Association of High Calcitriol Serum Levels and Its Hydroxylation Efficiency Ratio with Disease Risk in SLE Patients with Vitamin D Deficiency
Mónica R. Meza-Meza, José Francisco Muñóz-Valle, Adolfo I. Ruiz-Ballesteros, Bárbara Vizmanos, Isela Parra‐Rojas, Erika Martínez‐López, Edith Oregon‐Romero, Fabiola Márquez‐Sandoval, Sergio Cerpa‐Cruz, Ulises De la Cruz-Mosso
Abstract
Vitamin D (calcidiol) deficiency in systemic lupus erythematosus (SLE) is more frequent than in healthy subjects (HS); it is associated with clinical activity and damage in SLE. Although calcidiol is considered the best indicator of the vitamin D serum status, its deficiency could not reflect its hydroxylation efficiency ratio and calcitriol serum status. This study was aimed at assessing the association of calcidiol and calcitriol serum levels and its hydroxylation efficiency ratio with the risk to clinical and renal disease activities in SLE patients. A cross-sectional study was conducted in 308 SLE and HS women; calcidiol and calcitriol serum levels were evaluated by immunoassays. SLE patients showed lower calcidiol serum levels vs. HS (21.2 vs. 24.2 ng/mL; <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>p</a:mi> <a:mo><</a:mo> <a:mn>0.001</a:mn> </a:math> ). Active SLE patients presented higher calcidiol/calcitriol ratio scores vs. inactive SLE patients (2.78 vs. 1.92 pg/ng; <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>p</c:mi> <c:mo>=</c:mo> <c:mn>0.02</c:mn> </c:math> ), and SLE patients with renal disease activity showed a pattern of calcidiol-deficient levels (19.5 vs. 25.3 ng/mL; <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>p</e:mi> <e:mo><</e:mo> <e:mn>0.04</e:mn> </e:math> ) with higher calcitriol levels (47 pg/mL vs. 41.5 pg/mL; <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>p</g:mi> <g:mo>=</g:mo> <g:mn>0.02</g:mn> </g:math> ) and calcidiol/calcitriol ratio scores (2.13 vs. 1.54 pg/ng; <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>p</i:mi> <i:mo><</i:mo> <i:mn>0.02</i:mn> </i:math> ) compared to SLE patients without renal disease activity. Calcidiol levels were negatively correlated with calcitriol levels ( <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>r</k:mi> <k:mo>=</k:mo> <k:mo>−</k:mo> <k:mn>0.26</k:mn> </k:math> ; <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M7"> <m:mi>p</m:mi> <m:mo>=</m:mo> <m:mn>0.001</m:mn> </m:math> ) and urine proteins (mg/dL) ( <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" id="M8"> <o:mi>r</o:mi> <o:mo>=</o:mo> <o:mo>−</o:mo> <o:mn>0.39</o:mn> </o:math> ; <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" id="M9"> <q:mi>p</q:mi> <q:mo><</q:mo> <q:mn>0.01</q:mn> </q:math> ). Regarding calcitriol levels, it was positively correlated with the blood lymphocyte count ( <s:math xmlns:s="http://www.w3.org/1998/Math/MathML" id="M10"> <s:mi>r</s:mi> <s:mo>=</s:mo> <s:mn>0.30</s:mn> </s:math> ; <u:math xmlns:u="http://www.w3.org/1998/Math/MathML" id="M11"> <u:mi>p</u:mi> <u:mo><</u:mo> <u:mn>0.001</u:mn> </u:math> ) and negatively correlated with the glomerular filtration rate ( <w:math xmlns:w="http://www.w3.org/1998/Math/MathML" id="M12"> <w:mi>r</w:mi> <w:mo>=</w:mo> <w:mo>−</w:mo> <w:mn>0.28</w:mn> </w:math> ; <y:math xmlns:y="http://www.w3.org/1998/Math/MathML" id="M13"> <y:mi>p</y:mi> <y:mo>=</y:mo> <y:mn>0.001</y:mn> </y:math> ). Moreover, the calcitriol/calcidiol ratio was positively correlated with urine proteins ( <ab:math xmlns:ab="http://www.w3.org/1998/Math/MathML" id="M14"> <ab:mi>r</ab:mi> <ab:mo>=</ab:mo> <ab:mn>0.38</ab:mn> </ab:math> ; <cb:math xmlns:cb="http://www.w3.org/1998/Math/MathML" id="M15"> <cb:mi>p</cb:mi> <cb:mo><</cb:mo> <cb:mn>0.01</cb:mn> </cb:math> ). The calcidiol deficiency ( <eb:math xmlns:eb="http://www.w3.org/1998/Math/MathML" id="M16"> <eb:mtext>OR</eb:mtext> <eb:mo>=</eb:mo> <eb:mn>2.27</eb:mn> </eb:math> ; 95% <gb:math xmlns:gb="http://www.w3.org/1998/Math/MathML" id="M17"> <gb:mtext>CI</gb:mtext> <gb:mo>=</gb:mo> <gb:mn>1.15</gb:mn> </gb:math> -4.49; <ib:math xmlns:ib="http://www.w3.org/1998/Math/MathML" id="M18"> <ib:mi>p</ib:mi> <ib:mo><</ib:mo> <ib:mn>0.01</ib:mn> </ib:math> ), high calcitriol levels ( <kb:math xmlns:kb="http://www.w3.org/1998/Math/MathML" id="M19"> <kb:mi>T</kb:mi> <kb:msup> <kb:mrow> <kb:mn>3</kb:mn> </kb:mrow> <kb:mrow> <kb:mtext>rd</kb:mtext> </kb:mrow> </kb:msup> </kb:math> , <mb:math xmlns:mb="http://www.w3.org/1998/Math/MathML" id="M20"> <mb:mtext>OR</mb:mtext> <mb:mo>=</mb:mo> <mb:mn>4.19</mb:mn> </mb:math> , 95% <ob:math xmlns:ob="http://www.w3.org/1998/Math/MathML" id="M21"> <ob:mtext>CI</ob:mtext> <ob:mo>=</ob:mo> <ob:mn>2.23</ob:mn> </ob:math> -7.90; <qb:math xmlns:qb="http://www.w3.org/1998/Math/MathML" id="M22"> <qb:mi>p</qb:mi> <qb:mo><</qb:mo> <qb:mn>0.001</qb:mn> </qb:math> ), and a high calcitriol/calcidiol ratio score ( <sb:math xmlns:sb="http://www.w3.org/1998/Math/MathML" id="M23"> <sb:mi>T</sb:mi> <sb:msup> <sb:mrow> <sb:mn>3</sb:mn> </sb:mrow> <sb:mrow> <sb:mtext>rd</sb:mtext> </sb:mrow> </sb:msup> </sb:math> , <ub:math xmlns:ub="http://www.w3.org/1998/Math/MathML" id="M24"> <ub:mtext>OR</ub:mtext> <ub:mo>=</ub:mo> <ub:mn>5.93</ub:mn> </ub:math> , 95% CI: 3.08-11.5; <wb:math xmlns:wb="http://www.w3.org/1998/Math/MathML" id="M25"> <wb:mi>p</wb:mi> <wb:mo><</wb:mo> <wb:mn>0.001</wb:mn> </wb:math> ) were associated with the risk for SLE. In conclusion, a pattern of calcidiol deficiency with high calcitriol