1. Response to standard Vitamin D treatment among Children with Chronic Kidney Disease and Primary Hypertension Bandana Paudyal, MD, Gail Prado MD, Morris Schoeneman MD, Hanan Tawadrous MD, Manoj K Nepal MD, Vaishali Bansilal MD, Valeriya Feygina MD, Shilpi Shrivastava, MD and Anil K. Mongia, MD. Department of Pediatrics, Div. of Pediatric Nephrology, SUNY, Brooklyn, NY
Abstract
Objectives
Results
Background: Children with vitamin D deficiency are treated with either ergocalciferol or cholicalciferol. Vitamin D treatment is standard fixed dose and duration as per serum 25 (OH) D levels, irrespective of age and weight. That means, the same dose might be sub therapeutic for some patients and toxic for other patients. However, limited studies are available looking at response of 25(OH) D level post treatment. Objective: To assess the normalization of serum 25 (OH)D level (>30 ng/ml) after standard treatment dosing among Primary Hypertension (PH) and Chronic Kidney disease (CKD) . Methods: We enrolled 144 patients aged 2 to 19 yrs, 34 (PH), 95 (CKD) 15 Control(C). Among CKD, 58 were (CKD I-IV), 16(Transplant), 21(Dialysis). We collected retrospective data on age, sex,race, cause of kidney disease, eGFR, Ht, Wt, BMI, BP z-scores, lipid panel, 25(OH) D level, PTH, Calcium, Phosphorus, Magnesium, medications, type and dosing of Vitamin D Supplements and follow up serum vitamin D level three months post treatment. Results: Mean age (yrs) was (12.99±5.05); CKD were older (13.65±5.29) p: 0.02, than PH (11.21±4.27) and C (11.17±3.21). Male and female were equal; white (2), African American (102), Hispanics (31), others (9). eGFR(ml/min/1.73m2 was significantly lower among CKD (57.22±43) than PH(89.49±13.3),p=0.002 and control(102.23±14.14),p=0.03. SBP z-score (2.4±2.7) was higher among PH p=0.07. Cholesterol (mg/dl) was higher among CKD (178±64.05) than PH (141±28.8) p=0.02 and C (165±14.4) p= BMI (kg/m2) was significantly higher among PH (28.7±9.4,) p= and Control (27.5±8.9) p= 0.03, than CKD (22.4±8.3). Prevalence of Vitamin D deficiency was (88%); 60% had level <20 ng/ml. Mean pretreatment 25(OH) D (ng/ml) was (19.25±10.69), no significant difference among PH (19.33±9.6), CKD (18.77±11.25) and Control (22.89±7.84). Pretreatment 25(OH) D didn't correlate with PTH, eGFR, BMI, SBP/DBP Z-score, serum cholesterol. Mean post treatment 25(OH) D(ng/ml) was (25.72±9.3). After completion of standard treatment almost 64 % patients had 25 (OH) D level <30 ng/ml; PH(28.02±9.22) and CKD(25.38±9.8). None were in toxic range. Conclusions: The standard treatment dose of Vitamin D doesn't normalize 25(OH)D level in majority of patients. Newer treatment guidelines may be needed to optimize the treatment.
To assess the Prevalance of Vitamin D defeciency
To assess the normalization of serum 25 (OH)D level (>30 ng/ml) after standard treatment dosing among patients with Primary Hypertension (PH) and Chronic Kidney disease (CKD).
Table 2: Comparison between Primary Hypertension, Chronic Kidney Disease and Control.
Primary
Hypertension
( N=34)
CKD (N=95)
Control (N=15)
p- value
SBP Z-Score
2.8±1.9
-0.23±2.23
1.08±1.4
*0.07,***0.06
DBP Z-Score
0.24± 2.1
0.47±1.6
0.35±0.87 NS
eGFR( ml/min)
89.49±13.3
57.14±43
102.23±14.14
** 0.001,***0.02
PTH( pg/ml)
48.45±34.98
286.7±450.85 -
Calcium ( mg/dl)
9.3±1.5
9.21±1
9.7±1.8
Phosphorus (mg/dl)
4.5±0.72
4.3±0.9
5.3±1
Pre treatment 25 (OH) Vit D
(32-110ng/ml)
19.33±9.6
18.77±11.25
22.89±7.84
Post Treatment
25(OH) D
28.02±9.22
25.38±9.8 NA
1,25(OH)Vit D
(15-75 pg/ml)
54.7±23.11
56.22±24
66.25±11.47
*0.06
Cholesterol (mg/dl)
141±28.8
178±64.05
165±14.4
*0.02,**0.007
HDL (mg/dl)
41.38±10
48±18.29
55.41±23.56
*0.02
LDL (mg/dl)
91.33±26.25
100.96±52.46
98.5±19.27
TG (mg/dl)
88.09±39.02
149±102
82.44±33.14
**0.004,***0.05
*P <0.05 between Primary Hypertension and Control, * * P <0.05 between Primary Hypertension and CKD and
* * * p <0.05 between CKD and Control
Design/Methods
Retrospective data was collected from 144 patients aged 2-19 yrs. 34 were Primary hypertension (PH), 95 chronic kidney diseases (CKD),15 Control(C). Among CKD, 58 were (CKD stage I-IV), 16(Renal Transplant), 21(Dialysis).
