Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy

Lv, Jicheng; Zhang, Hong; Wong, Muh Geot; Jardine, Meg; Hladunewich, Michelle A.; Jha, Vivekanand; Monaghan, Helen; Zhao, Ming‐Hui; Barbour, Sean J.; Reich, Heather N.; Cattran, Daniel C.; Glassock, Richard J.; Levin, Adeera; Wheeler, David C.; Woodward, Mark; Billot, Laurent; Chan, Tak Mao; Liu, Fei; Johnson, David W.; Cass, Alan; Feehally, John; Floege, Jürgen; Remuzzi, Giuseppe; Wu, Yangfeng; Agarwal, Rajiv; Wang, Hai Yan; Perkovic, Vlado

doi:10.1001/jama.2017.9362

Cited by 409 publications

(421 citation statements)

References 24 publications

(47 reference statements)

Supporting

Mentioning

395

Contrasting

Unclassified

Order By: Relevance

“…Time-averaged proteinuria (TA-proteinuria) was calculated as the weighted mean of all the measurements during follow-up, with the weight representing the time elapsed since the previous measurement [11]. The change in proteinuria over time in the total population was estimated using the linear mixed-effects model with a random participant-specific intercept and a random time effect by regressing proteinuria against age, gender, MAP level, baseline proteinuria level and eGFR, MESTC score, follow-up time (months since baseline), and treatment group.…”

Section: Methodsmentioning

confidence: 99%

Effects of Hydroxychloroquine on Proteinuria in Immunoglobulin A Nephropathy

et al. 2018

Self Cite

View full text Add to dashboard Cite

Background: Hydroxychloroquine (HCQ) is a well-known immunomodulator that is useful as in the treatment for lupus because of its inhibitory effect on toll-like receptors and cytokines, which are speculated to play a role in the pathogenesis of Immunoglobulin A (IgA) nephropathy (IgAN). However, there was only one study that investigated the effect of HCQ on proteinuria in patients with IgAN. Methods: Ninety patients with IgAN who received HCQ in addition to optimized dosage of renin-angiotensin-aldosterone system inhibitors (RAASi) were recruited for this study, and 90 matched historical controls who received RAASi alone were selected from our registry by the propensity score matching method. Their clinical data were compared at baseline and during follow-up till the termination of HCQ or addition of immunosuppressive agents. Results: The median baseline proteinuria level of the 90 patients who received HCQ was comparable with the RAASi-alone group (1.5 [1.2, 2.1] vs. 1.5 [1.2, 1.9] g/day, p = 0.74). At 6 months post-study initiation, the median proteinuria level in the HCQ group was lower than that in the RAASi-alone group (0.8 [0.7, 1.2] vs. 1.2 [0.8, 1.8] g/day, p = 0.02). The percentage by which proteinuria was reduced in the HCQ group was significantly higher than that in the RAASi-alone group (–43% [–57, –12] vs. –19% [–46, 17], p = 0.01). No serious adverse effects were documented during treatment with HCQ. Conclusion: The addition of HCQ to RAASi resulted in a significant and safe reduction in proteinuria in patients with IgAN.

show abstract

Section: Methodsmentioning

confidence: 99%

Effects of Hydroxychloroquine on Proteinuria in Immunoglobulin A Nephropathy

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Pozzi’, STOP and TESTING studies were using methylprednisolone, NEFIGAN was using budesonide, and the rest were using prednisone as the choice of steroids. There were 4 studies [20, 23, 24, 26] with a steroid dosage less than 0.5 mg/kg/day, 5 studies [11, 21, 22, 27, 28] with a steroid dosage in the range 0.8 mg/kg/day to 1 mg/kg/day, 2 studies [10, 28] with a methylprednisolone dosage of 1 g for 3 days and then tapered prednisone 0.5 mg/kg every other day, and 1 study [12] with a 8 or 16 mg dosage of targeted-release formulation (TRF)-budesonide. The duration of the treatment ranged from 4 months up to 24 months (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Data regarding the effects of glucocorticoids on kidney included ESKD, double Scr, or 50% decreasing or more of eGFR were available from 10 trials [11, 12, 19-26] with 859 patients (Figure 2). Among whom 85 events were observed, comprising 23 events in the corticoids group (n = 436, 5.28%) and 62 events in the control group ( n = 423, 14.66%).…”

