Kennard A L, Jiang S H, Walters G D
Department of Renal Medicine, The Canberra Hospital, PO Box 11, Woden, ACT, 2605, Australia.
Department of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
BMC Nephrol. 2017 Jan 17;18(1):25. doi: 10.1186/s12882-016-0435-z.
Kidney transplantation confers superior outcomes for patients with end stage kidney disease, and live donor kidneys associate with superior outcomes compared to deceased donor kidneys. Modern immunosuppression has improved rejection rates and transplant survival and, as a result, recurrence of glomerulonephritis has emerged as a major cause of allograft loss. However, many glomerulonephritides have significant genetic risk which may manifest through kidney intrinsic or systemic mechanisms. We hypothesise that heritable kidney intrinsic predisposition to glomerulonephritis will result in increased risk of glomerulonephritis recurrence in kidneys transplanted from genetically related donors.
We investigated the effect of living related donation on rates of recurrence and subsequent graft outcomes in 7236 patient from 28 years of ANZDATA transplant registry data. Data were analysed in R, using Kaplan Meier Survival analysis and adjusted analyses performed using Cox Proportional Hazards methods. A competing risk model was also analysed.
Glomerulonephritis recurrence rates were significantly higher in living related donor grafts compared to either living unrelated or deceased donor grafts (p < 0 · 001). In IgA nephropathy, transplantation from living related donor kidneys demonstrated a 10 year recurrence rate of 16 · 7% compared to 7 · 1% in living unrelated donors and 9 · 2% in deceased donors (HR:1 · 7, 95% CI:1 · 26-2 · 26, p = 0 · 0005 for living related vs deceased donors). In focal segmental glomerulosclerosis, risk of recurrence at 10 years was 14 · 6% in living related donors compared to 10 · 8% in living unrelated donors and 6 · 6% in deceased donors (HR:2 · 2, 95% CI 1 · 34-3 · 64, p = 0 · 002) for living related vs deceased donors. Primary glomerulonephritis death censored graft survival was superior for living donor grafts, related or unrelated, compared to deceased donor grafts.
We identified a significant increase in the risk of glomerulonephritis recurrence in IgA Nephropathy and Focal Segmental Glomerulosclerosis in living related donors compared to a deceased donors.
肾移植为终末期肾病患者带来更好的治疗效果，与死体供肾相比，活体供肾的治疗效果更佳。现代免疫抑制疗法降低了排斥反应发生率，提高了移植肾存活率，因此，肾小球肾炎复发已成为移植肾丧失的主要原因。然而，许多肾小球肾炎具有显著的遗传风险，可能通过肾脏内在机制或全身机制表现出来。我们推测，遗传性肾脏内在易感性导致的肾小球肾炎会增加来自基因相关供体的移植肾发生肾小球肾炎复发的风险。
我们利用澳大利亚和新西兰透析与移植登记处28年的数据，调查了7236例患者中亲属活体供肾对复发率及后续移植肾结局的影响。使用R软件进行数据分析，采用Kaplan-Meier生存分析，并使用Cox比例风险法进行校正分析。还分析了竞争风险模型。
与活体非亲属供肾或死体供肾相比，亲属活体供肾的肾小球肾炎复发率显著更高（p < 0.001）。在IgA肾病中，亲属活体供肾移植的10年复发率为16.7%，而活体非亲属供肾为7.1%，死体供肾为9.2%（风险比：1.7，置信区间95%：1.26 - 2.26，亲属活体供肾与死体供肾相比，p = 0.0005）。在局灶节段性肾小球硬化症中，亲属活体供肾10年的复发风险为14.6%，活体非亲属供肾为10.8%，死体供肾为6.6%（风险比：2.2，置信区间95%：1.34 - 3.64，亲属活体供肾与死体供肾相比，p = 0.002）。与死体供肾移植相比，活体供肾（亲属或非亲属）的原发性肾小球肾炎死亡截尾移植肾存活率更高。
我们发现，与死体供肾相比，亲属活体供肾的IgA肾病和局灶节段性肾小球硬化症中肾小球肾炎复发风险显著增加。
