What are the similarities and differences in the design and the findings of Spiegel and Hill et al studies?
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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Rania Mahmoud
The similarities between both study
– Both study are small size , short duration and cross section
– The study was tightly controlled
– Both higher groups in 2 studies had positive calcium balance Differences between both study
– Steady State duration
– one depend on diet calcium ,the other study give calcium supplement
Both studies: small samples size and short duration 6 and 9 days.
Both studies showed that average calcium balance in patients consuming 800–1000 mg/day elemental calcium was near neutral, and that increasing calcium intake by diet or by CaCO3 tables produced a large positive calcium balance.
lower calcium intakes in both studies, patients with moderate CKD were heterogeneous in their overall calcium balance, with some in negative, neutral, or slightly positive balance.
all CKD patients on the higher calcium intakes were in positive balance
In both studies, patients with CKD had very low urine calcium output that remained low and nearly unchanged even though calcium intake was more than doubled.
Both studies demonstrated that serum calcium is not reflective of whole-body calcium balance, as high calcium intake increased whole-body calcium balance while serum calcium remained unchanged.
Spiegel : Evaluated calcium balance in 6 normal individuals and 6 patients with chronic kidney disease (CKD) on daily diets containing 800 then 9-days 2000 mg elemental calcium. Each diet phase was a total of 9 days, the first 7 as an outpatient. Following the first inpatient stay, subjects resumed their normal diet for a period of at least 1 week, but up to 4 weeks before initiating the second diet phase. On a total intake of 800 mg calcium/day, calcium balance was negative in normal individuals and neutral in patients with CKD. Both groups were in a positive calcium balance on 2000 mg of calcium/day. However, this was much higher in patients with CKD. Increased calcium intake significantly decreased 1,25-dihydroxy-vitamin D and intact parathyroid hormone levels with no difference in serum calcium or phosphorus levels between healthy individuals and patients with CKD stages III-IV Hill: studied calcium balance in 8 patients with stage 3 or 4 CKD who received a controlled diet with or without a calcium carbonate supplement (1500 mg/day calcium) during two 3-week balance periods in a randomized placebo controlled crossover design. Also, Calcium kinetics were determined using oral and intravenous 45calcium. Patients were in neutral calcium and phosphorus balance while on the placebo. Patients with CKD exhibited a positive calcium balance when the total calcium intake was 1500 mg compared to 1000 mg. NO EFFECT ON phosphorus balance.
No difference in serum calcium levels was reported between the two arms, proving again that serum calcium is not a true reflection of calcium balance. Low UCaE was again proved, and the cause is not decreased calcium absorption because fractional calcium absorption in the CKD patients was comparable to healthy adults. The calcium overload stayed in extracellular space (including soft tissue and bone) as proved by calcium kinetic modeling.
Both studies proved a positive calcium balance in CKD patients especially in more than 800-1000 mg elemental calcium per day.
Similar at
Duration short, sample small, case control,cross sectional, use high and low calcium supplementation groups
Different at
Steady state of calcium , measurement of fecal calcium
David M. Spiegel’s study is a prospective case-control (one-tailed study) that included 6 patients, while Hill’s study included only 3 patients, had a shorter duration, and could not approve the steady state.
What are the similarities and differences in the design and the findings of Spiegel and Hill et al studiesstudy by Spiegel and Brady studies in six patients with late stage 3 and stage 4 CKD and six control subjects consumingan 800- and a 2000-mg elemental calcium
they found markedly positive calcium balance when ingesting 2000 mg elemental calcium, with calcium balance being significantly greater in CKD patients than in controls (759 versus 464 mg / d, mean). while When ingesting an 800 mg calcium diet, conversely, both CKD patients and controls were in neutral to slightly negative calcium balance.
feces and urine were collected for only a short time period. the 24- h calcium losses in stool were calculated rather than directly determined.
so the authors conclude that total elemental calcium intake should be within 800– 1200 mg/ d to prevent calcium deficiency and calcium loading, respectively.
the 7-day equilibration period in the study is rather short and might have been too short.
There increase of the net fractional absorption during calcium loading. Second, parathyroid hormone levels significantly decreased during calcium loading, but the absolute decline was marginal and much less than one would expect if the calcium balance was truly positive by 759 mg / d.
Hill et al.study 3 week balance study in CKD patients ( n = 3) corroborate the findings
Patients ingesting 500 mg of elemental calcium three times a day with meals showed a markedly positive calcium balance ( + 404 mg / d), despite stable parathyroid hormone levels.
this study, besides low patient number, is equally hampered by unproven steady state, despite the longer equilibration period.
similarity both cross sectionastudy l, small samplem short durtion , both with positive ca balance
Differences hill didnt determine stge of ckd, was longer, unproven steady state, , stable parathyroid, type of ca intake, no assessment of feacal ca
Similarities
Short Duration, small sample, case control, use high and low calcium supplements, results
Differences
Steady state of calcium unproven in hill and short in speigel
Measure fecal calcium in speigel
Both studies are cross over studies.
The study by Spiegel and Brady performed balance studies in six patients with late stage 3 and stage 4 CKD and six control subjects consuming an 800- and a 2000-mg elemental calcium diet.
In the study by Spiegel and Brady,feces and urine were collected for only a short time period.
Classical balance studies provide data for apparent absorption (intake minus fecal) and net retention (intake minus fecal minus urinary) and the corresponding coefficients.
There is positive calcium balance when ingesting 2000 mg elemental calcium, with calcium balance being significantly greater in CKD patients than in controls (759 versus 464 mg/d, mean). When ingesting an 800- mg calcium diet, conversely, both CKD patients and controls were in neutral to slightly negative calcium balance.
the 7-day equilibration period in the study by Spiegel and Brady3 is rather short and might have been too short.
3–week balance study in CKD patients (n = 3) by Hill et al.used 1500 mg elemental calcium carbonate daily on top of a diet with 957 mg elemental calcium and 1564 phosphate in CKD 3,4 randomized to placebo.
this study, besides low patient number, is equally hampered by unproven steady state, despite the longer equilibration period.
Similarities: Small sample, 2 groups (control and CKD pts compared low and high Ca diet), short duration, results, conclusion
Difference: Hill used Ca supplements with the dietary calcium
Similarities : -small sample/ short duration -cross section -two groups high calcium and lower calcium Differences: -Steady State duration -dietay ca vs supplements -fecal ca
similarities are both studies are cross sectional in 2 groups with small number of patients and in short study duration.
the differences are one study was using calcium supplement and the other dietary calcium
two groups high calcium and lower calcium small sample with short duration . cross sectional studies. The results were similar positive calcium balance with higher calcium intake.
Differences between both study
Steady State duration
one depend on diet calcium ,the other study give calcium supplement
The similarities between both study
Using the same study desion cross sectional study-small no. Of patient -short duration-the same study group ckd and non ckd.
Difference between both study:
One study given ca in diet and the other study given fixed amount from ca supplement .
Findings the CKD patients had a positive calcium balance and consumed more calcium than healthy controls and maintain ca supplement orally between 800 to 2000/day to maintain positive balance
Both studies have a small sample size; both of studies compare two groups of high-calcium and low-calcium, and the study population is divided to CKD patients versus non-CKD patients.
In HIll study 8 patients with a mean estimated GFR 36 ml/min per 1.73 m2.
used 1500 mg elemental calcium carbonate daily on top of a diet with 957 mg elemental calcium and 1564 phosphate in CKD 3,4 randomized to placebo the duration 3 weeks
In spiegle and bradystudy study 6pt. with late stage 3 & stag 4 and 6 control subjects both consuming an 800-and 2000mg elemental ca diet duration of study 7 days the main finding of the study is that CKD and healthy control are in markedly positive ca balance when ingestion 2000elemental ca , but the study observed when ingestion 800mg ca diet conversely both CKD pt. and control were in neutral to slightly negative ca balance
Both studies conducted for short time and were unproven steady state
Similarities in design
1 small sample size
2 randomised cross over trial
3 two groups high calcium and lower calcium
4 CKD patient and non CKD patient
Differences in Design
Steady State duration
one was diet + calcium the other was fixed amount of calcium in diet and placebo or calcium supplement
Similarities in Results
Both higher groups in 2 studies had positive calcium balance
Differences in Results
Hill et Al had increased in net fractional absorption of calcium during calcium loading which is not case in other study? why is that unexpected?
