Mineralocorticoid receptor antagonists (steroidal: spironolactone, eplerenone; non-steroidal: finerenone)

Removal by dialysis

What each drug's prescribing information says about removal by (haemo)dialysis. Where the label is silent, this page says so rather than inferring from protein binding.

• SpironolactoneLabel does not address dialysis removal

  The spironolactone label contains no statement on dialysis.

• EplerenoneNot removed (or not meaningfully removed)

  • “Eplerenone is not removed by hemodialysis”

    INSPRA (eplerenone) PI, Viatris (2026)· 12.3 Pharmacokinetics, Renal Impairment Source

  • “Compared with control subjects, steady state AUC and Cmax were increased by 38% and 24%, respectively, in patients with severe renal impairment and were decreased by 26% and 3%, respectively, in patients undergoing hemodialysis.”

    INSPRA (eplerenone) PI, Viatris (2026)· 12.3 Pharmacokinetics, Renal Impairment Source
• FinerenoneNot removed (or not meaningfully removed)

  • “Finerenone is unlikely to be efficiently removed by hemodialysis given its fraction bound to plasma proteins of about 90%.”

    KERENDIA (finerenone) PI, Bayer (2026)· 10 OVERDOSAGE Source

After starting: what a change in creatinine, eGFR or potassium means

Drugs and doses

Status by kidney stage

Cutoffs recorded from the sources

• egfr < 25 mL/min/1.73m2 → not-recommended (initiate; finerenone)
  “Initiation of Kerendia in patients with heart failure and an eGFR <25 mL/min/1.73m2 is not recommended.” — fda-finerenone, Warnings and Precautions 5.2
• egfr < 60 mL/min/1.73m2 → start 10 mg (HF target 20 mg); >=60 start 20 mg (HF target 40 mg) (initiate; finerenone)
  “Patients with eGFR ≥ 25 to <60 mL/min/1.73m2 initiated Kerendia 10 mg and patients with eGFR ≥60 mL/min/1.73m2 initiated Kerendia 20 mg, and both groups were titrated up to a target dose of Kerendia 20 mg and 40 mg, respectively.” — fda-finerenone, Section 14.3 Heart Failure (LVEF ≥ 40%)
• egfr <= 60 mL/min/1.73m2 → start 10 mg, target 20 mg (ESC boundary; conflicts with label at exactly 60) (initiate; finerenone)
  “Finerenone has a different starting and target dose according to eGFR (10–20 mg, if eGFR ≤60 mL/min/1.73 m2; 20–40 mg, if eGFR >60 mL/min/1.73 m2).” — esc2026, p. 37 (Table 11, footnote g)
• potassium > 5 mmol/L → not-recommended (do not initiate) (initiate; finerenone)
  “Measure serum potassium and eGFR in all patients before initiation of treatment with Kerendia and dose accordingly [see Dosage and Administration (2.1)]. Do not initiate Kerendia if serum potassium is > 5.0 mEq/L.” — fda-finerenone, Warnings and Precautions 5.1
• potassium > 4.8 mmol/L → caution: 4.8–5.0 may initiate with extra K+ monitoring in first 4 weeks (CKD indication) (initiate; finerenone)
  “if serum potassium levels are > 4.8 to 5.0 mEq/L, initiation of Kerendia treatment may be considered with additional serum potassium monitoring within the first 4 weeks based on clinical judgment and serum potassium levels [see Warnings and Precautions (5.1)].” — fda-finerenone, Section 2.3 Monitoring and Dosage Adjustment (CKD)
• potassium < 5 mmol/L → increase dose (HF); hold dose if eGFR fell >30% (uptitrate; finerenone)
  “< 5.0 | Increase the dose to 20 mg once dailyIf eGFR has decreased by more than 30% compared to previous measurement, maintain current dose.” — fda-finerenone, Section 2.3 Table 3 (Heart Failure (LVEF ≥ 40%))
• potassium >= 5.5 mmol/L → 5.5–<6.0: decrease one step (withhold if on 10 mg; restart 10 mg when K+ <5.5) (dose_reduce; finerenone)
  “≥ 5.5 to < 6.0 | Withhold Kerendia. Restart at 10 mg once daily when serum potassium < 5.5 mEq/L. | Decrease to 10 mg once daily. | Decrease to 20 mg once daily.” — fda-finerenone, Section 2.3 Table 3 (Heart Failure (LVEF ≥ 40%))
• potassium >= 6 mmol/L → withhold; restart 10 mg when K+ <5.5 (hold; finerenone)
