Development of a blood urea monitoring system for the closed loop control of dialysis

Optimal hemodialysis prescription through real-time blood urea (BU) monitoring and closed loop control of urea removal would be of significant clinical value. Progress toward a bedside BU analyzer and a control system is described here. An Amicon Minifilter inserted into the arterial bloodline provides a 1 ml/min stream of protein free ultrafiltrate for analysis. In vitro tests with bovine blood have shown excellent correlation between plasma (CP) and ultrafiltrate (CU) urea levels: CP = 0.961CU + 0.071, (n = 34, r = 0.998). In clinical hemodialysis studies, CU accurately represented the decay in CP. The BU analyzer uses a standard UV endpoint assay with a proportioning roller pump. The absorbance of the reacted mixture is read in a spectrophotometer after a 5 min incubation. For future control system design, the transfer function (TF) of the BU analyzer was measured using multifrequency binary testing. The data indicated that the analyzer may be modeled by a second order TF with a pure time delay. The same form of TF was also found to describe the Minifilter. Control of the removal rate of NaCl (substituted for urea) through automatic dialysate flow adjustment has been achieved with a simulated dialyzer-patient circuit (using a conductivity probe in place of the BU analyzer). A modified BU analyzer using computer controlled precision syringes for improved sample processing time and accuracy is also reported.