IN Hill et al;
study of 8 pt. with mean estimated GFR 36 ml/min per 1.73 m2.
used 1500 mg elemental calcium carbonate daily on top of a diet with 957 mg elemental calcium and 1564 phosphate in CKD 3,4 randomized to placebo
the duration 3w
In spiegle and bradystudy
study 6pt. with late stag 3 & stag 4 and 6 control subjects
both consuming an 800-and 2000mg elemental ca diet duration of study 7day
the main finding of the study is that CKD and healthy control are in markedly positive ca balance when ingestion 2000elemental ca but the study observed when ingestion 800mg ca diet conversely both CKD pt. and control were in neutral to slightly negative ca balance
so final conclusion of this study , observation that total elemental ca intake should with 800-1200 /dto prevent ca deficiency and ca load
==both study cross over design
==Short duration
==Unproven steady state
Hill et al; 36 ml/min per 1.73 m2. In a crossover design, individuals were randomized to 1500 mg calcium carbonate or placebo against a controlled diet of 957 mg calcium and 1564 mg phosphate. After 7 days of equilibration on the 957- and 2457-mg-calcium diets, individuals were assessed by collecting blood, urine, and feces for calcium and phosphate assays.
Both of these designs are crossovers.
Results of both studies :
Both investigations came to the same conclusion, which was that CKD patients had a positive calcium balance and consumed more calcium than healthy controls.
Similar that both study were too short in duration, not taking into consideration that calcium equilibrium time may take up to 90day. There was too little Patients enrolled in (6-9people). It was cross sectional studies.they both put groups on high vs low calcium diet.
The calcium excretion in Stool is mathematically calculated and not directly measured(assuming that both group are on normal phosphat consumption).
Finding was the same: that patient on CKD are at risk to develop positive calcium balance.
What are the similarities and differences in the design and the findings of Spiegel and Hill et al studies? Design
Both are crossover design
Hill et al. used 1500 mg elemental calcium carbonate daily on top of a diet with 957 mg elemental calcium and 1564 phosphate in CKD 3,4 randomized to placebo while in Spiegel & Brady study the subjects are randomized to either diet with 800 mg elemental calcium/1600 mg phosphate or 2000 mg in CKD 3,4 versus subject without CKD
Finding
The findings were similar between the two studies; positive calcium balance with higher calcium intake in CKD subjects. i.e. Hill et al. emphasized the findings of Spiegel & Brady study
The similarities between both study
– Both study are small size , short duration and cross section
– The study was tightly controlled
– Both higher groups in 2 studies had positive calcium balance
Differences between both study
– Steady State duration
– one depend on diet calcium ,the other study give calcium supplement
Both studies: small samples size and short duration 6 and 9 days.
Both studies showed that average calcium balance in patients consuming 800–1000 mg/day elemental calcium was near neutral, and that increasing calcium intake by diet or by CaCO3 tables produced a large positive calcium balance.
In both studies, patients with CKD had very low urine calcium output that remained low and nearly unchanged even though calcium intake was more than doubled.
Both studies demonstrated that serum calcium is not reflective of whole-body calcium balance, as high calcium intake increased whole-body calcium balance while serum calcium remained unchanged.
Hill: fecal Ca, not asset
Here is a suggested answer:
Spiegel : Evaluated calcium balance in 6 normal individuals and 6 patients with chronic kidney disease (CKD) on daily diets containing 800 then 9-days 2000 mg elemental calcium. Each diet phase was a total of 9 days, the first 7 as an outpatient. Following the first inpatient stay, subjects resumed their normal diet for a period of at least 1 week, but up to 4 weeks before initiating the second diet phase.
On a total intake of 800 mg calcium/day, calcium balance was negative in normal individuals and neutral in patients with CKD.
Both groups were in a positive calcium balance on 2000 mg of calcium/day. However, this was much higher in patients with CKD.
Increased calcium intake significantly decreased 1,25-dihydroxy-vitamin D and intact parathyroid hormone
levels with no difference in serum calcium or phosphorus levels between healthy individuals and patients with CKD stages III-IV
Hill: studied calcium balance in 8 patients with stage 3 or 4 CKD who received a controlled diet with or without a calcium carbonate supplement (1500 mg/day calcium) during two 3-week balance periods in a randomized placebo controlled crossover design. Also, Calcium kinetics were determined using oral and intravenous 45calcium.