  “≥ 6.0 | Withhold Kerendia. Restart at 10 mg once daily when serum potassium < 5.5 mEq/L.If repeated serum potassium measurements are ≥5.5 mEq/L, restart Kerendia at 10 mg once daily when serum potassium < 5.0 mEq/L.” — fda-finerenone, Section 2.3 Table 3 (Heart Failure (LVEF ≥ 40%))
• potassium > 5.5 mmol/L → withhold (CKD+T2D/T1D indication); restart 10 mg when K+ <=5.0 (hold; finerenone)
  “> 5.5 | Withhold Kerendia. Consider restarting at 10 mg once daily when serum potassium ≤ 5.0 mEq/L.” — fda-finerenone, Section 2.3 Table 2 (CKD associated with T2DM or T1DM)
• potassium > 5 mmol/L → not-recommended (label requires K+ <=5.0 to start) (initiate; spironolactone)
  “In patients with serum potassium ≤5.0 mEq/L and eGFR >50 mL/min/1.73 m2, initiate treatment at 25 mg once daily.” — fda-spironolactone, Section 2.2 Treatment of Heart Failure
• egfr <= 50 mL/min/1.73m2 → eGFR 30–50: consider 25 mg every other day (initiate; spironolactone)
  “In patients with an eGFR between 30 and 50 mL/min/1.73 m2, consider initiating therapy at 25 mg every other day because of the risk of hyperkalemia [see Use in Specific Populations (8.6)].” — fda-spironolactone, Section 2.2 Treatment of Heart Failure
• other <= 30 mL/min → contraindicated (all patients, also continuation) (initiate; eplerenone)
  “INSPRA is contraindicated in all patients with: •serum potassium >5.5 mEq/L at initiation, • •creatinine clearance ≤30 mL/min, or” — fda-eplerenone, Section 4 Contraindications
• potassium > 5.5 mmol/L → contraindicated (initiate; eplerenone)
  “Serum potassium >5.5 mEq/L at initiation (4)” — fda-eplerenone, Section 4 Contraindications (Highlights)
• other < 50 mL/min → contraindicated for HYPERTENSION indication only (not HF post-MI) (initiate; eplerenone)
  “Creatinine clearance <50 mL/min (4)” — fda-eplerenone, Section 4 Contraindications (Highlights, hypertension)
• potassium >= 5.5 mmol/L → 5.5–5.9: reduce one step (50->25 mg daily->25 mg every other day->withhold) (dose_reduce; eplerenone)
  “Patients who develop hyperkalemia (5.5-5.9 mEq/L) may continue INSPRA therapy with proper dose adjustment.” — fda-eplerenone, Warnings and Precautions 5.1
• potassium >= 6 mmol/L → withhold; restart 25 mg every other day when K+ <5.5 (hold; eplerenone)
  “Withhold and restart at 25 mg every other day when potassium levels fall to <5.5 mEq/L” — fda-eplerenone, Section 2.1 Table 1 Dose Adjustment in Heart Failure Post-MI
• potassium < 5 mmol/L → titrate 25 -> 50 mg (EPHESUS) (uptitrate; eplerenone)
  “Patients randomized to INSPRA were given an initial dose of 25 mg once daily and titrated to the target dose of 50 mg once daily after 4 weeks if serum potassium was <5.0 mEq/L.” — fda-eplerenone, Section 14.1 Heart Failure Post-Myocardial Infarction
• potassium >= 5 mmol/L → caution (ESC 2026) (initiate; spironolactone, eplerenone, finerenone)
  “Caution should be exercised when MRAs are started in patients with impaired kidney function (MRAs have not been tested in patients with eGFR <25 mL/min/1.73 m2) and in those with potassium levels ≥5.0 mmol/L.” — esc2026, p. 32 (Section 6.1.2.2)
• egfr < 25 mL/min/1.73m2 → caution (not tested) (initiate; spironolactone, eplerenone, finerenone)
  “Caution should be exercised when MRAs are started in patients with impaired kidney function (MRAs have not been tested in patients with eGFR <25 mL/min/1.73 m2) and in those with potassium levels ≥5.0 mmol/L.” — esc2026, p. 32 (Section 6.1.2.2)
• potassium > 5.5 mmol/L → dose reduction or temporary discontinuation (recheck first) (dose_reduce; spironolactone, eplerenone, finerenone)
  “In patients taking MRAs whose serum potassium is >5.5 mEq/L, there might be an indication for dose reduction of the MRA or temporary discontinuation of the MRA to avoid life-threatening hyperkalaemia.” — esc2026, p. 32 (Section 6.1.2.2)
