Renal allograft rupture caused by acute tubular necrosis

Renal allograft rupture is a rare but potentially lethal complication of kidney transplantation. A renal allograft recipient receiving quadruple immunosuppressive therapy developed a spontaneous allograft rupture 13 days after kidney transplantation. Warm ischaemia time during the transplant was 80 minutes. The ruptured kidney graft could not be salvaged because of the patient's haemodynamic instability. The histopathological examination showed interstitial oedema with severe acute tubular necrosis with no signs of acute rejection. The most common causes of renal graft rupture are acute rejection and vein thrombosis, while acute tubular necrosis may only rarely be responsible for this complication. Renal graft rupture may be the result of interstitial damage attributed both to the prolonged warm ischaemia time during the transplant and to post-transplant acute tubular necrosis in the absence of graft rejection. In those patients whose haemodynamic status cannot be stabilized by appropriate aggressive haemodynamic support therapy, graft nephrectomy should be considered the only definitive treatment.     

Renal allograft rupture.

In the present material of 448 consecutive renal transplants the incidence of allograft rupture was 3.6%. Among 389 first transplants there were two ruptures in the living donor group (126 patients, 1.5%) and 12 ruptures in the cadaveric donor group (263 patients, 4.6%). Only one ruptured kidney (living donor) achieved long term function. Four patients with first graft rupture were retransplanted with early loss of the kidney in all, in two because of rupture. Two of these patients received a 3rd cadaveric graft, of which one is functioning well after two years. All ruptures occurred within three weeks after transplantation, 14 kidneys ruptured during the first week. The clinical course and the operative findings suggested that rejection was the cause of rupture in all cases. This was confirmed by light and immunofluorescent microscopy of specimens from 15 kidneys, while one kidney only demonstrated extensive intrarenal vessel thrombosis. It is concluded that renal allograft rupture signals a strong immunological response in the recipient with poor graft prognosis. The chance of a successful retransplantation is small.     

Higher graft salvage rate in renal allograft rupture associated with acute tubular necrosis

BACKGROUND: Renal allograft rupture is an early postoperative complication threatening graft and patient survival. We reviewed the etiology and prognostic factors for renal allograft rupture. MATERIAL AND METHODS: Among 657 renal transplants performed between 1990 and 2001, renal allograft rupture was diagnosed in 10 cases. Statistical analysis by Student t test, ANOVA, and chi-square was performed to assess donor and recipient characteristics. Multivariate logistic regression to predict renal allograft rupture used variables with P <.15 in the univariate analysis. RESULTS: Patients with renal allograft rupture were mainly men and young. Renal allograft rupture incidence was higher among allografts from non-heart-beating donors, kidneys with delayed graft function, or patients with a high antibody titer. Histopathological findings revealed that six renal allograft ruptures were secondary to acute rejection, three to acute tubular rejection and one to allograft infarction. Only one of six renal allograft ruptures (17.7%) secondary to rejection was resolved by surgery; two of the three patients (66.7%) with acute tubular necrosis were successfully operated and a nephrectomy was performed for the patient with allograft infarction. By multivariate logistic regression analysis, factors shown to be predictive for renal allograft rupture were: delayed graft function, age of recipient, peak panel-reactive antibody >25%, and initial immunosuppressive treatment without antithymocyte globulin. CONCLUSIONS: Higher graft salvage rates are possible in cases of graft rupture associated with acute tubular necrosis.     

