High Prevalence and Low Awareness of Albuminuria in the Community Setting in the KDSAP.

INTRODUCTION: Albuminuria is a sign of kidney disease and associated with adverse outcomes. However, most individuals with albuminuria are unaware of it. The Kidney Disease Screening and Awareness Program (KDSAP) aims for early detection and raising awareness of albuminuria, targeting underserved populations in communities. This study will assess the prevalence and awareness of albuminuria and identify associated risk factors among KDSAP participants. METHODS: KDSAP participants ≥18 years old without a history of dialysis or kidney transplant were included. Albuminuria was identified by dipstick urinalysis. Individuals with albuminuria who answered yes to either of the following 2 questions were defined as being aware: (i) Have you ever had protein in the urine? (ii) Do you have kidney disease? RESULTS: Among 2304 participants, 461 (20.0%) had albuminuria: 16.3% with trace or 1+ (low degree) and 3.7% with 2+ or more (high degree). Correlating factors of albuminuria included young age, male sex, African American descent, self-reported diabetes, hypertension, family history of kidney disease, and smoking. Overall albuminuria awareness was 15.8%, but awareness inversely correlated to younger age groups: 7.0% for ages 18-39 years, 13.5% for ages 40-59 years, and 24.0% for ages ≥60 years (P < 0.001). A high degree of albuminuria (vs. low, odds ratio: 5.04, P < 0.001) and concurrent hematuria (odds ratio: 2.12, P=0.024) were both associated with higher awareness; conversely, risk factors for low awareness included African American and better self-assessments of health. CONCLUSIONS: There was a high albuminuria prevalence among KDSAP participants, yet low awareness. KDSAP can potentially be a useful model for detecting albuminuria and raising awareness in communities.

The response of Escherichia coli to the alkylating agents chloroacetaldehyde and styrene oxide.

DNA damage is ubiquitous and can arise from endogenous or exogenous sources. DNA-damaging alkylating agents are present in environmental toxicants as well as in cancer chemotherapy drugs and are a constant threat, which can lead to mutations or cell death. All organisms have multiple DNA repair and DNA damage tolerance pathways to resist the potentially negative effects of exposure to alkylating agents. In bacteria, many of the genes in these pathways are regulated as part of the SOS reponse or the adaptive response. In this work, we probed the cellular responses to the alkylating agents chloroacetaldehyde (CAA), which is a metabolite of 1,2-dichloroethane used to produce polyvinyl chloride, and styrene oxide (SO), a major metabolite of styrene used in the production of polystyrene and other polymers. Vinyl chloride and styrene are produced on an industrial scale of billions of kilograms annually and thus have a high potential for environmental exposure. To identify stress response genes in E. coli that are responsible for tolerance to the reactive metabolites CAA and SO, we used libraries of transcriptional reporters and gene deletion strains. In response to both alkylating agents, genes associated with several different stress pathways were upregulated, including protein, membrane, and oxidative stress, as well as DNA damage. E. coli strains lacking genes involved in base excision repair and nucleotide excision repair were sensitive to SO, whereas strains lacking recA and the SOS gene ybfE were sensitive to both alkylating agents tested. This work indicates the varied systems involved in cellular responses to alkylating agents, and highlights the specific DNA repair genes involved in the responses.

4-Aminopyridine, A Blocker of Voltage-Dependent K+ Channels, Restores Blood Pressure and Improves Survival in the Wistar Rat Model of Anaphylactic Shock.

OBJECTIVES: Anaphylactic shock is associated with severe hypotension. Potassium channel blockers, such as 4-aminopyridine, induce vasoconstriction. The objective of this study was to test the ability of 4-aminopyridine to restore blood pressure and increase survival in anaphylactic shock. DESIGN: Experimental study. SETTING: Physiology laboratory. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Rats were sensitized with ovalbumin (1 mg SC), and anaphylactic shock was induced by IV injection of ovalbumin (1 mg). Experimental groups included non-allergic rats (NA) (n = 6); allergic rats (Controls) (n = 6); allergic rats treated with 4-aminopyridine (4-aminopyridine) (1 mg/kg) (n = 6); and allergic rats treated with epinephrine (EPI) (10 µg/kg) (n = 6). Treatments were administered 1 minute after induction of anaphylactic shock. MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure, heart rate, and survival were measured for 60 minutes. Plasma levels of histamine, leukotriene B4, prostaglandin E2, prostaglandin F2, pH, and HCO3 were measured. Mean arterial blood pressure was normal in the NA group; severe hypotension and high mortality were observed in controls; normalization of mean arterial blood pressure, heart rate, and increased survival were observed in 4-aminopyridine and EPI groups. All allergic 4-aminopyridine-treated rats survived after the induction of anaphylactic shock. Histamine level was higher in controls and the 4-aminopyridine group but reduced in the EPI group. Prostaglandin E2 increased in controls and EPI group and decreased in 4-aminopyridine group; prostaglandin F2 increased in controls but decreased in 4-aminopyridine and EPI groups. Leukotriene B4 decreased in 4-aminopyridine and EPI groups. Metabolic acidosis was prevented in the 4-aminopyridine group. CONCLUSIONS: Our data suggest that voltage-dependent K+ channel inhibition with 4-aminopyridine treatment restores blood pressure and increases survival in the Wistar rat model of anaphylactic shock. 4-aminopyridine or related voltage-dependent K channel blockers could be a useful additional therapeutic approach to treatment of refractory anaphylactic shock.