ACE inhibitors

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.

• CaptoprilRemoved by haemodialysis

  • “While captopril may be removed from the adult circulation by hemodialysis, there is inadequate data concerning the effectiveness of hemodialysis for removing it from the circulation of neonates or children.”

    Captopril tablets PI (generic)· PRECAUTIONS, Pediatric Use Source

  • “Recent clinical observations have shown an association of hypersensitivity-like (anaphylactoid) reactions during hemodialysis with high-flux dialysis membranes (e.g., AN69) in patients receiving ACE inhibitors.”

    Captopril tablets PI (generic)· WARNINGS, Hemodialysis Source
• EnalaprilRemoved by haemodialysis

  • “Enalaprilat is dialyzable at the rate of 62 mL/min.”

    VASOTEC (enalapril) PI, Bausch Health (2026)· CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism Source

  • “Dialysis PatientsSee WARNINGS, Anaphylactoid Reactions During Membrane Exposure . | Dialysis PatientsSee WARNINGS, Anaphylactoid Reactions During Membrane Exposure . 2.5 mg ondialysis days”

    VASOTEC (enalapril) PI, Bausch Health (2026)· DOSAGE AND ADMINISTRATION, Hypertension Source
• LisinoprilRemoved by haemodialysis

  The label adjusts the dose for haemodialysis (initial 2.5 mg) and notes dialysis-membrane anaphylactoid reactions; it does not give a dialysis clearance figure.

  • “For patients on hemodialysis or creatinine clearance < 10 mL/min, the recommended initial dose is 2.5 mg once daily”

    ZESTRIL (lisinopril) PI (2025)· 2.4 Dose in Patients with Renal Impairment Source
• ramiprilRemoval not studied

  • “Similarly, it is not known which, if any, of these substances can be effectively removed from the body by hemodialysis.”

    Ramipril capsules, prescribing information, Lupin Pharmaceuticals (no Altace SPL currently on DailyMed) (2026)· 10 OVERDOSAGE Source
• trandolaprilRemoved by haemodialysis

  • “Trandolaprilat is removed by hemodialysis.”

