Quality of Life after Dietary Self-Management Intervention for Persons with Early Stage CKD.

Dietary recommendations that potentially delay the progression of chronic kidney disease (CKD) can be perceived as restrictive and unpalatable, negatively impacting quality of life (QOL). This pilot study examined the effect of a six-week small group intervention, "Self-Management of Dietary Intake Using Mindful Eating," on QOL, health literacy, and dietary self-efficacy among persons with CKD Stages 1-3. Improvements (n=19) were found from pre-test to post-test in total scores for Kidney Disease Quality of Life Short Form-36 (p=0.003), health literacy (p=0.001), and self-efficacy (p=0.003). The intervention had promising results for improving both diet management and QOL, which supports further testing in randomized control trials.

Self-management of dietary intake using mindful eating to improve dietary intake for individuals with early stage chronic kidney disease.

Using mindful eating to improve specific dietary recommendations has not been adequately studied. This feasibility study examined an intervention, self-management of dietary intake using mindful eating, with 19 participants that had mild to moderate chronic kidney disease, using a prospective, single group, pretest-posttest design. The intervention had six weekly classes focused on self-management using mindful eating, goal-setting, problem-solving, and food label reading. Weight, body mass index (BMI), 3-day 24-h dietary recalls and fasting blood samples were measured. Participants improved significantly in mean weight (203.21 ± 42.98 vs 199.91 ± 40.36 lbs; P = 0.03) and BMI (32.02 ± 5.22 vs 31.57 ± 5.27 kg/m2; P = 0.04), but not in dietary intake nor blood measures with the exception of cis-beta-carotene levels (0.020 + 0.012 vs 0.026 + 0.012 mcg/mL; P = 0.008), which correlates to fruit and vegetable servings. These promising results warrant further testing of the intervention in randomized control trials.

The application of ICH S6 to the preclinical safety evaluation of plasma derivative therapeutic products.

The ICH S6 guidance was developed to describe a rational science-based flexible approach to the preclinical evaluation for biotechnology-derived pharmaceutical products. It also suggested that some of the principles described may be suitable for plasma-derived therapeutics. Some of the specific concerns unique to protein-based therapeutics include complexity in structure and potential immunogenicity. S6 has been interpreted by some industry and regulatory authorities, often due to lack of experience with these types of products, as encouraging a broader or more conventional toxicology program similar to that normally conducted for small molecules. The guidance does encourage important and necessary preclinical evaluations but also recognizes the limitations of studies in non-relevant animal species because they are without pharmacological interaction with the biologic. In addition, studies of human proteins are often limited in useful chronic, reproductive and carcinogenic toxicity evaluations by the immunological response in animals. Thus the safety evaluation of biopharmaceuticals and plasma derivatives in animals has limitations that cannot be adequately addressed by the use of testing paradigms used for small molecule pharmaceuticals. S6 focuses evaluations on well-designed studies in relevant species for reasonable time periods to make the best use of available resources and enable clinical trials.

Similarities and differences in design considerations for cell therapy and pharmacologic cardiovascular clinical trials.

Cell therapies hold the potential for suppression, modification, or cure of disease. Several unique challenges have been recognized as this field has developed. Many of these involve considerations of trial design. This paper summarizes the discussion and suggestions constructed during the 8th Cardiovascular Clinical Trialists Workshop, a meeting involving cardiovascular clinical trialists, biostatisticians, National Institutes of Health scientists, European and United States regulators, and pharmaceutical industry scientists. Investigators must adapt research methods to accommodate the scientific advances associated with cell therapy. Safety and efficacy of cell therapy for cardiovascular indications should be evaluated with the same degree of scientific rigor required of pharmacologic agents, and the same fundamental regulatory requirements and scientific processes apply to both. Clinical trials for these indications should also meet standards similar to those set for drug therapies. Safety should be determined throughout development, dose responsiveness should be established and, while surrogate endpoints are important development tools, the ultimate demonstration of efficacy must rely on clinical benefit. The establishment of a global safety database for cell therapy would significantly advance the field. Efforts to discover innovative therapies must be balanced by a commitment to comprehensively evaluate the safety and efficacy of the new treatments.

