Kidney Week

Abstract: SA-PO436

Mathematical Modeling of Allo-Hemodialysis as Acute Treatment for Urea Cycle Disorders

Session Information

• Hemodialysis and Frequent Dialysis: Clearance, Technology, Infection
  November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

• 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

• Maheshwari, Vaibhav, Renal Research Institute, New York, New York, United States

Vaibhav Maheshwari,

• Filler, Guido, London Health Sciences Centre, London, Ontario, Canada

Guido Filler,

• Deep, Akash, King's College Hospital, London, London, United Kingdom

Akash Deep,

• Hussein, Rasha Hassan, Pontificia Universidade Catolica do Parana, Curitiba, Brazil

Rasha Hassan Hussein,

• Ferris, Maria E., University of North Carolina System, Chapel Hill, North Carolina, United States

Maria E. Ferris,

• Wang, Xin, Renal Research Institute, New York, New York, United States

Xin Wang,

• Patel, Amrish U., Renal Research Institute, New York, New York, United States

Amrish U. Patel,

• Kotanko, Peter, Renal Research Institute, New York, New York, United States

Peter Kotanko,

Background

Urea cycle disorders (UCD) are inborn errors of metabolism characterized by a reduced activity of enzymes that convert nitrogenous waste to urea, resulting in accumulation of ammonia (NH₃). UCDs can result in neonatal death or severe neurological complications. Clinically, swift reduction of NH₃ levels towards the normal range is key to prevent sequelae.
Previously, we have developed allo-hemodialysis (alloHD), a simple extracorporeal dialytic modality where a patient is dialyzed against a healthy subject (buddy) [Maheshwari (2020) KIR 5, S29]. Here, we model alloHD as a treatment for UCD.

Methods

We adapted a model of human NH₃ metabolism [Griffin (2019) Theor Biol Med Model 16, 11]. The model considers constant NH₃ absorption, renal excretion, and the activities of key urea cycle enzymes (glutamine synthase, glutaminase, carbamoyl phosphate synthetase I). To simulate UCD, neonate enzyme function was set to 5% of healthy capacity. For alloHD simulation, a mini dialyzer with surface area 0.075 m² was used. Neonate and buddy blood flow rates were 15 and 30 mL/min, respectively, ultrafiltration was zero.

Results

The NH₃ concentration gradient results in rapid diffusion of NH₃ and glutamine from the neonate to the buddy (Fig.1). Within 60 min of alloHD, the neonate NH₃ plasma concentration drops to around 50%. The subsequent steady state NH₃ is still above normal levels because in our simulations the neonate’s NH₃ production is kept unchanged. However, in clinical practice, the UCD patients’ protein intake is reduced to zero, which lowers the NH₃ production rate.

Conclusion

Our simulations indicate that alloHD is a potential option for the initial, emergency treatment of UCD.

Fig. 1: AlloHD treatment simulation for UCD.