Occurrence Of Microalbuminuria Research Articles

Microalbuminuria in nondiabetic patients with nonalcoholic fatty liver disease: association with liver fibrosis

Recent evidence has suggested an association between microalbuminuria and ultrasound-diagnosed nonalcoholic fatty liver disease (NAFLD) in patients with diabetes and prediabetes. However, few data are available on the occurrence of microalbuminuria in nondiabetic subjects with histologically proven NAFLD. We thus evaluated the relationships between microalbuminuria and liver histology in a hospital-based sample of 87 adults with biopsy-proven NAFLD from Turkey. An albumin excretion rate less than 30 mg/d was considered within the reference range, whereas an albumin excretion rate from 30 to 300 mg/d was considered to indicate microalbuminuria. Compared with those without microalbuminuria (n = 73), NAFLD patients with microalbuminuria (n = 14) had significantly higher homeostasis model assessment of insulin resistance values (3.9 ± 1.3 vs 5.8 ± 3.7, P < .001). There were no differences in the prevalence of microalbuminuria in patients with definite nonalcoholic steatohepatitis, borderline nonalcoholic steatohepatitis, and simple fatty liver. In the entire study cohort, mean fibrosis scores were significantly higher in patients with microalbuminuria than in those without (1.27 ± 0.26 vs 0. 80 ± 0.11, P < .05). This difference persisted after adjustment for potential confounders. These results indicate the presence of a significant association between the severity of insulin resistance and microalbuminuria in patients with NAFLD. In addition, microalbuminuria may identify NAFLD patients with higher fibrosis scores.

Mikroalbuminurie und Albuminurie: Differenzialdiagnose und therapeutische Konsequenzen

The occurrence of microalbuminuria or albuminuria indicates a disturbance of the barrier function of endothelial cells, basement membrane or of a structural-renal disease (including diseased podocytes). The prevalence of microalbuminuria in the general population is about 8 %, however, in high risk groups, prevalence rates of 50 % and more have been observed. Its incidence is strongly associated with increased cardiovascular morbidity and mortality. Blood pressure control and the blockade of the renin-angiotensin-aldosteron-system (RAAS), respectively, is the central mechanism to reduce cardio-vascular-renal end points as well as mortality.

Dosagem de microalbuminúria em hipertensos e em pacientes portadores de doença coronariana

The normal 24-hour albumin excretion rate is of 20 mg. A persistent rate of 30 to 300 mg/day is called microalbuminuria and is related to a higher prevalence of cardiovascular disease. 1) To determine the prevalence of microalbuminuria in a group of hypertensive patients and in a group of patients with coronary artery disease; 2) To determine the relationship between the presence of microalbuminuria and hypertension, diabetes mellitus, dyslipidemia, smoking and obesity. The presence of microalbuminuria in a group of hypertensive patients (73 individuals) and in a group of patients with coronary artery disease (39 individuals) was determined and compared with a control group (43 individuals). Microalbuminuria was defined as an albumin/creatinine ratio higher than 30 and lower than 300 in a spot morning urine sample. The chi-square test and the Fishers exact test were used in the statistical analysis. Microalbuminuria was present in 9.5% of the hypertensive individuals and in 33% of the patients with coronary artery disease, and was absent in individuals of the control group. When the occurrence of microalbuminuria was analyzed according to the different clinical parameters, regardless of the group involved, a statistically significant correlation was found with age, diabetes and dyslipidemia. 1) The prevalence of microalbuminuria in hypertensive individuals is high, and is even higher in patients with coronary artery disease; 2) There is a correlation of the presence of microalbuminuria with age, diabetes and dyslipidemia.

Microalbuminuria in Thai Essential Hypertensive Patients

Essential hypertensive patients (176 males and 329 females), aged 58.0+/-11.2 years were enrolled in a cross-sectional study conducted from February to March 2006 to investigate the prevalence and risk factors for microalbuminuria in hypertensive patients attending the Outpatient Department of Siriraj Hospital, Bangkok, Thailand. Macroalbuminuria was detected in 11 (2.2%) patients and microalbuminuria in 94 (18.6%) patients. Only male aged>or=45 years or female aged>or=55 years correlated significantly with a high occurrence of microalbuminuria, while calcium channel blocker and statin users were protected against microalbuminuria. The presence of microalbuminuria was not associated with age>or=60 years, male gender, current/previous smokers, hypertension duration>or=10 years, lack of blood pressure normalization, metabolic syndrome, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and multi-drug use. Risk factor recognition for microalbuminuria will enable physicians to identify cases that should be screened for microalbuminuria.

