title: Renal function in cancer patients treated with hyperthermic isolated limb perfusion with recombinant tumor necrosis factor-alpha and melphalan.
abstract: Hyperthermic isolated limb perfusion (HILP) with recombinant tumor necrosis factor-alpha (r-TNF alpha) and melphalan has been shown to result in a sepsis-like syndrome due to leakage of r-TNF alpha from the perfusion system to the systemic circulation. We have studied renal function parameters in 11 cancer patients, who underwent 12 perfusions. Three patients, perfused with melphalan only, served as controls. All patients treated with r-TNF alpha developed a sepsis syndrome and needed volume replacement and inotropes to remain normotensive; controls had an uneventful postoperative course. Creatinine clearance decreased transiently on the day of perfusion in both groups (mean preperfusion clearance 118 ml/min, mean post-perfusion clearance 68 ml/min, p < 0.02, n = 15). Follow-up measurements of renal plasma flow and glomerular filtration rate in 9 r-TNF alpha-treated patients did not suggest permanent damage. One patient became hypotensive and developed transient multiple organ dysfunction with renal failure needing hemofiltration. In r-TNF alpha-treated patients, but not in controls, a transient increase in clearance of beta2-microglobulin (0.05 vs. 8 ml/min, p < 0.001) and urinary excretion of phosphate (12 vs. 48 mmol/l, p < 0.05) was seen, compatible with proximal tubular dysfunction. These data suggest that HILP with melphalan decreases glomerular function, whether or not r-TNF alpha is added to the perfusion circuit. Extension of the treatment regimen with r-TNF alpha may result in additional proximal tubular dysfunction. If hypotension can be avoided, this deterioration in renal function seems to be transient, with full recovery within weeks.
authors.affiliation: Division of Intensive Care, University Hospital Groningen, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Zwaveling
authors.forename: H J
authors.initials: HJ
authors.lastname: Hoekstra
authors.forename: J K
authors.initials: JK
authors.lastname: Maring
authors.forename: R J
authors.initials: RJ
authors.lastname: v Ginkel
authors.forename: H
authors.initials: H
authors.lastname: Schraffordt Koops
authors.forename: A J
authors.initials: AJ
authors.lastname: Smit
authors.forename: A R
authors.initials: AR
authors.lastname: Girbes
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure; D010478:Chemotherapy, Cancer, Regional Perfusion; D003404:Creatinine / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006801:Humans; D006979:Hyperthermia, Induced; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology*; D008558:Melphalan / Q000008:administration & dosage / Q000627:therapeutic use*; D009369:Neoplasms / Q000503:physiopathology* / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012039:Regional Blood Flow; D012079:Renal Circulation; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin; D003404:Creatinine; D008558:Melphalan