What type of vitamin D supplementation, if any, should be used in adults with CKD?

Ref ID: 66
ReferenceStudy type/Evidence levelNumber of patientsPatient characteristicsInterventionComparisonLength of follow-upOutcome measuresSource of funding
Coyne D, Acharya M, Qiu P et al. Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD.[see comment]. American Journal of Kidney Diseases. 2006; 47(2):263–276. Ref ID: 66RCT 1+

Pooled analysis of 3 RCTs with identical inclusion/exclusion criteria and different dosing regimens (3X weekly or once daily)

multicenter USA, Poland

Not ITT
N = 220

Drop out rate 11% in Paricalcitol, 17% in placebo
Inclusion criteria: identical for all 3 RCTs: people> 18 years diagnosed with CKD for at least 2 months and not expected to require dialysis for at least 6 months, 2 consecutive iPTH that average ≥ 150 pg/ml (all values must be ≥ 120 pg/ml) and 2 consecutive Ca 1.99–2.40 mmol/l and 2 consecutive P ≤ 1.68 mmol/l.

Exclusion criteria: identical for all 3 RCTs: people taking vitamin D therapy 4 weeks prior to trial, acute renal failure in previous 12 months, GI or liver disease, malignancy, active granulomatous disease, pregnancy, hypersensitivity to vitamin D, urinary Ca:creatinine ratio > 0.2, renal stones, using calcitonin or bisphosphonates, or using glucocorticoids > 14 days within previous 6 months.

Baseline characteristics: There were NS differences between people receiving placebo or paricalcitol for sex, race, age (62 years), eGFR (23 ml/min/1.73 m2), P, iPTH, bone ALP, osteocalcin, urinary deoxypryidinoline, urinary pyridinoline. Serum Ca was significantly higher in the paricalcitol group than the placebo group, p=0.039. NS differences between baseline characteristics for thrice weekly or once daily studies.
N=107 Paricalcitol (19-nor-1,25-dihydroxyvitamin D2)

Procedure: Patients attended a screening visit (to assess eligibility), pre-.treatment phase (1–4 weeks to confirm eligibility), treatment phase (24 weeks of active treatment), and follow-up phase (discontinuation of drugs and monitoring of adverse events for 1 month). Participants were randomised to paricalcitol (either thrice weekly or once/daily) or placebo. The initial dose of paricalcitol was 2 microg thrice weekly in people with baseline iPTH ≤ 500 pg/ml or 4 microgram thrice weekly if baseline iPTH > 500 pg/ml. In the daily dose trial, the initial dose was 1 microg/day if baseline iPTH ≤ 500 pg/ml or 2 microg/day if iPTH > 500 pg/ml. Dose was titrated every four weeks by 2 microg (thrice weekly studies) and 1 microg (once daily study) based on serum Ca (adjusted for albumin), P, iPTH levels to achieve a 30% decrease in iPTH levels. Dose decreased if iPTH decreased by > 60%, Ca elevated, or P consistently elevated. Patients allowed phosphate binders. Serum iPTH, P, Ca, albumin measured at baseline and every 2 weeks. eGFR (MDRD), bone specific ALP, osteocalcin, urinary deoxypryidinoline, urinary pyridinoline measured at baseline and at study end (after 6 months of treatment)
N=113 placebo6 monthsPrimary outcome: 2 consecutive decreases ≥ 30% of iPTH from baseline

Serum Ca
P
iPTHz
GFR
Osteocalcin
Bone ALP

urinary
deoxypryidinoline

urinary
pyridinoline

Adverse Events: hypercalcaemia (2 consecutive Ca > 2.62 mmol/l)

Hyperphosphataemia (2 consecutive P > 1.78 mmol/l)
Abbott
Effect size
In the thrice/weekly studies (2 RCTs), N=73 placebo and N=72 paricalcitol. In the once daily RCT, N=40 placebo and N=35 paricalcitol.
The mean daily dose of paricalcitol was 1.3 to 1.4 microg/day. Overall paricalcitol exposure was 43.2 patient years. Average weekly dose of paricalcitol was titrated upwards, peaking at week 13 (12.2 microg) and then titrated downward thereafter.
The majority of participants did NOT take Ca supplements or Ca-based phosphate binders (83/107 paricalcitol and 84/113 placebo).

Primary outcome: 2 consecutive decreases ≥ 30% of iPTH from baseline
After 6 months of treatment, 91% of people on paricalcitol (N=101) and only 13% of people on placebo (N=108) achieved 2 consecutive ≥ 30% decreases in serum iPTH from baseline (p<0.001 between groups). Similar results when thrice weekly and once/daily RCTs were analysed separately. Also similar results when stratified by baseline iPTH (150–300 ng/l, 301–500 ng/l, and > 500 ng/l)

28% of paricalcitol treated people reached the primary endpoint by week 5, 68% reached the primary endpoint by week 9, 77% achieved it by week 11.

After 6 months of treatment, 74% of people on paricalcitol (N=101) and 0% of people on placebo (N=108) achieved 4 consecutive ≥ 30% decreases in serum iPTH from baseline (p<0.001 between groups).

75% of the paricalcitol group (N=101) and only 12% of the placebo group (N=108) achieved iPTH < 110 ng/l (significant between groups but p not given).

Serum iPTH:
Serum iPTH decreased significantly from baseline to 6 months treatment with paricalcitol. A significant decrease in iPTH was seen at 3 weeks treatment with paricalcitol and a sustained decrease thereafter. The maximum mean decrease was 45.2% in the paricalcitol group compared with an increase of 13.9% in the placebo group (p<0.001 between groups).

Adverse Events:
Adverse events were similar between placebo and paricalcitol groups.

Death: N=2 paricalcitol, N=1 placebo (but not causally attributed to paricalcitol)

Serious adverse events: N=20 paricalcitol, N=18 placebo (only 1 adverse event thought to be attributed to treatment N=1 bradycardia in the paricalcitol group)

Dicontinued due to adverse events: N=6 paricalcitol, N=5 placebo.

Hypercalcaemia (2 consecutive Ca > 2.62 mmol/l) occurred N=2 on paricalcitol and N=0 in placebo, p=0.237, NS.

Hyperphosphataemia (2 consecutive P > 1.78 mmol/l) occurred in N=11 paricalcitol and N=13 placebo, p=0.830 NS

Serum Ca:
Mean serum calcium increased slightly in people taking paricalcitol (change Ca 0.02 mmol/l from baseline to 6 months or 1% increase) while there were small decreases in serum Ca in the placebo group, NS between groups.

