First-year eGFR slope demonstrates a U-shaped association with mortality in newly diagnosed multiple myeloma, whereby both excessive declines and excessive increases in eGFR are linked to elevated mortality risk.
Key Findings
Results
The association between first-year eGFR slope and all-cause mortality in newly diagnosed multiple myeloma exhibited a statistically significant U-shaped (nonlinear) pattern.
p for nonlinearity = 0.0145
Both excessive declines and excessive increases in eGFR during the first year were linked to elevated mortality
Analysis used Cox proportional-hazards regression and restricted cubic splines (RCS)
Study included 974 newly diagnosed MM patients from a single center (2008–2022) with a median follow-up of 40 months
Results
The U-shaped eGFR slope-mortality pattern was consistent across all baseline renal function strata.
Subgroup analyses were stratified by baseline eGFR of <40, 40–90, and ≥90 mL/min/1.73 m²
The U-shaped association persisted regardless of baseline kidney function level
This suggests the pattern is not driven by any single level of baseline renal impairment
Results
In patients achieving partial response (PR) or better, a rising eGFR slope was paradoxically associated with increased mortality risk.
Hazard ratio exceeded 1 when the annual eGFR increment exceeded 4.3 mL/min/1.73 m²
Excessive eGFR elevation in good treatment responders was associated with increased death risk
This finding highlights a paradoxical relationship between apparent renal improvement and mortality in this subgroup
Results
In patients achieving less than partial response, mortality risk was predominantly driven by eGFR slope declines rather than increases.
Hazard ratio exceeded 1 when the eGFR slope fell below 1.18 mL/min/1.73 m²/year
This pattern is in contrast to the PR-or-better group, where rising eGFR was the primary risk driver
The association between eGFR slope and mortality varied substantially by treatment response subgroup
Methods
The first-year eGFR slope was calculated as the average annual rate of eGFR change using least-squares regression applied to all monitored eGFR values during the first year.
Creatinine levels were prospectively monitored throughout follow-up
The study was a single-center, retrospective design enrolling 974 NDMM patients diagnosed between 2008 and 2022
Subgroup analyses were stratified by first-year treatment response (PR or better vs. less than PR) and by baseline eGFR strata
Median follow-up period was 40 months
Background
Renal impairment is recognized as a late-stage indicator of kidney dysfunction in multiple myeloma, motivating examination of earlier markers such as eGFR slope.
RI increases mortality risk in MM but represents a relatively late stage of kidney dysfunction
Whether early indicators such as eGFR slope predict mortality in MM was previously unknown
This study is positioned as the first to examine the eGFR slope-mortality relationship in NDMM
Conclusions
The authors concluded that response-stratified interpretation of renal dynamics is needed to guide early clinical decision-making in multiple myeloma.
Excessive eGFR elevation, particularly in patients achieving PR or better, is paradoxically associated with increased death risk
The findings highlight the importance of not uniformly treating rising eGFR as a favorable prognostic sign
Authors call for response-stratified interpretation of renal function changes in clinical practice
What This Means
This research suggests that tracking how quickly kidney function changes during the first year of multiple myeloma treatment can help predict which patients are at higher risk of death — but the relationship is more complex than expected. Rather than a simple pattern where declining kidney function means worse outcomes, the study found a U-shaped curve: both patients whose kidneys got much worse and patients whose kidneys improved very rapidly had higher mortality risks compared to those with more moderate changes. This finding came from analyzing 974 newly diagnosed myeloma patients followed for a median of over three years.
Perhaps the most surprising finding is that patients who responded well to treatment (achieving at least a partial response) but also showed large rapid improvements in kidney function were paradoxically at greater risk of death. In contrast, patients who did not respond well to treatment faced higher mortality mainly when their kidney function declined. This suggests that a rapid rise in kidney function in good responders may be a signal of something abnormal — possibly reflecting other disease complications — rather than a straightforward sign of recovery.
This research suggests that doctors should not automatically interpret improving kidney function in myeloma patients as reassuring, particularly in those who are responding well to treatment. Instead, the rate and direction of kidney function change may need to be interpreted in the context of how well the myeloma itself is responding to therapy. These findings point to the potential value of monitoring kidney function trajectories early in treatment as a tool for identifying patients who may need closer observation or adjusted management.
Li L, Liu X, Guan M, Li H, Tang W, Niu T. (2026). A U-Shaped Association: The First-Year eGFR Slope and Mortality Risk in Multiple Myeloma.. Cancer medicine. https://doi.org/10.1002/cam4.72168