Dataset Information

Kidney microRNA-21 Expression and Kidney Function in IgA Nephropathy.

ABSTRACT:

Rationale & objective

Previous studies have suggested that microRNA-21 (miR-21) plays an important role in kidney fibrosis. We examined the relationship between intrarenal miR-21 level and rate of kidney function loss in immunoglobulin A nephropathy (IgAN).

Study design

Prospective cohort study.

Setting & participants

40 patients with IgAN and 10 with hypertensive nephrosclerosis as controls.

Predictors

miR-21 levels in kidney biopsy specimen and urinary sediment, quantified as ratio to the housekeeping gene.

Outcomes

Kidney event-free survival and rate of kidney function decline.

Analytic approach

Time-to-event and correlation analysis.

Results

The IgAN group had significantly higher intrarenal miR-21 expression compared with the hypertensive nephrosclerosis group (1.71 [IQR, 0.99-2.77] vs 0.31 [IQR, 0.25-1.32]; P < 0.0001), but urinary miR-21 levels were similar. Intrarenal miR-21 expression had significant but modest correlation with severity of glomerulosclerosis (r = 0.293; P = 0.05) and tubulointerstitial fibrosis (r = 0.341; P = 0.03). Patients with high intrarenal miR-21 expression had significantly higher risk for developing kidney end points compared with those with low expression (log-rank test, P = 0.017). Univariate Cox analysis showed that intrarenal miR-21 expression significantly predicted the development of kidney end points (unadjusted HR, 1.586; 95% CI, 1.179-2.134; P = 0.002). However, the result was just short of statistical significance after adjusting for the severity of histologic damage (P = 0.06). There was also a significant correlation between intrarenal miR-21 expression and the slope of kidney function decline by univariate analysis (r = -0.399; P = 0.02).

Limitations

Small sample size; uncertain cellular origin of miR-21.

Conclusions

We found that intrarenal miR-21 expression is increased in patients with IgAN, modestly correlated with the severity of histologic damage, and predictive of subsequent kidney function loss.

SUBMITTER: Szeto CC

PROVIDER: S-EPMC7873829 | biostudies-literature | 2021 Jan-Feb

REPOSITORIES: biostudies-literature

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Publications

Kidney microRNA-21 Expression and Kidney Function in IgA Nephropathy.

Szeto Cheuk-Chun CC Ng Jack Kit-Chung JK Fung Winston Wing-Shing WW Luk Cathy Choi-Wan CC Wang Gang G Chow Kai-Ming KM Lai Ka-Bik KB Li Philip Kam-Tao PK Lai Fernand Mac-Moune FM

Kidney medicine 20201204 1

<h4>Rationale & objective</h4>Previous studies have suggested that microRNA-21 (miR-21) plays an important role in kidney fibrosis. We examined the relationship between intrarenal miR-21 level and rate of kidney function loss in immunoglobulin A nephropathy (IgAN).<h4>Study design</h4>Prospective cohort study.<h4>Setting & participants</h4>40 patients with IgAN and 10 with hypertensive nephrosclerosis as controls.<h4>Predictors</h4>miR-21 levels in kidney biopsy specimen and urinary sediment, qu ...[more]