Serum P:
There were NS changes in serum P in the paricalcitol or placebo groups.

Serum osteocalcin:
Serum osteocalcin decreased from baseline to 6 months in the paricalcitol group (N=100, change osteocalcin: −21.6 ng/ml), compared with an increase in osteocalcin in the placebo group (N=104, change osteocalcin +10.7 ng/ml, p<0.001 between groups).

Bone-specific alkaline phosphatase
Bone ALP significantly decreased from baseline to 6 months in the paricalcitol group (N=101, change bone ALP: −7.89 microg/l), compared with a smaller decrease in bone ALP in the placebo group (N=107, change bone ALP: −1.44 microg/l, p<0.001 between groups).

Urinary deoxypryidinoline
There were NS differences between paricalcitol (n=96) or placebo (N=100) groups for changes in urinary deoxypryidinoline.

Urinary pyridinoline
Urinary pyridinoline decreased in the paricalcitol group (N=99, change urinary pyridinoline: −3.61 nmol/mmol creatinine), compared with an increase in the placebo group (N=104, change urinary pyridinoline +3.77 nmol/mmol creatinine, p=0.006 between groups)

Change in GFR:
After 6 months, eGFR decreased in both placebo (N=93, change in eGFR: −1.57 ml/min/1.73 m2 or −6.95% change) and paricalcitol (N=82, change in eGFR: −2.52 ml/min/1.73 m2 or −10.40 % change) groups, but there were NS differences between treatments (p=0.269).
Ref ID: 347
ReferenceStudy type/Evidence levelNumber of patientsPatient characteristicsInterventionComparisonLength of follow-upOutcome measuresSource of funding
Hamdy NA, Kanis JA, Beneton MN et al. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure.[see comment]. British Medical Journal. 1995; 310(6976):358–363. Ref ID: 347RCT 1+

Randomised, double-blind prospective study

17 centres in UK, Belgium, France, Netherlands

ITT
N =176

Drop out rate 18% in Alfacalcidol, 25% in placebo
Inclusion criteria: people with CrCl 15–50 ml/min and no clinical, biochemical, radiographic evidence of renal bone disease

Exclusion criteria: symptomatic bone disease, increased serum Ca or alkaline phosphatase (ALP) or disturbance in liver function (≥ 1.5 fold increase liver aminotransferase activity)

Baseline characteristics: There were NS differences between people receiving placebo or alfacalcidol for sex, age (53 years), type of renal disease, SBP, DBP, biochemical, radiographic bone histology, other drug regimens. Mean CrCl was 31.6 ml/min (alfacalcidol)
N=89 Alfacalcidol (1α-hydroxycholecalciferol or 1α-hydroxyvitamin D3)

Procedure: People randomised to alfacalcidol
(0.25 microg/day and adjusted between 0.25 microg every other day up to 1 microgram/day to maintain Ca at upper normal lab limit) or placebo. Ca supplementation (max dose 500 mg/day) permitted. Phosphate binding drugs other than Ca permitted when dietary P restriction was inadequate to maintain serum P < 2.2 mmol/l. Other drugs for disease management permitted. Serum creatinine, P, Ca (corrected for albumin), ALP (SMAC analyser) measured at baseline and every month for first 6 months, then every three months for following six months, then every six months. 24-h urine sample collected at baseline and every 6 months for calculation of CrCl (Cockcroft-Gault). PTH measured at baseline and every 6 months (chemiluminescent assay). Serum aluminium measured in 60% of patients. Bone histology determined with a tetracycline double labelled transiliac bone biopsy at baseline and at end of the study and samples were subjected to light and UV microscopy.
N=87 placebo2 yearsSerum Ca
P
iPTH
CrCl

Osteitis fibrosa

Osteomalacia (defined as ≥ 5 osteoid lamellae)

Bone indices

Adverse Events: hypercalcaemia GI pseudogout
Not stated
Effect size
Retrospective analysis of bone biopsy showed that, at baseline, 132 people had evidence of bone disease.

Adverse Events:
18% (N=16/89) of people on alfacalcidol and 25% of people on placebo (N=22/87) withdrew from the trial (p=0.24, NS). The main reason for withdrawal was initiation of dialysis (8 on alfa, 10 on placebo), death (4 alfa, 1 placebo), other reason (4 on alfa, 10 on placebo), hypocalcaemia (0 alfa, 1 placebo).
Mild GI disturbances were reported in 6 people on alfacalcidol and 1 on placebo.
Pseudogout was reported by 2 people on alfacalcidol.
No withdrawal due to unexpected progression of renal disease, or hypercalcemia

Serum Ca:
Mean serum calcium increased significantly in people taking alfacalcidol (+0.07 mmol/l by 24 months, N=89), while there were NS changes in calcium in people taking placebo, p<0.001 between groups. Mild hypercalcaemia (Ca > 2.63 mmol/l on 2 occasions) was seen in 10 patients receiving alfacalcidol and 3 patients receiving placebo (p=0.09, NS). Severe hypercalcaemia (Ca > 3.00 mmol/l on 1 occasion) was observed in 4 people taking alfacalcidol and 0 people on placebo.

Serum P:
Serum P increased in both placebo and alfacalcidol groups with NS differences between the groups.

Serum iPTH:
iPTH decreased NS from baseline to 18 months treatment with alfacalcidol (−1.6 pmol/l), whereas iPTH increased significantly from baseline to 18 months in those taking placebo (+7.3 pmol/l, p<0.001). At 24 months, iPTH returned to baseline levels in those with alfacalcidol treatment.

Change in CrCl:
After 24 months, CrCl decreased in both placebo (−4.0 ml/min) and alfacalcidol groups (−5.7), NS between treatments, p=0.94,

Bone abnormalities:
The proportion of people with bone abnormalities at the beginning of the study were similar between the placebo (N=45, 73%) and alfacalcidol (N=55, 76%). After 24 months treatment, 54% of people taking alfacalcidol (N=39) and 82% on placebo (N=51) had bone abnormalities (no p given).

Fibrosis:
In people with histological bone abnormalities at baseline (N=100), fibrosis significantly decreased in people taking alfacalcidol (N=55, −0.58), while fibrosis increased in the placebo group (N=45, +0.07), p=0.0002.

