The Association of Vitamin D With Estimated Glomerular Filtration Rate and Albuminuria:
5th Korean National Health and Nutritional Examination Survey 2011–2012
Jong Park, MD, PhD, So-Yeon Ryu, MD, PhD, Mi-ah Han, MD, PhD, and Seong-Woo Choi, MD, PhD
Objectives: The kidney plays a key role in the metabolism of vitamin D. However, the relationship between GFR and 25(OH)D is not well understood. Moreover, few studies have investigated the effect of albuminuria, a known mediator of kidney function, on vitamin D levels. Our aim was to investigate the associations among estimated GFR (eGFR), albumin-creatinine ratio (ACR), and 25(OH)D.
Methods: We investigated the relationship of 25-hydroxyvitamin D (25[OH]D) with eGFR and albuminuria in 11,336 adults who partic- ipated in the 5th Korea National Health and Nutrition Examination Survey (KNHANES) 2011–2012. The eGFR, ACR, and serum 25(OH)D were measured in participants who met the detailed inclusion criteria.
Results: We found that after adjusting for covariates and log-ACR values, the mean (95% CI) eGFR decreased significantly with increasing 25(OH)D levels (Q1: 93.4 [92.7-94.0]; Q2: 91.9 [91.2-92.5]; Q3: 90.9 [90.3-91.6]; and Q4: 90.2 [89.5-90.8] mL/min/1.73m2; P , .001). However, the mean 25(OH)D value was highest at eGFR 61–90 mL/min per 1.73 m2 and decreased significantly with decreasing eGFR levels (.90: 17.3 [17.1-17.5]; 61-90: 17.6 [17.4-17.8]; 46-60: 17.1 [16.2-18.0]; 31-45: 16.2 [14.2-18.2]; #30: 13.8 [17.0-10.7] ng/mL; P5 .008). After adjusting for covariates and log-eGFR, the mean ACR decreased significantly with increasing 25(OH)D quartiles (Q1: 22.0 [18.1-25.9]; Q2: 20.4 [16.6-24.2]; Q3: 16.3 [12.5-20.0]; Q4: 15.0 [11.2-18.8]mg/mg; P 5 .043).
Conclusions: The mean eGFR values were negatively associated with 25(OH)D levels independently of ACR. However, the mean 25(OH)D values were decreased significantly with decreasing eGFR levels in moderate and severe chronic kidney disease stages.
Also, the mean ACR values were negatively associated with 25(OH)D levels independently of eGFR in an Korean adult population.
Ó2016 by the National Kidney Foundation, Inc. All rights reserved.
Editorial, p. 349
Introduction
Chronic kidney disease (CKD), which is characterized by low glomerular filtration rate (GFR), affects 10%-15%
of American adults.1Impaired GFR is a risk factor for car- diovascular disease2 and is correlated with cardiovascular mortality and morbidity in high-risk groups3,4 and the general population.5Albuminuria is a well-known predic- tor of CKD progression, end stage renal disease, cardiovas- cular events, and mortality.6-8Previous studies have shown that a decrease in urine albumin excretion mediated by renin-angiotensin-aldosterone system antagonists was asso- ciated with a decrease in the risks of unfavorable renal and
cardiovascular outcomes.9,10Thus, detection and treatment of the risk factors associated with decreased GFR and albuminuria will help prevent the progression of advanced kidney disease and reduce the risk of cardiovascular events.11,12
In humans, 80%-90% of vitamin D is derived from 7-dehydrocholesterol in the skin on adequate exposure to ultraviolet light compared with 10%-20% derived from di- etary sources such as oily fish, milk, butter, eggs, and various supplements.13 The primary circulating vitamin D metabolite, 25-hydroxyvitamin D (25[OH]D)14 is metabolized to the biologically active 1,25- dihydroxyvitamin D through enzymatic modification in the liver and kidney.15Thus, the kidney plays a key role in the metabolism of vitamin D. However, the relationship between GFR and 25(OH)D is not well understood.16-19 Moreover, few studies have investigated the effect of albuminuria, a known mediator of kidney function, on vitamin D levels.