• potassium > 6 mmol/L → temporary down-titration or discontinuation (ESC 2026 main text: >5.5 or >6) (hold; spironolactone, eplerenone, finerenone)
  “Severe hyperkalaemia (potassium >5.5 or >6 mmol/L) should lead to temporary down-titration or discontinuation of MRAs and/or ARNIs/ACE-Is/ARBs” — esc2026, p. 35 (Section 6.1.6)
• egfr < 15 mL/min/1.73m2 → temporary discontinuation may be needed (with AKI) (hold; spironolactone, eplerenone, finerenone)
  “However, temporary discontinuation of MRAs/ARNIs/ACE-Is/ARBs and SGLT2-Is may be needed in cases with acute kidney injury and eGFR <15 mL/min/1.73 m2.” — esc2026, p. 35 (Section 6.1.6)
• creatinine_rise_pct < 50 % above baseline → acceptable, continue (provided eGFR stays >15) (continue; spironolactone, eplerenone, finerenone)
  “An increase in serum creatinine of <50% above baseline, as long as eGFR remains >15 mL/min/1.73 m2, is considered acceptable.” — esc2026, p. 66 (Section 10.3)
• potassium > 5 mmol/L → caution/seek specialist advice (initiate; spironolactone, eplerenone, finerenone)
  “Significant hyperkalaemia before initiation (K+ >5.0 mmol/L).” — esc2026-supp, Table S8, p. 18
• egfr < 30 mL/min/1.73m2 → caution/seek specialist advice (initiate; spironolactone, eplerenone)
  “Steroidal MRA: eGFR <30 mL/min/1.73 m2.” — esc2026-supp, Table S8, p. 18
• egfr < 25 mL/min/1.73m2 → caution/seek specialist advice (initiate; finerenone)
  “Non-steroidal MRA: eGFR <25 mL/min/1.73 m2.” — esc2026-supp, Table S8, p. 18
• potassium > 5.5 mmol/L → halve dose, monitor closely (dose_reduce; spironolactone, eplerenone, finerenone)
  “If K+ rises above 5.5 mmol/L, halve a dose and monitor blood chemistry closely.” — esc2026-supp, Table S8, p. 18
• potassium > 6 mmol/L → interrupt immediately, specialist advice (hold; spironolactone, eplerenone, finerenone)
  “If K+ rises to >6.0 mmol/L, interrupt MRA immediately and seek specialist advice.” — esc2026-supp, Table S8, p. 18
• other > 30 % decline from baseline → halve dose, monitor, consider specialist (dose_reduce; spironolactone, eplerenone, finerenone)
  “If eGFR decreases to >30%, halve the dose, monitor blood chemistry closely, and consider seeking specialist advice.” — esc2026-supp, Table S8, p. 18
• egfr < 30 mL/min/1.73m2 → caution if eGFR decreases below 30 (steroidal) (continue; spironolactone, eplerenone)
  “Potassium increase >5.5 mmol/L If eGFR decreases <30 mL/min/” — esc2026-supp, Table S3, p. 10
• egfr < 15 mL/min/1.73m2 → caution if eGFR decreases below 15 or by >40% (finerenone) (continue; finerenone)
  “Potassium increase >5.5 mmol/L If eGFR decreases <15 mL/min/” — esc2026-supp, Table S3, p. 10
• other > 40 % decline from baseline → caution (finerenone) (continue; finerenone)
  “1.73 m2 or eGFR decreases >40%” — esc2026-supp, Table S3, p. 10
• egfr <= 30 mL/min/1.73m2 → not-recommended (AHA: recommendation applies only if eGFR >30 and K+ <5.0) (initiate; spironolactone, eplerenone)
  “In patients with HFrEF and NYHA class II to IV symptoms, an MRA (spironolactone or eplerenone) is recommended to reduce morbidity and mortality, if eGFR is >30 mL/min/1.73 m 2 and serum potassium is <5.0 mEq/L.” — aha2022, p. 44 (MRA recommendation 1, COR 1, LOE A)
• potassium >= 5.5 mmol/L → discontinue if K+ cannot be maintained <5.5 (AHA COR 3: Harm) (hold; spironolactone, eplerenone)
  “In patients taking MRA whose serum potassium cannot be maintained at <5.5 mEq/L, MRA should be discontinued to avoid life-threatening hyperkalemia (8,9).” — aha2022, p. 44 (MRA recommendation 3, COR 3: Harm)
• egfr < 30 mL/min/1.73m2 → steroidal MRA recommendation applies only at eGFR >=30 (rec table) / >30 (footnote, text) (initiate; spironolactone, eplerenone)
  “Treatment with a steroidal MRA is recommended in patients with HF and CKD with an eGFR ≥30 mL/min/1.73 m2 and HFrEF, to reduce the risk of HF hospitalization and death.” — esc2026-ckd, p. 39 (Recommendation Table 15)