Rimonabant as a potential new treatment for an emerging epidemic of obesity-related glomerulopathy?

Obesity and being overweight are risk factors for kidney diseases. The spectrum ranges from glomerulomegaly with or without focal or segmental glomerulosclerosis, to diabetic nephropathy, to carcinoma of the kidney and nephrolithiasis. The first sign of renal injury is microalbuminuria or frank proteinuria, in particular in the presence of hypertension. The occurrence of microalbuminuria and/or chronic kidney insufficiency (glomerular filtration rate < 60 ml/min/1.73 m2) is related to the increasing number of components of the metabolic syndrome; that is, central obesity, elevated fasting blood glucose level, hypertriglycerides, low high-density lipoprotein cholesterol level and hypertension. Obesity-associated renal disease should be prevented or retarded by weight reduction following lifestyle modification (salt restriction, hypocaloric diet, aerobic exercise) or eventually by antiobesity medication or bariatric surgery. Rimonabant, a new antiobesity medication, showed beneficial potential effect in treating clusters of metabolic syndrome, which may ultimately suggest potential benefit in treating obesity-related glomerulopathy.

Renal Disease in Obesity: The Need for Greater Attention

Excess body weight may be associated with various functional/structural lesions of the kidney. The spectrum ranges from glomerulomegaly with or without focal or segmental glomerulosclerosis, to diabetic nephropathy, to carcinoma of the kidney and nephrolithiasis. The first sign of renal injury is microalbuminuria or frank proteinuria, in particular in the presence of hypertension. The occurrence of microalbuminuria and/or chronic kidney insufficiency (glomerular filtration rate < 60 mL/min/1.73 m2) is related to the increasing number of components of the metabolic syndrome, ie, central obesity, elevated fasting blood glucose level, hypertriglycerides, low high-density lipoprotein cholesterol, and hypertension. In the long run, end-stage renal failure may develop. An increased body mass index is particularly harmful in patients with reduced renal functional mass (unilateral renal agenesis or nephrectomy) and other renal diseases (immunoglobulin A nephritis and chronic graft dysfunction after kidney transplantation). In the pathogenesis of obesity-associated glomerulopathy, hyperfiltration is of fundamental importance. The factors involved are energy intake (high protein and salt), hyperinsulinemia, and enhanced tubuloglomerular feedback because of increased sodium reabsorption. The adrenergic and renin-angiotensin-aldosterone systems as well as glucocorticoids are stimulated. In addition, several active proteins generated in the central adipose tissue, such as leptin, proinflammatory cytokines, plasminogen activator inhibitor-1, angiotensinogen, and growth factors (transforming growth factor-beta1), as well as low levels of the protective adiponectin, may contribute to renal injury. Of greatest importance is the development of hypertension and of diabetes, which are directly related to the severity of central obesity. Obesity-associated renal disease should be prevented or retarded by weight reduction following lifestyle modification (salt restriction, hypocaloric diet, aerobic exercise), or eventually by antiobesity medication or bariatric surgery. In the presence of glomerulopathy and/or hypertension, angiotensin converting enzyme inhibitors or angiotensin II type I receptor blockers are the drugs of choice to improve glomerular hyperfiltration.

Preventing microalbuminuria in patients with diabetes: rationale and design of the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study

Diabetic nephropathy has developed into a worldwide epidemic and is responsible for the majority of end-stage renal disease in most countries. Antihypertensive treatment slows the progression of the disease. In addition, blockade of the renin-angiotensin system reduces the degree of albuminuria and angiotensin II receptor blockers (ARBs) have been shown to delay the progression from microalbuminuria to overt proteinuria in patients with diabetes. However, few studies have examined whether the initial stage of diabetic nephropathy (i.e. the development of microalbuminuria) in patients with type 2 diabetes can be slowed or prevented by ARB treatment. The Randomised Olmesartan And Diabetes MicroAlbuminuria Prevention (ROADMAP) study is a placebo-controlled, multicentre, double-blind, parallel group study investigating the effect of the ARB, olmesartan medoxomil, on the incidence of microalbuminuria. A total of 4400 type 2 diabetes patients with normoalbuminuria will be randomized to treatment with 40 mg of olmesartan medoxomil once daily or placebo. Goal blood pressure will be 130/80 mmHg. The primary endpoint of the study is the occurrence of microalbuminuria. In ROADMAP, we will also assess as secondary endpoints the effects of olmesartan on fatal and non-fatal cardiovascular events in patients with diabetes. In addition, within subgroups of the ROADMAP patients, the effects of olmesartan on retinopathy and other microvascular circulations will be analysed. The study is expected to last a median of 5 years. The ROADMAP study will answer the question whether an ARB can prevent or delay the onset of microalbuminuria and whether this translates into protection against cardiovascular events and renal disease.

