Reduction In Urinary Albumin Excretion Research Articles

Reduction of albumin urinary excretion is associated with reduced cardiovascular events in hypertensive and/or diabetic patients. A meta-regression analysis of 32 randomized trials

BackgroundThe association between renal dysfunction and risk of cardiovascular (CV) events and mortality has been reported in several studies. However, it is unclear whether reduction in urinary albumin excretion (UAE) is associated with reduced risk of clinical events. Therefore, we sought to investigate, in a meta-regression analysis of randomized studies enrolling hypertensive and/or diabetic patients, whether changes in UAE are associated with changes in CV outcomes and all-cause mortality. MethodsMEDLINE, ISI Web of Science, Cochrane Database and Scopus were searched for randomized trials enrolling more than 200 diabetic and/or hypertensive patients, reporting UAE at baseline and at end of follow-up and CV events [CV death, myocardial infarction (MI), and stroke], as well all-cause mortality. ResultsThirty-two trials enrolling 80,812 participants were included in analyses. Meta-regression analysis showed that each 10% reduction of UAE was significantly associated with 13% reduction of MI (Regression Coefficient [RC]:0.0055; 95% Confidence Interval [CI]:0.0014 to 0.0095; p=0.010), with 29% reduction of stroke (RC:0.0124; CI:0.0030 to 0.0218; p=0.013) and with 14% reduction of the composite outcome (CV death, MI, stroke)(RC:0.0059; CI:0.0027 to 0.0090; p=0.001), whereas not significantly associated with all-cause (RC:0.0028; CI:−0.0047 to 0.0103; p=0.486) and CV mortality (RC:0.0028; CI:−0.0047 to 0.0103; p=0.447). Results were mostly confirmed by sensitivity analysis. No heterogeneity or publication bias was detected. ConclusionsReduction in UAE is associated with reduced risk of MI and stroke in diabetic and/or hypertensive patients. These findings suggest that UAE changes may represent a valuable intermediate end-point for CV risk evaluation in clinical practice.

Sitagliptin improves albuminuria in patients with type 2 diabetes mellitus.

The aim of the present study was to determine the effect of sitagliptin on microalbuminuria in patients with type2 diabetes mellitus. A total of 85 patients with type2 diabetes mellitus (age >20years, <80years, hemoglobin A1c [HbA1c] <8.4%) were randomized to patients taking sitagliptin 50mg or other oral glucose-lowering agents. The following parameters were evaluated at 0, 3 and 6months after the treatment: bodyweight, blood pressure, HbA1c, fasting plasma glucose, fasting plasma insulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate and urinary albumin excretion. The primary outcome was changes in urinary albumin excretion at 6months. Significant and comparable falls in HbA1c and fasting plasma glucose were found in both groups. However, sitagliptin significantly reduced urinary albumin excretion within 6months, especially in patients with high urinary albumin at baseline. A total of 27 patients with normoalbuminuria showed a reduction in urinary albumin excretion, suggesting that sitagliptin prevents the development of albuminuria. A total of 15 patients with albuminuria showed a reduction in urinary albumin excretion, suggesting the beneficial effect of sitagliptin in the early stage of diabetic nephropathy. There was a significant correlation between improvement of proteinuria and that of diastolic blood pressure. The results suggested that sitagliptin improved albuminuria, in addition to improving glucose. The mechanism of the reduction of albuminuria by sitagliptin could be a direct effect, as well as an increase in active glucagon-like peptide-1, independently affecting blood pressure, bodyweight and glucose metabolism. This trial was registered with the University Hospital Medical Information Network (UMIN no. #000010871).