Bone volume:
In people with histological bone abnormalities at baseline (N=100), There were NS differences in bone volume in the placebo (N=45, 1.09) or alfacalcidol (N=55, 1.22), p=0.75
Osteoid volume: decreased significantly in alfacalcidol (N=55, −0.30, p<0.001 from baseline) NS change in placebo (N=45, 0.09), p=0.005 between groups
Osteoid surface: decreased significantly in alfacalcidol (N=55, −6.85, p<0.01 from baseline) NS change in placebo (N=45, 1.35), p=0.008 between groups
Osteoblast surface: decreased significantly in alfacalcidol (N=55, −0.54, p<0.01 from baseline) NS change in placebo (N=45, 0.37), p=0.009 between groups
Osteoclast surface: NS change in alfacalcidol (N=55, −0.30) NS change in placebo (N=45, 0.17), p=0.002 between groups

Mineral apposition rate: NS changes in alfacalcidol or placebo and NS between groups (p=0.34)

Bone formation rate: decreased significantly in alfacalcidol (N=55, −4.66, p<0.05 from baseline) NS change in placebo (N=45, 0.51), p=0.15 NS between groups

Osteomalacia
In people with histological bone abnormalities at baseline (N=100), Osteomalacia improved in people taking alfacalcidol as the number of osteoid lamellae decreased (N=55, −0.73) whereas the number of osteoid lamellae increased in the placebo group (N=45, 0.32), p=0.002.

Bone resorption:
In people with histological bone abnormalities at baseline (N=100), Bone resorption decreased in people taking alfacalcidol compared with placebo. The eroded bone surface significantly decreased in the alfacalcidol group (N=55, −3.76 eroded surface), while it increased in the placebo group (N=45, eroded surface +0.45), p=0.04. Also, alfacalcidol (−0.86 active eroded surface) was associated with a significant decrease of active eroded surface compared with placebo (+0.49 active erode surface), p=0.0006.

Assessment of bias: ITT analysis only for biochemical analysis, not bone histology, European multicentre trial, applicable to people with mild/moderate CKD with subclinical/early bone disease, no discussion of concealment.
Ref ID: 428
ReferenceStudy type/Evidence levelNumber of patientsPatient characteristicsInterventionComparisonLength of follow-upOutcome measuresSource of funding
Nordal KP, Dahl E. Low dose calcitriol versus placebo in patients with predialysis chronic renal failure. Journal of Clinical Endocrinology & Metabolism. 1988; 67(5):929–936. Ref ID: 428RCT 1+

Randomised, double-blind prospective study

1 centre Norway No ITT
N =30

Drop out rate 9.9% in 1,25-dihydroxyvitamin D3, 9.9% in placebo
Inclusion criteria: consecutive non-dialysed people with serum creatinine > 180 micromol/l and stable renal function for previous 4 months.

Exclusion criteria: not stated

Baseline characteristics: Creatinine range 186–840 micromol/l. NS differences between 2 groups for age (48 years), creatinine, Ca, ionised Ca, P, ALP, PTH, bone histomorphometric measures
N=14
Calcitriol (1,25-dihydroxyvitamin D3)

Procedure: People randomised to 1,25-dihydroxyvitamin D3 (0.25 microg/day for the first 14 days, and then 0.5 microg/day for duration of study) or placebo. Treatment was stopped if hypercalcemia occurred (Ca > 2.7 mmol/l), and then once levels were normal, treatment resumed at half the previous dose. Other drugs for disease management permitted. Serum creatinine, P, Ca, ALP, PTH (mid-region radioimmunoassay) and CrCl (24-h urine collection) measured at baseline and at 1, 2, 4, 6, weeks and then once monthly thereafter. A transiliac crest bone biopsy was performed at baseline and at end of the study.
N=14 placebo8 monthsSerum Ca
P
iPTH
CrCl
Alkaline phosphatase (ALP)

Bone indices

Mineralisation

Adverse Events: hypercalcaemia
Norwegian Research Council for Science and the Humanities
Effect size
NS difference in cumulative or daily dose of phosphate binders between placebo or calcitriol.
Median values of most bone indices were within normal range in both trial arms.
Normal range: Ca 2.2–2.6 mmol/l; P 0.8 to 1.6 mmol/l; ALP 60–180 U/l; PTH <0.6 microg/l

Adverse Events:
8 patients on 1,25-dihydroxyvitamin D3 had hypercalcemia. There was no discussion of hypercalcemia in placebo group.

Serum Ca:
Median serum calcium significantly increased in people taking 1,25-dihydroxyvitamin D3 (N=14, 2.30 mmol/l at baseline to 2.50 mmol/l at 8 months, p<0.01), whereas Ca decreased significantly in the placebo group (N=14, 2.40 mmol/l at baseline and 2.30 mmol/l at 8 months). P<0.01 for end of study values in placebo versus 1,25-dihydroxyvitamin D3.

Serum P:
Median serum P did NS change in either the placebo or 1,25-dihydroxyvitamin D3 groups. 8 patients in each group took aluminium-containing phosphate binders.

Serum iPTH:
Median serum iPTH decreased significantly from baseline to 8 months treatment with 1,25-dihydroxyvitamin D3 (N=14, 1.33 at baseline to 0.98 microg/l at 8 months, p<0.01). In the placebo group iPTH significantly increased (N=14, 0.94 at baseline to 1.37 microg/l at 8 months, p<0.01).

Serum alkaline phosphatase (ALP)
Median serum ALP decreased significantly in people taking 1,25-dihydroxyvitamin D3 (N=14, 201 U/l at baseline to 155 U/l at 8 months, p<0.05). By contrast, ALP did NS change in the placebo group (209 U/l at baseline to 200 U/l at 8 months, NS). P<0.05 for end of study values in placebo versus 1,25-dihydroxyvitamin D3.

Change in CrCl:
After 8 months, median CrCl decreased in both placebo (approx. − 5 ml/min estimated from Figure 1) and 1,25-dihydroxyvitamin D3 (approx. − 5 ml/min estimated from Figure 1) groups, but there were NS differences between treatments.

Bone Indices:
Bone volume: NS change in bone volume in placebo or 1,25-dihydroxyvitamin D3 groups. Both groups within normal reference range (13–32%).

Osteoid volume: significantly decreased in the 1,25-dihydroxyvitamin D3 group (5% at baseline to 3% after 8 months, p<0.01) but not in the placebo group (8% at baseline to 6% at 8 months, NS). P<0.01 for end of study values in placebo versus 1,25-dihydroxyvitamin D3.

Osteoid thickness significantly decreased in the 1,25-dihydroxyvitamin D3 group (9.6 micometer at baseline to 6.1 micrometer after 8 months, p<0.01) but not in the placebo group (9.0 micrometer at baseline to 10 micrometer at 8 months, NS).

