Treatment algorithm

Your Organisational Guidance

ebpracticenet urges you to prioritise the following organisational 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

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

Back
ACUTE
|
GFR category G1 to G2
1st line – 

ACE inhibitor or angiotensin-II receptor antagonist

Renin-angiotensin system (RAS) blockade (e.g., with an ACE inhibitor or an angiotensin-II receptor antagonist) can preserve kidney function by reducing intra-glomerular pressure, independently of blood pressure (BP) and glucose control.​​[60][81][83]​​​​​

ACE inhibitors and angiotensin-II receptor antagonists slow the progression of chronic kidney disease (CKD) and delay the need for kidney replacement therapy in both diabetic and non-diabetic CKD.[119][120][121]

An ACE inhibitor or angiotensin-II receptor antagonist is recommended for patients with CKD (with or without diabetes) who have severely increased albuminuria (albumin to creatinine ratio [ACR] ≥30 mg/mmol [≥300 mg/g]), even in the absence of high BP.[1]​ If albuminuria is moderately increased (ACR ≥3 mg/mmol [≥30 mg/g]), an ACE inhibitor or angiotensin-II receptor antagonist is recommended in patients with diabetes, and should be considered for those without diabetes.[1] Patients with CKD and high BP or heart failure may receive an ACE inhibitor or angiotensin-II receptor antagonist regardless of albuminuria.[1]

ACE inhibitors or angiotensin-II receptor antagonists should be used at the highest tolerated dose to maximise benefits.[1] Monitor BP, serum creatinine, and potassium within 2-4 weeks. Hyperkalaemia should be managed without reducing the dose or discontinuation of the ACE inhibitor or angiotensin-II receptor antagonist, if possible. Continue treatment even if the estimated GFR (eGFR) decreases to <30 mL/minute/1.73 m².[1][87]​​​​​

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: 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

Plus – lifestyle and dietary measures

Back
ACUTE
|
GFR category G1 to G2
Plus – 

lifestyle and dietary measures

Treatment recommended for ALL patients in selected patient group

Tobacco cessation and maintaining a healthy weight are recommended. Physical activity (e.g., moderate-intensity physical activity for at least 150 minutes per week), adopting a healthy diet, and achieving a healthy weight should be encouraged.[1]​​[54][169]​​​​ Evidence for cardiovascular or mortality benefit from weight loss interventions, including lifestyle changes, appetite-suppressing drugs, and weight-loss surgery, is lacking. However, general health benefits and improvement in body weight are likely.[170]

Individualised dietary education (including advice on sodium, phosphorus, potassium, and protein intake) should be considered for patients with CKD.[1] Guidelines suggest that patients at risk of progression should avoid high protein intake.​[80][92]​​​​ Severe protein restriction should not be recommended until late GFR category G4 or G5 disease as a management strategy to delay the initiation of dialysis.[171]​ Severe protein restriction may result in malnourishment and poorer outcomes.[172]

For patients with CKD and high blood pressure, reducing sodium intake to <2 g per day (equivalent to <5 g of sodium chloride per day) is suggested.[81]

Consider – sodium-glucose co-transporter-2 (SGLT2) inhibitor

Back
ACUTE
|
GFR category G1 to G2
Consider – 

sodium-glucose co-transporter-2 (SGLT2) inhibitor

Additional treatment recommended for SOME patients in selected patient group

SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin) can preserve kidney function by reducing intra-glomerular pressure independently of blood pressure (BP) and glucose control.​[60][81][82]​​​​​​

SGLT2 inhibitors are recommended for the treatment of chronic kidney disease (CKD), particularly in patients 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

Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend SGLT2 inhibitors for patients with CKD (if estimated GFR [eGFR] level ≥20 mL/minute/1.73 m²) and increased albuminuria (albumin to creatinine ratio [ACR] ≥20 mg/mmol [≥200 mg/g]), or type 2 diabetes, or heart failure. SGLT2 treatment should be considered for patients with ACR <20 mg/mmol (<200 mg/g) and eGFR level 20-45 mL/minute/1.73 m².[1]

Use of SGLT2 inhibitors is not generally recommended in patients with an eGFR of <20 mL/minute/1.73 m².[1][80]​​​​ However, renal and cardiovascular benefits with SGLT2 therapy are seen at eGFR levels as low as 20 mL/minute/1.73 m²; if tolerated, SGLT2 therapy may continue at eGFR levels below 20 mL/minute/1.73 m² unless kidney replacement therapy is started.[1]

Use of SGLT2 inhibitors is not recommended in patients with end-stage kidney disease who are on dialysis.[105]

Primary options

dapagliflozin: 10 mg orally once daily

OR

empagliflozin: 10 mg orally once daily

OR

canagliflozin: 100-300 mg orally once daily

Consider – statin

Back
ACUTE
|
GFR category G1 to G2
Consider – 

statin

Additional treatment recommended for SOME patients in selected patient group

Statins are recommended for patients with chronic kidney disease (CKD) (not on kidney replacement therapy) aged ≥50 years, and those aged <50 years with additional cardiovascular risk factors.[1]

Statin therapy has been shown to have cardioprotective effects in patients with CKD.[88][89][90][91]​​​​ One large meta-analysis reported that statins reduce death and major cardiovascular events by about 20% in patients with CKD not requiring dialysis, including patients without existing cardiovascular disease.[125]​ There was no difference in adverse effects for statin users compared with those in the placebo arms. The use of statins did not reduce the risk of stroke or kidney failure.[125]

Kidney Disease: Improving Global Outcomes guidelines recommend that CKD patients not on dialysis should start treatment with a statin without the need for routine follow-up to check lipid values, or to change treatment regimen based on set targets (i.e., a 'treat and forget' approach).[84]

For patients aged ≥50 years with CKD GFR category G1 or G2, a statin is recommended.[1][124]​​​​​ For patients aged 18-49 years with CKD, statin treatment is recommended in the presence of known coronary disease, diabetes mellitus, prior ischaemic stroke, or estimated 10-year incidence of coronary death or non-fatal myocardial infarction >10%.[1]

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
Consider – 

additional antihypertensive therapy

Additional treatment recommended for SOME patients in selected patient group

Hypertension is one of the most important risk factors for the progression of chronic kidney disease (CKD), regardless of aetiology. Most patients with CKD will require at least two or three different types of antihypertensive agent to achieve optimal blood pressure (BP) control.