Patients were in neutral calcium and phosphorus balance while on the placebo.
Patients with CKD exhibited a positive calcium balance when the total calcium intake was 1500 mg compared to 1000 mg. NO EFFECT ON phosphorus balance.
Both studies proved a positive calcium balance in CKD patients especially in more than 800-1000 mg elemental calcium per day.
Similar at
Duration short, sample small, case control,cross sectional, use high and low calcium supplementation groups
Different at
Steady state of calcium , measurement of fecal calcium
David M. Spiegel’s study is a prospective case-control (one-tailed study) that included 6 patients, while Hill’s study included only 3 patients, had a shorter duration, and could not approve the steady state.
What are the similarities and differences in the design and the findings of Spiegel and Hill et al studiesstudy by Spiegel and Brady studies in six patients with late stage 3 and stage 4 CKD and six control subjects consumingan 800- and a 2000-mg elemental calcium
they found markedly positive calcium balance when ingesting 2000 mg elemental calcium, with calcium balance being significantly greater in CKD patients than in controls (759 versus 464 mg / d, mean). while When ingesting an 800 mg calcium diet, conversely, both CKD patients and controls were in neutral to slightly negative calcium balance.
feces and urine were collected for only a short time period. the 24- h calcium losses in stool were calculated rather than directly determined.
so the authors conclude that total elemental calcium intake should be within 800– 1200 mg/ d to prevent calcium deficiency and calcium loading, respectively.
the 7-day equilibration period in the study is rather short and might have been too short.
There increase of the net fractional absorption during calcium loading. Second, parathyroid hormone levels significantly decreased during calcium loading, but the absolute decline was marginal and much less than one would expect if the calcium balance was truly positive by 759 mg / d.
Hill et al.study 3 week balance study in CKD patients ( n = 3) corroborate the findings
Patients ingesting 500 mg of elemental calcium three times a day with meals showed a markedly positive calcium balance ( + 404 mg / d), despite stable parathyroid hormone levels.
this study, besides low patient number, is equally hampered by unproven steady state, despite the longer equilibration period.
similarity both cross sectionastudy l, small samplem short durtion , both with positive ca balance
Differences hill didnt determine stge of ckd, was longer, unproven steady state, , stable parathyroid, type of ca intake, no assessment of feacal ca
Similarities ;
-small sample ,short duration.
-cross section .
-2 groups high calcium and lower calcium .
Differences;
-Steady State duration.
-Dietary calcium vs supplements .
-Fecal calcium .
Similarities
Short Duration, small sample, case control, use high and low calcium supplements, results
Differences
Steady state of calcium unproven in hill and short in speigel
Measure fecal calcium in speigel
Both studies are cross over studies.
The study by Spiegel and Brady performed balance studies in six patients with late stage 3 and stage 4 CKD and six control subjects consuming an 800- and a 2000-mg elemental calcium diet.
In the study by Spiegel and Brady,feces and urine were collected for only a short time period.
Classical balance studies provide data for apparent absorption (intake minus fecal) and net retention (intake minus fecal minus urinary) and the corresponding coefficients.
There is positive calcium balance when ingesting 2000 mg elemental calcium, with calcium balance being significantly greater in CKD patients than in controls (759 versus 464 mg/d, mean). When ingesting an 800- mg calcium diet, conversely, both CKD patients and controls were in neutral to slightly negative calcium balance.
the 7-day equilibration period in the study by Spiegel and Brady3 is rather short and might have been too short.
3–week balance study in CKD patients (n = 3) by Hill et al.used 1500 mg elemental calcium carbonate daily on top of a diet with 957 mg elemental calcium and 1564 phosphate in CKD 3,4 randomized to placebo.
this study, besides low patient number, is equally hampered by unproven steady state, despite the longer equilibration period.
Similarities: Small sample, 2 groups (control and CKD pts compared low and high Ca diet), short duration, results, conclusion
Difference: Hill used Ca supplements with the dietary calcium
both study are small size and short duration
,randomised , both groups have high calcium and lower calcium, CKD patient and non CKD patient
Differences in
Steady State duration
amount of calcium intake
Similarities in Results
Both higher groups in 2 studies had positive calcium balance
Differences in Results
Hill had increased in net fractional absorption of calcium during calcium loading which is not case in other study?
