Apolipoprotein (a) levels and phenotypes in NIDDM patients with microalbuminuria and albuminuria

This study was conducted to determine whether circulating levelsof lipoprotein (a), an independent risk factor of macrovasculardisease, are increased in non-insulin-dependent diabetes mellitus(NIDDM) patients with microalbuminuria who have an increasedrisk of cardiovascular mortality. Apolipoprotein (a) [apo(a)levels and phenotypes, and other circulating lipid levels weredetermined in 227 Chinese NIDDM patients with varying stagesof diabetic nephropathy. None was on lipid-lowering therapy.Apo(a) levels in normoalbuminuric (geometric mean 166 U/L; 95%confidence intervals 137, 200; n = 105) and microalbuminuricpatients (162; 132, 209; n = 77) were similar to values in controls(166; 143, 193, n = 168). Albuminuric patients, however, hadhigher apo(a) levels than both normoalbuminuric patients andcontrols (242; 184, 317; n = 45; p <0.05). The overall sizerange of the apo(a) phenotypes and the frequency of having atleast one small isoform, i.e. <700 kDa, were similar amongthe four groups of subjects. A positive correlation was foundbetween log apo(a) and log plasma creatinine levels (p<0.01).Compared to normoalbuminuric patients, both microalbuminuricand albuminuric patients were older (p<0.01) and had higherHbA1c (p<0.01), greater BMI (p<0.05) and longer diseaseduration (p< 0.05) compared to normoalbuminuric patients.Nevertheless, using multiple linear regression analysis, itwas found that the presence of nephropathy conferred an independentinfluence on increasing total cholesterol (p<0.001), triglyceride(p< 0.001) and apoB (p<0.01), and decreasing HDL cholesterol(p<0.05) levels even when only the normoalbuminuric and microalbuminuricgroups were analysed. The prevalence of macrovascular diseasewas significantly increased in microalbuminuric and albuminuricpatients (45.1 and 48.7% respectively vs 20.2% in normoalbuminuricpatients, p<0.01). It is concluded that circulating apo(a)levels were not increased in Chinese NIDDM patients with microalbuminuria.However, atherogenic changes in other lipid and lipoproteinlevels may contribute to an increased risk of macrovasculardisease in these patients.     

Urinary protein excretion and renal function in young people with diabetes mellitus.

To detect early renal involvement in young diabetic patients (IDDM), urinary protein excretion and renal function were examined in 110 patients aged 5.9-25.0 years. Clearances of inulin and PAH were determined as well as albumin (Alb), IgG, N-acetyl-beta-D-glucosaminidase (NAG) and creatinine (Cr) excretion rates (UV). The patients were grouped according to IDDM duration (2- less than 5, 5-10 and greater than 10 years) and albumin excretion rate (non-albuminuria less than 20, microalbuminuria 20-200, and albuminuria greater than 200 micrograms/min per 1.73 m2). Four patients had overt albuminuria, 17 microalbuminuria (equally distributed among the duration groups). Grouped according to albumin excretion rate, the mean GFR was increased in those without albuminuria but 'normalized' in patients with microalbuminuria/albuminuria. Grouped according to albumin excretion rate and the duration of the disease, the non-albuminuric patients with IDDM for greater than 10 years had a lower GFR than those with a shorter duration of IDDM. The patients with microalbuminuria/albuminuria and IDDM for less than 5 years had a reduced GFR. Patients with increased NAG excretion rate had lower Na excretion rate, lower fractional Na excretion and greater creatinine excretion than those with normal NAG excretion. Albumin excretion correlated with IgG excretion, but also with NAG excretion. Our results suggest that early albuminuria in IDDM is of both glomerular and tubular origin. The hyperfiltration declines with increasing albumin excretion but also with the duration of the disease.     

The DD genotype of the ACE gene polymorphism is associated with progression of diabetic nephropathy to end stage renal failure in IDDM