Endothelin-receptor blockade mitigates the adverse effect of preretrieval warm ischemia on posttransplantation renal function in rats.

BACKGROUND: Ischemia-reperfusion injury has been established as a nonimmunologic risk factor for the development of chronic graft nephropathy after renal transplantation. This objective of this study was to determine if oral administration of an endothelin-1 receptor (ET-R) antagonist over a 2-month period after renal transplantation would mitigate long-term dysfunction associated with 30 min of preretrieval warm ischemia (pre-WI). METHODS: The left kidney was retrieved from 250-g Lewis rats. Recipients underwent left nephrectomy and isografting using standard techniques. Animals were divided into three groups: nonischemic controls (no pre-WI, n=8); ischemic controls (pre-WI only, n=6); and pre-WI kidneys in which recipients received the ET(A/B) receptor antagonist, A182086, daily (30 mg/kg/day) (pre-WI/ET-R antagonist, n=6). Isograft glomerular filtration rate (GFR) was measured at 2 months. RESULTS: Measurement of GFR (mL/min) were as follows: no pre-WI, 2.1+/-0.26; pre-WI only, 1.24+/-0.14 (P<0.05 vs. no pre-WI); and pre-WI/ET-R antagonist, 2.3+/-0.45 (P<0.05 vs. pre-WI only and P=NS vs. no pre-WI). CONCLUSIONS: Chronic administration of a nonselective ET-R antagonist given after the ischemic insult, mitigated the decline in GFR at 2 months. These observations provide an experimental rationale for further investigation of the potential long-term protective effect of nonselective ET-R blockade versus ischemia-reperfusion injury in the clinical setting.

Endothelin receptor blockade during hypothermic perfusion preservation mitigates the adverse effect of preretrieval warm ischemic injury on posttransplant glomerular filtration rate.

BACKGROUND: Preretrieval warm ischemic injury predisposes to both short-term and long-term dysfunction of cadaveric renal allografts. We previously reported that the excretion of the vasoactive peptide, endothelin (ET), is significantly increased during hypothermic perfusion preservation (HPP) of kidneys subjected to preretrieval warm ischemia compared with nonischemic controls. As such, the purpose of this study was to determine if endothelin receptor (ET-R) blockade during HPP would improve glomerular filtration rate (GFR) of kidneys subjected to preretrieval warm ischemia when measured in situ at 2 weeks after transplantation (Tx). METHODS: The left kidney was retrieved from 300-g Lewis rats after in situ cold perfusion and transplanted after 2 hr of HPP. A 30-min period of preretrieval warm ischemia was induced. Kidneys were divided into four groups: nonischemic controls (n=9), ischemic (isch) kidneys not receiving ET-R blockade during HPP (n=7), isch kidneys receiving the ETA receptor antagonist (n=7), and isch kidneys receiving the ETA/B receptor antagonist (n=8). ET-R blockade was induced by adding the ETA, A-147627, or the ETA/B, A-182086, receptor antagonist (Abbott Laboratories, Abbott Park, IL) directly to the preservation solution (5x10-6M). The kidneys were then isografted into genetically identical Lewis rats and GFR, determined by measurement of urinary iohexol clearance, measured 2 weeks after Tx. RESULTS: Two-week GFRs (mL/min) for each of the study cohorts are as follows: nonischemic controls, 1.18+/-0.11; ischemic (isch) only, 0.57+/-0.08 (P< or =0.05 vs. nonischemic controls); isch + ETA blockade, 0.95+/-0.15 (P< or =0.05 vs. isch only); isch + ETA/B blockade, 0.90+/-0.08 (P< or =0.05 vs. isch only). CONCLUSION: Addition of an ETA, A-147627, or an ETA/B, A-182086, receptor antagonist to preservation solution used during HPP of kidneys subjected to preretrieval warm ischemia resulted in a normalization of GFR measured 2 weeks after Tx. The data provide a basis for further investigation of the impact of ET-R blockade on both the short- and long-term adverse effects of preretrieval warm ischemic injury in cadaveric renal Tx.