Similarities :
-small sample/ short duration
-cross section
-two groups high calcium and lower calcium
Differences:
-Steady State duration
-dietay ca vs supplements
-fecal ca
Similarities
Differences
similarities are both studies are cross sectional in 2 groups with small number of patients and in short study duration.
the differences are one study was using calcium supplement and the other dietary calcium
Both study
Differences;
Hill et al;
The similarities between both study
two groups high calcium and lower calcium
small sample with short duration .
cross sectional studies.
The results were similar positive calcium balance with higher calcium intake.
Differences between both study
Steady State duration
one depend on diet calcium ,the other study give calcium supplement
The similarities between both study
Using the same study desion cross sectional study-small no. Of patient -short duration-the same study group ckd and non ckd.
Difference between both study:
One study given ca in diet and the other study given fixed amount from ca supplement .
Findings the CKD patients had a positive calcium balance and consumed more calcium than healthy controls and maintain ca supplement orally between 800 to 2000/day to maintain positive balance
Both studies have a small sample size; both of studies compare two groups of high-calcium and low-calcium, and the study population is divided to CKD patients versus non-CKD patients.
In HIll study 8 patients with a mean estimated GFR 36 ml/min per 1.73 m2.
used 1500 mg elemental calcium carbonate daily on top of a diet with 957 mg elemental calcium and 1564 phosphate in CKD 3,4 randomized to placebo
the duration 3 weeks
In spiegle and bradystudy
study 6pt. with late stage 3 & stag 4 and 6 control subjects
both consuming an 800-and 2000mg elemental ca diet duration of study 7 days
the main finding of the study is that CKD and healthy control are in markedly positive ca balance when ingestion 2000elemental ca , but the study observed when ingestion 800mg ca diet conversely both CKD pt. and control were in neutral to slightly negative ca balance
Both studies conducted for short time and were unproven steady state
Similarities in design
1 small sample size
2 randomised cross over trial
3 two groups high calcium and lower calcium
4 CKD patient and non CKD patient
Differences in Design
Steady State duration
one was diet + calcium the other was fixed amount of calcium in diet and placebo or calcium supplement
Similarities in Results
Both higher groups in 2 studies had positive calcium balance
Differences in Results
Hill et Al had increased in net fractional absorption of calcium during calcium loading which is not case in other study?
why is that unexpected?
IN Hill et al;
study of 8 pt. with mean estimated GFR 36 ml/min per 1.73 m2.
used 1500 mg elemental calcium carbonate daily on top of a diet with 957 mg elemental calcium and 1564 phosphate in CKD 3,4 randomized to placebo
the duration 3w
In spiegle and bradystudy
study 6pt. with late stag 3 & stag 4 and 6 control subjects
both consuming an 800-and 2000mg elemental ca diet duration of study 7day
the main finding of the study is that CKD and healthy control are in markedly positive ca balance when ingestion 2000elemental ca but the study observed when ingestion 800mg ca diet conversely both CKD pt. and control were in neutral to slightly negative ca balance
so final conclusion of this study , observation that total elemental ca intake should with 800-1200 /dto prevent ca deficiency and ca load
==both study cross over design
==Short duration
==Unproven steady state
Hill et al; 36 ml/min per 1.73 m2. In a crossover design, individuals were randomized to 1500 mg calcium carbonate or placebo against a controlled diet of 957 mg calcium and 1564 mg phosphate. After 7 days of equilibration on the 957- and 2457-mg-calcium diets, individuals were assessed by collecting blood, urine, and feces for calcium and phosphate assays.
Both of these designs are crossovers.
Results of both studies :
Both investigations came to the same conclusion, which was that CKD patients had a positive calcium balance and consumed more calcium than healthy controls.
Similar that both study were too short in duration, not taking into consideration that calcium equilibrium time may take up to 90day. There was too little Patients enrolled in (6-9people). It was cross sectional studies.they both put groups on high vs low calcium diet.
The calcium excretion in Stool is mathematically calculated and not directly measured(assuming that both group are on normal phosphat consumption).
Finding was the same: that patient on CKD are at risk to develop positive calcium balance.
What are the similarities and differences in the design and the findings of Spiegel and Hill et al studies?
Design
Finding