CHANGES OF URINARY ??1-MICROGLOBULIN IN THE ASSESSMENT OF PROGNOSIS IN RENAL TRANSPLANT RECIPIENTS1

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Abstract
After transplantation, even if the graft starts functioning immediately, there are morphological and functional changes in tubular structures. In addition, acute allograft rejection causes damage in the tubular epithelium, tubular basement membrane, and intertubular connective tissue. It also affects the functional capacity of proximal tubular cells resulting in impaired reabsorption and thus increased urinary excretion of low molecular weight proteins. We present a double-antibody radioimmunoassay for determination of the concentration of alpha1-microglobulin (alpha1 M) in urine. It was used to measure urinary excretion of alpha1 M approximately once a week during the first 1-6 posttransplant weeks in 136 consecutive patients: 30 patients developing acute rejection (75 24-hr urine samples) and 106 patients with stable graft function (223 24-hr urine samples). The results are expressed as alpha1 M/creatinine ratios. Approximately 8 days after transplantation the mean (+/-SD) urinary alpha1 M/creatinine ratio of all patients was 17.0+/-14.8 mg/mmol, being about the same both in patients with uncomplicated posttransplantation course (16.3+/-14.0 mg/mmol) and in those who later developed rejection (19.3+/-15.1 mg/mmol), but about 60-fold higher than in healthy controls (0.27+/-0.15 mg/mmol). At that time, when all patients were included there was a correlation (r=0.3465, P<0.001) between alpha1 M/creatinine ratio and duration of cold ischemia. Thereafter, during the second week alpha1 M/creatinine ratio decreased in 89% of patients with stable graft function, but only in 14% of patients who later developed rejection (P<0.001). On the contrary, a significant increase (P<0.01) of alpha1 M/creatinine ratio was observed 4 to 1 day before rejection in all 15 patients, who had urines collected at that time. At the end of the follow-up period, alpha1 M/creatinine ratio in patients with rejection was 3-fold compared with the nonrejecting patients, and 100-fold compared with the healthy controls. These results show that cadaveric transplantation results in impaired low molecular weight protein reabsorption, the degree of dysfunction relating to the duration of cold ischemia, and suggest that during the posttransplant weeks decreasing alpha1 M/creatinine ratio in consecutively collected urine samples indicates improved tubular function and in most cases rules out development of acute rejection.