Decrease In Urinary Albumin Excretion Research Articles

Effect of Thiazolidinediones on Renal Outcomes in Diabetic Patients with Microalbuminuria or Macroalbuminuria-A Systematic Review and Meta-analysis

Introduction: Diabetic nephropathy (DN), has recently become the leading cause of end-stage renal disease (ESRD) in most countries, recent studies suggest that thiazolidinediones (TZDs) have renal benefits. The aim of this meta-analysis was to assess the effect of TZDs on renal outcomes in type 2 diabetic patients with microalbuminuria or macroalbuminuria. Methods: Medline, Embase, Web of Science and Cochrane Central Register of Controlled Trials were searched from 1991 to September 2017. Randomized controlled trials (RCTs) were selected to evaluate the impact of TZDs on urinary albumin, protein excretion, eGFR or Scr in diabetic patients. Weighted (WMDs) and standardized mean differences (SMDs) were used for changes in urine albumin or protein excretion, eGFR and Scr between the TZDs and control groups. Results: 26 RCTs (9 with rosiglitazone and 17 with pioglitazone) involving 8129 patients with type 2 diabetes were included in this review. Meta-analysis of RCTs showed that in patients with baseline normo- and/or microalbuminuria, the WMD of proportional changes between the TZDs and control groups in urinary albumin excretion was -64.77% (95% CI, -75.60 to -53.94) and the WMD of changes in albumin-creatinine ratio was -24.94% (95% CI, -38.83 to -11.05). Overall, in participants with normo- and/or microalbuminuria, TZDs treatment was associated with a significant decrease in urinary albumin excretion (SMD, -0.91 units of standard deviation [SD]; 95% CI, -1.19 to -0.64). Similarly, TZDs were associated with a significant decrease in urinary protein excretion in patients with macroalbuminuria (SMD, -1.units of SD; 95% CI, -1.86 to -0.27). However, TZDs treatment couldn’t effectively improve eGFR or the level of Scr in diabetic patients whether with microalbuminuria or macroalbuminuria. Conclusions: Treatment with TZDs can benefit patients with early diabetic nephropathy in absence of renal dysfunction. Disclosure Y. Qin: None. X. Wang: None. M. Zhang: None.

Beneficial Effects of Pentoxifylline Plus Losartan Dual Therapy in Type 2 Diabetes with Nephropathy

BackgroundThis study was designed to comparatively assess the effects of add-on pentoxifylline to losartan versus increasing the dose of losartan on serum N-terminal pro-brain natriuretic peptide (NT-proBNP), serum highly sensitive C-reactive protein (hsCRP) and the urinary albumin excretion (UAE) rate in patients with type 2 diabetes and nephropathy. MethodsIn an open-label, single-center, parallel-group, randomized clinical trial (NCT03006952), 30 patients received b.i.d. dose of pentoxifylline 400mg plus daily dose of losartan 50mg (pentoxifylline arm) and 29 patients received b.i.d. dose of losartan 50mg (losartan arm) during a 12-week follow-up period. ResultsSerum NT-proBNP, serum hsCRP and UAE levels all significantly decreased from baseline in both trial arms. The pentoxifylline and losartan trial arms were equally effective in reducing serum NT-proBNP levels during the course of trial (multivariable adjusted model P value = 0.864, effect size = 0.2%). There was a greater decrease in UAE and serum hsCRP levels in the pentoxifylline arm (P = 0.034, effect size = 7.8%; P = 0.009, effect size = 11.7%, respectively). Conversely, patients in the losartan arm achieved better systolic and diastolic blood pressure control (P < 0.001, effect size = 25.4%; P = 0.010, effect size = 11.3%, respectively). ConclusionsCirculating NT-proBNP levels equally and significantly reduced from baseline in the pentoxifylline and losartan treatment arms, in parallel with comparatively superior decreases of UAE and serum hsCRP in the pentoxifylline arm, and larger decreases of systolic and diastolic blood pressures in the losartan arm.

