The short answer
Lisinopril is an ACE inhibitor, while losartan is an angiotensin II receptor blocker (ARB). Both block the renin-angiotensin system, which helps regulate blood pressure and pressure inside the kidney’s filtering units, called glomeruli.
In people with CKD—particularly those with albuminuria (excess albumin in the urine)—ACE inhibitors and ARBs can reduce pressure within the glomeruli, lower albumin leakage, control blood pressure, and help slow kidney disease progression. KDIGO recommends using an ACE inhibitor or ARB at the highest tolerated dose when indicated. ([KDIGO][1])
The important point is that lisinopril is not automatically better than losartan, or vice versa. They work through closely related pathways, and the choice often depends on blood pressure, albuminuria, side effects, potassium, kidney function, other medical conditions, and previous treatment response.
Why lowering glomerular pressure can protect the kidneys
Each kidney contains millions of tiny filtering units called glomeruli.
When pressure inside these filters becomes excessive, the glomerular barrier can allow more albumin to pass into the urine. Persistent high pressure and albumin leakage can contribute to kidney damage over time.
Angiotensin II normally causes the efferent arteriole—the small blood vessel leaving the glomerulus—to constrict. This helps maintain pressure inside the glomerulus.
ACE inhibitors and ARBs reduce the effect of angiotensin II. The efferent arteriole relaxes, which lowers intraglomerular pressure.
That is one reason a person may see:
Lower glomerular pressure → less albumin leakage → lower albuminuria → kidney-protective effects over time.
This mechanism also explains an important point: eGFR can fall slightly and creatinine can rise after starting treatment without the drug necessarily damaging the kidneys. An initial hemodynamic change is expected in some patients. (KDIGO)
Lisinopril vs losartan: what is the difference?
| Feature | Lisinopril | Losartan |
|---|---|---|
| Drug class | ACE inhibitor | ARB |
| Main action | Reduces formation of angiotensin II | Blocks angiotensin II from activating its AT1 receptor |
| Kidney effect | Lowers intraglomerular pressure and albuminuria when indicated | Similar |
| Common issue | Dry cough can occur | Cough is generally less common |
| Important risks | High potassium, low blood pressure, kidney-function changes, rare angioedema | High potassium, low blood pressure, kidney-function changes, rare angioedema |
| Used in CKD | Yes, when clinically indicated | Yes, when clinically indicated |
Both can provide kidney protection, but the reason for prescribing them matters. Albuminuria is an especially important factor when deciding whether renin-angiotensin system blockade is appropriate. ACE inhibitors or ARBs may also be used for conditions such as hypertension or certain forms of heart disease. ([KDIGO][1])
Why does creatinine sometimes rise after starting one?
This can seem confusing.
If an ACE inhibitor or ARB lowers pressure inside the glomerulus, the filtration rate can initially decrease. As a result, serum creatinine may rise.
That does not automatically mean the medicine is destroying kidney tissue.
KDIGO recommends checking serum creatinine and potassium within about 2–4 weeks after starting or increasing an ACE inhibitor or ARB. A creatinine increase of more than about 30% within four weeks warrants evaluation for problems such as volume depletion, AKI, medication interactions, or renal artery disease rather than simply assuming the drug caused permanent damage. ([KDIGO][1])
The person’s previous creatinine, current eGFR, hydration, blood pressure, other medicines, and clinical condition all matter.
What about potassium?
ACE inhibitors and ARBs can increase blood potassium because blocking angiotensin II also reduces aldosterone activity. Aldosterone normally helps the kidneys eliminate potassium.
This means the risk of hyperkalemia (high blood potassium) can be greater in people with CKD.
However, high potassium does not automatically mean an ACE inhibitor or ARB must be permanently stopped. KDIGO notes that hyperkalemia associated with these medicines can often be managed by addressing contributing factors and treating the potassium level when appropriate. (KDIGO)
This is why monitoring potassium is an important part of treatment.
Should you take lisinopril and losartan together?
Generally, no.
Lisinopril and losartan both block the renin-angiotensin system, and combining an ACE inhibitor with an ARB is generally avoided in CKD because the combination increases the risk of complications such as hyperkalemia, low blood pressure, and acute kidney injury without providing enough additional benefit to justify routine dual therapy.
The usual approach is to use one or the other, not both. ([KDIGO][1])
Does everyone with CKD need an ACE inhibitor or ARB?
No.
CKD is not one single condition, and the benefit of these medicines depends on the clinical situation.
For example, albuminuria, hypertension, diabetes, cardiovascular disease, potassium level, and current kidney function can all influence treatment decisions.
Someone with CKD but little or no albuminuria may have a different reason for receiving an ACE inhibitor or ARB—or may appropriately use another blood-pressure medicine instead. KDIGO specifically emphasizes albuminuria when recommending renin-angiotensin system inhibitors for CKD. ([KDIGO][1])
What should be monitored?
After starting or increasing an ACE inhibitor or ARB, clinicians commonly monitor:
- Blood pressure
- Serum creatinine
- eGFR
- Serum potassium
- Symptoms such as dizziness or unusually low blood pressure
The trend matters more than one isolated number.
For example:
Previous creatinine → new creatinine → percentage change → time since medication started → potassium → hydration and other medicines
This provides much more useful information than looking at the new creatinine value alone.
NSAIDs, dehydration, diuretics, and other medications can also contribute to kidney-function changes and should be considered when a significant creatinine rise occurs. (KDIGO)
What if kidney function is already quite low?
A low eGFR does not automatically mean an ACE inhibitor or ARB should be stopped.
KDIGO recommends continuing ACE inhibitor or ARB treatment in appropriate patients even when eGFR falls below 30 mL/min/1.73 m², provided there is no specific reason to discontinue it. Decisions should instead consider factors such as persistent uncontrolled hyperkalemia, symptomatic low blood pressure, significant kidney-function changes, and the person’s overall clinical situation. (KDIGO)
What should a patient do?
If you take lisinopril, losartan, or another ACE inhibitor/ARB:
- Do not stop it simply because creatinine has risen slightly without discussing the result with your clinician.
- Have creatinine/eGFR and potassium monitored as recommended after starting or changing the dose.
- Tell your clinician about NSAIDs, supplements, diuretics, and other medicines.
- Seek medical advice if you develop significant dizziness, weakness, dehydration, or other concerning symptoms.
- Never combine lisinopril and losartan on your own.
Bottom line
Lisinopril and losartan can protect kidneys by reducing excessive pressure inside the glomeruli, particularly in CKD with albuminuria. Lisinopril is an ACE inhibitor; losartan is an ARB. Neither is universally “better.”
A modest early change in creatinine can be an expected effect of lowering intraglomerular pressure rather than evidence of kidney destruction. However, a substantial rise in creatinine or potassium requires evaluation rather than being ignored. ([KDIGO][1])
The sensible goal is not simply to achieve the lowest possible creatinine. It is to use the appropriate treatment while maintaining safe blood pressure, potassium, and kidney function, with ongoing monitoring and individualized care.