Surgical repair of spontaneous renal allograft rupture: a new procedure

Background: The purpose of the present paper is to introduce a new surgical procedure using the external oblique aponeurosis (EOA) for repair of spontaneous renal allograft rupture. Methods: Thirty‐eight cases with spontaneous renal allograft rupture were encountered in 1000 consecutive kidney transplants between April 1991 and August 2000. Thirty‐three cases underwent surgical exploration with two grafts undergoing nephrectomy, while a further 31 were repaired using the new surgical procedure. The external oblique aponeurosis (EOA) from the incision was trimmed into 1 cm × 1 cm square pieces. A 2/0 Dexon suture was placed through each piece of the EOA, then through the parenchyma of the kidney perpendicular to the rupture. Each suture was then placed through another piece of EOA and tied. Results: Two repaired grafts were removed on day 7 and day 10, one due to graft re‐rupture and another with ischaemia secondary to irreversible acute rejection. The graft function of 29 cases had recovered completely at 30 days following surgical repair with one graft improving rapidly. Thirteen grafts were diagnosed as undergoing mild to moderate acute rejection, whereas a further 20 cases were considered to have acute tubular necrosis on histopathology. The allograft survival rate at 1 year and 5 years post grafting was 86% and 64%, respectively. No patients died from postoperative complications following repair using this procedure. Conclusions: Spontaneous renal allograft rupture is a relatively common post‐transplant complication secondary to either acute tubular necrosis or acute rejection. This new surgical procedure is proposed as a reliable and practical method of repair following graft rupture. Preservation of graft function and viability following rupture appears achievable both in the medium and long‐term.     

Polyoma virus infection after renal transplantation. Use of immunostaining as a guide to diagnosis

BACKGROUND: Polyoma virus infection is characterized by lymphocytic interstitial infiltrate in the kidney, and it mimics acute rejection. The purpose of this study is to estimate renal allograft outcome with this infection and characterize the lymphocytic infiltrates in polyoma virus-infected renal allografts. METHODS: Patients who had polyoma virus inclusions in renal allograft biopsies were identified. Other viral inclusions were excluded by immunohistochemistry. The lymphocytic infiltrates of six cases of polyoma virus infection were compared with six cases of definite acute rejection by immunostaining for T and B cells. RESULTS: There were 10 cases of polyoma virus infections in renal transplant recipients. Immunosuppressants consisted of mycophenolate mofetil with tacrolimus in eight cases and mycophenolate mofetil with cyclosporine in two. The median time of diagnosis of polyoma virus infection after transplantation was 9.5 months, and the time to graft failure after the diagnosis was 4 months. Reduced allograft survival was seen in patients who had polyoma virus infection. Immunostaining for T and B cells revealed marked increase in the B cells (CD20) in renal allografts with polyoma virus infection of 21% (range, 5-40%) compared with 6% (range, 0-10%) in those with acute rejection (P=0.039). Reduced cytotoxic T cells (TIA-1: median, 7%; range, 2-15%) were seen in polyoma virus-infected allografts compared with 24% (range, 15-30%) in those patients who had acute rejection (P=0.0159). CONCLUSION: Irreversible graft failure is more prevalent with polyoma virus infection. Enhanced immunosuppressants with mycophenolate mofetil with tacrolimus may play a role in the development of this infection. An increase in CD20 and a decrease in cytotoxic T cells in allografts is characteristic of polyoma virus infection.     

接受同一供体肝肾联合移植与肾移植的临床研究

目的探讨肝肾联合移植肝脏对肾脏的保护作用。方法我院移植中心2002年5月至2006年9月间共进行8例肝肾联合移植手术，对此8例患者及接受同一供体对侧供肾8例肾移植患者及移植物存活率、排斥反应发生率进行分析。结果肝肾联合移植患者及移植物存活率为100％，无可证实排斥反应发生。术后8例患者移植肝功能迅速恢复正常，7例移植肾功能迅速恢复正常，1例移植肾发生急性肾小管坏死，于术后第52天肾功能恢复正常。对应8例单纯肾移植患者，发生急性排斥反应1例，予甲基强的松龙冲击治疗及应用抗人T淋巴细胞免疫球蛋白（anti-thymocyte globulin，ATG）后，于术后50d移植肾功能恢复正常，余7例患者恢复良好，至末次随访肾功能均正常。结论肝肾联合移植肝脏对肾脏有一定的保护作用。     