An individualised approach should be used for BP targets, taking into account age, comorbidities, risk of progression of CKD, and tolerance to treatments.[1]​ Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest a target systolic BP of less than 120 mmHg, if tolerated, in patients with CKD, with and without diabetes, and not receiving dialysis.[1][81]​​​​[113][114]​​​ Clinic BP measurement must be standardised when using this target. Less intensive BP-lowering therapy may be considered for specific patients, such as those with frailty, high risk of fracture and falls, postural hypotension, or limited life expectancy.[1] Certain guidelines advocate less intensive BP targets, which might be more achievable.[54][115]

There may be benefit in strict BP control to reduce the relative risk of death, and delay the onset of end-stage kidney disease, particularly in some subgroups of patients with CKD.[116][117]​​​ However, one Cochrane systematic review suggests little to no difference in outcomes between standard (≤140 to 160/90 to 100 mmHg) and low (≤130/80 mmHg) BP targets in people with CKD.[118]

A combination of antihypertensive agents is often needed to meet the target BP goal, but ACE inhibitors and angiotensin-II receptor antagonists should not be combined within the same regimen.[81]​​​​​​

Other classes of antihypertensive agents should be added when the target BP is not achieved with the use of an ACE inhibitor or an angiotensin-II receptor antagonist.[81]

Evidence supporting the choice of additional antihypertensive agents in patients with CKD is lacking. KDIGO guidelines suggest adding a calcium-channel blocker (e.g., nifedipine, amlodipine, felodipine) and/or a thiazide-like diuretic (e.g., chlortalidone, hydrochlorothiazide), based on evidence of improved cardiovascular outcomes in primary hypertension. Non-dihydropyridine calcium-channel blockers (e.g., diltiazem, verapamil) may have the additional benefit of reducing proteinuria.[81][123]​​​​

If BP cannot be controlled with a combination of three drugs (ACE inhibitor or angiotensin-II receptor antagonist, calcium-channel blocker, and diuretic), then additional agents may be considered, including: aldosterone antagonists (e.g., spironolactone), alpha-blockers (e.g., prazosin), beta-blockers (e.g., atenolol, metoprolol), hydralazine, minoxidil, or centrally acting agents (e.g., clonidine).[81] Note that some agents may be recommended for specific indications, such as beta-blockers for angina pectoris.[81]

Primary options

chlortalidone: 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

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

diltiazem: 60-120 mg orally (extended-release) twice daily initially, adjust dose gradually according to response, maximum 360 mg/day

OR

verapamil: 80 mg orally (immediate-release) three times daily initially, adjust dose gradually according to response, maximum 480 mg/day; 180 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 480 mg/day given in 1-2 divided doses

Secondary options

spironolactone: 12.5 mg orally (tablet) once daily initially, adjust dose gradually according to response, maximum 100 mg/day given in 1-2 divided doses

OR

prazosin: 1 mg orally two to three times daily initially, adjust dose gradually according to response, maximum 20 mg/day

OR

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

OR

metoprolol: 25 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 400 mg/day

OR

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

Plus – glycaemic control

Back
ACUTE
|
GFR category G1 to G2
|
with diabetes
Plus – 

glycaemic control

Treatment recommended for ALL patients in selected patient group

In patients with diabetes, glycaemic goals should be individualised. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend an HbA1c target ranging from <48 mmol/mol to <64 mmol/mol (<6.5% to <8.0%) for patients with diabetes and chronic kidney disease (CKD) not receiving dialysis. A lower target (e.g., <48 mmol/mol or <53 mmol/mol [<6.5% or <7.0%]) may be appropriate for individuals in whom preventing complications is the key goal, whereas a higher target (e.g., <58 mmol/mol or <64 mmol/mol [<7.5% or <8.0%]) may be preferred in those with multimorbidity or increased burden of hypoglycaemia.[92][93]​​​​​​ In patients with diabetes and CKD, there is a risk for hypoglycaemia because of impaired kidney clearance of drugs (such as insulin or sulfonylureas) and because of impaired kidney gluconeogenesis.