MPS 14-02 Comparison of Decrease in Urinary Albumin Excretion According to Fimasartan Dosing of Evening versus Morning in Never-Treated Hypertensive Patients

MPS 14-02 Comparison of Decrease in Urinary Albumin Excretion According to Fimasartan Dosing of Evening versus Morning in Never-Treated Hypertensive Patients

Albuminuria in Hypertensive Patients: Where the Choice of Antihypertensive Medications Matters:: Commentary on "Several Conventional Risk Markers Suggesting Presence of Albuminuria Are Weak Among Rural Africans With Hypertension".

Albuminuria in Hypertensive Patients: Where the Choice of Antihypertensive Medications Matters:: Commentary on "Several Conventional Risk Markers Suggesting Presence of Albuminuria Are Weak Among Rural Africans With Hypertension".

PP.21.10

Objective: To compare cardiovascular outcomes depending on the albuminuria decrease due to combined antihypertensive therapy. Design and method: 59 patients with arterial hypertension (AH) 2–3 degrees were included in prospective study. We constructed a Markov model on the basis of the influence on albuminuria(AU) and glomerular filtration rate (GFR) and the results of a cohort study, containing the most comprehensive information on the incidence of cardiovascular hypertension complications and mortality depending on these parameters. As an alternative to the model were: the treatment of the original fixed combination of valsartan / amlodipine and generic free combination of losartan / amlodipine. Results: Antihypertensive drugs for 12 weeks allowed to firm decrease in urinary albumin excretion in both groups, with 19,2 ± 22,6 to 7,8 ± 9,9 ml / min / m2 (p < 0.05) in group V/A a and 17,6 ± 19,8 to 12,7 ± 14,6 (p < 0.05) in the L /A. There were obtained significant group differences in the more pronounced reduction of albuminuria due to influence of drugs B/A -44,8 ± 44,4 vs. -20,5 ± 31,6 (p < 0.05). Significant changes in GFR (increase) in the treatment from 74 ± 16,8 to 78,8 ± 16,2 (p < 0.05) were obtained in the group B/A. In group L/A showed a slight decline in GFR (74 ± 19,7 and 73,2 ± 16,2, respectively). In the modeling results was obtained that the death chance within 5 years in group B/A will be 81 per 1,000 people, in the groupL/A - 96 by 1000. The probability of stroke - 27 and 32 per 1,000 people; infarction - 54 and 61 respectively. That is a fixed combination therapy original V/A avoids 15 deaths, 5 strokes and 7 myocardial infarctions for every 1,000 patients. Conclusions: So that more pronounced nephroprotective effect of original fixed combination of V/A can further prevent fatal and non-fatal cardiovascular events.

Effect of imidapril versus ramipril on urinary albumin excretion in hypertensive patients with type 2 diabetes and microalbuminuria

Objective: Aim of this study was to compare the antiproteinuric effect of imidapril (I) and ramipril (R) in diabetic hypertensive patients with microalbuminuria.Research design and methods: One hundred and seventy-six patients were randomised to I 10 – 20 mg once daily (od) (n = 88) or R 5 – 10 mg od (n = 88) for 24 weeks. Clinic, ambulatory, central blood pressure (BP), urinary albumin excretion (UAE), plasma Angiotensin II (Ang II), bradykinin and brain natriuretic peptide (BNP) were assessed at baseline and after 6, 12 and 24 weeks.Results: Both I and R produced a similar decrease in clinic, ambulatory and central BP (p < 0.001 vs baseline). Both treatments significantly reduced UAE throughout the study, but the decrease in UAE associated with I was more pronounced, being evident at week 6 (p = 0.05) and maximal at week 24 end-point (−42 vs –29%, p < 0.01). BNP and Ang II levels were similarly reduced by I and R, while bradykinin increased more with R (+132 vs +86%, p < 0.05).Conclusions: These findings showed that in diabetic hypertensive patients with microalbuminuria, despite equivalent BP-lowering effect, I produced a greater antiproteinuric effect than R, which might be due to different intrinsic molecular properties of the two drugs.

