An evaluation of the Banff classification of early renal allograft biopsies and correlation with outcome.

BACKGROUND: The Banff classification for assessment of renal allograft biopsies was introduced as a standardized international classification of renal allograft pathology and acute rejection. Subsequent debate and evaluation studies have attempted to develop and refine the classification. A recent alternative classification, known as the National Institutes of Health Collaborative Clinical Trials in Transplantation (NIH-CCTT) classification, proposed three distinct types of acute rejection. The 1997 Fourth Banff meeting appeared to move towards a consensus for describing transplant biopsies, which incorporated both approaches. Patients who received a renal allograft at the Oxford Transplant Centre were managed by a combination of protocol and clinically indicated biopsies. We have undertaken a retrospective analysis of the biopsies correlated with the clinical outcome to test the prognostic value of the original Banff (Banff 93-95) and NIH-CCTT classifications. METHODS: Three hundred and eighty-two patients received renal allografts between May 1985 and December 1989, and were immunosuppressed using a standard protocol of cyclosporine, azathioprine and steroid. Adequate 5-year follow-up data were available on 351 patients, and of these, 293 had at least one satisfactory biopsy taken between days 2 and 35 after transplantation, the latter patients forming the study group. The D2-35 biopsies taken from these patients, which were not originally reported according to the Banff classification, were re-examined and classified according to the Banff 93-95 protocols. For each patient the biopsy found to be the most severely abnormal was selected, and the Banff and NIH-CCTT grading compared with the clinical outcome. RESULTS: Seven hundred and forty-three biopsies taken from 293 patients between days 2 and 35 after transplantation were examined and the patients categorized on the basis of the 'worst' Banff grading as follows. Normal or non-rejection, 20%; borderline, 34%; acute rejection grade I (AR I), 18%; AR IIA, 6%; AR IIB, 14%; AR III, 1%; AR IIIC, 3%; widespread necrosis 3%. The clinical outcome for the last two groups combined was very poor with 18% of grafts functioning at 3 months and 6% at 5 years. The other groups with vascular rejection (AR IIB and AR III) had an intermediate outcome, graft survival being 78% at 3 months and 61% at 5 years. The remaining four groups (normal, borderline, cellular AR I and AR IIA) had the best outcome: graft survival 95% at 3 months and 78% at 5 years with virtually no difference between the four groups. Three forms of acute rejection, namely tubulo-interstitial, vascular and transmural vascular, were identified, but only the latter two categories were associated with a poor outcome. CONCLUSIONS: The eight sub-categories of the Banff classification of renal allograft biopsies are associated with three different prognoses with respect to graft survival in the medium term. These three prognostic groups correspond to the three NIH-CCTT types. The data provide support for the consensus developed at Banff 97 separating tubulo-interstitial, vascular and transmural vascular rejection (types I, II and III acute rejection).     

改良早期预警评分对腹部闭合性创伤预后的预测价值

目的观察改良早期预警评分（MEWS）用于腹部闭合性创伤评估的临床效果。 方法收集2008年1月至2017年11月芜湖市第五人民医院收治的160例腹部闭合性创伤患者资料,回顾性分析并统计所有患者临床诊治及预后资料,采用MEWS评分系统进行评估,观察患者分诊情况（门诊或专科保守治疗、ICU抢救、中转手术）、治疗过程中并发症发生情况及30 d内预后状况。 结果160例患者中保守治疗64例（40.0%）,入住ICU抢救96例（60.0%）;中转手术34例（21.3%）。MEWS评分>8分者16例,均分诊为入住ICU抢救,保守治疗率明显低于其他各分值段（MEWS评分>6~8分除外）,入住ICU抢救率明显高于其他各分值段（MEWS评分>6~8分除外）,中转手术率明显低于MEWS评分<3分及3~4分值段,上述差异均有统计学意义（P<0.05）。160例患者30 d内预后良好124例（77.5％）,MEWS评分为（2.44±1.32）分;预后不良36例（22.5%）,MEWS评分为（6.84±2.12）分,其中死亡12例（7.5％）,感染16例（10.0％）,多器官衰竭4例（2.5％）,应激溃疡4例（2.5％）。ROC曲线分析显示MEWS评分对腹部闭合性创伤患者预后不良有一定预测价值,曲线下面积为0.919（P<0.001,95% CI=0.797~1.000）,预测预后不良最佳截断值为5.970分,敏感度0.667,特异度0.986。 结论采用MEWS预警评分对评估腹部闭合性创伤患者就诊时分诊及预后具有重要作用,减少并发症及死亡率,改善预后。     

Comparison of early renal function parameters for the prediction of 5-year graft survival after kidney transplantation.