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

In patients with type 2 diabetes, some specific anti-hyperglycaemic drugs significantly reduce all-cause or cardiovascular mortality, or major cardiovascular events or kidney complications, in some patient subgroups, and should be considered independently of HbA1c targets.[94][95][96][97][98]

A sodium-glucose co-transporter-2 (SGLT2) inhibitor is recommended for glycaemic control in type 2 diabetes to reduce kidney disease progression. SGLT2 inhibitors prevent major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease) and cardiovascular events in people with type 2 diabetes.[82][99]​​[100]​​​​​[101][102]​​​​​ Renoprotection attributable to SGLT2 inhibition involves glucose-dependent and independent effects.[103][104]​​​​​​

KDIGO guidelines advise that most patients with type 2 diabetes and CKD would benefit from treatment with metformin (if estimated GFR [eGFR] ≥30 mL/minute/1.73 m²) and an SGLT2 inhibitor (if eGFR ≥20 mL/minute/1.73 m²).[92] 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.[80]

Use of SGLT2 inhibitors is not generally recommended in patients with an eGFR of <20 mL/minute/1.73 m².[1][80]​​​​​ However, renal and cardiovascular benefits with SGLT2 therapy are seen at eGFR levels as low as 20 mL/minute/1.73 m²; if tolerated, SGLT2 therapy may continue at eGFR levels below 20 mL/minute/1.73 m² unless kidney replacement therapy is started.[1][92]​​​ Use of SGLT2 inhibitors is not recommended in patients with end-stage kidney disease who are on dialysis.[105]

If additional glycaemic 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) receptor agonist is the preferred option.[1][92]​​​​ 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.[92]​ GLP-1 receptor agonists and DPP-4 inhibitors should not be used in combination.[92]

GLP-1 receptor agonists have beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes.[106][107][108]​​​​​​ GLP-1 receptor agonists may be considered for cardiovascular risk reduction.[80]

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

DPP-4 inhibitors are renoprotective but do not have a cardiovascular benefit.[109][110][111]​​​​​​​ Some DPP-4 inhibitors require dose adjustment in renal impairment.

Consider – finerenone

Back
ACUTE
|
GFR category G1 to G2
|
with diabetes
Consider – 

finerenone

Additional treatment recommended for SOME patients in selected patient group

Finerenone, a non-steroidal selective mineralocorticoid receptor antagonist, reduces the progression of kidney disease in patients with type 2 diabetes mellitus and known chronic kidney disease (CKD).[112] Finerenone is approved by the US Food and Drug Administration (FDA) to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalisation for heart failure in adults with CKD associated with type 2 diabetes.

Guidelines recommend finerenone for patients with type 2 diabetes and albuminuria (albumin to creatinine ratio [ACR] ≥3 mg/mmol [≥30 mg/g]) despite maximum tolerated dose of a renin-angiotensin system (RAS) inhibitor (if eGFR is ≥25 mL/minute/1.73 m² and serum potassium level is normal).​[80][92]​​​​​ Finerenone can be added to a sodium-glucose co-transporter-2 (SGLT2) inhibitor and an ACE inhibitor or an angiotensin-II receptor antagonist.

Primary options

finerenone: 10-20 mg orally once daily

Consider – weight loss programme

Back
ACUTE
|
GFR category G1 to G2
|
with obesity
Consider – 

weight loss programme

Additional treatment recommended for SOME patients in selected patient group

Advise patients with obesity and chronic kidney disease (CKD) to lose weight.[1]​ Options for weight loss in patients with CKD include lifestyle interventions, pharmacotherapy, and metabolic surgery.[128]

The glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide may have a role in preventing CKD progression in patients with CKD and obesity (independent of diabetes). Improved kidney outcomes have been reported in patients with overweight/obesity and non-diabetic CKD receiving semaglutide.[129][130]​​ Patients with obesity, type 2 diabetes, and CKD may benefit from a GLP-1 receptor agonist for weight loss (in addition to improved cardiovascular and kidney outcomes).[92]

Primary options

semaglutide: 0.25 mg subcutaneously once weekly for 4 weeks, adjust dose gradually according to response, maximum 2.4 mg/week

Consider – antiplatelet agent

Back
ACUTE
|
GFR category G1 to G2
|
with ischaemic heart disease
Consider – 

antiplatelet agent

Additional treatment recommended for SOME patients in selected patient group

Use of low-dose aspirin is recommended for secondary prevention (of cardiovascular disease events) in patients with chronic kidney disease (CKD) and ischaemic cardiovascular disease.[1]​ There is a higher risk for minor bleeding than in the general population. Other antiplatelet agents (e.g., clopidogrel) may be considered for patients with intolerance to aspirin.

When assessing 10-year cardiovascular risk, a validated tool that incorporates CKD should be used to guide treatment for prevention of cardiovascular disease.

Primary options

aspirin: 75-100 mg orally once daily

Secondary options

clopidogrel: 75 mg orally once daily

Consider – revascularisation

Back
ACUTE
|
GFR category G1 to G2
|
with ischaemic heart disease
Consider – 

revascularisation

Additional treatment recommended for SOME patients in selected patient group

In patients with chronic kidney disease (CKD) and stable stress-test confirmed ischaemic heart disease, Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a conservative approach with intensive medical therapy, rather than initial revascularisation, which may increase risk of dialysis initiation, stroke, and death.[1][127]​​​​​ In those with acute or unstable coronary disease, unacceptable levels of angina (e.g., patient dissatisfaction), left ventricular systolic dysfunction attributable to ischaemia, or left main disease, revascularisation should be considered.[1]

GFR category G3 to G4

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

Back
ACUTE
|
GFR category G3 to G4
1st line – 

ACE inhibitor or angiotensin-II receptor antagonist

Renin-angiotensin system (RAS) blockade (e.g., with an ACE inhibitor or an angiotensin-II receptor antagonist) can preserve kidney function by reducing intra-glomerular pressure independently of blood pressure (BP) and glucose control.​​[60][81][83]

ACE inhibitors and angiotensin-II receptor antagonists slow the progression of chronic kidney disease (CKD) and delay the need for kidney replacement therapy in both diabetic and non-diabetic CKD.[119][120][121]