The overall prevalence of vitamin D deficiency in Korea is 1.3-to-1.5-fold higher than that in the United States,16 and the burden of CKD is increasing in Korea. Thus, we assessed the associations among estimated GFR (eGFR), albumin-creatinine ratio (ACR), and 25(OH)D after ad- justing for covariates including eGFR and ACR in an adult Korean population.
Department of Preventive Medicine, Chosun University Medical School, Gwangju, Republic of Korea.
Financial Disclosure: The authors declare that they have no relevant financial interests.
Address correspondence to Seong-Woo Choi, MD, PhD, Department of Pre- ventive Medicine, Chosun University Medical School, 375, Seosuk-dong, Gwangju 501-759, Republic of Korea.E-mail:jcsw74@hanmail.net
Ó2016 by the National Kidney Foundation, Inc. All rights reserved.
1051-2276/$36.00
http://dx.doi.org/10.1053/j.jrn.2016.07.003
360 Journal of Renal Nutrition, Vol 26, No 6 (November), 2016: pp 360-366
Methods Study Population
Our study used data obtained in the Korean National Health and Nutrition Examination Survey (KNHANES) 2011–2012, representing the second and third year of KNHANES-V (2010–2012). The KNHANES is a cross- sectional, nationally representative survey with a multistage and stratified sampling design conducted by the Korea Centers for Disease Control and Prevention (KCDCP).20 After the first KNHANES was conducted in 1998, the sec- ond, third, fourth, and fifth surveys were conducted in 2001, 2005, 2007, and 2010-2012, respectively. The KCDCP ethics committee approved our study protocol, and written informed consent was obtained from all sub- jects or their parents. The field survey was conducted by specially trained interviewers at mobile centers and in the participants’ households. The health interview and health examination surveys were performed in specially designed and equipped mobile centers that traveled to locations throughout the country.
A total of 16,576 subjects were enrolled in our study, and the response rate was 80.2% (8,518 of 10,589 participants in 2011 and 8,058 of 10,069 participants in 2012). The exclusion criteria included age ,20 years; missing vital data, such as 25(OH)D or serum creatinine; pregnant women; and a high urine albumin-creatinine ratio (ACR;$3,000 mg/g) indicative of nephrotic-range albuminuria because a previous study found an association between altered vitamin D meta- bolism and nephrotic syndrome.21A total of 11,336 subjects (4,860 males and 6,476 females) were included in the analysis.
Data Collection
Trained examiners interviewed the patients using a questionnaire that included items on residential area, smoking, alcohol intake, physical activity, use of dietary supplements, history of diabetes, hypertension, and cardio-cerebrovascular disease (CCVD). Residential area was categorized as urban or rural. Smoking status was based on self-reported cigarette use: never smokers had smoked,100 cigarettes in their lifetime, and participants who had smoked$ 100 cigarettes were classified as past or current smokers based on their current smoking habit.
Alcohol intake was assessed according to the participants’
drinking behavior during the month before the interview.
Physically active was indicated as ‘‘yes’’ when the partici- pant performed moderate or strenuous exercise on a reg- ular basis (,30 minutes at a time .5 times a week for moderate exercise and for.20 minutes at a time .5 times a week for strenuous exercise) or walked for.30 minutes at a time.5 times a week. Use of dietary supplements was indicated as ‘‘yes’’ when the participant takes dietary sup- plements regularly, that is, for.2 weeks during the previ- ous 1 year. Weight was measured to the nearest 0.1 kg, whereas the subjects were dressed in light clothing. Height was measured to the nearest 0.1 cm in stocking feet. Body
mass index was calculated as weight in kilograms divided by the square of the height in meters. Waist circumference (WC) was measured using a flexible tape at the narrowest point between the lowest rib and the uppermost lateral border of the right iliac crest. Blood pressure was measured after the subject had rested for 5 minutes in a sitting posi- tion. Three readings each of systolic and diastolic blood pressure were recorded, and the average value was used in the analyses. The blood samples were taken by a trained nurse and transported daily to the Central Laboratory (NEODIN Medical Institute, Seoul, Korea). The concen- trations of total cholesterol (TC), triglycerides (TG), and high-density lipoprotein (HDL) cholesterol were deter- mined according to standard procedures using a Hitachi Automatic Analyzer 7600 (Hitachi Ltd., Tokyo, Japan).
