Why is losartan (an angiotensin II receptor antagonist) recommended to protect the kidneys in patients with non-insulin-dependent diabetes mellitus (NIDDM) despite initial concerns about its impact on kidney function?

Why Losartan is Recommended for Kidney Protection in Type 2 Diabetes

Losartan is specifically recommended to protect kidneys in patients with type 2 diabetes and proteinuria because it reduces intraglomerular pressure and proteinuria through mechanisms independent of blood pressure lowering, thereby slowing progression to end-stage renal disease—the initial transient decline in GFR after starting losartan is hemodynamic and expected, not harmful. 1

Understanding the Apparent Paradox

The confusion arises from misunderstanding the initial hemodynamic changes that occur when starting losartan:

• Losartan causes efferent arteriolar vasodilation, which temporarily lowers glomerular filtration rate (GFR) by reducing intraglomerular pressure 1
• This modest rise in serum creatinine (10-20%) is expected and hemodynamic in nature, not indicative of kidney injury unless persistent 1
• The European Renal Association notes this temporary GFR reduction occurs shortly after initiation and is generally not harmful 1
• Continue losartan unless serum creatinine rises by more than 30% within 4 weeks of initiation or dose increase 1, 2

Proven Long-Term Renoprotective Benefits

The landmark RENAAL trial definitively established losartan's kidney-protective effects in type 2 diabetes:

• Losartan reduced the composite endpoint of doubling serum creatinine, ESRD, or death by 16% (P=0.02) 3
• Losartan reduced progression to ESRD by 28% (P=0.002) 3, 4
• Losartan reduced doubling of serum creatinine by 25% (P=0.006) 3
• Losartan reduced proteinuria by 13-18.5% independent of blood pressure effects 1

Specific Indications for Losartan in Diabetic Kidney Disease

For patients with type 2 diabetes and moderately to severely increased albuminuria (≥30 mg/24h), ARBs like losartan are strongly recommended (Grade 1B) 1, 2:

• ARBs are more effective than other antihypertensive classes in slowing GFR decline and preventing kidney failure in patients with type 2 diabetes and macroalbuminuria 3
• The beneficial effect may be greater in patients with decreased GFR at baseline, as the kidney benefits appear greater than expected from blood pressure lowering alone 3
• Either ARBs or ACE inhibitors can be used for diabetic kidney disease with macroalbuminuria, but losartan is preferred when ACE inhibitors cause intolerable cough 1

Practical Implementation and Monitoring

Start losartan and monitor appropriately to distinguish expected hemodynamic changes from true kidney injury:

• Check serum creatinine and potassium within 2-4 weeks after initiation or dose increase 1, 2
• A creatinine rise up to 30% within 4 weeks is acceptable and should not prompt discontinuation 1, 2
• Discontinue immediately if creatinine rises to >310 μmol/L (3.5 mg/dL) or potassium rises to ≥6.0 mmol/L 1
• Halve the dose if creatinine rises to >220 μmol/L (2.5 mg/dL) or potassium rises to >5.5 mmol/L 1

Critical Situations Requiring Temporary Discontinuation

Counsel patients to temporarily hold losartan during specific high-risk situations 1, 2:

• Intercurrent illness with volume depletion
• Planned IV radiocontrast administration
• Bowel preparation for colonoscopy
• Prior to major surgery

Important Contraindications and Precautions

Never combine losartan with ACE inhibitors or direct renin inhibitors (Grade 1B)—this increases adverse effects without additional benefit 1, 2:

• Avoid bilateral renal artery stenosis patients, as they depend on angiotensin II for glomerular filtration 1, 5
• Correct volume or salt depletion prior to initiating losartan to prevent symptomatic hypotension 5
• Monitor potassium closely in patients with advanced CKD, diabetes, or those taking potassium-sparing diuretics 1, 5

The Bottom Line

The initial concern about losartan "not being good for kidneys" stems from the expected hemodynamic reduction in GFR that occurs when blocking the renin-angiotensin system. However, this short-term functional change is precisely the mechanism by which losartan provides long-term kidney protection by reducing intraglomerular hypertension and proteinuria 3, 1. The RENAAL trial's robust evidence showing 28% reduction in ESRD progression over 3.5 years definitively proves that losartan's long-term benefits far outweigh the initial transient creatinine rise 3, 4, 6.