Effects of Active Form of Vitamin D on Renal Blood Flow, Glomerular Filtration Rate, Proteinuria and Inflammation in Patients With Chronic Kidney Disease and Hyperparathyroidism
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Change in proteinuria compared to baseline as determined by spot urine protein to creatinine ratio (PCR)
研究概览
简要总结
Active forms of vitamin D and its analogs are used to treat elevated parathyroid hormone levels and bone disease in chronic kidney disease (CKD). More recent animal and human studies suggest that treatment with vitamin D may be associated with reduction of inflammation and urinary protein loss as well as reduction the activity of the renin angiotensin system (RAS) in addition to its effects on the bone metabolism. The investigators of this study have used the new technique of contrast enhanced ultrasound (CEU) to measure the flow of blood to the kidney in other human studies. In this study, the investigators will investigate if 3 month of treatment with an active form of vitamin D in individuals with kidney disease and high parathyroid hormone levels would reduce protein loss in the urine. The investigators will also look at the potential changes in blood flow to the kidney using CEU, kidney function (GFR), inflammation and activity of RAS in response to treatment with active form of vitamin D. Finally, they will examine the association between reduction of protein loss in the urine as shown in other studies with any of the other factors measured (e.g, change in blood flow or inflammation).
详细描述
Screening visit, (Day 1) Most subjects will be contacted during their visit to the Kidney Center Clinic. In some cases, subjects are identified a few days after their visit with their nephrologists and once their laboratory results are available. If a subject is eligible for participation in the study, screening visit will occur at the Nephrology Clinical Research Center located right next to the Kidney Center Clinic. The following will occur during the screening visit,
- Inclusion and exclusion criteria will be reviewed
- Details of the study procedures will be reviewed with the subject
- Informed consent is signed and the subjects will be enrolled in the study.
- A physical exam will be performed.
- Vital Signs will be taken (blood pressure and heart rate)
- A urine pregnancy test will be performed for women of child bearing age. If positive subjects will be excluded.
- If a urine test for proteinuria is not ordered at the clinic visit by subjects' nephrologist, a urine sample will be collected and sent to the laboratory for urine creatinine and urine protein.
- Subjects will be asked to present to the CRU within one week of their screening visit in the morning.
- Subjects will be asked not to start vitamin D pills prescribed by their nephrologists until after completing study visit 2 procedures.
Visit 2 (Day 2 - 7).
- Eligibility will be reviewed.
- A physical exam will be performed.
- Vital Signs will be taken (blood pressure and heart rate)
- A urine sample will be collected and will be tested for,
- Urine creatinine (baseline)
- Urine protein (baseline)
- Urine hcg to check for pregnancy in women of child bearing age
- Urinalysis
- Subjects with a positive urine pregnancy test will be excluded
- A large bore intravenous catheter will be placed in a peripheral vein for the purpose of infusion of Definity and will be locked with heparin.
- Blood samples will be collected at the time of IV catheter placement. These samples will be checked for baseline concentrations of ,
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults (ages 18 - 75 years)
- •A diagnosis of chronic kidney disease (CKD) with a glomerular filtration rate (GFR) in the range of 20 - 60 ml/min/1.73 m
- •Proteinuria confirmed at least twice by one of the following (at least one sample within the last 6 months),
- •24-hour urine protein excretion of at least 150 mg/day OR
- •spot urine protein to creatinine ratio (PCR) of greater than 0.15 OR
- •spot urine albumin to creatinine ratio (ACR) greater than 100 mg/g
- •A recent diagnosis of secondary hyperparathyroidism of renal origin by the patient's nephrologist scheduled for treatment with an active from of vitamin D.
- •Available results for serum intact parathyroid hormone (iPTH), calcium and phosphorus within 6 months from the study enrollment date.
- •Treatment with a stable dose of an angiotensin receptor blocker (ARB), angiotensin converting enzyme inhibitor (ACE-I) or rennin inhibitor within the last 2 months before enrollment in the study.
排除标准
- •GFR less than 20 or greater than 60 ml/min/1.73 m
- •Treatment with an active form of vitamin D, including Calcitriol (Rocaltrol), Paricalcitol (Zemplar) and Doxercalciferol (Hectorol) within the last 3 months.
- •Need for renal replacement therapy within the next three months.
- •History of any organ transplantation requiring immunosuppressive therapy.
- •Chronic treatment with anti-inflammatory agents including NSAIDs, steroids or cytotoxic agents.
- •Diagnoses of primary or tertiary hyperparathyroidism.
- •Serum intact parathyroid hormone (PTH) concentration greater than 250 pg/mL.
- •Serum calcium greater than 10.4 mg/dL.Serum phosphorous greater than 5 mg/dL.
- •Active malignancy.
- •History of systemic inflammatory diseases such as, systemic lupus, rheumatoid arthritis or vasculitis.
- •History of pulmonary hypertension, intracardiac shunt or unstable cardiopulmonary disease.
- •Women who are pregnant.
结局指标
主要结局
Change in proteinuria compared to baseline as determined by spot urine protein to creatinine ratio (PCR)
时间窗: Subjects must be on Vitamin D for 90 days (plus or minus 10 days)
The pre to post-intervention change in urinary protein to creatinine ratio (PCR) will be analyzed either by way of the common paired Students t-test or the by way of paired Wilcoxon test. The paired Student t-test will be utilized if the measurements of the pre to post-intervention change in PCR are normally distribution, otherwise the ranked based paired Wilcoxon test will be utilized.
次要结局
- Change in renal blood flow compared to baseline as determined by contrast enhanced ultrasound.(Subjects must be on Vitamin D for 90 days (plus or minus 10 days))
- Association between changes from baseline in PCR and RBF(Subjects must be on Vitamin D for 90 days (plus or minus 10 days))
- Association between changes from baseline in PCR and GFR(Subjects must be on Vitamin D for 90 days (plus or minus 10 days))
- Association between changes from baseline in PCR and concentration of biomarkers of inflammation(Subjects must be on Vitamin D for 90 days (plus or minus 10 days))
- Association between changes from baseline in PCR and activity of the renin angiotensin system.(Subjects must be on Vitamin D for 90 days (plus or minus 10 days))
研究者
Kambiz Kalantarinia
MD, Principal Investigator
University of Virginia