Changes of urinary albumin excretion and cardiovascular events: a meta-regression analysis of 32 randomized trials and 80,812 patients

Background: The association between Urinary Albumin Excretion (UAE) and Cardiovascular (CV) risk has been well established. However, it has been not demonstrated whether regression of UAE is associated with reduced CV risk. The aim of the current study was to evaluate the relationship between changes of UAE induced by pharmacologic therapies and CV events. Methods: The MEDLINE, Cochrane, ISI Web of Science and SCOPUS database were searched for articles about UAE until October 2012. Randomized trials assessing UAE at baseline and at the end of follow-up, enrolling more than 200 hypertensive and/or diabetic patients and reporting clinical end-points (all-cause death, Myocardial Infarction (MI), stroke and CV death) were included in the study. Meta-regression analysis was performed to test the relationship between UAE changes and clinical end-points. The influence of baseline patients' characteristics, follow-up, study publication year, Detsky quality score, changes in blood pressure from baseline to the end of follow-up, degree of albuminuria, glomerular filtration rate, comorbidities and concomitant pharmacological treatments were also explored. Egger's method was used to assess publication bias. Results: 32 trials enrolling 80,812 participants were included. In meta-regression analysis, a relationship between UAE changes from baseline to end of follow-up and risk MI (change in Tau2 (t)=2.74; p Tau (p)=0.011), stroke (t=2.35; p=0.030) and CV events (including MI, stroke and CV death) (t=3.74; p=0.001) was found. Results were confirmed by sensitivity analysis. No heterogeneity among studies or publication bias were detected. Conclusions: In diabetic and/or hypertensive patients, a decrease in UAE is associated with reduced risk of MI, stroke and the composite of MI/stroke/CV death. These findings may have implications for monitoring CV risk in clinical practice.

Effect of aldosterone breakthrough on albuminuria during treatment with a direct renin inhibitor and combined effect with a mineralocorticoid receptor antagonist

We have reported observing aldosterone breakthrough in the course of relatively long-term treatment with renin-angiotensin (RA) system inhibitors, where the plasma aldosterone concentration (PAC) increased following an initial decrease. Aldosterone breakthrough has the potential to eliminate the organ-protective effects of RA system inhibitors. We therefore conducted a study in essential hypertensive patients to determine whether aldosterone breakthrough occurred during treatment with the direct renin inhibitor (DRI) aliskiren and to ascertain its clinical significance. The study included 40 essential hypertensive patients (18 men and 22 women) who had been treated for 12 months with aliskiren. Aliskiren significantly decreased blood pressure and plasma renin activity (PRA). The PAC was also decreased significantly at 3 and 6 months; however, the significant difference disappeared after 12 months. Aldosterone breakthrough was observed in 22 of the subjects (55%). Urinary albumin excretion differed depending on whether breakthrough occurred. For the subjects in whom aldosterone breakthrough was observed, eplerenone was added. A significant decrease in urinary albumin excretion was observed after 1 month, independent of changes in blood pressure. In conclusion, this study demonstrated that aldosterone breakthrough occurs in some patients undergoing DRI therapy. Aldosterone breakthrough affects the drug's ability to improve urinary albumin excretion, and combining a mineralocorticoid receptor antagonist with the DRI may be useful for decreasing urinary albumin excretion. When the objective is organ protection in hypertensive patients, a two-pronged approach using combination therapy to inhibit both the RA system and aldosterone may be highly effective.

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.

Efeito da perda de peso sobre a hemodinâmica renal em portadores da síndrome metabólica

We investigated the impact of weight loss on urinary albumin excretion (UAE) and creatinine clearance in obese patients with metabolic syndrome. Thirty-five obese patients undertook a 12-week calorie-restricted diet. The patients underwent a metabolic (oral glucose tolerance test, plasma lipids, and uric acid) and renal hemodynamic evaluations (creatinine clearance and urinary albumin excretion) before (phase 1), and after the 12-week diet (phase 2). After the dietary intervention, the subjects were divided into two groups: patients who achieved the target weight reduction (R: responders, n = 14), and patients who did not (NR: non-responders, n = 21). The patients in Group R showed an improvement in lipid profile, a decrease in UAE (median = 162.5 mg/24 hours, range: 0.8 to 292 mg/24 hours, at phase 1 versus 10.4 mg/24 hours, range: 1.6 to 22.4 mg/24 hours, at phase 2), and a significant reduction in creatinine clearance (121.4 ± 66.5 mL/min. in phase 1 to 92.9 ± 35.6 mL/min. at the end of phase 2, p = 0.001). In Group NR, no statistically significant differences were observed between phases 1 and 2. Body weight reduction has a positive impact on renal hemodynamics, decreasing urinary albumin excretion as well as glomerular hyperfiltration in obese patients with metabolic syndrome.

