Log Urinary Albumin Excretion Research Articles

PS-C21-6: RENOPROTECTIVE EFFECT OF ALISKIREN MONOTHERAPY IN HYPERTENSIVE PATIENTS WITH OBESITY AND TYPE 2 DIABETES MELLITUS

Objective: Renin-angiotensin system inhibitors have been reported to have protective effects from end-organ damages. However, roles of the direct renin inhibitor monotherapy have been still unknown. Therefore, in the present study, we compared effects of aliskiren monotherapy with those of amlodipine monotherapy on visceral fat area (VFA) and end-organ damages in hypertensive patients with obesity and type 2 diabetes. Design: A single-center, prospective, open-label and randomized study. Methods: Adult hypertensive patients with body mass index ≧ 25 kg/m2 and VFA ≧ 100 cm2 or those with type 2 diabetes, who had an office blood pressure 140–160/90–100 mmHg with or without antihypertensive drugs were randomly allocated to 24-week aliskiren or amlodipine monotherapy. The dose of amlodipine or aliskiren was increased up to 10 mg/day and 300 mg/day, respectively, and only doxazosin could be added at maximum to 8 mg/day if needed. The primary outcome of the study was the changes of waist circumference and VFA at 24 weeks of the study period. Changes in outcomes were analyzed using mixed-effects models for repeated measures, which included treatment, time, treatment-by-time interaction and the baseline values as fixed effects. Results: In a total of 62 participants (age, 57 ± 13 y.o.; 40 men; body mass index, 28.8 ± 4.8 kg/m2; waist circumference, 99.3 ± 11.9 cm; VFA, 134.8 ± 47.0 cm2; blood pressure, 141 ± 16/86 ± 13 mmHg), waist circumference and visceral fat area as a primary endpoint did not significantly change from baseline in both groups. Systolic blood pressure significantly decreased at 12 weeks (change in least squares means: -10 mmHg, P = 0.001) and 24 weeks (-10 mmHg, P = 0.001) in the amlodipine group and at 24 weeks (-11 mmHg, P = 0.001) in the aliskiren group. Diastolic blood pressure significantly decreased at 24 weeks (-6 mmHg, P = 0.009) only in the amlodipine group. Estimated glomerular filtration rates were not statistically different between the groups. Logarithm of urinary albumin excretion significantly decreased at 24 weeks only in the aliskiren group (-0.60, P < 0.001). The 24-weeks-changes in logarithm of serum pentraxin 3 levels, an inflammatory marker, were significantly lower in the aliskiren group than in the amlodipine group (-0.09 vs + 0.09, P = 0.017). Conclusions: These data suggested that aliskiren monotherapy may have a better renoprotective effect than amlodipine monotherapy while it does not affect VFA in hypertensive patients with obesity and type 2 diabetes mellitus.

Effects of Aliskiren Monotherapy versus Amlodipine Monotherapy in Hypertensive Patients with Obesity or Type 2 Diabetes Mellitus

Introduction: Renin-angiotensin system inhibitors have been reported to exert protective effects against organ damage and failure; however, the impact of the direct renin inhibitor as monotherapy has not been assessed. Here, we investigated the effects of 24-week monotherapy with aliskiren compared to amlodipine in hypertensive patients with type 2 diabetes or obesity. Methods: In this randomized intervention study, 62 adult hypertensive patients with visceral obesity (defined as a body mass index [BMI] greater than 25 kg/m2 and a visceral adipose tissue area [VFA] greater than 100 cm2) or type 2 diabetes mellitus (age 57 ± 13, 65% men, BMI 28.8 ± 4.8 kg/m2, VFA 134.8 ± 47.0 cm2, blood pressure 141 ± 16/86 ± 13 mm Hg) were randomized to receive 24-week treatment with aliskiren (max. 300 mg) or amlodipine (max. 10 mg). The primary outcome was the change in VFA at 24 weeks post-treatment. Results: Change in VFA did not differ significantly from baseline in either group. Systolic blood pressure significantly decreased at 12 weeks (−10 mm Hg, p = 0.001) and 24 weeks (−10 mm Hg, p = 0.001) in the amlodipine group and at 24 weeks (−11 mm Hg, p = 0.001) in the aliskiren group. Diastolic blood pressure significantly decreased at 24 weeks (−6 mm Hg, p = 0.009) only in the amlodipine group. Although the estimated glomerular filtration rates did not significantly change in either group, the logarithm of urinary albumin excretion significantly decreased at 24 weeks only in the aliskiren group (−0.60, p < 0.001). The 24-week changes in the urinary albumin excretion significantly correlated with the changes in the plasma renin activity in the aliskiren group (r = 0.51, p = 0.008). Conclusion: Aliskiren monotherapy did not show any superiority to amlodipine monotherapy on VFA, estimated glomerular filtration rates, or urinary albumin excretion in obese or type 2 diabetic hypertensive patients.