An ACE inhibitor or angiotensin-II receptor antagonist is recommended for patients with CKD (with or without diabetes) who have severely increased albuminuria (albumin to creatinine ratio [ACR] ≥30 mg/mmol [≥300 mg/g]), even in the absence of high BP.[1]​ If albuminuria is moderately increased (ACR ≥3 mg/mmol [≥30 mg/g]), an ACE inhibitor or angiotensin-II receptor antagonist is recommended in patients with diabetes, and should be considered for those without diabetes.[1] Patients with CKD and high BP or heart failure may receive an ACE inhibitor or angiotensin-II receptor antagonist regardless of albuminuria.[1]

ACE inhibitors or angiotensin-II receptor antagonists should be used at the highest tolerated dose to maximise benefits.[1] Monitor BP, serum creatinine, and potassium within 2-4 weeks. Hyperkalaemia should be managed without reducing the dose or discontinuation of the ACE inhibitor or angiotensin-II receptor antagonist, if possible. Continue treatment even if the estimated GFR (eGFR) decreases to <30 mL/minute/1.73 m².[1][87]

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: 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

Plus – lifestyle and dietary measures

Back
ACUTE
|
GFR category G3 to G4
Plus – 

lifestyle and dietary measures

Treatment recommended for ALL patients in selected patient group

Tobacco cessation and maintaining a healthy weight are recommended. Physical activity (e.g., moderate-intensity physical activity for at least 150 minutes per week), adopting a healthy diet, and achieving a healthy weight should be encouraged.[1]​​[54][169]​​​​ Evidence for cardiovascular or mortality benefit from weight loss interventions, including lifestyle changes, appetite-suppressing drugs, and weight-loss surgery, is lacking. However, general health benefits and improvement in body weight are likely.[170]

Individualised dietary education (including advice on sodium, phosphorus, potassium, and protein intake) should be considered for patients with chronic kidney disease (CKD).[1] Guidelines suggest that patients at risk of progression should avoid high protein intake, and that those with G3 or higher category disease with diabetes (not on dialysis) should aim for a target protein intake of 0.8 g/kg body weight per day.​[80][92]​​​​ Severe protein restriction should not be recommended until late GFR category G4 or G5 disease as a management strategy to delay the initiation of dialysis.[171]​ Severe protein restriction may result in malnourishment and poorer outcomes.[172]​ For patients with CKD and high blood pressure, reducing sodium intake to <2 g per day (equivalent to <5 g of sodium chloride per day) is suggested.[81]

Plus – risk assessment and education about kidney replacement therapy

Back
ACUTE
|
GFR category G3 to G4
Plus – 

risk assessment and education about kidney replacement therapy

Treatment recommended for ALL patients in selected patient group

Education can play a significant role in delaying progression of chronic kidney disease (CKD), as well as helping patients understand their options if CKD progresses.[134][135][136]​​​​

Educate patients about kidney replacement therapy such as haemodialysis, peritoneal dialysis, and kidney transplantation.[135][156]​​​​​

Patients should be offered an assessment using a validated risk equation to estimate the absolute risk of kidney failure. This can be used to personalise education, determine the need for referral, and inform plans for future care.[1][137][138][139] The Kidney Failure Risk Equation Opens in new window

[ Kidney Failure Risk (KFRE) (8 variable) Opens in new window ]

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.[135]

Guidelines suggest planning for dialysis or kidney transplantation when GFR is <15-20 mL/minute/1.73 m² or risk of kidney failure is >40% over 2 years.[1]​ Patients should be referred to surgery for dialysis access and/or evaluated for kidney transplantation, based on patient preference for kidney replacement modality.

All patients who are proceeding with haemodialysis should be educated about vein preservation with limiting venipuncture and intravenous access in the access arm.[157]

Consider – sodium-glucose co-transporter-2 (SGLT2) inhibitor

Back
ACUTE
|
GFR category G3 to G4
Consider – 

sodium-glucose co-transporter-2 (SGLT2) inhibitor

Additional treatment recommended for SOME patients in selected patient group

SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin) can preserve kidney function by reducing intra-glomerular pressure independently of blood pressure (BP) and glucose control.​[60][81][82]​​​​​​​​

SGLT2 inhibitors are recommended for the treatment of chronic kidney disease (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

Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend SGLT2 inhibitors for patients with CKD (if estimated GFR [eGFR] level ≥20 mL/minute/1.73 m²) and increased albuminuria (albumin to creatinine ratio [ACR] ≥20 mg/mmol [≥200 mg/g]), or type 2 diabetes, or heart failure. SGLT2 treatment should be considered for patients with ACR <20 mg/mmol (<200 mg/g) and eGFR level 20-45 mL/minute/1.73 m².[1]

Use of SGLT2 inhibitors is not generally recommended in patients with an eGFR of <20 mL/minute/1.73 m².[1][80]​​ However, renal and cardiovascular benefits with SGLT2 therapy are seen at eGFR levels as low as 20 mL/minute/1.73 m²; if tolerated, SGLT2 therapy may continue at eGFR levels below 20 mL/minute/1.73 m² unless kidney replacement therapy is started.[1]

Use of SGLT2 inhibitors is not recommended in patients with end-stage kidney disease who are on dialysis.[105]

Primary options

dapagliflozin: 10 mg orally once daily

OR

empagliflozin: 10 mg orally once daily

OR

canagliflozin: 100-300 mg orally once daily

Consider – statin

Back
ACUTE
|
GFR category G3 to G4
Consider – 

statin

Additional treatment recommended for SOME patients in selected patient group

Statins are recommended for patients with chronic kidney disease (CKD) (not on kidney replacement therapy) aged ≥50 years, and those aged <50 years with additional cardiovascular risk factors.[1]

