Treatment algorithm

Your Organizational Guidance

ebpracticenet urges you to prioritize the following organizational guidance:

Chronisch nierlijden (multidisciplinaire aanpak)Published by: WORELLast published: 2017GPC pluridisciplinaire sur la néphropathie chronique (IRC)Published by: Groupe de travail Développement de recommandations de première ligneLast published: 2017

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

GFR category G1 to G2 without uremia

1st line – ACE inhibitor or angiotensin-II receptor antagonist

Back
ACUTE
|
GFR category G1 to G2 without uremia
1st line – 

ACE inhibitor or angiotensin-II receptor antagonist

Several classes of agents have been shown to slow CKD progression. Renin-angiotensin system blockade (e.g., with an ACE inhibitor or an angiotensin-II receptor antagonist) can preserve kidney function by reducing intraglomerular pressure independently of blood pressure (BP) and glucose control.​[64][65]

ACE inhibitors and angiotensin-II receptor antagonists have been shown in numerous clinical trials to slow the progression of CKD and delay the need for renal replacement therapy in both diabetic and nondiabetic CKD.[90][91][92]

The 2014 Joint National Committee 8 redefined the target BP goal for patients with CKD as <140/90 mmHg, given the evidence from clinical trials that this is associated with the lowest risk of cardiovascular outcomes and mortality.[86] However, the 2017 American College of Cardiology/American Heart Association guideline recommends adults with hypertension and CKD should be treated to a BP goal of less than 130/80 mmHg.[87] The Kidney Disease: Improving Global Outcomes guideline recommends a target systolic BP of less than 120 mmHg, if tolerated, in patients with CKD, with and without diabetes, and not receiving dialysis.[64]

ACE inhibitors and angiotensin-II receptor antagonists may be associated with hyperkalemia and acute kidney injury, more commonly in older people, those with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m², and with use of longer-acting agents. These complications are usually reversible with discontinuation of the drug and appropriate treatment.

Doses should be low initially and adjusted gradually according to clinical response.

Primary options

lisinopril: 2.5 to 5 mg orally once daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

ramipril: 1.25 mg orally once daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

enalapril: 2.5 mg orally once daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

perindopril erbumine: 2 mg orally once daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

trandolapril: 0.5 mg orally once daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

captopril: 12.5 to 25 mg orally two to three times daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

losartan: 50 mg orally once daily initially, adjust dose gradually according to response, maximum 100 mg/day

OR

irbesartan: 75 mg orally once daily initially, adjust dose gradually according to response, maximum 300 mg/day

OR

telmisartan: 20 mg orally once daily initially, adjust dose gradually according to response, maximum 80 mg/day

Consider – sodium-glucose cotransporter-2 (SGLT2) inhibitor

Back
ACUTE
|
GFR category G1 to G2 without uremia
Consider – 

sodium-glucose cotransporter-2 (SGLT2) inhibitor

Treatment recommended for SOME patients in selected patient group

SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin) can preserve kidney function by reducing intraglomerular pressure independently of blood pressure (BP) and glucose control.[65][66][71]

There is evidence that the use of SGLT2 inhibitors prevents major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease) in people with type 2 diabetes.[66][76][77] SGLT2 inhibitors, in addition to reducing hyperglycemia, have renal benefits through independent effects on renal tubular glucose reabsorption, weight, BP, intraglomerular pressure, albuminuria, and slowed GFR loss.[78][79]

SGLT2 inhibitors are recommended for the treatment of CKD, particularly in adults at risk of progression, in combination with an ACE inhibitor or an angiotensin-II receptor antagonist. BMJ Rapid Recommendation: SGLT2-inhibitors for adults with CKD Opens in new window

Recommendations for the use of SGLT2 inhibitors in patients with different degrees of kidney disease may vary; consult your local drug information source for more information.

Use of SGLT2 inhibitors is not recommended in patients with end-stage renal disease who are on dialysis.[80]

Primary options

dapagliflozin: 10 mg orally once daily

OR

empagliflozin: 10 mg orally once daily

OR

canagliflozin: 100-300 mg orally once daily

Plus – statin

Back
ACUTE
|
GFR category G1 to G2 without uremia
Plus – 

statin

Treatment recommended for ALL patients in selected patient group

Statin therapy has been shown to have cardioprotective effects in patients with CKD.[94][95][96][97] In those individuals not on dialysis therapy, the use of statins in a large meta-analysis resulted in the reduction of all-cause mortality by 21% (relative risk [RR] 0.79, 95% CI 0.69 to 0.91) and cardiovascular mortality by 23% (RR 0.77, 95% CI 0.69 to 0.87).[98]

Kidney Disease: Improving Global Outcomes guidelines recommend that CKD patients ≥50 years or those with a high risk of cardiovascular mortality (not on dialysis) should be treated with a statin without the need for routine follow-up to check lipid values, or to change dose regimen based on set targets (i.e., a "treat and forget" approach).[67]

Statin therapy has been associated with liver dysfunction and myopathy and should be monitored in patients with CKD.

Primary options

simvastatin: 20-40 mg orally once daily

OR

pravastatin: 40 mg orally once daily

OR

rosuvastatin: 5-10 mg orally once daily

OR

atorvastatin: 10-20 mg orally once daily

Consider – additional antihypertensive therapy

Back
ACUTE
|
GFR category G1 to G2 without uremia
Consider – 

additional antihypertensive therapy

Treatment recommended for SOME patients in selected patient group

Hypertension is one of the greatest risk factors for the progression of CKD, regardless of the underlying etiology of CKD. Most patients with CKD will require at least two or three different types of antihypertensive agent to achieve the optimal BP control. A combination of antihypertensive agents should be used. ACE inhibitors and angiotensin-II receptor antagonists should not be combined within the same regimen.​[64]​​​​

Other classes of antihypertensive agents (e.g., thiazide, or thiazide-like diuretics, beta-blockers, dihydropyridine calcium-channel blockers, aldosterone antagonists, vasodilators, alpha-2 adrenergic agonists) should be added when the target blood pressure is not achieved with the use of an ACE inhibitor or an angiotensin-II receptor antagonist, or if there are other specific clinical indications, such as beta-blockers for angina pectoris.[64]​ 

Primary options

chlorthalidone: 12.5 to 25 mg orally once daily initially, adjust dose gradually according to response, maximum 50 mg/day

OR

hydrochlorothiazide: 12.5 mg orally once daily initially, adjust dose gradually according to response, maximum 50 mg/day

OR

atenolol: 25 mg orally once daily initially, adjust dose gradually according to response, maximum 25-50 mg/day

OR

metoprolol succinate: 25 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 100 mg/day

OR

nifedipine: 30-60 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 90 mg/day (120 mg/day for some brands)

OR

amlodipine: 5 mg orally once daily initially, adjust dose gradually according to response, maximum 10 mg/day

OR

felodipine: 2.5 mg orally once daily initially, adjust dose gradually according to response, maximum 20 mg/day

OR

spironolactone: 12.5 mg orally once daily initially, adjust dose gradually according to response, maximum 200 mg/day given in 2-4 divided doses

Secondary options

hydralazine: 10 mg orally three to four times daily initially, adjust dose gradually according to response, maximum 300 mg/day