Aldosterone-to-Renin Ratio Is Associated with Diabetic Nephropathy in Type 2 Diabetic Patients: A Single-Center Retrospective Study.

BackgroundIt is well established that primary aldosteronism (PA) and aldosterone-to-renin ratio (ARR) are associated with kidney disease. The aim of this study was to retrospectively investigate the relationship between ARR, urinary albumin excretion (UAE), and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes from a single center.Material/MethodsWe included 70 patients with type 2 diabetes, UAE ≤100 mg/day, not taking renin-aldosterone system inhibitors, did not meet the diagnostic criteria for PA, and had an ARR <20. The patients were divided into 3 groups: the normal low (NL) group (33 patients) with a UAE <10 mg/day, the normal (N) group (22 patients) with a UAE of 10–29 mg/day, and the microalbuminuria (M) group (15 patients) with a UAE of 30–100 mg/day. The ARR, plasma renin activity (PRA), and plasma aldosterone (PAC) were compared among groups.ResultsThe ARR was highest in group M (10.1±4.6), 6.5±0.3 in group NL, and 7.0±2.7 in group N. The PRA and PAC were significantly lower in group M (P<0.001). The ARR showed a significant positive correlation with log UAE (r=0.37, P<0.001) and a significant negative correlation with eGFR (r=−0.33, P<0.01).ConclusionsHigh levels of aldosterone relative to renin, which did not fulfill confirmatory criteria for PA, may be one of the risk factors for the development of diabetic nephropathy in patients with diabetes. The present results are supported by previous research showing that an increased ARR without PA was a risk factor for kidney disease.

Associations of Homocysteine with B Vitamins and Zinc in Serum Levels of Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

The association of homocysteine metabolism-related nutrients along with renal function to homocysteine levels is not well known in patients with type 2 diabetes mellitus (T2DM). We investigated the relevance of kidney function, albuminuria, and nutritional factors to serum homocysteine in T2DM patients. This cross-sectional study enrolled 149 T2DM patients (96 men and 53 postmenopausal women), and patient characteristics and laboratory data including kidney-related data [glomerular filtration rate (eGFR), urinary albumin excretion (UACR), uric acid] and metabolism parameters (hemoglobin A1c and lipids) were collected from the medical record and serum levels of vitamin B12, folic acid, zinc, homocysteine and UACR were also acquired. In total subjects, serum levels of homocysteine, vitamin B12, and folic acid were within reference intervals, but zinc levels were close to lower limits of its reference interval. A multivariate-adjusted analysis showed that gender (β=-0.259, p<0.001), uric acid (β=0.267, p<0.001), eGFR (β=-0.188, p=0.001), log UACR (β=0.190, p=0.002), log folic acid (β=-0.259, p<0.001), log vitamin B12 (β=-0.224, p<0.001) and zinc (β=-0.169, p=0.006) were correlated to log homocysteine. In multiple regression analysis by gender, these correlations were found similarly in men, but neither log folic acid nor zinc showed correlations with log homocysteine in women. The present study suggests that renal function parameters and the certain nutritional factors have a possible influence on serum homocysteine, in T2DM patients including diabetes kidney disease.

