PENGARUH PEMBERIAN 1,25 DIHYDROXYVITAMIN D (CALCITRIOL) TERHADAP KADAR FIBROBLAST GROWTH FACTOR-23 DAN ALBUMINURIA PADA PASIEN PENYAKIT GINJAL KRONIK STADIUM V YANG MENJALANI HEMODIALISIS

Intan Herlina, Bambang Purwanto, Sugiarto Sugiarto

DOI: https://doi.org/10.23917/biomedika.v9i1.4344

Abstract

Penyebab utama morbiditas dan mortalitas pada pasien Penyakit Ginjal Kronik adalah insiden kardiovaskuler yang didasari oleh proses aterosklerosis yang menyebabkan meningkatnya morbiditas dan mortalitas. Ginjal merupakan tempat utama sintesa 1,25 Dihydroxyvitamin D (Calcitriol), sehingga dengan adanya kerusakan ginjal menyebabkan defisiensi 1,25 Dihydroxyvitamin D (Calcitriol). Pada pasien Penyakit Ginjal Kronik terjadi peningkatan Fibroblast Growth Factor-23 dan Albuminuria akibat dari aktifitas Renin Angiotensin Aldosteron Sistem. Aktifitas RAAS mempengaruhi 1,25 Dihydroxy vitamin D (Calcitriol), Fibroblast Growth Factor-23 melalui Angiotensin 2 dengan cara menghambat reseptor Angiotensin I (AT1) melalui Nicotinmide Adenine Dinucleotide Phosphate Oxidase (NADPH Oksidase) dan Stress Oxidativ. Beberapa penelitian menyimpulkan pemberian 1,25 Dihydroxyvitamin D (Calcitriol) mempunyai efek renoprotektif, anti inflamasi dan antiproteinuric dengan cara menghambat reseptor Angoitensin I (AT1) sehingga mengakibatkan menurunnya albuminuria. Tujuan Penelitian ini adalah untuk membuktikan pemberian 1,25 Dihydroxyvitamin D (Calcitriol) dapat menurunkan kadar Fibroblas Growth Factor-23 dan albuminuria pada pasien Penyakit Ginjal Kronik stadium V yang menjalani hemodialisis. Penelitian ini merupakan penelitian eksperimen dengan randomisasi, subyek penelitian 30 orang, dibagi dalam dua kelompok sampel, kelompok plasebo 15 orang dan kelompok perlakuan 15 orang. Dalam perjalanan, kelompok placebo drop out 4 pasien karena keluarga pasien tidak menyetujui untuk melanjutkan penelitian dan satu lagi mengalami perburukan, sehingga jumlah sampel menjadi 26 orang, terbagi menjadi kelompok placebo sebanyak 11 orang yang diberi placebo dan kelompok perlakuan 15 orang diberi calcitriol 1x0,5 μg peroral selama 4 minggu. Karakteristik penelitian yang berupa variabel kualitatif, uji homogenitas dilakukan menggunakan uji Chi Square. Uji beda dua Rerata menggunakan uji t pada p<0.005. Pada kelompok plasebo (n=11) ; Kadar Fibroblast Growth Factor-23 sebelum dan sesudah perlakuan (876,24±795,93 RU/mL vs 1235,69±791,71 RU/mL; p=0,059) dan Albuminuria (72,30±195,06 μg/ mg vs 320,14±208,90 μg/mg; p=0,001). Pada kelompok perlakuan (n=15); Kadar Fibroblast Growth Factor-23 sebelum dan sesudah perlakuan (1210,96±845,97 RU/mL vs 612,33±487,32 RU/mL; p=0,002) dan Albuminuria (206,63±327,25 μg/mg vs 192,89±316,00 μg/mg; p=0,001). Terdapat perbedaan yang bermakna pada selisih ratarata kadar Fibroblast Growth Factor-23 (Delta-FGF-23) sebelum dan sesudah perlakuan pada kelompok placebo vs kelompok perlakuan (-359,45±560,23 RU/mL vs 598,63±608,27 RU/mL; p=0,001) dan selisih rata-rata Albuminuria (Delta-albuminuria) sebelum dan sesudah perlakuan pada kelompok placebo vs kelompok perlakuan (-247,84±189,48 μg/mg vs 13,73±23,15μg/mg;p=0,001. Pemberian suplementasi 1,25 Dihydroxyvitamin D (calcitriol) menurunkan kadar FGF-23 albuminuria secara bermakna pada pasien penyakit ginjal kronik stadium V yang menjalani hemodialisis