Statin therapy has been shown to have cardioprotective effects in patients with CKD.[88][89][90][91]​​​​ One large meta-analysis reported that statins reduce death and major cardiovascular events by about 20% in patients with CKD not requiring dialysis, including patients without existing cardiovascular disease.[125]​ There was no difference in adverse effects for statin users compared with those in the placebo arms. The use of statins did not reduce the risk of stroke or kidney failure.[125]

Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend that CKD patients not on dialysis should start treatment with a statin without the need for routine follow-up to check lipid values, or to change treatment regimen based on set targets (i.e., a 'treat and forget' approach).[84]

For patients aged 18-49 years with CKD, statin treatment is recommended in the presence of known coronary disease, diabetes mellitus, prior ischaemic stroke, or estimated 10-year incidence of coronary death or non-fatal myocardial infarction >10%.[1]

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 – ezetimibe

Back
ACUTE
|
GFR category G3 to G4
Consider – 

ezetimibe

Additional treatment recommended for SOME patients in selected patient group

For patients aged ≥50 years with chronic kidney disease (CKD) GFR category G3 or G4, ezetimibe can be combined with a statin.[1]​ The addition of ezetimibe to statin therapy may improve tolerability and reduce the risk of adverse effects in patients with advanced CKD who are less able to tolerate higher doses of statins.[84][85]

Primary options

ezetimibe: 10 mg orally once daily

Consider – additional antihypertensive therapy

Back
ACUTE
|
GFR category G3 to G4
Consider – 

additional antihypertensive therapy

Additional treatment recommended for SOME patients in selected patient group

Hypertension is one of the most important risk factors for the progression of chronic kidney disease (CKD), regardless of aetiology. Most patients with CKD will require at least two or three different types of antihypertensive agent to achieve optimal blood pressure (BP) control.

An individualised approach should be used for BP targets, taking into account age, comorbidities, risk of progression of CKD, and tolerance to treatments.[1]​ Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest a target systolic BP of less than 120 mmHg, if tolerated, in patients with CKD, with and without diabetes, and not receiving dialysis.[1][81][113][114]​​​ Clinic BP measurement must be standardised when using this target. Less intensive BP-lowering therapy may be considered for specific patients, such as those with frailty, high risk of fracture and falls, postural hypotension, or limited life expectancy.[1] Certain guidelines advocate less intensive BP targets, which might be more achievable.[54][115]

There may be benefit in strict BP control to reduce the relative risk of death, and delay the onset of end-stage kidney disease, particularly in some subgroups of patients with CKD.[116][117]​​ However, one Cochrane systematic review suggests little to no difference in outcomes between standard (≤140 to 160/90 to 100 mmHg) and low (≤130/80 mmHg) BP targets in people with CKD.[118]

A combination of antihypertensive agents is often needed to meet the target BP goal, but ACE inhibitors and angiotensin-II receptor antagonists should not be combined within the same regimen.[81]​​​​

Other classes of antihypertensive agents should be added when the target BP is not achieved with the use of an ACE inhibitor or an angiotensin-II receptor antagonist.[81]

Evidence supporting the choice of additional antihypertensive agents in patients with CKD is lacking. KDIGO guidelines suggest adding a calcium-channel blocker (e.g., nifedipine, amlodipine, felodipine) and/or a thiazide-like diuretic (e.g., chlortalidone, hydrochlorothiazide), based on evidence of improved cardiovascular outcomes in primary hypertension. Non-dihydropyridine calcium-channel blockers (e.g., diltiazem, verapamil) may have the additional benefit of reducing proteinuria.[81][123]

If BP cannot be controlled with a combination of three drugs (ACE inhibitor or angiotensin-II receptor antagonist, calcium-channel blocker, and diuretic), then additional agents may be considered, including: aldosterone antagonists (e.g., spironolactone), alpha-blockers (e.g., prazosin), beta-blockers (e.g., atenolol, metoprolol), hydralazine, minoxidil, or centrally-acting agents (e.g., clonidine).[81] Note that some agents may be recommended for specific indications, such as beta-blockers for angina pectoris.[81]

Primary options

chlortalidone: 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

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

diltiazem: 60-120 mg orally (extended-release) twice daily initially, adjust dose gradually according to response, maximum 360 mg/day

OR

verapamil: 80 mg orally (immediate-release) three times daily initially, adjust dose gradually according to response, maximum 480 mg/day; 180 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 480 mg/day given in 1-2 divided doses

Secondary options

spironolactone: 12.5 mg orally (tablet) once daily initially, adjust dose gradually according to response, maximum 100 mg/day given in 1-2 divided doses

OR

prazosin: 1 mg orally two to three times daily initially, adjust dose gradually according to response, maximum 20 mg/day

OR

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

OR

metoprolol: 25 mg orally (extended-release) once daily initially, adjust dose gradually according to response, maximum 400 mg/day

OR

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

Plus – glycaemic control

Back
ACUTE
|
GFR category G3 to G4
|
with diabetes
Plus – 

glycaemic control

Treatment recommended for ALL patients in selected patient group

In patients with diabetes, glycaemic goals should be individualised. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a HbA1c target ranging from <48 mmol/mol to <64 mmol/mol (<6.5% to <8.0%) for patients with diabetes and chronic kidney disease (CKD) not receiving dialysis. A lower target (e.g., <48 mmol/mol or <53 mmol/mol [<6.5% or <7.0%]) may be appropriate for individuals in whom preventing complications is the key goal, whereas a higher target (e.g., <58 mmol/mol or <64 mmol/mol [<7.5% or <8.0%]) may be preferred in those with multimorbidity or increased burden of hypoglycaemia.[92][93]​​​ In patients with diabetes and CKD, there is a risk for hypoglycaemia because of impaired kidney clearance of drugs (such as insulin or sulfonylureas) and because of impaired kidney gluconeogenesis.

