Published ahead of print on March 5, 2008
Clin J Am Soc Nephrol 3: 836-843, 2008
© 2008 American Society of Nephrology
doi: 10.2215/CJN.02910707
Contribution of Bone and Mineral Abnormalities to Cardiovascular Disease in Patients with Chronic Kidney Disease
Paolo Raggi*, and
Michael Kleerekoper
* Department of Medicine and Radiology, Emory University School of Medicine, Atlanta, Georgia; and Department of Endocrinology, Saint Joseph Mercy Hospital, Ann Arbor, and Department of Internal Medicine, Wayne State University, Detroit, Michigan
Correspondence: Dr. Paolo Raggi, Emory University School of Medicine, 1365 Clifton Road NE, AT-504, Atlanta, GA 30322. Phone: 404-778-5414; Fax: 404-778-3540; E-mail: praggi{at}emory.edu
 |
Abstract
|
|---|
1,25-Dihydroxyvitamin D3 levels begin to drop early in the course of kidney disease, leading to elevated parathyroid hormone levels and disrupted mineral metabolism. Impaired mineral metabolism seems to be associated not only with bone disease but also with vascular calcification. Animal models have identified molecular mechanisms by which high mineral levels and other uremic substances induce vascular smooth muscle cells to undergo phenotypic changes that initiate the calcification process. Moreover, several epidemiologic and clinical studies showed strong associations between bone loss, arterial calcification, and cardiovascular disease in populations with and without kidney disease. This review discusses evidence that two early complications of chronic kidney disease—vitamin D deficiency and secondary hyperparathyroidism—contribute to bone and cardiovascular disease. New treatment strategies aimed at the prevention of bone loss and parathyroid hyperplasia, such as vitamin D receptor ligand therapy, calcimimetic agents, and noncalcifying phosphate binders, are being investigated for their impact on improving overall outcome in dialysis patients.
|
Introduction
|
|---|
Chronic kidney disease (CKD) is now the ninth leading cause of death, affecting approximately 20 million adults in the United States (1,2). Nearly 80,000 people receive a diagnosis of CKD annually, with diabetes and hypertension being the most common causes (3). More than 8 million Americans have significant impairment of kidney function, and nearly 400,000 receive maintenance dialysis (4–7). Two of the early complications of CKD include deficiency of 1,25-dihydroxyvitamin D3 (1,25-D) and development of secondary hyperparathyroidism (SHPT), complications that lead to bone loss and, likely, cardiovascular disease (CVD) (8–11). Although bone loss contributes to abnormally high fracture rates in patients with CKD, emerging data also indicate that the disorders of bone metabolism typical of kidney failure contribute to the high rates of CVD observed (12–15). This review identifies recent studies that describe the impact of 1,25-D deficiency, SHPT, and bone metabolism derangements on the development of CVD in patients with CKD and summarizes new treatment strategies that are expected to have a substantial impact on mortality in this patient population.
|
1,25-D Deficiency in CKD
|
|---|
The progressive effects of CKD lead to a deficiency in serum calcitriol levels, which begin to decline when the GFR drops below 70 ml/min in stage 2 CKD (16). 1,25-D regulates calcium and phosphate levels in the blood by enhancing calcium and phosphate absorption in the intestine, enhancing calcium reabsorption in the kidney tubules, and suppressing parathyroid hormone (PTH) secretion (17,18). Accordingly, 1,25-D–deficient individuals are hypocalcemic and have elevated serum levels of PTH (19,20). Moreover, 1,25-D deficiency is the probable primary initiating event behind the elevated PTH levels seen in the majority of patients with stage 3 CKD. Indeed, serum levels of calcitriol begin to decline when GFR falls below 70 ml/min, corresponding to the point at which elevated PTH levels are usually first noted (16,20). It is not until much later (GFR <30 ml/min) that hyperphosphatemia, a condition that further inhibits the 1 
-hydroxylase enzyme, and hypocalcemia also become apparent and act additionally to stimulate PTH production and parathyroid gland enlargement (21–23).
The recent finding that vitamin D receptor ligand (VDRL) therapy is crucial in preventing and inducing regression of parathyroid hyperplasia in CKD underscores the importance of low 1,25-D levels in the pathogenesis of this disease (24). These low levels of calcitriol contribute to the development of bone disease in patients with CKD. Decreased VDR activation, caused by low calcitriol levels, is directly responsible for bone loss through decreased osteoblast recruitment (25). Furthermore, 1,25-D deficiency leads to elevated serum PTH levels, which can cause bone loss through the stimulation of excess bone resorption.
|
Hyperparathyroidism in CKD
|
|---|
Parathyroid gland cells express receptors for the ionic form of calcium and proliferate in response to low serum calcium levels, resulting in an overall enlargement of the glands and elevation of circulating levels of PTH (19). In addition, 1,25-D deficiency and hyperphosphatemia can further stimulate secretion of PTH. In healthy individuals, PTH regulates serum calcium levels by increasing bone remodeling, decreasing the renal reabsorption of phosphates, elevating the renal reabsorption of calcium, and increasing renal production of calcitriol. In turn, increasing levels of calcium suppress PTH levels in healthy individuals in an autoregulatory manner. In CKD, both calcium and phosphorus serum levels may rise as bone tissue is remodeled in response to the PTH action, although phosphate levels also rise as a result of loss of renal function (26). Importantly, hyperphosphatemia lowers the ability of the parathyroid gland to detect changes in serum calcium levels by interacting with free calcium ions, hence indirectly promoting PTH synthesis (8). In addition, high levels of phosphates have been shown to lead to downregulation of calcium-detecting receptors in parathyroid gland cells, inducing resistance of the parathyroid glands to respond to high levels of serum calcium (8). Thus 1,25-D deficiency and renal dysfunction both promote SHPT, resulting in adverse impacts on bone tissue via decreased osteoblast recruitment, decreased formation of bone tissue, and increased breakdown of bone tissue by osteoclasts (26).
|
Renal Failure–Associated Bone Disease
|
|---|
The most frequently encountered types of bone disease in patients with CKD are high-turnover and adynamic bone disease (ABD) with a minority of patients showing a combination of the two. High-turnover bone disease is characterized by excessive rates of bone resorption and formation that occur in response to high levels of PTH (9,26). In this condition, both osteoblast and osteoclast activity is increased and the extremely rapid remodeling rate prevents adequate mineralization of newly formed bone (9). This results in a structurally weak bone with decreased overall density. In contrast, ABD is characterized by decreased rates of bone formation as a result of decreased osteoblast recruitment and activity and defects in bone mineralization (9,27). This type of bone anomaly often occurs in patients with relatively low levels of PTH (<150 pg/ml) and may result in part from 1,25-D deficiency (18).
