Kidney symptom questionnaire: Development, content validation and relationship with quality of life.

BACKGROUND: Chronic kidney disease (CKD) is associated with a range of symptoms, even at early stages. The importance of patient symptom experience is increasingly recognised, but validated symptom scores are lacking. OBJECTIVES: This study aimed to refine an existing symptom questionnaire for use with patients not requiring renal replacement therapy (RRT), carry out content validity testing and explore convergent validity by comparing symptom scores with quality of life (QoL). DESIGN: A mixed-methods approach involving questionnaires, semi-structured interviews and a focus group. PARTICIPANTS: Patients with CKD not undergoing RRT and expert health professionals. APPROACH: Two hundred and nineteen patients completed an existing symptom questionnaire. The most commonly reported symptoms were identified, and descriptions refined in 11 semi-structured interviews. The questionnaire design was reviewed by a focus group. Content validity was established by a panel of expert health professionals. Seventy patients completed both the symptom questionnaire and a health-related QoL questionnaire (EQ-5D-5L). RESULTS: Thirteen common symptoms were identified. During the content validity phase, 13/16 experts responded (81%); 10/13 symptoms had 'excellent' or 'good' evaluation scores, and the content validity index of the whole questionnaire was 0.81, falling within the recommended threshold. Total symptom frequency scores, number of symptoms and the frequencies of 10/13 individual symptoms were all strongly associated with health-related QoL (EQ-5D-5L index score; p < 0.002 for all). CONCLUSION: This work has provided a new, validated symptom score for patients with CKD not requiring RRT for clinical management and research purposes.

Symptom burden in patients with chronic kidney disease not requiring renal replacement therapy.

BACKGROUND: Although evidence shows that patients with end stage renal disease (ESRD) experience a high symptom burden which impacts on quality of life (QoL), less is known about patients with earlier stages of chronic kidney disease (CKD). This study aimed to explore symptom burden and potential contributing factors in patients with CKD Stage 1-5 not requiring renal replacement therapy (RRT). METHODS: Patients with CKD Stage 1-5 and not on RRT were asked to report their symptoms using the Leicester Uraemic Symptom Score (LUSS), a questionnaire which assesses the frequency and intrusiveness of 11 symptoms commonly reported by kidney patients. RESULTS: Symptoms were assessed in 283 CKD Stage 1-5 patients: 54% male, mean age 60.5 standard error± 1.0, mean eGFR 38ml/min/1.73m2. Some 96% (95% confidence interval 93.2-98.0) of participants reported experiencing at least one symptom, the median reported being six. Excessive tiredness (81%;76.0-85.6), sleep disturbance (70%;64.3-75.3) and pain in bones/joints (69%;63.4-74.6) were reported most commonly. Overall, few significant associations were found between biochemical markers of disease severity and symptom burden. Men tended to report fewer symptoms than women and South Asian patients often described experiencing symptoms with a greater severity. Older patients found musculoskeletal symptoms more intrusive whereas younger patients found reduced concentration more intrusive. CONCLUSIONS: Our findings suggest that patients with CKD stages 1-5 experience a multitude of symptoms that could potentially impact QoL. Using multidimensional tools like the LUSS, more exploration and focus could provide a greater opportunity for patient focussed symptom control from the earliest stages of CKD.

Triethylenetetramine Synergizes with Pharmacologic Ascorbic Acid in Hydrogen Peroxide Mediated Selective Toxicity to Breast Cancer Cell.

Breast cancer is characterized by overexpression of superoxide dismutase (SOD) and downregulation of catalase and more resistance to hydrogen peroxide (H2O2) than normal cells. Thus, relatively high H2O2 promotes breast cancer cell growth and proliferation. However, excessive intracellular H2O2 leads to death of breast cancer cells. In cancer cells, high level ascorbic acid (Asc) is able to be autoxidized and thus provides an electron to oxygen to generate H2O2. In the present study, we demonstrated that triethylenetetramine (TETA) enhances Asc autoxidation and thus elevates H2O2 production in MCF-7 cells. Furthermore, Asc/TETA combination significantly impaired cancer cell viability, while having much milder effects on normal cells, indicating Asc/TETA could be a promising therapy for breast cancer. Moreover, SOD1 and N-acetyl-L-cysteine failed to improve MCF-7 cells viability in the presence of Asc/TETA, while catalase significantly inhibited the cytotoxicity of Asc/TETA to breast cancer cells, strongly suggesting that the selective cytotoxicity of Asc/TETA to cancer cells is H2O2-dependent. In addition, Asc/TETA induces RAS/ERK downregulation in breast cancer cells. Animal studies confirmed that Asc/TETA effectively suppressed tumor growth in vivo. In conclusion, TETA synergizes pharmacologic Asc autoxidation and H2O2 overproduction in breast cancer cells, which suppresses RAS/ERK pathway and results in apoptosis.