BACKGROUND: Early graft function (EGF) has an enduring effect on the subsequent course after kidney transplantation. This study compares quantitative parameters of EGF for the prediction of graft survival. METHODS: We involved 300 consecutive transplant recipients from deceased donors from 1989 to 2005. Urine output during 24 h post-transplant (UO), and serum creatinine after 1 week (Cr7) were taken for explanatory variables. We generated Kaplan-Meier (K-M) estimates of graft survival, by quintiles of the explanatory variable. Cox regression was applied to control for various recipient factors. RESULTS: K-M survival estimates indicate a threshold effect of UO and Cr7, which can dissect the risk of graft failure. The thresholds referring to the 2nd quintile correspond to a UO >630 ml and a Cr7 <2.5 mg/dl and were associated with a proportional hazard ratio of 0.52 (95% CI 0.33-0.84) and 0.34 (95% CI 0.18-0.65), respectively. Combining both of the parameters predicted a 5-year graft survival probability >90%, according to a hazard ratio of 0.21 (95% CI 0.09-0.46). Requirement of dialysis post-transplant lost its discriminatory power and was not a significant explanatory variable in the multivariate analysis. CONCLUSION: Routine parameters for monitoring of EGF display a threshold effect allowing accurate prediction of 5-year graft survival at the earliest point in time. The quantitative threshold levels for an optimum discriminatory power require validation in a larger, preferably multicentre database.     

肾损伤标志物对肾移植受者发生DGF的早期预测价值

目的  探讨血中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、尿NGAL、血清胱抑素C（Cys-C）以及血清肌酐（Scr）预测肾移植受者发生肾功能延迟恢复（DGF）的价值。方法  收集159肾移植受者的临床资料及血液、尿液标本,根据是否发生DGF,分为DGF组（42例）和即刻肾功能恢复（IGF）组（117例）。分析两组受者的临床资料,对比两组受者的血NGAL、尿NGAL、Cys-C及Scr变化情况,分析不同指标对DGF的早期预测价值。结果  159例肾移植受者中,42例发生DGF,发生率为26.4%。两组供者年龄、供肾冷缺血时间及补体依赖淋巴细胞毒性试验（CDC）比较,差异有统计学意义（均为P < 0.05）。DGF组血NGAL在术后2周内均高于IGF组（均为P < 0.05）;DGF组Cys-C、Scr、尿NGAL在术后3周内均高于IGF组（均为P < 0.001）。血NGAL、尿NGAL、Cys-C和Scr对肾移植受者发生DGF具有一定预测价值,其中Cys-C预测价值最高,截取值为4.73 mg/L,灵敏度为0.833,特异度为0.812,曲线下面积（AUC）为0.895。结论  Cys-C早期预测肾移植受者发生DGF的价值高于血NGAL、尿NGAL及Scr。     

Complement activation in early protocol kidney graft biopsies after living-donor transplantation