The most prevalent metabolic bone abnormality in patients with CKD is high-turnover bone disease. In predialysis CKD, more than 90% of patients have this form of bone histology, whereas fewer than 5% have the adynamic variety of bone histology (28). In dialysis patients, however, the percentage with ABD is often larger (20 to 40%), although this is highly dependent on the type of dialysis and on the extent of calcium loading in any given patient (27–30). Although it is clear that high bone turnover contributes to bone loss and fractures, it is less clear that ABD is associated with an increased fracture risk because of a paucity of bone biopsy data in large prospective studies (11,31–34). Excess calcium loading, often seen in ABD, has been proposed as a risk factor for bone loss in dialysis patients as shown by the reduction of bone mineral density (BMD) measured by sequential quantitative computed tomography (35). The purported mechanism for such paradoxic effect is the suppression of the pulsatile release of PTH induced by constant administration of calcium supplements. This in turn suppresses bone remodeling. Recent data suggest that ABD may also constitute a risk for CVD if there is concomitant aluminum or calcium overload, because of the inability of bone to buffer calcium (36,37). Whether the induction of ABD by low PTH levels, without evidence of aluminum or calcium overload, is related to increased CVD morbidity and mortality remains a point of debate. Recent studies of dialysis patients who underwent parathyroidectomy showed a long-term survival benefit after parathyroid gland removal (38). Although controversial, this finding lends support to the notion that PTH levels lower than those recommended by recent consensus guidelines may be preferable for dialysis patients (4). Further prospective studies will be needed to confirm the survival benefit associated with lower PTH levels, particularly in light of the findings reported by Avram et al. (39); a 14-yr prospective observational study of more than 600 dialysis patients showing that very low levels of PTH (<65 pg/ml) are associated with increased mortality.
|
CVD in CKD
|
|---|
Within the Medicare population, CVD is twice as common and advances at twice the rate in patients with CKD (40). Moreover, there is a 40-fold higher CVD death rate in dialysis patients compared with the general population (41). This extraordinary burden of disease can be only partially explained by the presence of traditional risk factors for CVD and suggests that other mechanisms may be involved (42). A growing body of evidence indicates that abnormalities of mineral metabolism may contribute to the development of cardiovascular disease, with the most likely link being the development of vascular calcification. It is now clearly established that vascular calcification is closely associated with cardiovascular events in non-CKD populations, and evidence is building rapidly in the CKD population (43–48). In advanced stages of CKD, arterial calcification occurs both in the subintimal space, where it is associated with classic atherosclerosis, and in the medial muscular layer of the vessel wall. It is interesting that patients with ESRD do not seem to have a greater amount of atherosclerotic plaques but, instead, qualitative differences in plaque composition (49). In fact, histologic studies of coronary arteries reveal that hemodialysis patients have an increased thickness of the medial layer of the coronary arteries, a marked increase in the number of calcified plaques, and an increased severity of calcification when compared with control subjects without CKD (49).
Calcification is associated with CVD via multiple mechanisms; atherosclerotic calcification is obviously a marker of inflammatory vascular disease that typically is seen in the general population as well as the CKD population. As such, coronary calcification has been linked with atherosclerosis-related events in the general population and all-cause mortality in dialysis patients (45,50,51).
Intimal and medial calcification is also closely associated with reduced vascular compliance, resulting in reduced coronary perfusion and increased rates of heart failure and ultimately death (11,52,53). Increased vascular stiffness causes increase in peripheral radiation of a perfusion pulse (increased pulse wave velocity) and accelerated return of the so-called reflective waves. Whereas reflective waves are timed to return in diastole in individuals with a healthy vascular system, helping the retrograde filling of the coronary arteries, their early return in patients with reduced vascular compliance causes an increase in afterload with increases in myocardial stress, oxygen consumption, and reduced coronary perfusion (53). Ultimately, this causes left ventricular hypertrophy, increased myocardial fibrosis, myocyte death, and heart failure often secondary to isolated diastolic dysfunction and preserved systolic function (47,54–56). The development of left ventricular hypertrophy, however, is likely driven by additional factors besides vascular calcification and stiffness, such as alteration of the renin-angiotensin system, anemia, and elevated PTH (57). Other forms of cardiovascular calcifications, demonstrated by simple imaging tests, have also been linked with unfavorable outcome in dialysis patients (58–60).
In addition to intimal and media calcification, patients with advanced CKD may experience calcific uremic arteriolopathy (CUA), a rare condition characterized by extensive calcification of the vessel wall of subcutaneous arterioles often not associated with obstructive disease of capacitance arteries (61). CUA typically causes cutaneous ischemia and necrosis and may eventually lead to death as a result of severe complicating infections. The pathogenesis of CUA remains largely unknown, although excessive calcium supplementation, especially in patients with diabetes, has been associated with its occurrence (61,62). Some investigators reported symptom resolution after parathyroidectomy, which suggests a link between excessive PTH secretion and CUA (63,64). Evidently, more research is required to elucidate its relationship with bone disease, mineral metabolism, and CVD in patients with CKD.
Pathogenesis and Molecular Mechanisms of Vascular Calcification in Patients with CKD
Multiple factors have been shown to contribute to vascular calcification in patients with CKD. Studies have found that the use of calcium-based phosphate binders, episodes of hypercalcemia and hyperphosphatemia, and elevated PTH levels all are associated with the progression of vascular calcification, whereas the use of non–calcium-based phosphate binders and the control of serum mineral levels attenuate calcification (65–67). In addition, diabetes, age, inflammation, and BMI all correlate positively with the extent of calcification in patients with CKD, whereas bone density is inversely correlated with high levels of calcification (68).
