The RENAAL Study is a double-blind, placebo-controlled trial to evaluate the renal protective effects of losartan in Type 2 diabetic patients with nephropathy. The study has enrolled 1513 patients and is expected to continue for 3.5 years after the last patient has been entered. Eligible patients must have a urinary albumin:creatinine ratio of at least 300 mg/g and serum creatinine between 1.3 to 3.0 mg/dL. Eligible hypertensive or normotensive patients are randomised to receive either losartan or placebo, in addition to their existing antihypertensive therapy. Medications that block angiotensin production or action, are excluded. The primary endpoint is a composite of the time to first event of doubling of serum creatinine, end-stage renal disease, or death; secondary endpoints include cardiovascular events, progression of renal disease, and changes in proteinuria; tertiary endpoints include quality of life, healthcare resource utilisation, and amputations. Patients include Caucasians (48.6%), Blacks (15.2%), Asians (16.7%), and Hispanics (18.2%). Baseline urinary albumin:creatinine ratio and serum creatinine levels average 1867 mg/g and 1.9 mg/dL, respectively. Mean systolic and diastolic blood pressures are 153 and 82 mmHg, respectively. RENAAL will document whether blockade of the AII receptor with losartan produces clinical benefits in patients with Type 2 diabetes and nephropathy.

Abstract-Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP Ն140 mm Hg, Ͻ180 mm Hg, diastolic BP Ͻ110 mm Hg) were randomly assigned (age 59Ϯ9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria Ͼ20 and Ͻ500 g/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril.

BackgroundHypertensive patients with reduced blood pressure fall (BPF) at night are at higher risk of cardiovascular events (CVE).MethodsWe evaluated in hypertensive diabetic patients, if a reduced nocturnal BPF can precedes the development of diabetic nephropathy (DN). We followed 70 patients with normal urinary albumin excretion (UAE) for two years. We performed 24-hours ambulatory BP monitoring in baseline and at the end of the study.ResultsFourteen (20%) patients (GI) developed DN (N = 11) and/or CVE (n = 4). Compared to the remaining 56 patients (GII) in baseline, GI had similar diurnal systolic (SBP) and diastolic BP (DBP), but higher nocturnal SBP (138 ± 15 vs 129 ± 16 mmHg; p < 0.05) and DBP (83 ± 12 vs 75 ± 11 mmHg; p < 0,05). Basal nocturnal SBP correlated with occurrence of DN and CVE (R = 0.26; P < 0.05) and with UAE at the end of the study (r = 0.3; p < 0.05). Basal BPF (%) correlated with final UAE (r = -0.31; p < 0.05). In patients who developed DN, reductions occurred in nocturnal systolic BPF (12 ± 5 vs 3 ± 6%, p < 0,01) and diastolic BPF (15 ± 8 vs 4 ± 10%, p < 0,01) while no changes were observed in diurnal SBP (153 ± 17 vs 156 ± 16 mmHg, NS) and DBP (91 ± 9 vs 90 ± 7 mmHg, NS). Patients with final UAE < 20 μg/min, had no changes in nocturnal and diurnal BP.ConclusionsOur results suggests that elevations in nocturnal BP precedes DN and increases the risk to develop CVE in hypertensive patients with T2DM.

Background/Aims: To evaluate cystatin C as a marker of diabetic kidney disease in normoalbuminuric diabetic patients without chronic kidney disease (CKD). Methods: A cross- sectional study was carried out comprising 243 hypertensive patients, 61 of them with type 2 diabetes, presenting normoalbuminuria and an estimated glomerular filtration rate (eGFR) ≧60 ml/min/1.73 m². Renal function assessment included determinations of serum creatinine and cystatin C levels, microalbuminuria, as well as eGFR through Cockcroft-Gault and Modification of Diet in Renal Disease equations. Results: Diabetic patients presented higher cystatin C levels than nondiabetic patients (0.95 ± 0.19 vs. 0.89 ± 0.17 mg/l; p < 0.05). In the binary logistic regression, the presence of diabetes and metabolic syndrome was significantly associated with elevated cystatin C levels. Diabetic patients also presented a slightly greater albuminuria (6.72 ± 4.43 vs. 5.07 ± 3.59 µg/min; p < 0.05). Conclusions: Our results suggest that elevated cystatin C levels in diabetic patients may identify a certain degree of renal dysfunction even when albuminuria and eGFR do not mirror CKD. Longitudinal studies with direct GFR measures need to be done in order to confirm the value of cystatin C as an indicative of worse renal outcomes in the diabetic population.

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SUMMARY Plasma levels of kininogen, kallikrein, and prekalllkrein were determined in patients with malignant hypertension (MH) and compared to nonnotensive controls (NC) and patients with mild to moderate essential hypertension (EH). Also, a recently described kinin potentiating factor (KPF) was estimated by dividing the value of kininogen determined by trypsln (Kgn-Try) by that of kininogen determined by human urinary kallikrein (Kgn-HuUK). No significant alterations were detected among plasma values of prekallikrein and kallikrein of MH as compared to NC. However, Kgn-HuUK values were significantly lower in MH (1.9 ± OJ MgLBK/ml) as compared to EH and NC (2.7 ± 0.1 MgLBK/ml and 3.0 ± 0.2 MgLBK/ml respectively,p < 0.05). Furthermore, KPF values were also low (p < 0.05) in MH (1.6 ± 03) when compared with similar values obtained in EH and NC (3.0 ± 0.2 and 2.8 ± 0.1, respectively). Adequate control of blood pressure levels for 90 days in MH group caused no significant alterations in plasma levels of kininogen and KPF. It is suggested that diminished kininogen levels as well as a decrease in a kinin potentiation KPF that is generated in plasma by trypsln may be involved in the patbogenesis of human malignant hypertension. which several humoral alterations ofvasopressor systems like renin-angiotensin system, 1 catecholamines,* and more recently vasopressin 8 have been implicated in the pathogenesis of the vascular lesion. The kallikrein-kinin system has been implicated in several hypertensive states, since kinins are vasodilators 4 and also influence water and electrolyte excretion.8 -• A defective kallikrein-kinin system has been recently suggested in malignant, but not benign, hypertension in the rat.'In the present work we evaluated the levels of some plasma precursors of kallikrein-kinin system in malignant hypertension, compared to "benign" hypertension and normal subjects, by studying plasma levels of kininogen, kallikrein, and prekallikrein. Also, a newly described kinin potentiating factor* was estimated in these subjects since it is known that several potentiating substances of both exogenous' 110 or endogenous origin 11 ' " may influence the activity of the kallikrein-kinin system.

Eugenia species have been appreciated for their edible fruits and medicinal properties. This paper aims to investigate the chemical composition and in vitro antileishmanial, antifungal and antiproliferative activities of essential oil from aerial parts of Eugenia pyriformis (EP-EO). The oil showed strong antileishmanial activity against promastigote forms of Leishmania amazonensis (IC 50 = 2.16 µg/mL). It also exhibited high antifungal activity against Malassezia furfur (MIC = 30 µg/mL), which was determined by the broth microdilution method. Its antiproliferative activity was evaluated against the following cells: GM07429A (normal cell), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma) and M059J (human glioblastoma). Its major constituents, which were determined by GC-FID and GC-MS, were limonene (14.8%), nerolidol (11.0%), α-cadinol (10.3%), caryophyllene oxide (9.9%) and β-pinene (7.1%). These results showed, for the first time, the effectiveness of EP-EO as a natural product which has promising biological activities, a fact that enables its ethnopharmacological use.

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