BACKGROUND: The insertion-deletion (I/D) polymorphism of the angiotensin converting enzyme gene is a diallelic polymorphism that constitutes a genetic influence on the progression of renal diseases such as IgA nephropathy. Patients with the DD genotype have an accelerated progression towards end stage renal failure in these diseases. The role of the I/D polymorphism in the pathogenesis of diabetic nephropathy in IDDM is unresolved. PATIENTS AND METHODS: We therefore set out to study the contribution of the I/D polymorphism in 79 patients (age 39.5 +/- 7.6 years (mean +/- SD) with end stage renal failure due to diabetic nephropathy, who were recipients of a combined kidney-pancreas transplantation (n = 60), or who were on the waiting list for such a procedure (n = 19). The control series consisted of 82 patients (age 39.5 +/- 9.6 years) without microalbuminuria after fifteen years of IDDM. RESULTS: The ACE genotype distribution in patients was not in accordance with the Hardy-Weinberg equilibrium due to a significant overrepresentation of the DD genotype (X2 = 8.9, p = 0.01). This resulted in a significant increase of the D-allele frequency in the cases compared to controls (X2 = 4.9, p = 0.03). The presence of one D-allele did not increase the risk of end stage renal failure (odds ratio ID/II = 1.0, 95% CI 0.4-2.2). The presence of the DD genotype increased the risk of end stage renal failure twofold compared to the other genotypes (odds ratio 2.1, 95% CI 1.1-4.0). The risk estimate seemed slightly higher in patients with good metabolic control (odds ratio 2.6, 95% CI 1.0-7.1), than in patients with poor control (odds ratio 1.6, 95% CI 0.59-4.3). CONCLUSION: It is concluded that the risk of end-stage renal failure in patients with IDDM is twofold increased in patients with the DD genotype as compared to patients with other genotypes.     

Clinical correlates with microalbuminuria in non-insulin dependent diabetes: Preliminary results of the appropriate blood pressure control in diabetes trial

Summary: Clinical correlates associated with urinary albumin excretion (UAE) in non-insulin dependent diabetes (NIDDM) are less well known than in insulin dependent diabetes (IDDM). We therefore performed a cross sectional study examining the relationships of clinical risk factors and diabetic complications with UAE in 950 NIDDM patients. the UAE status was classified into the following categories: (i) no albuminuria (<20 μmg/min), (ii) microalbuminuria (20–200 μg/min); and (iii) overt albuminuria (>200 μg/min). Univariate and miltivariate analyses were initially performed evaluating the associations between clinical risk factors and UAE. Univariate and multivariate analyses were then performed examining the relationships between UAE and the diabetic complications (retinopathy, neuropathy and cardiovascular disease). Using multivariate logistic regression analyses controlling for diabetes duration, glycosylated haemoglobin, gender and race, the most significant predictors of microalbuminuria and overt albuminuria were systolic hypertension, increased body mass index (BMI), decreased high-density lipoprotein (HDL) cholesterol, insulin use and smoking pack years. Univariate and multivariate analyses evaluating the associations between UAE and diabetic complications revealed that UAE was a strong predictor of retinopathy (odds ratio [OR]=1.31:95% confidence interval [CI]=1.05,1.66), neuropathy (OR=1.47; CI=1.19,19.83), and cardiovascular diseases (OR=1.28; CI=1.05,1.52). Thus, in the present study increases in UAE were associated with retinopathy, neuropathy and cardiovascular disease. Urinary albumin excretion may therefore be a marker of diffuse vascular disease in NIDDM. Aggressive treatment of smoking, cholesterol and hypertension may not only diminish UAE but may also play a significant role in decreasing the other NIDDM vascular complications.     

Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria.

BACKGROUND: Intervention studies in microalbuminuric type 2 diabetic patients have demonstrated that it is possible to avoid progression to overt diabetic nephropathy and even to achieve regression to normoalbuminuria. However, the long-term impact of stabilization/regression in albuminuria on decline in glomerular filtration rate (GFR) has not been established. METHODS: 151 patients with type 2 diabetes and microalbuminuria at baseline in whom GFR was measured at least three times during 7.8 years of follow-up were divided into three groups according to the level of albuminuria during follow-up. Overt nephropathy was diagnosed as a urinary albumin excretion rate (AER) >300 mg/24 h and remission to normoalbuminuria was defined as an AER <30 mg/24 h at the last examination. RESULTS: During follow-up, 46 patients achieved remission to normoalbuminuria, 58 remained microalbuminuric and 47 patients progressed to overt nephropathy. The mean (+/- SE) yearly decline in GFR was lowest (2.3+/-0.4 ml/min/year) in patients who obtained remission, in comparison with patients remaining microalbuminuric, in whom the decline was 3.7+/-0.4 ml/min/year, and patients progressing to overt nephropathy, who had a decline in GFR of 5.4+/-0.5 ml/min/year (ANOVA, P<0.001). Start of antihypertensive treatment during follow-up was strongly associated with remission to normoalbuminuria [odds ratio: 2.32; 95% confidence interval (CI): 1.09-4.93] whereas a decrease in HbA(1c) by 1% increased the probability for remission (odds ratio: 1.48; 95% CI: 1.11-1.97). CONCLUSIONS: Remission to normoalbuminuria was associated with a decreased GFR decline during 7.8 years of follow-up in type 2 diabetic patients with microalbuminuria. Antihypertensive therapy and improved glycaemic control were independent predictors for remission.     

Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy.

