Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients: a Spanish Multicenter, Randomized, Controlled Parallel-group Trial: The TRAINING Study
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 80
- 试验地点
- 8
- 主要终点
- Presence of interstitial fibrosis/tubular atrophy (IFTA)
研究概览
简要总结
Background: Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α klotho levels, progression of IFTA, and loss of kidney function.
Methods: The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-TX, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of either sex, older than 18 years, with no immunological risk (PRA<20% and absence of DSA), who receive their first deceased donor or living donor KT.
- •Presence of BL, excluding isolated inflammation (t0, i>0) and isolated tubulitis (t>0, i0).
- •Patients receiving tacrolimus in combination with mycophenolic acid (MPA) and steroids.
- •Absence of clinical or subclinical and histological immunological dysfunction before randomization.
- •Absence of de novo DSA anti-HLA antibodies at the time of randomization.
- •Provision of written informed consent.
- •Acceptance of efficient contraception in women.
排除标准
- •Recipients of a multi-organ transplant.
- •Re-transplants.
- •Patients without inflammation in the third month protocol biopsy (i0,t0), or with isolated inflammation without tubulitis (t0,i>0) or isolated tubulitis without inflammation (t>0,i0).
- •Presence of DSA antibodies before transplantation or at randomization.
- •Cold ischemia time >30 hours.
- •Serum creatinine >2.5 mg/dl or proteinuria >1 g/day at randomization.
- •Presence of significant thrombopenia (<100,000/mm3) or leukopenia (<3000 mm/3) at randomization.
- •Previous episode of clinical or subclinical rejection (≥IA) before randomization.
- •CMV disease in the first three months after transplantation.
- •BK-polyomavirus nephropathy at randomization.
- •Recurrent or de novo glomerulonephritis.
- •Treatment with immunosuppressive drugs other than those in this clinical trial.
- •Patients who are positive for the human immunodeficiency virus (HIV) or with severe systemic infection, who, in the opinion of the investigator, require continued therapy.
- •Previous (within the last 5 years) or present malignancy, except excised basal or squamous cell carcinoma.
研究组 & 干预措施
Normal treatment
Normal treatment (Steroids, tacrolimus and mycophenolate) arm
干预措施: Normal Treatment (Drug)
Experimental
Normal treatment (Steroids, tacrolimus and mycophenolate) for first 90 days, then add Grafalon single-dose if borderline lesions are present in protocol biopsy (performed at third month post-transplantation).
干预措施: Grafalon (Drug)
结局指标
主要结局
Presence of interstitial fibrosis/tubular atrophy (IFTA)
时间窗: 24 months
Measurement at 24 months according to the Banff classification. The Banff Classification of Allograft Pathology is an international consensus classification for the reporting of biopsies from solid organ transplant.
Renal function measured with CKD-EPI
时间窗: 24 months
Renal function after kidney transplant in both groups at 24 months measured according to glomerular filtration rate determined by CKD-EPI formula
次要结局
- Graft Survival(24 months)
- Patient Survival(24 months)
- Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups(24 months)
- Incidence of Diabetes Mellitus(24 months)
- Blood Pressure mmHg(24 months)
- Number of Participants With Acute Rejection Lesions(24 months)
- Lipid Profile cholesterol, triglycerides(24 months)
- Klotho levels pg/ml(24 months)