PMID- 31046706 OWN - NLM STAT- MEDLINE DCOM- 20190618 LR - 20200225 IS - 1471-2334 (Electronic) IS - 1471-2334 (Linking) VI - 19 IP - 1 DP - 2019 May 2 TI - Impact of renal function-based anti-tuberculosis drug dosage adjustment on efficacy and safety outcomes in pulmonary tuberculosis complicated with chronic kidney disease. PG - 374 LID - 10.1186/s12879-019-4010-7 [doi] LID - 374 AB - BACKGROUND: Dosages of anti-tuberculosis (TB) drugs are recommended to be adjusted according to renal function for patients complicated with chronic kidney disease (CKD). However, the efficacy and safety outcomes of such renal function-based dosage adjustments are not fully elucidated. METHODS: We retrospectively reviewed cases of pulmonary TB susceptible to first-line drugs that were treated at Jikei University Daisan Hospital between 2005 and 2014 with standard regimens based on dosage adjustments according to renal function recommended by international guidelines. Patients were divided into four groups, those with no, mild, moderate or severe CKD. In-hospital TB-related mortality, the rate of sputum culture conversion at 2 months, the frequency of adverse events (AEs), for which at least the temporal discontinuation of the suspect drug was required for patient improvement, and the rate of regimen change due to AEs were assessed. RESULTS: In the 241 enrolled patients (mean age, 64.1 years; 143 men), fourteen patients (5.8%) died due to TB during their hospitalization. The rate of sputum culture conversion at 2 months was 78.0%. The frequency of in-hospital TB-related death and the conversion rate in the groups did not vary significantly according to CKD severity including those in the non-CKD group (P = 0.310 and P = 0.864). Meanwhile, a total of 70 AEs were observed in 60 patients (24.9%) and the difference between the groups in the overall frequency of AEs was almost significant (P = 0.051). Moreover, for the 154 patients with CKD, severe CKD stage was a significant risk factor for regimen change (OR = 5.92, 95% CI = 1.08-32.5, P = 0.041), as were drug-induced hepatitis and cutaneous reaction (OR = 35.6, 95% CI = 8.70-145, P < 0.001; OR = 17.4, 95% CI = 3.16-95.5, P = 0.001; respectively). CONCLUSIONS: Adjusting the dosage of TB treatment for CKD patients according to the guidelines was efficient in terms of similar therapeutic outcome to that of the non-CKD group. However, AEs warrant attention to avoid regimen change in patients with severe CKD, even if the renal function-based dosage adjustment is performed. FAU - Saito, Nayuta AU - Saito N AD - Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan. AD - Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Tokyo, 105-8461, Japan. FAU - Yoshii, Yutaka AU - Yoshii Y AUID- ORCID: 0000-0001-7908-7986 AD - Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan. y.yoshii@jikei.ac.jp. AD - Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Tokyo, 105-8461, Japan. y.yoshii@jikei.ac.jp. FAU - Kaneko, Yugo AU - Kaneko Y AD - Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan. FAU - Nakashima, Akio AU - Nakashima A AD - Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan. AD - Division of Molecular Epidemiology, The Jikei University School of Medicine, Minato-ku, Japan. FAU - Horikiri, Tsugumi AU - Horikiri T AD - Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan. FAU - Saito, Zenya AU - Saito Z AD - Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan. FAU - Watanabe, Sho AU - Watanabe S AD - Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan. FAU - Kinoshita, Akira AU - Kinoshita A AD - Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan. FAU - Saito, Keisuke AU - Saito K AD - Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan. FAU - Kuwano, Kazuyoshi AU - Kuwano K AD - Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Tokyo, 105-8461, Japan. LA - eng PT - Journal Article DEP - 20190502 PL - England TA - BMC Infect Dis JT - BMC infectious diseases JID - 100968551 RN - 0 (Antitubercular Agents) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antitubercular Agents/adverse effects/*therapeutic use MH - Chemical and Drug Induced Liver Injury/etiology MH - Female MH - Glomerular Filtration Rate MH - Humans MH - Male MH - Middle Aged MH - Odds Ratio MH - Renal Insufficiency, Chronic/complications/*diagnosis MH - Retrospective Studies MH - Risk Factors MH - Severity of Illness Index MH - Tuberculosis, Pulmonary/complications/diagnosis/*drug therapy PMC - PMC6498605 OTO - NOTNLM OT - Chronic renal insufficiency OT - Drug-related side effects OT - Glomerular filtration rate OT - Hospital mortality OT - Pulmonary tuberculosis COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was approved by the ethics committee of Jikei University School of Medicine [No. 27-031(7938)]. Informed consent was waived by the ethics committee because we retrospectively collected data without using identifying information or applying any interventions. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/05/03 06:00 MHDA- 2019/06/19 06:00 PMCR- 2019/05/02 CRDT- 2019/05/04 06:00 PHST- 2018/01/22 00:00 [received] PHST- 2019/04/22 00:00 [accepted] PHST- 2019/05/04 06:00 [entrez] PHST- 2019/05/03 06:00 [pubmed] PHST- 2019/06/19 06:00 [medline] PHST- 2019/05/02 00:00 [pmc-release] AID - 10.1186/s12879-019-4010-7 [pii] AID - 4010 [pii] AID - 10.1186/s12879-019-4010-7 [doi] PST - epublish SO - BMC Infect Dis. 2019 May 2;19(1):374. doi: 10.1186/s12879-019-4010-7.