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UNIVERSITY OF MEDICINE AND PHARMACY

CRAIOVA

DOCTORAL THESIS

SUMMARY

MINERAL AND BONE DISORDERS AND

CARDIOVASCULAR RISK IN PATIENTS WITH

CHRONIC KIDNEY DISEASE

Scientific Coordinator:

Univ. Prof. Dr. Eugen Moța

PhD Candidate:

Vladu Iulia-Daniela

Craiova, 2012

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CONTENTS

I.INTRODUCTION.................................................................................................................2

II. PERSONAL RESEARCH .................................................................................................. 3

II.1. Mineral and bone metabolism and cardiovascular risk factors in patients with chronic

kidney disease ....................................................................................................................3

II.1.2. Material and methods ..................................................... ....................................... 3

II.1.3. Results and discussions...............................................................................................4

III.CONCLUSIONS........................................................................................................5

IV. SELECTED REFERENCES ..............................................................................................

KEY WORDS

Chronic kidney disease-mineral bone disorders, cardiovascular risk, chronic kidney disease,

vitamin D, dialysis, vascular calcifications

I.INTRODUCTION

Chronic kidney disease (CKD) has an increasing prevalence both in Romania and

worldwide. Today we can speak about a 'endemic prevalence' of BCR globally. Despite

growing concerns of the medical community, the figures on the incidence and prevalence of

CKD in stages predialitice [1-3] remain unknown. United States reported a prevalence of 12-

13% [4] of BCR, although other estimates (for the period 1999-2004) go up to 15.3% [5].

Today it is considered that 1 in 10 Romanian suffering from this disease and nearly 10,000

receiving renal replacement therapy (TSFR) with a growth rate of 7.2% over the previous

year, in Dolj was a decrease by 4.1% prevalence of hemodialysis (HD) in 2011 compared to

2010 [6].

Mineral Bone disease is a common complication of chronic kidney disease [30.31]

and covers a wide range of disturbances of mineral metabolism that occur in this clinical

context and consequences both bone and extraosseous defined by one or more of the

following entities: abnormal serum Ca, P, PTH and vit. D abnormalities's turnover,

mineralization, volume, linear growth or bone hardness and vascular or soft tissue

calcification [31.32].

The idea of the present thesis is based on the premise outlined above and I aimed to

analyse and evaluate the impact of mineral metabolism disturbances on cardiovascular risk in

patients with chronic kidney disease. The objectives of the thesis are based on assessing,

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determinating the prevalence and correlations between serum calcium, phosphate, vascular

calcification, traditional risk factors and other variables in patients with chronic kidney

disease in order to assess behavioral risk factors in patients with BCR in relation to general

population. It is also useful therapeutic strategy addressed both in prevention and in reducing

cardiovascular risk and vascular calcifications.

II. PERSONAL RESEARCH

II.1. Mineral and bone metabolism and cardiovascular risk factors in patients with

chronic kidney disease

The main aim of this study was to establish the prevalence of mineral and bone

metabolism disorders (hypocalcemia, hyperphosphatemia, secondary hyperparathyroidism,

valvular and vascular calcification) and cardiovascular risk in patients with chronic kidney

disease.

II.1.2. Material and methods

This is a prospective, observational, longitudinal study based on data centralized after

obtaining written informed consent, personal medical history, complete clinical examination,

lumbar spine profile radiography highlighting abdominal aortic calcifications, ECG at rest,

cardiac and carotid vessels ultrasound, biological determinations (complete blood count,

creatinine, urea, calcium, phosphorus, intact parathormone, in patients with chronic kidney

disease in different stages Nephrology Clinic Clinical Emergency County Hospital Craiova.

A total of 271 patients were included in this study and they were divided into the following

groups:

- A: 3-5 stage CKD patients (n = 100)

- B: hemodialysis patients (incident and prevalent) (n = 100)

- C: continuous ambulatory peritoneal dialysis patients (n = 19)

- D: control group, subjects without chronic kidney disease (n = 52).

Each group was divided into 2: patients with and without diabetes mellitus and the sex ratio

was 1:1.

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II.1.3. Results and discussions

The mean age of the patients included in the study was 60.43±13.20 years and the

patients were evenly distributed. Of the whole study group, 18.45% of the patients had seric

phosphorus >5.5mg/dl and 26.94% had calcium <8.5mg/dl and 33.95% of the patiens had

iPTH lower than 65pg/ml. All patients in the control group had iPTH in target whereas only

34% of the patients in CKD stages 3-5 not on dialysis had iPTH in target.

