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      Effect of 12-Month Therapy with Omega–3 Polyunsaturated Acids on Glomerular Filtration Response to Dopamine in IgA Nephropathy

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          Background: ω–3 polyunsaturated acids therapy is efficient in primary IgA nephropathy. It is unknown whether doses of ω–3 smaller than those given previously are still effective. The aim of the study was to examine the effect of ω–3 therapy on renal vascular function in relation to proteinuria and urinary excretion of N-acetyl-β- D-glucosaminidase (NAG). Methods: 20 IgA patients aged 36.5 ± 10.77 with creatinine clearance (Cr<sub>cl</sub>) 105.71 ± 27.3 ml/min and proteinuria 3.31 ± 2.01 g/24 h were given orally 810 mg EPA and 540 mg DHA daily for 12 months. Before and at the end of the study, 24-hour proteinuria, serum homocysteine, and Cr<sub>cl</sub> were measured. At the same time, renal vascular function was estimated as dopamine-induced glomerular filtration response (DIR). DIR was measured as: two 120-min lasting Cr<sub>cl</sub> (before and during 2 µg/kg b.w./min i.v. dopamine). Results: The results obtained during follow-up were as follows (baseline vs. after therapy): DIR 14.9 ± 16.4 vs. 30.3 ± 14.3% (p < 0.01); urine protein 2.31 ± 2.01 vs. 1.31 ± 1.37 g/24 h (p < 0.01); (Cr<sub>cl</sub>) 105.71 ± 27.3 vs. 103.9 ± 20.9 ml/min (n.s.); NAG 8.3 ± 1.8 vs. 6.0 ± 1.2 U/g<sub>creat</sub> (p < 0.01), and homocysteine 16.2 ± 3.15 vs. 13.8 ± 2.6 µmol/l (p < 0.05). The only correlation found was linear correlation between basal DIR and DIR change (r = –0.570; p < 0.010) and basal NAG (r = –0.460; p < 0.50). Conclusions: ω–3 supplementation is associated with the improvement of both renal vascular function and tubule function.

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          Most cited references 18

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          Subtle acquired renal injury as a mechanism of salt-sensitive hypertension.

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            Urinary N-acetyl-beta-glucosaminidase excretion is a marker of tubular cell dysfunction and a predictor of outcome in primary glomerulonephritis.

            The urinary excretion of N-acetyl-beta-glucosamynidase (NAG) is increased in subjects exposed to substances toxic for renal tubular cells. In experimental and human glomerular diseases, its increased excretion is probably due to the dysfunction of tubular epithelial cells induced by increased traffic of proteins in the tubular lumen. The first aim of this study was to evaluate whether NAG excretion is correlated not only with the amount of proteinuria but also with some proteinuric components which reflect both glomerular capillary wall damage (IgG) and an impairment of tubular reabsorption of microproteins (alpha(1) microglobulin). The second aim was to assess whether NAG excretion has a predictive value on functional outcome and response to therapy. In 136 patients with primary glomerulonephritis [74 with idiopathic membranous nephropathy (IMN), 44 with primary focal segmental glomerulosclerosis (FSGS) and 18 with minimal change disease (MCD)] urinary NAG excretion was measured by a colorimetric method and expressed in units per gram of urinary creatinine. Using univariate linear regression analysis NAG excretion in all 136 patients was significantly dependent on IgG excretion, 24-h proteinuria, fractional excretion of alpha(1) microglobulin (FE alpha(1)m) and diagnosis. Using multiple linear regression analysis, NAG excretion was significantly dependent only on IgG excretion and 24-h proteinuria. Limiting the analysis to 67 patients with nephrotic syndrome (NS) and baseline normal renal function, by multiple linear regression, NAG excretion was significantly dependent on IgG excretion (P=0.0004), 24-h proteinuria (P=0.0067) and FE alpha(1)-m (P=0.0032) (R(2)=0.63). In 66 patients with NS and normal baseline renal function (MCD 10 patients; FSGS 20 patients; IMN 36 patients), according to values below or above defined cut-offs (IMN, 18 U/g urinary Cr; FSGS and MCD, 24 U/g urinary Cr), NAG excretion predicted remission in 86 vs 27% of IMN patients (P=0.0002) and 77 vs 14% of FSGS patients (P=0.005). Progression to chronic renal failure (CRF) was 0 vs 47% in IMN patients (P=0.001) and 8 vs 57% in FSGS patients (P=0.03). Using Cox model, in IMN patients only NAG excretion (P=0.01, RR 5.8), but not 24-h proteinuria, predicted progression to CRF. All MCD patients had NAG excretion values below the chosen cut-off, and 90% of them developed remission. Response to immunosuppressive therapy was significantly different in patients with NAG excretion values below or above the cut-offs. Urinary NAG excretion can be considered as a reliable marker of the tubulo-toxicity of proteinuria in the early stage of IMN, FSGS and MCD; the excretion values show a significant relationship with 24-h proteinuria, IgG excretion and FE alpha(1)m. Its determination may be a non-invasive, useful test for the early identification of patients who will subsequently develop CRF or clinical remission and responsiveness to therapy.
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              An "evidence-based" survey of therapeutic options for IgA nephropathy: assessment and criticism.

              Immunoglobulin A (IgA) nephropathy is a worldwide disease that causes end-stage renal failure in 15% to 20% of patients within 10 years of the apparent onset of disease and in 30% to 40% of individuals within 20 years. Severity of renal lesions, serum creatinine level, and severe proteinuria are adverse prognostic indicators. No specific treatment has been established, but several approaches have been experimented. We reviewed the literature and evaluated the quality of published randomized trials using standard methods and the quality of their reporting according to the revised version of the Consolidated Standards for Reporting Trials Statement. Meta-analyses of randomized trials on the efficacy of steroid treatment, cytotoxic agents, and fish oils on the outcome of renal function and daily proteinuria in patients with IgA nephropathy were performed. Only 10 randomized trials were available and included in the review. Their quality was very poor, and a limited amount of data was reported. Cytotoxic agents seem beneficial on both renal function (relative risk, 0.38; 95% confidence interval [CI], 0.22 to 0.66) and daily proteinuria (weighted mean difference [WMD], -1.16; 95% CI, -2.18 to -0.14) in patients with moderate to severe renal damage, steroids act mainly on proteinuria (WMD, -0.50; 95% CI, -0.78 to -0.21), and fish oils do not imply a particular benefit. This statement is based on the very limited and poor available published evidence. Only a few randomized trials, of low quality and inadequately reported, are available relating to treatment of IgA nephropathy. More properly designed and reported trials are necessary to reach a definitive assessment of this matter.

                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                October 2004
                01 December 2004
                : 24
                : 5
                : 474-482
                aDepartment of Transplantation, Nephrology and Internal Medicine, and bDepartment of Clinical Nutrition, Medical University of Gdańsk, Gdańsk, Poland
                80670 Am J Nephrol 2004;24:474–482
                © 2004 S. Karger AG, Basel

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                Figures: 5, Tables: 1, References: 37, Pages: 9
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                Original Report: Laboratory Investigation


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