Transcript Selective vitamin D receptor activation with paricalcitol for reduction

Selective vitamin D receptor activation with
paricalcitol for reduction of albuminuria in
patients with type 2 diabetes (VITAL study)
: a randomised controlled trial
Lancet 2010; 376: 1543–51
Dick de Zeeuw, Rajiv Agarwal, Michael Amdahl, Paul Audhya, Daniel Coyne,Tushar Garimella,
Hans-Henrik Parving,Yili Pritchett, Giuseppe Remuzzi, Eberhard Ritz, Dennis Andress
R1. SUNHEE PARK/PROF. SEUNGJOON OH
INTRODUCTION
• Diabetes mellitus represents a worldwide epidemic, and increases
macrovascular and microvascular risk.
• Drugs that intervene in the renin–angiotensin–aldosterone system
(RAAS) can retard both cardiovascular and renal morbidity and
mortality.
– angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers
(ARBs)
– partly due to the lowering of albuminuria
– However, residual cardiovascular and renal risk can be extremely high
• Because residual renal risk is positively associated with residual
albuminuria, therapies are needed to further reduce risk factors,
including high blood pressure and albuminuria.
 Lower calcitriol concentrations strongly correlated with higher risk of
diabetes, higher urinary albumin-to-creatinine ratio (UACR), and lower eGFR.
Kidney International 2007, vol. 71, 31–38
 A selective activator of the vitamin D receptor, paricalcitol, reduced
albuminuria and slowed the progression of kidney injury with little effect on
mineral metabolites.
J Am Soc Nephrol 2007,vol.18,1796–1806
Editorial lancer 2010, Vol. 376
Kidney international 2008, vol. 74, 22-36
 We undertook a randomised trial to prospectively test the effectiveness
of paricalcitol for the reduction of residual albuminuria in patients with
type 2 diabetic nephropathy who were receiving stable treatment with
an ACE inhibitor or ARB.
METHODS
2007.2~2008.10
33 hospitals and 27 clinics
Randomisation 3 group (1:1:1) : placebo, 1 μg paricalcitol, 2 μg paricalcitol
baseline
4wk
8wk
12wk
16wk
20wk
24wk
Treatment phase
+30d
+60d
Withdrawal phase
Medicaion (ACE inhibitors or ARB)
Exam) BP, PR, advers events, concomitant drug treatments, adherence to drug
regiments, blood chemistry(plasma paricalcitol concentration etc.), urine collection
– Primary efficacy : percentage change in geometric mean UACR from baseline to the last
measurement during treatment.
– Secondary efficacy : percentage change in geometric mean 24 h urinary albumin from baseline
to the last measurement during treatment + the proportion of patients achieving at least a
15% reduction in geometric mean UACR.
– change in primary and secondary measures during the 60 days after treatment completion
RESULTS
Table 1: Characteristics of patients at baseline
In the secondary efficacy analysis, reduction in
geometric mean 24 h rate of albumin excretion was much
higher in the 2 μg paricalcitol group than in the placebo group,
with a between-group diff erence of –28% (p=0・009)
Figure 3:
Change in urinary albuminto-creatinine ratio, estimated
glomerular fi ltration rate,
and systolic blood pressure
during treatment and
withdrawal
CONCLUSION
 Addition of 2 μg/day paricalcitol to RAAS inhibition safely
lowers residual albuminuria in patients with diabetic
nephropathy and could be a novel approach to lower residual
renal risk in diabetes.