Prolonged Duration of Erythropoiesis-Stimulating Agents' Action Delays Disease Progression in Anti-Thy 1 Antibody-Induced Chronic Glomerulonephritis Rats.

Abstract

BACKGROUND:

Although erythropoiesis-stimulating agents (ESAs) exert renoprotective effects in renal disease models, it has not been revealed whether the prolonged duration of action of ESAs contributes to their renoprotective effects.

OBJECTIVE:

We examined whether the prolonged duration of ESAs' action contributes to their renoprotective effects by comparing a divided administration of a short-acting ESA, epoetin beta (EPO), or a single administration of a long-acting ESA, epoetin beta pegol (continuous erythropoietin receptor activator; C.E.R.A.), to a single administration of EPO in chronic glomerulonephritis (GN) rats.

MATERIALS AND METHODS:

Chronic GN was induced by intravenous injection of anti-Thy 1.1 antibody (0.6 mg/kg) into uninephrectomized rats (day 0). Chronic GN rats were intravenously injected once with vehicle (disease control; DC), EPO 5,000 IU/kg (single EPO), or C.E.R.A. 25 μg/kg (single C.E.R.A.) on day 1; or 3 times during the first week with EPO 1,667 IU/kg from day 1 (divided EPO; total 5,000 IU/kg). Hemoglobin (Hb) level and urinary total protein (U-TP) level which are the indexes of hematopoiesis and renoprotective effects, respectively, were measured several times over 8 weeks.

RESULTS:

Divided EPO and single C.E.R.A. increased Hb levels more greatly than did single EPO. In all chronic GN rats, elevated U-TP levels decreased transiently 2 weeks after chronic GN induction and then flared again. Single EPO significantly suppressed this exacerbation of U-TP levels compared to DC. Divided EPO and single C.E.R.A. each significantly suppressed the exacerbation of U-TP levels compared to single EPO.

CONCLUSION:

Prolonged duration of ESAs' action contributed significantly to their renoprotective effects.

• Authors: Ryohei Kawasaki, Yoshihito Tashiro, Kenji Yogo, Kenichi Serizawa, Ken Aizawa, Koichi Endo, Michinori Hirata
• Journal: Pharmacology (Pharmacology) Vol. 106 Issue 1-2 Pg. 45-52 ( 2021) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 32829322 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2020 S. Karger AG, Basel.

Chemical References

• Hematinics
• Hemoglobins
• Isoantibodies
• Protective Agents
• Recombinant Proteins
• anti-Thy antibody
• continuous erythropoietin receptor activator
• epoetin beta
• Erythropoietin
• Polyethylene Glycols
• Iron

Topics

• Anemia (chemically induced, therapy)
• Animals
• Disease Models, Animal
• Disease Progression
• Drug Administration Schedule
• Erythropoiesis (drug effects)
• Erythropoietin (administration & dosage, pharmacology)
• Glomerulonephritis (chemically induced, diagnosis, therapy)
• Hematinics (administration & dosage, pharmacology)
• Hemoglobins (analysis, drug effects)
• Hypoxia
• Injections, Intravenous
• Iron (metabolism)
• Isoantibodies (toxicity)
• Kidney (drug effects, metabolism, physiopathology)
• Male
• Polyethylene Glycols (administration & dosage, pharmacology)
• Protective Agents (administration & dosage, pharmacology)
• Proteinuria (urine)
• Rats, Inbred F344
• Recombinant Proteins (administration & dosage, pharmacology)