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

In patients with type 2 diabetes, some specific anti-hyperglycaemic drugs significantly reduce all-cause or cardiovascular mortality, or major cardiovascular events or kidney complications, in some patient subgroups, and should be considered independently of HbA1c targets.[94][95][96][97][98]

A sodium-glucose co-transporter-2 (SGLT2) inhibitor is recommended for glycaemic control in type 2 diabetes to reduce kidney disease progression. SGLT2 inhibitors prevent major kidney outcomes (e.g., dialysis, transplantation, or death due to kidney disease) and cardiovascular events in people with type 2 diabetes.[82][99]​​[100]​​​​[101][102]​​​​​​ Renoprotection attributable to SGLT2 inhibition involves glucose-dependent and independent effects.[103][104]​​​​​​​

KDIGO guidelines advise that most patients with type 2 diabetes and CKD would benefit from treatment with metformin (if estimated GFR [eGFR] ≥30 mL/minute/1.73 m²) and an SGLT2 inhibitor (if eGFR ≥20 mL/minute/1.73 m²).[92] 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.[80]

Use of SGLT2 inhibitors is not generally recommended in patients with an eGFR of <20 mL/minute/1.73 m².[1][80]​​​​ However, renal and cardiovascular benefits with SGLT2 therapy are seen at eGFR levels as low as 20 mL/minute/1.73 m²; if tolerated, SGLT2 therapy may continue at eGFR levels below 20 mL/minute/1.73 m² unless kidney replacement therapy is started.[1][92]​​ Use of SGLT2 inhibitors is not recommended in patients with end-stage kidney disease who are on dialysis.[105]

If additional glycaemic 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) receptor agonist is the preferred option.[1][92]​​​ 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.[92]​ GLP-1 receptor agonists and DPP-4 inhibitors should not be used in combination.[92]

GLP-1 receptor agonists have beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes.[106][107][108]​​​​​​​ GLP-1 receptor agonists may be considered for cardiovascular risk reduction.[80]

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

DPP-4 inhibitors are renoprotective, but do not have a cardiovascular benefit.[109][110][111]​​​​​​​ Some DPP-4 inhibitors require dose adjustment in renal impairment.

Consider – finerenone

Back
ACUTE
|
GFR category G3 to G4
|
with diabetes
Consider – 

finerenone

Additional treatment recommended for SOME patients in selected patient group

Finerenone, a non-steroidal selective mineralocorticoid receptor antagonist, reduces the progression of kidney disease in patients with type 2 diabetes mellitus and known chronic kidney disease (CKD).[112] Finerenone is approved by the US Food and Drug Administration (FDA) to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalisation for heart failure in adults with CKD associated with type 2 diabetes.

Guidelines recommend finerenone for patients with type 2 diabetes and albuminuria (albumin to creatinine ratio [ACR] ≥3 mg/mmol [≥30 mg/g]) despite maximum tolerated dose of a renin-angiotensin system (RAS) inhibitor (if estimated GFR [eGFR] is ≥25 mL/minute/1.73 m² and serum potassium level is normal).​[80][92]​​​​​​ Finerenone can be added to a sodium-glucose co-transporter-2 (SGLT2) inhibitor and an ACE inhibitor or an angiotensin-II receptor antagonist.

Primary options

finerenone: 10-20 mg orally once daily

Consider – weight loss programme

Back
ACUTE
|
GFR category G3 to G4
|
with obesity
Consider – 

weight loss programme

Additional treatment recommended for SOME patients in selected patient group

Advise patients with obesity and chronic kidney disease (CKD) to lose weight.[1]​ Options for weight loss in patients with CKD include lifestyle interventions, pharmacotherapy, and metabolic surgery.[128]

The glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide may have a role in preventing CKD progression in patients with CKD and obesity (independent of diabetes). Improved kidney outcomes have been reported in patients with overweight/obesity and non-diabetic CKD receiving semaglutide.[129][130]​​ Patients with obesity, type 2 diabetes, and CKD may benefit from a GLP-1 receptor agonist for weight loss (in addition to improved cardiovascular and kidney outcomes).[92]

Primary options

semaglutide: 0.25 mg subcutaneously once weekly for 4 weeks, adjust dose gradually according to response, maximum 2.4 mg/week

Consider – antiplatelet agent

Back
ACUTE
|
GFR category G3 to G4
|
with ischaemic heart disease
Consider – 

antiplatelet agent

Additional treatment recommended for SOME patients in selected patient group

Use of low-dose aspirin is recommended for secondary prevention (of cardiovascular disease events) in patients with chronic kidney disease (CKD) and ischaemic cardiovascular disease.[1]​ There is a higher risk for minor bleeding than in the general population. Other antiplatelet agents (e.g., clopidogrel) may be considered for patients with intolerance to aspirin.

When assessing 10-year cardiovascular risk, a validated tool that incorporates CKD should be used to guide treatment for prevention of cardiovascular disease.

