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Biomedical subjects

James V Donadio

Publications and source records attributed to James V Donadio.

4 recordsLinked to original sources

The role of fish oil/omega-3 fatty acids in the treatment of IgA nephropathy.

Beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) have been reported in recent epidemiologic studies and randomized clinical trials in a variety of cardiovascular and autoimmune diseases. Fish and marine oils are the most abundant and convenient sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two major n-3 fatty acids that serve as substrates for cyclooxygenase and lipoxygenase pathways leading to less potent inflammatory mediators than those produced through the n-6 PUFA substrate, arachidonic acid. N-3 PUFA can also suppress inflammatory and/or immunologic responses through eicosanoid-independent mechanisms. Although the pathophysiology of IgA nephropathy is incompletely understood, it is likely that n-3 PUFA prevents renal disease progression by interfering with a number of effector pathways triggered by mesangial immune-complex deposition. In addition, potential targets of n-3 PUFA relevant to renal disease progression could be similar to those involved in preventing the development and progression of cardiovascular disease by lowering blood pressure, reducing serum lipid levels, decreasing vascular resistance, or preventing thrombosis. In IgA nephropathy, efficacy of n-3 PUFA contained in fish oil supplements has been tested with varying results. The largest randomized clinical trial performed by our collaborative group provided strong evidence that treatment for 2 years with a daily dose of 1.8 g of EPA and 1.2 g of DHA slowed the progression of renal disease in high-risk patients. These benefits persisted after 6.4 years of follow up. With safety, composition, and dosing convenience in mind, we can recommend two products that are available as pharmaceutical-grade fish-oil concentrates, Omacor (Pronova Biocare, Oslo, Norway) and Coromega (European Reference Botanical Laboratories, Carlsbad, CA).

Animals↗

IgA nephropathy.

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Adrenal Cortex Hormones↗

Proteinuria patterns and their association with subsequent end-stage renal disease in IgA nephropathy.

BACKGROUND: Proteinuria (UP) >1.0 g/24 h at diagnosis is a well-known indicator of progressive renal disease in patients with IgA nephropathy (IgAN). To determine if persistent UP is a more sensitive marker for later progression of IgAN, the hypothesis was tested that the prior level and trend (slope) in UP for 1 year was better at predicting later end-stage renal disease (ESRD) (dialysis or transplant) than a current 24-h UP, serum creatinine (SC), SC slope, hypertension, or total glomerular histopathological score on index renal biopsy in an observational study of 154 high-risk patients enrolled in two clinical trials (IgAN 1, IgAN 2). METHODS: Measurements of 24-h UP and SC were made at time 0, 6 weeks, 6 months and 1 year in all patients, who were then followed for an additional 5.76 years and 1.63 years in the two studies, respectively. The Cox proportional hazards model was used to identify predictors of ESRD following the 1-year visit. RESULTS: Adjusting only for randomized treatment, nearly all UP variables (number of high readings, 1-year level, slopes), SC at 1 year, and SC trends (slopes) over the prior year were significantly associated with subsequent ESRD (all P values <0.05) in both studies. However, among the UP variables, the 1-year readings had the strongest association with ESRD in IgAN 1 (hazard ratio (HR), 95% CI, for a 1g increase: 1.5, 1.2,1.9), and the second strongest association (similar to UP trends) in IgAN 2 (1.4, 1.2,1.6). Males had lower rates of ESRD in both studies (IgAN 1 HR: 0.5, 0.2,1.2, P=0.11; IgAN 2 HR: 0.2, 0.1,0.6, P=0.002). In the multivariate analyses that examined all clinical and histological variables, 1-year levels of 24-h UP and SC, and female gender were independently associated with subsequent ESRD. CONCLUSION: In a high-risk patient with IgAN, the current 24-h UP and SC measurements are as good predictors of subsequent ESRD as UP and SC trends and levels over the prior year. Additionally, it appears that females have poorer outcomes than males.

Biomarkers↗

A randomized trial of high-dose compared with low-dose omega-3 fatty acids in severe IgA nephropathy.

Tested was the hypothesis that high-dose omega (omega)-3 fatty acids will be more effective than low-dose omega-3 fatty acids in preserving renal function in patients with severe IgA nephropathy in a randomized, open-label, parallel-group clinical trial. Patients were assigned to receive either high-dose fatty acids (EPA 3.76 g and DHA 2.94 g) or low-dose fatty acids (EPA 1.88 g and DHA 1.47 g), both given daily in a highly purified ethyl ester concentrate (Omacor). Patients were treated for a minimum of 2 yr in the absence of a treatment failure or until study closure (January 2000). Seventy-three patients were enrolled in the trial with two ranges of elevated serum creatinine (SC): 63 patients (86%) with a range of 1.5 to 2.9 mg/dl and 10 patients (14%) with a range of 3.0 to 4.9 mg/dl. The primary end point, within-patient rates of change in SC (2-yr minimum), showed an annualized median increase in SC of 0.08 mg/dl per yr in the low-dose group and 0.10 mg/dl per yr in the high-dose group (P: = 0.51). Patients in the lower entry SC range had lower SC slopes (P: = 0.02) and less end-stage renal disease (ESRD) (P: < 0.001) compared with those in the higher entry SC range. No patient died, and 18 patients developed ESRD: 10 in the low-dose group and 8 in the high-dose group (P: = 0.56). SC slopes were significantly lower, and survival free of ESRD was significantly higher (both, P: = 0.04) in the 63 Omacor-treated patients compared with the 22 placebo-treated patients from our previously reported clinical trial in which both groups had a similar level of renal impairment. Patient compliance was excellent, and no serious adverse events were noted. Low-dose and high-dose omega-3 fatty acids were similar in slowing the rate of renal function loss in high-risk patients with IgA nephropathy, particularly those with moderately advanced disease.

Adult↗