Survival of Patients Undergoing Hemodialysis with Paricalcitol or Calcitriol Therapy

Teng, Ming; Wolf, Myles; Lowrie, Edmund G.; Ofsthun, Norma J.; Lazarus, J. Michael; Thadhani, Ravi

doi:10.1056/nejmoa022536

Cited by 856 publications

(688 citation statements)

References 38 publications

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“…Importantly, although our retrospective clinical data of activated vitamin D-treated hemodialysis subjects involved small numbers, the observed significant improvement in cardiac alterations is encouraging and suggestive of a potential for clinical intervention. These results, the accumulating data on the cardiovascular effects of activated vitamin D, and studies from our group and others suggesting a survival benefit associated with activated vitamin D therapy in dialysis patients (3,4,20) strongly support the basis for an interventional trial to directly assess the cardiacspecific effects of activated vitamin D administration in renalfailure subjects. Skin-derived 7-dehydrocholesterol undergoes liver hydroxylation to form 25(OH)D 3 , the storage form of vitamin D (21).…”

Section: Discussionsupporting

confidence: 62%

“…We recently demonstrated in observational studies that therapy with activated vitamin D to chronic hemodialysis patients is associated with reduction in cardiovascular-related mortality (3,4). Conversion of nutritional vitamin D (25(OH)D 3 ) to the hormonally active form of vitamin D (1,25(OH) 2 D 3 ) occurs primarily in the kidney; thus, patients with kidney failure commonly present with altered vitamin D status (5).…”

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confidence: 99%

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Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Bodyak

Ayus²,

Achinger³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Observations in hemodialysis patients suggest a survival advantage associated with activated vitamin D therapy. Left ventricular (LV) structural and functional abnormalities are strongly linked with hemodialysis mortality. Here, we investigated whether paricalcitol (PC, 19-nor-1,25(OH)2D2), an activated vitamin D compound, attenuates the development of LV abnormalities in the Dahl salt-sensitive (DSS) rat and whether humans demonstrate comparable findings. Compared with DSS rats fed a high-salt (HS) diet (6% NaCl for 6 weeks), HS؉PC was associated with lower heart and lung weights, reduced LV mass, posterior wall thickness and end diastolic pressures, and increased fractional shortening. Blood pressures did not significantly differ between the HS groups. Plasma brain natriuretic peptide levels, and cardiac mRNA expression of brain natriuretic peptide, atrial natriuretic factor, and renin were significantly reduced in the HS؉PC animals. Microarray analyses revealed 45 specific HS genes modified by PC. In a retrospective pilot study of hemodialysis patients, PC-treated subjects demonstrated improved diastolic function and a reduction in LV septal and posterior wall thickness by echocardiography compared with untreated patients. In summary, PC attenuates the development of LV alterations in DSS rats, and these effects should be examined in human clinical trials.cardiac hypertrophy ͉ heart failure ͉ paricalcitol ͉ renal failure T he rate of cardiovascular-related mortality in hemodialysis patients is 10-20 times higher than that observed in the general population (1). Left ventricular hypertrophy (LVH) and diastolic dysfunction are present in Ͼ50% of patients at dialysis initiation, and these abnormalities are strongly linked with dialysis-related mortality (2). Currently, there are no well accepted means to modify cardiac structural and functional alterations in renal-failure patients.We recently demonstrated in observational studies that therapy with activated vitamin D to chronic hemodialysis patients is associated with reduction in cardiovascular-related mortality (3, 4). Conversion of nutritional vitamin D (25(OH)D 3 ) to the hormonally active form of vitamin D (1,25(OH) 2 D 3 ) occurs primarily in the kidney; thus, patients with kidney failure commonly present with altered vitamin D status (5). There is growing evidence that vitamin D either directly or indirectly affects cardiac structure and function. The vitamin D receptor knockout mouse model demonstrates increased cardiac renin expression and marked cardiomyocyte hypertrophy (6), and 1,25(OH) 2 D 3 attenuates cardiomyocyte proliferation (7) and hypertrophy (8) in vitro. Here, we demonstrate that treatment with an activated vitamin D compound attenuates the development of cardiac hypertrophy and dysfunction in a recognized animal model of such abnormalities and that comparable findings are evident in humans.