BACKGROUND: To gain insight into complement activation in kidney grafts, we studied the deposition of components from all complement pathways in protocol biopsies from living-donor recipients that were taken 1 week (median 7 days) after transplantation. METHODS: Graft protocol biopsies (n=37) were taken consecutively and stained for two-color immunofluorescence, with antibodies to C4d, C3, C1q, factor B, C6, terminal C5b-9 complement complex, mannose-binding lectin (MBL), and MBL-associated serine protease-1, combined with an endothelial marker. Light and electron microscopy were performed in all cases. Clinical acute rejection (AR), graft loss, and long-term kidney function were recorded. Baseline biopsies from 15 of the patients served as controls. RESULTS: Endothelial C4d deposition was demonstrated in peritubular capillaries in 11 of 37 cases (30%), of which 9 of 11 (82%) experienced clinical AR but only 6 of 11 (55%) experienced AR as defined by histopathologic criteria. Biopsies from three patients, two with early graft loss, showed diffuse global C4d in the glomerular endothelium with codeposition of C3 in all patients and MBL-associated serine protease-1 in one patient. Focal peritubular capillary C3 deposition was found in two additional C4d-positive cases with AR. No posttransplant deposition was demonstrated for the other components. CONCLUSIONS: Early diffuse C4d deposition in the kidney graft capillaries is closely related to acute humoral rejection, whereas focal staining may occur with mild AR or, rarely, without rejection. Codeposition of C3 indicates early AR with a higher risk of graft loss. In most cases, activation was limited to C4d, indicating efficient in situ regulation of complement activation.     

Predictive value of an early Glasgow Outcome Scale score: 15-month score changes

OBJECT: Does an early Glasgow Outcome Scale (GOS) assessment provide a reliable indicator of later outcome in a patient with traumatic brain injury (TBI)? The authors examined the utility of the GOS during early treatment as a predictor of outcome score 15 months postinjury by analyzing outcome score change in a group of patients with closed head injuries. METHODS: Glasgow Outcome Scale scores assessed within 3 months of injury (baseline) were compared with scores obtained at 15 months postinjury in 121 patients, primarily young military personnel. Score changes between baseline and 8 months postinjury were also studied in a subgroup of 72 patients. The impact of initial injury severity (determined by the duration of unconsciousness) on score change was also explored. The GOS scores at three time points within the 15-month period-baseline (within 3 months of injury), 8, and 15 months postinjury-were examined to ascertain when the maximal GOS score had been reached. CONCLUSIONS: Baseline GOS score was a reliable predictor of outcome in patients with an initial score of 5 (no disability) or 4 (mild disability), but not in patients with an initial score of 3 (severe disability). Patients who remained unconscious for more than 24 hours did not have significantly lower outcome scores than those who experienced loss of consciousness for less than 24 hours at 15 months postinjury. Interestingly, the duration of unconsciousness did not affect the likelihood of an improved score during the study period in patients with a GOS score of 3 or 4 at baseline. An updated evaluation conducted after the early phases of treatment is needed to provide a realistic prognosis of severe TBI.     

Predictive value of urinary retinol binding protein for graft dysfunction after kidney transplantation

High concentrations of retinol binding protein (RBP) are found in the urine of patients with tubulointerstitial injury. We evaluated the predictive value of urinary RBP (RBPu) for development graft dysfunction after kidney transplantation. METHODS: Serum creatinine and RBPu were prospectively measured at months 3, 6, and 12 in 221 kidney transplant patients. Baseline graft function was defined as the lowest serum creatinine value during the first 3 months after transplantation. Graft dysfunction was assessed at 1 year as a >-20% or >-30% change in the inverse creatinine ((Delta)1/Cr) compared to baseline value at month 3. RESULTS: Among 183 patients with normal graft function (Cr 0.6 mg/L (95% CI = -13% to -1.3%, P =.018). The percentage of patients with >-20% or >-30% (Delta)1/Cr was higher among patients with RBPu > 0.6 mg/L (34% vs 47%, P =.042; 21% vs 34%, P =.035). RBPu > 0.6 mg/L was the only variable independently associated with >-30% (Delta)1/Cr at 1 year, with an odds ratio (OR) of 1.95 (95% CI 0.99 to 3.80, P =.05). CONCLUSIONS: RBPu may serve as a surrogate marker for graft dysfunction early after transplantation for patients with normal graft function, allowing early institution of intervention therapies to prolong allograft survival.     

