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Vitamin D: The effects besides the sceleton
Prof. Andrzej Więcek
Department of Nephrology, Endocrinology and Metabolic Diseases Medical University of Silesia, Katowice, Poland
e-mail: [email protected]
13-17 November 2013
30. Ulusal Nefrologii, Hipertansiyon, Diyaliz ve Transplantasyon Kongressi
30th Ntional Congress of Nephrology, Hypertension, Dialysis and Transplantation
13-17 November 2013
Cunningham J, Zehnder D. Kidney Int., 2011, 79, 702-709
Nomenclature of Vit. D precursors and metabolities
Nomenclature of Vit. D precursors and metabolities
25-OH-D best indicator of Vit. D status
• <=20 ng/ml (<= 50 nmol/l) - defficiency
• 21-29 ng/ml (51-74 nmol/l) - insufficiency
• 30 ng/ml ( 75 nmol/l) - normal level
Optimal serum concentration: o Children 20- 60 ng/ml (50-150 mmol/l) o Adults 30-80 ng/ml (75-200 nmol/l)
• ≥100 ng/ml (≥ 250 nmol/l ) – possible toxicity
Serum concentrations of 25-OH-D
Vitamin D deficiency/insufficiency
In 20-50% of general population Holick MF,Mayo Clin Proc,2006,81,353, van der Vielen RP, Lancet, 1995, 346,207
In > 50% femails with sever osteoporosis serum levels of Vit. D was below 30 ng/ml
Holick MF, J Clin Endocrinol Metab, 2005, 90, 3215
U 40-100% elderly population in both Europe and USA serum levels of Vit. D was below the normal value Holick MF, Mayo Clin Proc,2006, 81,353, Chapuy MC,Osteopor Int,1997,7, 439
Serum levels of Vit. D in 41504 subjects from general population in USA
Anderson JL et al.: Am J Cardiol 2010; 106: 963–968
Family with rickets, Paris, 1900
How the normal values for 25-OH-D were obtained?
At the level of 25-OH-D > 30 ng/ml (> 75 nmol/l) secretion of PTH is minimal and calcium absorption from GI tract is maximal
Serum 25-OH-D concentration 21-29 ng/ml is not sufficient because does not supress maximally PTH secretion and dose not lead to maxinal absorption of calcium from the GI tract
Serum 25-OH-D concentration <= 20 ng/ml (<= 50 nmol/l)
is accepted as a Vit. D defficient status
Walicka M. et al., Post. N. Med. 2012, 1, 14-22
Relationship between serum 25-OH-D concentration and all-cause and CV mortality in 10170 participants of the NHNES study
Am. J. Med. 2013, 126, 509-514
Relationship between the risk of all cause mortality (solid lines) and cardiovascular disease (dotted lines) and serum 25-OH-D concentration
Amer M. et al., Am. J. Med. 2013, 126, 509-514
Vitamin D and cardiovascular mortality and morbidity
Low serum vit. D is associated with increased blood pressure (especially in Afo-American patients)
(Schmitz KJ, Hypertens.,2009,22,867)
Documented increased risk of myocardial infarction in patients with Vit. D insufficiency
Scragg R, Int J Epidemiol,1990;19:563
Patients with congestive heart failure are characterized by decreased serum concentration of Vit. D
(Zitterman A, J Am Coll Cardiol, 2003,41:105-112
Vit. D reduces apoptosis and secretion of proinflammatory cytokines by myocardiocytes in culture
(Artaza JN et al., Clin J Am Soc Nephrol, 2009, 4: 1515-1522)
Vitamin D and blood preasure
J. Hypertens., 2009, 27, 1948 - 1954
Relationship between changes in flow mediated dilatation and changes in serum FGF23, 25-OH-D and phosphate concentrations after kidney transplantation
Yilmaz M.I. et al., Am J Nephrol 2013; 37:126–134
Artaza JN et al., Clin J Am Soc Nephrol, 2009, 4: 1515-1522
Protective role of Vit. D in the devlopment of atherosclerotic plaque
Parameters of Ca-P metabolism in patients with CKD
Pavik I. et al., Nephrol.Dial.Transpl., 2013, 28, 352 - 359
Prevalence of Vit. D deficiency in patients with different stages of chronic kidney disease
Yun Jung Oh et al., Nephrol. Dial. Transplant. 2012; 27: 2396-2403
Vit. D insufficiency and deficiency in different stages of CKD (n=2895)
Satirapoj B. et al., BMC Nephrology, 2013, 14, 206
Pathogenesis of Vitamin D deficiency in patients with CKD
Saliba W. J Am Board Fam Med 2009, 22: 574
Chronic kidney disease
Rojas-Rivera J, Nephrol. Dial. Transpl. 2010,
25, 2850-2865
Causes and consequences of Vit. D deficiency in CKD patients
Vit. D deficiency and cardiovascular complications in hemodialized patients with CKD
Drechsler Ch. et al. Eur. Heart J. 2010, 31, 2253–2261
Krause R et al. Anticancer Res. 2012;32:,391395
Serum 25-OH-D concentration and mortality in hemodialyzed patients with CKD
Retrospective study with
6518 patients
Serum levels of Vit. D in patients after kidney transplantation
Obi Y.et al.
