Preventing Progression to Renal Disease
By Wayne Kuznar
CHICAGO—In a comparison of 2 angiotensin receptor blockers (ARBs) in patients with type 2 diabetes and chronic kidney disease, telmisartan (Micardis) reduced protein in the urine to a greater degree than did losartan (Cozaar), reported George Bakris, MD, at the American Society of Hypertension annual meeting.
George Bakris, MD
The data suggest that telmisartan may confer greater protection against progression to end-stage renal disease, independent of blood pressure (BP)-lowering effects, but this hypothesis must be tested in a prospective study, said Dr Bakris, professor of medicine, University of Chicago, and director of the Hypertension Center in the Diabetes Institute.
The presence of proteinuria (or albuminuria) is associated with a high risk of renal disease progressing to an end stage, and with an elevated risk of cardiovascular (CV) events as well, he said.
"What is newly appreciated is that it's not good enough to just lower blood pressure," Dr Bakris said. "We have to see what's happening to albuminuria. Albumin is an even better predictor than proteinuria of outcomes in terms of both kidney disease and cardiovascular disease." The elevated CV risk with albuminuria is observed not only in the diabetic population but also in persons without diabetes or hypertension.
In previous clinical trials of ARBs conducted in patients with kidney disease, a 30% reduction in proteinuria at 6 months to 1 year following initiation of BP treatment correlated strongly with a slowing of the progression of diabetic nephropathy, independent of BP reduction, and a reduction in the incidence of CV events. Current hypertension treatment guidelines recommend ARBs for the treatment of diabetic nephropathy to slow the progression of kidney disease.
In this study, 860 patients with type 2 diabetes, hypertension (BP <130/80 mm Hg), and overt nephropathy were randomized to telmisartan, titrated to 80 mg/day, or to losartan, titrated to 100 mg/day. Hydrochlorothiazide and calcium antagonists could be added if BP remained above 130/80 mm Hg.
All patients had diabetes for an average of 14 to 16 years. The average urinary protein:creatinine ratio at baseline was approximately 2000 mg/gCr. "Normal is less than 30 mg/gCr, so these patients had huge elevations. If you were to look at estimated glomerular filtration rate, they had lost about 60% to 65% of their kidney function. This is well-advanced kidney disease," said Dr Bakris.
Treatment was stopped at 1 year, after which patients were followed for an additional 8 weeks to determine the persistent effect of the antihypertensive agents on urinary protein excretion independent of any BP reduction.
Despite comparable BP reductions between the 2 groups, the mean final urinary protein to creatinine ratio was 0.71 in the telmisartan-treated patients compared with 0.80 in the losartan-treated patients ( = .0284).
A far greater percentage of patients in the telmisartan group had a persistent antiproteinuric effect 2 months after the drugs were stopped.
Telmisartan also prolonged the time to a first CV event, produced a greater reduction in the incidence of an overall composite of a doubling of serum creatinine, end-stage renal disease, and all-cause death; and a greater lowering of the incidence of a CV composite end point consisting of myocardial infarction, stroke, a first hospitalization for heart failure or unstable angina, and a coronary or peripheral revascularization procedure.
Losartan is currently approved as a first-line treatment for diabetic nephropathy. The advantage of telmisartan in this study may lie in its longer duration of action and its greater binding to the angiotensin-1 receptor, Dr Bakris speculated.