BACKGROUND: Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes. Approximately 30% of type 1 patients with diabetic nephropathy (DN) have albuminuria >1 g/day, and blood pressure >135 and/or >85 mmHg despite antihypertensive therapy with recommended doses of ACE inhibitor (ACEI) and diuretics. We tested the effect of dual blockade of the renin-angiotensin system (RAS) in these patients. METHODS: We performed a randomised double blind crossover trial with 2 months treatment with Irbesartan 300 mg o.d. and placebo added on top of previous antihypertensive treatment. We included 21 type 1 patients with DN responding insufficiently to ACEI and diuretics, as defined above. At the end of each treatment period, albuminuria, 24-h blood pressure and glomerular filtration rate (GFR) were measured. RESULTS: Addition of 300 mg Irbesartan to the patients' usual antihypertensive therapy induced a mean reduction in albuminuria of 37% (95% CI 20-49, P<0.001); from 1574 mg/24 h (95% CI 1162-2132) to 996 mg/24 h (95% CI 699-1419), a reduction in 24-h blood pressure of 8 mmHg systolic (95% CI -2 to 18) and 5 mmHg diastolic (95% CI 1-9) (P=0.11 and 0.01, respectively) (from placebo, mean (SE) 146 (4)/80 (2) mmHg). GFR remained unchanged. Serum potassium increased (mean 4.3 to 4.6 mmol/l, P=0.02). Intervention to reduce serum potassium was needed in two patients with GFR <35 ml/min/1.73 m(2). Otherwise the dual blockade with Irbesartan was safe and well tolerated. CONCLUSIONS: Dual blockade of the RAS may offer additional renal and cardiovascular protection in type 1 patients with DN responding insufficiently to conventional antihypertensive therapy, including recommended doses of ACEI and diuretics.     

Low circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) are closely associated with the presence of macrovascular disease and hypertension in type 2 diabetes

The IGF system is increasingly implicated in the development of cardiovascular disease. The effects of circulating IGFs on the vasculature are largely modulated by IGFBPs, which control their access to cell-surface IGF receptors. IGFBP-1 has been proposed as the acute regulator of IGF bioavailability because of its metabolic regulation by glucoregulatory hormones. Posttranslational phosphorylation of IGFBP-1 significantly increases its affinity for IGF-I and therefore represents a further mechanism for controlling IGF bioavailability. We have therefore examined the IGF system and IGFBP-1 phosphorylation status, using specifically developed immunoassays, in a cohort of 160 extensively characterized type 2 diabetic subjects on two occasions 12 months apart. Total IGFBP-1 (tIGFBP-1), which is predominantly highly phosphorylated, was significantly lower in subjects with known macrovascular disease (geometric mean [95% CI], 48.7 microg/l [33.7-63.6]) than in patients with no vascular pathology (80.0 microg/l [52.2-107]; F = 5.4, P = 0.01). A similar relationship was found for highly phosphorylated IGFBP-1 (hpIGFBP-1) concentration (known macrovascular disease, 45.1 microg/l [35.1-55.2]; no macrovascular disease, 75.8 microg/l [56.2-95.3]; F = 4.8, P = 0.01). Logistic regression showed that for every decrease of 2.73 microg/l in IGFBP-1 concentration, there was a 43% increase in the odds of a subject having macrovascular disease (odds ratio 0.57 [95% CI 0.40-0.83]; P = 0.001). hpIGFBP-1 correlated negatively with systolic blood pressure (rho = -0.30, P < 0.01), diastolic blood pressure (rho = -0.45, P < 0.001), and mean arterial pressure (MAP) (rho = -0.41, P < 0.001). Linear regression modeling showed that 40% of the variance in tIGFBP-1 was accounted for by MAP, triglycerides, and nonesterified fatty acids. In contrast, levels of nonphosphorylated and lesser-phosphorylated IGFBP-1 (lpIGFBP-1) were unrelated to macrovascular disease or hypertension but did correlate positively with fasting glucose concentration (rho = 0.350, P < 0.01). tIGFBP-1 concentrations were higher in subjects treated with insulin alone (n = 29) than for any other group. This effect persisted after adjustment of tIGFBP-1 levels for BMI, C-peptide, age, and sex (F = 6.5, P < 0.001, rho = - 0.46). Such an effect was not apparent for lpIGFBP-1. We conclude that low circulating levels of hpIGFBP-1 are closely correlated with macrovascular disease and hypertension in type 2 diabetes, whereas lpIGFBP-1 isoforms are associated with glycemic control, suggesting a dual role for IGFBP-1 in the regulation of IGF actions in type 2 diabetes. Our data suggest that high circulating concentrations of highly phosphorylated IGFBP-1 may protect against the development of hypertension and cardiovascular disease by reducing the mitogenic potential of IGFs on the vasculature.     

Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000

The incidence of kidney failure treatment in the United States increased 57% from 1991 to 2000. Chronic kidney disease (CKD) prevalence was 11% among U.S. adults surveyed in 1988 to 1994. The objective of this study was to estimate awareness of CKD in the U.S. population during 1999 to 2000 and to determine whether the prevalence of CKD in the United States increased compared with 1988 to 1994. Analysis was conducted of nationally representative samples of noninstitutionalized adults, aged 20 yr and older, in two National Health and Nutrition Examination Surveys conducted in 1988 to 1994 (n = 15,488) and 1999 to 2000 (n = 4101) for prevalence +/- SE. Awareness of CKD is self-reported. Kidney function (GFR), kidney damage (microalbuminuria or greater), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine, spot urine albumin to creatinine ratio (ACR), age, gender, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation. Self-reported awareness of weak or failing kidneys in 1999 to 2000 was strongly associated with decreased kidney function and albuminuria but was low even in the presence of both conditions. Only 24.3 +/- 6.4% of patients at GFR 15 to 59 ml/min per 1.73 m(2) and albuminuria were aware of CKD compared with 1.1 +/- 0.3% at GFR of 90 ml/min per 1.73 m(2) or greater and no microalbuminuria. At moderately decreased kidney function (GFR 30 to 59 ml/min per 1.73 m(2)), awareness was much lower among women than men (2.9 +/- 1.6 versus 17.9 +/- 5.9%; P = 0.008). The prevalence of moderately or severely decreased kidney function (GFR 15 to 59 ml/min per 1.73 m(2)) remained stable over the past decade (4.4 +/- 0.3% in 1988 to 1994 and 3.8 +/- 0.4% in 1999 to 2000; P = 0.23). At the same time, the prevalence of albuminuria (ACR >/= 30 mg/g) in single spot urine increased from 8.2 +/- 0.4% to 10.1 +/- 0.7% (P = 0.01). Overall CKD prevalence was similar in both surveys (9% using ACR > 30 mg/g for persistent microalbuminuria; 11% in 1988 to 1994 and 12% in 1999 to 2000 using gender-specific ACR cutoffs). Despite a high prevalence, CKD awareness in the U.S. population is low. In contrast to the dramatic increase in treated kidney failure, overall CKD prevalence in the U.S. population has been relatively stable.     

Development of renal disease in people at high cardiovascular risk: results of the HOPE randomized study

In people with diabetes, renal disease tends to progress from microalbuminuria to clinical proteinuria to renal insufficiency. Little evidence has been published for the nondiabetic population. This study retrospectively analyzed changes of proteinuria over 4.5 yr in the HOPE (Heart Outcomes and Prevention Evaluation) study, which compared ramipril's effects to placebo in 9297 participants, including 3577 with diabetes and 1956 with microalbuminuria. This report is restricted to 7674 participants with albuminuria data at baseline and at follow-up. Inclusion criteria were known vascular disease or diabetes plus one other cardiovascular risk factor, exclusion criteria included heart failure or known impaired left ventricular function, dipstick-positive proteinuria (>1+), and serum creatinine >2.3 mg/dl (200 microM). Baseline microalbuminuria predicted subsequent clinical proteinuria for the study participants overall (adjusted odds ratio [OR], 17.5; 95% confidence interval [CI], 12.6 to 24.4), in participants without diabetes (OR, 16.7; 95% CI, 8.6 to 32.4), and in participants with diabetes (OR, 18.2; 95% CI, 12.4 to 26.7). Any progression of albuminuria (defined as new microalbuminuria or new clinical proteinuria) occurred in 1859 participants; 1542 developed new microalbuminuria, and 317 participants developed clinical proteinuria. Ramipril reduced the risk for any progression (OR, 0.87; 95% CI, 0.78 to 0.97; P = 0.0146). People without and with diabetes who are at high risk for cardiovascular disease are also at risk for a progressive rise in albuminuria. Microalbuminuria itself predicts clinical proteinuria in nondiabetic and in diabetic people. Ramipril prevents or delays the progression of albuminuria.     

