***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract Objective . Left ventricular hypertrophy ( LVH ) is highly prevalent in chronic kidney disease ( CKD ) and a risk marker for cardiovascular mortality . It was hypothesized that vitamin D deficiency could play an important role in the pathogenesis of left ventricular hypertrophy and dysfunction in CKD . An open-labelled r and omized study was performed comparing the effect of alfacalcidol versus no treatment in patients with CKD 4 , secondary hyperparathyroidism and LVH . The primary endpoint was regression of LVH . Secondary endpoints were changes in left ventricular function . Material and methods . Twenty-four patients were screened . Of these , 14 had LVH according to the criteria used . Six were r and omized to alfacalcidol and seven to no treatment . The patient follow-up was 6 months . Left ventricular mass and function were measured by echocardiography . Results . Parathyroid hormone decreased by 72 % and –3 % in the alfacalcidol-treated and non-treated groups , respectively ( p < 0.05 ) , while serum Ca2 + increased by 9 % and –1.6 % , respectively ( p < 0.05 ) , and serum phosphate was unchanged . The left ventricular mass index was unchanged , whereas fractional shortening ( 20 % vs 2 % , p < 0.005 ) and Tei index ( 36 % vs 12 % , p < 0.05 ) increased significantly . Systolic and diastolic blood pressure was unchanged . Conclusion . Short-term treatment with alfacalcidol did not induce regression of LVH ; however , left ventricular function became hyperdynamic but less effective in patients with CKD . This could be problematic in the long term CONTEXT Decreased calcitriol production due to impaired renal function may be a significant risk factor for falls in normal aging population . OBJECTIVE The objective of the study was to examine the association between creatinine clearance ( CrCl ) and the incidence of falls and fallers in groups treated with placebo , calcitriol , estrogen therapy (ET)/estrogen + progestin therapy ( HT ) , and calcitriol + ET/HT . DESIGN This was a 3-yr , double-blind , placebo-controlled study design ed to test the efficacy of calcitriol and ET/HT on bone loss and falls with analysis by intention to treat and post hoc . SETTING The study was conducted at an academic outpatient center . PARTICIPANTS Four hundred eighty-nine normal elderly women aged 65 - 77 yr ; 415 women completed the study . INTERVENTION Subjects were r and omized to placebo , calcitriol 0.25 mug twice a day , ET daily ( conjugated equine estrogens 0.625 mg ) , HT ( conjugated equine estrogen 0.625 mg + medroxyprogesterone acetate 2.5 mg ) and calcitriol + ET/HT . MAIN OUTCOME MEASURES Cumulative number of falls and fallers were compared between groups with 24-h urine CrCl less than 60 and 60 ml/min or greater . RESULTS Calcitriol treatment decreased the number of fallers and falls . Low CrCl less than 60 ml/min was a predictor of the number of falls per person but not fallers in the placebo group ( P = 0.007 ) . In the low CrCl group ( < 60 ml/min ) , the rate of falls decreased on calcitriol by 53 % [ 95 % confidence interval ( CI ) -71 % to -22 % ; P = 0.003 ] , calcitriol + ET/HT by 61 % ( 95 % CI -76 % to -37 % ; P = 0.001 ) , and ET/HT by 25 % ( 95 % CI : -55 % to + 24 % ; not significant ) . Calcitriol reduced the rate of falls by 30 % ( 95 % CI -49 % to -4 % ; P = 0.027 ) in the CrCl 60 ml/min or greater group . CONCLUSION Calcitriol treatment decreases falls in all subjects but especially in elderly women with decreased renal function ( < 60 ml/min ) and frequent fallers Thirteen patients in the predialysis phase of chronic renal failure ( CRF ) were treated with calcitriol ( 0.25 micrograms/day ) and 12 with placebo . After 1 year of study , an increase in bone mineral density in the calcitriol group measured by dual-energy X-ray absorptiometry was seen for the femoral neck and lumbar spine when compared to the placebo group ( p < 0.001 and p < 0.01 , respectively ) . We conclude that a steady low dose of calcitriol started in the predialysis phase of CRF is beneficial to the patients with CRF . This may be partly due to suppression of secondary hyperparathyroidism BACKGROUND Higher doses of calcitriol are effective in lowering markedly elevated 1,84 PTH levels of patients with renal secondary hyperparathyroidism . It has not been established , however , whether prophylactic administration of low doses of calcitriol prevents an increase of 1,84 PTH without causing side-effects , i.e. hypercalcaemia , hypercalciuria , or hyperphosphataemia . STUDY DESIGN We carried out a placebo-controlled , double-blind prospect i ve multicentre trial over 12 months in 45 patients with mild to moderate renal failure . Criteria for inclusion were S-creatinine 1.4 mg/dl and 1,84 PTH > 6 pmol/l ( normal 6 ) .  