ABSTRACT
BACKGROUND: Volume overload in patients on hemodialysis (HD) is an independent risk factor for cardiovascular mortality. B-lines detected on lung ultrasound (BLUS) assess extravascular lung water. This raises interest in its utility for assessing volume status and cardiovascular outcomes. METHODS: End-stage renal disease patients on HD at the Island Rehab Center being older than 18 years were screened. Patients achieving their dry weight (DW) had a lung ultrasound in a supine position. Scores were classified as mild (0-14), moderate (15-30), and severe (>30) for pulmonary congestion. Patients with more than 60 were further classified as very severe. Patients were followed for cardiac events and death. RESULTS: 81 patients were recruited. 58 were males, with a mean age of 59.7 years. 44 had New York Heart Association (NYHA) class 1, 24 had class 2, and 13 had class 3. In univariate analysis, NYHA class was associated with B-line classes (<0.001) and diastolic dysfunction (0.002). In multivariate analysis, NYHA grade strongly correlated with B-line classification (0.01) but not with heart function (0.95). 71 subjects were followed for a mean duration of 1.19 years. 9 patients died and 20 had an incident cardiac event. A Kaplan-Meier survival analysis demonstrated an interval decrease in survival times in all-cause mortality and cardiac events with increased BLUS scores (p = 0.0049). Multivariate Cox regression analysis showed the independent predictive value of BLUS class for mortality and cardiac events with a heart rate of 2.98 and 7.98 in severe and very severe classes, respectively, compared to patients in the mild class (p = 0.025 and 0.013). CONCLUSION: At DW, BLUS is an independent risk factor for death and cardiovascular events in patients on HD.
Subject(s)
Extravascular Lung Water/diagnostic imaging , Kidney Failure, Chronic/therapy , Lung/diagnostic imaging , Pulmonary Edema/diagnosis , Renal Dialysis , Ultrasonography/methods , Female , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged , Pulmonary Circulation , Pulmonary Edema/etiology , Pulmonary Edema/physiopathologyABSTRACT
Curcumin, an important component of the culinary spice turmeric, has been shown to harbor anticancer properties against a wide range of cancer cells with minimal toxicity toward normal cells. Two general tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib are currently used in treating renal cancer. Though the use of these TKIs has significantly improved survival, both elicit distressing side effects, limiting their long-term use. We tested the activity of sunitinib and sorafenib to eliminate 786-O renal cancer cells and the efficacy of curcumin to enhance this process. A four-fold decrease in the IC50 of sunitinib, from 4.5 µM to 1.2 µM, was observed in the presence of 20-µM curcumin. However, curcumin did not potentiate the activity of sorafenib. The sunitinib-curcumin (SunC) combination sharply inhibited hyperphosphorylation of the tumor suppressor protein Rb within 8 hours of SunC treatment. Although the levels of cyclin D1 did not change in 8 hours, its expression was dramatically inhibited after 24 hours of SunC exposure. Since curcumin is known to inhibit the cyclin D1-dependent G1/S-phase kinase CDK4 and the cyclin B-dependent G2/M-phase kinase CDK1 that catalyze phosphorylation-mediated inactivation of Rb, our results indicate that SunC containing a lower dose of sunitinib would be effective in restoring the tumor suppressor activity of Rb, thereby truncating cell cycle and triggering cell death. Our results submit the possibility of using SunC as an effective antitumor formulation to reduce the dose and risk of adverse effects of sunitinib.
Subject(s)
Antineoplastic Agents/pharmacology , Cell Cycle/drug effects , Curcumin/pharmacology , Cyclin D1/antagonists & inhibitors , Gene Expression Regulation, Neoplastic , Indoles/pharmacology , Pyrroles/pharmacology , Retinoblastoma Protein/metabolism , CDC2 Protein Kinase/genetics , CDC2 Protein Kinase/metabolism , Cell Cycle/genetics , Cell Death/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Cyclin D1/genetics , Cyclin D1/metabolism , Cyclin-Dependent Kinase 4/genetics , Cyclin-Dependent Kinase 4/metabolism , Drug Synergism , Humans , Inhibitory Concentration 50 , Niacinamide/analogs & derivatives , Niacinamide/pharmacology , Phenylurea Compounds/pharmacology , Phosphorylation/drug effects , Retinoblastoma Protein/genetics , Signal Transduction , Sorafenib , SunitinibABSTRACT
While immunosuppressive regimens improve the overall survival of renal transplant recipients, they also contribute to the long-term complications of post-transplant malignancies. Chronic immune suppression in renal transplant recipients (RTR) increases the risk of viral-associated cancers. In male RTR, human papillomavirus (HPV) is implicated in the development of penile, anal, oropharyngeal, and non-melanoma skin carcinomas. Despite the significance of this virus in RTR, there is an overall deficiency in the understanding of the natural history of HPV infection in male RTR. In the next 20 years, it is believed that cancers will be the leading cause of death in kidney transplant recipients. HPV-associated carcinomas are of particular interest since they are sexually transmitted and in theory may be preventable diseases. This commentary highlights some of the progress made in understanding how HPV is transmitted amongst couples in the general population. It also summarizes the current knowledge of HPV infection in male RTR and describes the deficiencies in published medical literature.
