Should You Add Lisinopril to This Patient Already on Synjardi (Valsartan)?
No, you should not add lisinopril to this patient who is already taking Synjardi (which contains valsartan, an ARB). Combining an ACE inhibitor with an ARB is explicitly contraindicated and increases adverse effects without providing additional benefit. 1
Why Dual RAS Blockade Is Contraindicated
KDIGO 2024 guidelines explicitly recommend avoiding any combination of ACE inhibitor, ARB, and direct renin inhibitor therapy in people with CKD, with or without diabetes. 1 This is a strong recommendation (Grade 1B) based on evidence showing increased harm without additional benefit.
The FDA drug label for lisinopril warns about the risks of combining RAS inhibitors, including increased risk of hyperkalemia, hypotension, and acute kidney injury. 2
What You Should Do Instead: Optimize Current Therapy
1. Maximize the Valsartan Dose in Synjardi
Ensure your patient is on the highest tolerated dose of valsartan within the Synjardi formulation. RAS inhibitors should be administered at the highest approved dose to achieve maximum antiproteinuric benefit, as proven benefits were achieved in trials using these doses. 1
Accept up to 30% increase in serum creatinine after uptitration—this is a hemodynamic effect and expected, not a reason to discontinue therapy unless hyperkalemia becomes refractory. 1, 3
2. Target Aggressive Blood Pressure Control
Target systolic blood pressure <120 mmHg using standardized office measurement in this patient with CKD and macroalbuminuria. 1 This intensive BP target provides additional renoprotection beyond the antiproteinuric effects of RAS blockade alone.
If BP remains elevated despite maximized Synjardi, add additional antihypertensive agents from other classes (see below).
3. Add SGLT2 Inhibitor (Critical Step)
Since your patient is already on insulin (Lantus), they have diabetes. KDIGO 2024 strongly recommends treating patients with type 2 diabetes, CKD, and eGFR ≥20 ml/min/1.73 m² with an SGLT2 inhibitor (Grade 1A). 1
SGLT2 inhibitors provide additive renoprotection to ARBs through complementary mechanisms and reduce both proteinuria and cardiovascular events. 4
4. Consider Adding Additional Antihypertensive Agents for BP Control
If blood pressure remains above target despite maximized valsartan:
Add a thiazide-like diuretic (chlorthalidone or indapamide preferred) as these enhance the antiproteinuric effects of RAS blockade. 5, 6
Consider adding a mineralocorticoid receptor antagonist (spironolactone 25-50 mg or eplerenone) for resistant proteinuria, with careful potassium monitoring. 5 This provides additional antiproteinuric effects through aldosterone blockade complementary to ARB therapy.
Calcium channel blockers (non-dihydropyridine preferred) can be added for BP control, though dihydropyridines like amlodipine may worsen edema and have less impact on proteinuria. 1
5. Implement Critical Lifestyle Modifications
Restrict dietary sodium to <2 g/day (<90 mmol/day or <5 g sodium chloride/day). 1 Sodium restriction synergistically enhances the antiproteinuric effects of ARBs and is as important as medication optimization. 3, 4
Counsel the patient to temporarily hold valsartan and diuretics during intercurrent illnesses with risk of volume depletion (diarrhea, vomiting, excessive sweating) to prevent acute kidney injury. 1, 4
Essential Monitoring Parameters
Check serum creatinine, eGFR, and potassium within 2-4 weeks after any medication adjustment. 1
Monitor urine albumin-to-creatinine ratio every 3-6 months, aiming for reduction to <300 mg/g or at least 30-50% reduction from baseline (current ACR is 323 mg/g). 3, 5
Continue RAS blockade even if eGFR falls below 30 ml/min/1.73 m², unless there is refractory hyperkalemia or symptomatic hypotension. 1
Common Pitfall to Avoid
The most critical error would be adding lisinopril to valsartan. While older studies from 2002-2014 suggested potential benefits of dual RAS blockade for proteinuria reduction 7, 8, 9, subsequent large trials demonstrated increased adverse events (hyperkalemia, hypotension, acute kidney injury) without mortality or hard renal outcome benefits, leading to the current strong recommendation against this practice. 1