Active processes that involve cells and enzymes that normally are responsible for bone formation seem to be instrumental for the initiation and progression of vascular calcification (69–74). Genetic mouse models have identified vascular smooth muscle cells (VSMC) as being central to the pathogenesis of arterial wall calcification. In addition, endogenous inhibitors of calcification may be lacking in the uremic state (75,76). It is now believed that arterial calcification is an active process that involves the phenotypic transformation of VSMC into bone-forming osteoblast-like cells that are capable of expressing the bone matrix proteins that are necessary to support the calcification process (77). Genes that are specific to osteoblasts are upregulated and VSMC genes become downregulated during this transition, including bone morphogenetic protein-2, osteopontin, matrix Gla protein, and osteoprotegerin (78–81).
Several new molecular markers, including adipokines such as leptin and resistin, which are tightly regulated by the kidney, were recently investigated as a link between CKD and CVD (82). The decreased GFR characteristic of CKD may dramatically alter the clearance of these adipokines, contributing to the progression of CVD (82). Leptin has been shown to be associated with coronary artery calcification (CAC) and increased carotid intima-media thickness (83–85). Furthermore, prospective studies have shown links between elevated leptin levels and an increased risk for CVD events (86,87). The role of leptin in calcification could potentially be the strong osteogenic differentiation capacity demonstrated by this adipokine, coupled with the fact that leptin receptors are expressed in human atherosclerotic arteries and that the hormone was shown to contribute to vascular calcification in mice (88,89); however, these are recent findings, and further research is still needed.
|
Relationship between Bone Loss and CVD
|
|---|
Several clinical studies reported strong associations between bone loss, arterial calcification, and CVD (90–92). Using lumbar spine and hand radiographs in 364 women and 190 men from the Framingham Heart Study over a 25-yr study period, Kiel et al. (90) noted that the metacarpal relative cortical area decreased by 22% in women and 13% in men. The aortic calcification score increased concomitantly, eight-fold in women and six-fold in men, and there was a significant association between the percentage change in metacarpal relative cortical area and the change in aortic calcification index in women.
In a retrospective analysis of ambulatory patients who underwent dual-energy x-ray absorptiometry (DEXA) bone scans and coronary angiography, 56% had clinically significant coronary artery disease as defined by a >50% luminal stenosis (93). The finding of osteoporosis of the proximal femur, ultradistal radius, and one-third distal radius correlated with coronary artery stenosis of 
50%. This was the first study to report an association between angiographically documented coronary artery disease and low BMD predominantly in women. In a population-based study by van der Klift et al. (94), low BMD of the femoral neck but not the spine correlated with the existence of peripheral arterial disease; findings that were also observed by Aksoy et al. (95) and Schulz et al. (96).
Similar findings are less readily available in CKD populations, although low BMD is a common finding in dialysis patients (31). Taal et al. (97) demonstrated that dialysis patients with bone loss (osteopenia or osteoporosis) have higher rates of cardiovascular death compared with patients with normal BMD. The first observation that many dialysis patients experience CAC was reported by Braun et al. (98) in a longitudinal assessment of dialysis patients. They found a 2.5- to five-fold higher prevalence of CAC compared with matched nondialysis patients. In addition, calcification of the aortic and mitral valves was present in more than 50% of the dialysis patients. Although there was no correlation of serum calcium, phosphate, or PTH levels with the extent of CAC, bone mass did correlate inversely with coronary calcium (98). Matsuoka et al. (51) recently reported that patients with aluminum bone deposition and high oral calcium intake had more extensive arterial calcification in conjunction with lower PTH levels and low bone turnover. Finally, Raggi et al. (85) showed that patients who were treated long term with calcium-based phosphate binders calcify their cardiovascular system while they progressively lost vertebral BMD.
Importantly, several of these studies used either plane x-rays or DEXA scans of the extremities or hip to establish an inverse association between vascular calcification and bone demineralization. The use of DEXA for bone density measurement of the spine is fraught with the frequent occurrence of vascular calcification, particularly in the dialysis population, rendering DEXA of little utility in this particular scenario (100).
|
Recent Findings and Therapeutic Advances
|
|---|
The previous discussion highlights the complex interplay among the skeletal, vascular, and renal systems (Figure 1). The mainstay of therapy in dialysis remains the use of phosphate binders. For the past two decades, calcium-based phosphate binders represented the therapeutic gold standard for treatment of hyperphosphatemia. They replaced aluminum salts that were found to cause long-term toxic effects such as encephalopathy, ABD, and microcytic anemia (101). Still widely used, often in large doses, calcium-containing binders provide a substantial calcium load, leading to progressive cardiovascular calcification (102,103). In hemodialysis patients with evidence of metastatic calcification, the use of calcium-based phosphate binders should be carefully monitored, and the use of calcium- and aluminum-free phosphate binders is recommended (104). Sevelamer hydrochloride is one of two calcium-free phosphate binders available on the market and the one with the most extensive clinical experience. Beyond the effects on mineral metabolism, sevelamer has other potentially favorable cardiovascular effects, such as reduction in serum uric acid, improvement in lipid profile, and anti-inflammatory activity (105–107).
In two randomized clinical trials, sevelamer controlled serum phosphate to a degree similar to calcium-based binders without causing hypercalcemia and arrested the progression of coronary, aorta, and valvular calcification in hemodialysis patients (102,103,108). In the recent study by Block et al. (50), randomization to sevelamer treatment as opposed to calcium salts significantly reduced the mortality rate in incident hemodialysis patients; however, in a larger randomized trial of prevalent hemodialysis patients, such a survival advantage was not seen in the overall cohort, although a survival benefit was noted in older patients (109).