OR

minoxidil: 5 mg orally once daily initially, adjust dose gradually according to response, maximum 40 mg/day

OR

clonidine: 0.1 mg orally (immediate-release) twice daily initially, adjust dose gradually according to response, maximum 0.6 mg/day

Consider – glycemic control

Back
ACUTE
|
GFR category G1 to G2 without uremia
Consider – 

glycemic control

Treatment recommended for SOME patients in selected patient group

In patients with diabetes, glycemic goals should be individualized. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a HbA1c target ranging from <6.5% to <8.0% for patients with diabetes and chronic kidney disease not receiving dialysis. A lower target (e.g., <6.5% or <7.0%) may be appropriate for individuals in whom preventing complications is the key goal, whereas a higher target (e.g., <7.5% or <8.0%) may be preferred in those with multimorbidity or increased burden of hypoglycemia.[20][70]​ In patients with diabetes and CKD, there is a risk for hypoglycemia because of impaired kidney clearance of drugs (such as insulin or sulfonylureas) and impaired kidney gluconeogenesis. 

Patients with type 1 diabetes require treatment with insulin, regardless of whether they are on dialysis or not.

Some specific antihyperglycemic drugs used by patients with type 2 diabetes significantly reduce all-cause or cardiovascular mortality, or major cardiovascular events or renal complications in some patient subgroups, and should be considered independently of HbA1c targets.[71][72][73][74][75]

There is evidence that the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors prevents major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease) in people with type 2 diabetes.[66][76]​​[77] SGLT2 inhibitors, in addition to reducing hyperglycemia, have renal benefits through independent effects on renal tubular glucose reabsorption, weight, blood pressure, intraglomerular pressure, albuminuria, and slowed glomerular filtration rate (GFR) loss.[78][79]​

KDIGO guidelines advise that most patients with type 2 diabetes and CKD would benefit from treatment with metformin (if eGFR ≥30 mL/minute/1.73 m²) and an SGLT2 inhibitor (if eGFR ≥20 mL/minute/1.73 m²).[20] The American Diabetes Association recommends the use of SGLT2 inhibitors in patients with CKD and type 2 diabetes (if eGFR ≥20 mL/minute/1.73 m²) regardless of urinary albuminuria.[63]​ Use of SGLT2 inhibitors is not recommended in patients with end-stage renal disease who are on dialysis.[80] 

If additional glycemic control is required for patients receiving metformin and an SGLT2 inhibitor, a drug from a different class should be selected. A glucagon-like peptide-1 (GLP-1) is the preferred option. If required, other agents (e.g., a dipeptidyl peptidase-4 [DPP-4] inhibitor, a sulfonylurea, insulin, a thiazolidinedione, or an alpha-glucosidase inhibitor) may be considered based on eGFR, comorbidities, and patient preference.[20]

As a class of drugs, GLP-1 agonists have beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes.[81][82] GLP-1 agonists may be considered for cardiovascular risk reduction.[63]

Liraglutide, dulaglutide, and semaglutide are not renally excreted and are the preferred agents in this class.

Studies report that DPP-4 inhibitors are renoprotective, but do not have a cardiovascular benefit.[83][84]​ Some DPP-4 inhibitors require dose adjustment in renal impairment. 

Consider – finerenone

Back
ACUTE
|
GFR category G1 to G2 without uremia
Consider – 

finerenone

Treatment recommended for SOME patients in selected patient group

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces the progression of kidney disease in patients with type 2 diabetes mellitus and known CKD.[85] Finerenone is approved by the Food and Drug Administration (FDA) to reduce the risk of kidney function decline, kidney failure, cardiovascular death, nonfatal heart attacks, and hospitalization for heart failure in adults with CKD associated with type 2 diabetes.

Guidelines recommend finerenone for patients with type 2 diabetes and albuminuria, despite maximum tolerated dose of an ACE inhibitor or an angiotensin-II receptor antagonist (if eGFR is ≥25 mL/minute/1.73 m² and serum potassium level is normal).[20][63]​ Finerenone can be added to an sodium-glucose cotransporter-2 (SGLT2) inhibitor and an ACE inhibitor or an angiotensin-II receptor antagonist.

Monitor serum potassium levels during treatment, and use caution when administering with other drugs that increase serum potassium levels.

Primary options

finerenone: 20 mg orally once daily

2nd line – nondihydropyridine calcium-channel blocker

Back
ACUTE
|
GFR category G1 to G2 without uremia
2nd line – 

nondihydropyridine calcium-channel blocker

If an ACE inhibitor or an angiotensin-II receptor antagonist needs to be discontinued due to adverse effects (such as cough, angioedema, hemodynamic decline in renal function, and/or hyperkalemia), then nondihydropyridine calcium-channel blockers have been demonstrated to have more proteinuric-lowering effects than other antihypertensive agents.[128]

Primary options

diltiazem: 120 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 360 mg/day

OR

verapamil: 120 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 360 mg/day

Consider – sodium-glucose cotransporter-2 (SGLT2) inhibitor

Back
ACUTE
|
GFR category G1 to G2 without uremia
Consider – 

sodium-glucose cotransporter-2 (SGLT2) inhibitor

Treatment recommended for SOME patients in selected patient group

SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin) can preserve kidney function by reducing intraglomerular pressure independently of blood pressure (BP) and glucose control.[65][66][71]

There is evidence that the use of SGLT2 inhibitors prevents major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease) in people with type 2 diabetes.[66][76][77] SGLT2 inhibitors, in addition to reducing hyperglycemia, have renal benefits through independent effects on renal tubular glucose reabsorption, weight, BP, intraglomerular pressure, albuminuria, and slowed GFR loss.[78][79]

SGLT2 inhibitors are recommended for the treatment of CKD, particularly in adults at risk of progression, in combination with an ACE inhibitor or an angiotensin-II receptor antagonist. BMJ Rapid Recommendation: SGLT2-inhibitors for adults with CKD Opens in new window

Recommendations for the use of SGLT2 inhibitors in patients with different degrees of kidney disease may vary; consult your local drug information source for more information.

Use of SGLT2 inhibitors is not recommended in patients with end-stage renal disease who are on dialysis.[80]

Primary options

dapagliflozin: 10 mg orally once daily

OR

empagliflozin: 10 mg orally once daily

OR

canagliflozin: 100-300 mg orally once daily

Plus – statin

Back
ACUTE
|
GFR category G1 to G2 without uremia
Plus – 

statin

Treatment recommended for ALL patients in selected patient group

Statin therapy has been shown to have cardioprotective effects in patients with CKD.[94][95][96][97] In those individuals not on dialysis therapy, the use of statins in a large meta-analysis resulted in the reduction of all-cause mortality by 21% (relative risk [RR] 0.79, 95% CI 0.69 to 0.91) and cardiovascular mortality by 23% (RR 0.77, 95% CI 0.69 to 0.87).[98]

KDIGO guidelines recommend that CKD patients not on dialysis should be treated with a statin without the need for routine follow-up to check lipid values, or to change dose regimen based on set targets (i.e., a "treat and forget" approach).[67]

Statin therapy has been associated with liver dysfunction and myopathy and should be monitored in patients with CKD.

