Classification of Response in Lupus Nephritis
The KDIGO 2024 guidelines provide the most current and authoritative definitions for treatment response in lupus nephritis, categorizing outcomes into complete response, partial response, and no kidney response based on proteinuria reduction and kidney function stabilization. 1
Complete Response Criteria
Complete response is defined as proteinuria <0.5 g/g (50 mg/mmol) measured as the protein-creatinine ratio (PCR) from a 24-hour urine collection, with stabilization or improvement in kidney function (±10%–15% of baseline), typically achieved within 6–12 months of starting therapy but potentially taking more than 12 months. 1
Additional criteria for complete response include:
- PCR ≤0.7 g/g (70 mg/mmol) 1
- No use of rescue therapy for treatment failure 1
- For children <18 years old, complete response is defined as <2 mg/kg per day or <300 mg/m² per day based on a 24-hour urine specimen 1
Partial Response Criteria
Partial response requires at least 50% reduction in proteinuria to <3 g/g (300 mg/mmol) measured as PCR from a 24-hour urine collection, with stabilization or improvement in kidney function (±10%–15% of baseline), within 6–12 months of starting therapy. 1
No Kidney Response
No kidney response is defined as failure to achieve either partial or complete response within 6–12 months of starting therapy. 1
Alternative Response Definitions from Clinical Trials
The EULAR/ERA-EDTA 2012 guidelines provide slightly different thresholds:
- Complete renal response: UPCR <50 mg/mmol with normal or near-normal GFR (within 10% of normal if previously abnormal) 1
- Partial renal response: ≥50% reduction in proteinuria to subnephrotic levels with normal or near-normal renal function, preferably by 6 months but no later than 12 months 1
FDA-Approved Response Criteria from Belimumab Trials
The FDA label for belimumab defines two additional response categories used in the pivotal BLISS-LN trial:
Primary Efficacy Renal Response (PERR): uPCR ≤0.7 g/g and eGFR ≥60 mL/min/1.73 m² or no decrease in eGFR of >20% from pre-flare value, confirmed at Week 100 and repeated at Week 104 2
Complete Renal Response (CRR): uPCR <0.5 g/g and eGFR ≥90 mL/min/1.73 m² or no decrease in eGFR of >10% from pre-flare value, confirmed at Week 100 and repeated at Week 104 2
Critical Timing Considerations
The timeframes for response assessment (6–12 months) refer to when outcomes are assessed in clinical trials, but improvement of proteinuria and eGFR is continuous over time, and the rate of improvement varies considerably among patients. 1
The KDIGO guidelines emphasize that while clinical trials evaluate response at 6–12 months for logistic and economic reasons, individual patients may require longer to achieve response criteria due to marked differences in baseline kidney abnormalities at disease presentation. 1
Prognostic Significance of Response
Several observational studies demonstrate that long-term kidney health is considerably more favorable in patients who respond to treatment, making response status at 24 months a significant predictor of long-term renal survival. 1, 3
Research shows that patients achieving complete remission by 24 months have significantly lower risk of ESRD or mortality (HR 0.254 for mBLISS-LN criteria; HR 0.228 for mALMS criteria) compared to those not in remission. 3
Change in proteinuria is a powerful predictor of renal failure (p = 0.001), death due to lupus nephritis (p < 0.001), and overall lupus mortality (p = 0.001). 4
Important Caveats
There is no universally accepted consensus on the appropriate time for assessing response, and there are marked differences between clinical and histologic remission. 1, 5
One-third of patients achieving complete clinical response after induction have persistently high histologic activity, and 62% of patients with complete histologic remission remain clinically active. 5 Chronic renal damage increases after induction even in complete clinical responders, suggesting that preservation of kidney function may require therapeutic targeting of both chronic damage and inflammation. 5
All response criteria currently used in clinical trials require improvement in proteinuria AND stabilization or improvement in kidney function—both components must be met. 1