403-P: Plasma Renin Level and Aldosterone-to-Renin Ratio Are Associated with Diabetic Kidney Disease

Aim: A close association between primary aldosteronism (PA) and atherosclerosis has been well established. We aimed to determine the association between plasma renin activity (PRA) and aldosterone levels (PAC) as well as their ratios (PAC-to-PRA ratio: ARR) with urinary albumin excretion (UAE) in type 2 diabetic patients who did not fulfill PA confirmatory criteria. Methods: The subjects were 70 type2 diabetic patients (age: 53.3±11.0 years, male: 51, female: 19) with UAE ≤100 mg/gCr. They did not take ACE inhibitors, angiotensin receptor blockers (ARB) or diuretic agents. Patients were selected for this study based on various criteria: PRA level ˂10 ng/ml/hr, PAC ˂20 ng/dl, and ARR ˂20 (ng/dl per ng/ml/hr). They were divided into three groups according to UAE levels: NL group (N=33) ˂ 10mg/gCr, N group (N=22) 10-29 mg/gCr, and M group (N=15) 30-100 mg/gCr. Results: There were no significant differences in age, BMI, HbA1c, and eGFR levels among the three groups. The systolic blood pressure in the M group was significantly higher than those in the NL and N groups. The ARR in the M group was 10.1±4.6, which was significantly higher than those in NL (6.5±0.3) or N (7.0±2.7) groups. In the M group, the levels of PRA and PAC were significantly lower than those in NL or N groups. Log UAE was positively correlated with ARR (r=0.34, p&amp;lt;0.0001) and negatively correlated with PRA (r=-0.32, p&amp;lt;0.001). Systolic blood pressure showed a significant positive correlation with ARR and negative correlation with PRA. Conclusion: These results suggest that a high ARR level, which did not fulfill confirmatory criteria for PA, was associated with diabetic nephropathy. The relative increase in PAC to PRA might contribute to the development of diabetic nephropathy, even if PAC remains normal level. Disclosure M. Higa: None. T. Suzuki: None. T. Kido: None. M. Zenri: None. K. Nao: None. M. Hijikata: None. K. Yamashita: None. K. Ikehara: None. T. Ichijo: None.

Low circulating arachidonic acid is associated with macroalbuminuria in diabetic patients: a cross-sectional examination of the KAMOGAWA-DM cohort study

BackgroundDiabetic nephropathy, a major complication of diabetes, is the primary risk factor for dialysis, cardiovascular diseases, and mortality. Dietary fatty acids (FAs) have been revealed to be related with cardiovascular diseases in the general populations. The aim of this study was to investigate the association of circulating FAs with diabetic nephropathy.MethodsIn this cross-sectional study, 190 Japanese patients with type 2 diabetes were included. Circulating FAs were measured by gas chromatography-mass spectrometry. Spearman rank correlation coefficients were used to investigate the association between the logarithm of FAs and the logarithm of urinary albumin excretion (UAE). We have performed logistic regression analysis to determine the effect of FAs on the presence of macroalbuminuria, defined as UAE value ≥300 mg/g creatinine.ResultsMean age, body mass index, and duration of diabetes were 62.7 ± 12.1 years, 25.0 ± 4.5 kg/m2, and 9.8 ± 8.7 years, respectively. In total, 26 patients were diagnosed with macroalbuminuria. The logarithm of circulating arachidonic acid (AA) was negatively associated with the logarithm of UAE (r = − 0.221, p = 0.002). Additionally, circulating AA in patients with macroalbuminuria was lower than that in patients without macroalbuminuria (112.3 ± 75.3 mg/day vs. 164.8 ± 66.0 mg/day, p < 0.001). The logarithm of circulating AA was associated with the presence of macroalbuminuria after adjusting for covariates (odds ratio of Δ1 incremental: 0.32, 95% confidence interval: 0.10–0.99, p = 0.042).ConclusionsCirculating AA was negatively associated with UAE and the presence of macroalbuminuria.