Cancer Rev. Res., 2012, 5, 1229 - 1235
Vitamin D levels in patients after kidney transplantation during the winter and summer time
Burkhalter F. et al. Swiss Med. Week. 2012, 142, w13672
Serum concentration of Vit. D and progression of diabetic nephropathy
Clin. J. Am. Soc. Nephrol., 2013, 8, 1870-1876
Kaplan Meier survival curves for the primary end-point (increase more than 50% creatinine, dialysis or death) comparing patients with 25-OH-D deficiency (15 ng/ml)
to those with 25-OH- D levels >=15 ng/ml)
Fernandez-Juarez G. et al., Clin. J. Am. Soc. Nephrol., 2013, 8, 1870-1876
Relationship between 25-OH-D serum concentrations and urinary P/C ratio and i-PTH levels in kidney transplant recipients
Lee D.R. i wsp., Transplant. Proc., 2011, 43, 3723 - 3789
The impact of pretransplant 25-OH-D deficiency on subsequent graft function
Kim H. et al., BMC Nephrology, 2012, 13, 22
Pretransplant 25-OH-D defficiency is a strog predictor of graft function decline in patients after kidney transplantation
Kim H. et al., BMC Nephrology, 2012, 13, 22
Relationship between serum 25-OH-D concentration 3 month after kidney transplantation
and graft function 12 month after transplantation
Bienaimé F. et al., J. Am. Soc. Nephrol., 2013, 24: 831–841
Association of baseline variables with interstitial fibrosis/tubular atrophy score progression in univariate analysis
Bienaimé F. et al., J. Am. Soc. Nephrol., 2013; 24: 831–841
Influence of Losartan and/or Paricalcitol on proteinuria and kidney function in db/db mouse
Deb D.K. et al.: Kidney Int., 2010; 77: 1000-1009
Influence of Losartan and/or Paricalitol on the glomerulosclerosis sccore in db/db mouse
Deb DK et al.: Kidney Int, 2010; 77: 1000-1009
Antiproteinuric effect of paricalcitol in CKD patients treated with maximal tolerated doses of RAAS inhibitors
De Nicola L. et al., BMC Nephrology, 2012, 13, 150
Proteinuria in CKD patients after 6 month of Paricalcitol therapy and 3 month after drug withdrawal
De Nicola L. et al., BMC Nephrology, 2012, 13, 150
Proteinuria in CKD patients after 6 month of Paracalcitol therapy and 3 month after drug withdrawal
De Nicola L. et al., BMC Nephrology, 2012, 13, 150
Serum calcium and phosphate remained within normal range in all patients (only one single episode of hyperphosphatemia)
Influence of Paricalcitoi on albuminuria in patients with diabetic nephropathy. Results from the VITAL study.