DECREASED URINARY ALBUMIN EXCRETION ASSOCIATED WITH THE NORMALIZATION OF THE CIRCADIAN BLOOD PRESSURE PATTERN BY ANGIOTENSIN RECEPTOR BLOCKADE: PP.15.48

Objectives: Administration of angiotensin-receptor blockers (ARB) at bedtime as opposed to upon wakening increases the sleep-time relative blood pressure (BP) decline and their efficacy in lowering nocturnal BP. Urinary albumin excretion in non-dippers has been shown to be significantly greater than in dippers, although the potential effects on renal function of reverting the non-dipping pattern have not been clearly elucidated. Accordingly, we evaluated the administration-time-dependent effects on urinary albumin excretion of treatment with ARB in subjects with essential hypertension. Methods: We studied 815 untreated non-proteinuric hypertensive subjects (321 men), 48.7 ± 13.5 years of age, assigned to receive an ARB in monotherapy either on awakening or at bedtime. BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h before and after 12 weeks of treatment. The subjects collected their urine during the first 24 h of each BP monitoring session. Results: The reduction in awake BP was similar for both treatment-times. Treatment at bedtime, however, was significantly more efficient in reducing asleep BP (17.2 versus 11.2 mmHg after morning treatment; P < 0.001). The sleep-time relative BP decline was increased towards a more dipping pattern only after bedtime dosing (P < 0.001). Urinary albumin excretion was significantly reduced after treatment, and to a significant larger extent after bedtime dosing (P = 0.032). This albumin reduction was independent of the change in awake BP after treatment, but highly correlated with both the decrease in asleep BP and the increase in sleep-time relative BP decline (r = 0.321; P < 0.001), independently of treatment-time. Conclusions: Bedtime administration of ARB provides higher efficacy, as compared to morning treatment, in reducing the asleep BP mean, and improves the sleep-time relative BP decline towards a more dipper profile. This might be clinically relevant, as nighttime BP is a better prognostic marker of cardiovascular mortality than awake BP. Most important, the normalization of the circadian BP pattern towards a more dipper profile is associated with a significant decrease in urinary albumin excretion.

Effect of Thiazolidinediones on Albuminuria and Proteinuria in Diabetes: A Meta-analysis

Because of the major clinical and economic burden of diabetic nephropathy, new therapeutic tools to delay its progression are needed. Recent studies suggest that thiazolidinediones have renal benefits. We aimed to evaluate the effect of thiazolidinediones on urinary albumin and protein excretion in patients with diabetes mellitus. Systematic review and meta-analysis by searching MEDLINE/PubMed, EMBASE, and Cochrane CENTRAL databases (1991 to September 2009). Patients with diabetes mellitus. Randomized controlled trials. Thiazolidinediones (rosiglitazone and pioglitazone) compared with placebo or other antidiabetic agents. Weighted (WMDs) and standardized mean differences (SMDs) for changes in urine albumin or protein excretion between the thiazolidinedione and control groups. Of 171 originally identified articles, 15 studies (5 with rosiglitazone and 10 with pioglitazone) involving 2,860 patients were included in the analysis. In participants with baseline normo- or microalbuminuria, the WMD of proportional changes between the thiazolidinedione and control groups in urinary albumin excretion measured using time-specified collections was -64.8% (95% CI, -75.6 to -53.9) and the WMD of changes in albumin-creatinine ratio was -24.8% (95% CI, -39.6 to -10.0). Overall, in participants with normo- and microalbuminuria, thiazolidinedione treatment was associated with a significant decrease in urinary albumin excretion (SMD, -0.6 units of standard deviation [SD]; 95% CI, -0.8 to -0.4). Similarly, thiazolidinediones were associated with a significant decrease in urinary protein excretion in patients with proteinuria (SMD, -1.1 units of SD; 95% CI, -1.8 to -0.4). Significant heterogeneity across included studies in several subgroup analyses; patient-level data not available. Treatment with thiazolidinediones significantly decreases urinary albumin and protein excretion in patients with diabetes. This finding calls for clinical trials with hard renal outcomes to elucidate the potential benefits of thiazolidinediones on diabetic nephropathy.

