Baseline Urine Protein Testing in Patients on Lenvatinib and Pembrolizumab
Order a spot urine protein-to-creatinine ratio (UPCR) as the baseline test for monitoring proteinuria in patients receiving lenvatinib and pembrolizumab. 1, 2
Recommended Testing Approach
Primary Test: Spot UPCR
- UPCR is the preferred initial screening test because it is simpler, less burdensome for patients, and highly correlates with 24-hour urine protein collection 1, 2
- A spot urine sample can be obtained at any time during a clinic visit, eliminating the need for overnight collection 2
- The correlation between UPCR and 24-hour urine protein is statistically significant (R² = 0.75, P < 2 × 10⁻¹⁶) 2
When to Escalate to 24-Hour Urine Collection
- If UPCR ≥2000 mg/g (or ≥2 g/24 hours equivalent), interrupt lenvatinib immediately and confirm with 24-hour urine protein collection before making further treatment decisions 1
- The UPCR cut-off value of 2.4 has 96.9% sensitivity and 82.5% specificity for distinguishing between grade 2 and grade 3 proteinuria 2
- Using UPCR as the initial screening tool can reduce the need for 24-hour urine collection in approximately 74% of patients 2
Critical Management Thresholds
Baseline and Ongoing Monitoring
- Establish baseline UPCR before initiating therapy to enable accurate comparison during treatment 1, 3
- Monitor UPCR regularly throughout treatment, as proteinuria is a major on-target adverse event of lenvatinib occurring in up to 71% of patients 3
- Target maintaining UPCR <3500 mg/g (nephrotic range threshold) to allow safe continuation of therapy 1, 3
Action Points Based on UPCR Values
- UPCR <2000 mg/g: Continue lenvatinib at current dose with routine monitoring 1
- UPCR ≥2000 mg/g but <3500 mg/g: Interrupt lenvatinib, confirm with 24-hour collection, and consider dose reduction upon resumption 1, 2
- UPCR ≥3500 mg/g (nephrotic range): Permanently discontinue lenvatinib and obtain immediate nephrology consultation for possible renal biopsy 1
Important Clinical Context
Risk Factors for Severe Proteinuria
Patients at higher risk for developing grade 3 proteinuria include those with:
- Age >65 years (OR 8.24,95% CI 1.74-39.00) 3
- History of diabetes mellitus (OR 7.79,95% CI 1.31-46.20) 3
- Pre-existing hypertension (OR 4.07,95% CI 1.22-13.60) 3
Renal Function Considerations
- In patients with stage IV RCC and impaired renal function, UPCR monitoring is particularly important as it allows for early detection without significantly worsening renal function when proteinuria is managed appropriately 3
- No significant deterioration in eGFR was observed in patients with grade 3 proteinuria compared to those with grades 0-2 proteinuria when UPCR was monitored and maintained <3.5 g/gCre 3
- Lenvatinib can be carefully continued with UPCR targeting <3500 mg/g, as this approach preserves renal function while maintaining treatment efficacy 3
Common Pitfalls to Avoid
- Do not rely solely on dipstick urinalysis, as it is qualitative and cannot accurately quantify proteinuria for dose modification decisions 1, 2
- Do not delay testing until symptoms appear, as proteinuria is often asymptomatic until severe 1, 3
- Do not automatically order 24-hour urine collection for all patients, as UPCR is sufficient for initial screening and routine monitoring in the majority of cases 2
- Do not continue lenvatinib without dose modification when UPCR ≥2000 mg/g, as this increases the risk of nephrotic-range proteinuria and potential permanent discontinuation 1