Effect of renin-angiotensin-aldosterone system inhibition, dietary sodium restriction, and/or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic proteinuric kidney disease: a post hoc analysis of a randomized controlled trial

BACKGROUND: Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using therapeutic interventions is associated with decreased urinary KIM-1 levels. STUDY DESIGN: Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial. SETTING & PARTICIPANTS: 34 proteinuric patients without diabetes from our outpatient renal clinic. INTERVENTION: Stepwise 6-week interventions of losartan, sodium restriction (low-sodium [LS] diet), their combination, losartan plus hydrochlorothiazide (HCT), and the latter plus an LS diet. OUTCOMES & MEASUREMENTS: Urinary excretion of KIM-1, total protein, and N-acetyl-beta-d-glucosaminidase (NAG) as a positive control for tubular injury. RESULTS: Mean baseline urine protein level was 3.8 +/- 0.4 (SE) g/d, and KIM-1 level was 1,706 +/- 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was decreased by using placebo/LS (1,201 +/- 388 ng/d; P = 0.04), losartan/high sodium (1,184 +/- 296 ng/d; P = 0.09), losartan/LS (921 +/- 176 ng/d; P = 0.008), losartan/high sodium plus HCT (862 +/- 151 ng/d; P = 0.008) and losartan/LS plus HCT (743 +/- 170 ng/d; P = 0.001). The decrease in urinary KIM-1 levels paralleled the decrease in proteinuria (R = 0.523; P < 0.001), but not blood pressure or creatinine clearance. 16 patients reached target proteinuria with protein less than 1 g/d, whereas KIM-1 levels normalized in only 2 patients. Urinary NAG level was increased at baseline and significantly decreased during the treatment periods of combined losartan plus HCT only. The decrease in urinary NAG levels was not closely related to proteinuria. LIMITATIONS: Post hoc analysis. CONCLUSIONS: Urinary KIM-1 level was increased in patients with nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by using losartan, sodium restriction, their combination, losartan plus HCT, and the latter plus sodium restriction. These results are consistent with the hypothesis of amelioration of proteinuria-induced tubular damage. Long-term studies are warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes in patients with CKD with proteinuria.     

Surgical considerations for ‘intrinsic＇ brainstem gliomas： proposal of a modification in classification

BACKGROUND： Brainstem gliomas are highly heterogeneous tumors both in their clinical manifestation and in their pathology. Despite significant advances in the surgery for brainstem gliomas many aspects of this pathology are still unelear. OBJECTIVE： To evaluate the clinical, radiological and surgical outcome of 40 focal ＂intrinsic＂ brainstem gliomas and propose a surgical strategyoriented classification. MATERIALS AND METHODS： A total of 40 focal ‘intrinsie’ （＂expanding variety＂） tumors have been operated over a period of 8.5-years （January 1998-June 2007）. Our criteria included patients with （1） well-defined gadolinium enhancing tumor, （2） relatively long duration of symptoms （〉 six months） and （3） good neurological functional status and independent for all activities of davy living. The cutoff size of 2 cm was not rigidly adhered to. RESULTS： The ＂intrinsic＂ brainstem tumors were classified into three types： Expanding, diffuse infiltrative and pure ventral varieties.     

Cognitive and emotional health risk perceptions among people living in poverty

Many theories of risk perception and health behavior examine cognitive dimensions of risk (i.e., perceived susceptibility or severity) but not emotional dimensions. To address this gap, the authors examined the emotional component of risk perception (as worry) and its relation to cognitive assessments of risk, self-efficacy and response efficacy, and health protective action. Although people in poverty are at high risk for many health conditions, little is known about how concerned they are about these conditions or how their risk perceptions influence health actions. African Americans and Whites with incomes≤$35,000 were surveyed (N=431). Participants reported their worry level for 10 health risks. Among their highest worry risks, they identified the risk they took the most action and the risk they took the least action to prevent. Worry was low or moderate for each health risk and chronic conditions were of the most concern. For high- and low-action risks, response efficacy moderated the relation between cognitive risk perception and health protective action. For low-action risks, decisions to act were affected independently by cognitive and emotional responses. The results support the Risk Perception Attitude Framework and indicate the importance of using cognitive and emotional dimensions of risk in behavior change models.     

Vaccine-elicited Human T Cells Recognizing Conserved Protein Regions Inhibit HIV-1

Virus diversity and escape from immune responses are the biggest challenges to the development of an effective vaccine against HIV-1. We hypothesized that T-cell vaccines targeting the most conserved regions of the HIV-1 proteome, which are common to most variants and bear fitness costs when mutated, will generate effectors that efficiently recognize and kill virus-infected cells early enough after transmission to potentially impact on HIV-1 replication and will do so more efficiently than whole protein-based T-cell vaccines. Here, we describe the first-ever administration of conserved immunogen vaccines vectored using prime-boost regimens of DNA, simian adenovirus and modified vaccinia virus Ankara to uninfected UK volunteers. The vaccine induced high levels of effector T cells that recognized virus-infected autologous CD4⁺ cells and inhibited HIV-1 replication by up to 5.79 log₁₀. The virus inhibition was mediated by both Gag- and Pol- specific effector CD8⁺ T cells targeting epitopes that are typically subdominant in natural infection. These results provide proof of concept for using a vaccine to target T cells at conserved epitopes, showing that these T cells can control HIV-1 replication in vitro.     

Multicentre randomized trial of sotalol vs amiodarone for chronic malignant ventricular tachyarrhythmias

Sotalol was compared with amiodarone in this open randomizedmulticentre study of patients with ventricular tachycardia orfibrillation not associated with acute myocardial infarctionrefractory to or intolerant of Class I drugs. 16 of 30 patientstreated with amiodarone completed 12 months on therapy, fivewere withdrawn because of recurrent ventricular tachycardiaand nine because of presumed adverse drug reactions, complianceproblems or protocol violation. Four of those who were withdrawndied within 12 months. Sixteen of 29 patients completed 12 months on sotalol, one waswithdrawn because of ventricular tachycardia and nine becauseof presumed adverse drug reactions, poor compliance or the needfor coronary artery surgery. Three died on treatment and twoafter withdrawal but within 12 months of entering the study. When the results are analysed by intention to treat there wasno significant difference in antiarrhythmic efficacy or in theincidence of side-effects severe enough to warrant withdrawalfrom the trial. There was an increase in left ventricular ejectionfraction in those treated with sotalol, which, because of itspharmacokine-tics, is an attractive alternative to amiodaronefor patients with malignant ventricular arrhythmias who cantolerate ß-adrenergic blockade.