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Section: Discussionsupporting

confidence: 62%

mentioning

confidence: 99%

Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Bodyak

Ayus²,

Achinger³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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301

249

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“…In historical/retrospective cohort studies (also known as nonconcurrent cohort studies), a group of individuals (the cohort) is identified on the basis of a common feature or features that were determined in the past (e.g., starting dialysis during a particular period; see references [3,4] for examples). Historical cohort studies represent studies in which exposures and outcomes were collected sometime in the past, but the ascertainment of exposures antedated the development of the outcomes, and hence the temporal sequence of events (provided that no subjects have the outcome at the time exposures are measured) is preserved.…”

Section: Selection Biasmentioning

confidence: 99%

Cohort Studies

Thadhani

Tonelli

2006

Clinical Journal of the American Society of Nephrology

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“…Vitamin D has a wide range of beneficial effects besides PTH suppression, including modulating immune response and cell differentiation (Nagpal et al 2005;Valdivielso et al 2009). Because of these effects of vitamin D, it may offer new means to control the inflammatory state of ESRD patients, and vitamin D administration has been shown to improve mortality in HD patients (Teng et al 2003;Teng et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Calcitriol Treatment Increases Serum Levels of the Soluble Receptor of Advanced Glycation End Products in Hemodialysis Patients with Secondary Hyperparathyroidism

Sung

Chung

Kim

et al. 2013

Tohoku J. Exp. Med.

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Cardiovascular disease is common in the patients with end-stage renal disease, who often suffer from secondary hyperparathyroidism (SHP). Vitamin D is considered for the first-line therapy managing SHP in hemodialysis (HD) patients and has a beneficial effect in the chronic inflammation and development of cardiovascular disease. The soluble receptor for advanced glycation end products (sRAGE) may be protective by binding AGE in the pathogenesis of atherosclerotic vascular complications, whereas extracellular RAGE-binding protein (EN-RAGE) represents pro-inflammatory ligands for RAGE. We have hypothesized that vitamin D treatment may alter the levels of sRAGE and EN-RAGE in HD patients. Therefore, this prospective observational study was performed in 51 HD patients with SHP who had low serum 1,25 dihydroxyvitamin D 3 (1,25D) levels and elevated intact parathyroid hormone (PTH) levels. We evaluated the changes in the values of sRAGE, EN-RAGE, and other inflammatory marker, interleukin-6 (IL-6), before and at the end of the 8-week calcitriol treatment. After calcitriol treatment, the serum levels of 1,25D were increased, whereas the serum intact PTH levels were decreased. In addition, the sRAGE levels were increased, whereas those of IL-6 were decreased after calcitriol treatment. A positive correlation between 1,25D and sRAGE levels (r = 0.609, P < 0.001) and a negative correlation between sRAGE and EN-RAGE levels (r = −0.368, P = 0.020) were detected after calcitriol treatment. This study suggests that calcitriol treatment could play an anti-inflammatory role through the increasing sRAGE in HD patients with SHP.

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Survival of Patients Undergoing Hemodialysis with Paricalcitol or Calcitriol Therapy

Abstract: Patients who receive paricalcitol while undergoing long-term hemodialysis appear to have a significant survival advantage over those who receive calcitriol. A prospective, randomized study is critical to confirm these findings.

Cited by 856 publications

References 38 publications

Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals

Cohort Studies

Calcitriol Treatment Increases Serum Levels of the Soluble Receptor of Advanced Glycation End Products in Hemodialysis Patients with Secondary Hyperparathyroidism

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