Anti Tuberculosis Drugs: Renal Adjustment

• The recommended initial TB treatment regimen for patients with renal failure or severe renal insufficiency is 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by 4 months of isoniazid and rifampicin
• There is significant renal excretion of ethambutol and metabolites of pyrazinamide, and doses should therefore be adjusted
• Pyrazinamide should be administered after hemodialysis to avoid premature drug removal
• All four antiTB drugs may be administered after hemodialysis to facilitate directly observed therapy.
• Because of an increased risk of nephrotoxicity and ototoxicity, streptomycin should be avoided in patients with renal failure.

First Line:
Pyrazinamide

• adjustment for CrCl less than 30 mL/min or patients receiving hemodialysis

Ethambutol

• CrCl less than 10 mL/min: The usual dose may be administered every 48 hours.
• CrCl 10 to 50 mL/min: The usual dose may be administered every 24 to 36 hour  

Second Line: 
Streptomycin

• If streptomycin need to be used, the dosage is 15 mg/kg, 2 or 3 times per week, to a maximum of 1 gram per dose, and serum levels of the drug should be monitored.

Ofloxacin

• 50 ml/min : 400mg BD or 15-20mg/kg (maximum 1000mg)
• 20-50 ml/min :  400mg OD
• <20 ml/min : 200mg OD

Drug Induced AKI

• Drug induced renal injury is lower (4.8%)

Drug	Renal Adverse Effect
Isoniazide	·      No established renal SE
Rifampicin	·      elevations in BUN and serum uric acid. ·      Hemoglobinuria, hematuria, interstitial nephritis, acute tubular necrosis, renal insufficiency, and acute renal failure have been reported. ·      generally associated with an immune-mediated reaction which occurs after interruption in rifampin therapy. ·      have been rare case reports of reversible acute renal failure due to glomerulonephritis and renal epithelial cell injury ·      Standard doses may produce orange-colored urine
Ethambutol	·      Renal side effects have rarely included reversible renal insufficiency ·      abnormalities include increases in serum creatinine and idiosyncratic interstitial nephritis
Pyrizinamide	·      Renal side effects have included dysuria and interstitial nephritis

Monitoring:

• Any increase of serum creatinine above normal limits should be considered acute renal insufficiency.
• A doubling of serum creatinine above baseline, even if within normal limits, should be considered worrisome for acute renal insufficiency and monitored carefully.
• Prerenal etiologies include hypovolemia due to dehydration from vomiting or diarrhea as a side effect of anti-TB therapy.
• Hypotensive shock in critically ill patients can also cause prerenal physiology
• Discontinue the suspected drug (usually the injectable). If the acute renal failure is severe, then stop all drugs
• If the acute renal insufficiency is severe or resolving slowly, the dose of other renally excreted drugs should be adjusted
• Consider other contributing etiologies (prerenal, intrinsic renal, and postrenal).

References:

1. www.drugs.com
2. www.lexicomp.com
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092156/
4. CPG: Management of Tuberculosis, 3^rd Edition
5. https://drtbnetwork.org/912-renal-nephrotoxicity-acute-renal-failure
6. Guidelines for the prevention and management of Mycobacterium tuberculosis infection and disease in adult patients with chronic kidney disease. Thorax 2010;65:559e570.
7. Treatment of tuberculosis in chronic renal failure, maintenance dialysis and renal transplant. Indian Journal of Nephrology 2003,13,69-71.