Primary options

simvastatin: 20-40 mg orally once daily

OR

pravastatin: 40 mg orally once daily

OR

rosuvastatin: 5-10 mg orally once daily

OR

atorvastatin: 10-20 mg orally once daily

Consider – additional antihypertensive therapy

Back
ACUTE
|
GFR category G1 to G2 without uremia
Consider – 

additional antihypertensive therapy

Treatment recommended for SOME patients in selected patient group

Hypertension is one of the greatest risk factors for the progression of CKD, regardless of the underlying etiology of CKD. Most patients with CKD will require at least two or three different types of antihypertensive agent to achieve the optimal BP control. A combination of antihypertensive agents should be used. ACE inhibitors and angiotensin-II receptor antagonists should not be combined within the same regimen.[64]​​​​

Other classes of antihypertensive agents (e.g., thiazide or thiazide-like diuretics, beta-blockers, dihydropyridine calcium-channel blockers, aldosterone antagonists, vasodilators, alpha-2 adrenergic agonists) should be added when the target blood pressure is not achieved with the use of a nondihydropyridine calcium-channel blocker, or if there are other specific clinical indications, such as beta-blockers for angina pectoris.[64] 

Primary options

chlorthalidone: 12.5 to 25 mg orally once daily initially, adjust dose gradually according to response, maximum 50 mg/day

OR

hydrochlorothiazide: 12.5 mg orally once daily initially, adjust dose gradually according to response, maximum 50 mg/day

OR

atenolol: 25 mg orally once daily initially, adjust dose gradually according to response, maximum 25-50 mg/day

OR

metoprolol succinate: 25 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 100 mg/day

OR

nifedipine: 30-60 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 90 mg/day (120 mg/day for some brands)

OR

amlodipine: 5 mg orally once daily initially, adjust dose gradually according to response, maximum 10 mg/day

OR

felodipine: 2.5 mg orally once daily initially, adjust dose gradually according to response, maximum 20 mg/day

OR

spironolactone: 12.5 mg orally once daily initially, adjust dose gradually according to response, maximum 200 mg/day given in 2-4 divided doses

OR

aliskiren: 150 mg orally once daily initially, adjust dose gradually according to response, maximum 300 mg/day

Secondary options

hydralazine: 10 mg orally three to four times daily initially, adjust dose gradually according to response, maximum 300 mg/day

OR

minoxidil: 5 mg orally once daily initially, adjust dose gradually according to response, maximum 40 mg/day

OR

clonidine: 0.1 mg orally (immediate-release) twice daily initially, adjust dose gradually according to response, maximum 0.6 mg/day

Consider – glycemic control

Back
ACUTE
|
GFR category G1 to G2 without uremia
Consider – 

glycemic control

Treatment recommended for SOME patients in selected patient group

In patients with diabetes, glycemic goals should be individualized. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a HbA1c target ranging from <6.5% to <8.0% for patients with diabetes and chronic kidney disease not receiving dialysis. A lower target (e.g., <6.5% or <7.0%) may be appropriate for individuals in whom preventing complications is the key goal, whereas a higher target (e.g., <7.5% or <8.0%) may be preferred in those with multimorbidity or increased burden of hypoglycemia.[20][70]​ In patients with diabetes and CKD, there is a risk for hypoglycemia because of impaired kidney clearance of drugs (such as insulin or sulfonylureas) and impaired kidney gluconeogenesis. 

Patients with type 1 diabetes require treatment with insulin, regardless of whether they are on dialysis or not.

Some specific antihyperglycemic drugs significantly reduce all-cause or cardiovascular mortality, or major cardiovascular events or renal complications in some patient subgroups, some should be considered independently of HbA1c targets.[71][72][73][74][75]​ 

There is evidence that the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors prevents major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease) in people with type 2 diabetes.[66][76][77]​ SGLT2 inhibitors, in addition to reducing hyperglycemia, have renal benefits through independent effects on renal tubular glucose reabsorption, weight, blood pressure, intraglomerular pressure, albuminuria, and slowed glomerular filtration rate (GFR) loss.[78][79]​

KDIGO guidelines advise that most patients with type 2 diabetes and CKD would benefit from treatment with metformin (if eGFR ≥30 mL/minute/1.73 m²) and an SGLT2 inhibitor (if eGFR ≥20 mL/minute/1.73 m²).[20] The American Diabetes Association recommends the use of SGLT2 inhibitors in patients with CKD and type 2 diabetes (if eGFR ≥20 mL/minute/1.73 m²) regardless of urinary albuminuria.[63] Use of SGLT2 inhibitors is not recommended in patients with end-stage renal disease who are on dialysis.[80] 

If additional glycemic control is required for patients receiving metformin and an SGLT2 inhibitor, a drug from a different class should be selected. A glucagon-like peptide-1 (GLP-1) is the preferred option. If required, other agents (e.g., a dipeptidyl peptidase-4 [DPP-4] inhibitor, a sulfonylurea, insulin, a thiazolidinedione, or an alpha-glucosidase inhibitor) may be considered based on eGFR, comorbidities, and patient preference.[20]

As a class of drugs, GLP-1 agonists have beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes.[81][82]​ GLP-1 agonists may be considered for cardiovascular risk reduction.[63]

Liraglutide, dulaglutide, and semaglutide are not renally excreted and are the preferred agents in this class.

Studies report that DPP-4 inhibitors are renoprotective, but do not have a cardiovascular benefit.[83][84]​ Some DPP-4 inhibitors require dose adjustment in renal impairment. 

Consider – finerenone

Back
ACUTE
|
GFR category G1 to G2 without uremia
Consider – 

finerenone

Treatment recommended for SOME patients in selected patient group

Finerenone, a nonsteroidal selective mineralocorticoid receptor antagonist, reduces the progression of kidney disease in patients with type 2 diabetes mellitus and known CKD.[85] Finerenone is approved by the Food and Drug Administration to reduce the risk of kidney function decline, kidney failure, cardiovascular death, nonfatal heart attacks, and hospitalization for heart failure in adults with CKD associated with type 2 diabetes.

Guidelines recommend finerenone for patients with type 2 diabetes and albuminuria (if eGFR is ≥25 mL/minute/1.73 m² and serum potassium level is normal).[20][63]

Monitor serum potassium levels during treatment, and use caution when administering with other drugs that increase serum potassium levels.