100% of the patients in the control group, 96% of the patients with CKD not yet on

dialysis, 84.21% of DP patients and 78% of the HD patients had CaXP<55mg/dl. Evaluating

the number of CKD-MBD biochemical parameters in target (Ca,P,CaXP, PTH) the

prevelance I found was: no DP patient had all 4 parameters in target- whereas 10.53% of the

patients had no parameter in target. The most important findings are found in the figures

below and are in agreement with data found in literature.

Figure 19, 20 and 22. Seric values for seric calcium, phosphorus and iPTH

Figure 29. Number of parameters in target and Figure 30. Prevalence of vascular and valvular calcifications

Control

Predializă

Stadiul 3

Stadiul 4

Stadiul 5

Hemodializă

Hemodializă incidentă

Hemodializă cronică

Dializă peritoneală continuă…

0

5

0

9.75

12.5

20

23.4

16.98

10.53

0

18

13.72

21.95

25

23

23.4

22.64

36.84

0

29

31.37

26.82

37.5

22

19.14

24.52

31.58

17.3

26

27.45

24.39

12.5

22

23.4

20.75

21.05

82.7

22

27.45

17.07

12.5

13

10.63

15.09

0

Numarul de parametrii în target 0 1 2 3 4

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Figure 35 and 36. The prevalence of calcification quartiles (Kauppila score) according to the

number of risk factors (diabetes, hypertension, dyslipidemia, and age> 60 years) and the

impact of these factors on vascular calcifications

Figure 38 and 39 Cumulative probability of survival in relation to the presence of vascular

calcifications

III. CONCLUSIONS

1. The prevalence of changes in mineral and bone metabolism parameters in the patients in

this study is similar to data found in literature (72.14% and 47.03% vascular and valvular

calcification among people with chronic kidney disease).

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2. Mineral and bone metabolism parameters had a significant impact on mortality (especially

vascular calcification (OR = 9.1, p <0.0001), valvular calcification (OR = 6.7, p <0.0001) and

hyperphosphataemia (OR = 2.4, p = 0.025)).

3. Cardiovascular risk score QRISK2-2012 is a predictor for vascular calcification in chronic

kidney disease patients.

4. Age> 60 years, diabetes, inflammation (risk generated by CRP), high blood pressure, CKD

stage and renal replacement therapy are predictors for vascular calcification.

5. Among diabetic patients with HbA1c values below 7% showed the lowest prevalence of

vascular calcifications (42.86%), the values of HbA1c≥ 7.5% - prevalence of vascular

calcifications was higher.

6. Patients treated with vitamin D had:

- Over 100% increase in serum levels of vit. D

- Sustained decrease of serum iPTH, more than 30%,

- Normalization of all parameters TMO-BCR for 26.67% of patients

- Decrease proteinuria/24h and

- Decrease in CRP.

7. Lumbar simple profile radiography and echocardiography are explorations cost-effective

for detecting vascular calcification, implicit in patients with increased cardiovascular risk.

IV SELECTED REFERENCES

1. Wen CP, Cheng TY, Tsai MK et al. All-cause mortality attributable to chronic kidney

disease: a prospective cohort study based on 462.293 adults in Taiwan. Lancet. 2008;

371(9631):2173-2182.

3. Foley RN, Parfey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in

chronic renal disease. Am J Kidney Dis. 1998; 32(5 Suppl 3):S112-S119.

4. Coresh J, Selvin E, Stevens LA et al. Prevalence of chronic kidney disease in the

United States. JAMA. 2007; 298(17):2038-2047.

5. Whaley-Connell AT, Sowers JR, Stevens LA. CKD in the United States: Kidney

Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey

(NHANES) 1999-2004. Am J Kidney Dis 2008; 51: S13-S20.

6. Raportul Anual al Registrului Renal Român 2011. Ministerul Sănătăţii - Spitalul

Clinic de Nefrologie „Dr Carol Davila”, Bucureşti, România, 2012

8. Keith DS, Nichols GA, Gullion CM et al. Longitudinal follow-up and outcomes

among a population with chronic kidney disease in a large managed care organization. Arch

Intern Med 2004; 164:659-663.

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10. Nitta K. Vascular calcification in patients with chronic kidney disease. Ther Apher

Dial. 2011; 15(6): 513-521.

11. Bhan I, Thadhani R. Vascular calcification and ESRD: a hard target. Clin J Am Soc

Nephrol. 2009; 4 Suppl 1:S102-105.

12. Schoppet M, Shroff RC, Hofbauer LC, Shanahan CM. Exploring the biology of

vascular calcification in chronic kidney disease. What's circulating? Vascular calcification in

CKD. Kidney Int. 2008; 73, 384-390.

15. Kalantar-Zadeh K, Kuwae N, Regido DL et al. Survival predictability of time-varying

indicators of bone disease in maintenance hemodialysis patients. Kidney Int, 2006, 70, 771–

780.

17. Zannad F, Kessler M, Lehert P et al. Prevention of cardiovascular events in end-stage

renal disease: results of a randomized trial of fosinopril and implicaţions for future studies.

Kidney Int. 2006; 70(7):1318-1324.

18. Wanner C, Krane V, Marz W et al. Atorvastatin in patients with type 2 diabetes

mellitus undergoing hemodialysis. The N Eng J Med. 2006; 355(20):2085-2098.

19. Pfeffer MA, Burdmann EA, Chen CY et al. Trial of Darbepoetin Alfa in Type 2

Diabetes and Chronic Kidney Disease. N Engl J Med 2009; 361:2019-2032

24. Kalantar-Zadeh K. Clinical outcomes of hypocalcemia in chronic kidney disease, US

Nephrology, 2008, 3(2): 19-23

25. Kottgen A, Russell SD, Loehr LR et al. Reduced kidney function as a risk factor for

incident heart failure: the atherosclerosis risk in communities (ARIC) study. J Am Soc

Nephrol. 2007; 18(4):1307-1315.

26. Mehrotra R. Disordered mineral metabolism and vascular calcification in nondialyzed

chronic kidney disease patients. Journal of Renal Nutrition, 2006, 16 (2): 100-118.

27. Elsayed EF, Tighiouart H, Griffith J et al. Cardiovascular disease and subsequent

kidney disease. Arch Intern Med. 2007;167(11): 1130-1136

28. McCullough PA, Li S, Jurkovitz CT et al. Chronic kidney disease, prevalence of

premature cardiovascular disease, and relationship to short-term mortality. American Heart

Journal. 2008;156(2):277-283.

29. Garcia-Donaire JA, Ruilope LM. Cardiovascular and Renal Links along the

Cardiorenal Continuum. Int J Nephrol. 2011; 2011:975782.

30. Block GA, Klassen PS, Lazarus JM et al. Mineral metabolism, mortality, and

morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004; 15: 2208-2218.

31. Kidney Disease: Improving Global Outcomes (KDIGO) CKD–MBD Work Group.

KDIGO clinical practice guideline for the diagnosis, evaluaţion, prevention, and treatment of

chronic kidney disease–mineral and bone disorder (CKD–MBD). Kidney International 2009;

76 (Suppl 113): S1–S130.

32. Kestenbaum B. Mineral metabolism disorders in chronic kidney disease. JAMA.

2011; 305:1138-1139.

33. Kalantar-Zadeh K, Kuwae N, Regidor DL et al. Survival predictability of time-

varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 2006;

70: 771-780.

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34. Levin A, Bakris GL, Molitch M et al. Prevalence of abnormal serum vitamin D, PTH,

calcium, and phosphorus in patients with chronic kidney disease: results of the study to

evaluate early kidney disease. Kidney Int 2007; 71: 31-38.

35. Palmer SC, Hayen A, Macaskill P, et al. Serum levels of phosphorus, parathyroid

hormone, and calcium and risks of death and cardiovascular disease in individuals with

chronic kidney disease: a systematic review and meta-analysis. JAMA. 2011; 305:1119-1127.

36. Covic A, Mircescu G, Schiller A, Ardeleanu S, Ghid de diagnostic si tratament al

tulburarilor minerale osoase asociate bolii cronice de rinichi (TMO-BCR). Casa Editoriala

Demiurg, 2010.

38. Moe SM, Chen NX. Mechanisms of vascular calcification in chronic kidney disease. J

Am Soc Nephrol. 2008; 19: 213-216.

40. Covic A, Kanbay M, Voroneanu L et al. Vascular calcification in chronic kidney

disease. Clin. Sci. 2010; 119: 111-121.

41. Guerin AP, London GM, Marchais SJ, Metivier F. Arterial stiffening and vascular

calcifications in end-stage renal disease. Nephrol Dial Transplant. 2000; 15:1014 –1021.

42. Blacher J, Guerin A, Pannier B, Marchais S, Safar M, London G. Impact of aortic

stiffness on survival in end-stage renal disease. Circulation. 1999;99:2434 –2439.

43. London GM, Guerin AP, Marchais SJ et al. Cardiac and arterial interactions in end-

stage renal disease. Kidney Int. 1996;50:600–608.

45. Block GA, Hulbert-Shearon TE, Levin NW, et al. Association of serum phosphorus

and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a

national study. Am J Kidney Dis 1998; 31: 607–617.

46. Dhingra R, Sullivan LM, Fox CS, et al. Relations of serum phosphorus and calcium

levels to the incidence of cardiovascular disease in the community. Arch Intern Med 2007;

167: 879–885.

Curriculum vitae

Name Vladu Iulia - Daniela Adresse Craiova, Dolj, Romania

E-mail Vladui@yahoo.com Nationality Romanian

Date of birth 18 September 1984 Gender Femele

Occupation October 2009-present Nephrology PhD student at the University od Medecine and Pharmacy Craiova January 2010-present Nephrology resident at Emergency County Hospital Craiova

Education and training

2003-2009 Faculty of Medecine, University of Medecine and Pharmacy Craiova 2008 Erasmus student - Faculte de Medecine Paris Decartes , 6 months

2010 17th Budapest Nephrology School

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2011

2012 Professional affiliation

7 months training in Service de Nephrologie, Hopital Bicatre, France : POSDRU grant ‘New trends in the diagnostics and treatment of glomerulonephritis’, Praga, Cehia, (ERA-

EDTA grant)

2010- present 2012

Romanian Nephrology Society European Renal Association - European Dialysis and Transplant Association (ERA-EDTA)

Scientific activity Enclosed Languages Understanding Speaking Writing

Listening Reading Spoken unteraction Spoken production

English C2 C2 C2 C2 C2

French C2 C2 C2 C2 C1

Personal skills and competences Microsoft Office: Word, Excel, Power Point; Adobe Reader

Other competences and aptitudes Participation in the Logos Radio Craiova - 2005-2007, empathy, team spirit, desire to work, perspicacity

Driving license B

SCIENTIFIC ACTIVITY

Articles:

1. Cardiovascular risk in patients with diabetes kidney disease. Grauntanu C, Mota E,

Mota M, Panduru NM, Bicu M, Vladu I. Rom J Int Med, 2010, 48(4): 313-319.

2. Chronic kidney disease-mineral bone disorder in diabetes melitus patients. Vladu I.,

Cana D, Vaduva C, Grauntanu C, Zaharie S, Dina R, Dina C, Mustata R, Mota E. Rom J

Diab Nutr Metab Dis 2012, 19(1): 89-98.

3. Advanced glycation end products measured by age reader in a group of patients with

obesity, Dina R, Vladu I, Dina C, Mitrea A. Rom J Diab Nutr Metab Dis 2012, 19(1): 59-

66.

4. Renal anemia and cardiac dysfunction in diabetic versus non-diabetic patients. Cana-

Ruiu D, Mota E, Trican E, Istrate N, Popescu M, Vasile R, Văduva C, Vladu I, Stoica L.

Rom J Diab Nutr Metab Dis 2012, 19 (2): 131-141.

5. Hepatic fibrosis, measured by fibroscan in a group of patients with obesity. Dina R ,

Moţa M, Vladu I , Dina C. Rom J Diab Nutr Metab Dis 2012, 19 (2): 123-129.

6. The relationship between periodontal disease and diabetes mellitus. Dina C, Iancau

M, Mota M, Dina R, Vladu I, Rom J Diab Nutr Metab Dis 2012, 19(2): 181-188.

7. Prognostic factors for vascular calcification in chronic kidney disease patients. Vladu I

et al. -in press

Presentations (oral and poster) at national and international congresses:

1. Case report: the use of hematopoietic growth factors in the management of neutropenia

induced by treatment with pegylated interferon in chronic viral hepatitis, G. Iliescu, V.

Biciusca, Vladu I., The 8th National Congress pharmacology, toxicology and clinical

therapy, Tg.Mures, 2007

2. Biochemical and hematological tests in non-invasive assessment of liver damage in

chronic hepatitis C G. Iliescu, V. Biciusca Mr. Manonelescu, A. Bold, Vladu I., The 6th

National Congress of Laboratory Medicine, Sibiu, 2007

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3. Laboratory tests in monitoring patients with hematologic chronic viral hepatitis treated

with interferon-G. Iliescu, V. Biciusca, F. Popescu, Vladu I., The 6th National Congress

of Laboratory Medicine, Sibiu, 2007

4. Study on the associations between certain variables with metabolic responses fibrinolitic

and blood clotting in the exercise, Vladu I., O. Olteanu, R. Sandoi, R. Radulescu, The

11th international congress for medical students and young Physicians, Timisoara 2007

5. Therapeutic options in hemodialysis patients with high cardiovascular risk- Vladu I., D.

Mary, C. Grauntanu, C. Vaduva, E. Mota, Le14eme international congress for medical

students and young doctors, Timisoara 2010

6. Proteinuria as a cardiovascular risk factor in patients with type 1 diabetes Grauntanu C.,

M. Bicu, C. Vaduva, S. Zaharie, Dena M., O. Jercan, Vladu I., M. Mota, Mota E., Days

of the University of Medicine and Pharmacy Craiova 2010

7. Screening in the general population (World Kidney Day 2010) compared to the late

presentation to nephrologists of patients with chronic kidney disease, Dena M., C.

Grăunţanu, C. Vaduva, Vladu I., M. Tudor, C. Militaru, Mota E. Days of the University

of Medicine and Pharmacy Craiova 2010

8. The evolution of anemia in hemodialysis patients, Jercan O., C. Militaru, C. Grauntanu,

C. Vaduva, D. Alexandru, Vladu I., E. Mota, Days of the University of Medicine and

Pharmacy Craiova 2010

9. The incidence of secondary hyperparathyroidism and disorders of the metabolism of

calcium and phosphorus in the initiation of dialysis- Vladu I., C.Grauntanu, C. Vaduva,

S. Zaharie, M. Dena, D. Giurka, E. Mota, Days of the University of Medicine and

Pharmacy Craiova 2010

10. Analysis of the social impact of sport in replacement therapy in renal function, A.

Arcereanu, C. Vaduva, Vladu I., E. Mota, Days of the University of Medicine and

Pharmacy Craiova 2010

11. Glucose tolerance in hemodialysis patients vs patients with renal transplantation-

C.Vaduva, C. Grauntanu, Vladu I., Dena M., D.Cana-Ruiu, E. Mota, Days of the

University of Medicine and Pharmacy Craiova 2010

12. Cardiovascular risk was the beginning of dialysis, S. Zaharie, Vladu I., E. Mota, Days of

the University of Medicine and Pharmacy Craiova 2010

13. The prevalence of disorders of bone and mineral metabolism associated with chronic

kidney disease at the initiation of dialysis- Vladu I., M. Mota, Mota E., Annual Congress

of the Romanian Medical Association, Bucharest 2010

14. Analysis of the social impact of sport in replacement therapy in renal function, A.

Arcereanu, C. Vaduva, Vladu I., E. Mota, Days of the University of Medicine and

Pharmacy Craiova 2010

15. Glucose tolerance in hemodialysis patients vs patients with renal transplantation-

C.Vaduva, C. Grauntanu, Vladu I., Dena M., D.Cana-Ruiu, E. Mota, Days of the

University of Medicine and Pharmacy Craiova 2010

16. Cardiovascular risk was the beginning of dialysis, S. Zaharie, Vladu I., E. Mota, Days of

the University of Medicine and Pharmacy Craiova 2010

17. The prevalence of disorders of bone and mineral metabolism associated with chronic

kidney disease at the initiation of dialysis-Vladu I., M. Mota, Mota E., Annual Congress

of the Romanian Medical Association, Bucharest 2010

18. Prevalence of vascular calcifications and secondary hyperparathyroidism in hemodialysis

patients, Vladu I., D. Cana, C. Grauntanu, C. Vaduva, E. Mota. National Congress for

Students and young medical doctors, Galati, 2011

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19. Cardiovascular complications in an obese incident hemodyalisis patient with severe

hyperparathyroidism – case report, Vladu I, C. Grauntanu, R. Mustafa, E Mota, 13th

Craiova International Medical Students Conference, 2011

20. Biochemical abnormalities of mineral metabolism in chronic kidney disease: prevalence

and correlations Cristina Capusa, Mihaela Badulescu, Simona Stancu, Liliana Barsan,

Mariana Lipan, Iulia Vladu, Eugen Mota and Gabriel Mircescu, 48th ERA-EDTA

Congress, June 23-26 2011, Prague, Czech Republic NDT Plus 2011. 4 (suppl 2)

21. Inflamation, anemia and cardiovascular risk factors in CKD patients, D.Cana, N.Istrate,

E.Trican, C.Vaduva, C.Grauntanu, Vladu I., E.Mota, The 7th National Congress of

Nephrology Timisoara 2011, Nefrologia, 2011, vol 15(36) :125.

22. Prevalence of vascular calcifications in hemodialysis patients, Vladu I., D.Cana,

C.Grauntanu, D.Maria, C.Vaduva, M.Dena, R.Mustafa, M.Popescu, E.Mota. The 7th

National Congress of Nephrology Timisoara 2011, Nefrologia, 2011, vol 15(36) :126.

23. Evaluation score of abdominal aorta calcification in non dyalised CKD patients – Vladu

I., C Grauntanu, C. Vaduva, R. Mustafa, E. Mota, The 15th National Congress for

students and young doctors, Bucharest, 2011.

24. The impact of haemoglobin levels on patients with diabetes and renal impairment. D

Cana-Ruiu, M Dena, N Istrate, Vladu I, E Mota. World congress of Nephrology, April 8-

12, 2011, Vancouver, Canada

25. Biochemical abnormalities of mineral metabolism in chronic kidney disease: prevalence

and correlations. C Capusa, M Badulescu, S Stancu, L Barsan, M Lipan, Vladu I, E

Mota, G Mircescu, 48th ERA-EDTA Congress, June 23-26 2011, Prague, Czech Republic

NDT Plus 2011. 4 (suppl 2)

26. Inflamation, anemia and cardiovascular risk factors in CKD patients, D.Cana, N.Istrate,

E.Trican, C.Vaduva, C.Grauntanu, Vladu I., E.Mota, The 7th National Congress of

Nephrology Timisoara 2011, Nefrologia, 2011, vol 15(36): 125

27. Clinical research of relationship between carotid intima-media thickness and

cardiovascular risk factors in hemodialysis patients. Vladu I, Vaduva C, Cana D, Zaharie

S, Mustafa R, Mota E, 49th ERA-EDTA Congress, Mai 2012, Paris, NDT 27, (S2) ii241

28. Is alkaline phosphatase a useful tool for chronic kidney disease - mineral and bone

disorder assessment in non-dialysis patients ?. Capusa C, Stancu S, Maria D, Vladu I,

Barsan L, Mota E, Mircescu G, 49th ERA-EDTA Congress, Mai 2012, Paris, NDT 27,

(S2) ii223

Participation at national and international congresses :

1. Certificate of Proficiency in English, University of Cambridge, Local examination

syndicate, Bucharest, 2002

2. Certificate of participation at ‘International Medical Students Conference’, Craiova 2005,

2007, 2011

3. Certificate of attendance in the workshop,, Methods of modern imaging in pathology

gastro - intestinal, Craiova, 2007

4. Certificate of attendance in the workshop 'The Laparoscopic Surgery - State of the Art',

Craiova, 2007

5. Certificate of attendance in the workshop-'Methodes analyzing DNA and RNA and their

applications in the field of medicine ', Craiova, 2007

6. Certificate of attendance in Prime 'above-the Medicine White Coat'. Craiova, 2007

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7. Degree participationau workshop 'The study of the neonatal cerebrocortical circulation

using intravital microscopy, Laser Doppler and Laser Speckle flowmetri contrast analysis

in animal models ", Craiova 2007

8. Certificate of attendance at ’International congress for medical students and young

doctors’, Timisoara 2007, 2010

9. Diploma of Erasmus student Faculty of Medicine Paris 6 months , France, 2008

10. Certificate of participation the ‘National Romanian Congress of Nephrology’, 2009,

2011

11. Certificate of participation at meetings ‘National Romanian Congress of Nephrology,

Dialysis and Transplantation’, 2010

12. Certificate of attendance at the 17th Budapest Nephrology School, 2010

13. Certificate of attendance at the ‘National Congress for students and young doctors’,

Bucarest, 2011

14. Certificate of attendance at the ‘National Congress for students and young doctors’,

Galati, 2011

15. Certificate of attendance at Nefrocardia, Timisoara, 2011