Osteoid surface significantly decreased in calcitriol group (p<0.05 change from baseline and p<0.01 compared with placebo), whereas there was NS change in the placebo group.

Eroded surface significantly decreased in calcitriol group (p<0.05 change from baseline and p<0.05 compared with placebo), whereas there was NS change in the placebo group.

Osteoclast surface significantly decreased in calcitriol group (p<0.01 change from baseline and p<0.01 compared with placebo), whereas there was NS change in the placebo group.

Bone formation rate significantly decreased in calcitriol group (p<0.01 change from baseline and p<0.05 compared with placebo), whereas there was NS change in the placebo group.

Bone mineralization:
Mineralization surface: significantly decreased in the calcitriol group (12% at baseline to 6.5% at 8 months, p<0.01) and significantly increased in placebo group (10% at baseline to 19% at 8 months, p<0.01 compared with end value of calcitriol treatment).

Mineral apposition rate: significantly decreased in calcitriol group (0.53 micrometer/day at baseline to 0.44 micrometer/day at 8 months, p<0.05). There was NS change in the placebo group ((0.55 micrometer/day at baseline to 0.50 micrometer/day at 8 months).

Doubly labelled trabecular surfaces: NS decrease in 1, 25-dihydroxyvitamin D3 and a NS increase in placebo group. Neither group was significantly different from normal controls

Singly labelled trabecular surfaces: significant decrease in calcitriol group (p<0.01 from baseline). NS increase in placebo group.

Note: authors caution about dosing with calcitriol due to hypercalcemia. Must monitor Ca and CrCl closely.
Assessment of bias: no ITT analysis.
Ref ID: 4010
ReferenceStudy type/Evidence levelNumber of patientsPatient characteristicsInterventionComparisonLength of follow-upOutcome measuresSource of funding
Przedlacki J, Manelius J, Huttunen K. Bone mineral density evaluated by dual-energy X-ray absorptiometry after one-year treatment with calcitriol started in the predialysis phase of chronic renal failure. Nephron. 1995; 69(4):433–437. Ref ID: 4010RCT 1+

Randomised, double-blind prospective study

1 centre Finland

No ITT
N =26

N=25 completed the study

Drop out rate 0% in 1,25-dihydroxyvitamin D3, 7% in placebo
Inclusion criteria: consecutive non-dialysed people with GFR < 51.2 ml/min, age < 70 years.

Exclusion criteria: pregnancy, renal stones, hypercalcemia (Ca > 2.6 mmol/l), diabetes, GI diseases, treatment with anticonvulsants, anticoagulants, vitamin D metabolites, steroids

Baseline characteristics: NS differences between placebo and calcitriol groups for clinical and biochemical results, baseline BMD, or for dose of calcium acetate phosphate binders. Serum 1,25-dihydroxyvitamin D3 was higher in the placebo group (p<0.01).
N=13
Calcitriol (1,25-dihydroxyvitamin D3)

Procedure: Patients randomised to 1,25-dihydroxyvitamin D3 (0.25 microg/day steady dose) or placebo. Patients were on a low-protein (0.6g/kg) and low-phosphate (800 mg/day) diets. Calcium acetate (0.75–1.5 g/day phosphate binder) prescribed to all patients when Ca < 2.6 mmol/l, P > 0.8 mmol/l). Other drugs for disease management permitted. BMD of lumbar spine (L2-L4), femoral neck, Ward’s triangle, and trochanter (DEXA) determined at baseline and at 12 months. GFR (99mTc DTPA) determined at baseline and at 12 months. Serum creatinine, P, Ca, ALP, PTH (radioimmunoassay), osteocalcin measured at baseline and at 12 months. Serum Ca and P also measured monthly.
N=12 placebo12 monthsSerum Ca
P
iPTH
GFR
Alkaline phosphatase (ALP) osteocalcin

Bone Mineral Density (BMD)

Adverse Events: hypercalcaemia hyperphosphataemia
Hoffmann-La Roche
Effect size
NS difference in cumulative or daily dose of phosphate binders (calcium acetate) between placebo or calcitriol.

Adverse Events:
1 patient in placebo withdrew due to death from MI.

Dialysis initiated in 2 from placebo group (at 11 and 9 months of the study) and in 1 from the calcitriol group (at 10 months).

Hypercalcaemia (Ca > 2.6 mmol/l): N=2 calcitriol and N= 0 in placebo. Resolved after calcium acetate was stopped for a few days.

Hyperionised calcaemia (blood ionised Ca > 1.29 mmol/l) in N=5 calcitriol and N=3 placebo group. Resolved after calcium acetate was stopped for a few days.

Hyperphosphataemia (P>1.5 mmol/l) occurred in N=3 placebo and N=10 calcitriol (NS between groups).

Bone Mineral Density (BMD):
BMD of the lumbar spine L2-L4 significantly increased in the calcitriol group (N=13, mean BMD 1.111 g/cm2 at baseline to 1.133 g/cm2 at 12 months, p<0.001). BMD of the lumbar spine L2–L4 significantly decreased in the placebo group (N=12, mean BMD 1.214 g/cm2 at baseline to 1.201 g/cm2 at 12 months, p<0.05).
The change in BMD of the lumbar spine was significantly different between the calcitriol (+0.028 g/cm2 or +3.93%/year) and the placebo (−0.022 g/cm2 or −0.62%/year, p<0.01) groups.

BMD of the femoral neck significantly increased in the calcitriol group (N=13, mean BMD 0.806 g/cm2 at baseline to 0.832 g/cm2 at 12 months, p<0.001). BMD of the femoral neck significantly decreased in the placebo group (N=12, mean BMD 0.860 g/cm2 at baseline to 0.845 g/cm2 at 12 months, p<0.05).
The change in BMD of the femoral neck was significantly different between the calcitriol (+0.035 g/cm2 or + 3.37%/year) and the placebo (−0.016 g/cm2 or −2.17%/year, p<0.001) groups.

There was NS change in the BMD of Ward’s triangle in the calcitriol group, whereas BMD of Ward’s triangle significantly decreased in the placebo group (0.720 g/cm2 at baseline to 0.702 g/cm2 at 12 months, p<0.05)

BMD of the trochanter significantly increased in the calcitriol group (N=13, mean BMD 0.708 g/cm2 at baseline to 0.724 g/cm2 at 12 months, p<0.05). BMD of the trochanter significantly decreased in the placebo group (N=12, mean BMD 0.800 g/cm2 at baseline to 0.783 g/cm2 at 12 months, p<0.05).

Serum Ca:
There were NS changes in mean serum calcium in people taking 1,25-dihydroxyvitamin D3 or placebo.