Long-term effects of addition of mineralocorticoid receptor antagonist to angiotensin II receptor blocker in patients with diabetic nephropathy: a randomized clinical trial

Addition of spironolactone (SPR) to angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) might provide antiproteinuric effects beyond what is gained by either medication alone. This study was designed to assess the long-term efficacy of SPR/ARB combination in comparison with the standard ACE/ARB regimen in diabetic nephropathy. In an open-label, parallel-group, single-center, randomized clinical trial (NCT01667614), 136 patients with diabetes and proteinuria, already treated with enalapril and losartan, were included. In 74 patients, ACE inhibitors were discontinued. After a wash-out period of 2 weeks, 25 mg SPR daily was initiated. The remainder of the patients (n = 62) received ACE inhibitors and ARBs as before. Patients were followed every 3 months for 18 months. During each visit, systolic and diastolic blood pressure (BP), urinary albumin excretion (UAE), serum creatinine, estimated glomerular filtration rate (eGFR) and serum potassium concentrations were determined. After 18 months, three patients in the SPR/ARB group developed asymptomatic hyperkalemia. SPR/ARB significantly reduced both systolic and diastolic BP (P < 0.001 and 0.001, respectively). SPR/ARB decreased UAE by 46, 72 and 59% after 3, 12 and 18 months, respectively. Compared with the continuation regimen, SPR/ARB was superior in UAE reduction (P = 0.017 after 18 months), independent of BP change. In both groups, eGFR declined significantly over the trial course and the decline rate did not differ significantly between the two groups. Addition of SPR to ARB provides added benefits with respect to BP control and proteinuria diminution. These antiproteinuric effects are not accompanied by prevention of eGFR loss compared with conventional therapy with ACE/ARB.

Regression of left ventricular hypertrophy and microalbuminuria changes during antihypertensive treatment

The objective of the present study was to assess the regression of left ventricular hypertrophy (LVH) during antihypertensive treatment, and its relationship with the changes in microalbuminuria. One hundred and sixty-eight previously untreated patients with echocardiographic LVH, 46 (27%) with microalbuminuria, were followed during a median period of 13 months (range 6-23 months) and treated with lifestyle changes and antihypertensive drugs. Twenty-four-hour ambulatory blood pressure monitoring, echocardiography and urinary albumin excretion were assessed at the beginning and at the end of the study period. Left ventricular mass index (LVMI) was reduced from 137 [interquartile interval (IQI), 129-154] to 121 (IQI, 104-137) g/m (P < 0.001). Eighty-nine patients (53%) had a reduction in LVMI of at least 17.8 g/m, and an LVH regression rate of 43.8 per 100 patient-years [95% confidence interval (CI) 35.2-53.9]. The main factor related to LVH regression was the reduction in SBP24 h [multivariate odds ratio (ORm) 4.49; 95% CI 1.73-11.63; P = 0.005, highest tertile compared with lower tertiles]. Male sex (ORm 0.39; 95% CI 0.17-0.90; P = 0.04) and baseline glomerular filtration rate less than 90 ml/min per 1.73 m (ORm 0.39; 95% CI 0.17-0.90; P = 0.03) were associated with a lower probability of LVH regression. Patients with microalbuminuria regression (urinary albumin excretion reduction >50%) had the same odds of achieving regression of LVH as patients with normoalbuminuria (ORm 1.1; 95% CI 0.38-3.25; P = 0.85). However, those with microalbuminuria at baseline, who did not regress, had less probability of achieving LVH regression than the normoalbuminuric patients (OR 0.26; 95% CI 0.07-0.90; P = 0.03) even when adjusted for age, sex, initial LVMI, GFR, blood pressure and angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) treatment during the follow-up. Patients who do not have a significant reduction in microalbuminuria have less chance of achieving LVH regression, independent of blood pressure reduction.

