Please click on the appropriate boxes to the right of the drug name to see information about use of this drug at different stages of kidney disease.

Please note that the above dosing of the drug for HFrEF is not generalizable to dosing of the drug for hypertension, erythrocytosis, or proteinuria.

Please click on the appropriate boxes to the right of the drug name to see information about use of this drug at different stages of kidney disease.

Please note that the above dosing of the drug for HFrEF is not generalizable to dosing of the drug for hypertension, erythrocytosis, aortic aneurysm, or proteinuria.

Initial dosing

If the patient is currently on an ACEI, a 36-hour washout period is required when switching from ACEI to ARNI.
If the patient is currently on an ARB, no washout period is required when switching from ARB to ARNI.

• If patient's prior dose of ACEI was > 10mg/day of enalapril or equivalent, or prior dose of ARB was > 160 mg/day of valsartan or equivalent:
  Start with sacubitril-valsartan 49-51mg BID.
  Double the dose as tolerated after 2 weeks to the target maintenance dose of 97-103 mg BID
• If patient's prior dose of ACEI was ≤ 10mg/day of enalapril or equivalent, or prior dose of ARB was ≤ 160 mg/day of valsartan or equivalent:
  Start with sacubitril-valsartan 24-26mg BID.
  Double the dose as tolerated in 2 week intervals until the target maintenance dose of 97-103mg BID is reached.
• If patient is not currently on an ACEI or ARB:
  Start with sacubitril-valsartan 24-26mg BID.
  Double the dose as tolerated in 2 week intervals until the target maintenance dose of 97-103mg BID is reached.

Dose titration

As above

Please click on the appropriate boxes to the right of the drug name to see information about use of this drug at different stages of kidney disease.

Please note that the above dosing of the drug for HFrEF is not generalizable to dosing of the drug for other disease states.

Please click on the appropriate boxes to the right of the drug name to see information about use of this drug at different stages of kidney disease.

Please note that the above dosing of the drug for HFrEF is not generalizable to dosing of the drug in angina, atrial fibrillation, other supraventricular arrhythmias, or hypertension.

Dose titration for finerenone

Start at finerenone 20mg once daily, unless eGFR ≥ 25 and < 60, then start at 10mg daily. Do not start if eGFR < 25

Maintenance dose is determined by serum potassium measured 4 weeks after initiation of therapy or after a dose adjustment.

• If K ≤ 4.8:
• If currently on 10 mg daily: Increase to 20mg daily
• If already on 20mg daily: Continue 20mg daily
• If K > 4.8 to 5.5
• If currently on 10 mg daily: Continue 10mg daily
• If already on 20mg daily: Continue 20mg daily
• If K > 5.5
• If currently on 10 mg daily: Stop finerenone. May consider restarting at 10 mg once daily when serum potassium ≤ 5
• If currently on 20mg daily: Stop finerenone. May consider restarting at 10 mg once daily when serum potassium ≤ 5

Please click on the appropriate boxes to the right of the drug name to see information about use of this drug at different stages of kidney disease.

Please note that the above dosing of the drug for HFrEF is not generalizable to dosing of the drug for hirsutism, hypertension, or primary aldosteronism.

Please click on the appropriate boxes to the right of the drug name to see information about use of this drug at different stages of kidney disease.

Please note that the above dosing of the drug for HFrEF is not generalizable to dosing of the drug for other disease states.

CKD 1-3

"In patients with symptomatic chronic HFrEF, SGLT2i are recommended to reduce hospitalization for HF and cardiovascular mortality, irrespective of the presence of type 2 diabetes" (AHA/ACC/HFSA, Class I)

CKD 4-5

"Once an SGLT2i is initiated, it is reasonable to continue an SGLT2i even if the eGFR falls below 20 ml/min per 1.73 m2, unless it is not tolerated or kidney replacement therapy is initiated." (KDIGO)

DAPA-HF for dapagliflozin did not enroll patients with eGFR < 30. EMPEROR-Reduced for empagliflozin did not enroll patients with eGFR < 20.

"The writing committee recognizes that glucosuric effects of SGLT2 inhibitors may be attenuated in those with eGFRs below these thresholds; benefits of SGLT2 inhibitors for HFrEF management in those with more advanced renal dysfunction than the patients in these recent studies remains less clear. Caution is advised when using SGLT2 inhibitors in patients with eGFRs below the inclusion criteria from pivotal studies, particularly as SGLT2 inhibitors have been associated with mild worsening of renal function during the first year of use." (ACC)

ESKD

"SGLT2i have not been adequately studied in kidney transplant recipients, who may benefit from SGLT2i treatment, but are immunosuppressed and potentially at increased risk for infections; therefore, the recommendation to use SGLT2i does not apply to kidney transplant recipients." (KDIGO)