Serum P:
Mean serum P did NS change in either the placebo or 1,25-dihydroxyvitamin D3 groups.

Serum iPTH:
Mean serum iPTH decreased significantly from baseline to 12 months treatment with 1,25-dihydroxyvitamin D3 (N=13, 150 ng/l at baseline to 105.8 ng/l at 12 months, p<0.05). In the placebo group there were NS changes in iPTH (N=13, 122.6 ng/l at baseline to 151.4 ng/l at 12 months, p not stated).

Serum alkaline phosphatase (ALP)
Mean serum ALP decreased significantly in people taking 1,25-dihydroxyvitamin D3 (N=13, 165.0 U/l at baseline to 143 U/l at 12 months, p<0.05). ALP did NS change in the placebo group.

Serum osteocalcin:
Mean serum osteocalcin significantly decreased in the calcitriol group (26.3 micromol/l at baseline to 20.0 micromol/l at 12 months, p<0.05). Mean serum osteocalcin significantly increased in the placebo group (24.6 micromol/l at baseline to 28.3 micromol/l at 12 months, p<0.05).

Change in GFR:
After 12 months, mean GFR significantly decreased in both placebo (31.3 ml/min at baseline to 26.3 ml/min at 1 year, p<0.05) and 1,25-dihydroxyvitamin D3 groups (21.5 ml/min at baseline to 18.7 ml/min at 1 year, p<0.05) groups, but there were NS differences between treatments.

Assessment of bias: no ITT analysis (but difficult to do this when there is no BMD-DEXA result at the end of the study). No discussion of concealment.
Ref ID: 4018
ReferenceStudy type/Evidence levelNumber of patientsPatient characteristicsInterventionComparisonLength of follow-upOutcome measuresSource of funding
Ritz E, Kuster S, Schmidt-Gayk H et al. Low-dose calcitriol prevents the rise in 1,84 iPTH without affecting serum calcium and phosphate in patients with moderate renal failure (prospective placebo-controlled multicentre trial). Nephrol Dial Transplant. 1995; 10(12):2228–2234. Ref ID: 4018RCT 1+

Randomised, double-blind prospective study

multi centre in Germany

ITT
N =52

Drop out rate 11 % in Calcitriol, 17 % in placebo
Inclusion criteria: people with serum creatinine > 1.4 mg/dl and < 6.5 mg/dl and iPTH > 6 pmol/l on 3 separate occasions.

Exclusion criteria: proteinuria > 3.5 g/day, diabetes, immunosuppressive therapy, vitamin D deficiency < 10 nmol/l 25 (OH) D3, anticonvulsant therapy, nephrocalcinosis

Baseline characteristics: NS differences between people receiving placebo or calcitriol. All patients were asymptomatic with respect to renal bone disease and had serum Ca < 2.7 mmol/l and P < 2.2 mmol/l on three separate occasions prior to randomisation.
N=28 Calcitriol (1, 25-dihydroxyvitamin D3)

Procedure: Participants randomised to calcitriol (0.125 microg/day) or placebo. Ca carbonate permitted when serum P > 1.7 mmol/l and up to 1.5 g aluminium hydroxide permitted if hypercalcaemia > 2.7 mmol/l. Serum creatinine, P, Ca, ALP, osteocalcin, 24-h urine collections, PTH measured at baseline and at the end of the study. Ca, P measured every 2 weeks for the first 6 months, then every 3 months for safety reasons.
N=24 placebo1 yearSerum Ca
P
iPTH

Adverse Events: hypercalcaemia hyperphosphataemia
Hoffmann-La Roche
Effect size

Serum iPTH:
ITT analysis: N=52
iPTH decreased from baseline in the calcitriol group (16.2 pmol/l at baseline to 18.2 pmol/l after 12 months, p not given, N=28) whereas iPTH increased from baseline in those taking placebo (14.0 pmol/l at baseline to 27.8 pmol/l at 12 months, N=24, p<0.05 between placebo and calcitriol).

Post-hoc analysis (N=45 who completed study)
NS difference between study end values of iPTH between placebo and calcitriol group. Post-hoc analysis stratifying participants by baseline serum creatinine showed NS difference end of study values of iPTH between placebo and calcitriol groups for people with creatinine < 3 mg/dl. In people with creatinine > 3 mg/dl, iPTH increased significantly in the placebo group (p<0.05 from baseline), but iPTH did not change in the calcitriol group (p=0.4, NS).

Adverse Events:
There was no hypercalcaemia (Ca > 2.7 mmol/l on three consecutive occasions) in either calcitriol or placebo groups.
There was no hyperphosphataemia (P> 2.2 mmol/l on 3 consecutive occasions) in either calcitriol or placebo groups.

N=3 calcitriol had a doubling of serum creatinine.

N=1 calcitriol and N=1 placebo progressed to ESRD during the trial.

Serum Ca:
There were NS differences between the calcitriol (N=24) and the placebo (N=21) group for changes in serum calcium

Serum P:
There were NS differences between the calcitriol (N=24) and the placebo (N=21) group for changes in serum phosphate.

Assessment of bias: no discussion of concealment.
Ref ID: 4008
ReferenceStudy type/Evidence levelNumber of patientsPatient characteristicsInterventionComparisonLength of follow-upOutcome measuresSource of funding
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 Transplant. 2004; 19(4):870–876. Ref ID: 4008RCT 1+

Randomised, double-blind prospective study

1 centre, Denmark

Not ITT
N =36

N=31 completed the study

Drop out rate 11% in Alfacalcidol, 17% in placebo
Inclusion criteria: people with CrCl 10–60 ml/min and plasma ionised Ca < 1.35 mmol/l and P < 2.0 mmol/l.

Exclusion criteria: dialysis, renal transplantation, use of vitamin D analogues, immunosuppressive agents, anti-epileptics, hormone replacement therapy.