Measurement of Serum Concentrations of 25(OH)D
Serum concentrations of 25(OH)D were measured by radioimmunoassay (RIA) using a 25(OH)D125I RIA kit (Diasorin, Stillwater, MN). Data from the radioimmuno- assay were collected using a 1470 WIZARD gamma counter (PerkinElmer, Turku, Finland).
Measurement of Kidney Function
Kidney function was assessed according to the eGFR, which was calculated using the modification of diet in renal disease formula as follows22: 186.3 3 (serum creatinine21.154) 3 (age20.203) 3 0.742 (if female) with the serum creatinine concentration expressed in mg/dL.
Urinary albumin and creatinine concentrations were measured using a turbidimetric immunoassay and the Jaffe method23 using a Hitachi-7600 analyzer (Hitachi Ltd.).
Albuminuria was defined according to the ACR, which was calculated by dividing the urinary albumin concentra- tion (mg) by the urinary creatinine concentration (mg).
Statistical Analysis
The results are expressed as means6 standard devia- tions or as percentages for categorical variables. An anal- ysis of variance (ANOVA) was performed to compare variables according to 25(OH)D quartiles (,13.15, 13.15-16.53, 16.54-20.49, and $20.50 ng/mL). The eGFR and ACR data were not distributed normally;
thus, to approximate normal distributions, the eGFR and ACR data were log-transformed before the analysis of covariance. Model 1 was adjusted for sex, age, residen- tial area, and WC. Model 2 included the model 1 variables and smoking status, alcohol intake, physical activity, dia- betes, hypertension, CCVD, TC, TG, HDL cholesterol, daily energy intake, and daily calcium intake. Finally, model 3 was further adjusted using log-ACR or log- eGFR data. Furthermore, the data were stratified by age quartiles, and mean eGFR values were compared accord- ing to 25(OH)D quartile across the age strata. The Statis- tical Package for the Social Sciences, version 15.0 (SPSS
Inc., Chicago, IL, USA), was used to conduct the statisti- cal tests, and P values,.05 were deemed to indicate sta- tistical significance.
Results
Baseline Characteristics of Subjects According to 25(OH)D Quartile
The baseline characteristics of the 11,336 subjects (4,860 males and 6,476 females) included in the study are shown in Table 1. Higher 25(OH)D levels tended to be associated with the male sex, older age, residence in a rural area, higher WC, higher levels of smoking and alcohol intake, more frequent physical activity, a his- tory of hypertension and CCVD, higher levels of TC,
blood urea nitrogen, serum creatinine, and higher daily energy and daily calcium intakes. Moreover, higher 25(OH)D levels were associated with lower HDL choles- terol levels and lower eGFR.