Japan-Indonesia Collaborative Study of Imidapril on Antiproteinuric Effect in Hypertensive Patients with Chronic Kidney Disease (CKD)

Chronic kidney disease (CKD) is a comprehensive disease concept that includes chronic glomerulonephritis such as IgA nephropathy or lupus nephritis, diabetic nephropathy and hypertensive nephrosclerosis. CKD is a risk factor for end stage kidney disease (ESKD) and cardiovascular diseases (CVD). It is considered that angiotensin-converting enzyme (ACE) in¬hibitors and angiotensin II receptor blockers (ARBs) induce a marked renoprotective effect in patients with CKD. The purpose of the present Japan-Indonesia collaborative study was to eval¬uate the antiproteinuric effect of imidapril, one of the ACEIs, in hypertensive patients with CKD.Methods : Twenty three hypertensive CKD patients were treated with imidapril and a calci¬um channel blocker (CCB). Imidapril was added for patients who had been treated with a CCB such as diltiazem at the start of this study. When blood pressure (BP) did not reach the target level (< 130/85 mmHg), imidapril dosage was increased to 10 mg/day and administered for 12 months. Alternatively, patients were treated with 5~10 mg/day of imidapril.Results : In the imidapril + CCB combination therapy, systolic blood pressure (SBP) and dia-stolic blood pressure (DBP) were significantly reduced, both at 6 months and at the end of the clinical study. Only DBP reached values below the target level. Urinary albumin excretion (UAE) levels were markedly decreased at 6 and 12 months when compared with the baseline values (0.45 ± 0.54g/g-Cr indicating typical overt proteinuria) and these decreases at both time points were significant. The UAE levels at both 6 and 12 months complied with the diagnostic criteria for microalbuminuria (< 0.299 g/g-Cr).Conclusion : In this collaborative study, a combination of imidapril and a CCB, such as diltiaz¬em, significantly reduced BP, and reduced UAE, suggesting strict BP control may induce an effi¬cient decrease in UAE. It appears that imidapril-based therapy has renoprotective effects in hy¬pertensive patients with CKD.

Add-On Benefits of Amlodipine and Thiazide in Nondiabetic Chronic Kidney Disease Stage 1/2 Patients Treated with Valsartan

Hypertension frequently requires combination therapy to attain efficient control to prevent cardiovascular diseases effectively. This study was conducted to determine which add-on treatment is better, namely calcium channel blockers or diuretics, in improving vascular damage. In 70 nondiabetic chronic kidney disease stage 1/2 patients who had been already treated with angiotensin II type 1 receptor blocker valsartan for at least 12 months, amlodipine or hydrochlorothiazide was added to their existing medication. Pulse wave velocity (PWV), intima-media thickness (IMT) of the carotid arteries, urinary albumin excretion (UAE), and 24-hour ambulatory blood pressure (BP) were determined before and 12 months after the start of add-on treatments. Add-on amlodipine and add-on hydrochlorothiazide significantly and similarly decreased 24-hour ambulatory BP by 18 and 19 mm Hg, respectively, PWV by 206 and 184 cm/s, respectively, and UAE, but did not change the IMT. The decreases in BP significantly contributed to the decreases in PWV and UAE and suggested that the decrease in serum cholesterol level brought about by add-on amlodipine also contributed to the decrease in UAE. These results suggest that 12 months of add-on treatment with either amlodipine or hydrochlorothiazide could have beneficial effects in nondiabetic chronic kidney disease stage 1/2 patients already being treated with valsartan.

