Good Microdialysate Yield and Reliable Urea Recovery Using Dextran 40 in Interstitial Microdialysis in Uremia

Introduction and Objectives: Uremic toxins may be distributed differentially within body fluid compartments. Microdialysis studies using low molecular weight cut off catheters during dialysis suggest a discrepancy between plasma and interstitial urea kinetics. High molecular weight cut off (HMWCO) catheters will enable simultaneous capture of interstitial urea and larger toxins but perfusate loss and unreliable analyte recovery limit their use. We compared dextran 40 to standard perfusing fluid (Ringer’s solution) in interstitial microdialysis with HMWCO catheters in uremic subjects. Methods: Two HMWCO microdialysis catheters were inserted into the subcutaneous interstitium of 2 healthy controls and perfused with standard fluid. A third control and 2 peritoneal dialysis patients were perfused with dextran 40. Flow rate was increased stepwise from 0.3 to 5 μL/mn. Dialysate recovery was compared to expected recovery. Urea concentrations in the dialysate were measured and plotted against flow rates to determine interstitial concentrations. Results: Dialysate recovery: 24 samples were collected using dextran 40 and 16 samples using standard fluid.There was significant perfusate loss when standard fluid was used, especially at lower flow rates of 0.3 to 1μL/mn. Dialysate recovery averaged 13.7 μL compared to an expected 36 μL (p = 0.003). Meanwhile, dialysate yield with dextran 40 averaged 67.52 μL compared to an expected 64.5 μL (p = 0.82). Dialysate yield with dextran 40 was significantly higher than yield with standard fluid for all flow rates (p <0.0001). Urea Recovery and Interstitial Urea: Measured urea from standard fluid dialysate showed no correlation with perfusion rate, hence determination of relative recovery and interstitial urea was not possible. Conversely, with dextran 40, dialysate urea concentration was inversely proportional to flow rate. The y-intercept on a graph of concentration against flow gave the interstitial urea concentration. This was always close to the theoretical interstitial urea, i.e. close to plasma urea and to the urea concentration at very low flow rates. Relative recovery of urea at various flows could hence be determined. Conclusion: Due to good dialysate yield and reliable analyte recovery, dextran 40 enables microdialysis with HMWCO catheters to study small and large uremic toxins in the interstitium.