Association of a Reduction in Central Obesity and Phosphorus Intake With Changes in Urinary Albumin Excretion: The PREMIER Study

Excess adiposity and dietary factors may be important determinants of urinary albumin excretion (UAE). Observational analysis of PREMIER, a randomized trial designed to lower blood pressure using behavioral interventions (counseling on weight loss, healthy diet, and exercise). 481 participants with normal kidney function who provided adequate 24-hour urine collections at baseline and 6 months. Change in waist circumference; 24-hour urine sodium, potassium, and phosphorus excretion; and protein intake estimated from urea nitrogen. The primary outcome was change in log-transformed 24-hour UAE over 6 months. After 6 months, the proportion of individuals with UAE ≥10 mg/d decreased from 18.7% to 12.7% (P < 0.001). Changes in mean waist circumference (-4.2 ± 6.6 [SD] cm), 24-hour excretion of sodium (-28.2 ± 71.7 mmol/d), potassium (+8.4 ± 27.8 mmol/d), phosphorus (-27.7 ± 314.1 mg/d), and protein intake (-1.7 ± 19.4 g/d) were observed. After adjustment for relevant covariates, the following variables were associated significantly with reduction in ln(UAE) in separate models: decrease in waist circumference (P = 0.001), decrease in 24-hour urine phosphorus excretion (P < 0.001), and decrease in protein intake (P = 0.01). In a multivariable model including these 3 predictors, decreases in waist circumference (P = 0.002) and 24-hour urine phosphorus excretion (P = 0.03), but not change in protein intake (P = 0.5), remained associated significantly with reduction in ln(UAE). These associations remained significant even after adjustment for changes in blood pressure and insulin resistance. Baseline UAE and metabolic syndrome modified the relationship of waist circumference with ln(UAE); specifically, individuals with higher UAE and baseline metabolic syndrome experienced greater reductions in ln(UAE) from decreases in waist circumference. Observational study with potential for confounding. In adults with normal kidney function, decreases in waist circumference and 24-hour urine phosphorus excretion are associated with reductions in UAE. These findings support the rationale for clinical trials to determine whether reducing dietary phosphorus intake or waist circumference could prevent chronic kidney disease or slow its progression.

Reduction in Morning Blood Pressure Is a Key Factor for Ameliorating Urinary Albumin Excretion in Patients With Morning Hypertension Irrespective of Treatment Regimen

The Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study has shown that losartan/hydrochlorothiazide (HCTZ) combination is superior to high-dose losartan in not only reducing morning systolic blood pressure (SBP) but also ameliorating urinary albumin excretion (UAE) after 3-month treatment. The purpose of the present study was to investigate factors associated with UAE reduction in on-treatment patients with morning hypertension. A total of 95 patients registered in the MAPPY study were analyzed. Patients were treated with either a losartan/HCTZ combination regimen (n=47) or a high-dose losartan regimen (n=48). Three-month treatment significantly reduced morning SBP, evening SBP, and clinic SBP (P<0.001, P<0.05, and P<0.01, respectively). UAE and serum uric acid were significantly decreased (P<0.01 for both) without the change in estimated glomerular filtration rate. Multiple linear regression analysis indicated that %morning SBP reduction and baseline UAE were independent determinants of the UAE reduction (P=0.001 for both). After adjustments for the reduction in morning-evening SBP difference, baseline UAE, and %uric acid reduction, estimated %UAE reduction level was positively correlated with the tertiles of the increasing %morning SBP reduction level (P=0.031 for trend). Moreover, subgroup analysis showed that morning SBP reduction was an independent determinant of UAE reduction in both treatment regimens. Reduction in morning SBP was a key factor in UAE reduction in patients with morning hypertension, irrespective of treatment regimen.

