CAR T Cell Therapy in Renal Diseases
CAR T cell therapy is not currently recommended as a standard treatment for renal diseases, with the exception of CD70-targeted allogeneic CAR T cells showing promising early results specifically for clear cell renal cell carcinoma (ccRCC). 1
Current Evidence for CAR T in Renal Diseases
Renal Cell Carcinoma
- CD70-targeted allogeneic CAR T cell therapy (CTX130) has shown promising results in a phase I clinical trial for advanced clear cell renal cell carcinoma:
- Disease control achieved in 81.3% of patients
- One patient maintained complete response for 3+ years
- No dose-limiting toxicities reported 1
Lupus Nephritis
- CAR T cell therapy is mentioned in the 2024 KDIGO guidelines for lupus nephritis only as an investigational therapy for refractory cases
- Currently considered among "other therapies under investigation" that "may offer potential options for refractory lupus nephritis" 2
- Not included in standard treatment algorithms for lupus nephritis
Other Renal Diseases
- No substantial evidence supporting CAR T cell therapy for other primary renal diseases
- Not mentioned in current treatment guidelines for other renal conditions
Renal Considerations with CAR T Cell Therapy
Renal Toxicity of CAR T Cell Therapy
- Acute kidney injury (AKI) occurs in approximately 30% of patients receiving CAR T cell therapy 3
- Most cases are mild (grade 1) and reversible within 30 days 3
- Severe AKI requiring renal replacement therapy is rare 3
Risk Factors for AKI with CAR T Cell Therapy
- Grade 3-4 cytokine release syndrome (CRS) 3
- Previous stem cell transplantation 3
- Need for intensive care unit level care 3
- Elevated baseline creatinine 4
- ICANS grade 2+ (Immune effector Cell-Associated Neurotoxicity Syndrome) 4
CAR T Cell Therapy in Patients with Pre-existing Renal Disease
- Limited data suggests CAR T cell therapy may be safely administered to patients with pre-existing chronic kidney disease (CKD) 4
- No significant difference in progression-free survival or overall survival between patients with and without CKD receiving CAR T cell therapy for lymphoma 4
- Some studies report successful treatment of dialysis-dependent patients with refractory lymphoma 5
Management Considerations
Monitoring Renal Function During CAR T Cell Therapy
- Daily monitoring of complete metabolic panel during treatment 2
- Monitor for signs of tumor lysis syndrome 2
- Consider continuous renal replacement therapy (CRRT) with extracorporeal cytokine adsorption for severe CRS cases 2
Management of CAR T-Related Renal Complications
- Early recognition and management of CRS is critical to prevent severe AKI 3
- For severe CRS:
- Anti-IL-6 therapy (tocilizumab)
- Corticosteroids (dexamethasone 10 mg IV every 6 hours for grade 3-4 CRS)
- Consider CRRT with extracorporeal cytokine adsorption for refractory cases 2
Future Directions
- Allogeneic CAR T cells may offer "off-the-shelf" options with reduced manufacturing time and potentially lower costs 2
- Ongoing research into CAR T cell therapy for solid tumors, including renal cancers 1
- Next-generation constructs (e.g., CTX131) with improved expansion and efficacy are in development 1
Conclusion
While CAR T cell therapy shows promise for advanced clear cell renal cell carcinoma, it remains investigational for other renal diseases including lupus nephritis. The therapy appears to have an acceptable safety profile even in patients with pre-existing renal impairment, with most cases of AKI being mild and reversible. Further research is needed to establish the role of CAR T cell therapy in the broader spectrum of renal diseases.