Uric acid, microalbuminuria and cardiovascular events in high-risk patients

BACKGROUND: Elevated levels of serum uric acid and albuminuria are associated with cardiovascular disease, but the relationships have not consistently been demonstrated to be independent of hypertension, other risk factors, or each other. The purpose of this study was to evaluate people at high risk for cardiovascular disease for the influence of uric acid and microalbuminuria on cardiovascular events. METHODS: Consecutive consenting patients undergoing elective angiography (n = 316) had coronary artery disease, risk factors, renal function and diuretic use assessed at baseline. Cardiovascular mortality and major clinical events (myocardial infarction, stroke, amputation, and kidney failure) were ascertained over 5 years. RESULTS: Cardiovascular events occurred in 10% of the patients. Significant correlates (p < 0.05) of cardiovascular events with baseline measures included uric acid > or =5.2 mg/dl, total cholesterol > or =200 mg/dl, severe angiographic coronary artery disease, loop diuretic therapy, and diagnosis of hypertension. A stepwise Cox modeling procedure identified uric acid (p = 0.040), the interaction of hypertension and uric acid (p = 0.029), the interaction of total cholesterol and severe coronary artery disease (p = 0.001) and loop diuretic therapy (p = 0.009) as significant independent predictors of events. Although microalbuminuria was not retained in the final multivariate model, it was associated with poorer cardiovascular disease outcomes. The mean event-free survival for albumin-to-creatinine >30 mg/g was 51 months and for albumin-to-creatinine <30 mg/g the mean was 57 months (p = 0.021). CONCLUSIONS: Uric acid > or =5.2 mg/dl independently imparted a 3.5-fold increased risk (OR 3.5, 95% CI 1.0-11.9) for cardiovascular death and major clinical events over a 5-year period. Uric acid may be a contributing factor to the progression of atherosclerosis and its complications.     

The prevalence and risk factors of microalbuminuria in normoglycemic, normotensive adults

AIMS: Microalbuminuria is a risk factor for renal and cardiovascular disease. Recent studies have established this important relationship in patients with diabetes or hypertension, yet few studies have shown this relationship in healthy subjects. The purpose of this study is to examine the prevalence and the risk factors of microalbuminuria in normoglycemic, normotensive adults. SUBJECTS AND METHODS: We examined the prevalence of microalbuminuria in the adults who voluntarily took part in a health examination program. As a cross-sectional study, we examined the risk factors of microalbuminuria in 4883 normoglycemic, normotensive healthy adults. RESULTS: The prevalence of microalbuminuria was 2.8% in the normoglycemic, normotensive group (n=4883), 10.1% in the hypertensive group (n=1250), 16.0% in the diabetes group (n=455) and 5.4% in the total subjects (n=6588). The systolic blood pressure, high sensitive C-reactive protein (hsCRP) and insulin resistance were independently related with microalbuminuria on the logistic regression analysis. The odds ratio of microalbuminuria were 1.04 (1.02 - 1.05, 95% CI), 1.29 (1.10 - 1.51, 95% CI), and 1.83 (1.15 - 2.92, 95% CI), respectively. CONCLUSIONS: These finding suggest that the systolic blood pressure, hsCRP and insulin resistance are the independent risk factors for microalbuminuria in normoglycemic, normotensive adults.     

Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74

Not all patients with type 2 diabetes develop renal dysfunction. Identifying those at risk is problematic because even microalbuminuria, often used clinically as an indicator of future renal dysfunction, does not always precede worsening renal function. We sought to identify clinical risk factors at diagnosis of type 2 diabetes associated with later development of renal dysfunction. Of 5,102 U.K. Prospective Diabetes Study (UKPDS) participants, prospective analyses were undertaken in those without albuminuria (n = 4,031) or with normal plasma creatinine (n=5,032) at diagnosis. Stepwise proportional hazards multivariate regression was used to assess association of putative baseline risk factors with subsequent development of albuminuria (microalbuminuria or macroalbuminuria) or renal impairment (Cockcroft-Gault estimated creatinine clearance <60 ml/min or doubling of plasma creatinine). Over a median of 15 years of follow-up 1,544 (38%) of 4,031 patients developed albuminuria and 1,449 (29%) of 5,032 developed renal impairment. Of 4,006 patients with the requisite data for both outcomes, 1,534 (38%) developed albuminuria and 1,132 (28%) developed renal impairment. Of the latter, 575 (51%) did not have preceding albuminuria. Development of albuminuria or renal impairment was independently associated with increased baseline systolic blood pressure, urinary albumin, plasma creatinine, and Indian-Asian ethnicity. Additional independent risk factors for albuminuria were male sex, increased waist circumference, plasma triglycerides, LDL cholesterol, HbA(1c) (A1C), increased white cell count, ever having smoked, and previous retinopathy. Additional independent risk factors for renal impairment were female sex, decreased waist circumference, age, increased insulin sensitivity, and previous sensory neuropathy. Over a median of 15 years from diagnosis of type 2 diabetes, nearly 40% of UKPDS patients developed albuminuria and nearly 30% developed renal impairment. Distinct sets of risk factors are associated with the development of these two outcomes, consistent with the concept that they are not linked inexorably in type 2 diabetes.     