Comparison of Mean eGFR and ACR According to 25(OH)D Quartile
Table 2shows the mean (95% confidence interval [CI]) eGFR and ACR values according to serum 25(OH)D quartile. After adjusting for covariates (sex, age, residential area, WC, smoking, alcohol intake, physical activity, dia- betes, hypertension, CCVD, TC, TG, HDL cholesterol, daily energy intake, and daily calcium intake) and log- ACR (Model 3), the mean eGFR decreased with increasing 25(OH)D quartiles (Q1: 93.4 [92.7-94.0]; Q2:
Table 1. Characteristics of the Subjects According to 25(OH)D Quartiles
Variables
25(OH)D (ng/mL)
Total P
Q1 (,13.15) Q2 (13.15-16.53) Q3 (16.54-20.49) Q4 ($20.50)
N (%) 2,834 (25.0) 2,833 (25.0) 2,838 (25.0) 2,831 (25.0) 11,336 (10)
Male (%) 877 (30.9) 1,140 (40.2) 1,361 (48.0) 1,482 (52.3) 4,860 (42.9) ,.001
Age (y) 47.26 16.5 49.16 15.9 51.76 15.8 56.86 15.0 51.26 16.2 ,.001
Season of blood collection ,.001
Spring (May-Apr) 1,035 (36.5) 781 (27.6) 544 (19.2) 421 (14.9) 2,781 (24.5)
Summer (Jun-Aug) 425 (15.0) 673 (23.8) 907 (32.0) 963 (34.0) 2,968 (26.2)
Autumn (Sep-Nov) 417 (14.7) 635 (22.4) 821 (28.9) 977 (34.5) 2,850 (25.1)
Winter (Dec-Feb) 957 (33.8) 744 (26.3) 566 (19.9) 470 (16.6) 2,737 (24.1)
Residential area ,.001
Urban (%) 2,442 (86.2) 2,365 (83.5) 2,247 (79.2) 1,961 (69.3) 9,015 (79.5)
Rural (%) 392 (13.8) 468 (16.5) 591 (20.8) 870 (30.7) 2,321 (20.5)
Height (cm) 161.46 9.0 162.26 9.2 162.76 9.3 161.96 9.4 162.16 9.2 ,.001
Weight (kg) 60.96 11.4 63.46 11.9 63.46 11.8 62.56 11.1 62.56 11.6 ,.001
BMI (kg/m2) 23.36 3.5 24.06 3.5 23.86 3.4 23.76 3.1 23.76 3.4 ,.001
Waist circumference (cm) 79.36 10.1 81.76 10.3 82.06 9.7 82.56 9.3 81.46 9.9 ,.001
Smoking (%) 528 (19.3) 542 (19.9) 575 (21.1) 574 (21.0) 2,219 (20.3) ,.001
Alcohol intake (%) 1,925 (70.4) 1,979 (73.0) 2,026 (74.4) 1,867 (68.4) 7,797 (71.5) ,.001 Physically active (%)* 949 (34.7) 968 (35.6) 1,042 (38.3) 1,078 (39.6) 4,037 (37.0) ,.001 Use of dietary
supplements (%)†
1,032 (41.1) 1,124 (45.1) 1,197 (47.5) 1,315 (51.6) 4,668 (46.3) ,.001
Diabetes (%)‡ 306 (11.1) 269 (9.8) 307 (11.2) 369 (13.5) 1251 (11.4) ,.001
Hypertension (%)§ 808 (29.4) 852 (31.1) 949 (34.5) 1,109 (40.2) 3,718 (33.8) ,.001
Cardiocerebrovascular disease (%)
120 (4.4) 122 (4.5) 136 (5.0) 170 (6.2) 548 (5.0) .007
Total cholesterol (mg/dL) 187.76 36.8 190.86 37.6 191.86 36.1 191.16 35.3 190.36 36.5 ,.001 Triglycerides (mg/dL) 131.06 110.0 135.46 116.6 135.76 107.2 128.16 83.6 132.56 105.1 .017 HDL cholesterol (mg/dL) 53.16 13.1 52.26 12.7 52.16 12.5 52.06 12.6 52.46 12.7 .003 eGFR (mL/min per 1.73 m2) 96.26 19.0 93.26 17.5 90.96 17.2 87.96 16.9 92.16 17.9 ,.001 CKD (%, eGFR,60 mL/min
per 1.73 m2)
66 (2.3) 76 (2.7) 85 (3.0) 124 (4.4) 351 (3.1) ,.001
ACR (mg/mg creatinine) 18.86 88.4 18.96 108.5 17.36 90.5 18.46 77.8 18.36 91.8 .925 Albuminuria (%, ACR.30
mg/mg creatinine)
225 (8.8) 198 (7.6) 194 (7.4) 246 (9.1) 863 (8.2) .058
25(OH)D, 25-hydroxyvitamin D; BMI, body mass index; HDL, high-density lipoprotein; eGFR, estimated glomerular filtration rate; CKD, chronic kidney disease; ACR, albumin-creatinine ratio.