移植肾破裂肾包膜切开止血法

移植肾自发性破裂是同种异体肾移植术后早期的一个严重并发症，采用肾包膜多处切开结合止血绫－粘涂胶止血法保肾，并行双滤过法血浆分离术（ＤＦＰＰ）和应用抗胸腺细胞球蛋白（ＡＴＧ）治疗６例严重移植肾破裂患者，止血效果达到１００％，４例肾脏得以保存，２例切除移植肾。认为肾包膜多处切开结合止血绫－粘涂胶止血术是治疗严重移植肾破裂的一个安全、可靠和简便的止血保肾法     

Early biological and immune response to semi-identical liver or kidney allograft in miniature swine

In inbred miniature swine, semi-identical liver allograft recipients survive up to 3 months without immunosuppression, whereas similarly mismatched kidney allografts are uniformly rejected within 2 weeks. The early biological and immunological events were assessed in this unique model. SLA(d/d) pigs (MGH, Harvard Medical School, Boston, MA, USA) received liver or kidney allograft from heterozygous SLA(c/d) miniature swine. Survival, graft function, histology, intragraft cytokines, peripheral lymphocyte and platelet count, plasma cortisol level and cellular/humoral anti-donor immune response were assessed. Kidney allografts were uniformly rejected within 2 weeks, whereas liver allografts survived for up to 87 days. After both liver and kidney transplantation, the peripheral lymphocyte count decreased during the first week concomitantly to a significant elevation of plasma cortisol level. Early decrease of peripheral platelet count was observed after liver but not renal transplantation. Up-regulation of transforming growth factor beta1 (TGF-beta1) and interferon-gamma (IFN-gamma) was observed during the first postoperative week in semi-identical liver allografts and IFN-gamma as well as IL-10 in kidney allografts. In liver recipients, labelled autologous lymphocytes accumulated in the liver graft and native spleen, whereas after renal allograft, lymphocytes accumulated in the native spleen and liver but never in the kidney allograft. Specific cellular anti-donor unresponsiveness was observed from the first post-transplant day in both liver and kidney recipients, while the humoral anti-donor response remained intact. In semi-identical liver allograft, recipient rejection is milder and slower than in similarly matched kidney allograft. The intragraft up-regulation of TGF-beta1 in semi-identical liver allograft might be one mediator to explain the modulation of rejection after liver transplant. The rapid, nonspecific accumulation of recipient lymphocytes in the liver allograft but not in kidney allograft might also play a role in the different survival time in this model.     

Circulating adhesion molecules during kidney allograft reperfusion

Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant recipients, including 13 cases of delayed graft function (DGF) and 11 cases of acute graft rejection (AR). Plasma concentrations of E-selectin, VCAM-1 and ICAM-1 after 3 min of reperfusion were significantly higher than in the iliac vein before reperfusion. There was no statistically significant difference between patients with and without DGF as regards E-selectin, VCAM-1 and ICAM-1 concentrations in the iliac vein before and in the renal vein after 3 min of reperfusion. Concentrations of adhesion molecules in the iliac vein before reperfusion and in the renal vein after 3 min of reperfusion did not differ significantly between patients with and without AR except for ICAM-1 iliac vein concentration which was significantly increased in AR patients. Plasma levels of E-selectin, ICAM-1 and VCAM-1 were increased after kidney allograft reperfusion. Moreover, elevated serum levels of ICAM-1 before transplantation correlated with subsequent acute kidney allograft rejection. The results suggest that elevated ICAM-1 levels may be implicated in acute graft rejection.     

C4d Immunoreactivity of Intraoperative Zero-Hour Biopsy in Renal Allograft

C4d deposition in the peritubular capillaries is known to be correlated with antibody-mediated rejection (AMR) in renal allografts. An intraoperative zero-hour biopsy during transplantation is considered an indicator to indirectly determine the status of the donor kidney. In this study, we investigated the relationship between C4d immunoreactivity of intraoperative zero-hour biopsy in renal allograft, thought to be due to donor condition, and acute rejection episodes during follow-up. We collected 147 renal transplantation cases examining intraoperative zero-hour biopsy with C4d immunohistochemical staining. All cases were from the Seoul National University Hospital between 2010 and 2011. Of the 147 cases, 24 (16.3%) showed strong C4d staining in the glomeruli, 38 (25.9%) showed weak staining, and the remainder (57.8%) showed negative staining. Nine cases (6.1%) showed positive C4d staining in the arterioles, and the remainder (93.9%) were negative. There were no significant differences between acute T-cell-mediated rejection and acute AMR episodes in the renal allograft specimens during follow-up according to the glomerular or arteriolar C4d immunoreactivity of the intraoperative zero-hour biopsy specimens.     

