Authors of a systematic review and meta-analysis of 16 randomized controlled trials involving 52,306 patients with chronic kidney disease (CKD) found that SGLT2 inhibitors were associated with slower eGFR decline and 34% lower odds of kidney disease progression compared with placebo. The analysis also highlighted a time-dependent pattern: an initial eGFR decline was observed during the first 1 to 13 weeks of treatment, followed by stabilization, with more favorable changes in eGFR emerging after 64 weeks. The magnitude of eGFR benefit appeared smaller at lower baseline kidney function, although kidney composite outcomes generally favored SGLT2 inhibition across eGFR subgroups.

Clinically, an early eGFR dip after starting an SGLT2 inhibitor does not necessarily indicate worsening CKD or treatment failure. The meta-analysis also found lower rates of acute kidney injury and serious adverse events overall, while identifying increased risks of volume-related adverse events, diabetic ketoacidosis, urinary tract infection, and genital mycotic infection. Because kidney outcome definitions varied across trials and heterogeneity was substantial for some analyses, the results support continued monitoring and individualized assessment rather than interpreting early changes in eGFR in isolation.

Reference: Cao MJ, Liang TT, Xu L, Shi FH. Evaluating the overall renal outcomes of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with chronic kidney disease (CKD). Diabetol Metab Syndr. 2025 Jan 6;17(1):5. doi: 10.1186/s13098-024-01547-x.

Investigators of a multinational analysis spanning 59 cohorts and more than 3 million individuals evaluated whether the widely used four-variable Kidney Failure Risk Equation (KFRE), based on age, sex, eGFR, and albuminuria, could be improved with additional clinical information. Using the 2021 chronic kidney disease (CKD)-EPI creatinine equation, the KFRE continued to perform well overall in patients with eGFR <60 mL/min/1.73 m². Adding prior eGFR trajectory, averaged eGFR or albuminuria measurements, or cardiovascular conditions such as heart failure, coronary disease, atrial fibrillation, and stroke did not meaningfully improve prediction.

In practice, the findings support continued use of the existing KFRE for risk stratification in patients with CKD stages G3 to G5 rather than routinely adding more variables. However, accuracy was less consistent in lower-risk patients with eGFR 45 to 59 mL/min/1.73 m² and for 5-year estimates in adults aged 65 years or older, highlighting the importance of clinical context and local calibration. The equation also performed poorly when eGFR was at least 60 mL/min/1.73 m², a population for which it was not designed, so alternative approaches may be more appropriate when assessing earlier-stage CKD.

Reference: Grams ME, Brunskill NJ, Ballew SH, et al. The Kidney Failure Risk Equation: Evaluation of Novel Input Variables including eGFR Estimated Using the CKD-EPI 2021 Equation in 59 Cohorts. J Am Soc Nephrol. 2023 Mar 1;34(3):482-494. doi: 10.1681/ASN.0000000000000050.

Authors of a prespecified post hoc analysis of the 6,001-patient FINEARTS-HF trial examined finerenone according to how recently patients had experienced a worsening heart failure (WHF) event. Patients enrolled during or within 7 days of WHF had the highest subsequent event rate, at 24.4 primary outcome events per 100 patient-years, compared with 11.3 among those enrolled more than 3 months after WHF or without a prior WHF event. Finerenone reduced the composite of total WHF events or cardiovascular death among patients enrolled within 7 days of WHF (RR, 0.74; 95% CI, 0.57-0.95) and 7 days to 3 months afterward (RR, 0.79; 95% CI, 0.64-0.97). However, the interaction between time since WHF and treatment effect was not statistically significant (P for interaction=0.07), so the analysis does not establish that finerenone works better when started earlier.

The practical message is that finerenone can be considered even in close proximity to a WHF event in patients with HFpEF, when baseline risk is particularly high and the potential absolute benefit may therefore be greater. The authors place these findings within an expanding heart failure with preserved ejection fraction treatment strategy that includes diuretic management, SGLT2 inhibitors, rapid optimization of guideline-directed therapy, close follow-up, and selected use of angiotensin receptor-neprilysin inhibitors and mineralocorticoid receptor antagonists. Because FINEARTS-HF was not designed specifically to test whether timing modifies finerenone efficacy, the results support early treatment implementation without proving a time-dependent treatment advantage.

Reference: Lindberg F, Savarese G. Worsening heart failure: an opportunity for treatment implementation even with a preserved ejection fraction? J Am Coll Cardiol. 2025 Jan 21;85(2):117-119. doi: 10.1016/j.jacc.2024.09.022.