Primary options

aspirin: 75-100 mg orally once daily

Secondary options

clopidogrel: 75 mg orally once daily

Consider – revascularisation

Back
ACUTE
|
GFR category G3 to G4
|
with ischaemic heart disease
Consider – 

revascularisation

Additional treatment recommended for SOME patients in selected patient group

In patients with chronic kidney disease (CKD) and stable stress-test confirmed ischaemic heart disease, Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a conservative approach with intensive medical therapy, rather than initial revascularisation, which may increase risk of dialysis initiation, stroke, and death.[1][127]​​​​​ In those with acute or unstable coronary disease, unacceptable levels of angina (e.g., patient dissatisfaction), left ventricular systolic dysfunction attributable to ischaemia, or left main disease, revascularisation should be considered.[1]

Consider – erythropoietin-stimulating agent

Back
ACUTE
|
GFR category G3 to G4
|
with anaemia
Consider – 

erythropoietin-stimulating agent

Additional treatment recommended for SOME patients in selected patient group

When GFR category G3a/G3b has been reached, identification of comorbidities such as anaemia is recommended and treatment begun if required. Treatment of anaemia with the use of erythropoietin-stimulating agents is recommended for patients with chronic kidney disease (CKD) after other causes of anaemia, such as iron, vitamin B12, or folate deficiency, or blood loss, have been excluded.[61] [ Cochrane Clinical Answers logo ] ​​​ [ Cochrane Clinical Answers logo ] ​​​ [ Cochrane Clinical Answers logo ] ​​​​ Patients with CKD frequently have iron deficiency, and iron replacement should be considered as a goal of treatment.

Erythropoietin-stimulating agents may be initiated if the haemoglobin (Hb) level falls to <100 g/L (<10 g/dL) and the patient has signs and symptoms of anaemia.

A target Hb of 100-115 g/L (10.0-11.5 g/dL) is appropriate, as normalisation of Hb (>130 g/L [>13 g/dL]) has resulted in increased risk for death and cardiovascular disease in this population.[140][141][142]​​ For most patients, Hb concentration should be maintained at <115 g/L (<11.5 g/dL) with erythropoietin-stimulating agents to manage anaemia.[61][143][144]

The results from one Cochrane review and network meta-analysis suggest that erythropoietin-stimulating agents are superior to placebo for preventing blood transfusion, but increase the risk of hypertension.[145]​ The impact of erythropoietin-stimulating agents on mortality, major cardiovascular events, and kidney failure is uncertain, and evidence is lacking to compare the efficacy and safety of different formulations.[145]

The potential risks and benefits of therapy with an erythropoietin-stimulating agent should be discussed with the patient prior to treatment initiation.[61][146]​​​[147][148]

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
|
with anaemia
Consider – 

iron

Additional treatment recommended for SOME patients in selected patient group

All patients should have an assessment of iron stores if erythropoietin therapy is planned. The goal ferritin for those not on haemodialysis is >100 micrograms/L (>100 nanograms/mL), while for those on haemodialysis it is >200 micrograms/L (>200 nanograms/mL). All patients should have a transferrin saturation >20%. Iron replacement can be given orally or parenterally.[149][150]

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
|
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 initial approach to managing secondary hyperparathyroidism is to maintain serum calcium and phosphorus levels in the normal range with dietary restriction and/or phosphate-binding drugs.[62]

Phosphate binders should be initiated to normalise phosphorus levels if patients are unable to sufficiently restrict phosphorus in the diet.[62]​​​​​​​​ Calcium-based phosphate binders should be restricted if there is associated hypercalcaemia, arterial calcification, suppressed parathyroid hormone (PTH), or adynamic bone disease.[62]

For patients with GFR category G3a/G3b, serum calcium and phosphorus levels should be measured every 6-12 months; frequency of PTH testing should be determined by baseline level and chronic kidney disease (CKD) progression. For patients with GFR category G4 CKD, serum calcium and phosphorus levels should be checked every 3-6 months, and PTH every 6-12 months.[62][Evidence C]​​​ The optimal PTH level is currently not known.

There is limited evidence that dietary restriction in calcium and phosphorus affects renal osteodystrophy.[173]

There is evidence that the use of non-calcium-based phosphate binders has a survival advantage over calcium-based phosphate binders in patients with CKD.[62][154][155]​​​[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
|
with secondary hyperparathyroidism
Consider – 

ergocalciferol

Additional 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 <75 nanomol/L (<30 nanograms/mL), vitamin D supplementation with ergocalciferol should be initiated.[151][152]

Primary options

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

Consider – active vitamin D analogue

Back
ACUTE
|
GFR category G3 to G4
|
with secondary hyperparathyroidism
Consider – 

active vitamin D analogue

Additional treatment recommended for SOME patients in selected patient group

Use of active vitamin D analogues is not routinely recommended due to the risk of hypercalcaemia and lack of improvement in clinically relevant outcomes.[62] Use of active vitamin D analogue therapy in patients with chronic kidney disease not requiring dialysis is only indicated if hyperparathyroidism is progressive or severe.[62][153]

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
|
with metabolic acidosis
Consider – 

oral sodium bicarbonate

Additional 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 chronic kidney disease.[158]​ Oral sodium bicarbonate is well tolerated in this group.

Primary options

sodium bicarbonate: consult specialist for guidance on dose

Consider – uric acid-lowering therapy

Back
ACUTE
|
GFR category G3 to G4
|
with symptomatic hyperuricaemia
Consider – 

uric acid-lowering therapy

Additional treatment recommended for SOME patients in selected patient group

Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend that people who have chronic kidney disease (CKD) wIth symptomatic hyperuricaemia should be offered uric acid-lowering therapy.[1]​ This can be considered after the first episode of gout, particularly where there is no avoidable precipitant or serum uric acid concentration is >535 micromol/L [>9 mg/dL]).

Xanthine oxidase inhibitors are preferred to uricosuric agents for patients with CKD and symptomatic hyperuricaemia. Low-dose colchicine or intra-articular/oral glucocorticoids are preferred for symptomatic treatment of acute gout in patients with CKD.