"Contraindicated [if] on dialysis" (ACC)

AKI

"Acute kidney injury and impairment in renal function: consider temporarily discontinuing [SGLT2i] in settings of reduced oral intake or fluid losses" (ACC)

"Sick day protocol (for illness or excessive exercise or alcohol intake): temporarily withhold sodium-glucose cotransporter 2 inhibitor (SGLT2i), keep drinking and eating (if possible), check blood glucose and blood ketone levels more often, and seek medical help early. Periprocedural/perioperative care: inform patients about risk of diabetic ketoacidosis, withhold SGLT2i the day of day-stay procedures and limit fasting to minimum required, withhold SGLT2i at least 2 days in advance and the day of procedures/surgery requiring one or more days in hospital and/or bowel preparation (which may require increasing other glucose-lowering drugs during that time), measure both blood glucose and blood ketone levels on hospital admission (proceed with procedure/surgery if the patient is clinically well and ketones are ,1.0 mmol/L), and restart SGLT2i after procedure/surgery only when eating and drinking normally."(KDIGO)

Should only be given to patients who are persistently symptomatic despite optimal medication for HFrEF, who are euvolemic, and who are in sinus rhythm with resting HR > 70 bpm despite being on a target or maximally tolerated dose of BB or if there is a contraindication to BB use.

Initial dose

ivabradine PO 5mg BID
OR
ivabradine PO 2.5mg BID

Dose titration

Adjust dose every ≥ 2 weeks as needed:

• If resting HR > 60 bpm: Increase dose by 2.5mg BID
  Maximum dose is 7.5mg BID
• IF resting HR is 50-60 bpm: Maintain dose
• If resting HR < 50 bpm or there are signs or symptoms of bradycardia: Decrease dose by 2.5mg BID.
  If current dose is already down to 2.5mg BID, discontinue ivabradine.

Please click on the appropriate boxes to the right of the drug name to see information about use of this drug at different stages of kidney disease.

Please note that the above dosing of the drug for HFrEF is not generalizable to dosing of the drug for inappropriate sinus tachycardia or stable angina.

There are no RCTs on ivabradine in CKD at the present time. There are no scientific society guidelines on ivabradine on CKD.

CKD 1-4

In chronic kidney disease patients with glomerular filtration rates (GFR) above 15 mL/min per 1.73 m2, no dose adjustment seems to be required." (Lullo, 2015)

CKD 5

No data. "At present, no data for patients with GFR < 15 mL/min per 1.73 m2 are available, although efficacy and safety may be preserved in these patients too; more trials are needed" (Lullo, 2015)

ESKD

No data. "ivabradine should be used carefully or avoided in ESRD patients." (Lullo, 2015)

AKI

No data.

CKD 1-2

"In patients with symptomatic HFrEF despite GDMT (or who are unable to tolerate GDMT), digoxin might be considered to decrease hospi-talizations for HF. (AHA/ACC/HFSA, Class IIb)

"The recommendation is guarded because "To date, there has been only 1 large-scale, RCT of digox-in in patients with HF.1 This trial, which predated current GDMT, primarily enrolled patients with NYHA class II to III HF and showed that treatment with digoxin for 2 to 5 years had no effect on mortality but modestly reduced the combined risk of death and hospitalization. The trial also found no significant effect on health-related QOL in a subset of the trial patients.3 The effect of digoxin on hospitalizations has been supported by retrospective analyses and meta-analyses.2,4–6 Additionally, observa-tional studies and retrospective analyses have shown improvement in symptoms and exercise tolerance in mild to moderate HF; however, they have mostly shown either lack of mortality benefit or increased mortality associated with digoxin.7 The benefit in patients on current GDMT is unclear because most trials preceded current GDMT. Thus, use of digoxin requires caution in patients with HF and is reserved for those who remain symptomatic de-spite optimization of GDMT."(AHA/ACC/HFSA)

CKD 3-5

"Reduce dose based on plasma concentrations" (KDIGO, Class I)

"Dosage adaptation is required, monitoring of serum digoxin levels " (KDIGO)

KDOQI and KDIGO do not comment on the use of digoxin in ESKD. However, there are a number of observational studies concerning for increased mortality from digoxin use in CKD.

In an "observational study of advanced CKD patients (stages 3b to 5) using ITT and AT analysis, digoxin use was associated with increased mortality after adjusting for patient characteristics, comorbidities, and co-administered medications." (Yang, 2021)

ESKD

KDOQI and KDIGO do not comment on the use of digoxin in ESKD. However, there are a number of observational studies concerning for increased mortality from digoxin use in CKD.