Abstract 9906: Losartan/hydrochlorothiazide Combination was Superior to High-dose Losartan in Controlling Morning Hypertension and Reducing Urinary Albumin Excretion

Background: There is little evidence for treatment of morning hypertension, an independent risk for cardiovascular events. Thus, we compared the efficacy of losartan/hydrochlorothiazide combination and high-dose losartan in patients with morning hypertension. Methods: A total of 216 outpatients having hypertension medication were enrolled in a 3-month, prospective, randomized, open-labeled, multicenter trial, when they had systolic blood pressure (SBP) greater than 135 mmHg and/or diastolic blood pressure greater than 85 mmHg in the morning on home blood pressure self-measurement. An antihypertensive drug was randomly switched to a 50-mg losartan/12.5-mg hydrochlorothiazide combination tablet (Combination group, N=109) or 100-mg losartan (High-dose group, N=106). Results: At baseline, SBP levels, clinical background, and biochemical parameters were similar in the two groups. Primary end-point: Morning SBP was reduced by 18 mmHg in Combination group and by 8 mmHg in High-dose group (p&lt;0.001 for both), whereas the resultant levels were lower in Combination group than in High-dose group (P&lt;0.001). Secondary end-points: Urinary albumin excretion (UAE) was reduced in Combination group (P&lt;0.05), but not in High-dose group, although estimated glomerular filtration rates were not changed in either group. Serum uric acid (UA) was decreased in High-dose group (P&lt;0.001), but was not changed in Combination group. %UAE reduction was significantly associated with %morning SBP reduction, UA reduction (negatively), or combination regimen. Multiple linear regression analysis exhibited that %morning SBP reduction was an independent factor associated with %UAE reduction (β=0.277, P&lt;0.05). After adjustments for treatment regimen and UA reduction, %UAE reduction was positively correlated with the tertiles based on morning SBP reduction levels (P=0.02 for trend). Conclusions: Losartan/hydrochlorothiazide combination was more effective than high-dose losartan for controlling morning hypertension and reducing UAE. The reduction in morning SBP was associated with UAE reduction in patients with morning hypertension.

Reduction in urinary albumin excretion with a moderate low-carbohydrate diet in patients with type 2 diabetes: a 12-month intervention

IntroductionUrinary albumin excretion (UAE) is a marker of the early phase of diabetic nephropathy. Although a low-carbohydrate diet (LCD) has been shown to effectively improve glycemic control in patients with type 2 diabetes (T2DM), its effects on UAE remain unknown.Patients and methodsA total of 124 patients (mean age ± standard deviation, 61.6 ± 9.2 years) with T2DM were instructed to consume a moderate LCD (1734 ± 416 kcal/d; % carbohydrate:fat:protein = 38:37:19) for 12 months. We measured the levels of UAE, hemoglobin A1c, fasting plasma glucose, fasting serum insulin (IRI), and the serum lipid profiles in the patients and recorded their dosages of antidiabetic drugs during this 12-month period.ResultsOf the 124 patients, 68 were normoalbuminuric, 50 were microalbuminuric, and six were macroalbuminuric at baseline. The patients had relatively good compliance with the moderate LCD diet. After 12 months, the mean levels of hemoglobin A1c, fasting plasma glucose, IRI, homeostasis model assessment-estimated insulin resistance, and the body mass index of all participants significantly decreased (P = 0.003 for IRI and P < 0.001 for the other parameters). Among the microalbuminuric patients (n = 50), remission to normoalbuminuria was frequently achieved (52%) and the geometric mean UAE significantly decreased by 53% (95% confidence interval: 43, 62) over 12 months (P < 0.001). After patients taking an angiotensin 2 receptor blocker were excluded, the UAE significantly decreased by 41% (n = 26, 95% confidence interval: 25, 54; P < 0.001). Moreover, the reduction in UAE was significantly and positively correlated with a reduction in homeostasis model assessment-estimated insulin resistance levels (rs = 0.308; P = 0.031).ConclusionA moderate LCD (38% carbohydrate diet) achieved a remarkable reduction in UAE over 12 months in microalbuminuric patients with T2DM.

Efeitos do controle glicêmico obtido em curto prazo sobre a microalbuminúria e a filtração glomerular em pacientes diabéticos do tipo 2 com controle glicêmico precário

The intensive glucose control significantly reduces the risk of microvascular complications, including nephropathy. We assess the impact of glycemic control through calculation of weekly mean glycemia (WMG) and glycemic variability (GV) on 24 hours ambulatory blood pressure (ABPM), urinary albumin excretion (UAE) and glomerular filtration rate (GFR). 53 patients with type 2 diabetes mellitus (DM2) were randomly divided into two groups to receive conventional or intensive treatment, which included weekly visits for medication adjustments and implementation of an educational plan for six weeks. We observed glycemic control (WMG < 150 mg/dL and VG < 50) in 75% (n = 21) of the patients on the intervention treatment (IT) (n = 28), and in 24% (n = 6) of the ones on the conventional treatment (CT) (n = 25) (p < 0.001). Considering patients of the two groups, 14 out of the 27 patients who achieved glycemic control showed initial mean systolic blood pressure (SBP) > 120 mmHg which was reduced from 138.4 ± 10.1 to 127.8 ± 11.6 mmHg (p = 0.023) at the end of week six. Reductions in SBP and diastolic BP (DBP) during wakefulness and sleep did not occur in the group (n = 17) without glycemic control and with SBP > 120 mmHg. Initially, 15 patients had GFR > 120 mL/min, and after six weeks, only the subgroup that achieved glycemic control (n = 7) showed a reduction of 137.2 ± 16 to 122.2 ± 25.2 mL/min (p = 0.02). At the beginning of the study, another fifteen patients presented with microalbuminuria. After six weeks, regardless of whether they achieved glycemic control or not, there was reduction in UAE, from 63.0 ± 43.1 to 24.8 ± 19.5 mg/g creatinine (p = 0.02). Thus short term glycemic control resulted in reductions of BP, GFR and the UAE in patients with DM2, which are beneficial for renal protection.

Is home blood pressure variability itself an interventional target beyond lowering mean home blood pressure during anti-hypertensive treatment?

It is unknown whether home blood pressure (BP) variability reduction is associated with target organ damage (TOD) protection independently of home mean BP reduction. We enrolled 310 hypertensive patients whose systolic BP (SBP) at home was over 135 mm Hg. The subjects measured their BP in the morning and evening for 7 days. In addition, we measured urinary albumin excretion (UAE) as a marker of TOD before and after 6 months of candesartan treatment (+thiazidediuretics). At baseline, UAE was associated with average home SBP (r=0.24, P<0.001), the s.d. of home SBP (r=0.15, P=0.011), and the maximum home SBP (r=0.27, P<0.001). During the intervention, significant reductions were found in average home SBP (146±13 vs. 132±12 mm Hg, P<0.001), s.d. of home SBP (12.9±4.8 vs. 11.8±4.4 mm Hg, P<0.001), and maximum home SBP (172.5±18.0 vs. 155.9±17.5 mm Hg, P<0.001). UAE levels were significantly reduced after 6 months of therapy compared with baseline (18.9 vs. 12.1 mg g(-1) Cre, P<0.001). In multiple regression analysis, the treatment-induced reduction in UAE was significantly associated with that of average home BP (P=0.003) but was not associated with that of s.d. of home SBP or that of maximum home SBP. Home BP variability is not itself an interventional target beyond lowering mean home BP during anti-hypertensive treatment.

Viper venom for diabetic nephropathy

Diabetic nephropathy is the leading cause of end-stage renal disease in the United States. Renin-angiotensin-aldosterone system (RAAS) blockers are thought to have a specific renoprotective effect in diabetes. Hirst et al. report the results of randomized clinical trials assessing the effects of RAAS inhibitors on urinary albumin excretion levels in diabetic patients. Although reductions in urinary albumin excretion were observed, whether RAAS inhibitors offer additional protection over other antihypertensive agents is unclear.

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.

