Albutran Research and Production Enterprise, Minsk, Belarus
Background: Serum albumin (SA) is the main carrier protein in the blood that transfers multiple metabolites, binds and uptake toxins to hepatocytes, carries medical drugs.
In patients developing intoxication, there the detoxifying activity of SA is of importance. SA molecules can be overloaded with excessively high levels of toxins and their detoxifying activity can be reduced because of that. Deactivating of the SA molecules leads to inadequate overall elimination of toxins from the body, following by further deterioration of SA and resulting in escalating intoxication. In patients with active malignant tumors, there is a specific modification to conformation of SA molecules that was demonstrated in series of clinical studies. Active malignant cells secrete numerous specific metabolites of low-molecular-mass which remain in the circulatory system in the conjugated state on carrier proteins, mostly on SA. Accumulation of the cancer-specific metabolites caused a significant change to a molecular conformation of SA that can be detected using Electron Paramagnetic Resonance (EPR).
Objective: To develop the in vitro laboratory test for detoxifying activity (DTE) and molecular conformation of SA.
Methods: The tests were developed basing on the spin probe method of EPR, using 16-doxyl stearic acid as the spin probe specific to albumin. The investigated material is 100 μl of serum or plasma EDTA. The tests are realized on the Analyzer EPR "AXM-09" as the platform and sets of reagents "ATA-test-T" and "ATA-test-C" (Albutran), which were approved as IVD devices. The test procedure takes 30 min; the sample measurement time is 4 min (15 samples per hour).
The clinical utility of the DTE-test was evaluated in the observational clinical studies performed on 136 post-surgery patients (20 of them had sepsis), 92 kidney transplant recipients (54 had the kidney transplant dysfunction) and 189 pregnant women (92 suffer from preeclampsia).
Utility of the EPR test of SA molecular conformation was evaluated in the series of observational clinical studies performed on 320 cancer patients with tumors of different localizations and 183 cancer-free individuals.
Results: The study of the post-surgery patients has confirmed that DTE-test of SA, that was performed in the first two hours after the surgery, allowed prediction and early diagnosis of sepsis and SIRS with accuracy of 80%.
In the patients with kidney transplant dysfunction, there DTE-test provided the diagnosis of kidney transplant dysfunction with the diagnostic sensitivity and specificity of 73% and 78%, respectively.
In the pregnant women with severe preeclampsia, there the diagnostic sensitivity and specificity of DTE-test were 64% and 92%, respectively, in second trimester, and 59% and 82% in third trimester.
In cancer patients, there the EPR test of the albumin conformation provided the diagnosis of patients with active malignancies with the diagnostic sensitivity and specificity above 80%
Conclusion: The in vitro EPR test of serum albumin is the novel noninvasive method which has demonstrated the diagnostic utility for early diagnosis of sepsis in post-surgery patients, diagnosis of kidney transplant dysfunction in recipients, severe preeclampsia in pregnant women, and diagnosis of malignant tumors in cancer and cancer-risk patients.