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Journal ArticleDOI

Outcomes Associated with Serum Calcium Level in Men with Non-Dialysis-Dependent Chronic Kidney Disease

01 Mar 2010-Clinical Journal of The American Society of Nephrology (American Society of Nephrology)-Vol. 5, Iss: 3, pp 468-476
TL;DR: Clinical trials are warranted to determine whether maintaining normal serum calcium can improve outcomes in patients with NDD CKD, and higher serum calcium is associated with increased long-term mortality, and lower calcium isassociated with increased short-term death in patients in the time-varying models.
Abstract: Background and objectives: Elevated serum calcium has been associated with increased mortality in dialysis patients, but it is unclear whether the same is true in non-dialysis-dependent (NDD) chronic kidney disease (CKD). Outcomes associated with low serum calcium are also not well-characterized. Design, setting, participants, & measurements: We examined associations of baseline, time-varying, and time-averaged serum calcium with all-cause mortality in a historic prospective cohort of 1243 men with moderate and advanced NDD CKD by using Cox models. Results: The association of serum calcium with mortality varied according to the applied statistical models. Higher baseline calcium and time-averaged calcium were associated with higher mortality (multivariable adjusted hazard ratio (95% confidence interval): 1.31 (1.13, 1.53); P Conclusions: Higher serum calcium is associated with increased long-term mortality (as reflected by the baseline and time-averaged models), and lower serum calcium is associated with increased short-term mortality (as reflected by the time-varying models) in patients with NDD CKD. Clinical trials are warranted to determine whether maintaining normal serum calcium can improve outcomes in these patients.

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Journal ArticleDOI
TL;DR: A major role is suggested for elevated P in promoting osteogenic/chondrogenic differentiation of VSMC, whereas elevated Ca has a predominant role in promoting VSMC apoptosis and vesicle release.
Abstract: Vascular calcification contributes to the high risk of cardiovascular mortality in chronic kidney disease (CKD) patients. Dysregulation of calcium (Ca) and phosphate (P) metabolism is common in CKD patients and drives vascular calcification. In this article, we review the physiological regulatory mechanisms for Ca and P homeostasis and the basis for their dysregulation in CKD. In addition, we highlight recent findings indicating that elevated Ca and P have direct effects on vascular smooth muscle cells (VSMCs) that promote vascular calcification, including stimulation of osteogenic/chondrogenic differentiation, vesicle release, apoptosis, loss of inhibitors, and extracellular matrix degradation. These studies suggest a major role for elevated P in promoting osteogenic/chondrogenic differentiation of VSMC, whereas elevated Ca has a predominant role in promoting VSMC apoptosis and vesicle release. Furthermore, the effects of elevated Ca and P are synergistic, providing a major stimulus for vascular calcification in CKD. Unraveling the complex regulatory pathways that mediate the effects of both Ca and P on VSMCs will ultimately provide novel targets and therapies to limit the destructive effects of vascular calcification in CKD patients.

759 citations

Journal ArticleDOI
TL;DR: FGF23 has recently emerged as one of the most powerful predictors of adverse outcomes in patients with CKD and ESRD and its physiology and pathophysiology is reviewed, and putative mechanisms of action responsible for its negative effects are described and potential therapeutic strategies to treat these are described.
Abstract: Traditional risk factors of cardiovascular morbidity and mortality such as hypertension, hypercholesterolemia and obesity are paradoxically associated with better outcomes in dialysis patients, and the few trials of interventions targeting modifiable traditional risk factors have yielded disappointing results in this patient population. Non-traditional risk factors such as inflammation, anemia and abnormalities in bone and mineral metabolism have been proposed as potential explanations for the excess mortality seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), but without clear understanding of what the most important pathophysiologic mechanisms of these risk factors are, which ones might be ideal treatment targets and which therapeutic interventions may be effective and safe in targeting them. Among the novel risk factors, fibroblast growth factor-23 (FGF23) has recently emerged as one of the most powerful predictors of adverse outcomes in patients with CKD and ESRD. FGF23 is a hormone produced by osteoblasts/osteocytes in bone that acts on the kidney to regulate phosphate and vitamin D metabolism through activation of FGF receptor/α-Klotho co-receptor complexes. It is possible that elevated FGF23 may exert its negative impact through distinct mechanisms of action independent from its role as a regulator of phosphorus homeostasis. Elevated circulating FGF23 concentrations have been associated with left ventricular hypertrophy (LVH), and it has been suggested that FGF23 exerts a direct effect on the myocardium. While it is possible that ‘off target’ effects of FGF23 present in very high concentrations could induce LVH, this possibility is controversial, since α-klotho is not expressed in the myocardium. Another possibility is that FGF23's effect on the heart is mediated indirectly, via ‘on target’ activation of other humoral pathways. We will review the physiology and pathophysiology of FGF23, the outcomes associated with elevated FGF23 levels, and describe putative mechanisms of action responsible for its negative effects and potential therapeutic strategies to treat these.

