Effect of paricalcitol on renin and albuminuria in non-diabetic stage III-IV chronic kidney disease: a randomized placebo-controlled trial

Thomas Larsen, Frank H Mose, Jesper N Bech, Erling B Pedersen, Thomas Larsen, Frank H Mose, Jesper N Bech, Erling B Pedersen

Abstract

Background: Vitamin D receptor activators reduce albuminuria, and may improve survival in chronic kidney disease (CKD). Animal studies suggest that these pleiotropic effects of vitamin D may be mediated by suppression of renin. However, randomized trials in humans have yet to establish this relationship.

Methods: In a randomized, placebo-controlled, double-blinded crossover study, the effect of oral paricalcitol (2 μg/day) was investigated in 26 patients with non-diabetic, albuminuric stage III-IV CKD. After treatment, plasma concentrations of renin (PRC), angiotensin II (AngII) and aldosterone (Aldo) were measured. GFR was determined by 51Cr-EDTA clearance. Assessment of renal NO dependency was performed by infusion of NG-monomethyl-L-arginine (L-NMMA). Albumin excretion rate (AER) was analyzed in 24-h urine and during 51Cr-EDTA clearance.

Results: Paricalcitol did not alter plasma levels of renin, AngII, Aldo, or urinary excretion of sodium and potassium. A modest reduction of borderline significance was observed in AER, and paricalcitol abrogated the albuminuric response to L-NMMA.

Conclusions: In this randomized, placebo-controlled trial paricalcitol only marginally decreased AER and did not alter circulating levels of renin, AngII or Aldo. The abrogation of the rise in albumin excretion by paricalcitol during NOS blockade may indicate that favourable modulation of renal NO dependency could be involved in mediating reno-protection and survival benefits in CKD.

Trial registration: ClinicalTrials.gov identifier: NCT01136564.

Figures

Figure 1
Figure 1
Flowchart.
Figure 2
Figure 2
Effect of L-NMMA on systolic and diastolic blood pressure (BP). L-NMMA bolus injection was administered at 0min, and sustained infusion continued until 60min. P-value represents the effect of paricalcitol versus placebo assessed by a general linear model for repeated measures (n = 26).
Figure 3
Figure 3
Effect of L-NMMA on albumin excretion rate. A) Mean albumin excretion rate in placebo (closed circles) and paricalcitol (open circles) at baseline (average for 3 periods of 30 minutes) and during nitric oxide synthase inhibition (NOSi). B) Mean changes in albumin excretion rate ± SEM at baseline and during NOSi. L-NMMA was continuously infused for 60 minutes. Within differences in each group were tested by Friedman’s two-way ANOVA, and comparisons between placebo and paricalcitol were made for each point in time by Wilcoxon’s signed rank test (*p < 0.05, **p < 0.005) (n = 21).

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