Serum uric acid level is positively related to albuminuria in type 2 diabetic patients

Objective To investigate association between serum uric acid (SUA), albuminuria and glomerular filtration rates (eGFR) in type 2 diabetic patients. Methods A total of 220 patients were enrolled in this cross-sectional study. According to urinary albumin excretion rates, patients were divided into 3 groups: normoalbuminuria (NAU) group, microalbuminuria (MAU) group, and macroalbumnuria group (MAAU). The first two groups were subdivided at SUA＞420 μmol/L (＞357 μmol/L, female) into normouricemia group and hyperuricemia group, at eGFR＞90 ml/min into high and low renal function groups. General information, blood biochemical results were collected to analyze the association between serum uric acid, eGFR, UAER and urine albumin quantification among different groups. Results The difference of SBP, duration of diabetes (DD), Scr, SUA and eGFR between every two groups were significant (P＜0.05). SBP, DD, Scr and SUA were highest in subjects with macroalbumnuria, second in microalbuminuria group, and lowest in normoalbuminuria group, while eGFR was lowest in macroalbumnuria group and highest in normoalbuminuria group. Prevalence of hyperuricemia in macroalbumnuria group (56.9%) and microalbuminuria group (51.2%) were also significantly higher than that in normoalbuminuria group (17.5%) (all P＜0.01). The difference of UAER in the subgroups of normouricemia and hyperuricemia was more significant in microalbuminuria group than in normoalbuminuria group. eGFR was significantly lower in hyperuricemia subgroups (P＜0.01). Age and SUA were significantlg higher in subjects with low renal function compared with high eGFR (P＜0.05). Linear regression analysis indicated SUA was negatively correlated with eGFR after adjusted age, DD and UAER (β＝-0.430, P＜0.01). Binary logistic regression analysis found that increased age, DD and SUA were risk factors of microalbuminuria [β＝1.092, 95％CI(1.025, 1.163), P＜0.01; β＝1.005, 95%CI(1.001, 1.009), P＜0.05; β＝1.407, 95％CI(1.052, 1.881), P＜0.05)] andSUA, age were risk factors of early renal function decline [β＝1.015, 95％CI(1.00, 1.023), P＜0.01; β＝1.098, 95％CI(1.006, 1.199), P＜0.05]. Conclusion SUA is independently associated with albumnuria and renal function decline in type 2 DM patients.     

Association of cigarette smoking with albuminuria in the United States: the third National Health and Nutrition Examination Survey

BACKGROUND: The association of cigarette smoking with albuminuria has been reported but not examined in a representative U.S. population. No study has evaluated the association between serum cotinine (a biological marker for tobacco exposure) and kidney damage. METHODS: A cross-sectional analysis was conducted among 15,719 adult participants of the third National Health and Nutrition Examination Survey to assess the association between smoking exposure and kidney damage. Smoking was assessed by self-reported lifetime cigarette use and serum cotinine. Kidney damage was assessed by urine albumin-to-creatinine ratio (ACR), with albuminuria defined as ACR of > or =17 microg/mg in males and > or =25 microg/mg in females. RESULTS: The analysis included 13,121 with normal albumin (mean ACR 6.3 microg/mg) and 2,414 with albuminuria (mean ACR 143 microg/mg); hypertension was prevalent in 27% and 59%, respectively. Former smoking was similar between groups (21%), while current smoking was more common in persons with albuminuria (26%) compared to normal ACR (21%). Adjusted for other risk factors, among hypertensives, current smokers were 1.85 (95% CI: 1.29, 2.64) times more likely to have albuminuria than never smokers. Current smokers with a > or =40 pack-year history were at highest risk for albuminuria. Among non-smoking hypertensives, those exposed to passive smoke (highest versus lowest quartile of serum cotinine) were 1.41 (95% CI: 1.04, 1.90) times more likely to have albuminuria. Former smoking with cessation of > or =1 year among hypertensives was not associated with albuminuria. Among non-hypertensives, smoking and albuminuria were not consistently associated. CONCLUSION: Current and passive smoking, but not former smoking, were associated with the presence of albuminuria in the general U.S. population with hypertension, indicating a benefit to the kidney from smoking cessation.     

Influence of aortic valve replacement, prosthesis type, and size on functional outcome and ventricular mass in patients with aortic stenosis.

OBJECTIVES: Two years after surgery for severe aortic stenosis, we prospectively evaluated the influence of aortic valve replacement, as well as valve type (mechanical or stented biologic) and size, on functional status, left ventricular function, and regression of mass. METHODS: Patients who received either a mechanical (n = 95) or a biologic valve (n = 42) were studied by echocardiography before the operation and after 2 years. RESULTS: The percentage of patients with severe dyspnea decreased from 53% to 13% (P =.001). The cardiac index increased from mean 2.6 L/min per square meter (95% CI: 2.48-2. 72 L/min per square meter) to 3.1 L/min per square meter (95% CI: 2. 94-3.26 L/min per square meter; P =.001). The percentage of the patients with mild-to-moderate diastolic dysfunction decreased from 43% to 18% (P =.001). The left ventricular mass index was reduced by 42.4 g (95% CI: 35-50 g; P =.001). In comparison with biologic valves of the same size, mechanical valves produced a more pronounced reduction in mass index (overall difference 21.7 g; 95% CI: 37.1-6.4 g; P =.007) and a lower mean Doppler gradient (overall difference 4 mm Hg; 95% CI: 2-6 mm Hg; P =.0002). CONCLUSIONS: Patients undergoing aortic valve replacement had an improvement in functional status, as well as systolic and diastolic left ventricular function, and a reduction in left ventricular mass index, irrespective of prosthesis size and type. Mechanical valves are somewhat less obstructive than stented bioprosthetic valves of the same size. They are also associated with a concomitantly more pronounced reduction of left ventricular mass.     