Whether VDRL therapy contributes directly to reduced cardiovascular mortality in dialysis patients still remains to be determined. Although it was suggested in one uncontrolled study that calcitriol treatment promotes adynamic bone, the study was confounded by the inclusion of patients who had a high oral intake of calcium and underwent dialysis with high dialysate calcium concentrations (110). This level of calcium intake may have contributed to the change in bone histology, because Raggi et al. (35) recently showed that calcium loading was associated with bone loss.
In contrast, several observational reports showed that dialysis patients who received injectable VDRL therapy had a 20% adjusted survival benefit compared with those who did not receive VDRL therapy and that patients who received intravenous paricalcitol had a 16% survival advantage compared with those who received intravenous calcitriol (111,112). This observation was corroborated by Kalantar-Zadeh et al. (66), who showed that patients who were treated with intravenous paricalcitol had a 25 to 40% adjusted survival benefit compared with those who did not receive any paricalcitol. Tentori et al. (113) suggested that the survival benefit afforded by the two forms of VDRL therapy that are available on the market may be equivalent. Conversely, a recent meta-analysis by Palmer et al. (114) failed to prove a definite survival benefit with these drugs. Although promising, the survival benefits of VDRL therapy should be evaluated in randomized trials to corroborate these findings further. Because VDRL therapy suppresses bone loss in CKD, future research should include prospective evaluations of VDRL therapies in the treatment of CKD to verify whether a beneficial effect on bone is associated with amelioration of CVD (115,116).
Calcimimetic agents are another class of drugs that have been investigated in the treatment of CKD and SHPT complications. Acting on the calcium receptor at the level of the parathyroid gland, drugs such as cinacalcet have been shown to reduce PTH secretion while minimizing hypercalcemia and hyperphosphatemia (117). Although approved for use in patients with stage 5 CKD, the long-term safety and efficacy of cinacalcet in predialysis patients have not been well established (88). Because the effects of cinacalcet on bone loss have not yet been reported, it should be evaluated in studies that measure bone disease markers and markers of vascular health (118).
|
Conclusions
|
|---|
Bone loss is a common complication seen in CKD, caused primarily by high bone turnover but increasingly by ABD as well. Vascular calcification, another common complication, presents an increased risk to patients with CKD and may be linked to the high rates of bone loss commonly observed with elevated PTH levels, although some evidence indicates that adynamic bone states may also be responsible for calcification development (37). On the basis of the recent evidence that vascular calcification is an active process within the arterial wall, an improved understanding of the pathologic changes that occur in patients with CKD may prove valuable in the development of strategies to reduce vascular calcification. Novel treatments will need to address the complexity of factors that contribute to CVD in CKD, and VDRL therapies seem to be important treatment options in this environment.
|
Disclosures
|
|---|
None.
|
Acknowledgments
|
|---|
We thank Dr. Fabian D'Souza and Dr. Fred W. Peyerl for technical assistance and manuscript preparation.
|
Footnotes
|
|---|
Published online ahead of print. Publication date available at www.cjasn.org.
|
References
|
|---|
- Arias E, Anderson RN, Kung HC, Murphy SL, Kochanek KD: Deaths: Final data for 2001.
Natl Vital Stat Rep52
:1
–115,2003[Medline]
- Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS: Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.
Am J Kidney Dis41
:1
–12,2003[Medline]
- State-specific trends in chronic kidney failure—United States, 1990–2001.
MMWR Morb Mortal Wkly Rep53
:918
–920,2004[Medline]
- K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification.
Am J Kidney Dis39
:S1
–S266,2002[CrossRef][Medline]
- Giannini S, D’Angelo A, Carraro G, Antonello A, Di Landro D, Marchini F, Plebani M, Zaninotto M, Rigotti P, Sartori L, Crepaldi G: Persistently increased bone turnover and low bone density in long-term survivors to kidney transplantation.
Clin Nephrol56
:353
–363,2001[Medline]
- Jones CA, McQuillan GM, Kusek JW, Eberhardt MS, Herman WH, Coresh J, Salive M, Jones CP, Agodoa LY: Serum creatinine levels in the US population: Third National Health and Nutrition Examination Survey.
Am J Kidney Dis32
:992
–999,1998[Medline]
- Young EW: An improved understanding of the causes of end-stage renal disease.
Semin Nephrol17
:170
–175,1997[Medline]
- Slatopolsky E, Brown A, Dusso A: Pathogenesis of secondary hyperparathyroidism.
Kidney Int Suppl73
:S14
–S19,1999[Medline]
- Elder G: Pathophysiology and recent advances in the management of renal osteodystrophy.
J Bone Miner Res17
:2094
–2105,2002[CrossRef][Medline]
- Elder GJ, Mackun K: 25-Hydroxyvitamin D deficiency and diabetes predict reduced BMD in patients with chronic kidney disease.
J Bone Miner Res21
:1778
–1784,2006[CrossRef][Medline]
- Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM: Mineral metabolism, mortality, and morbidity in maintenance hemodialysis.
J Am Soc Nephrol15
:2208
–2218,2004[Abstract/Free Full Text]
- Alem AM, Sherrard DJ, Gillen DL, Weiss NS, Beresford SA, Heckbert SR, Wong C, Stehman-Breen C: Increased risk of hip fracture among patients with end-stage renal disease.
Kidney Int58
:396
–399,2000[CrossRef][Medline]
- Meier C, Nguyen TV, Center JR, Seibel MJ, Eisman JA: Bone resorption and osteoporotic fractures in elderly men: The Dubbo Osteoporosis Epidemiology Study.
J Bone Miner Res20
:579
–587,2005[CrossRef][Medline]
- Eknoyan G, Lameire N, Barsoum R, Eckardt KU, Levin A, Levin N, Locatelli F, MacLeod A, Vanholder R, Walker R, Wang H: The burden of kidney disease: Improving global outcomes.
Kidney Int66
:1310
–1314,2004[CrossRef][Medline]
- Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G: Definition, evaluation, and classification of renal osteodystrophy: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).
