What is the treatment for Tuberculosis (TB) glomerulonephritis?

Treatment of Tuberculosis Glomerulonephritis

The treatment for tuberculosis glomerulonephritis should include standard anti-tuberculosis therapy with a four-drug regimen of isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months, followed by isoniazid and rifampin for 4 months, along with corticosteroids to manage the glomerular inflammation. 1, 2

Anti-Tuberculosis Therapy

First-Line Regimen

• A 6-month regimen consisting of isoniazid, rifampin, and pyrazinamide given for 2 months followed by isoniazid and rifampin for 4 months is the preferred treatment for drug-susceptible tuberculosis 2
• Ethambutol should be included in the initial regimen until drug susceptibility results are available 2
• For adults, standard dosing includes:
  • Isoniazid: 5 mg/kg up to 300 mg daily in a single dose 3
  • Rifampin: 10 mg/kg (usual adult dose 600 mg) daily 4
  • Pyrazinamide: 15-30 mg/kg daily 1
  • Ethambutol: 15-25 mg/kg daily 1

Drug Resistance Considerations

• Drug susceptibility testing should be performed on initial isolates from all patients with newly diagnosed tuberculosis 3
• If multidrug-resistant TB (MDR-TB) is suspected or confirmed, treatment must be individualized based on susceptibility studies 1
• For MDR-TB, a shorter all-oral bedaquiline-containing regimen of 9-12 months duration is recommended in eligible patients 1

Management of Glomerulonephritis Component

Corticosteroid Therapy

• Corticosteroids should be added to the treatment regimen for tuberculosis glomerulonephritis to manage the immune-mediated glomerular inflammation 1, 5
• For severe crescentic glomerulonephritis associated with TB, high-dose corticosteroids (methylprednisolone pulse therapy followed by oral steroids) have shown efficacy 6, 5

Supportive Care

• Manage hypertension with diuretics and antihypertensive medications, preferably ACE inhibitors or ARBs 7, 8
• Restrict dietary sodium to <2.0 g/day to help manage fluid overload and hypertension 7, 8
• Monitor for and treat fluid overload with diuretics 7, 8
• Consider renal replacement therapy (dialysis) for severe cases with acute kidney injury 9, 8

Monitoring During Treatment

Tuberculosis Response

• Perform sputum culture in addition to sputum smear microscopy monthly to monitor treatment response in pulmonary TB cases 1
• Monitor for adverse effects of anti-TB medications, particularly hepatotoxicity and nephrotoxicity 3, 4

Renal Function Monitoring

• Regularly assess kidney function through serum creatinine and estimated GFR 9, 7
• Monitor for a ≥40% decline in eGFR from baseline, which serves as a surrogate outcome measure for kidney failure 9, 7
• Assess proteinuria regularly - reduction in proteinuria is a marker of treatment response 7
• Monitor urine output and maintain adequate hydration 9

Special Considerations

HIV Co-infection

• Antiretroviral therapy is recommended for all patients with HIV and drug-resistant TB requiring second-line anti-TB drugs, irrespective of CD4 cell count, as early as possible (within the first 8 weeks) following initiation of anti-TB treatment 1
• In the presence of HIV infection, it is critically important to assess the clinical and bacteriologic response to TB treatment 2

Medication-Induced Glomerulonephritis

• Be aware that rifampin itself has been associated with various renal abnormalities, including rapidly progressive glomerulonephritis 10, 6, 11
• If worsening renal function occurs during treatment, consider the possibility of drug-induced nephropathy and modify the regimen accordingly 10, 6

Treatment Adherence

• Consider directly observed therapy (DOT) for all patients to ensure adherence 1, 2
• Health education and counseling on the disease and treatment adherence should be provided to patients 1
• A package of treatment adherence interventions may be offered to patients, including material support and psychological support 1

Duration of Therapy

• Standard tuberculosis treatment duration is 6 months for pulmonary TB 1, 2
• For extrapulmonary TB involving the kidneys, treatment may need to be extended to 9-12 months based on clinical and laboratory response 2
• Corticosteroid therapy duration should be individualized based on clinical response, typically starting with high doses and gradually tapering over several months 5

Pitfalls and Caveats

• Rifampin can itself cause glomerulonephritis, which may complicate the clinical picture and treatment response 10, 6, 11
• Delayed recognition and treatment of TB glomerulonephritis can lead to irreversible kidney damage and end-stage renal disease 5
• Monitor closely for drug interactions, especially with rifampin which is a potent inducer of drug-metabolizing enzymes 4
• Adjust medication doses appropriately for patients with renal insufficiency 1