Association of Vitamin D Levels With Kidney Volume in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Abstract

Vitamin D possesses renoprotective effects beyond mineral metabolism, potentially reducing arterial blood pressure and inflammation and vitamin D enzymes (CYP24A1 and CYP27B1) as well as vitamin D receptor (VDR) contribute to its homeostasis. In the present study, we aimed to determine vitamin D association with kidney volume, blood pressure parameters and inflammatory markers in ADPKD. This cross-sectional study, conducted from August 2011 through May 2016, evaluated 25(OH)D, 1,25(OH)2D and other hormonal/biochemical serum and urinary parameters, inflammatory markers and monocyte expression of VDR, CYP24A1, CYP27B1 in 74 ADPKD patients. The height-adjusted total kidney volume (htTKV) was determined by MRI and blood pressure (BP) measured through 24-h ambulatory BP monitoring (ABPM).Vitamin D insufficiency was present in 62% of patients and CYP24A1 was overexpressed in this group, raising a hypothesis of 25(OH)D increased catabolism. Serum 25(OH)D levels and VDR expression were negatively correlated with htTKV as was VDR with IL-6, IL-10, CRP, and NFκB. A multiple linear regression analysis with htTKV as dependent variable, including hypertension, CRP, eGFR, age, time since diagnosis, VDR, and 25(OH)D adjusted for season of the year showed that only the first three parameters were independent predictors of the former. There has been no association of serum 25(OH)D and VDR expression with ABPM parameters. Present findings suggested that low levels of serum 25(OH)D and VDR expression are associated with a higher kidney volume in ADPKD patients, but do not represent independent risk factors for htTKV.

Effect of Early and Delayed Commencement of Paricalcitol in Combination with Enalapril on the Progression of Experimental Polycystic Kidney Disease

“…In LPK rats, chronic dietary deficiency of vitamin D exacerbated proteinuria but unexpectedly caused a small but significant reduction in kidney cyst growth [19]. In contrast, in a small longitudinal cohort study of humans with ADPKD, low levels of 25-OH vitamin D did not predict changes in total kidney volume or blood pressure [36]. An important disease-specific finding of the current study was that neither early nor delayed treatment with paricalcitol altered kidney cyst growth [19].…”

Interactions between FGF23 and Genotype in Autosomal Dominant Polycystic Kidney Disease

“…However, very little is known about vitamin D levels as a predictor of progression in ADPKD. A recent, small, cross-sectional study observed no independent association of either 1,25(OH) 2 D and 25(OH)D levels with total kidney volume (28). In Lewis PKD rats (a hypertensive rodent model of PKD which phenotypically resembles ARPKD but is a genetic ortholog of human nephrocystin protein 9), chronic vitamin D deficiency had adverse effects on proteinuria, inflammation, cardiovascular health, and renal function, despite mild inhibitory effects on kidney enlargement (29).…”

Systems biology approaches toward autosomal dominant polycystic kidney disease (ADPKD)

“…The mechanisms of the newly introduced crucial genes such as PPIE remain to be identified with experimental studies. We pointed out TFs such as HNF4A, STAT3, VDR, TP53, and HIF1A associated with ADPKD [22,23]. In addition, other TFs as CLOCK in ADPKD pathogenesis firstly are described in this study.…”

“…Previous studies reported the association of ADPKD with some of TFs e.g. HNF4A, STAT3, VDR, TP53, and HIF1A [6, 20, 22, 23]. Also, the role of miR‐17 family and miR‐192 in cyst enlargement were identified [24,25].…”