    Trandolapril tablets, prescribing information, Lupin Pharmaceuticals (Mavik SPL only from a 2012 repackager) (2025)· 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 < 30 mL/min/1.73m2 → caution (initiate; all)
  “Treatment with ACE-Is or ARNIs is indicated, but should be given with caution, to patients with low blood pressures (systolic blood pressure <100 mmHg), kidney insufficiency (eGFR <30 mL/min/1.73 m2), or elevated serum potassium (>5.2 mEq/L).” — esc2026, p. 33, Section 6.1.4.1
• sbp < 100 mmHg → caution (initiate; all)
  “Treatment with ACE-Is or ARNIs is indicated, but should be given with caution, to patients with low blood pressures (systolic blood pressure <100 mmHg)” — esc2026, p. 33, Section 6.1.4.1
• potassium > 5.2 mmol/L → caution (initiate; all)
  “Significant hyperkalaemia (K+ >5.2 mmol/L).” — esc2026-supp, p. 10, Table S4 Cautions/seek specialist advice
• egfr < 30 mL/min/1.73m2 → caution (initiate; all)
  “Significant renal dysfunction (eGFR <30 mL/min/1.73 m2). May be considered in lower eGFR under close monitoring of eGFR after initiation.” — esc2026-supp, p. 10, Table S4 Cautions/seek specialist advice
• sbp < 90 mmHg → caution (initiate; all)
  “Symptomatic or severe asymptomatic hypotension (systolic blood pressure <90 mmHg).” — esc2026-supp, p. 10, Table S4 Cautions/seek specialist advice
• egfr < 15 mL/min/1.73m2 → no-data (initiate; all)
  “There are no data to support the use of these agents in patients with HFrEF with kidney failure (eGFR <15 mL/min/1.73 m2 or dialysis).” — esc2026-ckd, p. 36, Section 6.2.2.1.1
• potassium >= 5 mmol/L → caution (initiate; all)
  “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 (GDMT by eGFR)
• creatinine_rise_pct < 50 % above baseline → allowed (continue; all)
  “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
• egfr > 15 mL/min/1.73m2 → allowed (continue; all)
  “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
• other < 30 % eGFR decrease from baseline → allowed (continue; all)
  “A decrease in eGFR of <30% is acceptable.” — esc2026-supp, p. 11, Table S4 Problem solving
• potassium <= 5.5 mmol/L → allowed (continue; all)
  “An increase in potassium to ≤5.5 mmol/L is acceptable.” — esc2026-supp, p. 11, Table S4 Problem solving
• potassium > 5.5 mmol/L → not-recommended (hold; all)
  “If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.” — esc2026-supp, p. 12, Table S4 Problem solving
• creatinine_rise_pct > 100 % above baseline → not-recommended (hold; all)
  “If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.” — esc2026-supp, p. 12, Table S4 Problem solving
• egfr < 20 mL/min/1.73m2 → not-recommended (hold; all)
  “If potassium rises to >5.5 mmol/L or creatinine increases by >100% or to eGFR <20 mL/min/1.73 m2, the ACE-I (or ARB) should be stopped and specialist advice sought.” — esc2026-supp, p. 12, Table S4 Problem solving
• creatinine_rise_pct > 50 % above baseline (persisting despite adjusting co-medication) → caution (dose_reduce; all)
  “If greater rises in creatinine or potassium than those outlined above persist despite adjustment of concomitant medications, the dose of the ACE-I (or ARB) should be halved and blood chemistry rechecked within 1–2 weeks” — esc2026-supp, p. 12, Table S4 Problem solving
• egfr < 15 mL/min/1.73m2 → not-recommended (hold; all)
  “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
• potassium > 5.5 mmol/L → caution (dose_reduce; all)
  “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
• potassium >= 6 mmol/L → not-recommended (hold; all)
  “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
• potassium > 6 mmol/L → not-recommended (hold; all)
  “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
• creatinine_rise_pct <= 30 % above baseline within 4 weeks of start/dose increase → allowed (continue; all)
  “Practice Point 3.6.4: Continue ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose.” — kdigo2024-ckd, p. 44, Summary of recommendations, Practice Point 3.6.4 (repeated in Chapter 3.6, p. 98)
• egfr < 15 mL/min/1.73m2 → caution (dose_reduce; all)