Circulating adhesion molecules during kidney allograft reperfusion

Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant recipients, including 13 cases of delayed graft function (DGF) and 11 cases of acute graft rejection (AR).Plasma concentrations of E-selectin, VCAM-1 and ICAM-1 after 3 min of reperfusion were significantly higher than in the iliac vein before reperfusion. There was no statistically significant difference between patients with and without DGF as regards E-selectin, VCAM-1 and ICAM-1 concentrations in the iliac vein before and in the renal vein after 3 min of reperfusion.Concentrations of adhesion molecules in the iliac vein before reperfusion and in the renal vein after 3 min of reperfusion did not differ significantly between patients with and without AR except for ICAM-1 iliac vein concentration which was significantly increased in AR patients. Plasma levels of E-selectin, ICAM-1 and VCAM-1 were increased after kidney allograft reperfusion. Moreover, elevated serum levels of ICAM-1 before transplantation correlated with subsequent acute kidney allograft rejection.The results suggest that elevated ICAM-1 levels may be implicated in acute graft rejection.     

高度致敏肾移植患者的围术期处理

目的 探讨高度致敏肾移植患者的围手术期处理.方法 对22例高度致敏肾移植患者术前组织配型及预处理,术后抗排异方案以及肾功恢复情况进行研究.结果 17例患者术前经血浆置换3～8次后群体反应性抗体(PRA)降至30%以下,5例患者术前PRA仍大于50%.术后发生超急性排斥反应(HAR)1例(9.9%),抗排异反应未能逆转,予以切除移植肾;急性排斥反应(AR)8例(36.3%),经甲强龙+ATG(ALG)冲击治疗后6例肾功恢复正常,2例转为肾功能延迟恢复(DGF);术后DGF5例(22.7%),予以血液透析+低剂量抗排异药物维持,肾功均恢复正常.结论 避开相应抗体进行良好的组织配型,是高度致敏患者肾移植成功的关键;术前行血浆置换降低高度致敏患者PRA,使用ATG或ALG可降低手术风险,提高排斥反应逆转率.     

Morbidity of pancreas transplantation during cadaveric renal transplantation.

Simultaneous transplantation of the pancreas is an option for diabetic patients undergoing kidney transplantation to attempt to halt progression of diabetic complications, but the additional risk imposed by the procedure is unclear. Our aim was to determine the morbidity attributable to pancreas transplantation during simultaneous pancreas and kidney transplantation. We compared the first posttransplant year of 18 consecutive recipients of combined pancreas and kidney transplantation to 18 consecutive recipients of kidney transplantation alone. All patients received cadaver donor allografts between 1986 and 1989, and had type I diabetes mellitus with chronic renal failure. There were no differences in patient survival (94% both groups) or satisfactory renal allograft function (89% pancreas/kidney group, 83% kidney group) up to 18 months after transplantation. Eighty-eight percent of pancreas allografts were functioning satisfactorily at 18 months. There was a mean (+/- SD) of 1.5 +/- 1.0 acute rejection episodes per patient for the pancreas/kidney group compared to 0.8 +/- 6 for the kidney-only group (P less than 0.02). Cytomegalovirus infection and wound complications were each encountered more often after pancreas/kidney transplantation than kidney transplantation alone, and together with rejection accounted for a difference in days of hospitalization during the first year (71 +/- 34 vs. 27 +/- 13, P less than 0.001). We conclude that simultaneous pancreas transplantation during cadaver donor kidney transplantation accounted for more frequent rejection episodes, CMV infections, and wound complications. These complications resulted in more hospitalization for patients undergoing simultaneous pancreas/kidney transplantation than kidney transplantation alone.     