Kata Kunci: Penyakit Ginjal Kronis Stadium V, 1,25 Dihydroxyvitamin D (Calcitriol), Fibroblast Growth Factor-23, Albuminuria

Full Text:

PDF

References

Amico G dan Bazzi C. 2003. Pathophysiology of Proteinuria. Kidney Intl. 63: 809-25

Araya K, Fukumoto S, Backenroth R. 2005. A Novel Mutation in Fibroblast Growth Factor 23 Gene as a Cause of Tumoral Calcinosis. J Clin Endocrinol Metab. 90 (10): 5523‑527.

Bhan I, Burnett BSA, Ye J, Tonelli M, Thadhani R. 2010. Clinical Measures Identify Vitamin D Deficiency in Dialysis. Clin J Am Soc Nephrol.5: 460-67.

Brantsma AH, Bakker SJL, De Zeeuw. 2006. Urinary Albumin Excretion as a Predictor of the Development of Hypertension in The General Population. J Am Soc Nephrol. 17: 331-35.

Cachofeiro V, Goicochea M, Garcia de VS, Oubina P, Lahera V, Luno J, et al. 2008. Oxidative tress and Inflamation, a Link Between Chronic Kidney Disease and Cardiovascular Disease. Kidney Int. 74: 54-59.

Collins AJ. 2003. Cardiovascular Mortality in End Stage Renal Disease. Am J Med Sci. 325: 163-67.

De Groot T. 2009. Parathyroid Hormone Activates TRPV5 via PKA Dependent Phosphorylation. J Am Soc Nephrol.20: 1693-704.

Farrow EG, Davis SI, Summers LJ. 2009. Initial FGF23Mediated Signaling Occurs in the Distal Convoluted Tubule. J Am Soc Nephrol. 20(5):955‑60.

Gansevort. 2009. Healthy People With High Urinary Protein Levels Have Elevated Kidney Disease Risk. Available from URL: http://www.sciencedaily.com/.

Gibbons GH. 1997. Vasculoprotective and Cardioprotective Mechanism of Angiotensin-Converting Enzyme Inhibition the Homeostatic Balance Between Angiotensin II and Nitric Oxide. Clin Cardiol. 20: 18-25.

Goetz R, Beenken A, Ibrahimi OA. 2007. Molecular Insights Into the Klotho Dependent, Endocrine Mode of Action of Fibroblast Growth Factor 19 Subfamily Members. Mol Cell Biol. 27: 3417–28.

Inaba M, Okuno S, Imanishi Y et al. 2006. Role of Fibroblast Growth Factor-23 in Peripheral Vascular Nalcification in Non Diabetic and Diabetic Hemodialysis Patients. Osteoporos. 17: 1506-13.

Kendrick J dan Chonchol MB. 2008. Non Traditional Risk Factor for Cardiovascular Disease in Patients With Chronic Kidney Disease.Nat Clin Pract Nephrol. 4: 672-81.

Kovesdy CP, Lu JL, Malakauskas SM, Andress DL, Kalantar ZK, Ahmadzadeh S. 2012. Paricalcitol Versus Ergocalciferol For Secondary Hyperpara thyroidism in CKD Stages 3 and 4: A Randomized Controlled Trial. Am J Kidney Dis. 59(1): 58-66.

Kurosu H, Ogawa Y, Miyoshi M. 2006. Regulation of Fibroblast Growth Factor-23 Signaling by Klotho. J Biol Chem. 81: 6120–123.

Lang CL, Wang MH, Chiang CK, Cheng Lu K. 2014. Vitamin D and The Immune System From Nephrologist’s Viewpoint. ISRN Endocrinol: 2-10.

Liu S, Zhou J, Tang W. 2006. Pathogenic Role of Fgf23 in Hyp Mice. Am J Physiol Endocrinol Metab. 291: 38–49.