  “Practice Point 3.6.5: Consider reducing the dose or discontinuing ACEi or ARB in the setting of either symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment, or to reduce uremic symptoms while treating kidney failure (estimated glomerular filtration rate [eGFR] <15 ml/min per 1.73 m2).” — kdigo2024-ckd, p. 44, Summary of recommendations, Practice Point 3.6.5 (repeated in Chapter 3.6, p. 98)
• other > 30 % eGFR decrease → caution (dose_reduce; all)
  “kidney function, a decrease in eGFR of >30% or the” — acc2024-hfref, p. 18
• creatinine_abs > 3.5 mg/dL → not-recommended (hold; all)
  “In contrast, only if serum creatinine rises by >50% or above 3.5 mg/dl treatment should be discontinued with re-challenge when possible” — mullens2022, p. 13
• creatinine_abs < 3 mg/dL → allowed (continue; all)
  “Therefore, practice guidelines and a previous position paper from this working group propose to tolerate an increase of serum creatinine up to 50% if serum creatinine remains below 3.00 mg/dl and eGFR above >25 ml/min/1.73 m2 when titrating ACE-I/ARB/ARNI.” — mullens2022, p. 13
• creatinine_abs >= 2.5 mg/dL → caution (initiate; all)
  “Serum creatinine <221 mmol/l (<2.5 mg/dl) or eGFR > 30 ml/min per 1.73 m2” — kdigo2026-hf, p. 10, Table 2
• egfr <= 30 mL/min (CrCl) → caution (initiate; lisinopril)
  “In patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, reduce the initial dose of Zestril to half of the usual recommended dose i.e., hypertension, 5 mg; systolic heart failure, 2.5 mg and acute MI, 2.5 mg.” — fda-lisinopril, Section 2.4 Dose in Patients with Renal Impairment
• egfr < 10 mL/min (CrCl) → caution (initiate; lisinopril)
  “For patients on hemodialysis or creatinine clearance < 10 mL/min, the recommended initial dose is 2.5 mg once daily” — fda-lisinopril, Section 2.4 Dose in Patients with Renal Impairment
• egfr <= 30 mL/min (CrCl) → caution (initiate; enalapril)
  “For patients with creatinine clearance less than or equal to 30 mL/min (serum creatinine more than or equal to 3 mg/dL), the first dose is 2.5 mg once daily.” — fda-enalapril, DOSAGE AND ADMINISTRATION, Dosage Adjustment in Hypertensive Patients with Renal Impairment
• creatinine_abs > 1.6 mg/dL → caution (initiate; enalapril)
  “In patients with heart failure who have hyponatremia (serum sodium less than 130 mEq/L) or with serum creatinine greater than 1.6 mg/dL, therapy should be initiated at 2.5 mg daily under close medical supervision” — fda-enalapril, DOSAGE AND ADMINISTRATION, Dosage Adjustment in Patients with Heart Failure and Renal Impairment or Hyponatremia
• other < 130 mEq/L serum sodium → caution (initiate; enalapril, lisinopril)
  “The recommended starting dose in these patients with hyponatremia (serum sodium < 130 mEq/L) is 2.5 mg once daily.” — fda-lisinopril, Section 2.2 Heart Failure
• egfr <= 40 mL/min (CrCl) → caution (initiate; ramipril)
  “Usual regimens of therapy with ramipril may be followed in patients with estimated creatinine clearance >40 mL/min. However, in patients with worse impairment, 25 % of the usual dose of ramipril is expected to produce full therapeutic levels of ramiprilat” — fda-ramipril, Section 2.5 Dosage Adjustments, Renal Impairment
• egfr < 30 mL/min (CrCl) → caution (initiate; trandolapril)
  “For patients with a creatinine clearance <30 mL/min. or with hepatic cirrhosis, the recommended starting dose, based on clinical and pharmacokinetic data, is 0.5 mg daily.” — fda-trandolapril, DOSAGE AND ADMINISTRATION, Dosage Adjustment in Renal Impairment or Hepatic Cirrhosis
• creatinine_abs >= 1.6 mg/dL → caution (continue; captopril)
  “In patients with some degree of renal failure (serum creatinine at least 1.6 mg/dL) but no collagen vascular disease, the risk of neutropenia in clinical trials was about 1 per 500, a frequency over 15 times that for uncomplicated hypertension.” — fda-captopril, WARNINGS, Neutropenia/Agranulocytosis
• egfr < 60 mL/min (GFR) → not-recommended (initiate; all)
  “Avoid concomitant use of aliskiren with ramipril in patients with renal impairment (GFR <60 mL/min/1.73 m2).” — fda-ramipril, Section 5.7 Dual Blockade, Aliskiren