Comparison of renal allograft outcomes in combined liver-kidney transplantation versus subsequent kidney transplantation in liver transplant recipients: Analysis of UNOS Database

BACKGROUND: There may be an allograft-enhancing effect by the liver on the renal allograft in the setting of simultaneous combined liver-kidney transplantation (CLKT) from the same donor. This study was performed to investigate whether an existing liver allograft could protect a kidney allograft from immunologic injury due to histoincompatibility in liver transplant recipients who received sequential kidney transplantation (KALT). METHODS: Using the United Network for Organ Sharing database covering January 1996 to December 2003, outcomes of 352 KALT were compared to 1,136 CLKT. Incidence of acute and chronic rejection and rejection-free renal graft survival was compared between two groups. RESULTS: Renal half-life of KALT allografts was shorter than CLKT group (6.6+/-0.9 vs. 11.7+/-1.3 years, P < 0.001). Incidence of chronic rejection in KALT group was higher than CLKT group (4.6 vs. 1.2%, P < 0.001). One and three-year rejection-free renal graft survival of KALT and CLKT groups were different (77% and 67% KALT vs. 85% and 78% CLKT, respectively; P < 0.001). Among human leukocyte antigen mismatched and sensitized patients, rejection-free renal graft survival of KALT group was inferior to the CLKT group (75% at 1 year and 61% 3 years vs. 86% at 1 year and 79% 3 years, P < 0.001). CONCLUSION: Liver allograft provided renal graft immunoprotection if both organs are transplanted simultaneously (immunogenetic identity), but not for kidneys transplanted subsequently.     

Ten-year follow-up in patients with combined heart and kidney transplantation

BACKGROUND: Combined heart and kidney transplantation has been documented, although data regarding immunosuppression, rejection episodes, and graft or patient survival have not been detailed. We evaluated our experience and more than 10-year outcome with patients selected for combined heart and kidney transplantation. METHODS: Eight patients aged 29 to 59 years were selected for combined heart and kidney transplantation. The indications were end-stage heart disease and underlying renal pathology, or secondary renal insufficiency, or renal failure. Six patients were dialysis dependent before transplantation. There were 7 simultaneous procedures and 1 staged procedure. The heart was transplanted first in all cases. All patients were maintained after transplantation on azathioprine (2 mg x kg(-1) x d(-1)) and whole-blood monoclonal cyclosporine levels at greater than 200 microg/L; prednisone was not decreased to less than 10 mg/d. RESULTS: Seven (87.5%) patients have survived a mean duration of 100.4 months (range, 51-144 months), and each allograft has continued to function. The only death was due to pulmonary emboli and was not related to allograft rejection or failure. Only 4 cardiac and 4 kidney allograft rejections have occurred. Five patients have been free of kidney rejection, 1 patient has been rejection free for more than 8 years, and no patient has had simultaneous rejection. CONCLUSIONS: In select patients, combined heart and kidney transplantation can provide long-term graft function and patient survival. The low rates of rejection support our current approach to immunosuppression. Our experience indicates that end-stage failure of either heart or kidney does not necessarily preclude dual-organ transplantation.     

Longitudinal analysis of chronic allograft nephropathy: clinicopathologic correlations

BACKGROUND: Loss of the allograft from chronic allograft nephropathy and death of the patient from vascular, malignant, or infective disease are the major problems in renal transplantation today. Protocol biopsy of the long-term kidney has provided new data with which to develop strategies for prevention and treatment of chronic allograft nephropathy. METHODS: Two series of long-term protocol biopsies are reviewed. In the first, renal biopsies were obtained at time 0, and at 3 months and 12 months, and the recipients of the renal allografts were followed up for up to 15 years. In the second, the kidneys of recipients of simultaneous pancreas kidney transplants were biopsied annually for 10 years, and the results correlated with clinical events. RESULTS: Chronic allograft nephropathy is caused by acute and chronic immune-mediated damage, as well as by chronic calcineurin inhibitor nephrotoxicity. Both immune and nonimmune mechanisms exacerbate pre-existing donor disease and ischemia-reperfusion injury. Established interstitial fibrosis and arteriolar hyalinosis lead to progressive glomerular sclerosis and eventual loss of the graft. CONCLUSION: Protocol biopsies have shown that clinical parameters of renal function underestimate the severity of chronic graft damage. Strategies for preventing or treating chronic renal allograft dysfunction and subsequent graft loss must better control rejection and simultaneously avoid nephrotoxicity.     

