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Full-dose prednisone (FP) regimen in the treatment of high-risk immunoglobulin A nephropathy (IgAN) patients, is still controversial. The pulsed intravenous methylprednisolone combined with alternative low-dose prednisone (MCALP) might have a more favorable safety profile, which has not been fully investigated. Eighty-seven biopsy-proven IgAN adult patients and proteinuria between 1 and 3.5 g/24 h after ACEI/ARB for at least 90 days were randomly assigned to 6-month therapy: (1) MCALP group: 0.5 g of methylprednisolone intravenously for three consecutive days at the beginning of the course and 3rd month respectively, oral prednisone at a dose of 15 mg every other day for 6 months. (2) FP group: 0.8–1.0 mg/kg/days of prednisone (maximum 70 mg/day) for 2 months, then tapered by 5 mg every 10 days for the next 4 months. All patients were followed up for another 12 months. The primary outcome was complete remission (CR) of proteinuria at 12 months. The percentage of CR at 12th and 18th month were similar in the MCALP and FP groups (51% vs 58%, P = 0.490, at 12th month; 60% vs 56%, P = 0.714, at 18th month). The cumulative dosages of glucocorticoid were less in the MCALP group than FP group (4.31 ± 0.26 g vs 7.34 ± 1.21 g, P < 0.001). The analysis of the correlation between kidney biopsy Oxford MEST-C scores with clinical outcomes indicated the percentages of total remission was similar between two groups with or without M1, E1, S1, T1/T2, and C1/C2. More patients in the FP group presented infections (8% in MCALP vs 21% in FP), weight gain (4% in MCALP vs 19% in FP) and Cushing syndrome (3% in MCALP vs 18% in FP). These data indicated that MCALP maybe one of the choices for IgAN patients with a high risk for progression into ESKD. Trial registration: The study approved by the Chinese Clinical Trial Registry (registration date 13/01/2018, approval number ChiCTR1800014442, https://www.chictr.org.cn/). [ABSTRACT FROM AUTHOR]

Background/Aims: FK506 is an immunosuppressive drug and a calcineurin inhibitor that has been widely used in kidney disease in recent years. FK506 shows a wide range of biological and pharmaceutical effects; however, the mechanism of its anti- proliferative effect has not been well elucidated. An IgA nephropathy (IgAN) model was used to generate a mesangial cell proliferation model. This study aims to examine the effect of FK506 on IgAN rats and the underlying mechanisms. Methods: Hematuria, proteinuria and renal function were measured. To observe the pathological conditions, we performed HE (hematoxylin - eosin) and PAS (periodic acid - schiff) staining. Transcription and protein expression levels were detected by qRT - PCR (quantitative real-time polymerase chain reaction) and Wb (western blotting). The location and semi-quantitative expression levels of TRPCs, CaN (Calcineurin) and α-SMA were examined by IHC (Immunohistochemical staining). Results: We found that FK506 could improve hematuria, proteinuria and renal function, especially in the HF (high-dose FK506) groups. Renal pathological changes were ameliorated in the treatment groups. FK506 could significantly decrease TRPCs, CaN, phosphorylation of ERK1/2 and α-SMA expression. Conclusion: Taken together, these results suggest that the therapeutic effect of FK506 on IgAN might be partially associated with the down-regulated expression of TRPC channels, CaN and phosphorylation of ERK1/2. [ABSTRACT FROM AUTHOR]