title: Chronic effects of dietary vitamin D deficiency without increased calcium supplementation on the progression of experimental polycystic kidney disease.
abstract: Increasing evidence indicates that vitamin D deficiency exacerbates chronic kidney injury, but its effects on renal enlargement in polycystic kidney disease (PKD) are not known. In this study, male Lewis polycystic kidney disease (LPK) rats received a normal diet (ND; AIN-93G) supplemented with or without cholecalciferol (vitamin D-deficient diet, VDD; both 0.5% calcium), commenced at either postnatal week 3 (until weeks 10-20; study 1) or from week 10 (until week 20; study 2). Levels of 25-hydroxy vitamin D were reduced in groups receiving the VDD (12 ± 1 nmol/l vs. 116 ± 5 in ND; P < 0.001). In study 1, food intake and weight gain increased by ∼25% in LPK rats receiving the VDD ad libitum, and at week 20 this was associated with a mild reduction in the corrected serum calcium (SCa(2+), 7.4%) and TKW:BW ratio (8.8%), and exacerbation of proteinuria (87%) and hypertension (19%; all P < 0.05 vs. ND). When LPK rats were pair-fed for weeks 3-10, there was a further reduction in the SCa(2+) (25%) and TKW:BW ratio (22%) in the VDD group (P < 0.05 vs. ND). In study 2, the VDD did not alter food intake and body weight, reduced SCa(2+) (7.7%), worsened proteinuria (41.9%), interstitial monocyte accumulation (26.4%), renal dysfunction (21.4%), and cardiac enlargement (13.2%, all P < 0.05), but there was a trend for a reduction in the TKW:BW ratio (13%, P = 0.09). These data suggest that chronic vitamin D deficiency has adverse long-term actions on proteinuria, interstitial inflammation, renal function, and cardiovascular disease in PKD, and these negate its mild inhibitory effect on kidney enlargement.
authors.affiliation: Centre for Transplant and Renal Research, Level 2, Clinical Sciences Block, Westmead Hospital, Cnr Bridge and Darcy Rds., Westmead, NSW, Australia 2145. g.rangan@sydney.edu.au.
authors.forename: Gopala K
authors.initials: GK
authors.lastname: Rangan
authors.forename: Kristina G
authors.initials: KG
authors.lastname: Schwensen
authors.forename: Sheryl L
authors.initials: SL
authors.lastname: Foster
authors.forename: Mayuresh S
authors.initials: MS
authors.lastname: Korgaonkar
authors.forename: Anthony
authors.initials: A
authors.lastname: Peduto
authors.forename: David C
authors.initials: DC
authors.lastname: Harris
mesh_terms: D000818:Animals; D002136:Calcium, Dietary / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000150:complications*; D002762:Cholecalciferol / Q000097:blood / Q000494:pharmacology*; D019587:Dietary Supplements; D018450:Disease Progression; D007668:Kidney / Q000473:pathology*; D008297:Male; D010710:Phosphates / Q000097:blood; D007690:Polycystic Kidney Diseases / Q000150:complications / Q000188:drug therapy*; D011507:Proteinuria; D051381:Rats; D011917:Rats, Inbred Lew; D014808:Vitamin D Deficiency / Q000150:complications / Q000188:drug therapy*
chemical_list: D002136:Calcium, Dietary; D010710:Phosphates; D002762:Cholecalciferol
keywords: hypertension; kidney enlargement; polycystic kidney disease; vitamin D