Treatment of Moderate Albuminuria
For patients with moderate albuminuria, ACE inhibitors or angiotensin receptor blockers (ARBs) are recommended as first-line therapy, regardless of whether the patient has hypertension. 1
First-Line Therapy: RAS Blockade
Indications for ACEi/ARB Therapy
- ACE inhibitors or ARBs are recommended for all patients with moderate albuminuria (30-299 mg/g creatinine), even in normotensive individuals 1
- These medications should be titrated to the highest approved dose that is tolerated to achieve maximum benefits 1, 2
- The American Diabetes Association strongly recommends RAS blockade for patients with diabetes and moderate albuminuria 1
- For patients with sickle cell disease and albuminuria, ACEi or ARB therapy is also suggested 1
Mechanism and Benefits
- RAS blockade reduces albuminuria and slows progression to more severe kidney disease 1, 3
- Treatment with ACEi/ARB has been shown to improve clinical outcomes in patients with albuminuria, including reducing the risk of progression to end-stage kidney disease 4, 5
- In patients with type 2 diabetes and nephropathy, losartan (an ARB) reduced proteinuria by an average of 34% within 3 months of starting therapy 4
- The reduction in albuminuria during the first months of treatment correlates with the degree of long-term renal protection 3
Monitoring and Safety Considerations
Initial Monitoring
- Check serum potassium and creatinine within 2-4 weeks after initiating therapy with either ACEi or ARB 6
- Do not discontinue therapy with modest and stable increases in serum creatinine (up to 30%) 6, 2
- Monitor for hyperkalemia, particularly in patients with reduced kidney function 1, 2
Long-term Follow-up
- In patients with established kidney disease, urinary albumin and estimated glomerular filtration rate should be monitored 1-4 times per year depending on the stage of kidney disease 1
- Continue ACEi/ARB therapy even when eGFR falls below 30 ml/min/1.73 m², as they provide ongoing cardiovascular and renal protection 2
- Consider reducing the dose or discontinuing therapy only in cases of symptomatic hypotension, uncontrolled hyperkalemia despite medical treatment, or when needing to reduce uremic symptoms in end-stage CKD 2
Additional Treatment Considerations
Blood Pressure Management
- Optimize blood pressure control to reduce the risk or slow the progression of chronic kidney disease 1
- Many patients will require combination therapy to achieve target blood pressure of <120 mmHg systolic 6
- Consider calcium channel blockers as add-on therapy rather than dual RAS blockade 6
Glycemic Control
- Optimize glucose management in diabetic patients to reduce the risk or slow the progression of CKD 1
- For patients with type 2 diabetes and CKD, consider adding an SGLT2 inhibitor if eGFR ≥20 ml/min/1.73 m² 2
Important Precautions
- Avoid any combination of ACEi, ARB, and direct renin inhibitor therapy as this increases risk of hyperkalemia and acute kidney injury without additional benefits 2
- Counsel patients to temporarily hold ACEi or ARB during illness with risk of volume depletion, prior to procedures with contrast, or before major surgery 6
- Restrict dietary sodium to <2.0 g/d in CKD patients to enhance the antiproteinuric effect of RAS blockade 6
Special Populations
Diabetic Patients
- In patients with diabetes, ACEi/ARB therapy is particularly beneficial for reducing albuminuria and preventing progression to more severe kidney disease 1, 7
- The KDOQI guidelines recommend ACEi/ARB for normotensive people with diabetes and microalbuminuria 1
Sickle Cell Disease
- For children and adults with sickle cell disease and albuminuria, ACEi or ARB therapy is suggested despite very low certainty in the evidence about effects 1
- Studies have shown that 60% of patients with moderate albuminuria and sickle cell disease showed improvement with ARB therapy 1