510-P: Serum Mac-2 Binding Protein Is Associated with Diabetic Micro- and Macroangiopathy in People with Type 2 Diabetes

A close relationship between type 2 diabetes and nonalcoholic fatty liver disease, including liver fibrosis, has been reported. Mac-2 binding protein glycosylation isomer (M2BPGi) is reported as a non-invasive new serological glyco-biomarker for liver fibrosis. The purpose of this cross-sectional study was to investigate the association between serum M2BPGi levels and diabetic complications in people with type 2 diabetes. Serum M2BPGi levels were measured in terms of cut-off index (C.O.I.) units. Urinary albumin excretion (UAE) was calculated and nephropathy was graded as normo-, micro-, or macroalbuminuria. Retinopathy was divided into three groups: no- (NDR), simple- (SDR), or proliferative diabetic retinopathy (PDR). Mean age for 363 people (212 males) was 66.4 (10.6) years, the median M2BPGi level was 0.77 (0.57-1.04) C.O.I., and the median UAE was 22 (9-82.1) mg/g Cr. Serum M2BPGi level was increased with levels of diabetic microangiopathy. Furthermore, the M2BPGi levels in people with a history of cardiovascular diseases were higher than that in people without (0.82 [0.65-1.22] vs. 0.76 [0.55-1.03] C.O.I., p = 0.019). The logarithm of M2BPGi was associated with the logarithm of UAE after adjusting for covariates (β = 0.107, p = 0.031). This study reveals a close association between serum M2BPGi levels and diabetic micro- and macroangiopathy in people with type 2 diabetes. Disclosure Y. Hashimoto: None. M. Hamaguchi: None. M. Fukui: None.

Decreased microcirculatory function measured by perfusion index is a novel indicator of diabetic kidney disease in patients with type2 diabetes.

Aims/IntroductionDiabetic kidney disease has been considered as an important risk factor of cardiovascular disease. Chronic hypoxia is considered to be the main cause of renal injury. Diminished microcirculatory blood flow could be associated with hypoxia in the kidney. Whether diminished microcirculation is associated with diabetic kidney disease has not yet been reported. Here, we investigated the correlation between microcirculatory function and diabetic kidney disease in patients with type 2 diabetes.Materials and MethodsOur cross‐sectional study included 574 patients who were admitted to Matsushita Memorial Hospital in Moriguchi, Japan, for type 2 diabetes. Microcirculatory function was assessed using the perfusion index (PI), which represents the level of circulation through peripheral tissues. We measured the PI for all patients.ResultsThe median age and PI values were 70 years (range 60–77 years) and 2.8% (range 1.6–4.8%). Multiple regression analyses showed that the PI independently correlated with the logarithm of urinary albumin excretion (P = 0.009) and estimated glomerular filtration rate (P = 0.005), respectively. Multiple logistic regression analyses showed that patients with systolic blood pressure (SBP) greater than the median and PI less than or equal to the median (high‐low group) had a significantly increased odds of albuminuria compared with those with SBP less than or equal to the median and PI greater than the median (low‐high group), and patients with SBP greater than the median and PI less than or equal to the median (high‐low group) had a significantly increased odds of estimated glomerular filtration rate <60 mL/min per 1.73 m2 compared with those with SBP less than or equal to the median and PI greater than the median (low‐high group) or SBP greater than the median and PI greater than the median (high‐high group).ConclusionsPI could be a novel indicator of diabetic kidney disease in patients with type 2 diabetes.

