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

Moriyama, Takahito; Kumon, Saeko; Kamiyama, Takahiro; Karasawa, Kazunori; Uchida, Keiko; Nitta, Kosaku

doi:10.2169/internalmedicine.9155-17

Cited by 7 publications

(3 citation statements)

References 31 publications

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“…91 In the kidney, increasing clinical evidence suggests that n-3 PUFA supplementation has therapeutic potential in reducing proteinuria and kidney dysfunction in IgA nephropathy and other chronic kidney diseases and in reducing inflammation in dialysis patients. 92,93 n-3 PUFA supplementation also appeared to diminish nephrotoxicity and the attendant complication of hypertension toward the inhibition of inflammatory and atherogenic mechanisms in lupus nephritis. 94 The current study suggested that a deficiency in PUFA might cause pathological damage in vivo, with PUFA supplementation exerting protective effects in the same pathological situation.…”

Section: F I G U R Ementioning

confidence: 98%

Polyunsaturated fatty acid deficiency affects sulfatides and other sulfated glycans in lysosomes through autophagy‐mediated degradation

et al. 2020

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Metabolic changes in sulfatides and other sulfated glycans have been related to various diseases, including Alzheimer's disease (AD). However, the importance of polyunsaturated fatty acids (PUFA) in sulfated lysosomal substrate metabolism and its related disorders is currently unknown. We investigated the effects of deficiency or supplementation of PUFA on the metabolism of sulfatides and sulfated glycosaminoglycans (sGAGs) in sulfatide-rich organs (brain and kidney) of mice. A PUFA-deficient diet for over 5 weeks significantly reduced the sulfatide expression by increasing the sulfatide degradative enzymes arylsulfatase A and galactosylceramidase in brain and kidney. This sulfatide degradation was clearly associated with the activation of autophagy and lysosomal hyperfunction, the former of which was induced by suppression of the Erk/mTOR pathway. A PUFA-deficient diet also activated the degradation of sGAGs in the brain and kidney and that of amyloid precursor proteins in the brain, indicating an involvement in general lysosomal function and the early developmental process of AD. PUFA supplementation prevented all of the above abnormalities. Taken together, a PUFA deficiency might lead to sulfatide and sGAG degradation associated with autophagy activation and general lysosomal hyperfunction and play a role in many types of disease development, suggesting a possible benefit of prophylactic PUFA supplementation.

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Section: F I G U R Ementioning

confidence: 98%

Polyunsaturated fatty acid deficiency affects sulfatides and other sulfated glycans in lysosomes through autophagy‐mediated degradation

et al. 2020

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“…Furthermore, addition of DHA to EPA was found to stabilize renal function of IgAN patients, with improvements in clinical parameters and possible further pleiotropic effects. 54 Well-designed molecular experiments and clinical trials are necessary to better understand the mechanisms by which these agents may affect IgAN.…”

Section: Supportive Therapymentioning

confidence: 99%

Primary IgA nephropathy: current challenges and future prospects

Prendecki¹,

McAdoo²,

Tam³

2018

IJNRD

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IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, exhibiting a variable clinical and pathological course and significantly contributing to the global burden of chronic kidney disease and end-stage renal disease. Current standards of care focus on optimization of antihypertensive and antiproteinuric therapies (typically renin- angiotensin system blockade) to reduce disease progression. Much recent attention has focused on whether additional immunosuppression confers better outcomes than supportive management alone, and indeed, several trials have demonstrated renoprotective effects following the use of oral corticosteroids. However, results have been inconsistent, and perceived benefits must be balanced against risks and adverse effects associated with generalized immunosuppression, as highlighted by the high-profile STOP-IgAN and TESTING clinical trials. Recent translational research in vitro and animal models of IgAN have generated greater insight into potential therapeutic targets for this complex autoimmune disease. Deeper understanding of the roles of the mucosal immune barrier, complement activation and deposition, T-cell dependent and independent mechanisms of B cell activation, and of the deposition and downstream inflammatory signaling pathways of nephritogenic polymeric IgA1 complexes (e.g., signaling of immune receptors via spleen tyrosine kinase) has formed the rationale for the development of novel agents and clinical trials of more targeted therapies. However, translating findings into clinical practice is challenging, with many immunopathological features of IgAN specific to humans. Recent comprehensive reviews outline current understanding of mechanisms of IgAN as well as ongoing and future clinical trials; it is not our aim to replicate this here. Instead, we take a mechanistic approach to current treatment strategies, outlining advantages and limitations of each before exploring ongoing research with potential translation into future targeted therapies for this complex disease.

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“…Besides, their use in CKD-related dyslipidemia may obviate the need for hypolipidemic intervention with statins. Recent studies 21,22 and guidelines 14,23 underscore their potential benefits in IgAN when low and high doses were used, although there are conflicting results from some clinical trials. 16 Thus, the use of omega-3 PUFAs as a supportive therapy in IgAN remains controversial.…”

Section: Introductionmentioning

confidence: 99%

<p>The Supportive Treatment of IgA Nephropathy and Idiopathic Nephrotic Syndrome: How Useful are Omega-3 Polyunsaturated Fatty Acids?</p>

Uwaezuoke¹,

Muoneke²,

Mbanefo³

2020

IJNRD

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IgA nephropathy (IgAN) is the most prevalent glomerular disease in young adults worldwide, while idiopathic nephrotic syndrome (INS) represents the most frequent manifestation of glomerular disease in childhood. Over the years, studies have speculated about the potential benefits of omega-3 polyunsaturated fatty acids (PUFAs) in improving morbidity in both forms of chronic kidney disease (CKD). The proposed mechanisms of action include reduction of proteinuria and modulation of dyslipidemia. Although in vitro and in vivo experimental studies report the suppressive effect of omega-3 PUFAs on inflammatory pathways linked with the progression of nephropathy, the evidence supporting their beneficial effect in IgAN and INS is still weak. Also, their ability to regulate levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) suggests that they could delay both dyslipidemia-associated nephrotoxicity and atherosclerosis. Most of the clinical trials that were conducted on their therapeutic benefits in IgAN patients reported positive outcomes with low and high doses of omega-3 PUFAs. However, few of the trials noted inconclusive findings, with low-quality evidence suggesting potential improvements in surrogate renal function outcomes. If the beneficial effect of omega-3 PUFAs is predicated on their hypolipidemic action, much higher doses could be used in welldesigned randomized-controlled trials (RCTs) to determine if they could produce better renal function outcomes and provide much stronger evidence of their therapeutic benefits in IgAN and INS. However, the current hypothetical mechanisms of action in these forms of CKD also include the effect of omega-3 PUFAs on renal inflammatory pathways and glomerular proteinuria. Perhaps, the unresolved therapeutic efficacy of these fatty acids in IgAN and INS suggests that their exact mechanisms of action are yet to be fully established. In this narrative review, we aim to appraise the current evidence of their potential therapeutic benefits in these diseases.

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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

Cited by 7 publications

References 31 publications

Polyunsaturated fatty acid deficiency affects sulfatides and other sulfated glycans in lysosomes through autophagy‐mediated degradation

Polyunsaturated fatty acid deficiency affects sulfatides and other sulfated glycans in lysosomes through autophagy‐mediated degradation

Primary IgA nephropathy: current challenges and future prospects

<p>The Supportive Treatment of IgA Nephropathy and Idiopathic Nephrotic Syndrome: How Useful are Omega-3 Polyunsaturated Fatty Acids?</p>

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