Kidney Int69
:1945
–1953,2006[CrossRef][Medline]
- Rickers H, Christiansen C, Christensen P, Christensen M, Rodbro P: Serum concentrations of vitamin D metabolites in different degrees of impaired renal function: Estimation of renal and extrarenal secretion rate of 24,25-dihydroxyvitamin D.
Nephron39
:267
–271,1985[Medline]
- Holick MF: Vitamin D deficiency.
N Engl J Med357
:266
–281,2007[Free Full Text]
- Hendy GN, Hruska KA, Mathew S, Goltzman D: New insights into mineral and skeletal regulation by active forms of vitamin D.
Kidney Int69
:218
–223,2006[CrossRef][Medline]
- Rodriguez M, Canadillas S, Lopez I, Aguilera-Tejero E, Almaden Y: Regulation of parathyroid function in chronic renal failure.
J Bone Miner Metab24
:164
–168,2006[CrossRef][Medline]
- Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL: Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: Results of the study to evaluate early kidney disease.
Kidney Int71
:31
–38,2007[CrossRef][Medline]
- Kates DM, Sherrard DJ, Andress DL: Evidence that serum phosphate is independently associated with serum PTH in patients with chronic renal failure.
Am J Kidney Dis30
:809
–813,1997[Medline]
- Fukagawa M, Nakanishi S, Fujii H, Hamada Y, Abe T: Regulation of parathyroid function in chronic kidney disease (CKD).
Clin Exp Nephrol10
:175
–179,2006[CrossRef][Medline]
- Reichel H, Deibert B, Schmidt-Gayk H, Ritz E: Calcium metabolism in early chronic renal failure: Implications for the pathogenesis of hyperparathyroidism.
Nephrol Dial Transplant6
:162
–169,1991
- Brown AJ: Therapeutic uses of vitamin D analogues.
Am J Kidney Dis38
:S3
–S19,2001[Medline]
- Panda DK, Miao D, Bolivar I, Li J, Huo R, Hendy GN, Goltzman D: Inactivation of the 25-hydroxyvitamin D 1alpha-hydroxylase and vitamin D receptor demonstrates independent and interdependent effects of calcium and vitamin D on skeletal and mineral homeostasis.
J Biol Chem279
:16754
–16766,2004[Abstract/Free Full Text]
- Hruska KA, Saab G, Mathew S, Lund R: Renal osteodystrophy, phosphate homeostasis, and vascular calcification.
Semin Dial20
:309
–315,2007[CrossRef][Medline]
- Coen G: Adynamic bone disease: An update and overview.
J Nephrol18
:117
–122,2005[Medline]
- Hamdy NA: The spectrum of renal bone disease.
Nephrol Dial Transplant10
[Suppl 4]:14
–18, discussion 37–43,1995[Free Full Text]
- Buargub MA, Nabulsi MF, Shafeh TA: Prevalence and pattern of renal osteodystrophy in chronic hemodialysis patients: A cross sectional study of 103 patients.
Saudi J Kidney Dis Transpl17
:401
–407,2006[Medline]
- Salusky IB, Goodman WG: Adynamic renal osteodystrophy: Is there a problem?
J Am Soc Nephrol12
:1978
–1985,2001[Free Full Text]
- Rix M, Andreassen H, Eskildsen P, Langdahl B, Olgaard K: Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure.
Kidney Int56
:1084
–1093,1999[CrossRef][Medline]
- Jadoul M, Albert JM, Akiba T, Akizawa T, Arab L, Bragg-Gresham JL, Mason N, Prutz KG, Young EW, Pisoni RL: Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study.
Kidney Int70
:1358
–1366,2006[CrossRef][Medline]
- Martin KJ, Olgaard K, Coburn JW, Coen GM, Fukagawa M, Langman C, Malluche HH, McCarthy JT, Massry SG, Mehls O, Salusky IB, Silver JM, Smogorzewski MT, Slatopolsky EM, McCann L: Diagnosis, assessment, and treatment of bone turnover abnormalities in renal osteodystrophy.
Am J Kidney Dis43
:558
–565,2004[CrossRef][Medline]
- Coco M, Rush H: Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone.
Am J Kidney Dis36
:1115
–1121,2000[Medline]
- Raggi P, James G, Burke SK, Bommer J, Chasan-Taber S, Holzer H, Braun J, Chertow GM: Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis.
J Bone Miner Res20
:764
–772,2005[CrossRef][Medline]
- Kurz P, Tsobanelis T, Roth P, Werner E, Ewald U, Grutzmacher P, Schoeppe W, Vlachojannis J: Differences in calcium kinetic pattern between CAPD and HD patients.
Clin Nephrol44
:255
–261,1995[Medline]
- London GM, Marty C, Marchais SJ, Guerin AP, Metivier F, de Vernejoul MC: Arterial calcifications and bone histomorphometry in end-stage renal disease.
J Am Soc Nephrol15
:1943
–1951,2004[Abstract/Free Full Text]
- Kestenbaum B, Andress DL, Schwartz SM, Gillen DL, Seliger SL, Jadav PR, Sherrard DJ, Stehman-Breen C: Survival following parathyroidectomy among United States dialysis patients.
Kidney Int66
:2010
–2016,2004[CrossRef][Medline]
- Avram MM, Mittman N, Myint MM, Fein P: Importance of low serum intact parathyroid hormone as a predictor of mortality in hemodialysis and peritoneal dialysis patients: 14 years of prospective observation.
Am J Kidney Dis38
:1351
–1357,2001[Medline]
- Collins AJ, Li S, Gilbertson DT, Liu J, Chen SC, Herzog CA: Chronic kidney disease and cardiovascular disease in the Medicare population.
Kidney Int SupplS24
–S31,2003
- Sarnak MJ, Levey AS: Cardiovascular disease and chronic renal disease: A new paradigm.
Am J Kidney Dis35
:S117
–S131,2000[Medline]
- Longenecker JC, Coresh J, Powe NR, Levey AS, Fink NE, Martin A, Klag MJ: Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study.
J Am Soc Nephrol13
:1918
–1927,2002[Abstract/Free Full Text]
- Shaw LJ, Raggi P, Schisterman E, Berman DS, Callister TQ: Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality.
