Impact of renal function-based anti-tuberculosis drug dosage adjustment on efficacy and safety outcomes in pulmonary tuberculosis complicated with chronic kidney disease

Abstract

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. Electronic supplementary material The online version of this article (10.1186/s12879-019-4010-7) contains supplementary material, which is available to authorized users.

Clinical Characteristics and Outcomes in Chronic Kidney Disease Patients with Tuberculosis in China: A Retrospective Cohort Study

“…A retrospective analysis in Japan found that the adverse events increased with the severity of CKD (20.4–44.4%) in 241 CKD patients with TB (including 11 dialysis patients). 21 Some previous studies have reported that the rate of adverse effects of anti-TB drugs ranges from 24.9% to 46.34% in dialysis patients. 9 , 21 Ezer et al reported that the incidence of optic neuropathy associated with ethambutol was 2.3%; 22 however, in our cohort, 15.3% of patients on dialysis had optic neuropathy, which was higher than pre-HD (6.4%) and non-CKD (6.1%) patients.…”

Preventing tuberculosis in paediatric kidney transplant recipients: is there a role for BCG immunisation pre-transplantation in low tuberculosis incidence countries?

“…Isoniazid is potentially hepatotoxic and may cause pyridoxine-dependent peripheral neuropathy if the child is nutritionally compromised; rifampicin is a potent cytochrome P450 enzyme inducer leading to numerous potential drugdrug interactions. Although for both drugs, many clinicians do not recommend dose adjustments in CKD, they may need adjustments during peritoneal or haemodialysis [54].…”

“…There are a number of potential treatment regimens for LTBI, including isoniazid, rifampicin and rifapentine as monotherapy or combination treatment [55]. As noted above, drug regimen adjustments may be necessary during dialysis [54]. To avoid potential interactions of rifampicin with immunosuppressive medication post kidney transplant, isoniazid monotherapy appears the better option in that setting.…”

Pyrazinamide-induced Polyarthralgia and Myalgia in a Case of Stable Chronic Kidney Disease

“…The literature reports, creatinine > 2.0 mg/ dL in response to drug administration must be evaluated for drug-induced nephropathy. 10 As per Naranjo's scale of ADR assesment, 11 this case scored 8 out of 13 points, where a score of 5 to 8 indicates the "probable" association between pyrazinamide administration and the occurrence of polyarthralgia and myalgia.…”