A balanced view of calcium and
phosphate homeostasis in
chronic kidney disease
Calcium balance in normal individuals and in patients
with chronic kidney disease on low- and high-calcium
diets
Calcium balance in chronic kidney
disease: walking the tightrope
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In their commentary on Spiegel study, Evenepoel et al. discussed their concerns about the study limitations. What are these limitations? What do you think about them and did Hill et al. manage to avoid them during their study?
The main limitations were too small sample size. feces and urine collected for only a short time period, The unproven steady state of the Ca . Equilbration times less than 90 days, validity of balance data obtained during calcium load
Hill’s study avoids some limitations. E.g: using calcium isotopes
Here is a suggested answer:
A first question to be asked is whether or not the study participants were in steady state during calcium loading.
What is sufficient time for calcium equilibration? Although there is no strong guidance from the literature, the 7-day equilibration period in the study by Spiegel and Brady3 is rather short and might have been too short. The mean duration of balances in 210 studies from eight publications used in a recent report from the Food and Agriculture Association of the United Nations and the World Health Organization was 90 days.
Small sample size
A second question relates to the validity of the balance data obtained during calcium loading. The validity of the results largely depends on how accurately the intake and output parameters are estimated. In the study by Spiegel and Brady,3 feces and urine were collected for only a short time period.
balance studies should be combined with validated isotope techniques to define the destination of the excess calcium — the soft tissues or the bone.
Hill’s study avoids some limitations. E.g: using calcium isotopes.
There are a number of limitations in this study:
1-The sample size was small.
2- Because of inaccuracies in the stool dye technique, they were unable to measure a true 24-h stool sample.
3-Although a stable calcium isotope could be used to measure GI calcium absorption, the method is expensive.
4-They therefore chose to estimate the 24-h stool production by assuming that patients were in neutral phosphorus balance, and normalizing the stool calcium to 24h based on these calculations.
Hill et al’s study included also small sample size and they studied calcium kinetics by stable-isotope techniques and complex compartmental modeling. This is the best approach at present to calculate calcium distribution in tissues, its transport between pools, and the sizes of the individual pools. However, this method has limitations. Calcium kinetic modeling is unable to estimate the rate of calcium deposition into extraskeletal tissues, and it relies on assumptions that have not been validated in CKD.
The main limitations of spşegel’s study were too small sample size. Additionally, the 24-hour calcium losses in stool were calculated rather than directly determined. The problem with this is that it is built on the assumption of neutral phosphorus balance, which is not proven. They reported that but stated that the participants were tightly controlled and the results were consistent. They could not use a stable calcium isotope to measure GI calcium absorption because the method is expensive. Alternatively, they used indirect calculations.
In their commentary on Spiegel study, Evenepoel et al. discussed their concerns about the study limitations. What are these limitations?
most imptant limitation
small sample size
short duration,
overestimation of ca absorption ,
do not account for impaired calcium release from food (digestion and solubilization), which may be especially relevant in pathological conditions such as CKD.
no real estimation of feacal and urine ca loss during 24h,
intestinal calcium fluxes are only small component of overall balance; what really matters is the movement in and out of the bone, where 99 % of the body calcium is stored.
What do you think about them andneed more studies with larger number of patients, longer duration frequant investigations a
with adequate equilibration times and long collecting periods Preferably, these balance studies should be combined with validated isotope techniques to define the destination of the excess calcium — the soft tissues or the bone
did Hill et al. manage to avoid them during their studypartial correction with unproven steady state
*Limitations
Small size sample, unproven steady state, feces and urine collected for only a short time period, 24hr calcium loss in stool calculated rather than determined which overestimate the true amount of calcium retention,
Tracer technique may overestimate real calcium absorption because they don’t account for impaired calcium release from food
*limitations cannot be avoided
*Hill could not avoid them
Limitations :
Sample size small , steady state of Ca not identified, no valid technique confirming position of Ca deposition.
What I think
We need further studies trying to avoid giving answers to those important questions regarding Ca balance and deposition in CKD patients
Hill et al. failed to avoid all of them.
What are these limitations? Small sample size.
The unproven steady state of the Ca .
Absence of isotope techniques to know where the CA is deposited.
What do you think about them?