Trial evidence (informational)

• CONSENSUS · NYHA IV HFrEF (n=253), enalapril 2.5-40 mg/day
  6-month mortality: 26% vs 44%, 40% relative reduction
  “The crude mortality at the end of six months (primary end point) was 26 percent in the enalapril group and 44 percent in the placebo group--a reduction of 40 percent (P = 0.002).” — consensus1987, Abstract
• SOLVD-Treatment · Symptomatic HF, LVEF <=0.35 (n=2569), creatinine <=2.5 mg/dL
  All-cause mortality: 39.7% vs 35.2%, RRR 16% (95% CI 5-26%)
  “There were 510 deaths in the placebo group (39.7 percent), as compared with 452 in the enalapril group (35.2 percent) (reduction in risk, 16 percent; 95 percent confidence interval, 5 to 26 percent; P = 0.0036).” — solvd1991, Abstract, Results
• SOLVD-Treatment · Symptomatic HF, LVEF <=0.35
  Death or hospitalization for worsening HF: RRR 26% (95% CI 18-34%)
  “Fewer patients died or were hospitalized for worsening heart failure (736 in the placebo group and 613 in the enalapril group; risk reduction, 26 percent; 95 percent confidence interval, 18 to 34 percent; P less than 0.0001).” — solvd1991, Abstract, Results
• SOLVD-Treatment CKD subgroup · eGFR <60 (MDRD), n=1036
  All-cause mortality: HR 0.88 (0.73-1.06), no significant heterogeneity vs non-CKD
  “Among the 1036 patients with CKD, all-cause mortality occurred in 45% of those in the placebo group and 42% of those in the enalapril group (HR, 0.88; 95% CI, 0.73–1.06; p=0.164; Figure 1-a and Table 2).” — bowling2013, Results 3.3
• SOLVD-Prevention · Asymptomatic LVEF <=35% (n=4228)
  HF hospitalization: 32% fewer first HF hospitalizations; no significant mortality effect
  “No statistically significant mortality effect was demonstrated in this population. Enalapril-treated subjects had 32% fewer first hospitalizations for heart failure, and 32% fewer total heart failure hospitalizations.” — fda-enalapril, CLINICAL PHARMACOLOGY, Heart Failure, Mortality Trials
• ATLAS · NYHA II-IV, LVEF <=30% (n=3164), lisinopril 32.5-35 vs 2.5-5 mg/day
  Death or all-cause hospitalization (high vs low dose): 12% lower (P=0.002); death 8% lower (NS); 24% fewer HF hospitalizations
  “When compared with the low-dose group, patients in the high-dose group had a nonsignificant 8% lower risk of death (P=0.128) but a significant 12% lower risk of death or hospitalization for any reason (P=0.002) and 24% fewer hospitalizations for heart failure (P=0.002).” — packer1999, Abstract, Methods and Results
• AIRE · Post-MI with clinical HF (n=2006), ramipril target 5 mg b.i.d.
  All-cause mortality: 27% reduction (p=0.002)
  “The use of ramipril was associated with a 27% reduction (p=0.002) in the risk of death from any cause; about 90% of the deaths that occurred were cardiovascular, mainly sudden death.” — fda-ramipril, Section 14.3 Heart Failure Post-Myocardial Infarction
• TRACE · Post-MI LV dysfunction (n=1749), trandolapril target 4 mg o.d.
  All-cause mortality: 16% reduction (p=0.042)
  “The use of trandolapril was associated with a 16% reduction in the risk of all-cause mortality (p=0.042), largely cardiovascular mortality.” — fda-trandolapril, CLINICAL PHARMACOLOGY, Heart Failure Post Myocardial Infarction
• SAVE · Post-MI LVEF <=40% (n=2231), captopril target 50 mg t.i.d.
  All-cause mortality: 19% reduction (P=0.02)
  “The risk reduction for all cause mortality was 19% (P = 0.02) and for cardiovascular death was 21% (P = 0.014).” — fda-captopril, CLINICAL PHARMACOLOGY, Pharmacodynamics (SAVE)

Acute kidney injury

Separate haemodynamic eGFR dips after start/uptitration (expected; do not stop if creatinine rise <50% and eGFR >15 per ESC main text, <30% eGFR fall per ESC supp, <=30% creatinine rise per KDIGO) from true AKI. ESC 2026: temporary discontinuation may be needed with AKI and eGFR <15, with severe hyperkalaemia, or with severe haemodynamic instability; restart at the prior dose if paused <14 days. Sick-day rules (temporary hold during dehydrating illness) are endorsed by KDIGO and ESC CVD-CKD but are evidence-poor; failure to restart is the main documented harm.