Correlation between the Banff 97 classification of renal allograft biopsies and clinical outcome

The 1997 fourth Banff meeting revised the consensus for describing transplant biopsies. We have conducted a retrospective analysis of biopsies correlated between the Banff 97 classification and clinical outcome. The patients (n=149), who had a total of 404 biopsy-proven rejections, were assessed and the biopsies taken from these patients were re-examined and classified according to the Banff 97 classification. Morphological changes in the glomeruli (g), interstitium (i), tubules(t), and arterial vessels (v) were scored. Severity of acute rejection was statistically associated with unresponsiveness to anti-rejection treatment (P<0.0001) and predicted an increased risk of graft failure (P<0.05). Each quantitative criterion (g, i, t, and v) was also statistically associated with unresponsiveness to anti-rejection treatment. Mean serum creatinine levels were significantly higher in the groups graded Banff 97 type I--III after 1 and 2 years of follow-up. The Banff 97 classification correlated with reversibility of rejection episodes and long-term graft survival.     

移植肾早期功能对其长期存活的影响

通过对应用环孢素Ａ、移植满５年且有完整资料的２１２例肾移植受者进行回顾性分析，观察早期血清肌酐（ＳＣｒ）水平对移植肾３年、５年存活率（ＧＳ）的影响。结果表明：１个月内ＳＣｒ恢复正常者（ＳＣｒ≤１４０μｍｏｌ／Ｌ）的３年ＧＳ较尚未恢复者（ＳＣｒ≥１７７μｍｏｌ／Ｌ）提高２０％，５年ＧＳ提高３０％（Ｐ〈０．０１￣０．００１）；３个月内ＳＣｒ降至１７７μｍｏｌ／Ｌ以下者３年及５年ＧＳ较未降至该水平者提高     

HLA mismatch is important for 20-year graft survival in kidney transplant patients

BackgroundHuman leukocyte antigens (HLA) matching is gradually being omitted from clinical practice in evaluation for renal allograft transplant. While such practices may yield shorter wait times and adequate short-term outcomes, graft longevity in HLA mismatched patients remains unclear. This study aims to demonstrate that HLA matching may still play an important role in long-term graft survival.MethodsWe identified patients undergoing an index kidney transplant in the United Network for Organ Sharing (UNOS) data from 1990 to 1999, with one-year graft survival. The primary outcome of the analysis was graft survival beyond 10 years. We explored the long-lasting impact of HLA mismatches by landmarking the analysis at established time points.ResultsWe identified 76,530 patients receiving renal transplants in the time frame, 23,914 from living donors and 52,616 from deceased donors. On multivariate analysis, more HLA mismatches were associated with worse graft survival beyond 10 years for both living and deceased donor allografts. HLA mismatch continued to remain an essential factor in the long term.ConclusionsA greater number of HLA mismatches was associated with progressively worse long-term graft survival for patients. Our analysis reinforces the importance of HLA matching in the preoperative evaluation of renal allografts.     

移植肾临界改变的演变及其预后

目的 探讨移植肾临床改变的演变过程及其对肾移植长期效果的影响。方法 肾移植术后常规进行肾活检。对４６例首次病理确诊为“临界改变”,临床上伴有或不伴有移植肾功能异常者进行长期随访。结果 ４６例临界改变多发生于术后３个月内（４２例,占９１．３％）。１５例临界改变伴肾功能异常者经甲泼尼龙冲击强化治疗后,１２例于治疗后１个月,血肌酐降至正常,临界改变治疗组３年移植肾存活率明显高于对照组和临床改变未治疗组。     

Silent acute rejection during prolonged delayed graft function reduces kidney allograft survival

