Kidney Renin-Angiotensin System: Lost in a RAS Cascade.

Renin was discovered more than a century ago. Since then, the functions of the renin-angiotensin system in the kidney have been the focus of intensive research revealing its importance in regulation of renal physiology and in the pathogenesis of heart, vascular, and kidney diseases. Inhibitors of renin-angiotensin system components are now foundational therapies for a range of kidney and cardiovascular diseases from hypertension to heart failure to diabetic nephropathy. Despite years of voluminous research, emerging studies continue to reveal new complexities of the regulation of the renin-angiotensin system within the kidney and identification of nonclassical components of the system like the prorenin receptor (PRR) and ACE2 (angiotensin-converting enzyme 2), with powerful renal effects that ultimately impact the broader cardiovascular system. With the emergence of a range of novel therapies for cardiovascular and kidney diseases, the importance of a detailed understanding of the renin-angiotensin system in the kidney will allow for the development of informed complementary approaches for combinations of treatments that will optimally promote health and longevity over the century ahead.

The economic costs of routine INR monitoring in infants and children--examining point-of-care devices used within the home setting compared to traditional anticoagulation clinic monitoring.

INTRODUCTION: The use of point-of-care (POC) devices within the home for routine INR monitoring has demonstrated reliability, safety and effectiveness in the management of infants and children requiring long-term warfarin therapy. However, a comprehensive cost-analysis of using this method of management, compared to attending anticoagulation clinics has not been reported. The aim of this study was to compare the estimated societal costs of attending anticoagulation clinics for routine INR monitoring to using a POC test in the home. MATERIALS AND METHODS: This study used a comparative before-and-after design that included 60 infants and children managed via the Haematology department at a tertiary paediatric centre. Each participant was exposed to both modes of management at various times for a period of ≥3 months. A questionnaire, consisting of 25 questions was sent to families to complete and return. Data collected included: the frequency of monitoring, mode of travel to and from clinics, total time consumed, and primary carer's income level. RESULTS: The home monitoring cohort saved a total of 1 hour 19 minutes per INR test compared to attending anticoagulation clinics and had a cost saving to society of $66.83 (AUD) per INR test compared to traditional care; incorporating health sector costs, travel expenses and lost time. CONCLUSIONS: The traditional model of care requires a considerable investment of time per test from both child and carer. Home INR monitoring in infants and children provides greater societal economic benefits compared to traditional models.

A decision-analytic economic evaluation of valaciclovir prophylaxis for the prevention of cytomegalovirus infection and disease in renal transplantation.

OBJECTIVE: This analysis evaluates the cost-effectiveness of valaciclovir prophylaxis using clinically and economically important health outcomes including graft failure, life-years, and quality-adjusted life-years (QALYs). METHODS: A Markov model was developed using a randomized, placebo-controlled trial of valaciclovir prophylaxis, together with a published epidemiological study and national renal transplant registry data. The model's population was stratified into two risk groups by donor/recipient cytomegalovirus (CMV) serostatus at transplantation: donor-positive/recipient-negative (D+R-) and recipient-positive (R+) patients. The model estimated costs and health outcomes over a 30-yr period from the perspective of Australian health care providers. RESULTS: The total health care cost was $3619 lower for D+R- patients receiving valaciclovir prophylaxis compared with those not receiving prophylaxis. D+R- patients receiving valaciclovir gained an extra 0.33 yr of life and 0.27 QALYs. R+ patients receiving valaciclovir prophylaxis gained an extra 0.07 yr of life and 0.05 QALYs, with an incremental cost of $914. This equates to $17 127 per QALY gained, which is highly cost-effective compared with other drugs and health interventions. CONCLUSIONS: Valaciclovir for the prophylaxis of CMV disease in renal transplant recipients is a cost-effective intervention, significantly reducing the burden of CMV disease to patients and health care providers.

Burden of hospitalization of patients with Candida and Aspergillus infections in Australia.

OBJECTIVES: This study examined the burden of hospitalization of patients with Aspergillus and Candida infections in Australia from 1995 to 1999. METHODS: Data were extracted from the National Hospital Morbidity Database. A hospitalization with an aspergillosis diagnosis was defined as any discharge with a diagnosis of aspergillosis. A hospitalization with a candidiasis diagnosis was defined as any discharge with a diagnosis of disseminated, invasive, or non-invasive candidiasis. Outcome measures included number of hospitalizations, length of stay (LOS), cost (AUS$), and mortality. RESULTS: 4583 hospitalizations with an aspergillosis diagnosis and 57,758 hospitalizations with a candidiasis diagnosis were identified. These hospitalizations were associated with a total of 813,398 hospital days, AUS$563 million in cost, and 4967 in-hospital deaths during the study period. The mean LOS for a hospitalization with an aspergillosis diagnosis was 12 days, cost AUS$9,334, and was associated with 8% mortality. For disseminated, invasive, and non-invasive candidiasis, the respective mean LOS were 31, 17, and 12 days; costs were AUS$33,274, AUS$12,954, and AUS$7,694; and mortality was 26%, 9%, and 8%. CONCLUSIONS: Hospitalizations with diagnoses for fungal infections were associated with lengthy hospital stays, high costs, and high mortality.

Introduction of lamivudine for the treatment of chronic hepatitis B: expected clinical and economic outcomes based on 4-year clinical trial data.

BACKGROUND: Chronic hepatitis B (CHB) is associated with a significant burden of illness and treatment involves substantial health-care costs. This study estimates clinical outcomes and cost-effectiveness of lamivudine compared with other treatment scenarios for CHB, from an Australian health-care provider perspective. METHODS: A two-step modeling approach depicted clinical progression of hepatitis B in hypothetical patient cohorts using three different treatment scenarios: scenario A, lamivudine and alpha-interferon (IFN-alpha) available; scenario B, IFN-alpha available only; and scenario C, no treatment available. Assumptions were based on clinical trials, published studies, a hepatologist's questionnaire and an expert panel follow up. One-year clinical outcomes and costs were estimated using a decision tree, while lifetime costs and outcomes were estimated using available clinical trial data for lamivudine (up to 4 years therapy duration) and a Markov model. RESULTS: The analysis considered only patients with pretreatment elevated alanine aminotransferase levels > or = 2 x upper limit of normal. In the short term, the introduction of lamivudine is expected to result in almost 3.5 times more CHB patients receiving therapy (lamivudine or IFN-alpha) compared to IFN-alpha only (67% compared to 20%, respectively). Hence, scenario A subsequently doubled the seroconversion rate. The incremental cost-effectiveness ratio was $3341 Australian per additional seroconversion. Also, non-seroconverted lamivudine patients are less likely to progress to cirrhosis than those receiving IFN-alpha/no treatment. One-year progression to cirrhosis was estimated at 5.1% with scenario A, compared to 12.2% and 12.7%, scenarios B and C, respectively. From the long-term analysis, lamivudine is expected to increase life expectancy by years and reduce the lifetime risk of compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma by 6%, 12% and 12%, respectively. Additionally, the introduction of lamivudine decreases lifetime costs by $548, thus making it a cost-saving and life-extending strategy. In both short- and long-term models, worst case scenarios in sensitivity analyses still associate lamivudine with a favorable cost-effectiveness ratio. CONCLUSION: Introduction of lamivudine is expected to improve health outcomes in CHB patients, resulting in overall savings in health-care costs. In this model, compared with IFN-alpha only and no treatment, lamivudine allowed more CHB patients to be treated, increased the seroconversion rate, delayed disease progression and prolonged life expectancy.