Thread by @drdschwartzmd

7 most impactful clinical trials focussed on slowing progression of chronic kidney disease

A Thread 🧵

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

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 ARB 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.

nejm.org/doi/full/10.10…

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. Published at the same time as the IDNT study.

nejm.org/doi/full/10.10…

3) The Effect of Angiotensin-Converting-Enzyme Inhibition on Diabetic Nephropathy

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.

An important study as showed captopril ass'd w/ 50% reduction in the risk of combined end points of death, dialysis and transplantation. Notably, it was significantly more effective than blood-pressure control alone.

nejm.org/doi/full/10.10…

4) CREDENCE: Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

The first primary CKD 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.

nejm.org/doi/full/10.10…

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.

Found that among patients with CKD, regardless of the presence or absence of diabetes, composite of sustained decline in eGFR of >=50%, ESKD, or death from renal or CV causes was significantly lower with dapagliflozin than with placebo

nejm.org/doi/full/10.10…

6) FIDELIO: Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes

While MRAs, including finerenone shown to reduce albuminuria in short-term trials, long-term benefits on kidney and cardiovascular outcomes were unknown

@BakrisGeorge

1st study to show in CKD and T2D pts, tx with finerenone (a nonsteroidal, selective mineralocorticoid receptor antagonist) led to lower risks of CKD progression and CV events than placebo.

nejm.org/doi/full/10.10…

7) EMPA-KIDNEY: Empagliflozin in Patients with Chronic Kidney Disease

1st study to show that an SGLT2i can reduce kidney and cardiovascular outcomes in both diabetic and non-diabetics, independent of whether albuminuria is present.

Authors found that among a wide range of patients with CKD at risk for disease progression, empagliflozin led to a lower risk of progression of kidney disease or death from cardiovascular causes.

nejm.org/doi/full/10.10…

What other studies should be added to this list of most impactful trials in CKD progression?
#askrenal

Follow for more lists of ideas on NotePD notepd.com/profile/daniel…