Sains Malaysiana 49(3)(2020): 613-624

http://dx.doi.org/10.17576/jsm-2020-4903-16

Vitamin K Status in Diabetic Patients with Chronic Kidney Disease Stage 3-5 and its Effects on Chronic Kidney Disease - Mineral Bone Disorder

(Status Vitamin K pada Pesakit Kencing Manis dengan Kegagalan Ginjal Kronik Tahap 3-5 dan Kesannya kepada Penyakit Ginjal Kronik - Gangguan Mineral Tulang)

S. JAYAKUMAR¹, ELENA AZIZAN², SHAMSUL AZHAR SHAH³, ARBAIYAH BAIN¹ & ABDUL HALIM ABDUL GAFOR¹*

¹Nephrology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Federal Territory, Malaysia

²Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Federal Territory, Malaysia

³Department of Community Health, UKM Medical Molecular Biology Institute, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Federal Territory, Malaysia

Diserahkan: 9 Oktober 2019/Diterima: 13 November 2019

ABSTRACT

Diabetic kidney disease (DKD) is common in Malaysia. Vitamin K deficiency among DKD patients may be associated with higher incidence of chronic kidney disease-mineral bone disorder (CKD-MBD).  This study was conducted to determine the prevalence of vitamin K deficiency in diabetic patients with CKD stage 3-5. We also correlated vitamin K deficiency with baseline demographic, biochemical results and analysed the effects of vitamin K levels on CKD-MBD. This was a single centre cross-sectional study on diabetic patients with CKD stage 3-5. Demographic profiles were recorded, blood samples were measured for vitamin K level (phylloquinone, proteins induced by vitamin K absence II (PIVKA-II), prothrombin time) and bone markers (parathyroid hormone (PTH), alkaline phosphatase, corrected calcium and phosphate). This study was approved by UKM ethic and research committee (FF-2018-375). Forty-five patients with a median age of 70 (IQR:13) years were recruited.  Majority were females (53.3%) and Malays (64.4%).  Prevalence of patients with insufficient vitamin K was 28.9 % based on the low level of phylloquinone (<0.4 nmol/L), 93.3% based on high PIVKA-II level (>0.66 ng/mL) and 2.2% based on prolonged prothrombin time (>14.5 s). PIVKA-II was found to be positively correlated with serum creatinine and PTH levels. There were positive correlations between phylloquinone with serum triglyceride and total cholesterol. Prothrombin time was found to be negatively correlated with corrected calcium and total cholesterol. Malay race (p = 0.039) and high serum PTH (p = 0.016) were significantly associated with higher PIVKA-II concentrations. Multivariable analysis showed serum triglyceride (OR 0.112; CI 95 % (0.02-0.66); p = 0.017) and serum PTH (OR 1.997; CI 95 % (1.01-3.95); p = 0.047) were independent predictors for abnormal phylloquinone and PIVKA-II levels, respectively. In conclusion, the prevalence of Vitamin K deficiency was high in diabetic patients with CKD stage 3-5. Serum triglyceride and serum PTH were independent predictor of Vitamin K deficiency.

Keywords: Chronic kidney disease-mineral bone disease; diabetic kidney disease; phylloquinone; protein induced by vitamin K absence II (PIVKA II); prothrombin time

ABSTRAK

Penyakit ginjal yang disebabkan oleh kencing manis (DKD) sangat kerap berlaku di Malaysia. Kekurangan vitamin K dalam kalangan pesakit DKD mungkin berhubung kait dengan kejadian penyakit ginjal kronik-gangguan mineral tulang (CKD-MBD) yang tinggi. Kajian ini dijalankan untuk menentukan kelaziman kekurangan vitamin K pada pesakit DKD tahap 3-5. Kami juga mengkaji hubung kait kekurangan vitamin K dengan demografi dan biokimia asas dan menganalisis kesan paras vitamin K pada CKD-MBD. Ini adalah satu kajian rentas pada pesakit DKD tahap 3-5. Profil demografi direkodkan, sampel darah diambil untuk tahap vitamin K (filokuinon, proteins teraruh dengan ketiadaan vitamin K II (PIVKA-II), tempoh protrombin) dan penanda penyakit CKD-MBD (hormon paratiroid (PTH), fosfatase beralkasi, kalsium dan fosfat). Kajian ini telah diluluskan oleh Jawatankuasa Etika dan Penyelidikan UKM (FF-2018-375). Empat puluh lima pesakit dengan umur median 70 (IQR: 13) tahun telah direkrut. Majoriti adalah perempuan (53.3 %) dan Melayu (64.4 %). Peratusan pesakit dengan kekurangan vitamin K adalah 28.9 % berdasarkan tahap rendah filokuinon (<0.4 nmol/L), 93.3 % berdasarkan tahap PIVKA-II yang tinggi (> 0.66 ng/mL) dan 2.2 % berdasarkan masa protrombin yang berpanjangan (> 14.5 saat). PIVKA-II didapati mempunyai kaitan positif dengan nilai serum kreatinin dan PTH. Terdapat hubung kait positif antara filokuinon dengan serum trigliserida  dan  kolesterol. Tempoh protrombin didapati berhubung kait secara negatif dengan kalsium dan tahap kolesterol. Bangsa Melayu (p = 0.039) dan serum tinggi PTH (p = 0.016) adalah berkaitan dengan kepekatan PIVKA-II. Analisis pelbagai pemboleh ubah menunjukkan trigliserida serum (OR 0.112; CI 95% (0.02-0.66); p = 0.017) dan tahap PTH (OR 1.997; CI 95% (1.01-3.95); p = 0.047) adalah peramal untuk keabnormalan filokuinon dan tahap PIVKA-II. Kesimpulannya, kekurangan vitamin K kerap berlaku pada pesakit diabetes dengan CKD tahap 3-5. Serum trigliserida dan serum PTH adalah peramal bebas kekurangan Vitamin K.

Kata kunci: Filokuinon; penyakit buah pinggang diabetes; penyakit ginjal kronik - penyakit mineral tulang; protein teraruh dengan ketiadaan vitamin K II (PIVKA II); tempoh protrombin

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