Vitamin D and renal outcome: the fourth outcome of CKD-MBD? Oshima Award Address 2015

Abstract

Bone fracture, cardiovascular events, and mortality are three outcomes of chronic kidney disease-mineral and bone disorder (CKD-MBD), and the umbrella concept originally described for dialysis patients. The reported association of serum phosphorus or fibroblast growth factor 23 (FGF23) levels with renal outcome suggests that the fourth relevant outcome of CKD-MBD in predialysis patients is renal outcome. We found that proteinuria of 2+ or greater with a dipstick test was associated with low vitamin D status due to urinary loss of 25-hydroxyvitamin D (25D). Moreover, active vitamin D or its analogues decrease proteinuria. Given our finding that maxacalcitol does not repress renin, the reduction of proteinuria by this agent is likely due to direct upregulation of the nephrin and podocin in podocytes. Moreover, this agent downregulates the mesenchymal marker desmin in podocytes and blocks transforming growth factor—beta autoinduction, leading to attenuation of renal fibrosis in a unilateral ureteral obstructive (UUO) model. These facts are reminiscent of the suppression of epithelial–mesenchymal transition (EMT) by vitamin D. EMT blockage may explain our finding that vitamin D prescription in renal transplant recipients is associated with a lower incidence of cancer. We also reported that low vitamin D status and high FGF23 levels predict a worse renal outcome. However, administration of massive doses of 25D exacerbates renal fibrosis in UUO kidneys in 1alpha-hydroxylase knockout mice. Moreover, FGF23 inhibits 1alpha-hydroxylase in proximal tubules and monocytes. Taken together, local 1,25(OH)2D in the kidney tissue but not 25D seems to protect the kidney.

Impact of Vitamin D Receptor Gene Polymorphism on Chronic Renal Failure Susceptibility

“…Besides, a large body of evidence demonstrates that VDR agonists can effectively attenuate the progression of DN . In addition, vitamin D and its analog therapy could improve kidney and cardiovascular functions in patients with CKD .…”

The effect of vitamin D supplementation on fibroblast growth factor‐23 in patients with chronic kidney disease: A systematic review and meta‐analysis

“…After full‐text examination, 36 publications were excluded for the following reasons: none‐randomized controlled trials (n = 8) (Alshayeb, Josephson, & Sprague, 2013; Block, 2011; Brandenburg & Kruger, 2014; Cozzolino et al, 2009; Donate‐Correa et al, 2014; Fish & Cunningham, 2012; Galassi et al, 2017; Hamano, 2018), RCTs conducted on participants younger than 18 years (n = 1) (Lerch et al, 2018), trials conducted on patients who did not have CKD (n = 6) (Burnett‐Bowie et al, 2012; Cheng et al, 2018; Macdonald et al, 2013; Mesinovic et al, 2019; Trummer et al, 2019; Uzum et al, 2010), non‐experimental studies (n = 1) (Saki, Ranjbar Omrani, & Koohpeyma, 2019), vitamin D supplementation was combined with other treatments (n = 2) (Wetmore, Liu, Krebill, Menard, & Quarles, 2010a; Wetmore, Liu, Krebill, Menard, & Quarles, 2010b), studies without suitable group for vitamin D administration (n = 10) (Albuquerque et al, 2018; Alshayeb et al, 2014; Batacchi et al, 2017b; Bleskestad, Bergrem, Hartmann, Godang, & Goransson, 2012; Cozzolino et al, 2014; Hansen, 2011; Hansen et al, 2011; Hansen, Rasmussen, Pedersen, Rasmussen, & Brandi, 2012; Hansen, Rasmussen, Rasmussen, Bruunsgaard, & Brandi, 2014; Sprague et al, 2015), lack of control group (n = 5) (Cancela et al, 2011; Chitalia et al, 2014; De Niet et al, 2018; Garcia‐Lopes et al, 2012; Zelnick, de Boer, Kestenbaum, Chonchol, & Kendrick, 2018), vitamin D administered via injection (n = 1) (Zhang et al, 2017), and insufficient data reported in the manuscript (n = 2) (Alvarez et al, 2013; Carvalho et al, 2017). Two additional studies were extracted during the full‐text evaluation by hand‐searching the reference lists of related articles, reviews, and meta‐analyses.…”

“…After full-text examination, 36 publications were excluded for the following reasons: none-randomized controlled trials (n = 8) (Alshayeb, Josephson, & Sprague, 2013;Block, 2011;Brandenburg & Kruger, 2014;Cozzolino et al, 2009;Donate-Correa et al, 2014;Fish & Cunningham, 2012;Galassi et al, 2017;Hamano, 2018), RCTs conducted on participants younger than 18 years (n = 1) (Lerch et al, 2018)…”

Hypovitaminosis D Is Prevalent in Patients With Renal AL Amyloidosis and Associated With Renal Outcome

“…However, it has been postulated that vitamin D may be renoprotective via modulation of several pathways including the renin-angiotensin, NF-kB and Wnt/β-catenin signaling pathways ( 35 ). In addition, vitamin D deficiency can downregulate the generation of nephrin and podocin, essential structures of the podocytes, an effect which would then be expected to damage the glomerular filtration barrier leading to a pro-proteinuric effect ( 36 ). However, as low vitamin D levels were associated with higher renal stage, one cannot rule out that vitamin D deficiency is not directly involved in progression to ESRD, but rather represents a marker of advanced renal impairment and progression to ESRD.…”