The Renoprotective Effects of Docosahexaenoic Acid as an Add-on Therapy in Patients Receiving Eicosapentaenoic Acid as Treatment for IgA Nephropathy: A Pilot Uncontrolled Trial

Abstract

Objective Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been reported to have beneficial effects in patients with IgA nephropathy (IgAN). Although DHA and EPA have different mechanisms of action, no study to date has assessed their individual actions in patients with IgAN. This study therefore analyzed the effects administering DHA in addition to EPA for the treatment of IgAN. Methods Twenty-one IgAN patients who were being treated with EPA (1,800 mg/day) were switched to EPA (1,860 mg/day) and DHA (1,500 mg/day). The changes in their clinical parameters from 6 months before to 6 months after switching treatment were analyzed. Results The triglyceride levels did not change during treatment with EPA alone, but tended to decrease-although not to a statistically significant extent-after the switch. The patients' low-density-lipoprotein cholesterol, blood pressure, proteinuria, and hematuria levels were similar before and after switching. The estimated glomerular filtration rate (eGFR) tended to decrease during EPA therapy, but became stable after switching and the median %⊿eGFR changed from -7.354% during EPA therapy to +1.26% during the 6 months after switching to EPA and DHA therapy (p=0.00132), and renal the function remained stable for another 6 months. Moreover, the median %⊿eGFR during the 6 months after switching was significantly higher in comparison to IgAN patients who were treated with EPA alone as a control (-3.26%, p=0.0361). No clinical parameters were independently associated with a stable renal function without switching to DHA/EPA. Conclusion The addition of DHA to EPA stabilized the renal function of IgAN patients, and it seemed that there were pleiotropic effects beyond the improvement of the clinical parameters.

Keywords: IgA nephropathy; docosahexaenoic acid; eicosapentaenoic acid; fish oil; omega-3 polyunsaturated acid.

Figure 1.

The levels of (a) triglycerides (TG), (b) LDL cholesterol (LDL-C), (c) blood pressure and (d, e) the urinary findings starting 6 months before, and at 3-month intervals until 6 months after switching from EPA monotherapy to a combination of EPA and DHA. a: The patients’ TG levels were unchanged from 6 months before switching treatment to baseline, but tended to decrease at 3 and 6 months after the switch (p=0.6545). The results are expressed as the mean ± SE, and were compared by an ANOVA. b: The patients’ LDL-C levels remained unchanged from 6 months before to 6 months after switching treatment (p=0.8456). The results are expressed as the mean ± SE, and were compared by an ANOVA. c: The patients’ S-BP (p=0.7805) and D-BP (p=0.3710) levels remained unchanged from 6 months before to 6 months after switching treatment. The results are expressed as the mean ± SD and were compared by an ANOVA. d: The patients’ U-Prot concentrations remained unchanged from 6 months before to 6 months after switching treatment (p=0.7956). The results are expressed as the median (IQR) and were compared by a Wilcoxon signed-rank test. e: The patients’ U-RBC concentrations remained unchanged from 6 months before to 6 months after switching treatment (p=0.8851). The results are expressed as the median (IQR), and were compared by a Wilcoxon signed-rank test.

Figure 2.

(a) The mean eGFR, (b) individual eGFR’s, and (c) median ⊿eGFR, at 3-month intervals starting from 6 months before switching and continuing until 12 months after switching from EPA monotherapy to a combination of EPA and DHA. a: The mean eGFR tended to decrease from 6 months before switching treatment to baseline, but did not change after switching (p=0.9996). The results are expressed as the mean ± SE and were compared by an ANOVA. b: In almost all patients, the eGFR decreased before switching treatment, but increased or stabilized after switching. c: The median ⊿eGFR decreased by 7.35 (14.89 and 1.56) % before switching treatment, but increased by 1.26 (4.13 and 6.77) % during the 6 months after switching-a difference that was statistically significant (p=0.0132) according to a Mann-Whitney U-test-and remained stable from 6 months to 12 months after switching [0.37 (6.24 and 6.91) %, p=0.6163]. The median ⊿eGFR decreased in IgAN patients who were treated with EPA/DHA after switching and was significantly higher than that in patients who were treated with EPA alone (control) [1.26 (-4.1 and 6.77) % vs. -3.26 (-8.63 and 1.52) %, p=0.0361].