Section: Resultsmentioning

confidence: 99%

“…However, this study that had the short follow-up for evaluating the renal function deterioration included patients who were on only > 0.75 g/day of proteinuria (thus showing slow progress). Moreover, recent data from the Therapeutic Evaluation of Steroids in IgA Nephropathy Study (TESTING) [11] and Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN) [12] have provided further evidence on the benefits and side effects of corticosteroid treatment in patients with IgAN. These studies remain the latest and the largest in the world for the steroids therapy of IgAN.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Corticosteroid for IgA Nephropathy: Are They Really Therapeutic?

et al. 2018

View full text Add to dashboard Cite

Background: IgA nephropathy (IgAN) is a common chronic glomerular disease that, in most patients, slowly progresses to end-stage kidney disease. The therapy with corticosteroid in IgAN is still a worldwide problem that is confusing the clinicians. Methods: MEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) that compared corticosteroids with placebo and any other non-immunosuppressive agents in treating IgAN. Twelve RCTs involving 1,057 patients were included. Results: Overall, we found that steroids had statistically significant effects in preventing the decline in renal function (relative risk 0.42, 95% CI 0.25–0.71, p < 0.001) and reducing proteinuria (SMD: –0.58 g/day, 95% CI –0.80 to –0.36 g/day) in patients with IgAN. The association between glucocorticoid and risk of kidney outcome was not modified by steroids’ type (prednisone or methylprednisone), dose (≤30 or > 30 mg/day), duration (≤8 or > 8 months), or serum creatinine (< 1.10 or ≥1.10 mg/dL). But steroids increased the risk of side effects such as gastrointestinal and endocrinium symptoms. Conclusion: This study provides the clear beneficial effects of the steroids therapy on the kidney function and proteinuria, although it should be used with caution.

show abstract

“…However, the issue of side effects was raised (one death due to pneumogenic sepsis and two neoplasms in the immunosuppressive group), which was further claimed by the results of the TESTING RCT in mostly Chinese patients [29]. The latter trial was prematurely discontinued because of an imbalance of adverse events, mostly infectious, in the corticosteroid arm, in spite of greater protection against renal failure progression.…”

Section: Indications For Corticosteroid Therapy For Igan In Europe Dementioning

confidence: 99%

IgA Nephropathy: A European Perspective in the Corticosteroid Treatment

Coppo

2018

Kidney Dis

View full text Add to dashboard Cite

Background: IgA nephropathy (IgAN) is detected in Europe in 22% of glomerular diseases diagnosed by biopsy. The frequency of IgAN as cause of ESRD in Europe has increased in the last decades, accounting for 35% of young and adult transplanted patients. These data justify the interest for risk factors and a possible therapeutic approach. Summary: Insight into a European perspective of IgAN was allowed by the multicenter study VALIGA, on 1,147 patients, almost all Caucasians, with follow-up of 4.7 years. The predictive value of mesangial hypercellularity (M), segmental sclerosis (S), tubular atrophy interstitial fibrosis (T) as independent biomarkers of progression was validated. Endocapillary hypercellularity was predictive of increased follow-up proteinuria. Two groups of patients selected by a propensity score to perfectly match for histologic features (MEST) and clinical data treated with renin-angiotensin system blockers (RASBs) and corticosteroids, or RASBs alone were compared and a beneficial effect of corticosteroids in addition to RASB was found in patients with proteinuria > 1 g/day, with an initial eGFR < 50 mL/min/1.73 m². On the contrary, the STOP-IgAN RCT found that immunosuppressive therapy in addition to optimal supportive care did not provide substantial kidney-related benefits in European patients with IgAN, because there was no difference in the rate of decrease in eGFR, although corticosteroid/immunosuppressive therapy induced complete remission of proteinuria more frequently than supportive care alone. The NEFIGAN trial evaluated a targeted release formulation of budesonide (TRF budesonide) delivering the drug in the distal ileum. TRF budesonide, additionally to optimized RAS blockade, reduced proteinuria and maintained eGFR in IgAN patients, suggesting a reduced risk of future progression to ESRD. Key Messages: In Europe, there is a reasoned search of a balanced approach to corticosteroid therapy for patients with IgAN, with particular attention to selecting the patients at risk of progression while limiting the unwanted systemic adverse events.

show abstract

Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy

Abstract: clinicaltrials.gov Identifier: NCT01560052.

Cited by 409 publications

References 24 publications

Effects of Hydroxychloroquine on Proteinuria in Immunoglobulin A Nephropathy

Effects of Hydroxychloroquine on Proteinuria in Immunoglobulin A Nephropathy

Corticosteroid for IgA Nephropathy: Are They Really Therapeutic?

IgA Nephropathy: A European Perspective in the Corticosteroid Treatment

Contact Info

Product

Resources

About