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Effect of high doses of methylprednisolone on the isolated, perfused canine kidney
Abstract:
The administration of methylprednisolone (MP) (2.125-4.125 G) To the cryoprecipitated plasma perfusate of 41 canine kidneys preserved with hypothermic pulsatile perfusion is associated with increased vascular resistance, decreased plasma flow, and rising perfusion pressure that become more pronounced over periods up to 20 hr. The magnitude of the increase in renal resistance is directly related in a bimodal fashion to the dose of MP and to the interval following drug administration. The increase in renal resistance is generally irreversible (three or four cases) under conditions of high MP dosage (2.125 g) administered for 4 hr or longer. Severe histological changes occurred in kidneys perfused with MP 20 hr or longer. These changes were primarily glomerular changes consisting of necrosis of capillary loops, occlusion of Bowman's space, basement membrane thickening, and endothelial cell damage; tubular changes consisting of occlusion of tubular lumens and tubular epithelial cell damage; and arteriolar changes consisting of occlusion primarily of afferent arterioles with dense eosinophilic material. These studies demonstrate that the administration of high doses of MP can produce irreversible hemodynamic and histological changes in the isolated, perfused kidney and may preclude its use in pretreating kidneys for transplantation.
Insights
High doses of methylprednisolone (MP) in kidney perfusion increase resistance and cause irreversible damage. This suggests MP may not be suitable for pre-transplant kidney treatment due to adverse hemodynamic and histological effects.
Area of Science:
- Nephrology
- Pharmacology
- Transplantation Science
Background:
- Hypothermic pulsatile perfusion is a method for preserving organs for transplantation.
- Methylprednisolone (MP) is a corticosteroid sometimes used in organ preservation protocols.
Purpose of the Study:
- To investigate the effects of methylprednisolone administration on isolated canine kidneys during hypothermic pulsatile perfusion.
- To determine the dose- and time-dependent hemodynamic and histological consequences of MP in perfused kidneys.
Main Methods:
- 41 canine kidneys were preserved using hypothermic pulsatile perfusion.
- Cryoprecipitated plasma perfusate was administered with varying doses of methylprednisolone (2.125-4.125 g).
- Hemodynamic parameters (vascular resistance, plasma flow, perfusion pressure) and histological changes were assessed up to 20 hours.
Main Results:
- MP administration led to increased renal vascular resistance, decreased plasma flow, and rising perfusion pressure.
- These hemodynamic changes were dose- and time-dependent, becoming more pronounced with higher MP doses and longer perfusion intervals.
- High-dose MP (≥2.125 g for ≥4 hr) resulted in generally irreversible resistance increases and severe glomerular, tubular, and arteriolar histological damage.
Conclusions:
- High-dose methylprednisolone administration during hypothermic pulsatile perfusion can induce irreversible hemodynamic and histological alterations in canine kidneys.
- These findings suggest that MP pretreatment may be detrimental and could preclude its use in preparing kidneys for transplantation.