Utilization of lacrimal urea assay in the monitoring of hemodialysis: conditions, limitations and lacrimal arginase characterization

Abstract

The lacrimal urea content was found to be proportional to that of blood, which suggested its possible utilization in the monitoring of hemodialysis as a less invasive method. On the other hand, however, arginase activity was detected in tears, which may influence the urea content independently of blood urea concentration. The feasibility of using lacrimal urea measurement to replace blood urea measurement in the monitoring hemodialysis was also investigated. Blood and tear samples of 35 healthy persons and 43 renal patients undergoing hemodialysis were tested. Tear samples were collected on Schirmer paper strips. After elution the lacrimal urea content was measured by a colorimetric method. The determination of arginase activity was based on the release of urea and ornithine. The correlation between blood and lacrimal urea and arginase was studied by multivariate regression analysis. The lacrimal arginase isoenzyme pattern was investigated by native polyacrylamide gel electrophoresis and Western blotting. The effect of partially isoform-specific inhibitors was also studied. Blood urea levels in blood were significantly higher in the renal patients before dialysis than in the control patients (12·86±0·59 vs. 6·45±0·41 m m, p<0·0001). Blood sera arginase activity was very low. Lacrimal arginase activity was significantly higher in tears than in sera ( p<0·0001 for each group). The tear/serum ratio of urea content was significantly different between controls and renal patients, particularly in postdialytic samples (1·89±0·07 vs. 3·49±0·31, p<0·0001). The correlation between lacrimal and blood sera urea was best in controls ( r=0·89) and was better in predialytic ( r=0·75) than in postdialytic ( r=0·52) samples, depending on the level of arginase activity. In postdialytic samples a stronger correlation ( r=0·77) between tear urea and arginase was observed. Both arginase isoforms were detected in tears, but the extrahepatic (arginase II) isoenzyme was present in higher concentration. In conclusion, the determination of lacrimal urea level as a possible less invasive replacement for blood urea determination could only be utilized in the monitoring of hemodialysis if lacrimal arginase is also measured. Blood urea levels can be correctly determined by using equations, which take into account arginase activity. The accuracy of these equations was checked on a new patient population. Both arginase isoenzymes were observed in lacrimal samples.