Association between Body Weight Gain from 20 Years of Age and Diabetic Nephropathy in Japanese Patients with Type 2 Diabetes

Background/Aims: It has been reported that the body mass index shows a U-shaped association with death from cardiovascular disease (CVD) in the Asian population. The relationship between body weight (BW) gain from early adulthood and diabetic nephropathy remains to be elucidated in Japanese patients with type 2 diabetes. Our aim was to investigate the association between BW gain from early adulthood and diabetic nephropathy in Japanese patients with type 2 diabetes. Methods: We assessed the BW of 471 consecutive patients with type 2 diabetes and calculated the change in BW from the age of 20 years to the lifetime maximum (ΔBW_max-20y). We then evaluated the relationship of ΔBW_max-20y with the degree of urinary albumin excretion (UAE), which is a useful marker for CVD. Results: ΔBW_max-20y negatively correlated with the logarithm of UAE (r = –0.160, p = 0.002). Multiple regression analysis demonstrated that ΔBW_max-20y was independently correlated with the logarithm of UAE (β =–0.112, p =0.034). Conclusions: BW gain from the age of 20 years is correlated with diabetic nephropathy in Japanese patients with type 2 diabetes.

Home Blood Pressure Variability From the Stored Memory Is Correlated With Albuminuria, but From the Logbook Is not.

The aim of this study was to evaluate whether the mean and the variability of home blood pressure (HBP) from the logbook correlate with albuminuria as well as HBP from the stored memory in patients with type 2 diabetes. This study is a post hoc analysis of a cross-sectional multicenter study. HBP measurements were performed for 14 consecutive days in 276 patients with type 2 diabetes. Patients were requested to write down their HBP values in logbooks and were not informed about the memory function of their BP monitoring devices. HBP values from the logbook were significantly lower and less variable than those from the stored memory. The mean of morning systolic BP (SBP) from the logbook (adjusted β = 0.326, P < 0.001) as well as that from the stored memory (adjusted β = 0.336, P < 0.0001) was significantly associated with logarithm of urinary albumin excretion (UAE). The SD of morning SBP (adjusted β = 0.134, P = 0.017) from the stored memory was significantly associated with logarithm of UAE, in contrast, the SD of morning SBP (adjusted β = 0.104, P = 0.057) from the logbook was not associated with logarithm of UAE. Patients with type 2 diabetes might report inaccurate HBP measurements and, as a result, the variability of HBP from the logbook is underestimated and poorly correlates with albuminuria. The use of stored BP measurements is recommended to accurately evaluate the relationship with diabetic nephropathy.

Association of Soluble Receptor for Advanced Glycation End Products Levels with Hypertensive Albuminuria

Soluble receptor for advanced glycation end products (sRAGE) levels have been found to be decreased in chronic inflammatory diseases including atherosclerosis, hypertension and renal failure. This study evaluated the relationship between sRAGE concentrations and urinary albumin excretion in patients with essential hypertension. A total of 200 consecutive patients with essential hypertension were enrolled and were divided into 3 groups. Plasma sRAGE levels were significantly lower in hypertensive patients with micro- or macroalbuminuria compared with those in hypertensive patients with normoalbuminuria, and the values in the macroalbuminuria group were even lower than in the microalbuminuria group (128.6±24.2, 244.6±37.6±313.6±30.7 pg/ml, respectively). In addition, plasma sRAGE level was an independent determinant of log urinary albumin excretion in patients with essential hypertension (β=-0.267, P<0.05). sRAGE may play a role in the pathogenic processes that link albuminuria, chronic inflammation and oxidative stress in hypertensive patients.

Switching to multiple daily injection therapy with glulisine improves glycaemic control, vascular damage and treatment satisfaction in basal insulin glargine‐injected diabetic patients

Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established. Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire. Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores. Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients.

