Chronic Kidney Disease Management

Introduction to CKD Treatment

A comprehensive treatment approach for patients with chronic kidney disease should include ACE inhibitors or ARBs as first-line therapy, with SGLT2 inhibitors added for those with type 2 diabetes, and additional medications tailored to manage specific complications including hypertension, albuminuria, hyperkalemia, and cardiovascular risk 1, 2

ACE inhibitors or ARBs are recommended first-line therapy for patients with diabetes, hypertension, and albuminuria, as well as for patients with albuminuria even with normal blood pressure, according to the Kidney International guidelines 1
The dose of ACE inhibitors or ARBs should be titrated to the highest approved dose tolerated by the patient, with monitoring of serum creatinine and potassium within 2-4 weeks after starting or changing the dose 1, 2
Therapy with ACE inhibitors or ARBs should be continued unless serum creatinine rises >30% within 4 weeks or specific contraindications develop, and should not be discontinued due to an expected initial small decrease in eGFR 1, 2, 3
The American College of Cardiology recommends that ACE inhibitors or ARBs should not be discontinued in pregnant women or those considering pregnancy without consulting a healthcare provider 1
The Kidney International guideline strongly recommends starting ACEi or ARB for patients with diabetes and moderately-to-severely increased albuminuria (ACR ≥30 mg/g) with a strength of evidence of 1B, and suggests starting ACEi or ARB for patients with severely increased albuminuria (A3, ACR >300 mg/g) with a strength of evidence of 1B 2, 3, 4, 1

SGLT2 inhibitors should be added to the treatment regimen for patients with type 2 diabetes and CKD with an eGFR ≥20 ml/min per 1.73 m², including those with urine ACR <200 mg/g (eGFR 20-45 ml/min per 1.73 m²) 2
The Kidney International guideline strongly recommends adding SGLT2 inhibitor for patients with eGFR ≥20 ml/min per 1.73 m² (1A), and suggests that SGLT2 inhibitors can be used in patients with CKD and type 2 diabetes, with the initial eGFR decrease not being a reason to discontinue therapy 2
SGLT2 inhibitors provide benefits including slowing CKD progression and reducing cardiovascular events 1, 5

Nonsteroidal MRAs, such as finerenone, are suggested for patients with type 2 diabetes and eGFR >25 ml/min per 1.73 m², normal serum potassium, and persistent albuminuria despite maximum RAS inhibitor dose 2
Nonsteroidal MRAs can be added to the RASi and SGLT2i regimen, with potassium levels monitored regularly after initiation 2, 6

Statins are recommended for all adults ≥50 years with eGFR <60 ml/min per 1.73 m², as well as for those with CKD and eGFR ≥60 ml/min per 1.73 m², according to the Kidney International guidelines (1A and 1B) 2, 6
Non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over warfarin for CKD G1-G4 patients with atrial fibrillation 2

An individualized approach, including dietary and pharmacologic interventions, should be implemented to manage hyperkalemia, with potassium binders considered if hyperkalemia limits optimal RAS inhibitor dosing 2, 6
Pharmacological treatment should be considered for serum bicarbonate <18 mmol/l, with treatment monitored to ensure that bicarbonate levels do not exceed the upper limit of normal 2, 6
Hyperkalemia can often be managed without stopping RASi, according to the Kidney International guideline, with options including dietary potassium restriction, diuretics, sodium bicarbonate, and GI cation exchangers 2, 7

Uric acid-lowering therapy should be used to treat symptomatic hyperuricemia, with a preference for xanthine oxidase inhibitors over uricosuric agents 6
Uric acid-lowering agents should be avoided in asymptomatic hyperuricemia 2

Non-pharmacological interventions such as dietary sodium restriction, exercise, and smoking cessation should not be overlooked 1
Sodium intake should be restricted to <2g per day (<5g sodium chloride) for most CKD patients (2C), but sodium restriction is not appropriate for patients with sodium-wasting nephropathy 2
CKD stage should be determined using eGFR and albuminuria, and comorbidities such as diabetes, hypertension, and cardiovascular disease should be assessed 2
Baseline labs including creatinine, potassium, and lipids should be checked, and creatinine and potassium should be monitored 2-4 weeks after starting or increasing RASi 2

GLP-1 RAs are effective regardless of kidney function, with low hypoglycemia risk, and are recommended for patients not achieving glycemic targets despite metformin and SGLT2 inhibitors 5, 2
Metformin is the preferred agent but the dose should be reduced when eGFR <45 ml/min/1.73 m² and stopped when <30 ml/min/1.73 m² 5
The Kidney International guideline strongly recommends avoiding combination RAS blockade, as it increases adverse effects without providing additional benefits (1B) 2
Dual RAS blockade, including the combination of ACEi, ARB, and direct renin inhibitors, should be avoided (1B) 2
The American Heart Association suggests monitoring blood pressure regularly, targeting <120 mmHg systolic when tolerated, and continuing surveillance of albuminuria to assess treatment response 3, 8, 2