Primary options

finerenone: 20 mg orally once daily

GFR category G3 to G4 without uremia

1st line – ACE inhibitor or angiotensin-II receptor antagonist

Back
ACUTE
|
GFR category G3 to G4 without uremia
1st line – 

ACE inhibitor or angiotensin-II receptor antagonist

Several classes of agents have been shown to slow CKD progression. Renin-angiotensin system blockade (e.g., with an ACE inhibitor or an angiotensin-II receptor antagonist) can preserve kidney function by reducing intraglomerular pressure independently of blood pressure (BP) and glucose control.​[64][65]

ACE inhibitors and angiotensin-II receptor antagonists have been shown in numerous clinical trials to slow the progression of CKD and delay the need for renal replacement therapy in both diabetic and nondiabetic CKD.[90][91][92]

The Joint National Committee 8 redefined the target BP goal for patients with CKD as <140/90 mmHg, given the evidence from clinical trials that this is associated with the lowest risk of cardiovascular outcomes and mortality.[86] However, the 2017 American College of Cardiology/American Heart Association guideline recommends adults with hypertension and CKD should be treated to a BP goal of less than 130/80 mmHg.[87] The Kidney Disease: Improving Global Outcomes guideline recommends a target systolic BP of less than 120 mmHg, if tolerated, in patients with CKD, with and without diabetes, and not receiving dialysis.[64]

ACE inhibitors and angiotensin-II receptor antagonists may be associated with hyperkalemia and acute renal failure, more commonly in older people, those with an estimated GFR <30 mL/minute/1.73 m², and with use of longer-acting agents. These complications are usually reversible with discontinuation of the drug and appropriate treatment.

Primary options

lisinopril: 2.5 to 5 mg orally once daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

ramipril: 1.25 mg orally once daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

enalapril: 2.5 mg orally once daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

perindopril erbumine: 2 mg orally once daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

trandolapril: 0.5 mg orally once daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

captopril: 12.5 to 25 mg orally two to three times daily initially, adjust dose gradually according to response, maximum dose depends on level of impairment

OR

losartan: 50 mg orally once daily initially, adjust dose gradually according to response, maximum 100 mg/day

OR

irbesartan: 75 mg orally once daily initially, adjust dose gradually according to response, maximum 300 mg/day

OR

telmisartan: 20 mg orally once daily initially, adjust dose gradually according to response, maximum 80 mg/day

Consider – sodium-glucose cotransporter-2 (SGLT2) inhibitor

Back
ACUTE
|
GFR category G3 to G4 without uremia
Consider – 

sodium-glucose cotransporter-2 (SGLT2) inhibitor

Treatment recommended for SOME patients in selected patient group

SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin) can preserve kidney function by reducing intraglomerular pressure independently of blood pressure (BP) and glucose control.[65][66][71]​​

There is evidence that the use of SGLT2 inhibitors prevents major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease) in people with type 2 diabetes.[66][76][77] SGLT2 inhibitors, in addition to reducing hyperglycemia, have renal benefits through independent effects on renal tubular glucose reabsorption, weight, BP, intraglomerular pressure, albuminuria, and slowed GFR loss.[78][79]

SGLT2 inhibitors are recommended for the treatment of CKD, particularly in adults at risk of progression, in combination with an ACE inhibitor or an angiotensin-II receptor antagonist. BMJ Rapid Recommendation: SGLT2-inhibitors for adults with CKD Opens in new window

Recommendations for the use of SGLT2 inhibitors in patients with different degrees of kidney disease may vary; consult your local drug information source for more information.

Use of SGLT2 inhibitors is not recommended in patients with end-stage renal disease who are on dialysis.[80]

Primary options

dapagliflozin: 10 mg orally once daily

OR

empagliflozin: 10 mg orally once daily

OR

canagliflozin: 100-300 mg orally once daily

Plus – statin ± ezetimibe

Back
ACUTE
|
GFR category G3 to G4 without uremia
Plus – 

statin ± ezetimibe

Treatment recommended for ALL patients in selected patient group

Statin therapy has been shown to have cardioprotective effects in patients with CKD.[94][95][96][97] In those individuals not on dialysis therapy, the use of statins in a large meta-analysis resulted in the reduction of all-cause mortality by 21% (relative risk [RR] 0.79, 95% CI 0.69 to 0.91) and cardiovascular mortality by 23% (RR 0.77, 95% CI 0.69 to 0.87).[98]

Kidney Disease: Improving Global Outcomes guidelines recommend that GFR category G3 or G4 CKD patients not on dialysis should be treated with a statin without the need for routine follow-up to check lipid values, or to change dose regimen based on set targets (i.e., a "treat and forget" approach).[67] For patients ages ≥50 years with CKD category G3 or G4, ezetimibe can be added to simvastatin.[68]

Statin therapy has been associated with liver dysfunction and myopathy and should be monitored in patients with CKD.

Primary options

simvastatin: 20-40 mg orally once daily

OR

pravastatin: 40 mg orally once daily

OR

rosuvastatin: 5-10 mg orally once daily

OR

atorvastatin: 10-20 mg orally once daily

OR

ezetimibe/simvastatin: 10 mg (ezetimibe)/20 mg (simvastatin) orally once daily

Consider – additional antihypertensive therapy

Back
ACUTE
|
GFR category G3 to G4 without uremia
Consider – 

additional antihypertensive therapy

Treatment recommended for SOME patients in selected patient group

Hypertension is one of the greatest risk factors for the progression of CKD, regardless of the underlying etiology of CKD. Most patients with CKD will require at least two or three different types of antihypertensive agent to achieve the optimal BP control. A combination of antihypertensive agents should be used. ACE inhibitors and angiotensin-II receptor antagonists should not be combined within the same regimen.[64]​​​​​​

Other classes of antihypertensive agents (e.g., thiazide or thiazide-like diuretics, beta-blockers, dihydropyridine calcium-channel blockers, aldosterone antagonists, vasodilators, alpha-2 adrenergic agonists) should be added when the target blood pressure is not achieved with the use of an ACE inhibitor or an angiotensin-II receptor antagonist, or if there are other specific clinical indications, such as beta-blockers for angina pectoris.[64]

Primary options

chlorthalidone: 12.5 to 25 mg orally once daily initially, adjust dose gradually according to response, maximum 50 mg/day

OR

hydrochlorothiazide: 12.5 mg orally once daily initially, adjust dose gradually according to response, maximum 50 mg/day

OR

atenolol: 25 mg orally once daily initially, adjust dose gradually according to response, maximum 25-50 mg/day

OR

metoprolol succinate: 25 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 100 mg/day

OR

nifedipine: 30-60 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 90 mg/day (120 mg/day for some brands)

OR

amlodipine: 5 mg orally once daily initially, adjust dose gradually according to response, maximum 10 mg/day

OR

felodipine: 2.5 mg orally once daily initially, adjust dose gradually according to response, maximum 20 mg/day

OR

spironolactone: 12.5 mg orally once daily initially, adjust dose gradually according to response, maximum 200 mg/day given in 2-4 divided doses

Secondary options

hydralazine: 10 mg orally three to four times daily initially, adjust dose gradually according to response, maximum 300 mg/day

OR

minoxidil: 5 mg orally once daily initially, adjust dose gradually according to response, maximum 40 mg/day

OR

clonidine: 0.1 mg orally (immediate-release) twice daily initially, adjust dose gradually according to response, maximum 0.6 mg/day

Consider – glycemic control

Back
ACUTE
|
GFR category G3 to G4 without uremia
Consider – 

glycemic control

Treatment recommended for SOME patients in selected patient group

In patients with diabetes, glycemic goals should be individualized. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a HbA1c target ranging from <6.5% to <8.0% for patients with diabetes and chronic kidney disease not receiving dialysis. A lower target (e.g., <6.5% or <7.0%) may be appropriate for individuals in whom preventing complications is the key goal, whereas a higher target (e.g., <7.5% or <8.0%) may be preferred in those with multimorbidity or increased burden of hypoglycemia.[20][70]​ In patients with diabetes and CKD, there is a risk for hypoglycemia because of impaired kidney clearance of drugs (such as insulin or sulfonylureas) and impaired kidney gluconeogenesis. 

