Procyanidin displayed a synergistic effect with roxadustat on renal anemia in mice

TL;DR

A compound in berries and mulberries, when combined with roxadustat, improves anemia and kidney health in mice with chronic kidney disease.

Contribution

The study reveals a synergistic effect of procyanidin and roxadustat in treating renal anemia with reduced adverse effects.

Findings

Procyanidin improved erythropoiesis, kidney function, and reduced renal injury in CKD mice.

The combination of procyanidin and roxadustat enhanced iron mobilization and reduced inflammation and fibrosis.

Procyanidin mitigated thrombopoiesis caused by roxadustat, improving treatment safety.

Abstract

Chronic kidney disease (CKD) often leads to renal anemia, a complication traditionally treated with erythropoiesis-stimulating agents (ESAs) and iron supplementation. However, these treatments may increase cardiovascular risks. Procyanidin, a compound found in black goji berries and mulberries, has known kidney-protective properties. This study aimed to explore the synergistic effects of procyanidin and roxadustat in alleviating renal anemia in CKD.

A mouse model of CKD was induced by administering adenine, followed by treatment with procyanidin (250 mg/kg/day), roxadustat (5 mg/kg/day), or both. The effects on erythropoiesis, kidney function, iron metabolism, and inflammation were assessed through hematological analyses, histopathology, and gene expression profiling.

Procyanidin alone improved erythropoiesis, kidney function, and reduced renal injury. Roxadustat enhanced erythropoiesis and iron metabolism but showed no significant effect on kidney function. The combination of both compounds resulted in superior improvements in hematological parameters, reduced kidney injury, fibrosis, and inflammation, and enhanced iron mobilization and absorption. Notably, procyanidin mitigated the thrombopoiesis induced by roxadustat.

The combination of procyanidin and roxadustat provides a promising therapeutic approach for renal anemia by improving erythropoiesis, kidney function, and iron metabolism while reducing adverse effects, such as thrombosis. These findings suggest that procyanidin may enhance the safety and efficacy of roxadustat in CKD-related renal anemia. Further studies are needed to optimize treatment regimens for clinical application.

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