In an "observational cohort of 120,864 incident HD patients, the use of digoxin was associated with an increased risk for death. The mortality effect was significantly potentiated by high serum digoxin and low serum K levels, which seemed independent of patient characteristics, propensity for treatment, the facility, the physician, disease severity, or time." (Chan, 2010)

There has been no RCTs on this topic.

AKI

"We recommend temporary discontinuation of potentially nephrotoxic and renally excreted drugs in people with a GFR < 60 ml/min/1.73 m2 (GFR categories G3a-G5) who have serious intercurrent illness that increases the risk of AKI. These agents include, but are not limited to: RAAS blockers (including ACE-Is, ARBs, aldosterone inhibitors, direct renin inhibitors), diuretics, NSAIDs, metformin, lithium, and digoxin." (KDIGO, Class I)

Statin Intensity

First, let's take a look at which statins are high, moderate, and low intensity. Notice that rosuvastatin and atorvastatin are the only two ones with high intensity doses.

What does high, moderate, and low intensity mean?

Who qualifies for a statin?

The two situations that bypass the table below are:

• If LDL ≥ 190: Go straight to a high-intensity statin, regardless of age
• If clinical ASCVD: Go straight to a high-intensity statin, unless >75yo, then moderate-intensity statin
• Other than ACS and stable ischemic heart disease, conditions included in ASCVD are stroke, transient ischemic attack, prior coronary revascularization, prior other arterial revascularization, and peripheral artery disease

Among individuals with LDL 70-189:

Please click on the appropriate boxes to the right of the drug name to see information about use of this drug at different stages of kidney disease.

Please note that the above dosing of the drug for HFrEF/CAD/HLD is not generalizable to dosing of the drug for other disease states.

CKD 1-2

Patients with "eGFR >60 ml/min/1.73 m2 (and no history of kidney transplantation) may be treated with any statin regimen that is approved for use in the general population" (KDIGO)

CKD 3-5

No contraindications or dose adjustments needed.

ESKD

"In adults with dialysis-dependent CKD, we suggest that statins or statin/ezetimibe combination not be initiated." (KDIGO, Class II)

"However, patients might reasonably choose statin treatment if they are interested in a relatively small, uncertain reduction in cardiovascular events. Since very high LDL-C might increase the likelihood of benefit from statin in a dialysis patient, patients who meet this criterion may be more inclined to receive a statin, recognizing that the benefit remains uncertain. Other factors that might influence a patient’s decision to receive statin could include recent MI or greater life expectancy (both favoring treatment), and more severe comorbidity or higher current pill burden (both favoring non-treatment)." (KDIGO)

"In patients already receiving statins or statin/ezetimibe combination at the time of dialysis initiation, we suggest that these agents be continued." (KDIGO, Class II)

No dose adjustment is necessary for patients on dialysis.

CKD 1-2

Patients with "eGFR >60 ml/min/1.73 m2 (and no history of kidney transplantation) may be treated with any statin regimen that is approved for use in the general population" (KDIGO)

CKD 3

No contraindications

CKD 4-5

"Decrease [rosuvastatin] to a maximum of 10 mg/day at GFR < 30; recommended starting dose is 5 mg/day" (Weiner, 2004)

Decrease [rosuvastatin] to a "10 mg/day" for "eGFR G3a-G5, including patients on dialysis or with a kidney transplant" (KDIGO)

ESKD

Maximum 10mg/day when on dialysis. (LexiComp)

Decrease [rosuvastatin] to a "10 mg/day" for "eGFR G3a-G5, including patients on dialysis or with a kidney transplant" (KDIGO)

AKI

Any data? Jiawei you wrote "no data to suggest harm. AKI may be from statin-induced rhabdomyolysis" in the excel sheet but I don't think there was an attached reference for that cell

CKD 1-2

Patients with "eGFR >60 ml/min/1.73 m2 (and no history of kidney transplantation) may be treated with any statin regimen that is approved for use in the general population" (KDIGO)

CKD 3

No contraindications or dose adjustments needed.

CKD 4-5

In the general KDIGO CKD guideline, it was specified: "No increase in toxicity for simvastatin dosed at 20 mg per day or simvastatin 20 mg /ezetimide 10 mg combinations per day in people with GFR < 30 ml/min/1.73 m2 or on dialysis" (KDIGO)

Subsequently, in the KDIGO lipids guideline, it was specified that simvastatin "40 mg/day" is acceptable in patients with "eGFR G3a-G5, including patients on dialysis or with a kidney transplant" (KDIGO)

ESKD

Regarding the question of simvastatin dosing, in the general KDIGO CKD guideline, it was specified: "No increase in toxicity for simvastatin dosed at 20 mg per day or simvastatin 20 mg /ezetimide 10 mg combinations per day in people with GFR < 30 ml/min/1.73 m2 or on dialysis" (KDIGO)