Baseline characteristics: NS differences between people receiving placebo or alfacalcidol for sex, age (52.5 years), Ca, P, iPTH, bone ALP, osteocalcin, BMD. Mean CrCl was 49 ml/min (alfacalcidol) and 39 ml/min(placebo), p<0.05
N=18
Alfacalcidol (1α-hydroxycholecalciferol or 1α-hydroxyvitamin D3 )

Procedure: Participants randomised to alfacalcidol(0.25 microg/day titrated up to 0.75 microg/day providing NS increase in creatinine and no Ca>1.35 mmol/l and no P> 2.0 mmol/l) or placebo. Serum creatinine, iPTH, P, Ca, bone specific ALP, osteocalcin, PICP, and ICTP measured at baseline and every three months. BMD(DEXA) of the lumbar spine L2–L4, total femur, femoral neck, distal forearm, and total body were determined at baseline and every 6 months.
N=18 placebo18 monthsSerum Ca
P
iPTH
CrCl
Osteocalcin
Bone ALP

Carboxy-terminal propeptide of type I collagen(PICP)

Carboxy-terminal telopeptide of type-I collagen(ICTP)

Bone mineral density

Adverse Events: hypercalcaemia
Not stated
Effect size
The mean daily dose of alfacalcidol was 0.44 microg/day with 53% taking 0.5 microg/day, 35% taking 0.25 microg/day, and 12% taking 0.75 microg/day.

Adverse Events:
Hypercalcaemia occurred in 1 person on alfacalidol and it resolved after decreasing the dose.

Bone Mineral Density
There was NS change in BMD of the spine from baseline to 18 months treatment with alfacalcidol (+2.9% change, NS) or in placebo (−1.1% change, NS). However, there was a significant difference for BMD of the spine in the alfacalcidol versus placebo group (4.2%, p<0.05).

There was NS change in BMD of the femoral neck from baseline to 18 months treatment with alfacalcidol (+1.5% change, NS) or in placebo (−1.5% change, NS). However, there was a significant difference for BMD of the femoral neck in the alfacalcidol versus placebo group (4.9%, p<0.05).

There were NS changes in total body BMD in the placebo or the alfacalcidol groups after 18 months treatment.

There were NS changes in forearm BMD in the placebo or the alfacalcidol groups after 18 months treatment.

Serum Ca:
Mean serum calcium increased significantly in people taking alfacalcidol (N=16, mean Ca 1.20 mmol/l at baseline to 1.24 mmol/l at 18 months), while there were NS changes in calcium in people taking placebo (N=15). There was a significant difference of 4.5% between the two groups (p<0.05)

Serum P:
There were NS changes in serum P in the alfacalcidol or placebo groups.

Serum iPTH:
iPTH decreased significantly from baseline to 18 months treatment with alfacalcidol (N=16, change iPTH −29% at 3 month and −47% at 9 months, p<0.05 for 3 and 9 months from baseline), whereas there were NS changes in iPTH in the placebo group (N=15). There was a significant difference between the groups for changes in iPTH, p<0.05.

Baseline iPTH < 60 pg/ml: N=7 alfacalidol and N=4 placebo.
After 18 months treatment iPTH < 60 pg/ml: N=10 alfacalcidol and N=4 placebo.

Serum osteocalcin:
Osteocalcin significantly decreased by 24% in the alfacalcidol group (N=16, p<0.05 from baseline), whereas there was NS (+25%, NS) change in osteocalcin in the placebo group. (p<0.05 between groups). At the end of the study only 1 patient in the alfacalcidol group had osteocalcin levels > reference range (4.2–31.4 ng/ml), whereas 6 people in the placebo group had osteocalcin levels exceeding reference ranges.

Bone-specific alkaline phosphatase
Bone ALP significantly decreased by 48% in the alfacalcidol group (N=16, p<0.05 from baseline), whereas there was NS change in ALP in the placebo group.

Plasma PICP:
There were NS changes in PICP in the placebo or the alfacalcidol groups.

Plasma ICTP:
There were NS changes in ICTP (bone resorption marker) in the alfacalidol group, whereas ICTP significantly increased by 32% from baseline in the placebo group, p<0.05.

Change in CrCl:
After 18 months, CrCl decreased significantly in both placebo and alfacalcidol groups, but there were NS differences between treatments.
Ref ID: 601
ReferenceStudy type/Evidence levelNumber of patientsPatient characteristicsInterventionComparisonLength of follow-upOutcome measuresSource of funding
Al-Aly Z, Quazi RA, Gonzalez EA et al. Changes in Serum 25-Hydroxyvitamin D and Plasma Intact PTH Levels Following Treatment With Ergocalciferol in Patients With CKD. American Journal of Kidney Diseases. 2007; 50(1):59–68. Ref ID: 601Retrospective case series

Evidence Level: 3

1 centre, Veterans’ Affairs Medical Centre USA
N total CKD=66

N Stage 3 CKD =44

N Stage 4 CKD =22
Inclusion criteria: men with Stage 3 CKD and plasma iPTH > 70 ng/l) or Stage 4 CKD and plasma iPTH > 110 ng/l.

Exclusion criteria: Failure to complete follow-up within 12 months, total Ca > 2.54 mmol/l, history of vitamin D use

Baseline characteristics: People receiving ergocalciferol with Stage 3 CKD had significantly lower iPTH, lower degree of vitamin D deficiency, and were administered phosphate binders less than people with Stage 4 CKD receiving ergocalciferol. Mean age (Stage 3= 71.7 years, Stage 4= 67.5 years). Mean eGFR MDRD (Stage 3 = 45.7 Stage 4 = 22.2 ml/min/1.73m2)
N=44 Stage 3 CKD After treatment with Ergocalciferol (vitamin D2 )

After treatment with Ergocalciferol(vitamin D2 ) in N=22 Stage 4 CKD

Procedure: Ergocalciferol (50000 IU once/week for 12 weeks, then once/month for additional 3 months) was administered to people with increased iPTH and 25-hydroxyvitamin D < 75 nmol/l or 30 ng/ml). Serum Ca, P, iPTH measured before and after 6 months of ergocalciferol.
N=44 Stage 3 CKD Before treatment with Ergocalciferol (vitamin D2 )

Before treatment with Ergocalciferol (vitamin D2 ) in N=22 Stage 4 CKD
Median 6 months(range 4–12 months)Serum Ca

P

iPTH

Adverse Events: hypercalcaemia hyperphosphataemia
None
Effect size
Serum iPTH:
In the total group (N CKD =66), iPTH significantly decreased after 6 months of ergocalciferol treatment (231 pg/ml pre-ergocalciferol iPTH to 193 pg/ml post-ergocalciferol, p<0.005).

In the Stage 3 CKD group (N=44) iPTH significantly decreased after 6 months of ergocalciferol treatment (174 pg/ml pre-ergocalciferol iPTH to 136 pg/ml post-ergocalciferol, p<0.005).

In the Stage 4 CKD group (N=22) there was NS change in iPTH after 6 months of ergocalciferol treatment (345 pg/ml pre-ergocalciferol iPTH to 306 pg/ml post-ergocalciferol, p=0.195, NS).

