**6. Role of renal replacement therapy**

### **6.1 Ammonia clearance by dialysis**

In general, solute-related factors that may affect the extent of its removal by dialysis include its molecular size, its water solubility, its volume of distribution, and its protein binding. Ammonia is a small molecule with a molecular mass of 17 mg/ mmol, it is water soluble, has a volume of distribution that is considered to be equal to the total body water, and is not significantly protein-bound [11]. Therefore, it is highly dialyzable.

Hemodialysis prescription-related factors affecting the clearance of ammonia include the blood flow rate (Qb), the dialysate flow rate (Qd), and the dialyzer surface area [12]. This is supported by an *in vitro* study of the clearance of ammonia with single-pass dialyzers, which showed that ammonia clearance by dialysis is between 62% and 99% and could approach that of the liver [12]. In this study, ammonia clearance was directly dependent on the blood flow rate, which was modulated by the dialysate flow rate. For example, when the dialysate flow rate is 300 ml/min, an increase in ammonia clearance was observed with an increase in blood flow until a plateau was reached at 200 ml/min. When the dialysate flow is 500 ml/min, the same was observed but it plateaued at a blood flow rate of 300 ml/min [12]. At a dialysate flow rate of 800 ml/min, a further degree of ammonia clearance was observed with increasing blood flow rate but no plateau was observed within the range of the blood flow rate used. In other words, with a blood flow rate of 200 to 300 ml/min and a dialysate flow rate of 800 ml/min, a rate of ammonia extraction of up to 99% can be seen if there is no ongoing generation of ammonia [12, 13]. The influence of the dialyzer surface area on ammonia clearance depends on the blood flow rate. With a blood flow rate of 500 ml/min and a large surface area dialyzer (2.1 m<sup>2</sup> ), ammonia clearance may approach 450 ml/min. However, the ammonia clearance was not affected when using large surface area dialyzers at a blood flow rate of 100–200 ml/min. Of note, hemodialysis removes urea and glutamine, which may magnify the ammonia-lowering effects and benefits of hemodialysis [12].