Radiology228
:826
–833,2003[Abstract/Free Full Text]
- Arad Y, Goodman KJ, Roth M, Newstein D, Guerci AD: Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: The St. Francis Heart Study.
J Am Coll Cardiol46
:158
–165,2005[Abstract/Free Full Text]
- Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC: Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals.
JAMA291
:210
–215,2004[Abstract/Free Full Text]
- Blacher J, Demuth K, Guerin AP, Safar ME, Moatti N, London GM: Influence of biochemical alterations on arterial stiffness in patients with end-stage renal disease.
Arterioscler Thromb Vasc Biol18
:535
–541,1998[Abstract/Free Full Text]
- Guerin AP, London GM, Marchais SJ, Metivier F: Arterial stiffening and vascular calcifications in end-stage renal disease.
Nephrol Dial Transplant15
:1014
–1021,2000[Abstract/Free Full Text]
- Raggi P, Boulay A, Chasan-Taber S, Amin N, Dillon M, Burke SK, Chertow GM: Cardiac calcification in adult hemodialysis patients: A link between end-stage renal disease and cardiovascular disease?
J Am Coll Cardiol39
:695
–701,2002[Abstract/Free Full Text]
- Schwarz U, Buzello M, Ritz E, Stein G, Raabe G, Wiest G, Mall G, Amann K: Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure.
Nephrol Dial Transplant15
:218
–223,2000[Abstract/Free Full Text]
- Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM: Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients.
Kidney Int71
:438
–441,2007[CrossRef][Medline]
- Matsuoka M, Iseki K, Tamashiro M, Fujimoto N, Higa N, Touma T, Takishita S: Impact of high coronary artery calcification score (CACS) on survival in patients on chronic hemodialysis.
Clin Exp Nephrol8
:54
–58,2004[CrossRef][Medline]
- Raggi P, Bellasi A, Ferramosca E, Islam T, Muntner P, Block GA: Association of pulse wave velocity with vascular and valvular calcification in hemodialysis patients.
Kidney Int71
:802
–807,2007[CrossRef][Medline]
- Watanabe H, Ohtsuka S, Kakihana M, Sugishita Y: Coronary circulation in dogs with an experimental decrease in aortic compliance.
J Am Coll Cardiol21
:1497
–1506,1993[Abstract]
- Weiner DE, Tighiouart H, Vlagopoulos PT, Griffith JL, Salem DN, Levey AS, Sarnak MJ: Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease.
J Am Soc Nephrol16
:1803
–1810,2005[Abstract/Free Full Text]
- Kingwell BA, Ahimastos AA: Arterial stiffness and coronary ischemic disease.
Adv Cardiol44
:125
–138,2007[Medline]
- Cheriyan J, Wilkinson IB: Role of increased aortic stiffness in the pathogenesis of heart failure.
Curr Heart Fail Rep4
:121
–126,2007[CrossRef][Medline]
- Saleh FN, Schirmer H, Sundsfjord J, Jorde R: Parathyroid hormone and left ventricular hypertrophy.
Eur Heart J24
:2054
–2060,2003[Abstract/Free Full Text]
- Wang AY, Wang M, Woo J, Lam CW, Li PK, Lui SF, Sanderson JE: Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in long-term peritoneal dialysis patients: A prospective study.
J Am Soc Nephrol14
:159
–168,2003[Abstract/Free Full Text]
- Adragao T, Pires A, Lucas C, Birne R, Magalhaes L, Goncalves M, Negrao AP: A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients.
Nephrol Dial Transplant19
:1480
–1488,2004[Abstract/Free Full Text]
- London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H: Arterial media calcification in end-stage renal disease: Impact on all-cause and cardiovascular mortality.
Nephrol Dial Transplant18
:1731
–1740,2003[Abstract/Free Full Text]
- Rogers NM, Teubner DJ, Coates PT: Calcific uremic arteriolopathy: Advances in pathogenesis and treatment.
Semin Dial20
:150
–157,2007[CrossRef][Medline]
- Goldsmith D, Ritz E, Covic A: Vascular calcification: A stiff challenge for the nephrologist—Does preventing bone disease cause arterial disease?
Kidney Int66
:1315
–1333,2004[CrossRef][Medline]
- Duh QY, Lim RC, Clark OH: Calciphylaxis in secondary hyperparathyroidism: Diagnosis and parathyroidectomy.
Arch Surg126
:1213
–1218, discussion 1218–1219,1991[Abstract/Free Full Text]
- Girotto JA, Harmon JW, Ratner LE, Nicol TL, Wong L, Chen H: Parathyroidectomy promotes wound healing and prolongs survival in patients with calciphylaxis from secondary hyperparathyroidism.
Surgery130
:645
–650, discussion 650–651,2001[CrossRef][Medline]
- Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB: Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis.
N Engl J Med342
:1478
–1483,2000[Abstract/Free Full Text]
- Kalantar-Zadeh K, Kuwae N, Regidor DL, Kovesdy CP, Kilpatrick RD, Shinaberger CS, McAllister CJ, Budoff MJ, Salusky IB, Kopple JD: Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients.
Kidney Int70
:771
–780,2006[CrossRef][Medline]
- Chertow GM, Raggi P, Chasan-Taber S, Bommer J, Holzer H, Burke SK: Determinants of progressive vascular calcification in haemodialysis patients.
Nephrol Dial Transplant19
:1489
–1496,2004[Abstract/Free Full Text]
- Barreto DV, Barreto FC, Carvalho AB, Cuppari L, Cendoroglo M, Draibe SA, Moyses RM, Neves KR, Jorgetti V, Blair A, Guiberteau R, Fernandes Canziani ME: Coronary calcification in hemodialysis patients: The contribution of traditional and uremia-related risk factors.
Kidney Int67
:1576
–1582,2005[CrossRef][Medline]
- Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ, Proudfoot D, Jahnen-Dechent W, Weissberg PL, Shanahan CM: Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: A potential mechanism for accelerated vascular calcification in ESRD.
