EVALUATION OF NEPHROTOXICITY WITH RENAL ANTIGENS IN CHILDREN - ROLE OF TAMM-HORSFALL PROTEIN

Renal antigens are proteins that originate from the kidney and are detectable in urine by immunological techniques. After renal injury cell fragments are shed and appear in urine. Thus, the appearance of cellular fragments represents acute damage to renal cells caused by various means. With this approach proximal tubular cell injury can be detected using the proteins intestinal alkaline phosphatase (IAP) a brush border enzyme, or villin, a protein of the cytoskeleton. Both proteins have been found in urine from children receiving immunosuppressive treatment, including ifosfamide and aminoglycosides. In contrast, Tamm-Horsfall protein (THP) is an actively secreted protein that has been found by mRNA-analysis to occur only in the kidney. Immuno-reactivity to THP is restricted to the ascending loop of Henle and the early distal tubule. In human fetal specimens, THP expression was consistently found in the 16th week of gestation. In amniotic fluid THP was detectable after the 20th week, rising to a median value of 1.3 mg . l-1 at birth. In disturbed pregnancies with the feto-fetal transfusion syndrome, THP was not detectable, indicating reduced tubular THP secretion and renal function. Postnatally, THP excretion increases steadily, reaching a maximum in early adulthood. THP-excretion is low immediately after renal transplantation, reflecting acute renal failure in the early phase of transplantation, and increases to a normal values two to three weeks later. In severe diabetic ketoacidosis THP excretion is extremely low, with partial recovery 12 days later. The combination of low THP excretion and high proximal tubular enzyme release indicates both proximal (renal cortical) and distal tubular (renal medullary) damage in diabetic ketoacidosis. In conclusion, THP is a valuable marker of the function of the thick ascending loop of Henle in humans.