109 citations


Cites background from "Outcomes Associated with Serum Calc..."

  • ...Abnormalities of bone and mineral metabolism associated with increased mortality in CKD include hyperphosphatemia [11, 12], hypo- and hypercalcemia [13], hypo- and hyperparathyroidism [14] and hyperphosphatasemia [15]; these have recently been grouped under the umbrella term of CKDrelated mineral and bone disorders (CKD-MBD) [16]....

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Journal ArticleDOI
TL;DR: By understanding better the molecular pathways and genetic circuitry responsible for the pathological mineralization process novel drug targets may be identified and exploited to combat and reduce the detrimental effects of vascular calcification on human health.
Abstract: Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events, including myocardial infarction and stroke. Previously vascular calcification was thought to be a passive process which involved the deposition of calcium and phosphate in arteries and cardiac valves. However, recent studies have shown that vascular calcification is a highly regulated, cell-mediated process similar to bone formation. In this article, we outline the current understanding of key mechanisms governing vascular calcification and highlight the clinical consequences. By understanding better the molecular pathways and genetic circuitry responsible for the pathological mineralization process novel drug targets may be identified and exploited to combat and reduce the detrimental effects of vascular calcification on human health.

104 citations


Cites background from "Outcomes Associated with Serum Calc..."

  • ...A number of clinical studies have also shown an association between elevated serum calcium and increased risk of myocardial infarction and vascular calcification in both CKD patients and in the general population (Yamada et al., 2007; Kovesdy et al., 2010; Larsson et al., 2010; West et al., 2010)....

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Journal ArticleDOI
TL;DR: Whereas in hemodialysis patients cumulatively high or low calcium levels are associated with higher death risk, subtle but meaningful interactions with phosphorus, PTH, paricalcitol dose and race exist.
Abstract: Background: The outcome-predictability of baseline and instantaneously changing serum calcium in hemodialysis patients has been examined. We investigated the mortality-predictabilit

82 citations

Journal ArticleDOI
16 Dec 2013-PLOS ONE
TL;DR: To improve the overall quality of life of hemodialysis patients, a multidisciplinary intervention that includes medical, dietetic and psychosocial strategies that address factors associated with mental and physical quality ofLife are warranted to reduce further health complications and to improvequality of life.
Abstract: Although hemodialysis treatment has greatly increased the life expectancy of end stage renal disease patients, low quality of life among hemodialysis patients is frequently reported. This cross-sectional study aimed to determine the relationship between medical history, hemodialysis treatment and nutritional status with the mental and physical components of quality of life in hemodialysis patients. Respondents (n=90) were recruited from Hospital Kuala Lumpur and dialysis centres of the National Kidney Foundation of Malaysia. Data obtained included socio-demography, medical history, hemodialysis treatment and nutritional status. Mental and physical quality of life were measured using the Mental Composite Summary (MCS) and Physical Composite Summary (PCS) of the Short-Form Health Survey 36-items, a generic core of the Kidney Disease Quality of Life Short Form. Two summary measures and total SF-36 was scored as 0–100, with a higher score indicating better quality of life. Approximately 26 (30%) of respondents achieved the body mass index (24 kg/m2) and more than 80% (n=77) achieved serum albumin level (>35.0 mg/dL) recommended for hemodialysis patients. The majority of respondents did not meet the energy (n=72, 80%) and protein (n=68,75%) recommendations. The total score of SF-36 was 54.1±19.2, while the score for the mental and physical components were 45.0±8.6 and 39.6±8.6, respectively. Factors associated with a higher MCS score were absence of diabetes mellitus (p=0.000) and lower serum calcium (p=0.004), while higher blood flow (p=0.000), higher serum creatinine (p=0.000) and lower protein intake (p=0.006) were associated with a higher PCS score. To improve the overall quality of life of hemodialysis patients, a multidisciplinary intervention that includes medical, dietetic and psychosocial strategies that address factors associated with mental and physical quality of life are warranted to reduce further health complications and to improve quality of life.