• egfr < 25 mL/min/1.73m2 → non-steroidal MRA (HF LVEF >=40% + CKD) Class IIa only at eGFR >=25 (initiate; finerenone)
  “Treatment with a MRA, either steroidal or non-steroidal, should be considered in patients with HF with LVEF ≥40% and CKD with an eGFRc ≥25 mL/min/1.73 m2 to reduce the risk of HF hospitalization and cardiovascular death.” — esc2026-ckd, p. 39 (Recommendation Table 15)
• potassium > 5 mmol/L → do not initiate finerenone (ESC CVD-CKD) (initiate; finerenone)
  “These data support initiating finerenone when serum potassium is ≤5.0 mmol/L.” — esc2026-ckd, p. 30 (Section 5.5.3.1)
• potassium >= 6 mmol/L → stop finerenone; 5.5–6.0 optimize and consider dose reduction (hold; finerenone)
  “Stop ACEI/ARB/finerenone if potassium ≥6.0 mmol/L; in 5.5–6.0 mmol/L range, should optimize other factors and consider dose reduction, where applicable (Section 3.7.1).” — esc2026-ckd, p. 33 (Figure 8 footnote a)
• potassium >= 5 mmol/L → do not initiate when eGFR <60 (KDIGO HF conference) (initiate; spironolactone, eplerenone, finerenone)
  “In patients with eGFR <60 ml/min per 1.73 m2, initiate ACEi, ARB, sMRA, or nsMRA if serum potassium is <5 mEq/l.” — kdigo2026-hf, p. 11 (Figure 4)
• other <= 30 % decline from baseline → expected haemodynamic dip; do not discontinue (continue; spironolactone, eplerenone, finerenone)
  “Hemodynamic fluctuations in eGFR up to 30% can be seen and should not lead to discontinuation” — kdigo2026-hf, p. 10 (Table 2)
• potassium > 4.8 mmol/L → KDIGO (CKD+T2D): initiate at K+ <=4.8; 4.9–5.5 continue only; >5.5 hold, reinitiate at <=5.0 (initiate; finerenone)
  “The Work Group considers these potassium thresholds to be conservative, and it may be considered appropriate to continue MRAs in people with potassium of 5.5–6.0 mmol/l.” — kdigo2024-ckd, p. 45 (Figure 26; repeated p. 105)
• egfr < 30 mL/min/1.73m2 → contraindicated (ACC 2026 HFpEF ECDP, spironolactone; also SCr >=2.5 mg/dL, K+ >=5.0) (initiate; spironolactone)
  “Potassium $5.0 mmol/L eGFR <30 mL/min/1.73 m 2 or serum creatinine $2.5 mg/dL” — acc2026-hfpef, p. 15 (Table 5)
• egfr < 25 mL/min/1.73m2 → contraindicated (ACC 2026 HFpEF ECDP, finerenone; also K+ >=5.0) (initiate; finerenone)
  “eGFR <25 mL/min/1.73 m 2 Potassium $5.0 mmol/L” — acc2026-hfpef, p. 15 (Table 5)
• creatinine_abs > 2.5 mg/dL (men; >2.0 women) → contraindicated (ACC 2024 HFrEF ECDP) (initiate; spironolactone, eplerenone)
  “creatinine >2.5 mg/dL in men or creatinine >2 mg/dL” — acc2024-hfref, p. 18 (Section 4.2.1; two-column text, single line)
• other < 30 mL/min → discontinue MRA (ACC 2024 HFrEF ECDP) (hold; spironolactone, eplerenone)
  “antagonist if estimated creatinine clearance is <30 mL/min” — acc2024-hfref, p. 30 (Table: worsening kidney function or hyperkalemia; two-column text, single line)
• creatinine_rise_pct >= 50 % rise → rise 50–100% (or SCr up to 3.5 mg/dL, eGFR down to 20, K+ up to 5.5): consider halving MRA (dose_reduce; spironolactone, eplerenone)
  “50-100 3.5 mg/dL 20 5.5 WRF. Consider halving MRA and re-evaluate” — beldhuis2022, p. 7 (Figure 2C)
• creatinine_rise_pct > 100 % rise → rise >100% (or SCr >3.5 mg/dL, eGFR <20, K+ >6.0): consider stopping MRA (hold; spironolactone, eplerenone)
  “> 3.5 > 100 < 20 > 6.0 WRF. Consider stopping MRA and re-evaluate” — beldhuis2022, p. 7 (Figure 2C)
• potassium >= 5.5 mmol/L → 5.5–6: reduce dose; >6: stop temporarily; restart when <5.5 (dose_reduce; spironolactone, eplerenone, finerenone)
  “Generally, dose reduction of these agents is advised if potassium is between 5.5 mEq/L and 6 mEq/L and temporarily termination if potassium is above 6 mEq/L, with reinstitution of the drug only when the potassium drops below 5.5 mEq/L.” — mullens2022, p. 13

Trial evidence (informational)

• RALES · HFrEF, LVEF <=35%, NYHA III–IV; excluded SCr >2.5 mg/dL or K+ >5.0
  All-cause death: RR 0.70 (95% CI 0.60–0.82)
  “There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001).” — pitt1999, Abstract (Results)
• RALES (inclusion) · Kidney exclusion criteria
  Eligibility: SCr >2.5 mg/dL or K+ >5.0 excluded
  “Patients with a baseline serum creatinine of >2.5 mg/dL or a recent increase of 25% or with a baseline serum potassium of >5.0 mEq/L were excluded.” — fda-spironolactone, Section 14.1 Heart Failure
• EMPHASIS-HF · HFrEF, LVEF <=35%, NYHA II; excluded eGFR <30
  CV death or HF hospitalization: HR 0.63 (95% CI 0.54–0.74)
  “The primary outcome occurred in 18.3% of patients in the eplerenone group as compared with 25.9% in the placebo group (hazard ratio, 0.63; 95% confidence interval [CI], 0.54 to 0.74; P<0.001).” — zannad2011, Abstract (Results)
• EPHESUS · Post-MI LVEF <=40% with HF or diabetes; excluded K+ >5.0 or SCr >2.5 mg/dL
  All-cause death: HR 0.85 (95% CI 0.75–0.96)
  “The risk of death with INSPRA was reduced by 15% [hazard ratio equal to 0.85 (95% confidence interval 0.75 to 0.96; p = 0.008 by log rank test)].” — fda-eplerenone, Section 14.1 Heart Failure Post-Myocardial Infarction
• TOPCAT (Americas, post hoc) · HFpEF LVEF >=45%, Americas (n=1767); excluded eGFR <30
  CV death, aborted arrest or HF hospitalization: significant reduction in Americas only (overall trial neutral)
  “In contrast, in the Americas, the rates of the primary outcome, cardiovascular death, and hospitalization for heart failure were significantly reduced by spironolactone.” — pfeffer2015, Abstract (Methods and Results)
• FINEARTS-HF · HF LVEF >=40%, eGFR >=25, K+ <=5.0
  Total worsening HF events and CV death: RR 0.84 (95% CI 0.74–0.95)
  “Over a median follow-up of 32 months, 1083 primary-outcome events occurred in 624 of 3003 patients in the finerenone group, and 1283 primary-outcome events occurred in 719 of 2998 patients in the placebo group (rate ratio, 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = 0.007).” — solomon2024, Abstract (Results)
• FINEARTS-HF (inclusion) · Kidney/potassium inclusion criteria
  Eligibility: eGFR >=25 and K+ <=5.0
  “Patients were required to have an eGFR ≥25 mL/min/1.73m2 and serum potassium ≤5.0 mEq/L at screening and randomization and were receiving background heart failure medical treatment, including diuretics.” — fda-finerenone, Section 14.3 Heart Failure (LVEF ≥ 40%)
• MRA IPD meta-analysis (RALES, EMPHASIS-HF, TOPCAT, FINEARTS-HF; ESC 2026 ref 43) · 13 846 patients across LVEF
  CV death or HF hospitalization: HR 0.77 overall; HFrEF 0.66; HFmrEF/HFpEF 0.87
  “There was a statistically significant interaction by trials and treatment (p for interaction=0·0012) due to the greater efficacy in HFrEF (0·66 [0·59-0·73]) compared with HFmrEF or HFpEF (0·87 [0·79-0·95]).” — jhund2024, Abstract (Findings)
• MRA IPD meta-analysis (hyperkalaemia) · 13 846 patients
  Hyperkalaemia: OR 2.27; serious (>6.0) 2.9% vs 1.4%
  “With an MRA, the risk of hyperkalaemia was doubled compared with placebo (odds ratio 2·27 [95% CI 2·02-2·56]), but the incidence of serious hyperkalaemia (serum potassium >6·0 mmol/L) was low (2·9% vs 1·4%); the risk of hypokalaemia (potassium <3·5 mmol/L) was halved (0·51 [0·45-0·57]; 7% vs 14%).” — jhund2024, Abstract (Findings)
• RALES + EMPHASIS-HF pooled (eGFR fall <30) · HFrEF patients whose eGFR fell to <30 after randomization (n=295)
  CV death or HF hospitalization: HR 0.65 (0.43–0.99) vs 0.63 without eGFR fall
  “However, the risk reduction in the primary outcome with MRA therapy was similar in those who experienced a decrease in eGFR to <30 mL/min/1.73 m2 (HR: 0.65; 95% CI: 0.43-0.99) compared with those who did not (HR: 0.63; 95% CI: 0.56-0.71) (Pinteraction = 0.87).” — matsumoto2024, Abstract (Results)
• FIDELIO-DKD · CKD + T2D (eGFR 25–<75, albuminuric)
  Kidney composite: HR 0.82 (95% CI 0.73–0.93)
  “In FIDELIO-DKD, Kerendia reduced the incidence of the primary composite endpoint of a sustained decline in eGFR ≥ 40%, kidney failure, or renal death (HR 0.82, 95% CI 0.73-0.93, p=0.001) as shown in Table 5 and Figure 1.” — fda-finerenone, Section 14.1
• FIGARO-DKD · CKD + T2D (eGFR 25–90 albuminuric)
  CV death, MI, stroke or HF hospitalization: HR 0.87 (95% CI 0.76–0.98)
  “In FIGARO-DKD, Kerendia reduced the incidence of the primary composite endpoint of CV death, non-fatal MI, non-fatal stroke or hospitalization for heart failure (HR 0.87, 95% CI 0.76-0.98, p=0.026) as shown in Table 5 and Figure 4.” — fda-finerenone, Section 14.1
• ACHIEVE · Maintenance dialysis (n=2538)
  CV death or HF hospitalization: HR 0.92 (95% CI 0.78–1.09), stopped for futility
  “The composite primary outcome occurred in 258 participants (10·46 events per 100 patient-years) in the spironolactone group and in 276 participants (11·33 per 100 patient-years) in the placebo group (hazard ratio [HR] 0·92 [95% CI 0·78-1·09]; p=0·35).” — walsh2025, Abstract (Findings)
• ALCHEMIST · Haemodialysis, high CV risk (n=644)
  MACE: HR 1.00 (95% CI 0.73–1.36)
  “The primary endpoint occurred in 78 (24%) of 320 patients in the spironolactone group (10·66 per 100 patient-years [95% CI 8·54-13·31]) and 79 (24%) of 324 patients in the placebo group (10·70 per 100 patient-years [8·59-13·35]; hazard ratio [HR] 1·00 [95% CI 0·73-1·36]; p=0·98).” — rossignol2025, Abstract (Findings)

