Berger Stefan P, Roos Anja, Mallat Marko J K, Schaapherder Alexander F M, Doxiadis Ilias I, van Kooten Cees, Dekker Friedo W, Daha Mohamed R, de Fijter Johan W
Department of Nephrology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Netherlands.
J Am Soc Nephrol. 2007 Aug;18(8):2416-22. doi: 10.1681/ASN.2007030262. Epub 2007 Jul 18.
Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and renal failure. However, this procedure is characterized by a high rate of postoperative infections, acute rejection episodes, and cardiovascular mortality. The lectin pathway of complement activation contributes to cardiovascular disease in diabetes and may play an important role in inflammatory damage after organ transplantation. This study therefore sought to determine how mannose-binding lectin (MBL), a major recognition molecule of the lectin pathway of complement activation, influences outcome after SPKT. MBL serum levels were determined in 99 and MBL genotypes in 97 consecutive patients who received an SPKT from 1990 through 2000 and related to patient and graft survival. At 12 yr, cumulative death-censored kidney graft survival was 87.5% in patients with an MBL level <400 ng/ml and 74.8% in the group with MBL levels >400 ng/ml (P = 0.021). Pancreas graft survival was significantly better in patients with low MBL levels (P = 0.016). MBL levels >400 ng/ml were associated with a hazard ratio of 6.28 for patient death (95% confidence interval 1.8 to 20.3; P = 0.003). Accordingly, survival was significantly better in recipients with MBL gene polymorphisms associated with low MBL levels. These findings identify MBL as a potential risk factor for graft and patient survival in SPKT. It is hypothesized that MBL contributes to the pathogenesis of inflammation-induced vascular damage both in the transplanted organs and in the recipient's native blood vessels.
胰肾联合移植（SPKT）是1型糖尿病合并肾衰竭患者的首选治疗方法。然而，该手术的特点是术后感染率高、急性排斥反应发作频繁以及心血管死亡率高。补体激活的凝集素途径与糖尿病心血管疾病有关，可能在器官移植后的炎症损伤中起重要作用。因此，本研究旨在确定甘露糖结合凝集素（MBL）（补体激活凝集素途径的主要识别分子）如何影响SPKT后的预后。测定了1990年至2000年连续接受SPKT的99例患者的MBL血清水平和97例患者的MBL基因型，并将其与患者及移植物存活率相关联。12年后，MBL水平<400 ng/ml的患者中，经死亡校正后的肾移植累积存活率为87.5%，而MBL水平>400 ng/ml的组为74.8%（P = 0.021）。MBL水平低的患者胰腺移植物存活率明显更高（P = 0.016）。MBL水平>400 ng/ml与患者死亡的风险比为6.28（95%置信区间1.8至20.3；P = 0.003）。因此，具有与低MBL水平相关的MBL基因多态性的受者存活率明显更高。这些发现表明MBL是SPKT中移植物和患者存活的潜在危险因素。据推测，MBL在移植器官和受者自身血管中均促成炎症诱导的血管损伤的发病机制。