77 citations


Cites background from "Outcomes Associated with Serum Calc..."

  • ...Several studies have reported that elevated serum calcium was associated with increased mortality in dialysis patients because it increased the risk of cardiovascular diseases [50,51]....

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  • ...There are limited studies on the effects of low serum calcium on mental health status or mortality [17,50,52]....

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  • ...Therefore, for patients on HD, serum calcium in the low-normal range is important to minimise the complications associated with high serum calcium and to improve quality of life [49-51]....

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References
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Journal ArticleDOI
TL;DR: The purpose of this study was to develop an equation from MDRD Study data that could improve the prediction of GFR from serum creatinine concentration, and major clinical decisions in general medicine, geriatrics, and oncology are made by using the Cockcroft-Gault formula and other formulas to predict the level of renal function.
Abstract: The serum creatinine concentration is widely used as an index of renal function, but this measure is affected by factors other than the glomerular filtration rate (GFR). This study examined an equa...

14,711 citations


"Outcomes Associated with Serum Calc..." refers methods in this paper

  • ...(30) and was categorized according to the staging system introduced by...

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Journal Article
TL;DR: In the early 1990s, the National Kidney Foundation (K/DOQI) developed a set of clinical practice guidelines to define chronic kidney disease and to classify stages in the progression of kidney disease.

10,265 citations

Book
01 Jan 1979
TL;DR: In what case do you like reading so much? What about the type of the vitamin d the calcium homeostatic steroid hormone book? The needs to read? Well, everybody has their own reason why should read some books as discussed by the authors.
Abstract: In what case do you like reading so much? What about the type of the vitamin d the calcium homeostatic steroid hormone book? The needs to read? Well, everybody has their own reason why should read some books. Mostly, it will relate to their necessity to get knowledge from the book and want to read just to get entertainment. Novels, story book, and other entertaining books become so popular this day. Besides, the scientific books will also be the best reason to choose, especially for the students, teachers, doctors, businessman, and other professions who are fond of reading.

3,998 citations

Journal Article

2,609 citations

Journal ArticleDOI
TL;DR: Hyperphosphatemia and hyperparathyroidism were significantly associated with all-cause, cardiovascular, and fracture-related hospitalization, and the population attributable risk percentage for disorders of mineral metabolism was 17.5%, owing largely to the high prevalence of hyperph phosphatemia.
Abstract: Mortality rates in ESRD are unacceptably high. Disorders of mineral metabolism (hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism) are potentially modifiable. For determining associations among disorders of mineral metabolism, mortality, and morbidity in hemodialysis patients, data on 40,538 hemodialysis patients with at least one determination of serum phosphorus and calcium during the last 3 mo of 1997 were analyzed. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum phosphorus, calcium, calcium x phosphorus product, and intact parathyroid hormone (PTH) using proportional hazards regression. Also determined was whether disorders of mineral metabolism were associated with all-cause, cardiovascular, infection-related, fracture-related, and vascular access-related hospitalization. After adjustment for case mix and laboratory variables, serum phosphorus concentrations >5.0 mg/dl were associated with an increased relative risk of death (1.07, 1.25, 1.43, 1.67, and 2.02 for serum phosphorus 5.0 to 6.0, 6.0 to 7.0, 7.0 to 8.0, 8.0 to 9.0, and >/=9.0 mg/dl). Higher adjusted serum calcium concentrations were also associated with an increased risk of death, even when examined within narrow ranges of serum phosphorus. Moderate to severe hyperparathyroidism (PTH concentrations >/=600 pg/ml) was associated with an increase in the relative risk of death, whereas more modest increases in PTH were not. When examined collectively, the population attributable risk percentage for disorders of mineral metabolism was 17.5%, owing largely to the high prevalence of hyperphosphatemia. Hyperphosphatemia and hyperparathyroidism were significantly associated with all-cause, cardiovascular, and fracture-related hospitalization. Disorders of mineral metabolism are independently associated with mortality and morbidity associated with cardiovascular disease and fracture in hemodialysis patients.

2,475 citations


"Outcomes Associated with Serum Calc..." refers background in this paper

  • ...Some of the same studies have also suggested that extremely low calcium levels may themselves be deleterious (2,3), which has ultimately resulted in recommendations to attain a low-normal serum calcium level in dialysis patients (23)....

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