We collected data on age, sex, race, cause of kidney disease, eGFR, Ht, Wt, BMI, BP z-scores, lipid panel, 25(OH) D level, PTH, Calcium, Phosphorus, Magnesium, medications, type and dosing of Vitamin D Supplements and follow up serum vitamin D level three months post treatment.
Definition of CKD is done as per kidney disease improving global outcome (KDIGO). Causes of Kidney disease are categorized as Hypo/dysplasia, Obstructive uropathy, Focal Segmental Glomerular Sclerosis, lupus nephritis and others. CKD staging dose as per estimated Glomerular filtration rate (eGFR: ml/min/1.73m2). eGFR is calculated using modified Schwartz formula (eGFR = * height (cm)/creatinine (mg/dl).
Hypertension is defined as average SBP and/or diastolic BP (DBP) that is >95th percentile for gender, age, and height on >3 occasions. Systolic BP and Diastolic BP Z-scores are calculated. Body Mass Index (BMI) is calculated from a child's weight and height. CDC BMI-for-age growth charts (for either girls or boys) are used to obtain a percentile ranking. BMI categorized as underweight <5%ile, healthy weight 5-85%ile, overweight 85- <95%ile, obese >95%ile.
Spearman coefficient was used to determine the correlation between Vitamin D, SBP z-score, DBP z-score, GFR, and PTH, BMI, LDL, HDL, TG, Cholesterol, using SPSS version 2.0.
Background
Vitamin D deficiency is very common among children. Individuals at risk for deficiency are recommended to screen for vitamin D deficiency .
25(OH)D is the major circulating form of vitamin D, with a circulating half-life of 2–3 wk, and it is the best indicator to monitor for vitamin D status. Vitamin D deficiency is defined as 25(OH)D level below 20 ng/ml, insufficiency as a 25(OH)D of 21–29ng/ml, and sufficiency as a 25(OH)D of 30–100 ng/ml.
Children with vitamin D deficiency are treated with either ergocalciferol or cholecalciferol. Vitamin D treatment is standard fixed dose and duration as per serum 25 (OH) D levels, irrespective of age and weight. That means, the same dose might be sub therapeutic for some patients and toxic for other patients. However, limited studies are available looking at response of 25(OH) D level post treatment.
Although it is not known what the safe upper value for 25(OH)D is for avoiding hypercalcemia, most physicians might be reluctant to treat aggressively to avoid risk of hypercalemcia. Most studies in children and adults have suggested that the blood levels need to be above150 ng/ml before there is any concern.
There are sparse data to guide pediatric clinicians in the treatment of young children with vitamin D deficiency. As per Endocrinology Society guideline, children aged 1–18 yr who are vitamin D deficient, suggested treatment is with 2000 IU/d of vitaminD2 or vitamin D3 for at least 6 wk or with 50,000 IU of vitaminD2 once a week for at least 6 wk to achieve a blood level of 25(OH)D above 30 ng/ml followed by maintenance therapy of IU/d.
Chronic kidney disease stage 3-4 patients are treated as per NKF KDOQI guideline. Severe vitamin D deficiency (25(OH)D:<5ng/ml) treated with average ergocalciferol or cholecalciferol IU /week x 4 weeks followed with IU 2x per month x 2 months. Mild vitamin D deficiency (25(OH )D: 5- 15ng/ml) with IU every other week x 12 weeks, Vitamin D insufficiency (25( OH )D:16-30 ng/ml),50000 IU/month x 3 months. 25 (OH)D levels is checked after 3 months of treatment.
Results
Prevalence of Vitamin D deficiency in our study population was high. 88% had vitamin D <30ng/ml, of those 60% has level <20 ng/ml. Pretreatment 25(OH) D didn't correlate with PTH, eGFR, BMI, SBP/DBP Z-score, serum cholesterol. After completion of standard treatment almost 64 % patients had 25 (OH) D level <30 ng/ml; PH (28.02±9.22) and CKD (25.38±9.8). None were in toxic range.
Table 1: Demographics and Patient Characteristics
Conclusions
Primary
Hypertension (N=34)
CKD (N=95)
Control (N=15)
p- value
Age ( yrs)
11.21±4.27
13.65±5.29
11.17±3.21
**0.02
Sex (M / F)
16/18
75/50
3/12
Ethnicity (AA) 26 75 13
Causes Of CKD:
Hypodysplastic/Obstructive/FSGS/ Lupus/ others NA
16/12/25/14/28
BMI (kg/m2)
>95%ile (Obese) 14 19 5
** 0.002, ***0.03
The standard treatment dose of Vitamin D doesn't normalize 25(OH)D level in majority of patients. Newer treatment guidelines may be needed to optimize the treatment
References
1) Michael F. Holick, et al, Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab 96: 1911–1930, 2011
2) Holick MF et al, VitaminD deficiency. NEngl JMed357:266–281, 2007
3) Swiglo BA et al A case for clarity, consistency, and helpfulness: state-of-the-art clinical practice guidelines in endocrinology using the grading of recommendations, assessment, development, 2008
4) KDOQI Clinical Practice Guideline 2008 Update