Calcitriol 0.125 microgram/day per os was compared with placebo . The patients received calcium carbonate per os if serum P exceeded 1.7 mmol/l . RESULTS Baseline 1,84 iPTH concentrations were not significantly different , i.e. 14.0 pmol/l ( 6.7 - 63.3 ) on placebo vs 16.2 ( 6.85 - 82.0 ) on calcitriol . Intention to treat analysis revealed a significant difference of final 1,84 iPTH , i.e. 27.8 ( 4.2 - 68.5 ) on placebo vs 18.2 ( 4.45 - 75.5 ) on calcitriol . On post-hoc analysis the difference was even more pronounced at S-creatinine concentrations above 3 mg/dl . S-calcium , S-phosphate , and urinary excretion of calcium did not change significantly on either placebo or on calcitriol . There were no episodes of hypercalcaemia or hyperphosphataemia . There was no significant difference of final S-creatinine or change in S-creatinine between placebo and calcitriol . One patient on calcitriol and two on placebo progressed to terminal renal failure . Bone alkaline phosphatase as a non-invasive index of bone metabolism was not decreased to subnormal levels . CONCLUSION The results document that a therapeutic window exists in patients with moderate renal failure and elevated of 1,84 iPTH , where low-dose calcitriol ( 0.125 microgram/day ) prevents the increase in 1,84 iPTH without causing side-effects . This observation suggests that the parathyroid is more sensitive to calcitriol than intestine and bone Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND The safety and efficacy of paricalcitol injection have been well established for the prevention and treatment of  secondary hyperparathyroidism ( SHPT ) in patients with chronic kidney disease ( CKD ) stage 5 . The capsule form of paricalcitol was developed to provide a convenient dosage form for patients with stages 3 and 4 CKD . METHODS Three r and omized , placebo-controlled , phase-3 trials were conducted in patients with stages 3 and 4 CKD with SHPT . Enrollment criteria included an estimated glomerular filtration rate between 15 and 60 mL/min/1.73 m2 ( 0.25 and 1.00 mL/s/1.73 m2 ) , an average of 2 consecutive intact parathyroid hormone ( iPTH ) levels greater than 150 pg/mL ( ng/L ) , 2 consecutive serum calcium levels between 8.0 and 10.0 mg/dL ( 2.00 and 2.50 mmol/L ) , and 2 consecutive serum phosphorus levels of 5.2 mg/dL or less ( < or = 1.68 mmol/L ) . Two studies used a thrice-weekly dosing regimen and 1 study used a once-daily dosing regimen for 24 weeks . Dosing was based on serum iPTH , calcium , and phosphorus levels . The primary efficacy end point is 2 consecutive decreases in iPTH levels greater than 30 % from baseline .  RESULTS Two hundred twenty patients participated ( n = 107 , paricalcitol ; n = 113 , placebo ) . At least 2 consecutive decreases in iPTH levels of 30 % or greater from baseline occurred in 91 % of paricalcitol versus 13 % of placebo patients ( P < 0.001 ) . Incidences of hypercalcemia , hyperphosphatemia , and elevated calcium-phosphorus product levels were not significantly different between groups . Similarly , no significant differences in urinary calcium and phosphorus excretion or deterioration in kidney function were detected in patients administered paricalcitol compared with placebo . CONCLUSION Paricalcitol capsule was well tolerated and effectively decreased iPTH levels with minimal or no impact on calcium levels , phosphorus balance , and kidney function in patients with stages 3 and 4 CKD OBJECTIVE To study the efficacy of synthetic 1,25 dihydroxyvitamin D3 ( calcitriol ) in the treatment of osteoporosis . DESIGN Two-year , double-blind , r and omized clinical trial . SETTING University medical center . PATIENTS Fifty postmenopausal women with vertebral fractures recruited by referral . INTERVENTION Calcium intake was adjusted to 25 mmol/d ( 1000 mg/d ) at baseline . Patients were then r and omized to treatment with either calcitriol or placebo . During the study , calcium intake was reduced to 15 mmol/d ( 600 mg/d ) and the dose of calcitriol was adjusted to maintain serum calcium less than 2.74 mmol/L ( less than 11.0 mg/dL ) or urine calcium less than 9.96 mmol/d ( less than 400 mg/d ) . MEASUREMENTS AND MAIN RESULTS After 2 years , the mean dose of calcitriol in the treated group was 0.62 micrograms/d . Bone mineral density of the spine increased 1.94 % with calcitriol therapy and decreased 3.92 % with placebo ( P = 0.001 ) . Total body calcium increased 0.21 % with calcitriol therapy and decreased 1.85 % with placebo ( P = 0.004 ) . Patients receiving placebo had significant decreases in spine density ( P = 0.0007 ) and total body calcium ( P = 0.0004 ) . There were no differences in vertebral fracture rates between the groups . Renal function studies were not statistically different between the groups after 2 years . CONCLUSION The treatment of postmenopausal osteoporotic women with synthetic calcitriol for 2 years was associated with increases in spine density and total body calcium . No adverse effects on renal function were seen after long-term calcitriol therapy BACKGROUND Bone loss occurs during the first 6 months after renal transplantation ( RT ) , and corticosteroid therapy plays an important role . Although calcium plus vitamin D administration prevents corticosteroid-induced osteoporosis , its use in RT recipients is limited by the risk of hypercalcemia . METHODS This double-blind , r and omized , and controlled prospect i ve intervention trial examined the effect of intermittent calcitriol ( 0.5 microg/48 h ) during the first 3 months after RT , plus oral calcium supplementation ( 0.5 g/day ) during 1 year with calcium supplementation alone . The primary outcome measure was the change in bone mineral density ( BMD ) at 3 and 12 months after RT ; we also explored whether the effect of calcitriol on BMD was different among vitamin D receptor ( VDR ) genotypes ( BsmI ) . Forty-five recipients were r and omized to calcitriol therapy ( CT ) and 41 were r and omized to placebo ( PL ) . RESULTS Both groups had a similar degree of pre-existing hyperparathyroidism ( 197 + /- 229 vs. 191 + /- 183 pg/mL ) , but a more pronounced decrease of parathyroid hormone ( PTH ) levels after RT was observed in CT patients ( at 3 months : 61.4 + /- 42.2 vs. 85.7 + /- 53.1 pg/mL , P= 0.02 ; at 12 months : 67.3 + /- 33.7 
    Output:
    
Administration of VDRAs  increased serum creatinine levels .
Subgroup analysis of studies that did not use SCr-based measures did not indicate a lower GFR in the VDRA group .