PMID: 33604541

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Project description:IgA nephropathy (IgAN), the most frequent primary glomerulonephritis, affects young patients and is associated with a high risk of progression to end-stage renal disease. Consequently, patients with IgAN constitute an important proportion of candidates for kidney transplantation. Several studies showed a significant risk of IgAN recurrence on kidney graft, but the risks factors for recurrence remain to be accurately evaluated. Indeed, early identification of at risk patients may allow the optimization of treatment and the reduction of recurrence rate on the graft. In the present work, we studied the relationship between post-transplant serum IgA (sIgA) levels and the risk of IgAN recurrence after kidney transplantation. Recipients with IgAN had higher levels of sIgA as compared to patients with other nephropathies (p<0.05). The prevalence of IgAN recurrence was 20.8% during the period of analysis (mean follow-up of 6 ± 3.2 years). Serum IgA levels at M6, M12 and M24 post-transplant were significantly higher in patients with IgAN recurrence as compared to those without (p = 0.009, p = 0.035 and p = 0.029, respectively). Using receiver operating curve (ROC), sIgA at M6 and M12 post-transplant were significantly associated with IgAN recurrence (AUC = 0.771, p = 0.004 and AUC = 0.767, p = 0.016, respectively), while serum creatinine and proteinuria were not. Serum IgA level at month 6 was significantly associated with the occurrence of post-transplant IgA recurrence, whether it was analyzed as a continuous or a categorical variable. After successive adjustment on age, gender and proteinuria, sIgA remained a significant risk factor of post-transplant IgAN recurrence. Finally, survival free of IgAN recurrence was significantly better in patients with sIgA<222 mg/dL at month 6 as compare to IgAN patients with sIgA≥222 mg/dL (p = 0.03). Thus, the present work supports a link between post-transplant sIgA levels and IgAN recurrence and suggests that sIgA may be a valuable predictive biomarker of IgAN recurrence in kidney transplant recipients.

Project description:ImportanceThe effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain.ObjectiveTo evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline.Design, setting, and participantsAn international, multicenter, double-blind, randomized clinical trial that enrolled 503 participants with IgA nephropathy, proteinuria greater than or equal to 1 g per day, and estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m2 after at least 3 months of optimized background care from 67 centers in Australia, Canada, China, India, and Malaysia between May 2012 and November 2019, with follow-up until June 2021.InterventionsParticipants were randomized in a 1:1 ratio to receive oral methylprednisolone (initially 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136) or placebo (n = 126). After 262 participants were randomized, an excess of serious infections was identified, leading to dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning by 4 mg/d/mo) and addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent participants (121 in the oral methylprednisolone group and 120 in the placebo group).Main outcomes and measuresThe primary end point was a composite of 40% decline in eGFR, kidney failure (dialysis, transplant), or death due to kidney disease. There were 11 secondary outcomes, including kidney failure.ResultsAmong 503 randomized patients (mean age, 38 years; 198 [39%] women; mean eGFR, 61.5 mL/min/1.73 m2; mean proteinuria, 2.46 g/d), 493 (98%) completed the trial. Over a mean of 4.2 years of follow-up, the primary outcome occurred in 74 participants (28.8%) in the methylprednisolone group compared with 106 (43.1%) in the placebo group (hazard ratio [HR], 0.53 [95% CI, 0.39-0.72]; P < .001; absolute annual event rate difference, -4.8% per year [95% CI, -8.0% to -1.6%]). The effect on the primary outcome was seen across each dose compared with the relevant participants in the placebo group recruited to each regimen (P for heterogeneity = .11): full-dose HR, 0.58 (95% CI, 0.41-0.81); reduced-dose HR, 0.27 (95% CI, 0.11-0.65). Of the 11 prespecified secondary end points, 9 showed significant differences in favor of the intervention, including kidney failure (50 [19.5%] vs 67 [27.2%]; HR, 0.59 [95% CI, 0.40-0.87]; P = .008; annual event rate difference, -2.9% per year [95% CI, -5.4% to -0.3%]). Serious adverse events were more frequent with methylprednisolone vs placebo (28 [10.9%] vs 7 [2.8%] patients with serious adverse events), primarily with full-dose therapy compared with its matching placebo (22 [16.2%] vs 4 [3.2%]).Conclusions and relevanceAmong patients with IgA nephropathy at high risk of progression, treatment with oral methylprednisolone for 6 to 9 months, compared with placebo, significantly reduced the risk of the composite outcome of kidney function decline, kidney failure, or death due to kidney disease. However, the incidence of serious adverse events was increased with oral methylprednisolone, mainly with high-dose therapy.Trial registrationClinicalTrials.gov Identifier: NCT01560052.

Dataset Information

Kidney microRNA-21 Expression and Kidney Function in IgA Nephropathy.

Rationale & objective

Study design

Setting & participants

Predictors

Outcomes

Analytic approach

Results

Limitations

Conclusions

Publications

Kidney microRNA-21 Expression and Kidney Function in IgA Nephropathy.

Similar Datasets

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