Very low-density lipoprotein-apoprotein CI is increased in diabetic nephropathy: comparison with apoprotein CIII

BACKGROUND: Recent studies have suggested that apoprotein (apo) CI in very low-density lipoprotein (VLDL) plays an important role in causing hypertriglyceridemia independent of apo CIII, which is associated with coronary heart disease (CHD). Because the incidence of CHD is increased in diabetic patients and is even higher when diabetic nephropathy is developed, we measured apo CI levels in VLDL from type 2 diabetic patients, with various degree of nephropathy, and compared the results with those for healthy controls or nondiabetic patients with chronic renal failure (CRF). METHODS: This study enrolled healthy control subjects, type 2 diabetic patients with normoalbuminuria, microalbuminuria, overt proteinuria, and CRF on hemodialysis and nondiabetic hemodialysis patients. VLDL (density <1.006) was separated by ultracentrifugation. Then the apo CI, CIII, and B concentrations in VLDL were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The apo CI, CIII, and B concentrations in VLDL were respectively 3-, 2-, and 2-fold higher, respectively, in diabetic patients with overt proteinuria than in controls. Hemodialysis patients with diabetic nephropathy had levels of apo CI, CIII, and B in VLDL that were 2.6-, 2.7- and 2-fold higher, respectively, than those in controls. Nondiabetic hemodialysis patients also had a 2.7-fold higher level of VLDL apo CIII, whereas VLDL apo CI and VLDL apo B were not significantly increased. VLDL apo CI was significantly correlated with VLDL apo B independently of VLDL apo CIII level. CONCLUSION: An increase of VLDL apo CIII is a prominent feature of dyslipidemia in CRF patients, regardless of whether they are diabetic or nondiabetic, whereas an increase of VLDL apo CI is more specific to diabetic nephropathy and is closely associated with an increase of VLDL particle numbers, a new risk factor for CHD.     

Uric acid and nocturnal nondipping in hypertensive patients with normal renal function

BACKGROUND: The effect of uric acid on nocturnal dipping in hypertensive patients is unknown. We analyzed the specific relationship between uric acid and nocturnal dipping status in newly diagnosed essential hypertensive patients with normal renal function. METHODS: Two hundred fifteen patients with newly diagnosed essential hypertension underwent 24-hour ambulatory blood pressure monitoring, biochemistry analysis and 24-hour urine testing. RESULTS: Patients were classified as either dippers (157 patients) or nondippers (58 patients). Uric acid levels were higher in nondippers than in dippers (345.0 +/- 65.4 mmol/L vs. 270.6 +/- 59.5 mmol/L, p<0.0001) and positively correlated with the following blood pressure (BP) values: average nighttime ambulatory systolic BP (r=0.325, p<0.0001), average nighttime ambulatory diastolic BP (r=0.203, p=0.003), nighttime mean arterial BP (r=0.285, p<0.0001) and mean 24-hour arterial BP (r=0.197, p=0.004). Uric acid was also positively correlated with nighttime heart rate (r=0.293, p=0.001). Univariate logistic regression analysis showed that a high serum uric acid level (odds ratio [OR] = 3.566; 95% confidence interval [95% CI], 2.397-5.303; p<0.0001) and smoking (OR=2.294; 95% CI, 1.155-4.498; p=0.018) increased the risk of nocturnal nondipping. The results of multivariate analysis showed that serum uric acid levels (OR=3.453; 95% CI, 1.466-8.134; p=0.005) together with fasting blood glucose (OR=1.148; 95% CI, 1.028-1.281; p=0.014) were associated with the nondipping pattern. CONCLUSIONS: This study is the first to demonstrate that increased serum uric acid levels are associated with nondipping blood pressure patterns in patients with essential hypertension.     