Association of Home and Ambulatory Blood Pressure Changes With Changes in Cardiovascular Biomarkers During Antihypertensive Treatment

Our aim was to assess whether home blood pressure (HBP) and ambulatory BP monitoring measurement (ABPM), in addition to office BP (OBP) predict changes of cardiovascular biomarkers during antihypertensive treatment. Two hundred and fifty-two hypertensive patients (mean age, 68 years; men: 41%) underwent measurements of OBP, HBP, ABPM, and cardiovascular biomarkers (urinary albumin excretion (UAE) and brain natriuretic peptide (BNP)) before and after 6 months of treatment with candesartan (± thiazide-diuretics). During the intervention, the OBP, HBP, daytime and night-time BP, and UAE levels were all significantly reduced (all P < 0.01). BNP was reduced only in the patients using diuretics (P = 0.003). For predicting the treatment-induced change in UAE, each of home systolic BP (SBP) and night-time SBP changes, but not daytime SBP change, had independent and significant value beyond OBP measurement (both P < 0.05). In contrast, for predicting the treatment-induced change in BNP, night-time SBP changes, but not home or daytime SBP changes, had significant value beyond OBP measurement (both P < 0.05). Patients who achieved a reduction in all three SBP parameters (office, home, and night-time SBP; n = 122) showed a more significant reduction of UAE compared with those who did not (-52.6 vs. -32.5%; P = 0.001), and patients who achieved a reduction in both office and night-time SBP (n = 134) showed a more significant reductions of BNP than those who did not (-12.9 vs. +12.8%; P < 0.05). HBP and ABPM measurements, particularly night-time SBP values provide additional information for predicting treatment-induced changes of cardiovascular biomarkers when used in conjunction with office SBP measurement during antihypertensive treatment.

Efficacy and safety of combination therapy with candesartan cilexetil and pioglitazone hydrochloride in patients with hypertension and type 2 diabetes mellitus

Objective:To evaluate the efficacy and safety of combination therapy with candesartan cilexetil (CC) and pioglitazone hydrochloride (PIO) in patients with hypertension and type 2 diabetes mellitus.Methods:A 12-week, double-blind, randomized, parallel-group study in patients with mild-to-moderate essential hypertension and type 2 diabetes mellitus was followed by a 40-week, single-blind study. Patients (N = 377) were randomized to treatment with CC 8 mg/PIO 30 mg (n = 62), CC 8 mg/PIO 15 mg (n = 63), CC 4 mg/PIO 30 mg (n = 63), CC 4 mg/PIO 15 mg (n = 63), CC 8 mg/PIO 0 mg (n = 63), or CC 0 mg/PIO 30 mg (n = 63). Primary efficacy measures were changes in diastolic blood pressure (DBP) and HbA1C at Week 12.Results:CC/PIO combination therapy improved blood pressure (BP)/glycemic control for 52 weeks. At the end of 12-week treatment period, DBP decreased to a significantly greater extent in the 8/30 + 8/15 + 8/0 (combined CC 8 mg) group (−10.5 mmHg, p < 0.0001) and the 4/30 + 4/15 (combined CC 4 mg) group (−9.1 mmHg, p = 0.0022) than in the 0/30 (CC 0 mg) group (−5.3 mmHg). HbA1C significantly decreased in the 8/30 + 4/30 + 0/30 (combined PIO 30 mg) group (−0.35%, p < 0.0001) and the 8/15 + 4/15 (combined PIO 15 mg) group (−0.15%, p < 0.0001) compared with the 8/0 (PIO 0 mg) group (0.35%). Urinary albumin excretion reduction seen with the 0/30 and the 8/0 groups was significantly enhanced by CC/PIO combination. Clinical significance of this renoprotective effect of CC/PIO combination therapy needs to be studied further. Prolonged combined use of CC/PIO did not increase adverse events. Drug-related adverse events were similar to those during clinical use of CC and PIO.Conclusion:CC/PIO combination therapy improved BP/glycemic control and was well tolerated for 52 weeks. Thus, CC/PIO combination therapy is useful in patients with hypertension and type 2 diabetes mellitus.

