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The Relationship between Serum 25-Hydroxyvitamin D, Parathyroid Hormone and the Glomerular Filtration Rate in Korean Adults: The Korea National Health and Nutrition Examination Survey between 2009 and 2011

Background The glomerular filtration rate (GFR) decreases with age, while parathyroid hormone (PTH) increases. There are a few reports only on the relationship between GFR and PTH under the category of serum 25-hydroxyvitamin D (25[OH]D) concentration. Methods Using the Korea National Health and Nutrition Examination Survey (KNHANES) data, a cross-sectional study was conducted on the association between serum 25(OH)D concentration, GFR and PTH in Korean adults aged 50 years or older. Serum PTH concentration was compared to the tertiles of GFR after adjustment for relevant variables. In addition, the serum PTH concentration was compared with the GFR under the category of serum 25(OH) D concentration (<20, 20-30, >30 ng/mL). Results The mean estimated GFR (eGFR) was 74.8 mL/min in men and 73.1 mL/min in women. The mean PTH and 25(OH) D was 66.8 pg/mL, 20.5 ng/mL in men and 69.0 pg/mL, 18.2 ng/mL in women. The serum PTH concentration showed a significant negative correlation with the serum 25(OH) D and eGFR in both genders. The serum PTH concentration significantly increased at the lower tertile of eGFR in male adults In addition, a decrease of serum PTH concentration was marked in the vitamin D sufficient male adults (>30 ng/mL). Conclusion This present study demonstrated that serum PTH concentration showed negative correlation with eGFR, however, serum PTH increase may be minimized by maintaining proper serum 25(OH)D concentrations under similar eGFR status in Korean adults aged 50 and above.


INTRODUCTION
Vitamin D is a fat-soluble vitamin with various health benefits. [1][2][3] The traditional function of vitamin D is to increase the intestinal absorption of calcium for proper mineralization of bone, 4) to regulate blood pressure by various mechanisms [5][6][7][8][9] and to stimulate kidney reabsorption of calcium and phosphate, mainly

Lifestyle Questionnaires
Physical examinations were performed by a trained examiner following a standardized procedure. Body weight and height were measured in light indoor clothing without shoes to the nearest 0.1 kg and 0.1 cm, respectively. Physical activity was assessed by a questionnaire and categorized as "yes" or "no" with "yes" meaning 30 minutes of moderate physical activity three or more times in the last week in which the subject was tired compared to ordinary levels. Menarche age was determined by a health questionnaire administered by a trained examiner. Women were classified into women in menopausal status and women with a hormone replacement therapy.

Statistical Analysis
Complex sample analysis after data weighting was used for the KNHANES data for the assessment of all values following the statistics guidance of the Korea Centers for Disease Control and Prevention. After the assessment, the general characteristics for both genders were presented including age, waist circumference, body mass index, total cholesterol, high density lipoprotein, triglycerides, fasting blood glucose, daily total energy intake, daily calcium intake, serum parathyroid hormone concentrations, serum 25(OH)D concentrations and eGFR. To evaluate the association between serum 25(OH)D concentrations and serum PTH concentration with eGFR a partial correlation analysis was performed in female and male subjects after adjustment for age, body mass index (BMI), job, alcohol intake, smoking status and moderate physical activity. Serum PTH did not have normal distribution, however, we did not make a log-transformation, because log-transformed PTH did not show normal distribution either and authors decided that using PTH values as they were had more clinical relevance. We compared the difference in serum PTH concentrations by eGFR according to the serum 25(OH) D concentration category (<20, 20-30, and <30 ng/mL) in both genders. In addition, we evaluated the interaction of serum PTH and eGFR according to the serum 25(OH)D concentration category in both genders. Finally, to determine the association between eGFR and serum PTH concentration, eGFR was divided into tertiles in each gender. In these eGRF categories, the differences in serum PTH concentrations were determined across the tertiles with the analysis of covariance test after adjustment for age, BMI, job, alcohol intake, smoking, moderate physical activity, D concentration and additionally for women, menopausal status, the use of oral contraceptive, or a hormone replacement therapy. All P-values were P for trend used for assessment of the significance of all analysis and P < 0.05 was considered significant.

General Characteristics of Study Subjects
A total of 8,502 people were enrolled in this trial. The general characteristics of the study participants are shown in Table 1. The serum 25(OH)D concentration and the eGFR in male adults were on average higher than in females (20.5 ± 0.1 ng/mL vs. 18.2 ± 0.1 ng/mL and 74.8 ± 0.3 mL/min vs. 73.1 ± 0.3 mL/min, respectively). The Serum PTH concentration was higher in female (69.0 ± 0.6 pg/mL) than in male adults (66.8 ± 0.4 pg/mL).

Correlation between 25-Hydroxyvitamin D, Parathyroid Hormone and Estimated Glomerular Filtration Rate
To determine the association between serum 25(OH)D concentration and serum PTH concentration with eGFR, a partial correlation analysis was conducted (Table 2)  Values are presented as mean ± standard error after data weighting. Energy: daily total energy intake, Calcium: daily dietary calcium intake.

Serum Parathyroid Hormone Concentration by Tertiles of Estimated Glomerular Filtration Rate
Serum  PTH: parathyroid hormone, GFR: estimated glomerular filtration rate.

Korean J Fam Med
There are emerging data associating high levels of serum PTH with morbidity and increased mortality. Raised serum PTH has been associated with weight gain and adiposity 31,32) and with poor muscle function. 33) A high serum PTH was also associated with increased mortality 34) and time to first fall 35) in a frail elderly population. Although the evidence was far less than for vitamin D, a community-based prospective study predicted an elevated PTH level for cardiovascular mortality. By which mechanism the serum PTH may influence these variables is unknown. A graded association between lower eGFR and a higher prevalence of D level with at least 20 ng/mL is required to normalize PTH levels, to minimize the risk of osteomalacia and for optimal bone and muscle function. Many experts consider 30 ng/mL as the threshold for optimal bone health. 39) There is potentially a great upside (in terms of overall health improvement and well-being) to increasing the serum 25(OH)D levels above 30 ng/mL. 40  The difference of body composition, calcium intake, and other metabolic parameters might be some of the causes of gender difference in serum PTH concentration.
In conclusion, this study demonstrated that serum PTH concentration showed negative correlation with eGFR; however,