Uric acid-lowering therapy is not recommended in people with CKD and asymptomatic hyperuricaemia to delay CKD progression.

See Gout.

GFR category G5

1st line – dialysis

Back
ACUTE
|
GFR category G5
1st line – 

dialysis

Kidney replacement therapy should be initiated based on assessment of signs and symptoms, GFR, and patient preferences. It is usually indicated once patients have G5 disease (often when GFR is between 5 and 10 mL/minute/1.73 m²) and if any of the following are present: symptoms or signs of kidney failure, including neurological symptoms and signs due to uraemia, pericarditis, anorexia, acid-base or electrolyte abnormalities, intractable pruritus, serositis; loss of blood pressure control or control of volume status (fluid overload); progressive deterioration in nutritional status refractory to intervention; or cognitive impairment.[1]

Kidney 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 chronic kidney disease education for modality choice.[135]

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.

Haemodialysis is usually prescribed in a treatment centre 3 times a week for approximately 4 hours each session. Haemodialysis can also be carried out at home, usually 4-5 days a week, 3-4 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 centres.

2nd line – kidney transplant

Back
ACUTE
|
GFR category G5
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 centre 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.

2nd line – conservative management

Back
ACUTE
|
GFR category G5
2nd line – 

conservative management

Patients aged over 80 years and those with significant comorbidities, such as advanced congestive heart failure, may do poorly with dialysis and are frequently not considered transplant candidates. The survival benefits of dialysis compared with conservative management are uncertain for older, frail patients.[164][165][166]​​ For these patients, and for all patients approaching end-stage kidney disease, the treating nephrologist should discuss the option of conservative management with the patient, including palliative care and end-of-life care.​[164][166][167]​​​

Conservative management focuses on maintaining quality of life, managing symptoms, and preserving kidney function for as long as possible (but does not include kidney replacement therapy).[164][168]​ Decisions about conservative management should be made using an informed shared decision-making process.

Consider – erythropoietin-stimulating agent

Back
ACUTE
|
GFR category G5
|
with anaemia
Consider – 

erythropoietin-stimulating agent

Additional treatment recommended for SOME patients in selected patient group

Treatment of anaemia with the use of erythropoietin-stimulating agents is recommended for patients with chronic kidney disease (CKD) after other causes of anaemia, such as iron, vitamin B12, or folate deficiency, or blood loss, have been excluded.[61] [ Cochrane Clinical Answers logo ] ​​​​​ Patients with CKD frequently have iron deficiency, and iron replacement should be considered as a goal of treatment.

Erythropoietin-stimulating agents may be initiated once the haemoglobin (Hb) falls to 100 g/L (10 g/dL) and the patient has signs and symptoms of anaemia.

A target Hb of 100-115 g/L (10.0 to 11.5 g/dL) is appropriate, as normalisation of Hb (>130 g/L [>13 g/dL]) has resulted in increased risk for death and cardiovascular disease in this population.[140][141][142]​ For most patients, Hb concentration should be maintained at <115 g/L (<11.5 g/dL) with erythropoietin-stimulating agents to manage anaemia.[61][143][144]

The results from one Cochrane review and network meta-analysis suggest that erythropoietin-stimulating agents are superior to placebo for preventing blood transfusion, but increase the risk of hypertension.[145]​ The impact of erythropoietin-stimulating agents on mortality, major cardiovascular events, and kidney failure is uncertain, and evidence is lacking to compare the efficacy and safety of different formulations.[145]

The potential risks and benefits of therapy with an erythropoietin-stimulating agent should be discussed with the patient prior to treatment initiation.[61][146][147][148]

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
|
with anaemia
Consider – 

iron

Additional treatment recommended for SOME patients in selected patient group

All patients should have an assessment of iron stores if erythropoietin therapy is planned. The goal ferritin for those not on haemodialysis is >100 micrograms/L (>100 nanograms/mL), while for those on haemodialysis it is >200 micrograms/L (>200 nanograms/mL). All patients should have a transferrin saturation >20%. Iron replacement can be given orally or parenterally.[149][150]​​​​​​

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

Plus – dietary modification ± phosphate-binding drug

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

dietary modification ± phosphate-binding drug

Treatment recommended for ALL patients in selected patient group

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

Phosphate binders such as calcium, lanthanum, and sevelamer should be initiated to normalise phosphorus levels if patients are unable to sufficiently restrict phosphorus in the diet.[62]​​​​​​ Calcium-based phosphate binders should be restricted if there is associated hypercalcaemia, arterial calcification, suppressed PTH, or adynamic bone disease.[62]

Calcium and phosphorus testing every 1-3 months and PTH testing every 3-6 months should be performed for patients with GFR category G5 CKD and secondary hyperparathyroidism.[62][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 analogue

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

calcimimetic ± active vitamin D analogue

Additional 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 analogues (e.g., calcitriol, paricalcitol, doxercalciferol), or a combination of a calcimimetic with an active vitamin D analogue should be given.[62]

Cinacalcet lowers PTH levels in patients with chronic kidney disease and secondary hyperparathyroidism both prior to and after the initiation of dialysis, but it is associated with hypocalcaemia, and long-term benefits are not known.[162][163] [ Cochrane Clinical Answers logo ]

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 haemodialysis 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
|
with secondary hyperparathyroidism
Consider – 

ergocalciferol

Additional 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 <75 nanomol/L (<30 nanograms/mL), vitamin D supplementation with ergocalciferol should be initiated.[151][152]

Primary options

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

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