Steroids in the Treatment of IgA Nephropathy to the Improvement of Renal Survival: A Systematic Review and Meta-Analysis

Zhou, Yu; Tang, Li; Guo, Shi; Jin, Zhi; Wu, Mei Jing; Zang, Jiajie; Xu, Jin; Wu, Chun Fang; Qin, Ying; Cai, Qing; Gao, Qing; Zhang, Shan Shan; Yu, Dand Hui; He, Jia

doi:10.1371/journal.pone.0018788

Cited by 28 publications

(24 citation statements)

References 45 publications

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“…However, there are no appropriate treatments for GN. For the anti-inflammatory therapy in GN, steroids are widely used in patients especially with IgA nephropathy which is typical mesangial proliferative GN [22,44]. Steroids have great anti-inflammatory potency and reduce proteinuria, and then prevent the progression of kidney failure.…”

Section: Discussionmentioning

confidence: 99%

A Novel Vitamin K<sub>1</sub> 2,3-Epoxide Reductase (VKOR) Inhibitor, 3-Acetyl-5-Methyltetronic Acid, Reduces Experimental Glomerulonephritis

Uchida

Sakaguchi

Miyamoto

2012

The Journal of Veterinary Medical Science

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ABSTRACT. Excessive proliferation of mesangial cells is observed in various types of glomerular disease including glomerulonephritis (GN), which is progressive in nature and eventually results in end-stage renal disease (ESRD). Vitamin K 1 2,3-epoxide reductase (VKOR) and the vitamin K-dependent growth arrest-specific gene 6/Axl pathway play a key role in mesangial cell proliferation in GN.In the present study, we indicate the potential of a VKOR inhibitor, 3-acetyl-5-methyltetronic acid (AMT), to prevent the proliferation of glomerular mesangial cells and suppress the progression of GN. AMT was administered intravenously to rats once daily for 12 days and a mouse anti-Thy1 monoclonal antibody was injected intravenously after the AMT treatment on Day 6. Creatinine clearance (CCr) significantly increased and the albumin-to-creatinine ratio (ACR) significantly decreased in the AMT-treated group of the Thy-1 GN rats. In addition, glomerular and tubular damage was improved histopathologically in the AMT-treated group. AMT did not affect blood coagulation due to its unique pharmacokinetic properties. The concentration of AMT reached the IC 50 for VKOR in kidney, but not in liver. A novel VKOR inhibitor, AMT, reduced renal mesangial cell proliferation and could be a supportive treatment for GN. KEY WORDS: 3-acetyl-5-methyltetronic acid (AMT), glomerulonephritis (GN), mesangial cell, Thy-1, vitamin K 1 2,3-epoxide reductase (VKOR).

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Section: Discussionmentioning

confidence: 99%

A Novel Vitamin K<sub>1</sub> 2,3-Epoxide Reductase (VKOR) Inhibitor, 3-Acetyl-5-Methyltetronic Acid, Reduces Experimental Glomerulonephritis

Uchida

Sakaguchi

Miyamoto

2012

The Journal of Veterinary Medical Science

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“…During the four decades since immunoglobulin A nephropathy (IgAN) was first reported, many advances in our understanding of this disorder have been reported (1)(2)(3)(4)(5)(6). The renal function and the amount of proteinuria at the time of a renal biopsy and during the follow-up period appear to be related to the IgAN prognosis, as is the severity of the histological findings.…”

