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Chronic kidney disease (CKD) has an increased risk of contracting tuberculosis (TB), with an incidence rate of 3,718 cases per 100,000 CKD patients. Standard four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol) treatment are associated with side effects and poor adherence. Current guidelines provide comprehensive recommendations for managing TB in individuals with CKD. Pharmacokinetic studies of first-line anti-tubercular drugs in CKD are sparse, with most primarily focusing on patients on hemodialysis. Therefore, the aim of the study was to measure the drug concentrations in CKD and compare it with normal kidney function.
After permission from institutional ethics committee, we conducted a preliminary prospective observational study to assess the concentration of first-line anti-tubercular drugs in individuals with CKD and to compare it with individuals with normal kidney function. CKD was diagnosed and staged according to standard kidney disease improving global outcomes (KDIGO) guidelines. Demographic details were recorded in a case record form and plasma samples were collected both before and after drug administration to measure the trough and 2-hour post-dose drug levels using Liquid Chromatography-Mass Spectrometry (LC-MS). Data analysis was done using SPSS version 29.
Of 18 patients, eight were CKD. The mean age was 57.2±9.5 with six were male. Three patients had diabetes and five had hypertension. There were five cases of pulmonary TB and three cases of extrapulmonary tuberculosis. Trough levels of isoniazid, rifampicin, and ethambutol were higher in CKD than in normal kidney function, while post 2-hour concentrations were lower in CKD than in normal renal function. Only pyrazinamide concentration was observed to be lower in CKD at both the 0 and 2-hour time points when compared to normal renal function. (Table-1)
Table-1: - Comparison of drug concentrations between chronic kidney disease and normal kidney function
Drugs
Median (IQR) (ng/ml)
CKD (n-8)
Normal kidney function (n-10)
P value
Isoniazid 0-Hour
471.0 (253.6,725.3)
106.7 (46.6,141.1)
0.029
Isoniazid 2-Hour
1870.4 (509.1,3273.4)
3323.7 (724.7,5197.2)
0.183
Rifampicin 0-Hour
65.3 (20.0,208.6)
22.9 (17.9 (104.0)
0.398
Rifampicin 2-Hour
3334.0 (127.3,5284.7)
9824.3 (145.4,16455.4)
0.076
Pyrazinamide 0-Hour
1917.6 (530.3,8095.7)
3850.3 (1808.3,5136.3)
0.103
Pyrazinamide 2-Hour
3142.7 (119.7,29542.1)
36369.8 (15324.7,49667.3)
0.017
Ethambutol 0-Hour
856.5 (332.4,1297.9)
216.9 (154.4,474.6)
0.041
Ethambutol 2-Hour
852.2 (701.2,1452.1)
1397.6 (594.6,2900.5)
0.477
Our study highlights significant variations in first-line ATT drug concentrations between chronic kidney disease (CKD) and normal kidney function. Higher trough levels of isoniazid, rifampicin, and ethambutol in CKD, alongside lower post-2-hour concentrations and consistently lower pyrazinamide levels, emphasize the need for personalized dosing in CKD patients. This underscores the importance of further research to validate and refine dosing strategies for optimal tuberculosis management in this population.