Home-measured heart rate is associated with albuminuria in patients with type 2 diabetes mellitus: a post-hoc analysis of a cross-sectional multicenter study

Epidemiological studies have shown that elevated heart rate (HR) is associated with an increased risk of diabetic nephropathy, as well as cardiovascular events and mortality, in patients with type 2 diabetes mellitus. Recently, the advantages of the self-measurement of blood pressure (BP) at home have been recognized. The aim of this study was to investigate the relationship between home-measured HR and albuminuria in patients with type 2 diabetes mellitus. We designed a cross-sectional multicenter analysis of 1245 patients with type 2 diabetes mellitus. We investigated the relationship between the logarithm of urinary albumin excretion (log UAE) and home-measured HR or other factors that may be related to nephropathy using univariate and multivariate analyses. Multivariate linear regression analysis indicated that age, duration of diabetes mellitus, morning HR (β=0.131, P<0.001), morning systolic BP (β=0.311, P<0.001), hemoglobin A1C, triglycerides, daily consumption of alcohol, use of angiotensin II receptor blockers and use of beta-blockers were independently associated with the log UAE. Multivariate logistic regression analysis indicated that the odds ratio (95% confidence interval) associated with 1 beat per min and 1 mm Hg increases in the morning HR and morning systolic BP for albuminuria were 1.024 ((1.008-1.040), P=0.004) and 1.039 ((1.029-1.048), P<0.001), respectively. In conclusion, home-measured HR was significantly associated with albuminuria independent of the known risk factors for nephropathy, including home-measured systolic BP, in patients with type 2 diabetes mellitus.

Prevalence and factors related to urinary albumin excretion in obese youths

The aim of the present study is to assess whether obesity is associated with urinary albumin excretion and what the main determinants are. One hundred and thirty-four obese white children and adolescents of both sexes, ranging from 9 to 18 years of age (mean age 12.6 ± 2.0), were included in the study. Obesity was defined on the basis of a threshold BMI z-score of more than 2 (Cole's LMS method) and overweight with a BMI from the 85th to 95th percentile. Office blood pressure was measured using a mercury sphygmomanometer. Urinary albumin excretion was measured in the first voiding urine of the morning and expressed in albumin/creatinine ratio in mg/g. Reproducibility of the urinary albumin excretion was studied by the Bland and Altman technique in a subgroup. Triglycerides, uric acid, fasting glucose and insulin were measured and the homeostatic model assessment (HOMA) index was calculated. The prevalence of microalbuminuria was 2.4%. No differences in the prevalence of microalbuminuria were observed when the different groups of obesity degree were compared (0, 2.2 and 0% in overweight, moderate and severe obese, respectively). A significant relationship emerged between the Log urinary albumin excretion and BMI z-score, waist circumference, Log triglycerides, fasting insulin and HOMA index, adjusted by age and sex. In a multiple regression analysis, the main determinants of Log urinary albumin excretion were sex, waist circumference and Log triglycerides. In 17% of the individuals who fulfil criteria for metabolic syndrome, urinary albumin excretion was significantly higher than those without. The prevalence of elevated urinary albumin excretion is not prominent in obese children, and when it is increased, it depends mainly on metabolic factors.

Serum pepsinogen I/II ratio is correlated with albuminuria in patients with type 2 diabetes

Helicobacter pylori infection, which is a common cause of atrophic gastritis, has been reported to represent a causal factor increasing the vascular damage and consequent albuminuria. On the other hand, decreased serum pepsinogen (PG) I/II ratio can be used to assess gastric mucosal atrophy. To the best of our knowledge, there are no studies investigating the correlation between PG I/II ratio and diabetic nephropathy. Therefore, we investigated a relationship between PG I/II ratio and degree of urinary albumin excretion (UAE) in patients with type 2 diabetes. We evaluated relationships between PG I/II ratio and degree of UAE or estimated glomerular filtration rate as well as various factors, including age, body mass index, blood pressure, hemoglobin A1c, serum lipid concentrations, uric acid or C-reactive protein in 333 consecutive patients with type 2 diabetes. PG I/II ratio correlated positively with logarithm of UAE in all patients (r = 0.174, P = 0.0016) and in patients without Helicobacter pylori infection (r = 0.352, P < 0.0001). Multiple regression analysis identified that PG I/II ratio correlated independently with logarithm of UAE in all patients (β = 0.264, P = 0.0005) and in patients without Helicobacter pylori infection (β = 0.295, P = 0.0022). These data suggest that serum PG I/II ratio is correlated with diabetic nephropathy.

