This is a highly subjective list, but these trials have been included as they have had a meaningful impact on guidelines, patients and clinicians at a global scale.
1. IDNT: Irbesartan Diabetic Nephropathy Trial
A randomized, blinded, placebo-controlled trial designed to assess whether irbesartan or amlodipine slow the progression of nephropathy in patients with type 2 diabetes, independent of effects on systemic blood pressure (BP) lowering.
The primary outcome, a composite of doubling of serum creatinine, onset of end-stage renal disease, serum creatinine ≥6.0 mg/dl, or death from any cause, was reduced by 23% compared to the amlodipine group (32.6% vs. 41.1%, p=0.006).
The authors found that the angiotensin-II–receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of the reduction in blood pressure it causes.
2. RENAAL: Reduction in End Points in NIDDM with the Angiotensin II Antagonist Losartan study
In this study, it was shown that losartan reduced the incidence of a doubling of the serum creatinine concentration and end-stage renal disease. The benefit exceeded that attributable to changes in blood pressure.
It was published at the same time as the IDNT study.
3. The Effect of Angiotensin-Converting-Enzyme Inhibition on Diabetic Nephropathy
This was a randomized, controlled trial comparing captopril with placebo in patients with type 1 diabetes mellitus who had protein in the urine of ≥ 500 mg per day.
This was an important study as it showed that captopril treatment was associated with a 50 percent reduction in the risk of the combined end points of death, dialysis, and transplantation. Notably, it was significantly more effective than blood-pressure control alone.
4. CREDENCE: Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
The first study to show that an SGLT2i can reduce kidney outcomes in patients with diabetes and kidney disease.
This study showed that in patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group.
5. DAPA-CKD: Dapagliflozin in Patients with Chronic Kidney Disease
The first study to show that an SGLT2i can reduce kidney outcomes in both diabetic and non-diabetics.
Specifically, the authors found that among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo.
6. FIDELIO: Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes
While MRAs, including finerenone (a nonsteroidal, selective mineralocorticoid receptor antagonist) had been shown to reduce albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes, long-term benefits on kidney and cardiovascular outcomes were unknown.
This was the first study that showed that in patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo.
7. EMPA-KIDNEY: Empagliflozin in Patients with Chronic Kidney Disease
The first study to show that an SGLT2i can reduce kidney and cardiovascular outcomes in both diabetic and non-diabetics, independent of whether albuminuria is present.
Specifically, the authors found that among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin led to a lower risk of progression of kidney disease or death from cardiovascular causes.