Acute kidney injury

Do not start an MRA during AKI; resume/initiate once kidney function and volume are stable. On treatment, hold temporarily for AKI with very low eGFR (ESC: eGFR <15), severe hyperkalaemia, or dehydration (vomiting/diarrhoea/fever), and restart at the previous dose if off <14 days. Beldhuis 2022 table: creatinine rise <50% continue; 50–100% consider halving; >100% (or SCr >3.5 mg/dL, eGFR <20, K+ >6.0) consider stopping, rechallenge after 2–4 weeks. ESC CVD-CKD suggests 'sick day' withholding only for non-steroidal MRAs (weak evidence); ESC Table S8 tells patients on any MRA to contact the clinic when dehydrated.

• “However, temporary discontinuation of MRAs/ARNIs/ACE-Is/ARBs and SGLT2-Is may be needed in cases with acute kidney injury and eGFR <15 mL/min/1.73 m2.”

  2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 35 (Section 6.1.6) Source

• “If diarrhoea/vomiting occurs, or there is infection with fever leading to intense sweating, patients should be made aware of the risk of dehydration and electrolyte imbalance, and they should contact the physician/nurse.”

  2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· Table S8, p. 19 (Advice to the patient) Source

• “Although not supported by any strong evidence, patients may be counselled to withhold ACEI/ARBs, SGLT2 inhibitors, non-steroidal MRAs, and GLP-1RAs temporarily if not able to maintain oral intake (‘sick day rules’).”

  2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 31 (Section 5.5.5) Source

• “If MRA has been temporarily discontinued for less than 14 days, it should, in most cases, be safe to initiate directly at the previously tolerated doses in stable patients.”

  2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· Table S8, p. 18 Source

• “Consider delaying up-titration or interrupting treatment with Kerendia in patients who develop clinically significant worsening of renal function.”

  KERENDIA (finerenone) PI, Bayer (2026)· Warnings and Precautions 5.2 Source

Dialysis

Two 2025 RCTs of spironolactone in dialysis (ACHIEVE, n=2538, maintenance dialysis; ALCHEMIST, n=644, haemodialysis) were neutral for CV outcomes; an updated meta-analysis found little to no effect on CV mortality. ESC CVD-CKD 2026 makes routine MRA use on dialysis Class III ('not recommended'). Eplerenone is label-contraindicated (CrCl <=30) and is not removed by haemodialysis; finerenone has no dialysis data and is unlikely to be removed by haemodialysis. Spironolactone label is silent on dialysis.

Trials: ACHIEVE (Walsh, Lancet 2025), ALCHEMIST (Rossignol, Lancet 2025), Pyne 2025 meta-analysis (Lancet)

• “Routine use of MRAs is not recommended in patients on dialysis because of the risk of serious hyperkalaemia without evidence of clear benefit on cardiovascular death or hospitalizations for heart failure.”

  2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 69 (Recommendation table, Section 12; Class III) Source

• “MRA therapy did not improve cardiovascular outcomes in the Aldosterone Blockade for Health Improvement Evaluation in End-stage Renal Disease (ACHIEVE) and other high-quality trials in dialysis populations.”

  2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 69 (Section 12) Source

• “The composite primary outcome occurred in 258 participants (10·46 events per 100 patient-years) in the spironolactone group and in 276 participants (11·33 per 100 patient-years) in the placebo group (hazard ratio [HR] 0·92 [95% CI 0·78-1·09]; p=0·35).”

  Walsh M et al. Spironolactone versus placebo in patients undergoing maintenance dialysis (ACHIEVE). Lancet 2025 (PMID 40818850, abstract) (2025)· Abstract (Findings) Source

• “In patients with kidney failure on haemodialysis and with high risk of adverse cardiovascular outcomes, spironolactone did not reduce the incidence of major cardiovascular events.”

  Rossignol P et al. Spironolactone in patients on chronic haemodialysis (ALCHEMIST). Lancet 2025 (PMID 40818851, abstract) (2025)· Abstract (Interpretation) Source

• “Our findings suggest that steroidal mineralocorticoid receptor antagonists have little to no effect on cardiovascular mortality in patients requiring dialysis.”

  Pyne L et al. Steroidal MRAs in kidney failure requiring dialysis: systematic review and meta-analysis. Lancet 2025 (PMID 40840478, abstract) (2025)· Abstract (Interpretation) Source

• “Eplerenone is not removed by hemodialysis [see Warnings and Precautions (5.1)].”

  INSPRA (eplerenone) PI, Viatris (2026)· Section 12.3 Pharmacokinetics (Renal Impairment) Source

• “Finerenone is unlikely to be efficiently removed by hemodialysis given its fraction bound to plasma proteins of about 90%.”