Renin, Prorenin and the Putative (Pro)renin Receptor

Renin is an aspartic protease that consists of 2 homologous lobes. The cleft in between contains the active site with 2 catalytic aspartic residues.1 Unlike other aspartic proteases such as pepsin or cathepsin D, renin is monospecific and only cleaves angiotensinogen, to generate angiotensin (Ang) I. Ang I is the precursor of the active end-product of the renin-angiotensin system (RAS), Ang II. Renin has also been called active renin to underline that an enzymatically inactive form of renin exists. In 1971, Lumbers found that amniotic fluid, left at low pH in the cold, acquired renin activity.2 Later, Skinner described a similar phenomenon in plasma.3 Acidification was not strictly necessary for this increase in Ang I-generating activity, because incubation at low temperature also increased renin activity, albeit to only 15% of activity after acidification. Soon it was postulated that this inactive, but activatable “big” renin (its molecular weight was 5 kDa higher than that of renin) was the biosynthetic precursor of renin. Hence, it was named prorenin. Only with the cloning of the renin gene in 1984 was prorenin definitively proved to be the precursor of renin.4 For reasons that are unknown, prorenin circulates in human plasma in excess to renin, sometimes at concentrations that are 100-times higher.5 Prorenin has also been demonstrated in plasma of cat, dog, cattle, pig, horse, sheep, rabbit, rat, and mouse. A 43-amino acid N-terminal propeptide explains the absence of enzymatic activity of prorenin. This propeptide covers the enzymatic cleft and obstructs access of angiotensinogen to the active site of renin. (Pro)renin is synthesized as a preprohormone. It contains a signal peptide that directs the protein to the endoplasmic reticulum and ultimately to the exterior of the cell. Both renin and prorenin can be fractionated into multiple species by isoelectric focusing. …

Increased plasma adiponectin concentrations are associated with microangiopathy in type 1 diabetic subjects

Insulin resistance is related to an increased risk of diabetic retinopathy and nephropathy in type 1 diabetes. Patients with insulin resistance and/or macrovascular disease have abnormally low levels of adiponectin. The aim of this study was to investigate the relationships between adiponectin and renal and retinal diabetic complications in type 1 diabetic patients. In this 6-year prospective follow-up observational study, we evaluated the severity of retinopathy at baseline and determined the incident risk of microalbuminuria in 126 normoalbuminuric patients with type 1 diabetes. Each patient was age- and sex-matched to two non-diabetic control subjects. Plasma adiponectin concentrations were significantly higher in diabetic subjects than in control subjects (p < 0.0001). The adiponectin concentration was significantly higher in patients with severe diabetic retinopathy than in those without (39.1+/-14.0 vs 29.0+/-13.0 microg/ml, p = 0.0005). The 18 patients who developed persistent microalbuminuria had higher adiponectin concentrations than the other patients (35.8+/-14.5 vs 30.6+/-13.7 microg/ml). Increased adiponectin concentrations were independently associated with the occurrence of microalbuminuria (p = 0.0158) after adjustment for baseline urinary albumin concentration (p = 0.004), sex (p = 0.0054), blood pressure (NS) and metabolic control (NS). The elevated adiponectin concentrations observed in subjects with microvascular disease may indicate an altered regulation of this adipocytokine in patients with complications associated with type 1 diabetes.

Reduction of blood pressure and microalbuminuria by intensified antihypertensive treatment in diabetic and non-diabetic hypertensive patients

