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Saudi Journal of Kidney Diseases and Transplantation
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LETTER TO THE EDITOR Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 4  |  Page : 666-667
Measurement of plasma levels of isoniazid for dose adjustment in the hemodialysis patients

1 Service of Nephrology, Haemodialysis and Kidney Transplantation, Military Hospital Mohammed V Rabat, Morocco
2 Laboratory of Toxicology, Centre Anti Poison, National Institute of Hygiene, Rabat, Morocco

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Date of Web Publication8-Jul-2009

How to cite this article:
El Kabbaj D, Aatif M, Moussa LA, Khassouani CE, Oualim Z. Measurement of plasma levels of isoniazid for dose adjustment in the hemodialysis patients. Saudi J Kidney Dis Transpl 2009;20:666-7

How to cite this URL:
El Kabbaj D, Aatif M, Moussa LA, Khassouani CE, Oualim Z. Measurement of plasma levels of isoniazid for dose adjustment in the hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2022 Jun 28];20:666-7. Available from: https://www.sjkdt.org/text.asp?2009/20/4/666/53298
To the Editor

Tuberculosis remains a major public health pro­blem in the developing world, and the immune compromised patients receiving dialysis the­rapy are known to be at increased risk of tuber­culosis and occur primarily in extra-pulmonary sites. Isoniazid (INH), the hydrazide of isonico­tinic acid, is the primary drug prescribed for the treatment of active tuberculosis and the prophy­laxis of tuberculosis exposure. Mild, reversible hepatotoxicity is the most common adverse drug reaction associated with therapeutic do­sages. Acute neurologic toxicity associated with overdose, however, may be fatal if not recog­nised and treated promptly. [1],[2],[3],[4],[5],[6] We therefore measured INH levels in hemodialysis who were prescribed antituberculous therapy and predict the starting dose to avoid side effects.

In 40 hemodialysis patients 69 dosages of Iso­niazid were administered. INH concentration was measured at 3 and 6 hours after the single dose (5 mg/kg) intake and before a hemodia­lysis session by high-performance liquid chro­matography (HPLC) method. The adjustment of Isoniazid dosage was done according to the serum concentration of Isoniazid between 1 to 2 µg/mL that was converted to dosage in mg/kg by the Vivien method. [10]

The average concentration of Isoniazid in this population was 3.13 (0-13.5) µg/mL and the average adjusted dose was 2.75 (0.63-17.68) mg/kg.

The hepatic metabolism of Isoniazid is by N­acetyltransferase, this acetylation is monitored by a genetic polymorphism, the rapid acety­lators have failure in achieving adequate drug levels and therefore treatment failure, while slow acetylators have more side effects. The mean plasma half-life values of isoniazid do­cumented in previous studies was 1.54 ± 0.31 in normal subjects and 3.68 ± 0.59 hours in pa­tients with chronic renal failure. [7] The plasma half-life values of isoniazid in patients with chronic renal failure varied widely from 1.30 to 10.13 hours, but the values were significantly longer than those of normal subjects. Because isoniazid clearance is governed mainly by hepa­tic metabolism, such a significant prolongation of plasma half-life of isoniazid was unexpected. The decreased isoniazid clearance in chronic renal failure is caused in minor part by the decreased renal excretion of isoniazid and in major part by the depressed hepatic N-acety­lation of isoniazid. [7] The hemodialysis proce­dure decreases INH levels by 73% in less than 5 hours [8] and the isoniazid clearance is 124 mL/ min. [9] No author advised a therapeutic adap­tation of the Isoniazid in the hemodialysis pa­tients, even the recommendations of the Ame­rican Society of Pulmonology, [11] while our study demonstrates that the average dose advised (2.7 mg/kg) in our population is lower than the dose recommended by the various authors (5 mg/kg). In conclusion, our study demonstrates that INH dose should be 2.5 mg/kg in the hemodialysis patients and could be confirmed by the measurement of plasma concentration to avoid its side effects which may be severe and frequent.

   References Top

1.Wang HY. Encephalopathy caused by isoniazid in a patient with end stage renal disease with extra pulmonary tuberculosis. Ren Fail 2003;25 (1):135-8.  Back to cited text no. 1    
2.Altiparmak MR, Pamuk ON, Pamuk GE, et al, Is isoniazid ototoxic in patients undergoing hemodialysis? Nephron 2002; 92(2):478-80.  Back to cited text no. 2    
3.Kocabay G. Optic neuritis and bitemporal hemianopsia associated with isoniazid treatment in end stage renal failure. Int J Tuberc Lung Dis 2006;10(12):1418-9.  Back to cited text no. 3    
4.Temmerman W, Dhondt A, Vandewoude K. Acute isoniazid intoxication: seizures, acidosis and coma. Acta Clin Belg 1999;54(4):211-6.  Back to cited text no. 4    
5.Chan KL Recurrent acute pancreatitis induced by isoniazid. Tuber Lung Dis 1994;75(5):383-5.  Back to cited text no. 5    
6.Siskind MS. Isoniazid-induced neurotoxicity in chronic dialysis patients: report of three cases and a review of the literature. Nephron 1993;64 (2):303-6.  Back to cited text no. 6    
7.Kim YG. Decreased acetylation of isoniazid in chronic renal failure. Clin Pharmacol Ther 1993;54(6):612-20.  Back to cited text no. 7    
8.Gold CH. Isoniazid pharmacokinetics in pa­tients in chronic renal failure. Clin Nephrol 1976;6(2):365-9.  Back to cited text no. 8    
9.Malone RS. The effect of hemodialysis on iso­niazid, rifampin, pyrazinamide, and ethambutol. Am J Respir Crit care Med 1999;159(5 Pt 1): 1580-4.  Back to cited text no. 9    
10.Vivien J.N, Thibier R, Lepeuple A. La pharma­cocinetique de l'isoniazide dans la race blanche. Rev Fr Mal Resp 1973;1:753-72.  Back to cited text no. 10    
11.ATS/CDC/IDSA. Am J Respir Crit Care Med 2003; 167:603.  Back to cited text no. 11    

Correspondence Address:
Driss El Kabbaj
Service of Nephrology, Haemodialysis and Kidney Transplantation, Military Hospital Mohammed V Rabat
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Source of Support: None, Conflict of Interest: None

PMID: 19587514

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