  KERENDIA (finerenone) PI, Bayer (2026)· Section 10 Overdosage Source

Kidney transplant

No HF guideline, KDIGO or label statement on MRAs specific to kidney-transplant recipients. SPIREN (n=188, spironolactone vs placebo for 3 years, CNI-treated recipients) lowered measured GFR acutely and showed no kidney benefit; no HF outcomes. Use the eGFR stage of the graft.

• “Spironolactone reduced measured GFRs (up to –7.6 [95% confidence interval, −10.9 to −4.3] ml/min compared with placebo) independently of time since transplantation and BP with no effect on the kidney function curve over time and reduced 24-hour proteinuria after 1 year.”

  Mortensen LA et al. Effect of spironolactone on kidney function in kidney transplant recipients (SPIREN). Clin J Am Soc Nephrol 2024 (PubMed abstract, PMID 38416033) (2024)· Abstract (Results) Source

• “Spironolactone added to standard therapy for 3 years in kidney transplant patients did not improve kidney function, long-term proteinuria, or interstitial fibrosis.”

  Mortensen LA et al. Effect of spironolactone on kidney function in kidney transplant recipients (SPIREN). Clin J Am Soc Nephrol 2024 (PubMed abstract, PMID 38416033) (2024)· Abstract (Conclusions) Source

Albuminuria

Albuminuria matters only for finerenone's CKD+T2D indication (eGFR >=25 and UACR >=30 mg/g despite max RASi; KDIGO 2A, ESC CVD-CKD Class I). It does not change the HF recommendation. In FINEARTS-HF, finerenone reduced new-onset micro- and macroalbuminuria.

• “A non-steroidal MRA (finerenone) is recommended in patients with CKD who have type 2 diabetes with eGFR ≥25 mL/min/1.73 m2 and uACR ≥3 mg/mmol (≥30 mg/g) to reduce the risk of kidney failure and cardiovascular events.”

  2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 31 (Recommendation Table 12) Source

• “Recommendation 3.8.1: We suggest a nonsteroidal mineralocorticoid receptor antagonist with proven kidney or cardiovascular benefit for adults with T2D, an eGFR >25 ml/min per 1.73 m2, normal serum potassium concentration, and albuminuria (>30 mg/g [>3 mg/mmol]) despite maximum tolerated dose of RAS inhibitor (RASi) (2A).”

  KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44 (Recommendation 3.8.1; repeated p. 105) Source

• “Recommendation 1.4.1: We suggest a nonsteroidal mineralocorticoid receptor antagonist with proven kidney or cardiovascular benefit for patients with T2D, an eGFR ‡25 ml/min per 1.73 m2, normal serum potassium concentration, and albuminuria (‡30 mg/g [‡3 mg/mmol]) despite maximum tolerated dose of RAS inhibitor (RASi) (2A).”

  KDIGO 2022 Clinical Practice Guideline for Diabetes Management in CKD (2022)· p. 23 (Recommendation 1.4.1; repeated p. 49) Source

• “However, finerenone still reduced the risk of new-onset micro- and macroalbuminuria by 24% and 38%, respectively.”

  2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 66 (Section 10.3) Source

• “Steroidal and nonsteroidal MRA should not be combined due to risk of hyperkalemia.”

  KDIGO 2022 Clinical Practice Guideline for Diabetes Management in CKD (2022)· p. 52 Source

Monitoring

Check K+ and creatinine/eGFR before starting. Spironolactone: K+ within 1 week of start/titration, then regularly. Eplerenone: before, within first week, at 1 month, then periodically. Finerenone (HF): K+ and eGFR at 4 weeks after start and each dose change, then periodically. ESC Table S8: recheck urea, creatinine, K+ at 1–2 weeks after start and after final titration, then every 4–6 months. KDIGO (finerenone, CKD): K+ at 1 month then every 4 months. Expect a small early eGFR dip (FINEARTS-HF −2.9 mL/min/1.73 m2 in the first 3 months).

• “Monitor serum potassium within 1 week of initiation or titration of ALDACTONE and regularly thereafter. More frequent monitoring may be needed when ALDACTONE is given with other drugs that cause hyperkalemia or in patients with impaired renal function.”

  ALDACTONE (spironolactone) PI, Pfizer (2025)· Warnings and Precautions 5.1 Source

• “Measure serum potassium before initiating INSPRA therapy, within the first week, and at one month after the start of treatment or dose adjustment. Assess serum potassium periodically thereafter.”

  INSPRA (eplerenone) PI, Viatris (2026)· Section 2.3 Recommended Monitoring Source

• “Measure serum potassium and eGFR 4 weeks after initiating treatment and adjust dose (see Table 3).”

  KERENDIA (finerenone) PI, Bayer (2026)· Section 2.3 Monitoring and Dosage Adjustment (Heart Failure with LVEF ≥ 40%) Source

• “(remember: some MRA is better than no MRA). • Recheck blood chemistry (urea/BUN, creatinine, K+) 1–2 weeks after initiation and 1–2 weeks after final dose titration.”