J Am Soc Nephrol15
:2857
–2867,2004[Abstract/Free Full Text]
- Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, Morii H, Giachelli CM: Phosphate regulation of vascular smooth muscle cell calcification.
Circ Res87
:E10
–E17,2000[Medline]
- Moe SM, O’Neill KD, Duan D, Ahmed S, Chen NX, Leapman SB, Fineberg N, Kopecky K: Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins.
Kidney Int61
:638
–647,2002[CrossRef][Medline]
- Moe SM, Duan D, Doehle BP, O’Neill KD, Chen NX: Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels.
Kidney Int63
:1003
–1011,2003[CrossRef][Medline]
- Chen NX, O’Neill KD, Duan D, Moe SM: Phosphorus and uremic serum up-regulate osteopontin expression in vascular smooth muscle cells.
Kidney Int62
:1724
–1731,2002[CrossRef][Medline]
- Steitz SA, Speer MY, Curinga G, Yang HY, Haynes P, Aebersold R, Schinke T, Karsenty G, Giachelli CM: Smooth muscle cell phenotypic transition associated with calcification: Upregulation of Cbfa1 and downregulation of smooth muscle lineage markers.
Circ Res89
:1147
–1154,2001[Abstract/Free Full Text]
- El-Maadawy S, Kaartinen MT, Schinke T, Murshed M, Karsenty G, McKee MD: Cartilage formation and calcification in arteries of mice lacking matrix Gla protein.
Connect Tissue Res44
[Suppl 1]:272
–278,2003[CrossRef][Medline]
- Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G: Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein.
Nature386
:78
–81,1997[CrossRef][Medline]
- Giachelli CM, Bae N, Almeida M, Denhardt DT, Alpers CE, Schwartz SM: Osteopontin is elevated during neointima formation in rat arteries and is a novel component of human atherosclerotic plaques.
J Clin Invest92
:1686
–1696,1993[Medline]
- Bostrom K, Watson KE, Horn S, Wortham C, Herman IM, Demer LL: Bone morphogenetic protein expression in human atherosclerotic lesions.
J Clin Invest91
:1800
–1809,1993[Medline]
- Chen NX, Duan D, O’Neill KD, Wolisi GO, Koczman JJ, Laclair R, Moe SM: The mechanisms of uremic serum-induced expression of bone matrix proteins in bovine vascular smooth muscle cells.
Kidney Int70
:1046
–1053,2006[CrossRef][Medline]
- Shanahan CM, Cary NR, Metcalfe JC, Weissberg PL: High expression of genes for calcification-regulating proteins in human atherosclerotic plaques.
J Clin Invest93
:2393
–2402,1994[Medline]
- Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS: Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Genes Dev12
:1260
–1268,1998[Abstract/Free Full Text]
- Kataoka H, Sharma K: Renal handling of adipokines.
Contrib Nephrol151
:91
–105,2006[Medline]
- Ciccone M, Vettor R, Pannacciulli N, Minenna A, Bellacicco M, Rizzon P, Giorgino R, De Pergola G: Plasma leptin is independently associated with the intima-media thickness of the common carotid artery.
Int J Obes Relat Metab Disord25
:805
–810,2001[Medline]
- Iribarren C, Husson G, Go AS, Lo JC, Fair JM, Rubin GD, Hlatky MA, Fortmann SP: Plasma leptin levels and coronary artery calcification in older adults.
J Clin Endocrinol Metab92
:729
–732,2007[Abstract/Free Full Text]
- Reilly MP, Iqbal N, Schutta M, Wolfe ML, Scally M, Localio AR, Rader DJ, Kimmel SE: Plasma leptin levels are associated with coronary atherosclerosis in type 2 diabetes.
J Clin Endocrinol Metab89
:3872
–3878,2004[Abstract/Free Full Text]
- van der Vleuten GM, Veerkamp MJ, van Tits LJ, Toenhake H, den Heijer M, Stalenhoef AF, de Graaf J: Elevated leptin levels in subjects with familial combined hyperlipidemia are associated with the increased risk for CVD.
Atherosclerosis183
:355
–360,2005[CrossRef][Medline]
- Wallace AM, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A, Sattar N: Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS).
Circulation104
:3052
–3056,2001[Abstract/Free Full Text]
- Kang SM, Kwon HM, Hong BK, Kim D, Kim IJ, Choi EY, Jang Y, Kim HS, Kim MS, Kwon HC: Expression of leptin receptor (Ob-R) in human atherosclerotic lesions: Potential role in intimal neovascularization.
Yonsei Med J41
:68
–75,2000[Medline]
- Parhami F, Tintut Y, Ballard A, Fogelman AM, Demer LL: Leptin enhances the calcification of vascular cells: Artery wall as a target of leptin.
Circ Res88
:954
–960,2001[Abstract/Free Full Text]
- Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O’Donnell CJ, Wilson PW: Bone loss and the progression of abdominal aortic calcification over a 25 year period: The Framingham Heart Study.
Calcif Tissue Int68
:271
–276,2001[CrossRef][Medline]
- Samelson EJ, Kiel DP, Broe KE, Zhang Y, Cupples LA, Hannan MT, Wilson PW, Levy D, Williams SA, Vaccarino V: Metacarpal cortical area and risk of coronary heart disease: The Framingham Study.
Am J Epidemiol159
:589
–595,2004[Abstract/Free Full Text]
- Hak AE, Pols HA, van Hemert AM, Hofman A, Witteman JC: Progression of aortic calcification is associated with metacarpal bone loss during menopause: A population-based longitudinal study.
Arterioscler Thromb Vasc Biol20
:1926
–1931,2000[Abstract/Free Full Text]
- Marcovitz PA, Tran HH, Franklin BA, O’Neill WW, Yerkey M, Boura J, Kleerekoper M, Dickinson CZ: Usefulness of bone mineral density to predict significant coronary artery disease.
Am J Cardiol96
:1059
–1063,2005[CrossRef][Medline]
- van der Klift M, Pols HA, Hak AE, Witteman JC, Hofman A, de Laet CE: Bone mineral density and the risk of peripheral arterial disease: The Rotterdam Study.