Section: Introductionmentioning

confidence: 99%

Effects of Combination Therapy with Renin-Angiotensin System Inhibitors and Eicosapentaenoic Acid on IgA Nephropathy

et al. 2013

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Objective The beneficial effects of renin-angiotensin-aldosterone system inhibitors (RASI) and the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on IgA nephropathy (IgAN) have been reported. However, it is unknown whether these agents have any synergistic interactions. Methods We divided 38 IgAN patients into two groups: an EPA group (n=18) treated with RASI plus EPA and a DILAZEP group (n=20) treated with RASI plus dilazep dihydrochloride. We analyzed the clinical and histological background of each patient, any relevant clinical findings obtained one year after treatment and any factors significantly related to decreases in proteinuria. Results The clinical findings were largely similar between the groups, except for body mass index (24.9± 4.5 in the EPA group vs. 21.4±2.1 in the DILAZEP group, p=0.0041) and total cholesterol (median: 206.0 vs. 177.5 mg/dL, p=0.0493). The histological findings, evaluated according to the Oxford classification, were also similar between the groups. At one year after treatment, the EPA group demonstrated a significantly decreased mean blood pressure (from 94.7±9.0 to 86.4±7.2 mmHg, p=0.0007) and a significantly decreased median level of proteinuria (from 0.80 to 0.41 g/g creatinine, p<0.001). In the DILAZEP group, the mean blood pressure significantly decreased (from 95.2±13.2 to 88.1±7.7 mmHg, p<0.001) without any significant decrease in the median level of proteinuria (from 0.88 to 0.60 g/g creatinine). According to a multivariate logistic analysis, EPA was found to be the only independent factor related to decreases in proteinuria (odds ratio = 5.073, 95% CI: 1.18-26.7, p=0.0285). Conclusion We conclude that EPA accelerates the effects of RASI and thus decreases the proteinuria observed in patients with IgAN.

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“…However, these overviews were either a few years before without including the new trials 12 or lacked good evaluation of hard endpoints 13 or safety. 14 In this systematic review, we sought to synthesize all available clinical trial data to better define the balance of risks and benefits associated with steroid therapy in IgA nephropathy.…”

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confidence: 99%

Corticosteroid Therapy in IgA Nephropathy

Perkovic

et al. 2012

Journal of the American Society of Nephrology

170

110

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The benefits and risks of steroids for the treatment of IgA nephropathy remain uncertain. We systematically searched MEDLINE, EMBASE, and the Cochrane Library for randomized, controlled trials of corticosteroid therapy for IgA nephropathy published between 1966 and March 2011. We identified nine relevant trials that included 536 patients who had urinary protein excretion .1 g/d and normal renal function. Forty-six (8.6%) of these patients developed a kidney failure event, defined as doubling of the serum creatinine/halving of the GFR or ESRD. Overall, steroid therapy was associated with a lower risk for kidney failure (relative risk, 0. , with no evidence of heterogeneity in these outcomes. Subgroup analysis suggested that the dose modifies the effect of steroids for renal protection (P for heterogeneity=0.030): Relatively high-dose and short-term therapy (prednisone .30 mg/d or high-dose pulse intravenous methylprednisolone with duration #1 year) produced significant renal protection, whereas low-dose, long-term steroid use did not. Steroid therapy was associated with a 55% higher risk for adverse events. The quality of included studies was low, however, limiting the generalizability of the results. In conclusion, steroids appear to provide renal protection in patients with IgA nephropathy but increase the risk for adverse events. Reliably defining the efficacy and safety of steroids in IgA nephropathy requires a high-quality trial with a large sample size.

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Steroids in the Treatment of IgA Nephropathy to the Improvement of Renal Survival: A Systematic Review and Meta-Analysis

Cited by 28 publications

References 45 publications

A Novel Vitamin K<sub>1</sub> 2,3-Epoxide Reductase (VKOR) Inhibitor, 3-Acetyl-5-Methyltetronic Acid, Reduces Experimental Glomerulonephritis

A Novel Vitamin K<sub>1</sub> 2,3-Epoxide Reductase (VKOR) Inhibitor, 3-Acetyl-5-Methyltetronic Acid, Reduces Experimental Glomerulonephritis

Effects of Combination Therapy with Renin-Angiotensin System Inhibitors and Eicosapentaenoic Acid on IgA Nephropathy

Corticosteroid Therapy in IgA Nephropathy

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