All values are given as n (%) or mean6 standard deviation.
*Subjects who performed 30 minutes or more of walking at least 5 days a week.
†A user of dietary supplements was defined as a person who takes them regularly, ie, for longer than 2 weeks during the previous 1 year.
‡Diabetes was defined as fasting serum glucose$ 126 mg/dL or taking insulin or oral diabetes medication.
§Hypertension was defined as systolic blood pressure$ 140 mmHg or diastolic blood pressure $ 90 mmHg or taking antihypertension medication.
91.9 [91.2-92.5]; Q3: 90.9 [90.3-91.6]; Q4: 90.2 [89.5- 90.8] mL/min/1.73 m2; P , .001). After adjusting for the same covariates and log-eGFR (model 3), the mean ACR significantly decreased with increasing 25(OH)D levels (Q1: 22.0 [18.1-25.9]; Q2: 20.4 [16.6-24.2]; Q3:
16.3 [12.5-20.0]; Q4: 15.0 [11.2-18.8]mg/mg; P 5.043).
Prevalence of Hypovitaminosis D According to Age
Figure 1 shows the prevalence of hypovitaminosis D (25(OH)D,15 ng/mL) according to age. In total, 38.2%
of the subjects had hypovitaminosis D; the incidence was highest in the 20-to-30-year-old group (55.7%) and tended
to decrease with age the lowest incidence (28.2%) among subjects aged 60-70 years.
Comparison of Mean eGFR Values Stratified by Age Quartile According to 25(OH)D Quartile
The mean eGFR values (95% CI) stratified by age quar- tile according to 25(OH)D quartile are shown inTable 3.
After adjusting for covariates described above and log- ACR, the mean eGFR values decreased significantly with increasing 25(OH)D quartiles in each age stratum with the exception of the highest age quartile (age Q1 [20- 37 years]: 105.4 [104.2-106.6], 102.9 [101.5-104.2], Table 2. Comparison of Mean eGFR and ACR According to 25(OH)D Levels
Variables
25(OH)D (ng/mL)
P value Q1 (,13.15) Q2 (13.15-16.53) Q3 (16.54-20.49) Q4 ($20.50)
eGFR (mL/min per 1.73 m2)
Model 1 94.0 (93.4-94.6) 92.3 (91.7-92.9) 91.3 (90.7-91.9) 90.7 (90.1-91.3) ,.001
Model 2 94.0 (93.3-94.6) 92.3 (91.6-92.9) 91.2 (90.6-91.8) 90.4 (89.8-91.1) ,.001
Model 3 93.4 (92.7-94.0) 91.9 (91.2-92.5) 90.9 (90.3-91.6) 90.2 (89.5-90.8) ,.001
ACR (mg/mg creatinine)
Model 1 21.7 (18.1-25.3) 20.1 (16.5-23.6) 16.8 (13.3-20.3) 15.0 (11.5-18.5) .043
Model 2 20.8 (16.9-24.7) 20.1 (16.3-23.9) 16.7 (12.9-20.5) 16.0 (12.2-19.8) .230
Model 3 22.0 (18.1-25.9) 20.4 (16.6-24.2) 16.3 (12.5-20.0) 15.0 (11.2-18.8) .043
25(OH)D, 25-hydroxyvitamin D.
All values are given as mean (95% CI).
Model 1 is adjusted by sex, age, season of blood collection, residential area, and waist circumference.
Model 2 is adjusted by model 1 variables plus smoking, alcohol intake, physically active, use of dietary supplements, diabetes, hypertension, cardiocerebrovascular disease, total cholesterol, triglycerides, and HDL cholesterol.