Patients with type 1 diabetes require treatment with insulin, regardless of whether they are on dialysis or not.

Some specific antihyperglycemic drugs significantly reduce all-cause or cardiovascular mortality, or major cardiovascular events or renal complications in some patient subgroups, and should be considered independently of HbA1c targets.[71][72][73][74][75]

There is evidence that the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors prevents major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease) in people with type 2 diabetes.[66][76][77]​​ SGLT2 inhibitors, in addition to reducing hyperglycemia, have renal benefits through independent effects on renal tubular glucose reabsorption, weight, blood pressure, intraglomerular pressure, albuminuria, and slowed glomerular filtration rate (GFR) loss.[78][79]​

KDIGO guidelines advise that most patients with type 2 diabetes and CKD would benefit from treatment with metformin (if eGFR ≥30 mL/minute/1.73 m²) and an SGLT2 inhibitor (if eGFR ≥20 mL/minute/1.73 m²).[20]​ The American Diabetes Association recommends the use of SGLT2 inhibitors in patients with CKD and type 2 diabetes (if eGFR ≥20 mL/minute/1.73 m²) regardless of urinary albuminuria.[63] Use of SGLT2 inhibitors is not recommended in patients with end-stage renal disease who are on dialysis.[80] 

If additional glycemic control is required for patients receiving metformin and an SGLT2 inhibitor, a drug from a different class should be selected. A glucagon-like peptide-1 (GLP-1) is the preferred option. If required, other agents (e.g., a dipeptidyl peptidase-4 [DPP-4] inhibitor, a sulfonylurea, insulin, a thiazolidinedione, or an alpha-glucosidase inhibitor) may be considered based on eGFR, comorbidities, and patient preference.[20]

As a class of drugs, GLP-1 agonists have beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes.[81][82]​ GLP-1 agonists may be considered to achieve glycemic targets and for cardiovascular risk reduction.[63] 

Liraglutide, dulaglutide, and semaglutide are not renally excreted and are the preferred agents in this class.

Studies report that DPP-4 inhibitors are renoprotective, but do not have a cardiovascular benefit.[83][84]​ Some DPP-4 inhibitors require dose adjustment in renal impairment. 

Consider – finerenone

Back
ACUTE
|
GFR category G3 to G4 without uremia
Consider – 

finerenone

Treatment recommended for SOME patients in selected patient group

Finerenone, a nonsteroidal selective mineralocorticoid receptor antagonist, reduces the progression of kidney disease in patients with type 2 diabetes mellitus and known CKD.[85] Finerenone is approved by the Food and Drug Administration to reduce the risk of kidney function decline, kidney failure, cardiovascular death, nonfatal heart attacks, and hospitalization for heart failure in adults with CKD associated with type 2 diabetes.

Guidelines recommend finerenone for patients with type 2 diabetes and albuminuria, despite maximum tolerated dose of an ACE inhibitor or an angiotensin-II receptor antagonist (if eGFR is ≥25 mL/minute/1.73 m² and serum potassium level is normal).[20][63] Finerenone can be added to an sodium-glucose cotransporter-2 (SGLT2) inhibitor and an ACE inhibitor or an angiotensin-II receptor antagonist.

Monitor serum potassium levels during treatment, and use caution when administering with other drugs that increase serum potassium levels.

Primary options

finerenone: 20 mg orally once daily

Consider – education about renal replacement therapy

Back
ACUTE
|
GFR category G3 to G4 without uremia
Consider – 

education about renal replacement therapy

Treatment recommended for SOME patients in selected patient group

Educate patients about renal replacement therapy such as hemodialysis, peritoneal dialysis, and kidney transplantation.[102][117]​ Patient preference, family support, underlying comorbid conditions, and proximity to a dialysis facility should be addressed when choosing a modality or consideration for palliative care. All patients should undergo CKD education for modality choice.[102]

Patients should be referred to surgery for dialysis access and/or evaluated for kidney transplantation, based on patient preference for renal replacement modality at glomerular filtration rate (GFR) category G4.

All patients who are proceeding with hemodialysis should be educated on vein preservation with limiting venipuncture and intravenous access to the access arm.[118]

Kidney transplantation is indicated once the estimated GFR is <20 mL/minute and the patient has been evaluated and undergone the required testing process by a transplant team.

2nd line – nondihydropyridine calcium-channel blocker

Back
ACUTE
|
GFR category G3 to G4 without uremia
2nd line – 

nondihydropyridine calcium-channel blocker

If an ACE inhibitor or an angiotensin-II receptor antagonist needs to be discontinued due to adverse effects (such as cough, angioedema, hemodynamic decline in renal function, and/or hyperkalemia), then nondihydropyridine calcium-channel blockers have been demonstrated to have more proteinuric-lowering effects than other antihypertensive agents.[128]

Primary options

diltiazem: 120 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 360 mg/day

OR

verapamil: 120 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 360 mg/day

Consider – sodium-glucose cotransporter-2 (SGLT2) inhibitor

Back
ACUTE
|
GFR category G3 to G4 without uremia
Consider – 

sodium-glucose cotransporter-2 (SGLT2) inhibitor

Treatment recommended for SOME patients in selected patient group

SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin) can preserve kidney function by reducing intraglomerular pressure independently of blood pressure (BP) and glucose control.[64][65][66][71]

There is evidence that the use of SGLT2 inhibitors prevents major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease) in people with type 2 diabetes.[66][76][77] SGLT2 inhibitors, in addition to reducing hyperglycemia, have renal benefits through independent effects on renal tubular glucose reabsorption, weight, BP, intraglomerular pressure, albuminuria, and slowed GFR loss.[78][79] 

SGLT2 inhibitors are recommended for the treatment of CKD, particularly in adults at risk of progression, in combination with an ACE inhibitor or an angiotensin-II receptor antagonist. BMJ Rapid Recommendation: SGLT2-inhibitors for adults with CKD Opens in new window

Recommendations for the use of SGLT2 inhibitors in patients with different degrees of kidney disease may vary; consult your local drug information source for more information.

Use of SGLT2 inhibitors is not recommended in patients with end-stage renal disease who are on dialysis.[80]

Primary options

dapagliflozin: 10 mg orally once daily

OR

empagliflozin: 10 mg orally once daily

OR

canagliflozin: 100-300 mg orally once daily

Plus – statin ± ezetimibe

Back
ACUTE
|
GFR category G3 to G4 without uremia
Plus – 

statin ± ezetimibe

Treatment recommended for ALL patients in selected patient group

Statin therapy has been shown to have cardioprotective effects in patients with CKD.[94][95][96][97] In those individuals not on dialysis therapy, the use of statins in a large meta-analysis resulted in the reduction of all-cause mortality by 21% (relative risk [RR] 0.79, 95% CI 0.69 to 0.91) and cardiovascular mortality by 23% (RR 0.77, 95% CI 0.69 to 0.87).[98]

Kidney Disease: Improving Global Outcomes guidelines recommend that GFR category G3 or G4 CKD patients not on dialysis should be treated with a statin without the need for routine follow-up to check lipid values, or to change dose regimen based on set targets (i.e., a "treat and forget" approach).[67] For patients ages ≥50 years with CKD GFR category G3 or G4, ezetimibe can be added to simvastatin.[68]

Statin therapy has been associated with liver dysfunction and myopathy and should be monitored in patients with CKD.