Calcif Tissue Int70
:443
–449,2002[CrossRef][Medline]
- Aksoy Y, Yagmur C, Tekin GO, Yagmur J, Topal E, Kekilli E, Turhan H, Kosar F, Yetkin E: Aortic valve calcification: Association with bone mineral density and cardiovascular risk factors.
Coron Artery Dis16
:379
–383,2005[CrossRef][Medline]
- Schulz E, Arfai K, Liu X, Sayre J, Gilsanz V: Aortic calcification and the risk of osteoporosis and fractures.
J Clin Endocrinol Metab89
:4246
–4253,2004[Abstract/Free Full Text]
- Taal MW, Roe S, Masud T, Green D, Porter C, Cassidy MJ: Total hip bone mass predicts survival in chronic hemodialysis patients.
Kidney Int63
:1116
–1120,2003[CrossRef][Medline]
- Braun J, Oldendorf M, Moshage W, Heidler R, Zeitler E, Luft FC: Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients.
Am J Kidney Dis27
:394
–401,1996[Medline]
- Fujimoto N, Iseki K, Tokuyama K, Tamashiro M, Takishita S: Significance of coronary artery calcification score (CACS) for the detection of coronary artery disease (CAD) in chronic dialysis patients.
Clin Chim Acta367
:98
–102,2006[CrossRef][Medline]
- Raggi P, Bellasi A, Ferramosca E, Block GA, Muntner P: Pulse wave velocity is inversely related to vertebral bone density in hemodialysis patients.
Hypertension49
:1278
–1284,2007[Abstract/Free Full Text]
- Parkinson IS, Ward MK, Feest TG, Fawcett RW, Kerr DN: Fracturing dialysis osteodystrophy and dialysis encephalopathy: An epidemiological survey.
Lancet1
:406
–409,1979[Medline]
- Block GA, Spiegel DM, Ehrlich J, Mehta R, Lindbergh J, Dreisbach A, Raggi P: Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis.
Kidney Int68
:1815
–1824,2005[CrossRef][Medline]
- Chertow GM, Burke SK, Raggi P: Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients.
Kidney Int62
:245
–252,2002[CrossRef][Medline]
- K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease.
Am J Kidney Dis42
:S1
–201,2003[Medline]
- Garg JP, Chasan-Taber S, Blair A, Plone M, Bommer J, Raggi P, Chertow GM: Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: A randomized clinical trial.
Arthritis Rheum52
:290
–295,2005[CrossRef][Medline]
- Chertow GM, Burke SK, Dillon MA, Slatopolsky E: Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients.
Nephrol Dial Transplant14
:2907
–2914,1999[Abstract/Free Full Text]
- Ferramosca E, Burke S, Chasan-Taber S, Ratti C, Chertow GM, Raggi P: Potential antiatherogenic and anti-inflammatory properties of sevelamer in maintenance hemodialysis patients.
Am Heart J149
:820
–825,2005[CrossRef][Medline]
- Raggi P, Bommer J, Chertow GM: Valvular calcification in hemodialysis patients randomized to calcium-based phosphorus binders or sevelamer.
J Heart Valve Dis13
:134
–141,2004[Medline]
- Suki WN, Zabaneh R, Cangiano JL, Reed J, Fischer D, Garrett L, Ling BN, Chasan-Taber S, Dillon MA, Blair AT, Burke SK: Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients.
Kidney Int72
:1130
–1137,2007[CrossRef][Medline]
- Goodman WG, Ramirez JA, Belin TR, Chon Y, Gales B, Segre GV, Salusky IB: Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy.
Kidney Int46
:1160
–1166,1994[Medline]
- Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernan MA, Camargo CA Jr, Thadhani R: Activated injectable vitamin D and hemodialysis survival: A historical cohort study.
J Am Soc Nephrol16
:1115
–1125,2005[Abstract/Free Full Text]
- Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R: Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy.
N Engl J Med349
:446
–456,2003[Abstract/Free Full Text]
- Tentori F, Hunt WC, Stidley CA, Rohrscheib MR, Bedrick EJ, Meyer KB, Johnson HK, Zager PG: Mortality risk among hemodialysis patients receiving different vitamin D analogs.
Kidney Int70
:1858
–1865,2006[CrossRef][Medline]
- Palmer SC, McGregor DO, Macaskill P, Craig JC, Elder GJ, Strippoli GF: Meta-analysis: Vitamin D compounds in chronic kidney disease.
Ann Intern Med147
:840
–853,2007[Abstract/Free Full Text]
- Ruedin P, Rizzoli R, Slosman D, Leski M, Bonjour JP: Effects of oral calcitriol on bone mineral density in patients with end-stage renal failure.
Kidney Int45
:245
–252,1994[Medline]
- Rix M, Eskildsen P, Olgaard K: Effect of 18 months of treatment with alfacalcidol on bone in patients with mild to moderate chronic renal failure.
Nephrol Dial Transplant19
:870
–876,2004[Abstract/Free Full Text]
- Hudson JQ: Secondary hyperparathyroidism in chronic kidney disease: Focus on clinical consequences and vitamin D therapies.
Ann Pharmacother40
:1584
–1593,2006[Abstract/Free Full Text]
- Drueke TB: Calcimimetics versus vitamin D: What are their relative roles?
Blood Purif22
:38
–43,2004[CrossRef][Medline]
This article has been cited by other articles:
|
|
|
|
 
A. Covic, P. Kothawala, M. Bernal, S. Robbins, A. Chalian, and D. Goldsmith
Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of all-cause mortality, cardiovascular mortality and cardiovascular events in chronic kidney disease
Nephrol. Dial. Transplant.,
May 1, 2009;
24(5):
1506 - 1523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. B. Drueke
Arterial Intima and Media Calcification: Distinct Entities with Different Pathogenesis or All the Same?
Clin. J. Am. Soc. Nephrol.,
November 1, 2008;
3(6):
1583 - 1584.
[Full Text]
[PDF]
|
|
|
Top
Recent Findings and Therapeutic...
Conclusions