Model 3 is adjusted by model 2 variables plus log-ACR or log-eGFR.
Figure 1. Distribution of hypovitaminosis D according to age group.
100.8 [99.4-102.3], 99.8 [97.9-101.7], P, .001; age Q2 [38-51 years]: 96.6 [95.4-97.9], 94.9 [93.7-96.1], 93.6 [92.3-94.9], 92.1 [90.6-93.5], P , .001; age Q3 [52-64 years]: 91.1 [89.7-92.5], 90.6 [89.3-91.9], 89.4 [88.3-90.6], 87.9 [86.8-89.0], P 5 .002; age Q4 [.64 years]: 83.1 [81.5-84.6], 81.7 [80.2-83.2], 81.7 [80.3-83.0], 81.2 [80.1-82.4] mL/min/1.73 m2; P5.325).
Distribution of Mean 25(OH)D Values According to eGFR Levels
Figure 2shows the mean (95% CI) 25(OH)D values ac- cording to eGFR levels. After adjusting for covariates described above, the mean 25(OH)D value was highest at eGFR 61-90 mL/min per 1.73 m2and decreased signifi- cantly with decreasing eGFR levels (.90: 17.3 [17.1- 17.5]; 61-90: 17.6 [17.4-17.8]; 46-60: 17.1 [16.2-18.0];
31-45: 16.2 [14.2-18.2]; #30: 13.8 [17.0-10.7] ng/mL;
P5.008).
Discussion
We investigated the association of 25(OH)D with eGFR and albuminuria in an adult Korean population.
The mean eGFR values were negatively associated with 25(OH)D levels independently of ACR. However, the mean 25(OH)D values were decreased significantly with decreasing eGFR levels in moderate and severe chronic kidney disease (CKD) stages. Also, the mean ACR values were negatively associated with 25(OH)D levels independently of eGFR in a Korean adult population.
Several studies have investigated the association between renal function and vitamin D levels. However, the relation- ship between eGFR and vitamin D is debated. Although some studies have shown that eGFR increased as vitamin D levels increased,16,17 others found no association between vitamin D and GFR.18,19 The exact reason for these discrepancies is not clear; however, it may be that Table 3. Comparison of Mean eGFR Values Stratified by Age Quartiles According to 25(OH)D Quartiles
Age Quartiles
25(OH)D (ng/mL)
P value Q1 (,13.15) Q2 (13.15-16.53) Q3 (16.54-20.49) Q4 ($20.50)
Age Q1 (20-37 y) 105.4 (104.2-106.6) 102.9 (101.5-104.2) 100.8 (99.4-102.3) 99.8 (97.9-101.7) ,.001 Age Q2 (38-51 y) 96.6 (95.4-97.9) 94.9 (93.7-96.1) 93.6 (92.3-94.9) 92.1 (90.6-93.5) ,.001 Age Q3 (52-64 y) 91.1 (89.7-92.5) 90.6 (89.3-91.9) 89.4 (88.3-90.6) 87.9 (86.8-89.0) .002 Age Q4 (.64 y) 83.1 (81.5-84.6) 81.7 (80.2-83.2) 81.7 (80.3-83.0) 81.2 (80.1-82.4) .325 Values are adjusted by sex, season of blood collection, residential area, waist circumference, smoking, alcohol intake, physically active, use of dietary supplements, diabetes, hypertension, cardiocerebrovascular disease, total cholesterol, triglycerides, HDL cholesterol, and log-ACR.