Antiproteinuric Effect of Chemokine C-C Motif Ligand 2 Inhibition in Subjects with Acute Proliferative Lupus Nephritis

Background/Aims: To test the role of chemokine C-C motif ligand 2 (CCL2) in the pathogenesis of lupus nephritis (LN), we evaluated the effects of CCL2 inhibition by bindarit therapy in patients with systemic lupus and active renal disease. Methods: In this proof-of-concept, prospective, randomized, double-blind clinical study, 22 subjects with acute LN were assigned on a 1:1 ratio to 24-week treatment with bindarit (1,200 mg/day) or matching placebo. All subjects were on the same standardized steroid background therapy. Urinary CCL2, urinary albumin excretion (UAE), estimated glomerular filtration rate, time to remission and time to relapse of LN were compared between groups. Results: Urinary CCL2 significantly decreased during bindarit therapy (p = 0.008 vs. baseline) with a reduction that approximated 50% at study end. CCL2 reduction was paralleled by a persistent reduction in UAE that averaged 80% vs. baseline and approximated 90% at study end. Renal function recovery was similar and no difference was found in terms of time to remission and time to relapse of LN between treatment arms. Treatment was safe and well tolerated in all patients. Conclusion: In lupus subjects with active nephritis, bindarit significantly reduced albuminuria and urinary CCL2 levels. This study provides the background for longer trials to test renoprotective effect of CCL2 inhibition in LN.

Initial Angiotensin Receptor Blockade–Induced Decrease in Albuminuria Is Associated With Long-Term Renal Outcome in Type 2 Diabetic Patients With Microalbuminuria

OBJECTIVEWe aimed to investigate the individual impact of initial responses in urinary albumin excretion (UAE) and systolic blood pressure (SBP) to angiotensin II receptor blocker (ARB) treatment on long-term renal outcome in patients with type 2 diabetes and microalbuminuria.RESEARCH DESIGN AND METHODSIn a post hoc analysis of the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA)-2 trial we first assessed the individual variability in UAE and SBP response (0–6 months) in 531 subjects. Subsequently, we analyzed the individual effect of both response parameters on renal outcome defined as change in estimated glomerular filtration rate (eGFR) during 2 years of follow-up.RESULTSThe median reductions in UAE and SBP in the population were −18% and −11 mmHg, respectively. In irbesartan-treated patients, 85 (24.4%) had a robust (>median) reduction in UAE but not in SBP (discordant SBP response) and 67 (19.3%) had a robust (>median) reduction in SBP but not in UAE (discordant UAE response). The degree of reduction in UAE was independently associated with the rate of eGFR decline (P = 0.0037). SBP showed a similar trend (P = 0.087). The relation between a larger UAE reduction and a slower rate of renal function decline was present in both cohorts with a SBP change above and below the median.CONCLUSIONSWithin an individual, UAE response to ARB therapy may be discordant from SBP response. The initial change in UAE was independently associated with eGFR slope; the more UAE reduction the less eGFR decline, irrespective of the SBP change. These results suggest that in microalbuminuric patients with type 2 diabetes, UAE should be monitored after initiation of therapy and a separate target for renoprotective therapy.

Pioglitazone reduces urinary albumin excretion in renin−angiotensin system inhibitor-treated type 2 diabetic patients with hypertension and microalbuminuria: the APRIME study

The aim of his study was to compare the efficacy of pioglitazone with metformin on the reduction of albuminuria in type 2 diabetic patients with hypertension and microalbuminuria treated with renin-angiotensin system inhibitors (RAS-Is). The open-label, randomized trial was performed in type 2 diabetic patients with hypertension and microalbuminuria. On the basis of the treatment with RAS-Is, 68 patients with microalbuminuria received either pioglitazone (15-30 mg/day; n = 32) or metformin (500-750 mg/day; n = 31) for 52 weeks. Urinary albumin-to-creatinine ratio (UACR) was measured every 12 weeks. After 52 weeks of treatment, the changes in the log-UACR from baseline were -8.3% in the pioglitazone group and +4.2% in the metformin group (p = 0.01), with similar glycemic and blood pressure changes. The combination of pioglitazone and RAS-Is showed therapeutic benefit in the reduction of urinary albumin excretion for type 2 diabetic patients with hypertension and microalbuminuria.