• “Temporary discontinuation of beta-blockers and ARNIs/ACE-Is/ARBs is advised in patients with severe haemodynamic instability. If FMT has been temporarily discontinued for less than 14 days, it should, in most cases, be safe to initiate FMT directly at the previously tolerated doses in stable patients.”

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

• “Thus, a transient decrease in kidney function after the initiation of ACE-Is/ARNIs/ARBs and MRAs or SGLT2-Is should not prompt their interruption.”

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

• “Sick day rules have been endorsed as useful guidance to people with CKD in the setting of acute, dehydrating illness.”

  KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 136, Section 4.3 Source

• “Practice Point 4.3.2: If medications are discontinued during an acute illness, communicate a clear plan of when to restart the discontinued medications to the affected person and healthcare providers, and ensure documentation in the medical record.”

  KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 136, Practice Point 4.3.2 Source

• “In the context of uptitration of ACE inhibitors some increase in serum creatinine / drop in eGFR is expected and acceptable.”

  Beldhuis 2022 Circulation: Evidence-based medical therapy in HFrEF patients with CKD (2022)· p. 5, Figure 2A Source

• “Evaluate clinical status and other causes of WRF. Consider halving ACEi and re-evaluate”

  Beldhuis 2022 Circulation: Evidence-based medical therapy in HFrEF patients with CKD (2022)· p. 5, Figure 2A Source

• “Rechallenge after 2-4 weeks (if possible at lower dose) when dosing reduced or stopped all together if renal function has improved”

  Beldhuis 2022 Circulation: Evidence-based medical therapy in HFrEF patients with CKD (2022)· p. 5, Figure 2A Source

• “Therefore, the treatment benefit of ACE-I is well preserved if patients develop an acute drop in eGFR.”

  Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 6 Source

Dialysis

No randomized HF trial of ACE-I in dialysis. FDA labels provide dialysis dosing for lisinopril (start 2.5 mg) and enalapril (2.5 mg on dialysis days) and warn of anaphylactoid reactions with high-flux membranes (e.g. AN69). Dialysability: enalaprilat (62 mL/min), lisinopril, captopril (HD yes, PD no) and trandolaprilat are removed by HD; ramipril unknown. FOSIDIAL (fosinopril vs placebo, 397 HD patients with LVH) was neutral (HR 0.93) and underpowered; HEMO secondary analysis found no mortality association but more HF hospitalization with ACE-I use; a 2017 meta-analysis found ACE-I/ARB preserve residual function (mainly PD) but did not reduce CV events (ARB signal for HF events). Guidelines (ESC CVD-CKD, KDIGO 2026 HF, AHA 2022) list this as an evidence gap.

Trials: FOSIDIAL, ARCADIA, HDPAL (atenolol vs lisinopril)

• “Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor.”

  VASOTEC (enalapril) PI, Bausch Health (2026)· WARNINGS, Anaphylactoid Reactions During Membrane Exposure Source

• “Recent clinical observations have shown an association of hypersensitivity-like (anaphylactoid) reactions during hemodialysis with high-flux dialysis membranes (e.g., AN69) in patients receiving ACE inhibitors.”

  Captopril tablets PI (generic)· PRECAUTIONS, Hemodialysis Source

• “Enalaprilat is dialyzable at the rate of 62 mL/min.”

  VASOTEC (enalapril) PI, Bausch Health (2026)· CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism Source

• “Dose adjustment of Zestril is required in patients undergoing hemodialysis or whose creatinine clearance is ≤ 30 mL/min.”

  ZESTRIL (lisinopril) PI (2025)· Section 8.7 Renal Impairment Source

• “Peritoneal dialysis is not effective for removing captopril; there is no information concerning exchange transfusion for removing captopril from the general circulation.”

  Captopril tablets PI (generic)· OVERDOSAGE Source

• “Trandolaprilat is removed by hemodialysis.”