Figure 2. Distribution of mean 25(OH)D values according to eGFR levels.
previous findings differed depending on whether the subjects were patients with CKD or individuals with normal or mildly decreased eGFR.24Most studies in pa- tients with CKD have found a positive association between eGFR and vitamin D levels,17,25,26 whereas those conducted in the general population typically found no association.18,19,27
We found that vitamin D deficiency was more prevalent in the youngest age group (20–29 years;Fig. 1). This is sur- prising; previous studies have demonstrated that the preva- lence of hypovitaminosis was highest among subjects in the elderly population.28,29 However, some researchers reported that vitamin D deficiency was more prevalent in young aged people in the United Kingdom30and Korea.16 They hypothesize that less outdoor activities and more sun- screen use in younger age than in elderly population might cause the higher hypovitaminosis among the younger par- ticipants. Moreover, our data showed that the youngest aged people less used dietary supplements (28.8% in 20–29 years; 43.0% in.60 years).
In contrast to previous studies, we found a significant decrease in eGFR with increasing 25(OH)D levels. To our knowledge, few previous studies have reported an in- verse association between eGFR and 25(OH)D. The Meta- bolic Syndrome in Men study, which included a cohort of 909 Finish males,31 found that high levels of 25(OH)D were associated with decreased GFR and older age. The au- thors suggested that the inverse relationship may have been the result of an age-related impairment in renal function causing an increase in 25(OH)D levels. However, in our data, stratification by age quartile revealed that eGFR decreased significantly with increasing 25(OH)L levels in every age group with the exception of the oldest (Table 3). Our findings indicate that the relationship be- tween eGFR and 25(OH)D levels may be mediated by an age-independent mechanism. Several mechanisms may un- derlie the inverse association between eGFR and vitamin D. First, the positive association between vitamin D with serum creatinine may play a role,24as we observed a positive association between serum creatinine and 25(OH)D levels (Table 1). Second, the product of 25(OH)D metabolism is decreased in patients with CKD, resulting in decreased vitamin D metabolism.32Thus, it may be that the level of 25(OH)D is paradoxically higher among individuals in the early stages of CKD than among those with an adequate eGFR.32A previous study of 6,529 Korean adults16found that 25(OH)D levels started to increase below an eGFR threshold of 55.4 mL/min/1.73 m2(early stage 3 CKD).
In our study, the highest mean 25(OH)D values occurred at eGFR 61-90 mL/min per 1.73 m2 and significantly decreased as eGFR decreased (Fig. 2).
We found that after adjusting for covariates and log- eGFR, the mean ACR values significantly decreased as 25(OH)D levels increased. Several factors may underlie the well-documented relationship between albuminuria
and vitamin D.18,33,34First, vitamin D has a direct effect on cell proliferation, differentiation, and apoptosis.35,36 Previous studies in vitamin D–deficient animals have found that vitamin D therapy decreased podocyte apoptosis, prevented glomerulosclerosis, and decreased albuminuria.37,38 Second, vitamin D influences glucose metabolism via activation of relevant receptors in pancreatic b-cell39; furthermore, vitamin D enhances b-cell function and protects such cells from immune attack.40Third, vitamin D has been shown to suppress acti- vation of the renin-angiotensin-aldosterone system41and prevent albuminuria through hemodynamic and nonhe- modynamic mechanisms.42
The primary strengths of our study lie in its population- based design and use of a relatively large sample size, which minimized selection bias and provided sufficient statistical power. However, the study has several limitations. First, we used a cross-sectional design. Second, because only one serum 25(OH)D measurement was taken, our findings reflect a single point in time rather than long-term expo- sure. Finally, when we compared the prevalence of CKD with previous study,43the number of moderate and severe CKD patients was small (3.1% in our data; 6.7% in previous study). Because of these small number of CKD patients in our data, our results might reflect low statistical power.
In conclusion, the mean eGFR values were negatively associated with 25(OH)D levels independently of ACR.
However, the mean 25(OH)D values were decreased significantly with decreasing eGFR levels in moderate and severe chronic kidney disease (CKD) stages. Also, the mean ACR values were negatively associated with 25(OH)D levels independently of eGFR in an Korean adult population.
Practical Application
A significant positive association between 25(OH)D and eGFR in moderate and severe CKD stages and a significant negative association between 25(OH)D and albuminuria appear to have an effect on renal function in general population.
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