Chen Dhruti P, Zaky Ziad S, Schold Jesse D, Herlitz Leal C, El-Rifai Rasha, Drawz Paul E, Bruggeman Leslie A, Barisoni Laura, Hogan Susan L, Hu Yichun, O'Toole John F, Poggio Emilio D, Sedor John R
Division of Nephrology, UNC Kidney Center, University of North Carolina, Chapel Hill, NC, USA.
Glickman Urology and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
Clin Transplant. 2021 Apr;35(4):e14234. doi: 10.1111/ctr.14234. Epub 2021 Feb 10.
Variants in apolipoprotein L1 (APOL1) gene are associated with nondiabetic kidney diseases in black subjects and reduced kidney transplant graft survival. Living and deceased black kidney donors (n = 107) were genotyped for APOL1 variants. To determine whether allografts from high-risk APOL1 donors have reduced podocyte densities contributing to allograft failure, we morphometrically estimated podocyte number, glomerular volume, and podocyte density. We compared allograft loss and eGFR trajectories stratified by APOL1 high-risk and low-risk genotypes. Demographic characteristics were similar in high-risk (n = 16) and low-risk (n = 91) donors. Podocyte density was significantly lower in high-risk than low-risk donors (108 ± 26 vs 127 ± 40 podocytes/10 um , P = .03). Kaplan-Meier graft survival (high-risk 61% vs. low-risk 91%, p-value = 0.049) and multivariable Cox models (hazard ratio = 2.6; 95% CI, 0.9-7.8) revealed higher graft loss in recipients of APOL1 high-risk allografts over 48 months. More rapid eGFR decline was seen in recipients of high-risk APOL1 allografts (P < .001). At 60 months, eGFR was 27 vs. 51 mL/min/1.73 min in recipients of APOL1 high-risk vs low-risk kidney allografts, respectively. Kidneys from high-risk APOL1 donors had worse outcomes versus low-risk APOL1 genotypes. Lower podocyte density in kidneys from high-risk APOL1 donors may increase susceptibility to CKD from subsequent stresses in both the recipients and donors.
载脂蛋白L1（APOL1）基因变异与黑人非糖尿病肾病以及肾移植移植物存活期缩短有关。对107名活体和已故黑人肾供体进行APOL1基因变异基因分型。为了确定来自高危APOL1供体的同种异体移植物是否因足细胞密度降低而导致移植物失败，我们采用形态计量学方法估算足细胞数量、肾小球体积和足细胞密度。我们比较了根据APOL1高危和低危基因型分层的移植物丢失情况和估算肾小球滤过率（eGFR）轨迹。高危供体（n = 16）和低危供体（n = 91）的人口统计学特征相似。高危供体的足细胞密度显著低于低危供体（108±26对127±40个足细胞/10μm，P = 0.03）。Kaplan-Meier移植存活率（高危组61%对低危组91%，P值 = 0.049）和多变量Cox模型（风险比 = 2.6；95%置信区间，0.9 - 7.8）显示，在48个月内，APOL1高危同种异体移植物受者的移植物丢失率更高。高危APOL1同种异体移植物受者的eGFR下降更快（P < 0.001）。在60个月时，APOL1高危肾同种异体移植物受者和低危肾同种异体移植物受者的eGFR分别为27和51 mL/min/1.73 m²。与低危APOL1基因型相比，高危APOL1供体的肾脏预后更差。高危APOL1供体肾脏中较低的足细胞密度可能会增加受者和供者因后续应激而患慢性肾脏病的易感性。