Serum Ca:
Mean serum calcium did NS change after 6 months treatment with ergocalciferol in the whole group (N=66), Stage 3 CKD alone (N=44) or Stage 4 CKD alone (N=22).

Serum P:
Mean serum phosphorus did NS change after 6 months treatment with ergocalciferol in the whole group (N=66), Stage 3 CKD alone (N=44) or Stage 4 CKD alone (N=22).

Adverse Events:
There were no cases of hypercalcaemia before or after ergocalciferol.
There were no cases of hyperphosphataemia before or after ergocalciferol.

Note: Small N of people with Stage 4 CKD, therefore may not have the power to detect changes in iPTH in this subgroup. Results applicable to older men (average age 70 years). Also this was not an RCT, rather an observational study of parameters before and after ergocalciferol treatment.
Ref ID: 4006
ReferenceStudy type/Evidence levelNumber of patientsPatient characteristicsInterventionComparisonLength of follow-upOutcome measuresSource of funding
Baker LR, Abrams L, Roe CJ et al. 1,25(OH)2D3 administration in moderate renal failure: a prospective double-blind trial. Kidney International. 1989; 35(2):661–669. Ref ID: 4006RCT 1 -

Randomised, double-blind prospective study

No baseline characteristics, little statistical analysis, no detail on randomisation method, small trial

1 centre USA

No ITT
N =13

Drop out rate 12.5% in 1,25-dihydroxyvitamin D3, 25% in placebo
Inclusion criteria: people with CrCl 20–60 ml/min

Exclusion criteria: pregnancy, hypercalcemia, renal stones, poorly controlled hypertension, GI, or liver disease, urinary protein excretion > 3g/day, psychosis, tetracycline allergy, use of anticonvulsants, heparin, corticosteroids, vitamin D metabolites within the previous 6 months.

Baseline characteristics: not discussed or presented in a table
N=7
1,25-dihydroxyvitamin D3

Procedure: Ca supplements provided to ensure an intake of 800 mg/day. Patients randomised to 1,25-dihydroxyvitamin D3(0.25 microg/day and doubled after 4–8 weeks providing Ca < 2.6 mmol/l and urinary Ca <7 mmol/24-h.) Treatment was stopped if hypercalcemia occurred, and then once levels were normal, treatment resumed at half the previous dose. Other drugs for disease management permitted. Serum creatinine, P, Ca(corrected for albumin), ALP, PTH (C-terminal radioimmunoassay) and CrCl measured at baseline and every month. Transiliac crest bone biopsies were performed at baseline and at end of the study and samples were subjected to phase contrast and fluorescent light microscopy.
N=6 placebo1 yearSerum Ca
P
iPTH
CrCl
Alkaline phosphatase(ALP)

Bone structure

Bone formation

Bone resorption

Mineralisation

Adverse
Events: hypercalcaemia
Dialysis Clinics Inc.
Effect size
Retrospective analysis of bone biopsy showed that, at baseline, people had evidence of abnormal bone histology.
Normal range: Ca < 2.62 mmol/l; P < 1.65 mmol/l; ALP 110 IU/ml; PTH <0.9 microg/ml

Adverse Events:
No participants reported adverse events.

Withdrawals: 12.5% (N=1/8 for tetracycline hypersensitivity) of people on 1,25-dihydroxyvitamin D3 and 25% of people on placebo (N=2/8, MI and no satisfactory bone biopsy).

4 patients on 1,25-dihydroxyvitamin D3 had hypercalcemia upon receiving 0.5 microg/d vit D, but resolved within 1 week of stopping treatment. 1 patient on placebo had 1 episode of hypercalcemia.

Serum Ca:
Mean serum calcium was higher in people taking 1,25-dihydroxyvitamin D3 (2.47 mmol/l at baseline to 2.53 mmol/l at 12 months), compared with placebo (2.48 mmol/l at baseline and 2.45 mmol/l at 12 months) but there were NS differences between them.

Serum P:
Mean serum P increased in the placebo group (1.12 mmol/l at baseline to 1.24 mmol/l at 12 months) and decreased slightly in the people taking 1,25-dihydroxyvitamin D3 (1.40 to 1.37mmol/l).

Serum iPTH:
Mean serum iPTH decreased NS from baseline to 12 months treatment with 1,25-dihydroxyvitamin D3 (0.87 at baseline to 0.63 microg/l at 12 months, NS). There was NS change in iPTH in the placebo group (0.67 at baseline to 0.60 microg/l at 12 months, NS).

Serum alkaline phosphatase (ALP)
Mean serum ALP decreased significantly in people taking 1,25-dihydroxyvitamin D3 (73.7 IU/ml at baseline to 56.6 IU/ml at 12 months). By contrast, ALP did NS change in the placebo group (72.3 IU/ml at baseline to 75.5 IU/ml at 12 months).

Change in CrCl:
After 12 months, mean CrCl decreased in both placebo (−4.5 ml/min) and 1,25-dihydroxyvitamin D3 groups (−3.3 ml/min, NS between treatments).

Bone structure:
There was NS differences between placebo and 1,25-dihydroxyvitamin D3 groups for cancellous bone mass, trabecular diameter, trabecular plate density, wall thickness.

Bone formation
Lamellar osteoid volume (6.27 mm3/cm3 baseline to 6.49 mm3/cm3 at 12 months) did NS change in the placebo group, whereas lamellar osteoid volume significantly decreased in the 1,25-dihydroxyvitamin D3 group (4.66 mm3/cm3 baseline to 2.21 mm3/cm3 at 12 months, p<0.05 within group and compared to placebo)

Lamellar osteoid surface did NS change in either the placebo or the 1,25-dihydroxyvitamin D3 groups.

Mean osteoid seam thickness significantly decreased in the 1,25-dihydroxyvitamin D3 group (9.47 micrometer at baseline to 6.98 micrometer at 12 months, P<0.05 within group and compared with placebo). There was NS change in osteoid seam thickness in the placebo group.

Woven osteoid volume significantly decreased in the 1,25-dihydroxyvitamin D3 group (1.95 mm3/cm3 at baseline to 0.76 mm3/cm3 at 12 months, p<0.05). By contrast, woven osteoid volume significantly increased in the placebo group (0.58 mm3/cm3 at baseline to 2.27 mm3/cm3 at 12 months, p<0.05). Both groups were significantly higher at baseline than normal age and sex matched controls.

Woven osteoid surface significantly decreased in the 1,25-dihydroxyvitamin D3 group (4.20% at baseline to 2.06% at 12 months, p<0.05, whereas it significantly increased in the placeo group (1.56% at baseline to 5.04% at 12 months, p<0.05). Both groups were significantly higher at baseline than normal age and sex matched controls.

