, Hill coefficient and buffering power capacity was similar in all the groups. These data suggest that in vitro phenotypic abnormalities of long-term cultured fibroblasts from NIDDM patients with microalbuminuria and/ or hypertension are likely to be, at least in part, independent of the degree of metabolic control in vivo and to be an intrinsic feature of these cells.
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PMID:Abnormal Na+/H+ antiport activity in cultured fibroblasts from NIDDM patients with hypertension and microalbuminuria. 878 68

In IDDM, microalbuminuria (urinary albumin excretion rate (AER) of 20-200 micrograms/min) is a predictor of persistent proteinuria and diabetic nephropathy. Early intervention may prevent or reduce the rate of progression of renal complications. The Micral-Test strip can be used to establish a semi-quantitative estimate of AER. We assessed the field performance of the Micral-Test strip in detecting microalbuminuria in the EUCLID study, an European wide, 18 centre study of 530 IDDM participants, aged 20 to 59 years. People with macroalbuminuria were excluded. On entry, all participants had albumin concentrations from two overnight urine collections measured by a central laboratory, and the corresponding Micral-Test performed on the two collections locally. a cut off of > or = mg/l albumin from the first Micral-Test, to detect a centrally measured albumin concentration > or = 20 mg/l, yielded 29 (5.8%) false negative results and 58 (11.6%) false positive results (sensitivity 70%, specificity 87%). The mean AER, from two collections, was compared with the corresponding 'pooled' Micral-Test results (mean of the two readings). Receiver Operating Characteristic (ROC) curves were used to assess if there was a suitable 'pooled' Micral-Test result for screening microalbuminuria. A 'pooled' Micral-Test result (> or = 15 mg/l) was used to detect mean AER > or = 20 micrograms/min (sensitivity 78%, specificity 77%). This 'pooled cut-off' had already been used for screening on to the study and led to an over-estimate (154 vs. 77) of the true number of microalbuminuric participants on the study. In conclusion, our findings suggest that the Micral-Test strip is not an effective screening tool for microalbuminuria, using the 'pooled' result from two measurements did not improve the sensitivity of the test.
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PMID:The use of the Micral-Test strip to identify the presence of microalbuminuria in people with insulin dependent diabetes mellitus (IDDM) participating in the EUCLID study. 879 7

The objective of this study was to determine the prevalence of stages of diabetic nephropathy, defined by the albumin/creatinine ratio (AC ratio) in repeated measurements in random urine samples. Over a 30-month interval, 1613 patients with Type I diabetes (IDDM) (aged 15 to 44 yr, IDDM duration 1 to 39 yr), and 218 healthy control subjects provided multiple urine specimens. AC ratios measured in urine samples taken 5 months apart were highly reproducible (Spearman r = 0.83). A criterion for the boundary between normoalbuminuria and microalbuminuria was obtained by searching for a cutpoint that optimized agreement between serial specimens on individuals. The result was lower in men than women: 17 as compared with 25 micrograms/mg. These two values corresponded to the 95th percentiles of the respective distributions of the AC ratio in healthy control subjects. Also these sex-specific cutpoints, when converted to albumin excretion rates, became almost equal: 30 and 31 micrograms/min. Microalbuminuria appeared early in the course of IDDM (6% of those with only 1 to 3 yr of diabetes) and then increased rapidly during two intervals, the first and third decades, before leveling off at 52%. By that time the cumulative risk of overt proteinuria had risen to 27%. Determinations of the AC ratio in random urine samples are easily obtained and are reliable indices of elevated urinary albumin excretion (microalbuminuria) in IDDM. The pattern of occurrence of microalbuminuria according to duration of IDDM suggests that there may be two subsets of diabetic nephropathy, one appearing early and the other late. Patients with microalbuminuria and 25 yr of postpubertal IDDM have low risk of progression to advanced diabetic nephropathy.
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PMID:Effect of duration of type I diabetes on the prevalence of stages of diabetic nephropathy defined by urinary albumin/creatinine ratio. 879 3

Insulin-dependent diabetic (IDDM) subjects with microalbuminuria have an increased long-term risk of overt cardiovascular disease; however, the early exposure to cardiovascular risk factors may increase their predisposition to current silent myocardial ischaemia. The frequency of silent myocardial ischaemia detected by stress echocardiography and electrocardiography was significantly greater in 32 asymptomatic IDDM patients with microalbuminuria compared to 32 normoalbuminuric IDDM patients (25% [n = 8] vs 6.3% [n = 2]; p = 0.03, odds ratio [95% CI] 6.3 [1.2, 37.8]). Elective coronary artery bypass grafting was required in 1 patient with microalbuminuria and silent myocardial disease. Microalbuminuria and poorer autonomic function were independently associated with silent myocardial ischaemia in multivariate analysis (p = 0.03 and p = 0.02, respectively). Screening for silent myocardial ischaemia using these non-invasive tests may be warranted in microalbuminuric IDDM which patients could be of considerable clinical importance.
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PMID:Microalbuminuria as a marker of silent myocardial ischaemia in IDDM patients. 881 11