Difficult to applied in studies. Did Hill et al. manage to avoid them during their study?
to some degree.
Yes, partially .
The main limitation was:
Small sample size.
The unproven steady state of the Ca .
absence of isotope techniques to know where the CA is deposited.
Limitations: unproven Ca steady state, no data about bone and soft tissue Ca and phosphorus, lacking of isotope technique, stool Ca was calculated not measured
I think it is difficult to be avoided all
Hill partially avoided those limitations
their commentary on Spiegel’s study, Evenepoel et al. discussed their concerns about the study’s limitations.
Adequate equilibration times and long collecting periods are needed
Urine and feces were collected briefly.
No isotope techniques
What do you think about them?
Difficult to applied in studies.
Did Hill et al. manage to avoid them during their study?
to some degree. Yes, partially
Study Limitations
What do I think
Did Hill et al avoided them
limitations of study
Small sample size..
no full data about Ca deposition in tissues
short equilibration time ( less than recommended time).
Limitation;
Hill et al;
Study design to know about the pathophysiology and pattern of the tight regulatory mechanism of Ca, PO4, PTH, FGF23/Klotho
The limitations of study
Small sample size.
Expensive in isotopic dye in measure intestinal ca.
Difficulty for mesuring 24 hr stool ca.
No calipiration between isotopic method and bone deposition or extraskelatal way.
About my think it’s so difficult study to be applying
About hill management during study he manage some limitations like time and positive ca balance but cannot solve what about extra skeletal ca
In their commentary on Spiegel’s study, Evenepoel et al. discussed their concerns about the study’s limitations.
The main limitation was the steady state of the Ca adding to the absence of isotope techniques to know where the CA is deposited.
What do you think about them?
I think it is difficult to do such a study
In their commentary on Spiegel’s study, Evenepoel et al. discussed their concerns about the study’s limitations.
Equilbration times less than 90 days
Short urine and faeces collection time
No calibration with isotope techniques to know where calcium deposited bone or soft tissue
What do you think about them?
Although I believe that these restrictions are valid its not practically easy to do
Did Hill et al. manage to avoid them during their study?
to some degree.
yes partly but not 100%
Reply
yes there is study limitation in both study
small size sample
unproven steady state
methodology limitation
the study required sufficient equilibrium time
validity of balance data obtained during calcium load
HILL tried to manage and avoid only some limitation
# Hill and speigle commended for conducting this extremly important study that provid urgently needed data
Evenepoel et al. commented on limitations in the Spiegel study related to calcium balance.
uncertainty about the steady state, as the Spiegel study assumed a 7-day steady state but a more recent report suggested a 90-day steady state.
The 24 h calcium stool calculated and not directly measured.
Hill measured both calcium and phosphate in Stool and urine directly.
The issues with steady state remain a problem.
Both are small size study , validity of isotope technique is under questions because they don’t measure vascular calcification.
I don’t think that hill managed to avoid the main problem with equilibrium time and measuring where the calcium in positive balance is going.
They couldn’t directly measure where the extra calcium go and it still a subject of speculation today.
In their commentary on Spiegel’s study, Evenepoel et al. discussed their concerns about the study’s limitations.
Adequate equilibration times and long collecting periods are needed to determine whether—and to what extent—calcium supplementation makes the calcium balance positive.
Urine and feces were collected briefly. Due to transit marker issues, 24-h stool calcium losses were estimated rather than measured.
The balance studies should be combined with validated isotope techniques to define the destination of the excess calcium—the soft tissues or the bone.
What do you think about them?
Although I believe that these restrictions are valid, I think it will be difficult to apply them practically to the studies.
Did Hill et al. manage to avoid them during their study?
to some degree. Participants entered the assessment phase, when blood, urine, and feces were collected for direct measurements of calcium and phosphate.
But the author did not study calcium balance based on an average calcium intake for CKD patients.
-In their commentary on Spiegel study, Evenepoel et al. discussed their concerns about the study limitations.
What do you think about them ?
Did Hill et al. manage to avoid them during their study?
In their commentary on Spiegel study, Evenepoel et al. discussed their concerns about the study limitations. What are these limitations? What do you think about them and did Hill et al. manage to avoid them during their study?
Nice. Do you think that Hill et al were able to avoid them?