Corticosteroids pulse therapy and oral corticosteroids therapy for IgA nephropathy patients with advanced chronic kidney disease: results of a multicenter, large-scale, long-term observational cohort study

Abstract

BackgroundCorticosteroids are widely used to reduce the urine protein levels of patients with immunoglobulin A nephropathy (IgAN). However, their potential preventive effects on end-stage kidney disease (ESKD) are unclear.MethodsWe previously performed a large-scale, long-term multicenter cohort study of patients with biopsy-proven IgAN treated between 1981 and 2013 (n = 1923). Based on the results, we reported that corticosteroids pulse therapy was potentially effective for the treatment of patients with an eGFR ≥30 ml/min/1.73m2 and a urine protein amount of ≥1 g/gCr. In the present study, we extracted 766 patients with chronic kidney disease (CKD), stage G3–G4 (15 ≤ estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2) from the same cohort. We divided these patients into a steroid pulse (SP) group, oral steroid (OS) group, and no steroid (NS) group, and analyzed the risk of end-stage kidney disease (ESKD) stratified by eGFR and urine protein (UP) amounts.ResultsOver the median long-term follow-up of 70 ± 115 months, 37.1% of the patients with UP ≥1.0 g/day and 11.2% of the patients with UP < 1.0 g/day reached ESKD. Among the patients with UP ≥1 g/gCr, the SP group showed significantly better renal outcome (p < 0.001) than the OS and NS groups. In patients with UP < 1 g/gCr, there were no differences in renal survival among the treatment groups. These trends appeared even in the CKD stage G4 patients, and were also apparent in patients taking renin-angiotensin system inhibitors. The unprecedented long-term observation period in this study may have been necessary to reveal the favorable effect of corticosteroids on ESKD progression.ConclusionsIn our long-term multicenter study, Corticosteroids pulse therapy was associated with better renal outcomes in IgAN patients with higher UP values, even if their eGFR values were low.

PharmOmics: A Species- and Tissue-specific Drug Signature Database and Online Tool for Drug Repurposing

“…PharmOmics dose/time-segregated (64% AUC, p=0.001) and meta databases (61% AUC, p=0.028) both showed a significant performance ( Figure 8D ), whereas from the other tools evaluated only CMAP (63% AUC, p<0.001) showed a significant performance (L1000 43% and CREEDS 56% AUC, non-significant). The top 5 nephrotoxic drugs predicted by PharmOmics were dexamethasone (potential CKD alleviating agent) (57,58), naproxen (documented nephrotoxic drug in DrugBank), cholecalciferol (potential CKD alleviating agent) (59), beta-estradiol (potential alleviating agent in women) (60,61), and ibuprofen (documented nephrotoxic drug in DrugBank). We also examined the gene overlap patterns of the top drugs with the CKD gene network ( Figure 8E ) and found sparse overlap, which again is in contrast to the top hepatotoxicity drugs ( Figure 7E ).…”

Immunosuppressants or corticosteroids compared with supportive therapy: a systematic review and meta-analysis on the efficacy and safety for IgA nephropathy treatment

“…Further, the risk of ESKD within 6 years was significantly reduced, which seems to support an association between long-term renal outcomes and proteinuria in IgAN patients. In addition, a multicenter, large-scale, long-term follow-up observational c o h o r t s t u d y s h o w e d t h a t i m m u n o s u p p r e s s a n t / corticosteroid treatment in IgAN patients had better longterm renal outcomes (29). Meanwhile, a 15-year follow-up study of 1,243 children with IgAN in China showed that immunosuppressant/corticosteroid therapy improved longterm renal outcomes (30).…”

Immunopathogenesis of COVID-19 and early immunomodulators

“…The beneficial effects of corticosteroid on various infectious diseases, including viral infections such as Epstein-Barr virus infection and infectious croup as well as severe bacterial infections such as tuberculous meningitis and typhoid fever, are well known. Furthermore, methylprednisolone pulse therapy (30 mg/kg/day or 1 g/day for adults) is used for 3 or more consecutive days for severe infectious disease and immune-mediated diseases such as MP pneumonia, lupus nephritis, KD, acute central nervous system diseases, and even advanced chronic kidney diseases [ 117 , 118 ], although the diseases are rare in older individuals. During this pandemic, some organ transplant recipients treated with T-cell suppressants seem to be protected from pneumonia [ 119 ], and older patients receiving anticancer drugs can recover from severe COVID-19 [ 120 ].…”