  Trandolapril tablets, prescribing information, Lupin Pharmaceuticals (Mavik SPL only from a 2012 repackager) (2025)· OVERDOSAGE Source

• “Similarly, it is not known which, if any, of these substances can be effectively removed from the body by hemodialysis.”

  Ramipril capsules, prescribing information, Lupin Pharmaceuticals (no Altace SPL currently on DailyMed) (2026)· Section 10 Overdosage Source

• “Angiotensin-converting enzyme inhibitor use was associated with a higher risk of heart failure hospitalization (hazard ratio 1.41, 95% CI 1.11–1.80).”

  Chang TI, et al. Angiotensin-converting enzyme inhibitors and cardiovascular outcomes in patients on maintenance hemodialysis (HEMO secondary analysis). Am Heart J 2011 (PMC4122283) (2011)· Abstract, Results Source

• “In a well-characterized cohort of patients on maintenance hemodialysis, ACEI use was not significantly associated with mortality or cardiovascular morbidity.”

  Chang TI, et al. Angiotensin-converting enzyme inhibitors and cardiovascular outcomes in patients on maintenance hemodialysis (HEMO secondary analysis). Am Heart J 2011 (PMC4122283) (2011)· Abstract, Conclusions Source

• “This study demonstrates that ACE-Is/ARBs therapy decreases the loss of residual renal function, mainly for patients with peritoneal dialysis.”

  Liu Y, et al. Effects of ACEIs and ARBs on cardiovascular events and residual renal function in dialysis patients: a meta-analysis of RCTs. BMC Nephrol 2017;18:206 (PMC5493067) (2017)· Abstract, Conclusions Source

• “Efficacy and safety of GDMT in end-stage renal disease or in patients with eGFR <30 mL/min/1.73 m 2 .”

  2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (2022)· p. 107, Table 31 evidence gaps Source

• “There are no data to support the use of these agents in patients with HFrEF with kidney failure (eGFR <15 mL/min/1.73 m2 or dialysis).”

  2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 36, Section 6.2.2.1.1 Source

• “In CKD stage 5, the KDIGO guidelines still indicate the use of ACE-I and ARBs with moderate evidence for ACE-I/ARB if CKD stage 5 and dialysis and weak evidence supporting their use in patients with CKD stage 5 not on dialysis.”

  Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 6, ACE-I/ARB section Source

• “Sudden and potentially life threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor.”

  ZESTRIL (lisinopril) PI (2025)· Section 5 Anaphylactoid Reactions During Dialysis Source

Kidney transplant

No HF-specific evidence. In kidney transplant recipients KDIGO 2021 BP recommends a dihydropyridine CCB or ARB (not ACE-I) as first-line antihypertensive; ACE-I lowered BP/proteinuria but did not reduce mortality or graft loss and increased adverse events (angioedema, cough, hyperkalaemia, anaemia). Ramipril vs placebo in proteinuric transplant recipients (Knoll 2016) was neutral. ACE-I + mTOR inhibitor raises angioedema risk (labels). For HFrEF in a transplant recipient the ESC HFrEF indication still applies; an ARB may be a reasonable alternative (owner decision).

• “With regard to ACEi there was trial evidence showing that these agents were effective at reducing BP and proteinuria in kidney transplant recipients (Supplementary Table S35).”

  KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in CKD (2021)· p. 62, Chapter 4 rationale Source

• “These results do not support the use of angiotensin-converting enzyme inhibitors with the goal of improving clinical outcomes in this population.”

  Knoll GA, et al. Ramipril versus placebo in kidney transplant patients with proteinuria (RCT). Lancet Diabetes Endocrinol 2016;4:318-26 (PubMed abstract, PMID 26608067) (2016)· Abstract, Interpretation Source

• “Patients taking concomitant mTOR inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema.”

  ZESTRIL (lisinopril) PI (2025)· Section 5.2 Angioedema and Anaphylactoid Reactions Source

• “ACEi and ARB are commonly used for hypertension management but there are limited data to suggest their cardioprotective potential among KTR.”

