Mineral metabolism parameters throughout chronic kidney disease stages 1-5--achievement of K/DOQI target ranges

Craver, Lourdes; Marco, Maria Paz; Martínez, Isabel; Rué, Montserrat; Borràs, Mercè; Martín, María Luisa; Sarró, F.; Valdivielso, José M.; Fernàndez, Elvira

doi:10.1093/ndt/gfl718

Cited by 222 publications

(210 citation statements)

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“…(26,53,54) We have extended these studies by characterizing the natural progression of CKD-MBD in the jck mouse, a genetic model of PKD, (28) as a first step toward defining the mechanistic link between renal dysfunction, declining bone, and cardiovascular disease. Importantly, we confirm that changes in jck serums closely mirror those observed in clinical serum samples as reported by Craver and colleagues, (29) albeit with some differences (Fig. 1).…”

Section: Discussionsupporting

confidence: 91%

“…1B). (29) As expected, hyperphosphatemia is a late event with significant changes relative to baseline observed in 15-week-old jck mice similar to those observed in humans (Fig. 1C).…”

Section: Discussionsupporting

confidence: 84%

“…1F). (29) The observation that basal jck serum 1,25(OH) 2 D 3 levels are elevated at the start of the study relative to WT animals likely reflects the reduced dietary calcium and elevated phosphate levels in the jck mouse diet compared to the normal chow fed to WT mice. A similar rise in serum 1,25(OH) 2 D 3 was observed in WT mice when placed on this diet without causing bone abnormalities or vascular calcification (Supplemental Fig.…”

Section: Discussionmentioning

confidence: 96%

“…(28) jck mice develop concurrent serum biochemical changes characteristic of human CKD-MBD, (29) with approximately 40% to 60% of jck mice also developing vascular calcification and initial stages of LVH. Histomorphometric analysis revealed the presence of high-turnover (HTO) bone disease prior to a significant elevation of serum parathyroid hormone (PTH).…”

Section: Introductionmentioning

confidence: 99%

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Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

Sabbagh

Graciolli

O’Brien

et al. 2012

Journal of Bone and Mineral Research

240

224

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Chronic kidney disease–mineral bone disorder (CKD‐MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft‐tissue calcification. Emerging evidence suggests that features of CKD‐MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild‐type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD‐MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild‐type mice. To capture the early molecular and cellular events in the progression of CKD‐MBD we examined cell‐specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor‐Ser33/37‐β‐catenin was observed both in mouse and human bones. Overall repression of Wnt/β‐catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF‐κB ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late‐stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD‐MBD and suggest that repression of the Wnt/β‐catenin pathway is involved in the pathogenesis of renal osteodystrophy. © 2012 American Society for Bone and Mineral Research.

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Section: Discussionsupporting

confidence: 91%

“…1B). (29) As expected, hyperphosphatemia is a late event with significant changes relative to baseline observed in 15-week-old jck mice similar to those observed in humans (Fig. 1C).…”

Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

Sabbagh

Graciolli

O’Brien

et al. 2012

Journal of Bone and Mineral Research

240

224

View full text Add to dashboard Cite

show abstract

“…Recent clinical studies demonstrate a high fractional renal phosphate excretion despite the presence of normophosphatemia in early CKD (2)(3)(4). The increased renal phosphate excretion is driven, at least partly, by parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) (3,(5)(6)(7).…”

mentioning

confidence: 99%