The role of complement activation, detected by urinary C5b-9 and urinary factor H, in the excretion of urinary albumin in cisplatin nephropathy.

AIMS

Cis-diaminedichloroplatium II (CDDP) is an antineoplastic agent with serious renal toxicity, although the cause is not fully understood. The aim of this study was to clarify the functional roles of complement activation in cisplatin-nephropathy by examining the urinary complement components, C5b-9 and factor H.

SUBJECTS

Five patients with advanced lung cancer were included in this study as they were due to receive CDDP or 1,1-cyclobutanedicarboxylatoplatinum II (CBDA).

METHODS

Urine samples were collected before and after the chemotherapy for 13 days for measurements of C5b-9 (U-C5b-9), factor H (U-fH), albumin (U-Alb), beta2-microglobulin (U-beta2MG), and N-acetyl-beta-D-glucosamidase (NAG).

RESULTS

The mean level of U-Alb during the 5 - 8 day period after CDDP treatment was significantly higher than before treatment (p < 0.01). There was no significant correlation between U-Alb and NAG (r = -0.031, p = 0.994), or U-Alb and U-beta2MG (r = 0.061, p = 0.978) during the 5 - 8 day after CDDP treatment. U-Alb, U-C5b-9 and U-fH clearly increased on Days 4 - 10 after CDDP treatment. In our three patients treated with CDDP, mean estimated glomerular filtration rate (eGFR) was slightly decreased at 7 and 13 days after the treatment, compared to that of pretreatment, whereas there was no difference of eGFR between 7 and 13 days. In patients treated with CBDA, these parameters were clearly at lower levels compared to those patients treated with CDDP.

CONCLUSION

This study demonstrates that cisplatin may activate the complement pathway in the glomerulus, with factor H regulating the activation, resulting in decreased urinary albumin excretion and renoprotection.