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Evevident
Original paper
2001NEJMNephrology

RENAAL

Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy

RCTDiabetic kidney disease

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Overview

Losartan slowed kidney disease progression in type 2 diabetes with nephropathy.

Clinical takeaway

RENAAL established ARB-based RAAS blockade as kidney-protective therapy in proteinuric diabetic nephropathy, beyond blood-pressure lowering alone.

Key result

Losartan reduced the composite of creatinine doubling, ESRD, or death by about 16%.

Practice impact

RAAS blockade became foundational therapy for diabetic kidney disease with albuminuria.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

1,513

Follow-up

Mean 3.4 years.

Geography

Multinational

Clinical question

Does losartan improve renal outcomes in type 2 diabetes with nephropathy?

Population

  • Patients with type 2 diabetes and nephropathy with elevated serum creatinine and proteinuria.

Intervention

Losartan 50-100 mg daily added to conventional antihypertensive therapy.

Comparator

Placebo added to conventional antihypertensive therapy, excluding ACE inhibitors and ARBs.

Primary outcome

Composite of doubling of serum creatinine, end-stage renal disease, or death.

Losartan reduced major renal outcomes in type 2 diabetes with nephropathy.

Relative risk reduction / 16 / p=0.02

Key results

  • Primary composite was reduced by 16% with losartan.
  • Doubling of serum creatinine and ESRD were reduced.
  • Proteinuria fell substantially with losartan.

Harms

  • Hyperkalemia and creatinine rise require monitoring with RAAS blockade.
  • Hypotension can occur with multidrug antihypertensive therapy.

Clinical Use

When to cite

  • When explaining why ACE inhibitors or ARBs are first-line kidney-protective therapy in albuminuric diabetic CKD.

Practice impact

  • Established ARBs as kidney-protective therapy for proteinuric diabetic nephropathy.

Applicability

  • Patients with type 2 diabetes, CKD, and albuminuria/proteinuria, especially when ACE inhibitors are not used or not tolerated.

Limitations

  • Pre-SGLT2 inhibitor era.
  • Does not answer dual ACE inhibitor plus ARB therapy, which later proved harmful in many settings.

Common misinterpretations

  • Do not combine ACE inhibitors and ARBs for routine kidney protection; RENAAL tested losartan against non-RAAS background therapy.

Related evidence

CREDENCE - Later TrialDAPA-CKD - Later Trial

Citation

Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861-869. doi:10.1056/NEJMoa011161

Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy.