³Emergency Medicine Department of Istria, Umag, Croatia EFFECT OF CALCITRIOL AND PARICALCITOL ON SERUM PARATHYROID HORMONE LEVELS AND MINERAL METABOLISM DISORDER IN PATIENTS ON MAINTENANCE HEMODIALYSIS Ljušaj M¹, Livajić M¹, Kuzmanović L¹, Vidić Ž², Šiljegović S², Kalinić N², Dorčić G³, Devčić B², Rački S², Vujičić B² ¹Undergraduate study of Medicine, Faculty of Medicine, University of Rijeka, Rijeka, Croatia ²Department of Nephrology, Dialysis and Kidney Transplantation, Clinic of Internal Medicine, Clinical Hospital Centre Rijeka, Rijeka, Croatia ³Emergency Medicine Department of Istria, Umag, Croatia Rijeka,2015.

Contents Introduction Hypothesis Aim Patients Methods Results Conclusion

KIDNEY FUNCTION Blood filtration Regulation of electrolytes Production of urine Blood pressure Acid-bace balanse Production of hormones - calcitriol - erythropoietin - renin Vrhovac B, Jakšić B, Reiner Ž, Vucelić B , ur. Interna medicina. Zagreb: Naklada Ljevak, 2008.

CHRONIC KIDNEY DISEASE- CKD Progressive loss in renal function

PARATHYROID HORMONE AND MINERAL METABOLISM Guyton A, Hall J, Medicinska fiziologija. Zagreb: Medicinska naklada, 2012.

CHRONIC KIDNEY DISEASE – MINERAL BONE DISORDER (CKD-MBD) systemic disorder of mineral and bone metabolism due to CKD manifested by: abnormalities of calcium, phosporus, parathyroid hormone (PTH) or vitamin D metabolism abnormalities in bone turnover, mineralisation, volume linear growth, or strenght extraskeletal calcification Hyperphosphatemia, hyperparathyroidism and hypercalcemia all have potential roles in the pathogenesis of vascular calcification Management of secondary hyperparathyroidism and mineral metabolism abnormalities in dialysis patients, L Darryl Quarles, MD Michael Berkoben, MD: Overview of chronic kidney disease-mineral bone disorder (CKD-MBD), Wajeh Y Qunibi, MD, William L Henrich , MD, MACP

SECONDARY HYPERPARATHYROIDISM begins early in the course of CKD occurs in response of: phosphate retention decreased calcium concretration Decreased 1,25-dihydroxyvitamin D concentration increased fibroblast growth factor 23 (FGF-23) concentration Overview of chronic kidney disease-mineral bone disorder (CKD-MBD), Wajeh Y Qunibi, MD, William L Henrich , MD, MACP

THE MANAGEMENT OF SECONDARY HYPERPARATHYROIDISM IN DIALYSIS PATIENTS Phosphate binders Calcitriol or vitamin D analogs Calcimimetics Management of secondary hyperparathyroidism and mineral metabolism abnormalities in dialysis patients, L Darryl Quarles, MD Michael Berkoben, MD

CALCITRIOL AND PARICALCITOL ( 1-25-dihydroxycholecalciferol) active metabolite of vitamin D Paricalcitol 19-nor-1,25-(OH)2  Analog of 1,25-dihydroxyergocalciferol, the active form of vitamin D2 Darryl Quarles L, Berkoben M, Managment of secondary hyperparathyroidism and mineral metabolism abnormalities in dialysis patients. UpToDate, 2011. 20:49:10

To compare the efficacy of calcitriol and paricalcitol on the reduction of serum PTH levels, and incidence of hypercalcaemia and hyperphosphatemia

AIM Analyze demographic data of patients Statistical analysis of results of the study Potential clinical application of our results

PATIENTS 63 hemodialysis patients in Department of Nephrology,Dialysis and Kidney Transplantation, Clinical Hospital Centre Rijeka Age 67.3, 53 % male Treatment with calcitriol or paricalcitol in the period from January 1, 2014, to December 31, 2014. No statistically significant difference in demographic and laboratory parameters between groups at the baseline Screened for eligibility (n=63) Included with signed informed consent (n=58) Analysed at the follow up 55 Calcitriol group (n=26) Paricalcitol group (n=28)

EXCLUSION CRITERIA Patients younger than 18 Unsigned informed consent Pregnancy and lactation Clinical and laboratory signs of systemic inflammation Malignant disease in treatment, non-treatable or with a recidive in last 2 years Termination of HD treatment and vitamin D analogue treatment for any reason before the follow up after six months

METHODS We examined serum levels of PTH, Ca and P at the baseline, and after 6 months Hypercalcemia was defined as serum Ca>2.37 mmol/L Hyperphosphatemia was defined as serum P>1.78 mmol/L Am J Kidney Dis. 2010 May;55(5):773-99. doi: 10.1053/j.ajkd.2010.02.340. Epub 2010 Apr 3. KDOQI US commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD-Mineral and Bone Disorder (CKD-MBD). Uhlig K1, Berns JS, Kestenbaum B, Kumar R, Leonard MB, Martin KJ, Sprague SM, Goldfarb S.

RESULTS Table 1. Baseline characteristics of patients (mean±SD) Calcitriol group N(%)=26(47) Paricalcitol group N(%)=28(58) p Age (yrs) 71,78 ± 12,72 67,23 ± 12,16 0,05 Dialysis duration (months) 51,14 ± 67,96 53,94 ± 59,94 0,85 Male:Female (%) 12 (42):14 (58) 13(47):15(53) Etiology of ESRD [n(%)]: Diabetic nephropathy 6 (23) 13 (45) - Glomerulonephritis 4 (17) 1 (5) Hypertensive nephropathy 11 (42) 7 (23) Interstitial nephritis 2 (7) 4 (14) Polycystic kidney disease 2 (8) Other 1 (4) RRF (ml) 364,28 ± 465,24 321,05 ± 370,46 0,67 Barthel score 17,14 ± 2,99 16,86 ± 3,31 0,73 Davies score 0,82 ± 0,47 0,89 ± 0,64 0,61 Erythrocites 3,59 ± 0,43 3,64 ± 0,41 0,63 Leukocites 7,04 ± 2,15 6,56 ± 1,52 0,30 Haemoglobin [g/L] 104,03 ± 12,96 107,57 ± 12,04 0,25 Albumin [g/L] 37,16 ± 4,75 39,61 ± 3,66 <0,05 CRP [g/L] 11,01 ± 13,75 8,56 ± 11,66 0,43 Glucose [g/L] 6,91 ± 6,47 8,88 ± 4,99 0,16 Urea [mmol/L] 22,06 ± 5,52 20,32 ± 4,62 Chreatinine [umol/L] 682,2 ± 221,64 706,23 ± 196,68 0,64 Kt/V 1,23 ± 0,25 1,33 ± 0,3 0,18 PTH [pmol/L] 57.66±54.33 41.76±25,27 0,78 Ca [mmol/L] 2,13 ± 0,17 2,26 ± 0,11 P [mmol/L] 1,49 ± 0,5 1,44 ± 0,36

RESULTS No significant difference in PTH serum levels in the group treated with calcitriol (57.66±54.33 vs. 53.5±32.88; P=0.405), and the group treated with paricalcitol (41.76±25,27 vs. 34.44±23.55; P=0.127), after 6 months There was significantly higher percentage of patients with hypercalcemia in the group treated with calcitriol, after 6 months (0% vs. 23%; P=0.030) The percentage of patients with hyperphosphatemia changed, but not significantly, in both groups after 6 months: paricalcitol group (0% vs. 10%; P=0.309), and calcitriol group (11% vs. 21%; P=0.496)

CONCLUSIONS Calcitriol and paricalcitol are equally efficient in reduction of serum PTH levels in the patients on the maintenance HD, after 6 months patients treated with calcitriol had significantly higher incidence of hypercalcemia Further studies on bigger number of patients are required to see the survival benefits of paricalcitol over the calcitriol

Contact us: Merljinda Ljušaj merljinda.ljusaj@gmail.com Lara Kuzmanović lara.kuzmanovic@hotmail.com Marija Livajić marija.livajic@gmail.com