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Abstract: SA-PO436

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

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis


  • Maheshwari, Vaibhav, Renal Research Institute, New York, New York, United States
  • Filler, Guido, London Health Sciences Centre, London, Ontario, Canada
  • Deep, Akash, King's College Hospital, London, London, United Kingdom
  • Hussein, Rasha Hassan, Pontificia Universidade Catolica do Parana, Curitiba, Brazil
  • Ferris, Maria E., University of North Carolina System, Chapel Hill, North Carolina, United States
  • Wang, Xin, Renal Research Institute, New York, New York, United States
  • Patel, Amrish U., Renal Research Institute, New York, New York, United States
  • Kotanko, Peter, Renal Research Institute, New York, New York, United States

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.


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.


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.


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

Fig. 1: AlloHD treatment simulation for UCD.