肾移植2 123例临床总结

目的：总结肾移植的临床经验,探讨影响肾移植存活的因素,提高长期存活率。方法：回顾性总结2123例肾移植病例的临床资料,对人和（或）肾存活率,供肾的切取,灌注,热冷缺血时间对移植的影响,植肾技术,免疫抑制剂的应用,HLA配型,群体反应抗体（PRA）检测及术后并发症的发生情况等进行了分析。结果：1978－1990年423例中发生超急性排斥反应者9例（2．1％）,急性排斥反应198例（46．8％）,1,3和5年人和（或）肾存活率为86.7%/76.3%,72.5%/67.9%和69.5%/59.3%,1991-2001年,共1700例肾移植,其中未发生超急性排斥反应,急性排斥反应252例（14.8%),1,3和5年人（或）肾存活率高达98.6%/96.7%,93.1%/87.3%和88.1%／83.6%。结论：适应证的选择,高质量的供肾是保证肾移植成功的关键;PRA的检测,良好的HLA配型有利于减少移植肾的早期失功能并提高肾移植长期存活率;加强对肾移植患者的随访,指导康复治疗,对患者能否长期存活有重要意义。     

Conservative surgery of spontaneous rupture of renal grafts]

17 cases of spontaneous rupture of renal allografts were noted after 285 renal transplantations performed during the years 1967-1978. All ruptures occurred within the first two weeks after transplantation. Acute rejection, combined with hypertension, dialysis and/or anticoagulation seem to be the main etiological factors of graft rupture. Due to severe hemorrhage surgical exploration had to be performed in 15 patients. While removal of the graft was necessary in 4 patients the kidney could be preserved by tamponade and suture in 11 patients. 5 patients later lost their graft, due to chronic rejection, while 8 patients (6 of the 15 patients who needed surgical exploration) currently have satisfactory graft function.     

Incidence of Renal and Liver Rejection and Patient Survival Rate Following Combined Liver and Kidney Transplantation

Multiple organ transplantations are used to treat chronic multiple organ failure. However, long-term mortality and graft tolerance remain to be evaluated. We carried out a retrospective and comparative analysis of 45 patients who underwent a combined liver and kidney (LK) transplantation (LKT) from the same donor. They were compared to 86 matched patients who underwent kidney (K) transplantation (KT). All patients had an organic renal failure associated with cirrhosis (n = 35) or with inherited disease (n = 10). Nineteen (42.9%) had been transplanted previously. The patients' survival rate was 85% at 1 year and 82% at 3 years. Seven patients died within the first 3 months, due to severe polymicrobial infection. Two patients in the LK population (4.2%) developed acute rejection of the kidney graft compared to 24 of the 86 matched renal transplanted patients (32.6%). In parallel, acute liver rejection was observed in 14 cases (31.1%) in the LK population. The occurrence of acute rejection was not associated with panel-reactive lymphocytotoxic antibodies (n = 16), nor with positive cross-matches (n = 3). Four of the 45 patients (8.8%) subsequently developed chronic renal allograft rejection, and 16 cases of chronic hepatic dysfunction were noted (42.2%). In conclusion, the overall survival rate following combined liver kidney transplantation is acceptable, and LKT can be proposed to patients with kidney failure associated with liver dysfunction, primary oxaluria or amyloid neuropathy. The main cause of mortality in this population was severe infectious complications. The frequency of acute kidney rejection was lower than in single transplantation.