To examine Blood Pressure (BP) and occurrence of Microalbuminuria (MA) in hypertensive patients with BP > 140/90 mm Hg in general practice and to examine the effect of intensified BP-treatment. A total of 1396 patients (589 with type-2 diabetes) with hypertension were included in an open multicenter GP-study. 52,8% were male, 25% were smokers and the mean BMI was 28,9. We examined systolic and diastolic BP, MA (Micral test), cholesterol and triglycerides and Hgb-A1C. The BP treatment was intensified according to the doctors own choice at visits at 1, 2, 5 and 11 months and the patients were re-examined after 11 months. Target BP was 130/85 mm Hg for D, 140/90 for ND. Mean BP was 161/91 mm Hg at inclusion (156/87 in the diabetic group (D), 164/94 in the non-diabetic group (ND)). At 11 months BP was significantly reduced to 140/82 mm Hg (138/80 in D and 141/84 in ND). 21,3% of D reached a BP < 130/85 mm Hg. In ND 38,7% reached a BP < 140/90 mm Hg. MA was found at inclusion in 31,5% of the patients (41,7% in D, 23,9% in ND). At 11 months the number of patients with MA was significantly reduced to 19,1% (25,7% in D and 14,4% in ND). Se-total cholesterol was 5,45 in D and 5,84 in ND, se-triglycerides 2,25 in D and 1,79 ND and HgbA1C 7,5 in the diabetic group with no significant changes during the 11 months. The highly significant reduction of BP (18/7 mm Hg in D and 23/10 mm Hg in ND) shows that increased attention to the patients BP and intensified antihypertensive treatment results in a much better control of hypertension. MA was often found in the patients with type-2 diabetes. The proportion of patients with MA was reduced by 16% (relatively -38% in D). It is a new finding that 23,8% of hypertensive patients without diabetes have MA, which may be the first sign of incipient nephrosclerosis. In this group it was possible to reduce the occurrence by 9,4% (relatively - 40%) by intensified antihypertensive treatment.

Microalbuminuria in type 1 diabetes: Rates, risk factors and glycemic threshold

The occurrence of microalbuminuria in type 1 diabetes is strongly predictive of renal and cardiovascular disease and is still likely to occur despite improvements in glycemic control. A better understanding of microalbuminuria is required to inform new interventions. We determined the incidence and risk factors for microalbuminuria [albumin excretion rate (AER) 20 to 200 microg/min] in the EURODIAB Prospective Complications Study. This is a seven-year follow-up (between 1988 and 1991) of 1134 normoalbuminuric men and women (aged 15 to 60) with type 1 diabetes from 31 European centers. Risk factors and AER were measured centrally. The incidence of microalbuminuria was 12.6% over 7.3 years. Independent baseline risk factors were HbA1c (7.1 vs. 6.2%, P = 0.0001) and AER (9.6 vs. 7.8 microg/min, P = 0.0001) and, independent of these, fasting triglyceride (0.99 vs. 0.88 mmol/L, P = 0.01), low-density lipoprotein cholesterol (3.5 vs. 3.2 mmol/L, P = 0.02), body mass index (24.0 vs. 23.4 kg/m2, P = 0.01), and waist to hip ratio (WHR; 0.85 vs. 0.83, P = 0.009). Triglyceride and WHR risk factors were nearly as strong as AER in predicting microalbuminuria (standardized regression effects of 1.3 for triglyceride and WHR and 1.5 for AER). Blood pressure at follow-up, but not at baseline, was also raised in those who progressed. There was no evidence of a threshold of HbA1c on microalbuminuria risk. The incidence of microalbuminuria in patients with type 1 diabetes remains high, and there is no apparent glycemic threshold for it. Markers of insulin resistance, such as triglyceride and WHR, are strong risk factors. Systemic blood pressure is not raised prior to the onset of microalbuminuria.

Increase in serum prorenin precedes onset of microalbuminuria in patients with insulin-dependent diabetes mellitus.

The renin-angiotensin system is possibly involved in the pathogenesis of diabetic nephropathy. The most striking change in renin-angiotensin system components in blood of patients with diabetic nephropathy is an increased prorenin concentration. We investigated prospectively serum concentrations of renin-angiotensin system components and the time course of prorenin increase in normoalbuminuric diabetic patients developing microalbuminuria. Patients (n = 199) with Type I (insulin-dependent) diabetes mellitus and normoalbuminuria at baseline were prospectively followed for 10 years. The prorenin concentrations and other variables possibly associated with the occurrence of microalbuminuria, were investigated by Cox-regression analysis. Of the patients 29 developed microalbuminuria. Glycated haemoglobin values were higher at baseline in these patients. Serum prorenin was similar at baseline but rose in the 29 patients before the development of microalbuminuria and was stable in patients with stable albumin excretion. Renin, angiotensinogen and angiotensin converting enzyme serum concentrations were stable in both groups. Prorenin and glycated haemoglobin were independent prognostic factors for the development of microalbuminuria. A prognostic index, based on these variables, was constructed to estimate the relative risk of developing microalbuminuria. Increase in serum prorenin precedes onset of microalbuminuria in normotensive patients with insulin-dependent diabetes mellitus. High concentrations of prorenin in combination with high values of glycated haemoglobin can be used as a predictor of development of microalbuminuria.