De Zeeuw D et al.,: Lancet , 2010; 376: 1543-1551
Fishbane S, et al., Am. J. Kidney Dis. 2009, 54, 647-652
p= 0.04
p= 0.01 NS
NS
Influence of Paricalcitol on proteinuria in patients with CKD (eGFR 35-40ml/min, 65% of patients were with DN)
Fishbane S, et al., Am. J. Kidney Dis. 2009, 54, 647-652
p= 0.04
p= 0.01 NS
NS
No significant influence on eGFR !
Influence of Paricalcitol on proteinuria in patients with CKD (eGFR 35-40ml/min, 65% of patients with DN)
Comparison of reduction of proteinuria after treatment with Paricalcitol – results from different clinical trials
De Lorenzo et al., Nefrologia, 2013, 33, 709-715
Oral cholecalciferol decreases albuminuria and urinary TGF-β1 in patients with type 2 diabetic nephropathy
Kim M. J. et al.: Kidney Int. 2011; 80: 851-860
Thomas M.C., Cooper M.E., Lancet, 2010, 1521-1522
Influence of Vit. D on the renin - angiotensin - system
Renoprotective mechanisms of Vit. D receptor agonists
Agarwal R.: Kidney Int. 2010; 77: 943-945
Pathomechanisms of renoprotective effects of Vit. D receptor agonists
Li Y. Ch. Kidney Int., 2010, 78, 134-139
Localisation of Vitamin D receptors in humans
Cozzolino M., Clin. Kidney J., 5, 2012, 5, 285-287
Rojas-Rivera J, Nephrol. Dial.Transplant., 2010, 25, 2850-2865
1,25 (OH)D3
Vitamin D activity besides of the skeleton
Role of the calcidiol insufficiency in the pathogenesis of different diseases
Tuohimaa P.: J Steroid Biochem Mol Biol. 2009; 114: 78-84
Vit. D defficiency and increased risk of cardiometabolic complications in CKD patients
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Increased risk of 5-year probability of metabolic syndrome in patients with lower Vit. D serum concentration metabolicznego
Gagnon C. et al., J Clin Endocrinol Metab., 2012, 97: 1953–1961
Immunomodulatory effects of Vit. D
Fletcher J.M. et al..., Recent Patents on Inflammation and Drug Discovery, 2012, 6, 22-35
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Kempker J. A., i wsp. Dermato-Endocrinology, 2012, 4, 101- 108
Vitamin D and sepsis
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Kempker J. A., i wsp. Dermato-Endocrinology, 2012, 4, 101- 108
Kempker J. A., i wsp. Dermato-Endocrinology, 2012, 4, 101- 108
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Wolff A. Nat Clin Pract Rheumatol. 2008, 11:580-588
Association between vitamin D defficiency and hepatitis C virus infection
Villar L.M., et al..World J Gastroenterol., 2013,19, 5917-5924
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Estimared incidence of postransplant malignancy in (A) the entire cohort and (B) the propensity-score matched patients
Obi Y.et al., Cancer Rev. Res., 2012, 5, 1229 - 1235
Gonzalez-Parra E. i wsp., Nephrol. Dial. Transplant., 2012, 27, Suppl. 4, iv17-iv21)
Summary of key points
1. Vit. D deficiency or insufficiency is associated with renal
and cardiovascular diseases. A rapidly growing body of evidence
has suggested a role of Vit. D in renal and cardiovascular protection
2. Reno-protective actions of Vit. D have been demonstrated in a variety
of experimental models of kidney diease. The anti-proteinuric activity
of Vit. D or Vit. D analogs is confirmed by randimized clinical trials
3. The cardiovascular protective effect of Vit. D is supported by strong
epidemiological data. Anti-hypertrophic and anti-atherosclerotic activities
of Vit. D and Vit. D analogs have been reported in a number of animal
models
4. By contrast, the results from RCTs on vitamin D treatment and
cardiovascular risk are inconsistent regarding effects of vitamin D
in cardiovascular risk. We therefore have to wait for results of large
vitamin D RCTs to assess cardiovascular endpoints
Thank you very much for your attention!
Andrzej Więcek
Katowice
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