BACKGROUND: The relationship between the effects of early, silent, acute rejection (AR) and delayed graft function (DGF) on kidney allograft survival remain controversial, and the role of protocol biopsies during DGF is unclear. We hypothesized that protocol biopsies during DGF would reveal a high incidence of silent AR that may adversely affect long-term allograft survival. METHODS: We routinely carried out protocol biopsies in patients requiring dialysis 7 to 10 days posttransplant. We retrospectively examined the extent to which silent AR, diagnosed by protocol biopsies during prolonged DGF, may mediate the adverse effects of DGF on graft survival in 410 consecutive transplants using Cox proportional hazards analysis. RESULTS: By 40 days posttransplant, the cumulative incidence of AR was 57.2% among 65 patients who had a protocol biopsies during DGF, while it was only 15.1% among the 345 who did not need a protocol biopsy. Mild DGF (n=30) requiring one or two dialysis treatments had no effect on graft survival, but the unadjusted risk ratio (and 95% confidence interval) associated with more prolonged DGF (n=104) was 3.08 (2.09-4.52, P<0.0001). The risk for graft failure from AR detected on protocol biopsy was 2.91 (1.60-5.27, P=0.0004) and was similar to the risk from early AR in patients without DGF, 2.95 (1.72-5.07, P<0.0001). After taking the effects of AR into account, the risk of graft failure attributable to prolonged DGF was reduced to 1.76 (1.06-2.94, P=0.0294), suggesting that much of the risk of DGF was because of the risk of AR. CONCLUSIONS: Silent AR is common during DGF. Prolonged DGF is associated with reduced graft survival after kidney transplantation, and much of this association can be explained by silent AR. In the absence of data from randomized trials, protocol biopsies and treatment of silent AR during prolonged DGF appear to be warranted.     

Efficacy of early biopsy in kidney allograft recipients with delayed graft function

It is accepted that kidney transplants that display delayed graft function (DGF) show poorer survival and function, particularly when an acute rejection episode (ARE) occurs. A diagnostic biopsy to establish the reason for DGF, or acknowledge an ARE, even if borderline, can improve short- and long-term graft survivals. From January 2002 to September 2006 we retrospectively evaluated 358 kidney transplant recipients. We performed a biopsy to evaluate the cause of DGF in all patients who required dialysis, or had serum creatinine levels that increased, remained unchanged, or decreased less than 10% per day on three consecutive days during the first week after transplantation. An ARE was found in 18.8% (n = 19) of the biopsies. Early biopsy for patients with DGF is a safe method that allows uncovering of an ARE that would otherwise be undetected. The immediate recognition and treatment of rejection episodes can certainly increase long-term survival and function of renal transplants.     

Characteristics of early routine renal allograft biopsies

The assumption that renal allograft histology should be perfectly normal during quiescence in the absence of rejection or nephrotoxic insults has not been adequately investigated. To study this, routine renal allograft biopsies were performed at approximately 1 and 4 weeks, when patients often had normal function or stable acute tubular necrosis (ATN). These were compared with biopsies from other patients during autologous ATN or clinically evident allograft rejection. There were two new findings: (1) Almost all biopsies contained an interstitial infiltrate, so that only the presence of vasculitis provided a clear distinction between rejection and quiescence. Most of the biopsies with infiltrates were from patients who had never received cyclosporine, so that an infiltrate does not necessarily signify toxicity due to this drug. (2) A major proportion of the cells in some biopsies appeared to express both the helper/inducer and the cytotoxic/suppressor phenotype, and a similar finding after in vitro stimulation suggests that this represents a cell population that is activated in some way.     

Donor risk score and baseline biopsy CADI value predict kidney graft outcome

Different donor parameters and baseline biopsy have been used to assess the quality of donor organs. There is, however, no consensus which risk factors and chronic changes in the donor kidney can be accepted for transplantation. The study included 481 deceased organ donors and their 829 kidney recipients transplanted during 1995-2005. The biopsies were re-evaluated according to the Banff 97 classification. The prognostic significance of donor risk factors and Chronic Allograft Damage Index (CADI) was analyzed. We propose a new donor risk score, calculated as the count of positive risk factors from a defined set of factors in the medical history of the donor. This donor risk score predicts histological quality of the kidney, graft function, and survival. Transplantations from donors with donor risk score >4 had significantly decreased graft survival compared to those with donor risk scores 0-4; the five-yr death-censored graft survivals were 83% vs. 93%, respectively. High donor CADI score (>3) was associated with worse graft function and survival. Three-yr glomerular filtration rate declined from 82 to 49 mL/min with donor CADI increase from 0 to ≥4. Our results show that high donor risk score and CADI value reflect low functional reserve and risk for poor graft outcome.