Renin-angiotensin-aldosterone system blockade and urinary albumin excretion in community-based patients with Type 2 diabetes: The Fremantle Diabetes Study

To determine whether the reduction in urinary albumin excretion through renin-angiotensin-aldosterone system blockade found in intervention trials extends to community-based patients with Type 2 diabetes. We analysed data from 302 participants in the longitudinal observational Fremantle Diabetes Study who commenced angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy during follow-up and who had an annual assessment on either side of this therapeutic change. At baseline, the patients had a mean age of 63.8 years, a median diabetes duration of 4 years, a median HbA(1c) of 7.6% (60 mmol/mol) and a geometric mean (sd range) urinary albumin:creatinine ratio of 3.3 mg/mmol (0.8-13.1 mg/mmol). The percentages with normo-, micro- and macroalbuminuria were 49.0, 38.4 and 12.6%, respectively. During 6.1 ± 1.7 years of follow-up, initiation of renin-angiotensin-aldosterone system blockade was associated with a larger geometric mean (sd range) absolute albumin:creatinine ratio reduction in the patients with macroalbuminuria compared with those who had either normo- or microalbuminuria [-40.9 (-825.7 to 159.9) mg/mmol) vs. 1.7 (-1.6 to 20.0) mg/mmol and -0.5 (-23.0 to 39.5) mg/mmol, respectively; P < 0.001]. These changes remained significant after adjustment for changes in blood pressure and other potentially confounding variables, including drug dose and angiotensin-converting enzyme genotype. The post-treatment median albumin:creatinine ratios were 35.4 and 27.4% lower than before treatment in those with micro- or macroalbuminuria, respectively. Usual-care initiation of renin-angiotensin-aldosterone system blockade confers a quantitatively similar renal benefit to that in intervention trials in Type 2 diabetes.

Insulin in podocyte podiatry.

Insulin in podocyte podiatry.

New treatment for IgA nephropathy: enteric budesonide targeted to the ileocecal region ameliorates proteinuria

Systemic corticosteroid treatment has been shown to exert some protection against renal deterioration in IgA nephropathy (IgAN) but is not commonly recommended for long-term use due to the well-known systemic side effects. In this study, we investigated the efficacy and safety of a new enteric formulation of the locally acting glucocorticoid budesonide (Nefecon®), designed to release the active compound in the ileocecal region. The primary objective was to evaluate the efficacy of targeted release budesonide on albuminuria. Budesonide 8 mg/day was given to 16 patients with IgAN for 6 months, followed by a 3-month follow-up period. The efficacy was measured as change in 24-h urine albumin excretion, serum creatinine and estimated glomerular filtration rate (eGFR). The median relative reduction in urinary albumin excretion was 23% during the treatment period (interquartile range: -0.36 to -0.04, P = 0.04) with pretreatment values ranging from 0.3 to 6 g/24 h (median: 1.5 g/24 h). The median reduction in urine albumin peaked at 40% (interquartile range: -0.58 to -0.15) 2 months after treatment discontinuation. Serum creatinine was reduced by 6% (interquartile range: -0.12 to -0.02; P = 0.003), and eGFR [Modification of Diet in Renal Disease (MDRD)] increased ∼8% (interquartile range: 0.02-0.16, P = 0.003) during treatment. No major corticosteroid-related side effects were observed. In the present pilot study, enteric budesonide targeted to the ileocecal region had a significant effect on urine albumin excretion, accompanied by a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation, while eGFR calculated from Cockcroft-Gault equation and cystatin C was not changed. Enteric budesonide may represent a new treatment of IgAN warranting further investigation.