The Aging Kidney Anatomy Study

 描述（由申请方提供）：仅认为患有重度肾病的患者接受肾活检以评估结构病理学。已经花费了大量的努力来鉴定肾脏病理学的新生物标志物，但是肾脏病理学在多大程度上预测没有严重肾病的患者的不良结果是未知的。该更新提案将通过详细说明无重度肾病患者肾活检和CT扫描的年龄相关和亚临床疾病相关结构病理来填补这一关键知识空白。将分析基于活检（肾硬化和肾单位肥大）和计算机断层扫描（CT）扫描（皮质体积、表面粗糙度、囊肿）的结构病理学和形态学;以及肾单位数量（根据活检和CT估计），以确定它们与不良肾脏结局的关系。将研究三个未定义为重度肾病的互补人群：活体供肾者、与这些活体供肾者配对的肾移植受者和肿瘤肾切除术患者。这些特定人群也将从研究结果中受益最多。通过识别慢性肾脏疾病（CKD）风险最高的供体，将改善肾脏供体的选择和捐献后监测。由于选择有限，肾移植受者通常会接受任何捐赠的肾脏，但同种异体移植失败的主要决定因素是活体供体的年龄。确定预测肾衰竭风险的老年同种异体移植物的结构发现是改善肾受体管理的必要步骤。在肾肿瘤患者中，关于完全（根治性）还是部分（根治性）的决定 肾切除术与监测的比较将由非肿瘤肾病理学预测的肾衰竭风险来告知。研究假设为：1）肾硬化、肾单位肥大和肾单位数量减少可预测不良肾脏结局，与年龄、肾功能和（CKD）风险因素无关; 2）肾脏CT扫描可检测到这种潜在肾脏病理，可用于预测不良肾脏结局。三个具体的目标测试这些假设：1。在3，000例活体供肾者中，肾硬化、较大的肾单位大小和减少的肾单位数量（通过植入肾活检和捐献前CT扫描确定）可预测捐献后3-6个月和捐献后5-20年时较低的肾小球滤过率（GFR）、较低的残余GFR（rGFR）、蛋白尿和高血压。2.在与这些供体匹配的3，000名肾移植受者中，供体肾脏中相同的基线结构发现预测了死亡删失的移植物丢失（肾衰竭），全因移植物丢失（肾衰竭或死亡），GFR下降，蛋白尿和随后的方案活检中间质纤维化增加。3.在1，000例肿瘤肾切除术患者中，这些相同的肾脏结构发现可预测肾衰竭、非癌症死亡率和较低的rGFR（随访GFR/肾切除术前GFR）。

 DESCRIPTION (provided by applicant): Only patients thought to have a severe nephropathy undergo a kidney biopsy to assess structural pathology. Much effort has been expended to identify new biomarkers for kidney pathology, but the extent to which kidney pathology predicts adverse outcomes in patients without a severe nephropathy is unknown. This renewal proposal will fill this key knowledge gap by detailing the age-related and subclinical disease-related structural pathology on renal biopsy and CT scan of patients without a severe nephropathy. Structural pathology and morphology based on biopsy (nephrosclerosis and nephron hypertrophy) and computed tomography (CT) scans (cortical volume, surface roughness, cysts); and nephron number (estimated from biopsy and CT) will be analyzed to determine how they relate to adverse kidney outcomes. Three complementary populations not defined by a severe nephropathy will be studied: living kidney donors, kidney transplant recipients paired to these living donors, and tumor nephrectomy patients. These specific populations will also benefit most from the findings. Kidney donor selection and post-donation monitoring will be improved by identifying donors at highest risk for chronic kidney disease (CKD). Kidney transplant recipients usually take any donated kidney they can due to limited options, but a major determinant of allograft failure is the age of the living donor. Determining the structural findings in older allografts that predict kidney failure risk is a needed step to improved management of kidney recipients. In patients with a renal tumor, decisions regarding a complete (radical) versus partial nephrectomy versus monitoring would be informed by the risk for kidney failure as predicted by non-tumor kidney pathology. The study hypotheses are that 1) nephrosclerosis, nephron hypertrophy, and reduced nephron number are predictive of adverse kidney outcomes independent of age, kidney function, and (CKD) risk factors, and 2) CT scans of the kidneys detect this underlying renal pathology and can be used to predict adverse kidney outcomes. Three Specific Aims test these hypotheses: 1. In 3,000 living kidney donors, nephrosclerosis, larger nephron size, and decreased nephron number (as determined by implantation renal biopsy and pre-donation CT scan) are predictive of lower glomerular filtration rate (GFR), lower residual GFR (rGFR), proteinuria, and hypertension at 3-6 months after donation and at 5-20 years after donation. 2. In the 3,000 kidney transplant recipients matched to these donors, the same baseline structural findings in the donor kidney are predictive of death-censored graft loss (kidney failure), all-cause graft loss (kidney failure or death), GFR decline, proteinuria, and increased interstitial fibrosis on ensuing protocol biopsies. 3. In 1,000 tumor nephrectomy patients, these same kidney structural findings are predictive of kidney failure, non-cancer mortality, and lower rGFR (follow-up GFR/pre-nephrectomy GFR).