Altered urinary beta 2-microglobulin excretion as an index of nephrotoxicity

The experimental and clinical evidence indicate that beta 2-microglobulin (beta 2m) is actively reabsorbed from the glomerular filtrate by receptors on the brush border located in the proximal third of the proximal tubule. Increased beta 2m excretion in the absence of increased filtered load of beta 2m is indicative of nephrotoxicity. The data presented show that urine beta 2m increases and creatinine concentrations decrease within four hours of administration of diatrizoate megalumine (DMG). In 9 of the 20 patients, the urinary excretion of beta 2m (U beta 2m) increased to clearly abnormal values. In 12 of the 20 patients, the beta 2m excretion expressed as mg per g creatinine (Cr), increased from normal (less than 0.30) to an abnormal beta 2m excretion rate. The increased beta 2m excretion per g Cr occurring immediately after DMG administration lead us to conclude that this effect occurs when the nephrotoxic agent is present in the kidney. Based on these data we believe that the onset of abnormal urinary beta 2m excretion coincides with the presence of the causative agent. This criterion therefore, should prove to be useful in determining the time to conduct studies designed to search for the causative agent(s) in Balkan endemic nephropathy.