High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study

High-dose supplements of thiamine prevent the development of microalbuminuria in experimental diabetes. The aim of this pilot study was to assess whether oral supplements of thiamine could reverse microalbuminuria in patients with type 2 diabetes. Type 2 diabetic patients (21 male, 19 female) with microalbuminuria were recruited at the Diabetes Clinic, Sheikh Zayed Hospital, Lahore, Pakistan, and randomised to placebo and treatment arms. Randomisation was by central office in sequentially numbered opaque, sealed envelopes. Participants, caregivers and those assessing the outcomes were blinded to group assignment. Patients were given 3 x 100 mg capsules of thiamine or placebo per day for 3 months with a 2 month follow-up washout period. The primary endpoint was change in urinary albumin excretion (UAE). Other markers of renal and vascular dysfunction and plasma concentrations of thiamine were determined. UAE was decreased in patients receiving thiamine therapy for 3 months with respect to baseline (median -17.7 mg/24 h; p < 0.001, n = 20). There was no significant decrease in UAE in patients receiving placebo after 3 months of therapy (n = 20). UAE was significantly lower in patients who had received thiamine therapy compared with those who had received placebo (30.1 vs 35.5 mg/24 h, p < 0.01) but not at baseline. UAE continued to decrease in the 2 month washout period in both groups, but not significantly. There was no effect of thiamine treatment on glycaemic control, dyslipidaemia or BP. There were no adverse effects of therapy. In this pilot study, high-dose thiamine therapy produced a regression of UAE in type 2 diabetic patients with microalbuminuria. Thiamine supplements at high dose may provide improved therapy for early-stage diabetic nephropathy. CTRI (India) CTRI/2008/091/000112. Pakistan Higher Education Commission.

What Predicts Progression and Regression of Urinary Albumin Excretion in the Nondiabetic Population?

An increase or decrease in urinary albumin excretion (UAE) is associated with, respectively, a higher or lower risk for renal and cardiovascular disease, independent of widely known cardiovascular risk factors. This study aimed to identify factors that are associated with changes in UAE in the nondiabetic population using data of the Prevention of Renal and Vascular End stage Disease (PREVEND) Study, a community-based prospective cohort study. Data of the 6647 nondiabetic participants who completed the first (1997 through 2001) and second (2001 through 2003) screening were used. Change in UAE was categorized as regression (n = 650), stable (n = 5240), or progression (n = 757) on the basis of change in class during follow-up, with classes being a UAE <15, 15 to 30, 30 to 300, and >300 mg/24 h. With the use of stepwise forward multinomial regression analysis changes in BP, fasting glucose concentration, and start of antihypertensive drugs were found to be the most important modifiable variables associated with the risk for progression and regression (P < 0.01 for likelihood ratio test). The odds ratios to develop regression or progression of UAE during follow-up were 0.64 (95% confidence interval [CI] 0.57 to 0.73) and 1.91 (95% CI 1.72 to 2.12), respectively, per 10-mmHg increase in BP during follow-up, 0.89 (95% CI 0.80 to 0.98) and 1.09 (95% CI 1.01 to 1.17), respectively, per 1-mmol/L increase of fasting glucose levels during follow-up, and 1.57 (95% CI 1.21 to 2.06) and 0.70 (95% CI 0.51 to 0.95), respectively, for start of antihypertensive drugs during follow-up. These associations were independent of baseline BP, glucose, body mass index, estimated GFR, and UAE and changes in high-sensitivity C-reactive protein during follow-up. In conclusion, changes in glucose concentration and BP and start of antihypertensive drugs (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in >50% of cases) are associated with progression and regression of UAE in the nondiabetic population. Although associations do not necessarily suggest causality, it is hypothesized that in the general population, the most important ways to reduce UAE are by lowering glucose concentration and BP (including start of antihypertensive medication), even in normotensive, nondiabetic individuals.

The effect of spironolactone on circulating adipocytokines in patients with type 2 diabetes mellitus complicated by diabetic nephropathy