  2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· Table S8, p. 18 Source

• “Monitor blood chemistry 4–6 monthly thereafter. • If K+ rises above 5.5 mmol/L, halve a dose and monitor blood chemistry closely.”

  2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· Table S8, p. 18 Source

• “Monitor K+ at 1 month after initiation and then every 4 months”

  KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 45 (Figure 26; repeated p. 105) Source

• “A prespecified secondary analysis of the FINEARTS-HF trial, in patients with HF and LVEF ≥40%, reported an acute decline in eGFR of −2.9 mL/min/1.73 m2 (95% CI −3.4 to −2.4) during the first 3 months on finerenone vs placebo.”

  2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 66 (Section 10.3) Source

In-hospital initiation

MRA initiation in hospital (DHF phase 2, once stabilized) is feasible and safe per ESC 2026 and is listed as an appropriate setting (ESC Table S8, AHA 2022). Rapid in-hospital uptitration is allowed when closely monitored. FINEARTS-HF randomized 20% of patients during or within 7 days of an HF event. ESC: use a more conservative approach in low eGFR or prior hyperkalaemia.

• “Data from recent RCTs have demonstrated that initiating MRAs, SGLT2-Is, or ARNIs is feasible and safe in this phase of DHF.”

  2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 46 (Section 7.4.2) Source

• “A more conservative approach may be reserved for specific (high-risk) groups of patients, such as patients with low eGFR, hypotension, and history of hyperkalaemia.”

  2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 46 (Section 7.4.2) Source

• “In the community or in the hospital. Exceptions—see ‘Cautions/seek specialist advice’.”

  2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· Table S8, p. 18 Source

• “In patients with HFrEF, GDMT should be initiated during hospitalization after clinical stability is achieved”

  2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (2022)· p. 80 (GDMT during hospitalization, recommendation 3, COR 1) Source

• “The study included 3247 (54%) patients with a heart failure event in the past 3 months, including 1219 (20%) patients randomized during the hospitalization or within 7 days from the heart failure event.”

  KERENDIA (finerenone) PI, Bayer (2026)· Section 14.3 Heart Failure (LVEF ≥ 40%) Source

• “Implementing SGLT2-I and neurohormonal blockade, including MRA, can contribute to more effective and sustainable decongestion.”

  2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 48 (Section 7.5.3) Source

Outpatient

Start low in the community; double the dose at intervals of at least 2 weeks when close monitoring is not possible; ESC 2026 recommends uptitration of FMT at least every 1–2 weeks and intensive titration in the 6 weeks after an HF hospitalization.

• “dose should be doubled at not less than 2-week intervals. • Aim for the target dose (see above) or, failing that, the highest tolerated dose (remember: some MRA is better than no MRA).”

  2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· Table S8, p. 18 Source

• “Uptitration of FMT at least every 1–2 weeks in patients with HF, guided by symptoms, vital signs, and laboratory findings, to achieve optimal target doses shown to be efficacious in RCTs is recommended to reduce the risk of HFH or death.”

  2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 11 (table of new recommendations; also Recommendation Table 5, p. 37, Class I) Source

• “An intensive strategy of rapid initiation and uptitration of FMT before discharge and during frequent follow-up visits in the first 6 weeks following an HFH is recommended to reduce the risk of HF rehospitalization or death.”

  2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 47 (Recommendation table, Section 7.4.3) Source

Where sources disagree

Open questions

• Cells carry an extra 'byDrug' object (initiate/continue per drug) because eplerenone (label CrCl <=30 contraindication), spironolactone (no label floor) and finerenone (eGFR 25 floor, no continuation floor) differ inside G4/G5. Should the engine/matrix render per-drug rows for MRA?
• Eplerenone's label uses Cockcroft-Gault creatinine clearance, not CKD-EPI eGFR. The tool only has eGFR (and age/sex/creatinine, no weight). Use eGFR <30 as a proxy, or add weight to compute CrCl?
• Potassium exactly 5.0 mmol/L at initiation: labels (spironolactone, finerenone) allow it; AHA/ACC 2026/KDIGO 2026 HF and ESC main text treat >=5.0 as contraindication/caution. Proposed 'caution' — owner to confirm.
• Continuation of spironolactone at eGFR 15–29: proposed 'caution' (ESC CVD-CKD, Matsumoto 2024) vs ACC 2024 'discontinue if CrCl <30'. Owner to confirm.
• Dialysis is mapped to 'contraindicated' because ESC CVD-CKD 2026 gives a Class III ('Routine use ... not recommended'). Display as 'not recommended' wording to avoid implying a label contraindication for spironolactone/finerenone?
• Finerenone label HF dosing table steps down at K+ 5.5–<6.0 while the CKD table withholds at >5.5; which table should the engine use when the patient has both HF and CKD+T2D? Proposed: HF table when HF is the indication.
• ESC 2026 lists eplerenone as FMT for HFrEF generally, but the FDA indication is HFrEF after acute MI only. Show an 'off-label in US for non-post-MI HFrEF' note in the ACC/AHA view?