30th Ntional Congress of Nephrology, Hypertension ... · Department of Nephrology, Endocrinology...

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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: awiecek@spskm.katowice.pl

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