Longitudinal Analysis of Vascular Function and Biomarkers of Metabolic Bone Disorders before and after Renal Transplantation

Yılmaz, Mahmut İlker; Sönmez, Alper; Sağlam, Mutlu; Yaman, Halıl; Kılıç, Selim; Türker, Türker; Ünal, Hilmi Umut; Gök, Mahmut; Çetinkaya, Hakkı; Eyıleten, Tayfun; Oğuz, Yusuf; Çağlar, Kayser; Vural, Abdülgaffar; Mallamaci, Francesca; Zoccali, Carmine

doi:10.1159/000346711

Cited by 41 publications

(49 citation statements)

References 85 publications

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“…12 Alterations in mineral metabolism may play a major role in deranged endothelial function in patients with end-stage CKD because changes in 25-OH VD, serum phosphate, and FGF23 levels brought about by restored renal function after kidney transplantation correlate with improved endotheliumdependent vasodilatation. 19 Cross-sectional studies associated 25-OH VD, 1,25-OH 2 VD, and endothelium-dependent vasodilation in patients with stage 3 to 4 CKD 20 and in patients with end-stage kidney disease on dialysis, 21 suggesting that vitamin D insufficiency or deficiency may have adverse effects on the vascular system.…”

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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“…Although low vitamin D levels were not associated with a 3-year increased risk of CVD [61] , more recent data from stable KTRs showed an independent association between 25(OH)D levels <12 ng/ml and all-cause mortality [21] . Flow-mediated dilation consensually proved to increase 25(OH)D levels close to restored renal function and reduced FGF23 levels [62] .…”

Section: Vitamin D and Main Outcomes In Ktrs: Observational Datamentioning

confidence: 92%

Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy

Cianciolo¹,

Galassi

Capelli³

et al. 2016

Am J Nephrol

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Chronic kidney disease-mineral and bone disorder (CKD-MBD) is common in kidney transplant recipients (KTRs), where secondary hyperparathyroidism (HPTH) and post-transplantation bone disease (PTBD) are potential effectors of both graft and vascular aging. Reduced 25(OH)D levels are highly prevalent in KTRs. Experimental and clinical evidence support the direct involvement of deranged vitamin D metabolism in CKD-MBD among KTRs. This review analyzes the pathophysiology of vitamin D derangement in KTRs and its fall out on patient and graft outcome, highlighting the roles of both nutritional and active vitamin D compounds to treat PTBD, cardiovascular disease (CVD) and graft dysfunction. Fibroblast growth factor-23-parathyroid hormone (PTH)-vitamin D axis, immunosuppressive therapy and previous bone status have been associated with PTBD. Although several studies reported reduced PTH levels in KTRs receiving nutritional vitamin D, its effects on bone mineral density (BMD) remain controversial. Active vitamin D reduced PTH levels and increased BMD after transplantation, but paricalcitol treatment was not accompanied by benefits on osteopenia. Vitamin D is considered protective against CVD due to the widespread pleiotropic effects, but data among KTRs remain scanty. Although vitamin deficiency is associated with lower glomerular filtration rate (GFR) and faster estimated GFR decline and data on the anti-proteinuric effects of vitamin D receptor activation (VDRA) in KTRs sound encouraging, reports on related improvement on graft survival are still lacking. Clinical data support the efficacy of VDRA against HPTH and show promising evidence of VDRA's effect in counteracting post-transplant proteinuria. New insights are mandatory to establish if the improvement of surrogate outcomes will translate into better patient and graft outcome.

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“…All consecutive adult patients (n=272) who underwent a kidney transplant at our center between January of 2003 and January of 2012 were considered for this analysis. Some of these patients are part of an ongoing prospective study encompassing measurements of vascular function, which has been described in a separate publication (20). Because the scope of our study was that of investigating the reversibility of atherosclerosis (as measured by IMT) after restoration of renal function by renal transplantation and the functional relationship between the longitudinal changes in IMT and CKD-MBD biomarkers, by protocol, we excluded patients with risk factors that may distort the interpretation of carotid artery changes brought about by successful renal transplantation, including diabetes, background cardiovascular disease, smoking, rejection episodes, and use of mammalian target of rapamycin inhibitors, a class of drugs that may per se have a favorable effect on atherosclerosis (21,22).…”

Section: Patients and Controlsmentioning

confidence: 99%

A Longitudinal Study of Inflammation, CKD-Mineral Bone Disorder, and Carotid Atherosclerosis after Renal Transplantation

Yılmaz

Sönmez

Sağlam

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives The role of reversibility of nontraditional risk factors, like inflammation and CKDmineral bone disorder, in the reduction of cardiovascular risk after renal transplantation is still scarcely defined.Design, setting, participants, and measurements The longitudinal relationship between C-reactive protein, CKDmineral bone disorder biomarkers, and intima media thickness was investigated in a series of 178 patients (age=32610 years) with stage 5 CKD maintained on chronic dialysis who underwent echo-color Doppler studies of the carotid arteries before and after renal transplantation. Smokers and patients with diabetes were excluded from the study. In all patients, immunosuppression was performed by a standard regimen on the basis of calcineurin inhibitors. Healthy controls were specifically selected to match the age and sex distribution of the patients. Biochemical and intima media thickness assessments were repeated 6 months after transplantation.Results Before transplantation, intima media thickness in patients with stage 5 CKD on dialysis (average=0.960.2 mm) was higher (P,0.001) than in well matched healthy controls (0.660.1 mm) and reduced substantially (222%; 95% confidence interval, 224% to 220%) after transplantation (P=0.001). GFR (multivariable-adjusted b=0.23; P,0.001), C-reactive protein (b=0.15; P,0.001), and fibroblast growth factor 23 (b=0.28; P,0.001) were the strongest independent correlates of intima media thickness before transplantation. Similarly, longitudinal changes in the same biomarkers were the sole independent correlates of simultaneous changes in intima media thickness (C-reactive protein: b=0.25; fibroblast growth factor 23: b=0.26; P,0.001 for both) after renal transplantation. The evolution of intima media thickness after transplantation was largely independent of classic risk factors, including BP, LDL cholesterol, and insulin resistance, as measured by homeostatic model assessment.Conclusions Intima media thickness improves after renal transplantation. Such an improvement associates with parallel changes in serum C-reactive protein and fibroblast growth factor 23. These observations are in keeping with the hypothesis that the decline in cardiovascular risk after transplantation, in part, depends on partial resolution of nontraditional cardiovascular risk factors, like inflammation and CKD-mineral bone disorder.

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Longitudinal Analysis of Vascular Function and Biomarkers of Metabolic Bone Disorders before and after Renal Transplantation

Cited by 41 publications

References 85 publications

Paricalcitol and Endothelial Function in Chronic Kidney Disease Trial

Paricalcitol and Endothelial Function in Chronic Kidney Disease Trial

Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy

A Longitudinal Study of Inflammation, CKD-Mineral Bone Disorder, and Carotid Atherosclerosis after Renal Transplantation

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