rifampin and Renal-Insufficiency--Chronic

Topics: Animals; beta Catenin; Fibrosis; Humans; Mammals; Mice; Pregnane X Receptor; Receptors, Steroid; Renal Insufficiency, Chronic; Rifampin; Signal Transduction; Tumor Suppressor Protein p53; Wnt Signaling Pathway

Coproporphyrin I (CPI) is an endogenous biomarker of organic anion transporting polypeptide 1B transporter (OATP1B). CPI plasma baseline was reported to increase with severity of chronic kidney disease (CKD). Further, ratio of CPI area under the plasma concentration-time curve (AUCR) in the presence/absence of OATP1B inhibitor rifampin was higher in patients with CKD compared with healthy participants, in contrast to pitavastatin (a clinical OATP1B probe). This study investigated mechanism(s) contributing to altered CPI baseline in patients with CKD by extending a previously developed physiologically-based pharmacokinetic (PBPK) model to this patient population. CKD-related covariates were evaluated in a stepwise manner on CPI fraction unbound in plasma (f

Topics: Biomarkers; Coproporphyrins; Drug Interactions; Humans; Liver-Specific Organic Anion Transporter 1; Organic Anion Transporters; Prospective Studies; Renal Insufficiency, Chronic; Rifampin

Topics: Acute Kidney Injury; Administration, Intravesical; Aged; Antitubercular Agents; BCG Vaccine; Ethambutol; Humans; Isoniazid; Kidney; Male; Nephritis; Renal Insufficiency, Chronic; Rifampin; Treatment Outcome; Urinary Bladder Neoplasms

Chronic kidney disease (CKD) is an increased risk for the development of active tuberculosis, but few studies have analyzed the treatment outcome of pulmonary tuberculosis among CKD patients. A retrospective cohort study was conducted at Chiba-East Hospital in Chiba, Japan. Our study estimated the treatment outcomes in smear-positive pulmonary tuberculosis in relation to CKD and its stages. Total subjects were 759 patients (12-99 years) hospitalized between 2007 and 2012. Patients suffering from multi-drug-resistant tuberculosis were excluded. Patients with CKD were 19.3% aged <65 years (n = 384), and 49.6% aged ≥ 65 years, respectively (P < 0.001). Successful treatment was 52.7% in CKD (n = 260) and 67.3% in non-CKD (n = 499) (P < 0.001). Death was 25.4% in CKD and 12.4% in non-CKD (P < 0.001). Treatment outcome was especially poor in patients with low estimated glomerular filtration rate (eGFR) of <30 ml/min/1.73 m(2), as successful treatment was 20.0%, and death was 50.0%, significantly lower than in other CKD and non-CKD patients. After multivariate logistic regression analysis, eGFR<30 ml/min/1.73 m(2) was an independent factor affecting successful treatment and death, and its adjusted odds ratios (aOR) were 0.20 (95% confidence interval (CI) 0.07-0.50) and 2.99 (95%CI 1.20-7.51), respectively. Other factors affecting successful treatment were serum albumin <3.0 mg/dl, steroid therapy for underlying disease and cardiovascular disease, with aOR (95%CI) of 0.28 (0.20-0.39), 0.32 (0.16-0.63) and 0.49 (0.28-0.86), respectively. Several factors were associated with poor treatment outcome of smear-positive pulmonary tuberculosis. Advanced stage of CKD with eGFR of <30 ml/min/1.73 m(2) was a risk factor for poor treatment outcome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitubercular Agents; Cardiovascular Diseases; Child; Drug Therapy, Combination; Ethambutol; Female; Glomerular Filtration Rate; Humans; Isoniazid; Japan; Male; Middle Aged; Pyrazinamide; Renal Insufficiency, Chronic; Retrospective Studies; Rifampin; Risk Factors; Serum Albumin; Sputum; Steroids; Streptomycin; Survival Rate; Treatment Outcome; Tuberculosis, Pulmonary; Young Adult