Bone resorption:
Bone-osteoblast interface significantly decreased in the 1,25-dihydroxyvitamin D3 group (6.18% at baseline to 1.81% at 12 months, p<0.05). There were NS changes in bone-osteoblast interface in the placebo group (7.18% to 8.28%). Both groups had significantly higher baseline values than age and sex matched normal controls.

Osteoblastic index significantly decreased in the 1,25-dihydroxyvitamin D3 group (429 cells/100 mm boundary length at baseline to 127 cells/100 mm boundary length at 12 months, p<0.05 within group and compared to placebo). There were NS changes in osteoblastic index in the placebo group (7.18 to 8.28 cells/100 mm boundary length). Both groups had significantly higher baseline values than age and sex matched normal controls.

Bone-osteoclast interface decreased in both groups, but the changes were NS. Both groups had significantly higher baseline values than age and sex matched normal controls.

Osteoclastic index decreased in both groups, but the changes were NS. Both groups had significantly higher baseline values than age and sex matched normal controls.

Bone mineralization:
Mineralization rate: NS differences between the placebo and 1,25-dihydroxyvitamin D3 groups. Neither group was significantly different from normal controls.

Doubly labelled trabecular surfaces: NS decrease in 1, 25-dihydroxyvitamin D3 and a NS increase in placebo group. Neither group was significantly different from normal controls.

Note: authors caution about dosing at 0.5 microg/day with 1,25-dihydroxyvitamin D3 due to hypercalcemia. Must monitor Ca and CrCl closely.
Assessment of bias: no ITT analysis, no discussion of differences in baseline characteristics between 2 trial arms, applicable to people with mild/moderate CKD with subclinical/early bone disease, no discussion of concealment.
Ref ID: 480
ReferenceStudy type/Evidence levelNumber of patientsPatient characteristicsInterventionComparisonLength of follow-upOutcome measuresSource of funding
Christiansen C, Rodbro P, Christensen MS et al. Deterioration of renal function during treatment of chronic renal failure with 1,25-dihydroxycholecalciferol. Lancet. 1978; 2(8092:Pt1):700–703. Ref ID: 480RCT 1-

Randomised, prospective study

1 centre Denmark

No ITT
No concealment mentioned
No blinding mentioned
No assessment of statistical power.
N =18

N=17 completed the study

Drop out rate 11 % in 1,25-dihydroxy vitamin D3, 0 % in vitamin D3
Inclusion criteria: consecutive non-dialysed patients with chronic renal failure and stable renal function for 1 year and fulfilling at least 2 of the following 3 criteria: bone mineral content <90% of normal, Ca < normal minus 1 S.D., and ALP > normal plus 1 S.D.

Exclusion criteria: history of renal stones, liver or GI disease, treatment with corticosteroids or cytostatic drugs

Baseline characteristics: NS differences between vitamin D3 and calcitriol groups for clinical and biochemical results, BMC. Also NS differences in the spontaneous course of renal disease.
N=8
Calcitriol (1,25-dihydroxyvitamin D3)

Procedure: Patients were observed for 6 months to determine the spontaneous course of renal disease. People then randomised to 1,25-dihydroxyvitamin D3(1 microg/day) or vitamin D3(4000 UI/day) with dose adjustment according to serum Ca (measured 3x/week until Ca < 110 mg/l achieved). All patients received 0.5g Ca supplements daily. CrCl (24-h urine collections), bone mineral content (photon absorptiometry) and serum creatinine, P, Ca, ALP, PTH(N-terminal and C-terminal radioimmunoassays), measured 6 months before baseline, at baseline and after 6 months of active treatment.
N=9
vitamin D3(25-hydroxyvitamin D3)
6 monthsSerum Ca
P
iPTH
CrCl
Alkaline phosphatase(ALP)

Bone mineral content (BMC)
Danish Medical Research Council, Hoffmann-La Roche
Effect size
The daily dose of 1,25-dihydroxyvitamin D3 had to be reduced in 7/8 patients due to hypercalcaemia(four to 0.5 microg/day and three to 0.25 microg/day). No reduction of dose was required in the group receiving vitamin D3.

Adverse Events:
1 patient on 1,25-dihydroxyvitamin D3 died (bronchopneumonia).

Bone Mineral Content (BMC)
After 6 months of treatment, there were NS changes in BMC in either the 1,25-dihydroxyvitamin D3 (N=8, mean change BMC =0.8%, NS) or the 25-hydroxyvitamin D3 groups (N=9, mean change BMC −2.2%, NS) (p NS between groups).

Serum Ca:
After six months of treatment, mean serum calcium increased significantly in people taking 1,25-dihydroxyvitamin D3 (N=8, mean change Ca +12.1 mg/l, p<0.01), whereas there were NS changes in mean Ca in people taking vitamin D3 (N=9, mean change Ca + 2.2 mg/l, NS). P<0.01 for changes between the two groups.

Serum P:
Mean serum P did NS change in either the vitamin D3 or 1,25-dihydroxyvitamin D3 groups.

Serum iPTH:
After 6 months treatment, mean iPTH decreased significantly in both the 1,25-dihydroxyvitamin D3 group (N=8, mean change iPTH −0.24 microg/l, p<0.02) and the vitamin D3 group (N=9 mean change iPTH −0.15 microg/l, p<0.02). p NS for changes in iPTH between groups.

Serum alkaline phosphatase (ALP)
Mean serum ALP decreased significantly in people taking 1,25-dihydroxyvitamin D3 (N=8, mean change ALP −2.1 K.A.U./dl, p<0.01). By contrast, ALP did NS change in the vitamin D3 group. There were NS differences between the groups for change in ALP.

Change in CrCl:
After 6 months treatment, mean CrCl significantly decreased in both the vitamin D3 (N=9, mean change CrCl −3.3 ml/min, p<0.02) and the 1,25-dihydroxyvitamin D3 groups (N=8, mean change CrCl −5.7 ml/min, p<0.01). There were NS differences between treatments.

Assessment of bias: no ITT analysis. No discussion of concealment. NO discussion of blinding. No assessment of statistical power.

From: Evidence Tables

Cover of Chronic Kidney Disease
Chronic Kidney Disease: National Clinical Guideline for Early Identification and Management in Adults in Primary and Secondary Care.
NICE Clinical Guidelines, No. 73.
National Collaborating Centre for Chronic Conditions (UK).
Copyright © 2008, Royal College of Physicians of London.

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