From the Guidelines
Nintedanib should be used with caution in patients with chronic kidney disease (CKD), with close monitoring of renal function and adverse effects, as recommended by the KDIGO 2024 clinical practice guideline 1. When prescribing nintedanib to patients with CKD, it is essential to consider the benefits versus potential harms, as people with CKD may be more susceptible to the nephrotoxic effects of medications. Some key points to consider when using nintedanib in CKD patients include:
- Monitoring eGFR, electrolytes, and therapeutic medication levels, when indicated, in people with CKD receiving medications with narrow therapeutic windows, potential adverse effects, or nephrotoxicity 1.
- Reviewing and limiting the use of over-the-counter medicines and dietary or herbal remedies that may be harmful for people with CKD 1.
- Considering the potential for drug interactions, as patients with CKD often have multiple comorbidities and take various medications that may interact with nintedanib.
- Monitoring for gastrointestinal side effects, such as diarrhea, nausea, and vomiting, which are common and may lead to dehydration, potentially worsening kidney function.
- Regularly assessing liver function, as nintedanib can cause elevations in liver enzymes. It is also important to note that nintedanib is primarily metabolized by the liver with minimal renal excretion (<1%), which explains why dose adjustments are not mandatory in CKD, unlike many other medications. However, for patients with severe CKD (eGFR <30 mL/min/1.73m²), consider reducing the dose to 100 mg twice daily, with potential further reduction to 50 mg twice daily if not tolerated, as a precautionary measure to minimize potential adverse effects. Additionally, managing comorbidities, such as hypertension, is crucial in patients with CKD, and guidelines recommend a lower target of <130/80 mm Hg for all patients with CKD, as supported by the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1. The use of renin-angiotensin system inhibitors, such as ACE inhibitors or ARBs, is also recommended for patients with diabetes, hypertension, and albuminuria, as they slow the progression of kidney disease independent of their effects on blood pressure, as stated in the 2020 KDIGO clinical practice guideline 1.
From the Research
Nintedanib in CKD Patients
- Nintedanib is a tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF) 2.
- The use of nintedanib in patients with Chronic Kidney Disease (CKD) requires careful consideration due to potential nephrotoxicity, including renal thrombotic microangiopathy (TMA) 2.
- A study found that nintedanib-induced renal TMA is reversible and possibly dose-dependent 2.
Mechanism of Action
- Nintedanib inhibits multiple tyrosine kinases, including platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR), vascular endothelial growth factor receptor (VEGFR), and Src family kinase 3.
- This inhibition can attenuate renal fibrosis in CKD by blocking the activation of renal interstitial fibroblasts and inhibiting the expression of proinflammatory cytokines 3.
Safety and Efficacy
- The long-term safety and tolerability of nintedanib in patients with IPF have been established, with a manageable safety profile and no new safety signals 4.
- Nintedanib has been shown to reduce the decline in forced vital capacity (FVC) in patients with IPF, including those with advanced disease 5.
- However, the use of nintedanib in CKD patients may require dose adjustments and close monitoring of renal function due to the potential risk of nephrotoxicity 2, 3.
Biomarkers
- Nintedanib has been shown to affect circulating biomarkers of IPF, including surfactant protein D (SP-D) and cancer antigen 125 (CA-125), which may be useful in monitoring disease progression and treatment response 6.
- The effects of nintedanib on biomarkers of renal function and fibrosis in CKD patients require further study 3, 6.