  Ghimire A et al. Heart Failure in Kidney Transplant Recipients: Narrative Review of Risk Factors, Therapy, and Current Gaps. Cardiol Ther 2026 (PMC12988941) (2026)· RAS inhibitors Source

• “In fact, RCTs examining ACEi in KTR have shown an increased risk of hyperkalemia [61, 65].”

  Ghimire A et al. Heart Failure in Kidney Transplant Recipients: Narrative Review of Risk Factors, Therapy, and Current Gaps. Cardiol Ther 2026 (PMC12988941) (2026)· RAS inhibitors Source

• “Early initiation of ACEI/ARB within 3 months posttransplant proved to be basically safe and has renal function recovery benefits, however, hyperkalemia needs to be noted.”

  Fu D et al. Safety of ACEI/ARB in the early post kidney transplant period: meta-analysis. Front Pharmacol 2024 (PMC11670068) (2024)· Abstract, Conclusion Source

• “When initiating new treatment, consultation with the patient’s transplant team is advisable to ensure that there are no important considerations for the graft, and particularly relevant drug interactions.”

  2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 72, Section 13.2 Source

Albuminuria

Albuminuria does not change the HFrEF indication (HF is itself an indication). Outside HF, KDIGO recommends RASi for A3 (1B, non-diabetic) and A2-A3 (1B, diabetic), suggests for A2 non-diabetic (2C); ESC CVD-CKD recommends max tolerated ACEI/ARB in CKD except patients without albuminuria and with normal/low BP who do not have HF. Relevant mainly for HFpEF, where ACE-I is only IIb but CKD with albuminuria is a co-indication.

• “Treatment with maximally tolerated ACEI or ARB is recommended in patients with CKDc to achieve target blood pressure, reduce risk of progression of CKD and risk of 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

• “With the only potential exception of patients without albuminuria and normal/ low blood pressure (who do not have HF as an indication for ACEI/ARB).”

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

• “Recommendation 3.6.3: We recommend starting RASi (ACEi or ARB) for people with CKD and moderately-to-severely increased albuminuria (G1–G4, A2 and A3) with diabetes (1B).”

  KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 43, Summary of recommendations, Recommendation 3.6.3 (repeated in Chapter 3.6, p. 98) Source

• “Practice Point 3.6.6: Consider starting people with CKD with normal to mildly increased albuminuria (A1) on RASi (ACEi or ARB) for specific indications (e.g., to treat hypertension or heart failure with low ejection fraction).”

  KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44, Summary of recommendations, Practice Point 3.6.6 (repeated in Chapter 3.6, p. 98) Source

• “Although no strong recommendation is given to start these agents in patients with HFpEF, many have coexisting indications for ACE-I/ARB therapy (hypertension/diabetes/CKD).”

  2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 36, Section 6.1.7.1 Source

Monitoring

Check creatinine/eGFR and potassium before starting; recheck 1-2 weeks after initiation and after final titration step (ESC supp, ACC 2024), KDIGO says 2-4 weeks depending on GFR and K; then every 4-6 months (ESC supp). Monitor serially until creatinine and K plateau after any excessive rise. Captopril: WBC monitoring in renal impairment (neutropenia).

• “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)· p. 11, Table S4 How to use Source

• “Monitor blood chemistry 4–6 monthly thereafter.”

  2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 How to use Source

• “Practice Point 3.6.2: Changes in BP, serum creatinine, and serum potassium should be checked within 2–4 weeks of initiation or increase in the dose of a RASi, depending on the current GFR and serum potassium.”

  KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44, Summary of recommendations, Practice Point 3.6.2 (repeated in Chapter 3.6, p. 98) Source

• “Monitoring potassium after initiating an ACEI/ARB and MRA is recommended due to risk of hyperkalaemia.”

  2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 31, Section 5.5 Source

• “Blood chemistry should be monitored frequently and serially until potassium and creatinine have plateaued.”

