title: Low-density lipoprotein adsorption therapy can restore drug sensitivity for immunosuppressants via inhibitory effects upon MDR-1 gene expression.
abstract: In two patients with steroid-resistant nephrotic syndrome (SRNS), we investigated the relationship between clinical findings during immunosuppressive therapy and multiple drug resistant gene-1 (MDR-1) expression. MDR-1 was detected by real-time polymerase chain reaction (PCR). In a boy who initially developed SRNS at 3years, we observed MDR-1 expression over 3years. Maximal and minimal MDR-1 expression were 90,000 and 7800 copies/µg RNA, respectively. In a 4-year-old boy who initially developed SRNS at 3years, we determined MDR-1 expression over 2years. Maximal and minimal MDR-1 expression were 42,000 and 6900, respectively. MDR-1 evaluation requires determination of MDR-1 expression at several time points in a clinical course. Establishment of a normal expression may be needed for each individual patient. Increasing MDR-1 during remission was followed soon by recurrences, an observation that may be a guide for therapeutic choice. LDL influences a humoral factor involved in MDR-1 expression. Both patients responded to LDL adsorption therapy because of elevated LDL levels. While cyclosporine A therapy gradually decreased MDR-1 expression, LDL adsorption therapy decreased expression sharply. Based on the results of the present study, LDL adsorption therapy could contribute to the amelioration of drug sensitivity for immunosuppressants including corticosteroids via inhibitory effects on MDR-1 expression.
authors.affiliation: Department of Pediatrics, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueda
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Yanagida
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujita
authors.forename: Tomoki
authors.initials: T
authors.lastname: Miyazawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Sakata
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Okada
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Takemura
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000327:Adsorption; D001781:Blood Component Removal / Q000379:methods*; D002675:Child, Preschool; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D004351:Drug Resistance; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D008077:Lipoproteins, LDL; D016572:Cyclosporine