Publications

OBJECTIVE

Proteinuria occurs commonly among HIV-infected and uninfected injection drug users (IDUs) and is associated with increased mortality risk. Vitamin D deficiency, highly prevalent among IDUs and potentially modifiable, may contribute to proteinuria. To determine whether vitamin D is associated with proteinuria in this population, we conducted a cross-sectional study in the AIDS Linked to the IntraVenous Experience (ALIVE) Study.

METHODS

25(OH)-vitamin D levels were measured in 268 HIV-infected and 614 HIV-uninfected participants. The association between vitamin D deficiency (<10  ng/ml) and urinary protein excretion was evaluated by linear regression. The odds of persistent proteinuria (urine protein-to-creatinine ratio >200  mg/g on two occasions) associated with vitamin D deficiency was examined using logistic regression.

RESULTS

One-third of participants were vitamin D-deficient. Vitamin D deficiency was independently associated with higher urinary protein excretion (P < 0.05) among HIV-infected and diabetic IDUs (P-interaction < 0.05 for all). Persistent proteinuria occurred in 18% of participants. Vitamin D deficiency was associated with greater than six-fold odds of persistent proteinuria among diabetic IDUs [odds ratio (OR) 6.29, 95% confidence interval (CI) 1.54, 25.69] independent of sociodemographic characteristics, comorbid conditions, body mass index, and impaired kidney function [estimated glomerular filtration rate (eGFR) <60  ml/min per 1.73  m(2)]; no association, however, was observed among nondiabetic IDUs (OR 1.06, 95% CI 0.64, 1.76) (P-interaction <0.05).

CONCLUSIONS

Vitamin D deficiency was associated with higher urinary protein excretion among those with HIV infection and diabetes. Vitamin D deficiency was independently associated with persistent proteinuria among diabetic IDUs, although not in nondiabetic persons. Whether vitamin D repletion ameliorates proteinuria in these patients requires further study.

Transforming Growth Factor Beta (TGF-β) is involved in regulating many biological processes and disease states. Cells secrete cytokine as a latent complex that must be activated for it to exert its biological functions. We previously discovered that the epithelial-restricted integrin α(v)β(6) activates TGF-β and that this process is important in a number of in vivo models of disease. Here, we show that agonists of G-protein coupled receptors (Sphingosine-1-Phosphate and Lysophosphatidic Acid) which are ligated under conditions of epithelial injury directly stimulate primary airway epithelial cells to activate latent TGF-β through a pathway that involves Rho Kinase, non-muscle myosin, the α(v)β(6) integrin, and the generation of mechanical tension. Interestingly, lung epithelial cells appear to exert force on latent TGF-β using sub-cortical actin/myosin rather than the stress fibers utilized by fibroblasts and other traditionally "contractile" cells. These findings extend recent evidence suggesting TGF-β can be activated by integrin-mediated mechanical force and suggest that this mechanism is important for an integrin (α(v)β(6)) and a cell type (epithelial cells) that have important roles in biologically relevant TGF-β activation in vivo.

BACKGROUND

Awareness of chronic kidney disease (CKD) is low. Efforts are underway to increase recognition of CKD among patients, assuming that such an increase will lead to better outcomes through greater adherence to proven therapies. Few studies have tested this assumption.

METHODS

CKD awareness, defined by a 'yes' answer to 'Have you ever been told by a healthcare provider you have weak or failing kidneys?', was assessed among 2,404 adults with CKD stages 1-4, who participated in the 2003-2008 National Health and Nutrition Examination Surveys. Odds of blood pressure (BP) control, self-reported use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), and glycemic control, were determined among those aware vs. unaware of their CKD.

RESULTS

Optimal BP control, ACEI/ARB use and glycemic control were low in the US adult population with CKD, although there was a recent increase in attainment of guideline-concordant BP control. Odds of BP control and ACEI/ARB use were not different among individuals aware of their CKD compared to those unaware (adjusted odds ratio (AOR) 0.91; 95% CI 0.52-1.58 and AOR 0.75; 0.44-1.30, respectively). CKD awareness among diabetic participants was not associated with glycemic control (AOR 0.41; 95% CI 0.14-1.18).

CONCLUSION

Awareness of CKD is not associated with more optimal BP control, ACEI/ARB use or glycemic control. Future efforts in this area should further explore the measurement of CKD awareness and behaviors associated with CKD awareness.

PURPOSE

Little is known about parental attitudes toward return of individual research results (IRRs) in pediatric genomic research. The aim of this study was to understand the views of the parents who enrolled their children in a genomic repository in which IRRs will be returned.

METHODS

We conducted focus groups with parents of children with developmental disorders enrolled in the Gene Partnership (GP), a genomic research repository that offers to return IRRs, to learn about their understanding of the GP, motivations for enrolling their children, and expectations regarding the return of IRRs.

RESULTS

Parents hoped to receive IRRs that would help them better understand their children's condition(s). They understood that this outcome was unlikely, but hoped that their children's participation in the GP would contribute to scientific knowledge. Most parents wanted to receive all IRRs about their child, even for diseases that were severe and untreatable, citing reasons of personal utility. Parents preferred electronic delivery of the results and wanted to designate their preferences regarding what information they would receive.

CONCLUSIONS

It is important for researchers to understand participant expectations in enrolling in a research repository that offers to disclose children's IRRs in order to effectively communicate the implications to parents during the consenting process.