  2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 12, Table S4 Problem solving Source

• “In such patients, initiate ramipril therapy under close medical supervision and follow patients closely for the first 2 weeks of treatment and whenever the dose of ramipril or diuretic is increased.”

  Ramipril capsules, prescribing information, Lupin Pharmaceuticals (no Altace SPL currently on DailyMed) (2026)· Section 5.5 Hypotension, Congestive Heart Failure Source

In-hospital initiation

Continue (or rapidly reintroduce) existing ACE-I during decompensation unless hypoperfusion, severe haemodynamic instability, AKI with eGFR <15 or severe hyperkalaemia; start in hospitalised DHF patients after stabilisation, ideally before discharge, with rapid uptitration where monitoring allows (STRONG-HF strategy). First dose: observe BP (enalapril label: at least 2 h).

• “In patients already receiving FMT, continuation and/or rapid reintroduction as soon as possible is recommended. Discontinuation of FMT is not recommended unless there are clear signs of hypoperfusion or specific clinical indications.”

  2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 45, Section 7.4.1 Source

• “In patients hospitalized with DHF—after stabilizing (but ideally before discharge).”

  2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 Where? 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 8 Source

• “After the initial dose of VASOTEC, the patient should be observed under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour”

  VASOTEC (enalapril) PI, Bausch Health (2026)· DOSAGE AND ADMINISTRATION, Heart Failure Source

Outpatient

Start in stable outpatients (refer NYHA IV/advanced HF/recent exacerbation); double the dose no faster than every 2 weeks when close monitoring is not possible; ESC recommends uptitration of FMT at least every 1-2 weeks guided by vitals and labs. Some ACE-I is better than none; avoid stopping for intercurrent illness without haemodynamic compromise or for asymptomatic hypotension.

• “In the community in stable patients (NYHA class IV/patients with advanced HF and those with a current/recent exacerbation should be referred for specialist advice).”

  2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 Where? Source

• “In those patients where close monitoring is not possible, dose should be doubled at not less than 2-week intervals.”

  2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 11, Table S4 How to use 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, New recommendations table (also Recommendation Table 5, p. 37) Source

• “In general, incurrent illness or infections without haemodynamic compromise should not lead to down-titration or discontinuation of FMT.”

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

Where sources disagree

Open questions

• Potassium stop threshold: ESC supp Table S4 (stop >5.5) vs ESC main text / ESC CVD-CKD / Mullens (reduce 5.5-6.0, stop >=6.0). Proposed default 5.5 (conservative); owner to confirm.
• Creatinine-rise rule: ESC main text (<50% acceptable, eGFR >15) vs ESC supp (<30% eGFR fall acceptable; stop >100% or eGFR <20) vs KDIGO (30%). Which numbers become the user-adjustable defaults?
• G5 (non-dialysis) and dialysis initiation status: 'caution' (labels allow reduced-dose use) vs 'no-data' (ESC CVD-CKD: no data in kidney failure). Proposed 'caution' with specialist flag.
• AKI initiation set to 'not-recommended' by inference (ESC supp: start in DHF 'after stabilizing'; labels: consider withholding with significant renal decline). No source explicitly addresses de novo initiation during AKI.
• Transplant: should the tool suggest ARB preference in kidney transplant recipients (KDIGO 2021 BP Rec 4.1) or keep ACE-I/ARB equivalence for HFrEF?
• ESC CVD-CKD internal inconsistency: asymptomatic LV dysfunction with eGFR >=30 is 'may be considered' in text (p. 36) but 'is recommended' in the recommendation table (p. 39).
• Ramipril and trandolapril US HF indications are post-MI only; captopril, enalapril and lisinopril have broad HF indications. Show this on drug profiles?
• ESC Table 11 footnote 'b' (higher dose superior to lower dose, ATLAS) appears to attach to lisinopril, but the extracted text places the marker after the enalapril row; verify against the PDF.