title: Renal kallikrein excretion as a distal nephrotoxicity marker during cadmium exposure in rats.
abstract: Cadmium exposure is known to induce hypertension, but development of hypertension is not universal in exposed animals. However, the cellular uptake of cadmium could also exert renal cytotoxic effects which have been, until now, essentially only studied at the proximal tubule level. Kallikrein is an enzyme synthetized in renal cortex and excreted in the urine in the distal tubule. Therefore, to evaluate the distal renal effect of cadmium, we studied the daily urinary kallikrein excretion (UKE) in conscious unrestrained female Brown Norway rats during long-term chronic exposure to 2 dosages of cadmium given subcutaneously 3 times a week, a low dose (LD): 0.25 mg/kg and a high dose (HD): 1 mg/kg. Neither dose of cadmium was able to induce significant hypertension in the treated animals. HD administration for 24 weeks resulted in a decreased UKE associated with an increase in plasma renin activity and sodium and potassium excretions. LD administration had no significant effect on UKE. Twenty weeks after stopping cadmium administration, a persistent reduction in UKE was still observed; furthermore, the group which had been previously administered a LD of cadmium, now also exhibited a reduced UKE. During this re-examination period in both groups, the UKE reductions were associated with normal systolic blood pressure, glycosuria, natriuresis. Our data show that cadmium administration can influence UKE, plasma renin activity, plasma aldosterone concentration and electrolyte excretion without inducing any variation of blood pressure. This may reflect a nephrotoxic, non-hypertensive effect. Since this effect persisted after stopping cadmium administration, it may indicate a prolonged irreversible nephrotoxic effect at the distal nephron level. Thus, UKE may be a useful non-invasive index to evaluate distal nephrotoxicity.
authors.affiliation: INSERM U133, Faculté de Médecine Rangueuil, Toulouse, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Girolami
authors.forename: J L
authors.initials: JL
authors.lastname: Bascands
authors.forename: C
authors.initials: C
authors.lastname: Pécher
authors.forename: G
authors.initials: G
authors.lastname: Cabos
authors.forename: J P
authors.initials: JP
authors.lastname: Moatti
authors.forename: J F
authors.initials: JF
authors.lastname: Mercier
authors.forename: J M
authors.initials: JM
authors.lastname: Haguenoer
authors.forename: Y
authors.initials: Y
authors.lastname: Manuel
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D004573:Electrolytes / Q000652:urine; D005260:Female; D007610:Kallikreins / Q000652:urine*; D007672:Kidney Cortex / Q000201:enzymology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000652:urine; D007686:Kidney Tubules, Distal / Q000201:enzymology; D051381:Rats; D012083:Renin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004573:Electrolytes; D002104:Cadmium; D000450:Aldosterone; D007610:Kallikreins; D012083:Renin