Angiotensin II can influence adipocytokine levels in adipose tissue, but the association between aldosterone, which mediates the effect of angiotensin II, and adipocytokines has yet to be fully elucidated. This study was designed to investigate the effect of spironolactone, a representative aldosterone blocker, on adipocytokines such as adiponectin, visfatin, plasminogen activator inhibitor (PAI)-1 and tumor necrosis factor α in patients with type 2 diabetic nephropathy: the study included 33 patients, 22 of whom were randomly assigned to the spironolactone (50 mg/d) group and 11 to the amlodipine (2.5 mg/d) group. Data were collected at baseline and after 3 months of treatment and compared with baseline data for 25 age-matched healthy subjects. A significant decrease in plasminogen activator inhibitor 1 in the spironolactone group was observed (22.6 ± 13.4 to 19.2 ± 11.3 ng/mL, P =.0323), but this did not occur in the amlodipine group. Adiponectin and visfatin levels did not change in the spironolactone and amlodipine groups, but significant increases in these adipocytokines were found in a subgroup of patients in the spironolactone group with glycated hemoglobin A 1c (HbA 1c) 8.0% or greater (11.8 ± 6.4 to 13.3 ± 7.4 μg/mL, P = .0344; and 1.39 ± 0.92 to 2.26 ± 0.76 ng/mL, P =.0397, respectively). The tumor necrosis factor α level at baseline exceeded the lower detection limit of the assay in only 6 patients in the spironolactone group, and no change occurred in these patients. Moreover, neither spironolactone nor amlodipine therapy caused a change in high-sensitivity C-reactive protein or soluble CD40 ligand, but a significant decrease in the level of brain natriuretic peptide was found in the spironolactone group only. Furthermore, significant increases of HbA 1c, creatinine, potassium, and aldosterone levels and plasma renin activity, and a decrease in urinary albumin excretion were also observed only in the spironolactone group. The number of patients with HbA 1c 8.0% or greater increased after spironolactone treatment. A significant decrease in systolic but not in diastolic blood pressure was observed in both treatment groups. In conclusion, our data suggest that in patients with type 2 diabetes mellitus complicated by diabetic nephropathy, spironolactone can decrease plasminogen activator inhibitor 1 and brain natriuretic peptide levels in addition to urinary albumin excretion, and systolic blood pressure, and that in patients with poor glycemic control, spironolactone can increase the levels of adiponectin and visfatin. However, the significant elevation of HbA 1c levels by spironolactone should be emphasized.

Decrease in Urinary Albumin Excretion Associated With the Normalization of Nocturnal Blood Pressure in Hypertensive Subjects

Previous results have indicated that valsartan administration at bedtime as opposed to on wakening improves the diurnal/nocturnal ratio of blood pressure without loss in efficacy and therapeutic coverage. We hypothesized that increasing this ratio could reduce microalbuminuria. We conducted a prospective, randomized, open-label, blinded endpoint trial on 200 previously untreated nonproteinuric patients with grade 1 to 2 essential hypertension, assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The significant blood pressure reduction after 3 months of therapy was similar for both treatment times. The diurnal/nocturnal blood pressure ratio was unchanged after valsartan on awakening, but significantly increased from 7.5 to 12.2 (P<0.001) when valsartan was administered at bedtime. Urinary albumin excretion was significantly reduced by 41% after bedtime treatment. This reduction was independent of the 24-hour blood pressure decrease but highly correlated with the decrease in nocturnal blood pressure and mainly with the increase in diurnal/nocturnal ratio (P<0.001). Bedtime valsartan administration improves the diurnal/nocturnal blood pressure ratio to a more dipper profile. This normalization of the circadian blood pressure pattern is associated with a significant decrease in urinary albumin excretion and plasma fibrinogen, and could thus reduce the increased cardiovascular risk in nondipper hypertensive patients.

The decrease in urinary albumin excretion after irbesartan treatment in normotensive diabetes type 1 patients with incipient nephropathy is related to blood pressure, and not to changes in soluble cytokines and growth factors

P-237 Key Words: Microalbuminuria, Growth Factors, Irbesartan

A novel peroxisome proliferator-activated receptor (PPAR)γ agonist, NIP-222, reduces urinary albumin excretion in streptozotocin-diabetic mice independent of PPARγ activation

NIP-222 is a novel peroxisome proliferator-activated receptor (PPAR)γ agonist. This study provides evidence that NIP-222 decreases urinary albumin excretion (UAE) in diabetic mice independent of its PPARγ activation. We compared the effect of NIP-222 and another PPARγ agonist, troglitazone, on UAE, plasma glucose level, blood pressure, and creatinine clearance (C cr) in streptozotocin (STZ)-induced diabetic mice. Treatment for 3 weeks with NIP-222 (30 mg/kg) was associated with a significant decrease in UAE without any change in blood pressure, creatinine clearance, or plasma glucose level. In contrast, UAE did not decrease in mice treated with troglitazone (300 mg/kg). These results indicate that NIP-222 has PPARγ independent effects on UAE in diabetic mice and suggest that this agent may have potential to minimize the development and progression of diabetic nephropathy.