Urine laminin and kallikrein, markers of tubulointerstitial damage in experimental protein overload on pre-existing renal damage

We studied the response of urinary protein overload on preexisting tubuloin terstitial nephritis (TIN), which was induced in male Sprague Dawley rats b y hexachloro-1,3-butadiene (HCBD). Five days after the development of TIN, puromycin aminonucleoside (PAN) was administered to induce urinary protein overload. Urinary laminin and kallikrein were measured. Urine specimens wer e collected daily for 14 days and on day 21; and tissue specimens were coll ected on days 1, 4, 7, 10, 14 and 21. Urinalysis was correlated with the re nal pathology at the light microscopic level. Laminin excretion was increas ed on day 4; one day before total protein, indicating damage to the basemen t membrane. Kallikrein levels also fell early indicating distal tubular dam age. There is clear evidence that urine protein overload in a previously da maged kidney with tubulointerstitial injury leads to accelerated and more s evere renal damage. Laminin and kallikrein are early and sensitive markers of renal injury.