A U-Shaped Association: The First-Year eGFR Slope and Mortality Risk in Multiple Myeloma

Renal impairment (RI) increases mortality risk in multiple myeloma (MM), yet RI represents a relatively late stage of kidney dysfunction. Whether early indicators of renal dysfunction, such as the estimated glomerular filtration rate (eGFR slope), predict mortality risk in MM remains unknown.

This single center, retrospective study included 974 newly diagnosed MM (NDMM) patients (2008-2022), with prospectively monitored creatinine levels and survival status over a median follow-up period of 40 months. The first-year eGFR slope, representing the average annual rate of eGFR change, was calculated by least-squares regression using all monitored eGFR values during the first year. Cox proportional-hazards regression and restricted cubic splines (RCS) analyses were used to explore the association of first-year eGFR slope with all-cause mortality. Subgroup analyses were stratified by first-year treatment response (partial response (PR) or better response group and less than PR group), and baseline eGFR strata (< 40, 40-90, and ≥ 90 mL/min/1.73 m²).

In the overall population, the first-year eGFR slope-mortality association exhibited a U-shaped pattern (p for nonlinearity 0.0145), indicating that excessive declines and increases in eGFR were linked to elevated mortality. This pattern was consistent across baseline renal function strata. Notably, the association varied substantially by treatment response: in the PR or better group, a rise in eGFR slope conferred a higher mortality risk (HR > 1 when annual increment exceeded 4.3 mL/min/1.73 m²), whereas in the less than PR group, mortality risk was predominantly driven by eGFR slope declines (HR > 1 when slope fell below 1.18 mL/min/1.73 m²/year).

Overall, first-year eGFR slope demonstrates a U-shaped association with mortality in NDMM. Importantly, excessive eGFR elevation, particularly in patients achieving PR or better, is paradoxically associated with increased death risk, highlighting the need for response-stratified interpretation of renal dynamics to guide early clinical decision-making.