The Diabetes Control and Complications Trial (DCCT) demonstrated a reduction in the development and progression of the long-term complications of IDDM with intensive therapy aimed at achieving glycemic control as close to the nondiabetic range as possible. The DCCT subsequently showed that the total lifetime exposure to glycemia was the principal determinant of the risk of retinopathy and that there was a continuous nonlinear relationship between this risk and the mean level of HbA1c (DCCT Research Group, Diabetes 44:968-993, 1995). In contrast, other authors, based on a retrospective study (Krolewski et al., N Engl J Med 332:1251-1255, 1995), have suggested that a glycemic threshold for microabuminuria and for retinopathy exists at an HbA1c level of approximately 8%, below which there is no further appreciable reduction in risk. In this perspective, we examine whether the DCCT data demonstrate such a glycemic threshold for the development of retinopathy, nephropathy, or neuropathy. In the DCCT, 1,441 patients with IDDM were randomly assigned to intensive (n = 711) or conventional (n = 730) therapy and followed for a mean of 6.5 years. Retinopathy was assessed every 6 months by stereoscopic fundus photography; albumin excretion was measured annually in a 4-h collection; and neuropathy was assessed with a standardized protocol performed at baseline and at 5 years. Glycosylated hemoglobin was measured quarterly. Episodes of severe hypoglycemia were ascertained using standardized procedures. The risks (hazard rates) of retinopathy progression and of developing microalbuminuria and neuropathy were found to be continuous but nonlinear over the entire range of glycosylated hemoglobin values in the intensive, conventional, and combined treatment groups. These nonlinear relationships describe a constant relative risk gradient in which proportional reductions in HbA1c are accompanied by proportional reductions in the risk of complications. Although the magnitude of the absolute risk reduction declines with continuing proportional reductions in HbA1c, there are still meaningful further reductions in risk as the HbA1c is reduced toward the normal range. When the instantaneous risks for different complications associated with different HbA1c values are compounded over time, there are substantial differences in the cumulative incidence of patients experiencing a complication for patients with HbA1c values of 6 vs. 7 vs. 8% or higher. In fact, no HbA1c threshold could be identified, short of normal glycemia, below which there was no risk of the development or progression of these complications. Furthermore, as the HbA1c was reduced proportionately, the proportional rate of decline in the relative risk for each of these complications was similar for HbA1c levels < or = 8.0% and for levels > 8%. In contrast, although the absolute risk of severe hypoglycemia in the intensive treatment group increased as the HbA1c decreased, the relative risk gradients were significantly less for HbA1c levels < or = 8.0% than for levels > 8%. These extensive prospective DCCT data do not support the conjecture that a glycemic threshold for the development of complications exists at an HbA1c of 8% or that an HbA1c goal of 8% is maximally beneficial. In the DCCT, as HbA1c was reduced below 8% there were continuing relative reductions in the risk of complications, whereas there was a slower rate of increase in the risk of hypoglycemia. Therefore, the DCCT continues to recommend implementation of intensive therapy with the goal of achieving normal glycemia as early as possible in as many IDDM patients as is safely possible.
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PMID:The absence of a glycemic threshold for the development of long-term complications: the perspective of the Diabetes Control and Complications Trial. 882 62

Nephropathy is a serious microvascular complication of diabetes mellitus which is preceded by a period of microalbuminura. Increased loss of proteoglycan (PG) from glomerular basement (GBM) has been postulated to alter glomerular charge selectivity which contributes to urinary loss of albumin. In this study we measured the excretion of urinary glycosaminoglycans (GAG), the degradation products of PG, in 82 non-insulin-dependent (NIDDM) (Type 2) diabetic and 34 non-diabetic subjects. We found that diabetic subjects had a significantly higher GAG urinary excretion rate compared to non-diabetic subjects (12.54 +/- 5.67 vs 8.80 +/- 3.99 micrograms glucuronic acid min-1, p = 0.0001). Categorizing for albuminuric status shows that the diabetic normo-, micro- and macroalbuminuric groups have a higher GAG excretion rate than non-diabetic subjects. Heparan sulphate (HS) GAG urinary excretion was measured in 25 samples from diabetic subjects and 18 non-diabetic subjects. Diabetic subjects excreted more HS GAG than controls both as a rate or as a percentage of total GAG (3.70 +/- 1.94 vs 2.38 +/- 1.48 micrograms glucosamine min-1, p = 0.02; 31.6% +/- 12.5 vs 23.1% +/- 10.4, p = 0.02). Categorizing for albuminuric status shows that micro- and macro-albuminuric groups have a significantly higher HS GAG excretion rate than non-diabetic subjects. We conclude that, as in IDDM, excretion of GAG and HS GAG is higher in NIDDM and may precede the development of microalbuminuria.
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PMID:Urinary glycosaminoglycan excretion in NIDDM subjects: its relationship to albuminura. 886 53

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