Deletion at chromosome 3p21.3 is the earliest and the most frequently observed genetic alteration in lung cancer, suggesting that the region contains tumor suppressor gene(s) (TSG). Identification of those genes may lead to the development both of biomarkers to identify high-risk individuals and novel therapeutics. Previously, we cloned the H37/Luca15/RBM5 gene from 3p21.3 and showed its TSG characteristics. To investigate the physiologic function of H37 in the lung and its mechanism of tumor suppression, we have stably transfected H37 into A549 non-small cell lung cancer cells. A549/H37 cells show significant growth inhibition compared with the vector controls by in vitro and in vivo cell proliferation assays. Using this lung cancer cell model, we have found that the molecular mechanism of H37 tumor suppression involves both cell cycle (G 1 ) arrest and apoptosis. To further define H37's function in cell cycle/apoptotic pathways, we investigated differential expression profiles of various cell cycle and apoptosis regulatory proteins using Western blot analysis. Both cyclin A and phophorylated RB levels were decreased in H37-transfected cells, whereas expression of Bax protein was increased. Mitochondrial regulation of apoptosis further downstream of Bax was investigated, showing change in the mitochondrial membrane potential, cytochrome c release into the cytosol, and enhanced caspase-9 and caspase-3 activities. We also report that H37 may mediate apoptosis in a p53-independent manner, and Bax knockdown by small interfering RNA suggests Bax plays a functional role downstream of H37. Lastly, we proposed a tumor suppression model of H37 as a post-transcriptional regulator for cell cycle/apoptotic-related proteins.

BackgroundObesity is associated with higher end-stage renal disease incidence, but associations with earlier forms of kidney disease remain incompletely characterized.MethodsWe studied the association of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with rapid kidney function decline and incident chronic kidney disease in 4573 non-diabetic adults with eGFR ≥ 60 ml/min/1.73m2 at baseline from longitudinal Multi-Ethnic Study of Atherosclerosis cohort. Kidney function was estimated by creatinine and cystatin C. Multivariate analysis was adjusted for age, race, baseline eGFR, and hypertension.ResultsMean age was 60 years old, BMI 28 kg/m2, baseline eGFRCr 82 and eGFRCys 95 ml/min/1.73m2. Over 5 years of follow up, 25% experienced rapid decline in renal function by eGFRCr and 22% by eGFRCys. Incident chronic kidney disease (CKD) developed in 3.3% by eGFRCys, 11% by eGFRCr, and 2.4% by both makers. Compared to persons with BMI < 25, overweight (BMI 25 – 30) persons had the lowest risk of rapid decline by eGFRCr (0.84, 0.71 – 0.99). In contrast, higher BMI categories were associated with stepwise higher odds of rapid decline by eGFRCys, but remained significant only when BMI ≥ 35 kg/m2 (1.87, 1.41 – 2.48). Associations of BMI with incident CKD were insignificant after adjustment. Large WC and WHR were associated with increased risk of rapid decline only by eGFRCys, and of incident CKD only when defined by both filtration markers.ConclusionsObesity may be a risk factor for kidney function decline, but associations vary by filtration marker used.

BackgroundElectronic health record (EHR) data is increasingly used to identify patients with chronic kidney disease (CKD). EHR queries used to capture CKD status, identify comorbid conditions, measure awareness by providers, and track adherence to guideline-concordant processes of care have not been validated.MethodsWe extracted EHR data for primary-care patients with two eGFRcreat 15-59 mL/min/1.73 m^2 at least 90 days apart. Two nephrologists manually reviewed a random sample of 50 charts to determine CKD status, associated comorbidities, and physician awareness of CKD. We also assessed the documentation of a CKD diagnosis with guideline-driven care.ResultsComplete data were available on 1767 patients with query-defined CKD of whom 822 (47%) had a CKD diagnosis in their chart. Manual chart review confirmed the CKD diagnosis in 34 or 50 (68%) patients. Agreement between the reviewers and the EHR diagnoses on the presence of comorbidities was good (κ > 0.70, p < 0.05), except for congestive heart failure, (κ = 0.45, p < 0.05). Reviewers felt the providers were aware of CKD in 23 of 34 (68%) of the confirmed CKD cases. A CKD diagnosis was associated with higher odds of guideline-driven care including CKD-specific laboratory tests and prescriptions for statins. After adjustment, CKD diagnosis documentation was not significantly associated with ACE/ARB prescription.ConclusionsIdentifying CKD status by historical eGFRs overestimates disease prevalence. A CKD diagnosis in the patient chart was a reasonable surrogate for provider awareness of disease status, but CKD awareness remains relatively low. CKD in the patient chart was associated with higher rates of albuminuria testing and use of statins, but not use of ACE/ARB.Electronic supplementary materialThe online version of this article (10.1186/s12882-018-1156-2) contains supplementary material, which is available to authorized users.

The prevalence of end-stage renal disease is rising in the United States, which bears high financial and public health burden. The most common modality of renal replacement therapy (RRT) in the United States is in-center hemodialysis. Many patients report lack of comprehensive and timely education about their treatment options, which may preclude them from participating in home-based dialysis therapies and kidney transplantation evaluation. While RRT education has traditionally been provided in-person, the rise of telehealth has afforded new opportunities to improve upon the status quo. For example, technology-augmented RRT education has recently been implemented into telehealth nephrology clinics, informational websites and mobile applications maintained by professional organizations, patient-driven forums on social media, and multimodality programs. The benefits of technology in RRT education are increased access for geographically isolated and/or medically frail patients, versatility of content delivery, information repetition to enhance knowledge retention, and interpersonal connection for educational content and emotional support. Challenges center around privacy and accuracy of information sharing, in addition to differential access to technology due to age and socioeconomic status. A review of available scholarly and social media resources suggests that technology-aided delivery of education about treatment options for end-stage renal disease provides an important alternative and/or supplemental resource for patients and families.

Objectives To study the association of adiposity with longitudinal kidney function change in 544 HIV-infected persons in Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) cohort over 5 years of follow-up. Methods Regional distribution of muscle and adipose tissue was quantified by whole-body MRI, and total adiponectin and leptin levels were measured in serum. Kidney function was assessed by estimated glomerular filtration rate from serum cystatin C (eGFRCys), obtained at baseline and follow-up. Rapid kidney function decline was defined as annual loss of eGFRCys ≥ 3 ml/min/1.73m2, and incident chronic kidney disease (CKD) was defined at eGFRCys < 60 ml/min/1.73m2. Multivariate regression analysis was adjusted for age, race, gender, glucose, antihypertensive use, serum albumin, baseline and change in HIV viral load. Results At baseline, mean age was 43 years, mean eGFRCys 86 ml/min/1.73m2, and 21% had albuminuria. Mean (standard deviation) eGFRCys decline was −0.11 ± 4.87 ml/min/1.73m2 per year; 23% of participants had rapid kidney function decline, and 10% developed incident CKD. Lowest tertile of visceral adipose tissue and highest tertile of adiponectin were both marginally associated with annual kidney function decline of −0.5 ml/min/1.73m2 each, but these associations were not statistically significant after adjustment. We found no statistically significant associations of MRI-measured regional adiposity or serum adipokines with rapid kidney function decline or incident CKD (all p-values > 0.1 in adjusted models). Conclusions Contrary to findings in the general population, adiposity did not have a substantial association with longitudinal change in kidney function among HIV-infected persons.