Low daily salt intake is correlated with albuminuria in patients with type 2 diabetes

Both high and low salt intakes have been reported to be associated with an increased risk of cardiovascular events. The aim of this study was to investigate the relationship between daily salt intake and albuminuria, a marker of diabetic nephropathy and cardiovascular disease, in patients with type 2 diabetes. We classified 270 patients with type 2 diabetes, who were not receiving antihypertensive medication into four groups according to their daily salt intake (<8, 8-10, 10-12 and >12 g per day). We investigated the relationship between daily salt intake and the logarithm of urinary albumin excretion (UAE). A multivariate linear regression analysis was used to evaluate whether daily salt intake independently correlated with the logarithm of UAE. In addition, we assessed the contribution of the variables, including age, sex, duration of diabetes, body mass index, systolic blood pressure, hemoglobin A(1C), low-density lipoprotein cholesterol, triglycerides, serum creatinine, alcohol intake, smoking status and square of (daily salt intake-10) on albuminuria, defined as a UAE>30 mg g(-1) of creatinine, using a multiple logistic regression analysis. The logarithm of the UAE was lowest in the third quartile of daily salt intake. The multivariate linear regression analysis demonstrated that the logarithm of the UAE was significantly correlated with the quadratic term of daily salt intake centered at 10 g per day (β=0.170, P=0.008). The multivariate logistic regression analysis demonstrated that the odds ratio (95% confidence interval) of albuminuria was 3.996 (1.295-12.327; P=0.016) in patients whose daily salt intake was less than 8 g per day compared with patients whose daily salt intake was 10-12 g per day. In conclusion, low daily salt intake was correlated with albuminuria in patients with type 2 diabetes, who were not receiving antihypertensive medication.

Serum allograft inflammatory factor-1 is a novel marker for diabetic nephropathy

AimsRecent studies have identified macrophage-mediated injury as an important component in the development of diabetic nephropathy. The aim of this study was to investigate the correlations between serum allograft inflammatory factor-1 (AIF-1) concentration, which is a marker of activated macrophages, and diabetic nephropathy. MethodsSerum AIF-1 concentrations were measured in 284 patients with type 2 diabetes. We evaluated relationships of serum AIF-1 concentrations to degree of urinary albumin excretion (UAE) or estimated glomerular filtration rate (eGFR) in univariate and multivariate linear regression analyses. ResultsSerum AIF-1 concentrations positively correlated with logarithm of UAE (r=0.260, P<0.0001), whereas serum AIF-1 concentrations inversely correlated with eGFR (r=−0.312, P<0.0001). Mean serum AIF-1 concentration was higher in patients with macroalbuminuria than that in patients with normoalbuminuria (P=0.0001) or that in patients with microalbuminuria (P=0.0093). In multivariate linear regression analyses, serum AIF-1 concentrations were independently correlated with logarithm of UAE (β=0.213, P=0.0120) and with eGFR (β=−0.286, P=0.0011). ConclusionsSerum AIF-1 concentration correlated with albuminuria and eGFR in patients with type 2 diabetes and it could be a marker of diabetic nephropathy as well as activated macrophages.

Relation of Reduction in Urinary Albumin Excretion to Ten-Year Cardiovascular Mortality in Patients With Type 2 Diabetes and Systemic Hypertension

