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 tubulointerstitial nephritis (TIN), which was induced in male Sprague Dawley rats by 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 were collected daily for 14 days and on day 21; and tissue specimens were collected on days 1, 4, 7, 10, 14 and 21. Urinalysis was correlated with the renal pathology at the light microscopic level. Laminin excretion was increased on day 4; one day before total protein, indicating damage to the basement membrane. Kallikrein levels also fell early indicating distal tubular damage. There is clear evidence that urine protein overload in a previously damaged kidney with tubulointerstitial injury leads to accelerated and more severe renal damage. Laminin and kallikrein are early and sensitive markers of renal injury.