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

Larsen, Thomas; Mose, Frank Holden; Bech, Jesper Nørgaard; Pedersen, E. B.

doi:10.1186/1471-2369-14-163

Cited by 35 publications

(26 citation statements)

References 35 publications

(44 reference statements)

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“…This functional effect may depend on an interference of paricalcitol with the regulation of glomerular microcirculation by the NO system. 28 Of note, the increase in endothelium-dependent vasodilatation in our study occurred in the face of a doubling in plasma levels of FGF23, a biomarker that was associated to endothelial dysfunction in this population. 29 Observational studies in patients with CKD, like in the Chronic Renal Insufficiency Cohort (CRIC) study, 30 associated high FGF23 with adverse cardiovascular and renal outcomes.…”

Section: Discussionmentioning

confidence: 99%

Paricalcitol and Endothelial Function in Chronic Kidney Disease Trial

et al. 2014

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Abstract-Altered vitamin D metabolism and low levels of the active form of this vitamin, 1,25-dihydroxy-vitamin D, is a hallmark of chronic kidney disease (CKD), but there is still no randomized controlled trial testing the effect of active forms of vitamin D on vascular function in patients with CKD. Paricalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY) is a double-blinded randomized controlled trial (ClinicalTrials.gov, NCT01680198) testing the effect of an active form of vitamin D, paricalcitol (2 μg/d×12 weeks) on endothelium-dependent and endothelium-independent vasodilatation in 88 patients with stage 3 to 4 CKD and parathormone >65 pg/mL (paricalcitol, n=44; placebo, n=44). Paricalcitol treatment reduced parathormone (−75 pg/mL; 95% confidence interval, -90 to -60), whereas parathormone showed a small rise during placebo (21 pg/mL; 95% confidence interval, 5-36). Blood pressure did not change in both study arms. Baseline flow-mediated dilation was identical in patients on paricalcitol (3.6±2.9%) and placebo (3.6±2.9%) groups. After 12 weeks of treatment, flow-mediated dilation rose in the paricalcitol but not in the placebo group, and the betweengroup difference in flow-mediated dilation changes (the primary end point, 1.8%; 95% confidence interval, 0.3-3.1%) was significant (P=0.016), and the mean proportional change in flow-mediated dilation was 61% higher in paricalcitoltreated patients than in placebo-treated patients. Such an effect was abolished 2 weeks after stopping the treatment.

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Section: Discussionmentioning

confidence: 99%

Paricalcitol and Endothelial Function in Chronic Kidney Disease Trial

et al. 2014

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“…Details of all included studies are given in eTable 1 in the Supplement. Six trials 15–19,33 used 1-α-hydroxylated vitamin D derivatives or calcitriol; 4 trials, 23,29,49,62 paricalcitol; and the other trials, ergocalciferol or cholecalciferol.…”

Section: Resultsmentioning

confidence: 99%

Effect of Vitamin D Supplementation on Blood Pressure

et al. 2015

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“…De Zeeuw et al , Larsen et al ., and Joergensen et al . have shown that paracalcitol therapy, a VDR agonist, can lower albuminuria in advanced chronic kidney disease with or without diabetes; however, whether this effect is attributable to RAAS activity reduction remains to be proved(14, 97-99). …”

Section: Introductionmentioning

confidence: 99%

The renin–angiotensin–aldosterone system and calcium-regulatory hormones

2015

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There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact in order to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies, and provide insight into the results of prior and on-going intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent.

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

Cited by 35 publications

References 35 publications

Paricalcitol and Endothelial Function in Chronic Kidney Disease Trial

Paricalcitol and Endothelial Function in Chronic Kidney Disease Trial

Effect of Vitamin D Supplementation on Blood Pressure

The renin–angiotensin–aldosterone system and calcium-regulatory hormones

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