Microalbuminuria is one of the strongest predictors of both adverse renal and cardiovascular disease (CVD) outcomes in patients with type 2 diabetes mellitus. Although measurement of urinary albumin excretion (UAE) is widely recommended, limited data are available to suggest that reducing UAE translates into a reduction in long-term cardiovascular mortality, particularly among patients without overt nephropathy, who constitute most patients with type 2 diabetes worldwide. We assessed whether changes in the UAE at 1 year were associated with cardiovascular mortality in 393 patients with hypertension and type 2 diabetes during a 10-year period. On univariate analysis, CVD history, age, diabetes duration, and change in UAE at 1 year were associated with cardiovascular mortality risk (hazard ratio 2.60 for those with CVD history, 95% confidence interval [CI] 1.47 to 4.62; hazard ratio 1.59 per 10 years of diabetes duration, 95% CI 1.12 to 2.25; and hazard ratio 1.49 per log UAE increase, 95% CI 1.13 to 1.96). In a stepwise Cox regression model that included baseline UAE and CVD history, the 10-year predicted mortality of those with a decrease in UAE of 2 logs at 1 year was 4.7% (95% CI 1.4% to 7.8%). For those with an increase in UAE of 2 logs at 1 year, it was 24.5% (95% CI 10.1% to 36.5%). In conclusion, these data support current guideline recommendations to screen for UAE in all patients with type 2 diabetes, even in the absence of nephropathy, and suggest that serial UAE measurements even after the initiation of antihypertensive therapy has prognostic value independent of traditional cardiovascular risk factors.

E-009 THE COEFFICIENT VARIATION OF HOME BLOOD PRESSURE IS A NOVEL FACTOR ASSOCIATED WITH MACROALBUMINURIA IN TYPE 2 DIABETES MELLITUS

Backgrounds Home blood pressure (HBP) measurement has been found to have a stronger relationship with target organ damage. Recent studies have explored the association between variabilities of BP and target organ damage. Therefore, we investigated the relationship between day-by-day variabilities of HBP and diabetic nephropathy in Japanese patients with type 2 diabetes. Methods We compared the coefficient variation (CV) of HBP in 858 Japanese patients withand withoutmacroalbuminuria. Next, we analyzed the relationship between logarithm of urinary albumin excretion and the CV of HBP using linear regression analysis. Then, we evaluated the association of the CV of HBP with macroalbuminuria using logistic regression analysis. Results The CV of morning systolic blood pressure in patients with macroalbuminuria was significantly greater than that without (8.08 ± 3.35% vs. 7.19 ± 2.25%, p < 0.05). Multivariate linear regression analyses indicated that CV of morning systolic (P < 0.05) was the independent explanatory variables for logarithm of urinary albumin excretion. Multivariate logistic regression analysis demonstrated that the odds ratio of the CV of morning systolic blood pressure for macroalbuminuria was 1.35 (P < 0.05). Conclusions The CV of HBP correlated with macroalbuminuria independent of the known risk factors in Japanese patients with type 2 diabetes.

The coefficient variation of home blood pressure is a novel factor associated with macroalbuminuria in type 2 diabetes mellitus

The purpose of this study was to investigate the association between day-by-day variability in home blood pressure (HBP) on 14 consecutive days and macroalbuminuria in patients with type 2 diabetes. We compared the coefficient of variation (CV) of HBP in 858 Japanese patients with and without macroalbuminuria. Next, we analyzed the relationship between the logarithm of urinary albumin excretion (UAE) and the CV of HBP using linear regression analysis. Then, we evaluated the association between the CV of HBP and macroalbuminuria, defined as UAE ≥300 mg g(-1) creatinine, using logistic regression analysis. The CVs of morning and evening systolic blood pressure (SBP) were significantly greater in patients with macroalbuminuria than in those without (8.08±3.35 vs. 7.19±2.25%, P<0.05 and 9.01±3.58 vs. 7.98±2.57%, P<0.05, respectively). Multivariate linear regression analyses indicated that the CVs of morning SBP (P<0.05) and diastolic blood pressure (DBP; P<0.05), and those of evening SBP (P<0.05) were the independent explanatory variables for the logarithm of UAE. Multivariate logistic regression analyses also demonstrated that the odds ratio for the CVs of morning SBP, morning DBP and evening SBP for macroalbuminuria were 1.35 (P<0.05), 1.29 (P<0.05) and 1.44 (P<0.05), respectively. We conclude that the CV of HBP is correlated with macroalbuminuria, independent of the known risk factors, in Japanese patients with type 2 diabetes.