Primary options

simvastatin: 20-40 mg orally once daily

OR

pravastatin: 40 mg orally once daily

OR

rosuvastatin: 5-10 mg orally once daily

OR

atorvastatin: 10-20 mg orally once daily

OR

ezetimibe/simvastatin: 10 mg (ezetimibe)/20 mg (simvastatin) orally once daily

Consider – additional antihypertensive therapy

Back
ACUTE
|
GFR category G3 to G4 without uremia
Consider – 

additional antihypertensive therapy

Treatment recommended for SOME patients in selected patient group

Hypertension is one of the greatest risk factors for the progression of CKD, regardless of the underlying etiology of CKD. Most patients with CKD will require at least two or three different types of antihypertensive agent to achieve the optimal BP control. A combination of antihypertensive agents should be used. ACE inhibitors and angiotensin-II receptor antagonists should not be combined within the same regimen.[64]​​​​

Other classes of antihypertensive agents (e.g., thiazide, or thiazide-like diuretics, beta-blockers, dihydropyridine calcium-channel blockers, aldosterone antagonists, vasodilators, alpha-2 adrenergic agonists) should be added when the target blood pressure is not achieved with the use of a nondihydropyridine calcium-channel blocker, or if there are other specific clinical indications, such as beta-blockers for angina pectoris.[64]

Primary options

chlorthalidone: 12.5 to 25 mg orally once daily initially, adjust dose gradually according to response, maximum 50 mg/day

OR

hydrochlorothiazide: 12.5 mg orally once daily initially, adjust dose gradually according to response, maximum 50 mg/day

OR

atenolol: 25 mg orally once daily initially, adjust dose gradually according to response, maximum 25-50 mg/day

OR

metoprolol succinate: 25 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 100 mg/day

OR

nifedipine: 30-60 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 90 mg/day (120 mg/day for some brands)

OR

amlodipine: 5 mg orally once daily initially, adjust dose gradually according to response, maximum 10 mg/day

OR

felodipine: 2.5 mg orally once daily initially, adjust dose gradually according to response, maximum 20 mg/day

OR

spironolactone: 12.5 mg orally once daily initially, adjust dose gradually according to response, maximum 200 mg/day given in 2-4 divided doses

OR

aliskiren: 150 mg orally once daily initially, adjust dose gradually according to response, maximum 300 mg/day

Secondary options

hydralazine: 10 mg orally three to four times daily initially, adjust dose gradually according to response, maximum 300 mg/day

OR

minoxidil: 5 mg orally once daily initially, adjust dose gradually according to response, maximum 40 mg/day

OR

clonidine: 0.1 mg orally (immediate-release) twice daily initially, adjust dose gradually according to response, maximum 0.6 mg/day

Consider – glycemic control

Back
ACUTE
|
GFR category G3 to G4 without uremia
Consider – 

glycemic control

Treatment recommended for SOME patients in selected patient group

In patients with diabetes, glycemic goals should be individualized. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a HbA1c target ranging from <6.5% to <8.0% for patients with diabetes and chronic kidney disease not receiving dialysis. A lower target (e.g., <6.5% or <7.0%) may be appropriate for individuals in whom preventing complications is the key goal, whereas a higher target (e.g., <7.5% or <8.0%) may be preferred in those with multimorbidity or increased burden of hypoglycemia.[20][70]​ In patients with diabetes and CKD, there is a risk for hypoglycemia because of impaired kidney clearance of drugs (such as insulin or sulfonylureas) and impaired kidney gluconeogenesis. 

Patients with type 1 diabetes require treatment with insulin, regardless of whether they are on dialysis or not.

Some specific antihyperglycemic drugs significantly reduce all-cause or cardiovascular mortality, or major cardiovascular events or renal complications in some patient subgroups, and should be considered independently of HbA1c targets.[71][72][73][74][75]

There is evidence that the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors prevents major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease) in people with type 2 diabetes.[66][76][77]​ SGLT2 inhibitors, in addition to reducing hyperglycemia, have renal benefits through independent effects on renal tubular glucose reabsorption, weight, blood pressure, intraglomerular pressure, albuminuria, and slowed glomerular filtration rate (GFR) loss.[78][79]​ 

KDIGO guidelines advise that most patients with type 2 diabetes and CKD would benefit from treatment with metformin (if eGFR ≥30 mL/minute/1.73 m²) and an SGLT2 inhibitor (if eGFR ≥20 mL/minute/1.73 m²).[20]​ The American Diabetes Association recommends the use of SGLT2 inhibitors in patients with CKD and type 2 diabetes (if eGFR ≥20 mL/minute/1.73 m²) regardless of urinary albuminuria.[63] Use of SGLT2 inhibitors is not recommended in patients with end-stage renal disease who are on dialysis.[80] 

If additional glycemic control is required for patients receiving metformin and an SGLT2 inhibitor, a drug from a different class should be selected. A glucagon-like peptide-1 (GLP-1) is the preferred option. If required, other agents (e.g., a dipeptidyl peptidase-4 [DPP-4] inhibitor, a sulfonylurea, insulin, a thiazolidinedione, or an alpha-glucosidase inhibitor) may be considered based on eGFR, comorbidities, and patient preference.[20]

As a class of drugs, GLP-1 agonists have beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes.[81][82] GLP-1 agonists may be considered for cardiovascular risk reduction.[63]​ 

Liraglutide, dulaglutide, and semaglutide are not renally excreted and are the preferred agents in this class.

Studies report that DPP-4 inhibitors are renoprotective, but do not have a cardiovascular benefit.[83][84]​ Some DPP-4 inhibitors require dose adjustment in renal impairment.

Consider – finerenone

Back
ACUTE
|
GFR category G3 to G4 without uremia
Consider – 

finerenone

Treatment recommended for SOME patients in selected patient group

Finerenone, a nonsteroidal selective mineralocorticoid receptor antagonist, reduces the progression of kidney disease in patients with type 2 diabetes mellitus and known CKD.[85]​ Finerenone is approved by the Food and Drug Administration to reduce the risk of kidney function decline, kidney failure, cardiovascular death, nonfatal heart attacks, and hospitalization for heart failure in adults with CKD associated with type 2 diabetes.

Guidelines recommend finerenone for patients with type 2 diabetes and albuminuria (if eGFR is ≥25 mL/minute/1.73 m² and serum potassium level is normal).[20][63]​​

Monitor serum potassium levels during treatment, and use caution when administering with other drugs that increase serum potassium levels.

