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


METHODS
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.


CONCLUSIONS
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.
Fuke
Y
Y
Department of Medicine, Division of Nephrology, Hypertension and Endocrinology, Nihon University School of Medicine, Tokyo, Japan. fuke@med.nihon-u.ac.jp
Fujita
T
T
Satomura
A
A
Endo
M
M
Matsumoto
K
K
D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000175:diagnosis*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D003167:Complement Activation; D017242:Complement Factor H / Q000652:urine*; D015938:Complement Membrane Attack Complex / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000652:urine; D007677:Kidney Function Tests; D016014:Linear Models; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged
D000970:Antineoplastic Agents; D015938:Complement Membrane Attack Complex; D017242:Complement Factor H; D002945:Cisplatin