NP39 Nephrology

Landmark Nephrology Trials

Essential Med Notes 2015

Landmark Nephrology Trials

Trial

Reference

Results

4D

NEJM 2005; 353:238-48

Patients with type 2 DM receiving maintenance hemodialysis were randomized to 20 mg of atorvastatin per day or matching
placebo; no difference in composite index of death from cardiac causes, nonfatal myocardial infarction, and stroke

AASK

JAMA 2001; 285:2719-28

Ramipril, compared with amlodipine, slows progression of hypertensive renal disease and proteinuria and may benefit patients
without proteinuria as well

ACCOMPLISH

NEJM 2008; 359:2417-20

Combination treatment with an ACEI and a CCB (benazepril-amlodipine) was more successful than a combination of ACEI
and a thiazide diuretic (benzapril-HCTZ) in reducing cardiovascular events in patients with HTN who were at risk for such
events

ACEI and Diabetic

NEJM 1993; 329:1456-62

Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more
effective than blood pressure control alone

ALERT

Lancet 2003; 361:2024-31

The use of fluvastatin in renal transplant recipients did not significantly decrease the risk of the occurrence of a major
adverse cardiac event (defined as cardiac death, non-fatal MI, or coronary intervention procedure) compared with placebo;
however, there was a significant reduction in cardiac deaths or non-fatal MI

ALTITUDE

Early Termination (Unpublished

Results; protocol NDT 2009;
24:1663-71)

Combining Aliskiren with ACEI or ARB in high-risk patients with type 2 DM leads to increased incidence of nonfatal stroke,
hyperkalemia, and hypotension

ASTRAL

NEJM 2009; 361:1953-62

Renal artery revascularization compared to medical therapy does not improve renal function, BP, renal or cardiovascular
events, or mortality, and carries significant operative risks

AURORA

NEJM 2009; 360:1395-407

Patients receiving maintenance hemodialysis randomized to rosuvastatin 10 mg daily or placebo; rosuvastatin lowered the
LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes,
nonfatal myocardial infarction, or nonfatal stroke

BENEDICT

NEJM 2004; 351:1941-51

Treatment with ACEI trandolapril alone or trandolapril combined with verapamil decreased the incidence of microalbuminuria in
patients with type 2 DM and HTN with normoalbuminuria

CHOIR

NEJM 2006; 355:2085-98

Patients with CKD were randomly assigned to receive a dose of epoetin alfa targeted to achieve a hemoglobin level of
13.5 g/dL or 11.3 g/dL; the higher target group had an increased risk of death, myocardial infarction, hospitalization for
congestive heart failure (without renal replacement therapy), or stroke

CREATE

NEJM 2006; 355:2071-84

Patients with CKD (15-35 mL/min) and mild to moderate anemia (11-12.5 g/dL) were randomized to normal (13-15 g/dL)
or sub-normal (10.5-11.5 g/dL) hemoglobin levels; early and complete correction of hemoglobin did not reduce the risk of
cardiovascular events

DETAIL

NEJM 2004; 351:1952-61

The ARB telmisartan and the ACEI enalapril are equally effective in slowing renal function deterioration in type 2 DM with
mild to moderate HTN and early nephropathy

ELITE-SYMPHONY NEJM 2007; 357:2562-75

Daclizumab induction, MMF, steroids, and low-dose tacrolimus effectively maintain stable renal function following renal
transplantation, without the negative effects on renal function commonly reported for standard CNI regimens

FHN

NEJM 2010;363:2287-300

Patients were randomized to dialysis 6x/wk (frequent) or 3x/wk (conventional); frequent hemodialysis was associated with
improvement in composite outcomes of death, or change in left ventricular mass and death, or change in a physical-health
composite score; frequent hemodialysis caused more frequent interventions related to vascular access

HEMO

NEJM 2002; 347:2010-19

Use of high dose dialysis or high flux membranes vs. standard dose or low flux in thrice-weekly dialysis does not improve
survival or outcomes; possible benefit in cardiac-related outcomes with high flux membranes

IDEAL

NEJM 2010; 363:609-19

Patients with progressive CKD and GFR between 10 and 15 mL/min randomized to initiate dialysis at GFR of 10-14 mL/
min (early) or 5-7 mL/min (late); early initiation of dialysis in patients with stage G5 CKD was not associated with an
improvement in survival or clinical outcomes

IDNT

NEJM 2001; 345:851-60

Treatment with irbesartan reduced the risk of developing end-stage renal disease and worsening renal function in patients
with type 2 DM and diabetic nephropathy

IRMA

NEJM 2001; 345:870-8

Irbesartan is renoprotective independently of its blood pressure lowering effect in patients with type 2 DM and microalbuminuria

MDRD

Ann Intern Med 1995;

123:754-62

Patients with proteinuria of more than 1 g/d should have a target BP <125/75 mmHg; patients with proteinuria of 0.25-1.0
g/d should have a target BP <130/80 mmHg

ONTARGET

Lancet 2008; 372:547-53

Telmisartan and ramipril monotherapy reduced proteinuria and rise in Cr in patients with high vascular risk; combination of the
two agents led to increased acute renal failure episodes, syncope, and hypotension

REIN

Lancet 1999; 354:359-64

In non-diabetic nephropathy, ACEI were renoprotective in patients with non-nephrotic range proteinuria

REIN2

Lancet 2005; 365:939-46

In non-diabetic nephropathy already on ACEI, no further benefit from intensified BP control (sBP/dBP<130/80 mmHg) by
adding a CCB vs. conventional BP control (dBP<90 mmHg) on ACEI alone

RENAAL

NEJM 2001; 345:861-9

Losartan conferred significant renal benefits in patients with type 2 DM and nephropathy and was generally well-tolerated

RENAL

NEJM 2009; 361:1627-38

High intensity continuous renal-replacement therapy in AKI does not improve survival or outcomes compared to low
intensity treatment, and is associated with higher rates of hypophosphatemia