Primary options

finerenone: 20 mg orally once daily

Consider – education about renal replacement therapy

Back
ACUTE
|
GFR category G3 to G4 without uremia
Consider – 

education about renal replacement therapy

Treatment recommended for SOME patients in selected patient group

Educate patients about renal replacement therapy such as hemodialysis, peritoneal dialysis, and kidney transplantation.[102][117] Patient preference, family support, underlying comorbid conditions, and proximity to a dialysis facility should be addressed when choosing a modality or consideration for palliative care. All patients should undergo CKD education for modality choice.[102]

Patients should be referred to surgery for dialysis access and/or evaluated for kidney transplantation, based on patient preference for renal replacement modality at GFR category G4.

All patients who are proceeding with hemodialysis should be educated on vein preservation with limiting venipuncture and intravenous access to the access arm.[118]

Kidney transplantation is indicated once the estimated GFR is <20 mL/minute and the patient has been evaluated and undergone the required testing process by a transplant team.

Consider – erythropoietin-stimulating agent

Back
ACUTE
|
GFR category G3 to G4 without uremia
|
with anemia
Consider – 

erythropoietin-stimulating agent

Treatment recommended for SOME patients in selected patient group

When GFR category G3a/G3b has been reached, identification of comorbidities such as anemia is recommended and treatment begun if required.

Treatment of anemia with the use of erythropoietin-stimulating agents is recommended for patients with CKD after other causes of anemia such as iron, vitamin B12, folate, or blood loss have been excluded.[104] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ]

Due to the possibility of an increased risk of stroke in those on erythropoietin-stimulating agents, discussion between the patient and physician should ensue prior to treatment initiation.[104][107][109][110]

Erythropoietin-stimulating agents are initiated once the hemoglobin (Hb) falls to <10 g/dL and the patient has signs and symptoms of anemia.

The target Hb for patients with CKD on erythropoietin therapy is 10-11 g/dL, as normalization of Hb has resulted in increased risk for death and cardiovascular disease in this population.[105][106]

Primary options

epoetin alfa: consult specialist for guidance on dose

OR

darbepoetin alfa: consult specialist for guidance on dose

Consider – iron

Back
ACUTE
|
GFR category G3 to G4 without uremia
|
with anemia
Consider – 

iron

Treatment recommended for SOME patients in selected patient group

All patients should have an evaluation of iron stores if erythropoietin therapy is planned. The goal ferritin for those not on hemodialysis is >100 nanograms/mL, while for those on hemodialysis is >200 nanograms/mL. All patients should have a transferrin saturation >20%. Iron replacement can be given orally or parenterally.[111][129]

Primary options

ferrous sulfate: 60 mg orally once to three times daily

More

OR

ferrous gluconate: 60 mg orally once to three times daily

More

Secondary options

sodium ferric gluconate complex: consult specialist for guidance on dose

OR

iron sucrose: consult specialist for guidance on dose

OR

ferumoxytol: consult specialist for guidance on dose

OR

ferric carboxymaltose: consult specialist for guidance on dose

Plus – dietary modification ± phosphate-binding drug

Back
ACUTE
|
GFR category G3 to G4 without uremia
|
with secondary hyperparathyroidism
Plus – 

dietary modification ± phosphate-binding drug

Treatment recommended for ALL patients in selected patient group

When GFR category G3a/G3b has been reached, identification of comorbidities such as secondary hyperparathyroidism is recommended and treatment begun if required. The calcium and phosphorus levels should be maintained in the normal range with dietary restriction and/or phosphate-binding drugs.

Phosphate binders should be initiated to normalize phosphorus levels if patients are unable to sufficiently restrict phosphorus in the diet.[114] [ Cochrane Clinical Answers logo ] Calcium-based phosphate binders should be restricted if there is associated hypercalcemia, arterial calcification, suppressed parathyroid hormone (PTH), or adynamic bone disease.[114]

Calcium, phosphorus, and PTH testing should be performed every 6 to 12 months for patients with GFR category G3a/G3b CKD and secondary hyperparathyroidism. For patients with GFR category G4 CKD and secondary hyperparathyroidism, calcium and phosphate should be checked every 3 to 6 months, and PTH every 6 to 12 months.[114][Evidence C]

There is limited evidence that dietary restriction in calcium and phosphorus affects renal osteodystrophy.[130]

There is emerging evidence that the use of noncalcium-based phosphate binders has a survival advantage over calcium-based phosphate binders in patients with CKD.[114][116][Evidence B]

Primary options

sevelamer hydrochloride: 800-1600 mg orally three times daily initially, titrate according to serum phosphate level

OR

calcium acetate: 1334 mg orally with each meal initially, titrate according to serum phosphate level

OR

calcium carbonate: 1-2 g/day orally given in 3-4 divided doses

OR

lanthanum: 500-1000 mg orally three times daily initially, titrate according to serum phosphate level

OR

sucroferric oxyhydroxide: 500 mg orally three times daily initially, titrate according to serum phosphate level, maximum 3000 mg/day

Consider – ergocalciferol

Back
ACUTE
|
GFR category G3 to G4 without uremia
|
with secondary hyperparathyroidism
Consider – 

ergocalciferol

Treatment recommended for SOME patients in selected patient group

25-OH vitamin D deficiency should be excluded. If the serum level of 25-OH vitamin D is <30 nanograms/mL, vitamin D supplementation with ergocalciferol should be initiated.[112]​[113]​

Primary options

ergocalciferol (vitamin D2): dose depends on serum 25-OH vitamin D level; consult specialist for guidance on dose

Consider – active vitamin D analog

Back
ACUTE
|
GFR category G3 to G4 without uremia
|
with secondary hyperparathyroidism
Consider – 

active vitamin D analog

Treatment recommended for SOME patients in selected patient group

It is not routinely recommended to use active vitamin D analogs for CKD not requiring dialysis unless hyperparathyroidism is progressive or severe.[114]

The optimal parathyroid hormone level is currently not known.

Primary options

calcitriol: consult specialist for guidance on dose

OR

paricalcitol: consult specialist for guidance on dose

OR

doxercalciferol: consult specialist for guidance on dose

Consider – oral sodium bicarbonate

Back
ACUTE
|
GFR category G3 to G4 without uremia
|
with metabolic acidosis
Consider – 

oral sodium bicarbonate

Treatment recommended for SOME patients in selected patient group

For patients who develop metabolic acidosis, supplementation with oral sodium bicarbonate has been shown to slow progression of CKD.[119] Oral sodium bicarbonate is well tolerated in this group.

Primary options

sodium bicarbonate: consult specialist for guidance on dose

GFR category G5 or with uremia

1st line – dialysis

Back
ACUTE
|
GFR category G5 or with uremia
1st line – 

dialysis

Renal replacement therapy is initiated once patients have GFR category G5 disease and/or signs of uremia such as weight loss, lack of appetite, nausea, vomiting, acidosis, hyperkalemia, or fluid overload.[1]

Renal replacement therapy in the form of dialysis is designed to remove toxic waste products from the blood, such as urea, and normalise potassium and serum bicarbonate levels, as well as to remove fluid that will accumulate once the kidneys have failed.

All patients should undergo CKD education for modality choice.[102]

Peritoneal dialysis is performed at home and is available to all patients. A peritoneal dialysis catheter is inserted into the abdomen and dialysis fluid is instilled in order to allow for toxic waste products and fluid to be removed and drained from the body on a daily basis. [ Cochrane Clinical Answers logo ]

Continuous cycling peritoneal dialysis is done with a machine at night on a daily basis.

Continuous ambulatory peritoneal dialysis is done on a daily basis. Patients manually exchange the peritoneal fluid.

Hemodialysis is usually prescribed in a treatment center 3 times a week for approximately 4 hours each session. Hemodialysis can also be carried out at home, usually 4 to 5 days a week, 3 to 4 hours a day. The patient's blood is removed from the body through an arteriovenous fistula, an arteriovenous graft, or a dialysis catheter, and then returned after traversing a dialysis membrane and dialysis solution. Other dialysis options include short daily dialysis and nocturnal dialysis, which are available at some treatment centers.

2nd line – kidney transplant

Back
ACUTE
|
GFR category G5 or with uremia
2nd line – 

kidney transplant

Kidney transplant confers a significant survival advantage over maintenance dialysis therapy, predominantly due to a decrease in the risk of cardiovascular death. All patients who are on dialysis therapy are potentially eligible for kidney transplantation. A transplant center including a nephrologist and transplant surgeon will determine the final eligibility and status of the patient for kidney transplantation, after a complete medical history and evaluation. Kidneys may be transplanted from deceased or living donors.

Consider – erythropoietin-stimulating agent

Back
ACUTE
|
GFR category G5 or with uremia
|
with anemia
Consider – 

erythropoietin-stimulating agent

Treatment recommended for SOME patients in selected patient group

Treatment of anemia with the use of erythropoietin-stimulating agents is recommended for patients with CKD after other causes of anemia such as iron, vitamin B12, folate, or blood loss have been excluded.[104] [ Cochrane Clinical Answers logo ] Due to the possibility of an increased risk of stroke in those on erythropoietin-stimulating agents, discussion between the patient and physician should ensue prior to treatment initiation.[104][107][109][110]

Erythropoietin-stimulating agents are initiated once the hemoglobin (Hb) falls to <10 g/dL and the patient has signs and symptoms of anemia.

The target Hb for patients with CKD on erythropoietin therapy is 10-11 g/dL, as normalization of Hb has resulted in increased risk for death and cardiovascular disease in this population.[105][106]

Primary options

epoetin alfa: consult specialist for guidance on dose

OR

darbepoetin alfa: consult specialist for guidance on dose

Consider – iron

Back
ACUTE
|
GFR category G5 or with uremia
|
with anemia
Consider – 

iron

Treatment recommended for SOME patients in selected patient group

All patients should have an evaluation of iron stores if erythropoietin therapy is planned. The goal ferritin for those not on hemodialysis is >100 nanograms/mL, while for those on hemodialysis it is >200 nanograms/mL. All patients should have a transferrin saturation >20%. Iron replacement can be given orally or parenterally.[111][129] Oral iron will be sufficient to maintain and attain the Hb within targets in erythropoietin-stimulating agent-treated CKD patients on peritoneal dialysis; however, most patients on hemodialysis will require intravenous iron.[131]

Primary options

ferrous sulfate: 60 mg orally once to three times daily

More

OR

ferrous gluconate: 60 mg orally once to three times daily

More

OR

sodium ferric gluconate complex: consult specialist for guidance on dose

OR

iron sucrose: consult specialist for guidance on dose

OR

ferumoxytol: consult specialist for guidance on dose

OR

ferric carboxymaltose: consult specialist for guidance on dose

OR

ferric pyrophosphate citrate: consult specialist for guidance on dose

Plus – dietary modification ± phosphate-binding drug

Back
ACUTE
|
GFR category G5 or with uremia
|
with secondary hyperparathyroidism
Plus – 

dietary modification ± phosphate-binding drug

Treatment recommended for ALL patients in selected patient group

For patients with GFR category G5 CKD on dialysis, calcium, phosphorus, and intact parathyroid hormone (PTH) levels should be managed with phosphate binding agents, calcimimetics, active vitamin D analogs, or a combination of these based on serial laboratory assessments.

Phosphate binders such as calcium, lanthanum, and sevelamer should be initiated to normalize phosphorus levels if patients are unable to sufficiently restrict phosphorus in the diet.[114] [ Cochrane Clinical Answers logo ]  Calcium-based phosphate binders should be restricted if there is associated hypercalcemia, arterial calcification, suppressed PTH, or adynamic bone disease.[114]

Increasing dialytic phosphate removal may be required in cases of persistent hyperphosphatemia.

Calcium and phosphorus testing every 1 to 3 months and PTH testing every 3 to 6 months should be performed for patients with GFR category G5 CKD and secondary hyperparathyroidism.[114][Evidence C]

Primary options

sevelamer hydrochloride: 800-1600 mg orally three times daily initially, titrate according to serum phosphate level

OR

calcium acetate: 1334 mg orally with each meal initially, titrate according to serum phosphate level

OR

calcium carbonate: 1-2 g/day orally given in 3-4 divided doses

OR

lanthanum: 500-1000 mg orally three times daily initially, titrate according to serum phosphate level

OR

sucroferric oxyhydroxide: 500 mg orally three times daily initially, titrate according to serum phosphate level, maximum 3000 mg/day

Consider – calcimimetic ± active vitamin D analog

Back
ACUTE
|
GFR category G5 or with uremia
|
with secondary hyperparathyroidism
Consider – 

calcimimetic ± active vitamin D analog

Treatment recommended for SOME patients in selected patient group

For those requiring parathyroid hormone (PTH)-lowering therapy, calcimimetics (e.g., cinacalcet, etelcalcetide), active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol), or a combination of a calcimimetic with an active vitamin D analog should be given.[114]

Etelcalcetide is a second-generation, type II calcimimetic that may be used when treatment with a calcimimetic is indicated but cinacalcet is not a suitable option. It is given intravenously (rather than orally like cinacalcet) and has a longer half-life than cinacalcet.

Primary options

cinacalcet: 30 mg orally once daily initially, increase dose according to serum PTH level, maximum 180 mg/day

-- AND / OR --

calcitriol: consult specialist for guidance on dose

or

paricalcitol: consult specialist for guidance on dose

or

doxercalciferol: consult specialist for guidance on dose

Secondary options

etelcalcetide: adults: 5 mg intravenously three times weekly at the end of hemodialysis treatment, adjust dose according to PTH level and corrected serum calcium response, maintenance dose ranges from 2.5 to 15 mg three times weekly

-- AND / OR --

calcitriol: consult specialist for guidance on dose

or

paricalcitol: consult specialist for guidance on dose

or

doxercalciferol: consult specialist for guidance on dose

Consider – ergocalciferol

Back
ACUTE
|
GFR category G5 or with uremia
|
with secondary hyperparathyroidism
Consider – 

ergocalciferol

Treatment recommended for SOME patients in selected patient group

25-OH vitamin D deficiency should be excluded. If the serum level of 25-OH vitamin D is <30 nanograms/mL, vitamin D supplementation with ergocalciferol should be initiated.[112]​[113]​

Primary options

ergocalciferol (vitamin D2): dose depends on serum 25-OH vitamin D level; consult specialist for guidance on dose

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