Aprotinin in major orthopedic surgery: a systematic review of randomized controlled trials

Aprotinin therapy is a promising strategy for reducing blood loss and blood transfusion requirements. The efficacy and safety of aprotinin in orthopedic surgery, however, remain controversial. We searched electronic databases for randomized controlled trials on the efficacy and safety of the use of aprotinin in orthopedic surgery. Thirteen trials that included a total of 506 patients who underwent major orthopedic surgery were analyzed. The pooled intraoperative and perioperative blood loss was significantly less in the aprotinin-treated patients than in the control patients (weighted mean difference [WMD] for intraoperative blood loss = -229 mL, 95% confidence interval [CI] = -367 to -91 mL, P = 0.0011; WMD for perioperative blood loss = -557 mL; 95% CI = -860 to -254 mL; P < 0.0001). The pooled amounts of red blood cell (RBC) units (U) transfused intraoperatively and perioperatively were significantly less in the aprotinin-treated patients than in the control patients (WMD for intraoperative RBC U = -1.1 U; 95% CI = -1.7 to -0.4 U; P = 0.0001; WMD for perioperative RBC U = -1.1 U; 95% CI = -1.7 to -0.5 U; P < 0.0001). Aprotinin was not associated with an increased incidence of deep vein thrombosis (odds ratio = 0.39; 95% CI = 0.14 to 1.05, P = 0.061). The authors conclude that aprotinin reduces the intraoperative and perioperative blood loss and allogeneic blood transfusion requirement and may not be associated with increased risk of deep vein thrombosis in the presence of pharmacological or mechanical prophylaxis in patients undergoing major orthopedic surgery.     

Apolipoprotein(A) expression in intracranial aneurysms

OBJECTIVE: Elevated serum levels of lipoprotein(a), a risk factor for atherosclerosis (AS), are also associated with the presence of asymptomatic intracranial aneurysms. AS is present in some aneurysms, but its contribution to aneurysm formation and growth is unclear. Apolipoprotein(a) [apo(a)], the active moiety of lipoprotein(a), is present in atherosclerotic circle of Willis vessels but not in normal circle of Willis vessels. We wished to determine whether apo(a) is present in intracranial aneurysms independently of AS. METHODS: With a purified anti-apo(a) monoclonal antibody, aneurysms (n = 25) and feeding vessels (n = 23) were examined for apo(a) expression by immunohistochemical analysis. Circle of Willis arteries with and without AS (n = 19), cavernous angiomas (n = 5), and arteriovenous malformations (n = 6) acted as control samples. RESULTS: AS was present in 32% of aneurysms, and all of those aneurysms demonstrated mural immunopositivity for apo(a). However, aneurysms devoid of AS also demonstrated apo(a) immunopositivity. Apo(a) was demonstrated in 86% of available feeding vessels. Apo(a) deposition was not observed in cavernous angiomas but was present in arteriovenous malformations. Eleven Circle of Willis arteries (57.9%) were devoid of AS and demonstrated no apo(a) immunostaining, whereas the eight (42.1%) with AS were immunopositive for apo(a). CONCLUSION: Apo(a) expression in intracranial aneurysms may occur independently of AS. Apo(a) in feeding vessels suggests a possible role for apo(a) in early events leading to aneurysm formation. Multilayered transmural apo(a) deposition in established aneurysms suggests apo(a) involvement in aneurysm growth, possibly via cycles of injury and repair. The absence of apo(a) in cavernous angiomas suggests that such injury might be pressure-mediated.     

Risk factors associated with albuminuria in Kuwaiti adults with type 2 diabetes

There are no available data about the factors associated with diabetic nephropathy (DN) in Kuwaiti individuals with type 2 diabetes. This study was conducted on 154 consecutive Kuwaiti adults with type 2 diabetes who attended the diabetic out-patient clinic at Al-Sabah Hospital to determine the factors associated with albuminuria among them. Albuminuria was considered to be present if the urinary albumin:creatinine ratio test or 24-h collection was positive on two occasions. There were 102 (66.2%) women and 52 (33.8%) men, with a mean age of 49.1 ± 10.1 years and a median duration of diabetes for 6 years. Hypertension was found in 60.8% of the patients and 16.3% had an HbA 1c <7%. Albuminuria was found in 43.5% of the patients. The prevalence of microalbuminuria and macroalbuminuria was 27.3% and 16.2%, respectively. In the univariate analysis, the factors that were significantly associated with albuminuria were hypertension - both systolic and diastolic blood pressure levels, HbA 1c , retinopathy, duration of diabetes, and modality of treatment. Multiple logistic regression analysis indicated that hyper-tension was the main independent risk factor associated with albuminuria (OR 4.1, 95% CI 1.1- 15.0; P = 0.03). In conclusion, although albuminuria is common among Kuwaiti adults with type 2 diabetes, the prevalence is lower than that reported for other populations in spite of the poor glycemic control and the high prevalence of hypertension. Factors associated with albuminuria appear to be similar to other populations, and hypertension was the most independent factor. Early recognition and treatment of hypertension is an important strategy to prevent or delay DN as well as cardiovascular morbidity and mortality. A population-based study is warranted to confirm these findings and to search for genetic linkage for the development of DN.