Microalbuminuria in diabetes.

Microalbuminuria is still the only early abnormality of the diabetic kidney that has an established prognostic value. Microalbuminuria evolves into clinical nephropathy and renal failure in a majority of cases of insulin-dependent diabetic patients, and is defined by the detection of urinary albumin excretion rates of 20-200 microg/min in timed urine collections. The occurrence of microalbuminuria at rates of 5-27 % of non-proteinuric patients and cost-benefit considerations justify the screening for microalbuminuria in diabetic outpatient clinics. Both near-normalisation of glycaemic control and treatment with ACE-inhibitors are indicated in patients with insulin-dependent diabetes to correct the progression of micro- to macroalbuminuria. Other therapeutic perspectives are being considered, but the current notion that the available therapies may not arrest the course of nephropathy at this stage suggests that earlier interventions may be required. Prevention of microalbuminuria and overt nephropathy may require a primary approach to the subset of patients with a genetic predisposition to this complication, and several studies (candidate gene or genomic scan with microsatellite probes) now address the chromosomal loci and the nature of the genes that may be involved.

Serum lipoprotein-a levels and glyco-metabolic control in insulin and non-insulin dependent diabetes mellitus

Objectives: Conflicting results for lipoprotein-a (Lp(a)) levels in diabetic patients exist in the literature. Normal, increased, and decreased values are described, and a relation to glycometabolic control is not unequivocally established. Design and Methods: In our study Lp(a) was measured in a large group of diabetics (80 patients with IDDM and 90 patients with NIDDM) in relation to glycometabolic control and the presence of microalbuminuria, retino and/or neuropathy. Long-term and short-term glycometabolic control were assessed by HbA1 and fructosamine assays, respectively. Results: Statistically significant differences between Lp(a) levels in IDDM and NIDDM and a control group of 110 healthy nondiabetics could not be established. It appeared that the level of Lp(a) in IDDM and NIDDM is independent of short-term and long-term glycometabolic control or the occurrence of microalbuminuria, neuro or retinopathy. However, poor glycometabolic control affected the number of Lp(a) levels elevated above a threshold of 0.25 g/L in IDDM. Conclusion: These results suggest that the level of Lp(a) in serum is not influenced by diabetes imellitus, glycemic control, or the occurrence of microalbuminuria, neuro or retinopathy.

Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial

The Diabetes Control and Complications Trial has demonstrated that intensive diabetes treatment delays the onset and slows the progression of diabetic complications in subjects with insulin-dependent diabetes mellitus from 13 to 39 years of age. We examined whether the effects of such treatment also occurred in the subset of young diabetic subjects (13 to 17 years of age at entry) in the Diabetes Control and Complications Trial. One hundred twenty-five adolescent subjects with insulin-dependent diabetes mellitus but with no retinopathy at baseline (primary prevention cohort) and 70 adolescent subjects with mild retinopathy (secondary intervention cohort) were randomly assigned to receive either (1) intensive therapy with an external insulin pump or at least three daily insulin injections, together with frequent daily blood-glucose monitoring, or (2) conventional therapy with one or two daily insulin injections and once-daily monitoring. Subjects were followed for a mean of 7.4 years (4 to 9 years). In the primary prevention cohort, intensive therapy decreased the risk of having retinopathy by 53% (95% confidence interval: 1% to 78%; p = 0.048) in comparison with conventional therapy. In the secondary intervention cohort, intensive therapy decreased the risk of retinopathy progression by 70% (95% confidence interval: 25% to 88%; p = 0.010) and the occurrence of microalbuminuria by 55% (95% confidence interval: 3% to 79%; p = 0.042). Motor and sensory nerve conduction velocities were faster in intensively treated subjects. The major adverse event with intensive therapy was a nearly threefold increase of severe hypoglycemia. We conclude that intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy and nephropathy when initiated in adolescent subjects; the benefits outweigh the increased risk of hypoglycemia that accompanies such treatment. (J PEDIATR 1994;125:177-88)

Influence of Concomitant Hypertension on the Occurrence of Microalbuminuria in Patients with Gout.

Influence of Concomitant Hypertension on the Occurrence of Microalbuminuria in Patients with Gout.