leuprolide and Acute-Kidney-Injury

Suramin has demonstrated modest activity against prostate cancer and is being investigated in clinical trials. We describe a patient with metastatic prostate cancer who developed nonoliguric renal failure during treatment with suramin. Other potential causes of renal failure were not present in our patient and his renal function gradually recovered with the cessation of suramin treatment. Acute renal failure should be recognized as a potential complication of suramin treatment.

Topics: Acute Kidney Injury; Adenocarcinoma; Androgen Antagonists; Anti-Inflammatory Agents; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Flutamide; Humans; Hydrocortisone; Leuprolide; Lumbar Vertebrae; Male; Middle Aged; Prostatic Neoplasms; Sacrum; Spinal Neoplasms; Suramin; Thoracic Vertebrae

The significance of stress-induced hypogonadism remains unclear. Since plasma testosterone and LH have renotropic activity that is other than reproductive, we hypothesize that stress-induced hypogonadism is an adaptive response to protect the kidney. To examine this hypothesis, we prepared hypogonadal male rats with different levels of LH and testosterone through orchiectomy (castration), through chronic treatment with a slowly secreted form of gonadotropin-releasing hormone agonist (GnRHA; GnRHA pretreatment), or through both treatments concomitantly (castration with GnRHA pretreatment). Castrated rats had undetectable plasma testosterone and high plasma LH. GnRHA-pretreated rats had low plasma testosterone and normal plasma LH. Castrated rats with GnRHA pretreatment had undetectable plasma testosterone and normal plasma LH. We compared their sensitivity to HgCl2 nephrotoxicity and found that, when a low dose of HgCl2 (1.5 mg/kg body weight (BW)) was injected s.c. to induce acute renal failure, endogenous creatinine clearance (Ccr) decreased from 390 +/- 30 to 94 +/- 17 ml/h per kg BW in intact (unpretreated) rats. Such a decrease in Ccr was completely prevented in castrated rats (388 +/- 30 ml/h per kg BW) and partially prevented in GnRHA-pretreated rats (216 +/- 40 ml/h per kg BW). When a high dose of HgCl2 (2.25 mg/kg BW) was injected, half of the eight intact rats died but castrated rats and GnRHA-pretreated rats survived (P < 0.05). The elevated resistance in castrated rats was reduced when plasma LH was reduced with GnRHA pretreatment, but was restored by additional pretreatment with ovine LH (40 micrograms/day), as evidenced by changes in Ccr. Elevated resistance in castrated rats was also reduced by the administration of testosterone propionate. In conclusion, hypogonadism activated the preventive and defensive mechanisms that protect the kidney through both decreased plasma testosterone and high or even normal plasma LH.

Topics: Acute Kidney Injury; Adaptation, Physiological; Animals; Creatinine; Gonadotropin-Releasing Hormone; Hypogonadism; Kidney; Leuprolide; Luteinizing Hormone; Male; Mercuric Chloride; Metabolic Clearance Rate; Orchiectomy; Rats; Rats, Wistar; Stress, Psychological; Testosterone

The use of suramin, a polysulfonated naphthylurea, in the treatment of advanced prostate cancer currently is being investigated. A 52-year-old man developed acute renal dysfunction after receiving nine doses of suramin. His suramin therapy was discontinued, but his serum creatinine level continued to rise to 10.8 mg/dl during the next 6 days. The patient was not rechallenged with suramin, and his renal function returned to baseline within the next 3 weeks. Future investigators of this drug should be aware of the possibility of such a reaction with parenteral administration.

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Combined Modality Therapy; Creatinine; Flutamide; Humans; Hydrocortisone; Kidney; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Suramin