Llach F danYudd M. 1998. Pathogenic, Clinical and Therapeutic Aspects of Secondary Hyperparathyroidism in Chronic Renal Failure. Am J Kidney Dis. 32: 3–12

Montesa P, Rico G, Salguero S, Maicas T, Munoz T, Torino S, et al. 2009. Study ofoxidative stress in advanced kidney disease. Nefrologia. 29(5): 464-73.

Moscovici A dan Sprague SM. 2007. Role of Vitamin D Defficiency in Chronic Kidney Disease. J Bone Miner Res. 22: 91-94.

Newman D dan Price CP. 2001. Renal Function. In Tietz Fundamentals of Clinical Chemistry. Eds Burtis CA, Ashwood ER, 5th Edition. WB. Saunders Company. USA: 698-722.

Payson O, McMenamin E, Lee L. 2004. Increased Prevalence of Oxidant Stress andInflammation in Patients with Moderate to Severe Chronic Kidney DiseaseKidney Int. 65: 1009-16.

Pedrinelli R, Glampletro O, Carmassi F, Melillo E. 1994. Microalbuminuria and Endothelial Dysfunction In Essential Hypertension. Lancet. 344: 14-18.

Purwanto B. 2012. Hipertensi. Hipertensi (Patogenesis, Kerusakan Target Organ dan Penatalaksanaan. Sebelas Maret University Press: 3-58.

Rayner HC, Pisoni RL, Bommer J, Canaud B, Hecking E, Locatelli F, et al. 2004. Mortality and Hospitalization in Hemodialysis Patient in Five European Countries. Results From the Dialysis Outcomes and Practice Pattern Study (DOPPS). Nephrol Dial Transplant. 19: 108-120

Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm L, et al. 2003. Kidney Disease as aRisk Factor for Development of Cardiovascular Disease. Circulation. 108: 2154-69.

Shimada T, Hasegawa H, Yamazaki Y. 2004. FGF‑23 is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis. J Bone Miner Res. 19(3): 429‑35.

Shimada T, Mizutani S, Muto. 2001. Cloning and Characterization of FGF23 as a Causative Factor of Tumor-Induced Osteomalacia. Proc Natl Acad Sci. 98: 6500-505.

Suhardjono. 2009. Kelainan Kardiovaskular Pada Penyakit Ginjal Kronik. Penatalaksanaan Penyakit Ginjal Kronik dan Hipertensi. Jakarta, Pernefri: 36.

Teng M, Wolf M, Lowrie E, Ofshun N, Lazarus JM, Tadhani R, et al. 2003. Survival of Patients Undergoing Hemodialysis With Pericalcitriol and Calcitriol Therapy. N Eng J Med. 349: 446-56.

Tentori F, Blayney M, Albert JM, Gillespi BW, Kerr PG, Bommer J, et al. 2008. Mortality Risk for Dialysis Patient With Different Levels of Serum Calcium, Phosphorus and PTH. Am J Kidney Dis. 52: 519-30.

Thomas R, Kanso A, Sedor JR. 2008. Chronic Kidney Disease and Its Complications. Prim Care Clin Office Pract. 35: 329-24.

Torres PU, Prie D, Molina Bletry V. 2007. Klotho: an Antiaging Protein Involved in Mineral and Vitamin D Metabolism. Kidney Int. 71: 730–37.

Urakawa I, Yamazaki Y, Shimada T. 2006. Klotho Converts Canonical FGF Receptor Into a Specific Receptor for FGF23. Nature. 444: 770–74.

White KE, Evans WE, O’Riordan JLH. 2000. Autosomal Dominant Hypophos phataemic Rickets is Associated with Mutations in FGF23. Nat Genet. 26(3): 345‑48.

Wolf M, Shah A, Gutierrez O, Ankers E, Monroy M, Tamez H, et al. 2007. Vitamin D Levels and Early Mortality Among Incident Hemodialysis Patients. Kidney Int. 72: 1004-13.

Yamashita T, Yoshioka M, Itoh N. 2000. Identification of a Novel Fibroblast Growth Factor, FGF-23, Preferentially Expressed in the Ventrolateral Thalamic Nucleus of The Brain. Biochem Biophys Res Commun. 277: 494-98.

Article Level Metrics

Refbacks

  • There are currently no refbacks.