Subsequently, in the KDIGO lipids guideline, it was specified that simvastatin "40 mg/day" is acceptable in patients with "eGFR G3a-G5, including patients on dialysis or with a kidney transplant" (KDIGO)

Regarding the question of whether or not a statin should be used in ESKD: "In adults with dialysis-dependent CKD, we suggest that statins or statin/ezetimibe combination not be initiated." (KDIGO, Class II)

"However, patients might reasonably choose statin treatment if they are interested in a relatively small, uncertain reduction in cardiovascular events. Since very high LDL-C might increase the likelihood of benefit from statin in a dialysis patient, patients who meet this criterion may be more inclined to receive a statin, recognizing that the benefit remains uncertain. Other factors that might influence a patient’s decision to receive statin could include recent MI or greater life expectancy (both favoring treatment), and more severe comorbidity or higher current pill burden (both favoring non-treatment)." (KDIGO)

"In patients already receiving statins or statin/ezetimibe combination at the time of dialysis initiation, we suggest that these agents be continued." (KDIGO, Class II)

AKI

Any data? Jiawei you wrote "no data to suggest harm. AKI may be from statin-induced rhabdomyolysis" in the excel sheet but I don't think there was an attached reference for that cell

CKD 1-2

Patients with "eGFR >60 ml/min/1.73 m2 (and no history of kidney transplantation) may be treated with any statin regimen that is approved for use in the general population" (KDIGO)

CKD 3-5

In the KDIGO lipids guideline, it was specified that pravastatin "40 mg/day" is acceptable in patients with "eGFR G3a-G5, including patients on dialysis or with a kidney transplant" (KDIGO)

However, other sources do not require dose reduction (LexiComp)

ESKD

Regarding the question of simvastatin dosing, in the KDIGO lipids guideline, it was specified that pravastatin "40 mg/day" is acceptable in patients with "eGFR G3a-G5, including patients on dialysis or with a kidney transplant" (KDIGO)

However, other sources do not require dose reduction (LexiComp)

Regarding the question of whether or not a statin should be used in ESKD: "In adults with dialysis-dependent CKD, we suggest that statins or statin/ezetimibe combination not be initiated." (KDIGO, Class II)

"However, patients might reasonably choose statin treatment if they are interested in a relatively small, uncertain reduction in cardiovascular events. Since very high LDL-C might increase the likelihood of benefit from statin in a dialysis patient, patients who meet this criterion may be more inclined to receive a statin, recognizing that the benefit remains uncertain. Other factors that might influence a patient’s decision to receive statin could include recent MI or greater life expectancy (both favoring treatment), and more severe comorbidity or higher current pill burden (both favoring non-treatment)." (KDIGO)

"In patients already receiving statins or statin/ezetimibe combination at the time of dialysis initiation, we suggest that these agents be continued." (KDIGO, Class II)

AKI

Any data? Jiawei you wrote "no data to suggest harm. AKI may be from statin-induced rhabdomyolysis" in the excel sheet but I don't think there was an attached reference for that cell

CKD 1-2

Patients with "eGFR >60 ml/min/1.73 m2 (and no history of kidney transplantation) may be treated with any statin regimen that is approved for use in the general population" (KDIGO)

CKD 3-5

In the KDIGO lipids guideline, fluvastatin "80 mg/day" is acceptable in patients with "eGFR G3a-G5, including patients on dialysis or with a kidney transplant" (KDIGO). In other words, no dose adjustment is required.

ESKD

In the KDIGO lipids guideline, fluvastatin "80 mg/day" is acceptable in patients with "eGFR G3a-G5, including patients on dialysis or with a kidney transplant" (KDIGO). In other words, no dose adjustment is required.

Regarding the question of whether or not a statin should be used in ESKD: "In adults with dialysis-dependent CKD, we suggest that statins or statin/ezetimibe combination not be initiated." (KDIGO, Class II)

"However, patients might reasonably choose statin treatment if they are interested in a relatively small, uncertain reduction in cardiovascular events. Since very high LDL-C might increase the likelihood of benefit from statin in a dialysis patient, patients who meet this criterion may be more inclined to receive a statin, recognizing that the benefit remains uncertain. Other factors that might influence a patient’s decision to receive statin could include recent MI or greater life expectancy (both favoring treatment), and more severe comorbidity or higher current pill burden (both favoring non-treatment)." (KDIGO)

"In patients already receiving statins or statin/ezetimibe combination at the time of dialysis initiation, we suggest that these agents be continued." (KDIGO, Class II)

AKI

Any data? Jiawei you wrote "no data to suggest harm. AKI may be from statin-induced rhabdomyolysis" in the excel sheet but I don't think there was an attached reference for that cell