Significance of subclinical rejection in early renal allograft biopsies for chronic allograft dysfunction

To determine the significance of early subclinical rejection of renal allografts, we reviewed 127 biopsy specimens obtained soon after transplantation. Histological finding was categorized according to a modification of the Banff scheme as: acute rejection (AR), borderline changes (BL); non-specific inflammatory changes, (NI) and no rejection (NR). Subclinical rejection was defined as AR, BL or NI. Patients with BL or NI were divided into two groups; one was treated with high-dose methylprednisolone (MP), the other remained untreated. Freedom from chronic allograft dysfunction (defined as non-doubling of serum creatinine 5 yr after transplantation) was significantly more frequent in the NR group (89%) than in the BL (70%) and AR (64%) groups. At 1 yr after transplantation, mean serum creatinine had increased significantly only in the untreated group (p < 0.05), and re-biopsy showed that interstitial fibrosis had developed to a significantly greater extent in the untreated group than in the treated group (p < 0.01). Subclinical rejection in the early protocol biopsies correlated closely with subsequent allograft dysfunction. High-dose MP treatment for early subclinical rejection may be effective in suppressing the development of interstitial fibrosis at 1 yr after transplantation.     

Histological evaluation of renal allograft protocol biopsies in the early period and 1 year after transplantation

Abstract:  We histologically evaluated protocol biopsy specimens of renal allografts obtained in the early period and 1 year after transplantation. The patients were divided into those with at least one history of acute rejection (AR group) and no history of rejection (NAR group), and the histopathological features in the two groups were compared. A total of 45 early protocol biopsy specimens were obtained from 40 patients, and 31 1-year biopsy specimens were obtained from 30 patients. Acute rejection (AR) or borderline change was observed in the early protocol biopsy specimens from 19 (45.2%) cases. AR or borderline change was observed in 12 of 19 (63.2%) in the AR group, and in 7/26 cases (26.9%) in the NAR group. The incidence of AR or borderline change in the AR group was higher than in the NAR group. Toxic tubulopathy was found in the early protocol biopsy in 16 cases (35.6%). The 1-year biopsies tended to reveal more complicated findings. Chronic rejection (CR) was seen in 8/16 cases (50.0%) in the AR group, and it was more frequent than NAR group (two cases, 13.3%). In conclusion, the incidences of both AR and CR were higher in the cases with a previous episode of AR. The early protocol biopsy was useful in screening for subclinical AR and toxic tubulopathy. The 1-year biopsy was useful for evaluating various types of chronic graft damage. We expect that adequate treatment based on protocol biopsy findings in each patient will lead to better graft survival.     

Impact of immunosuppression on the incidence of early subclinical renal allograft rejection: implications for protocol biopsy policy

In order to determine the impact of immunosuppression (IS) on the incidence of early subclinical rejection (SCR), we studied two groups of patients receiving different immunosuppressive regimens. Patients received cyclosporin (CsA), azathioprine and prednisolone (group 1; n  = 304) or IS according to immunological risk (group 2; n  = 150). The highest-risk patients received basiliximab induction, tacrolimus, mycophenolate mofetil (MMF) and prednisolone; medium-risk patients CsA, MMF and prednisolone; low-risk CsA, azathioprine and prednisolone. Protocol biopsies were performed in all patients, irrespective of graft function, on days 7 and 28 post-transplantation. Only patients with good stable function at the time of biopsy were included for assessment of SCR. Group 2 patients showed significant reductions in total rejection frequency (32.6% vs. 57.2%, P  = <0.0001) and SCR frequency in day 7 protocol biopsies (2% vs. 13%, P  = <0.05). In group 2 patients, all SCRs, but not borderline changes, were treated. Untreated borderline changes did not have an adverse impact on graft function at 1 year post-transplantation. New immunosuppressive regimens may reduce subclinical in addition to clinical rejection-frequency, suggesting that the relative benefit of early protocol biopsies in detecting SCR is also reduced.     

Protocol biopsies in kidney transplant recipients: histologic findings as prognostic markers for graft function and outcome

The aim of the present study was to identify subclinical and borderline rejections as well as histological markers of chronic allograft nephropathy (CAN) among protocol biopsies performed at 1 and 6 months after living related kidney transplantation to assess their possible implications for graft function. Twenty paired allograft biopsies performed at 1 and 6 months were reviewed according to the Banff scoring scheme. The mean ages of donors and recipients were 59.6 +/- 13.8 and 34.4 +/- 8.7 years, respectively. Among all biopsies only 10% (4/40) showed no histopathological lesions. At the first month borderline rejection was shown in 35% and subclinical rejection in 10% of patients. At 6 months the proportion of findings was even higher, namely, 40% and 30%, respectively. When divided according to donor age, donors above 55 years showed a mean CAN score of 2.33 +/- 1.56 which increased to 5.0 +/- 2.26 on the 6 month biopsy (214.3%). Unexpectedly, the proportion of these changes in the younger donor group also increased by 173.3%, which might have been explained by the greater number of borderline and subclinical rejections in the younger donor group at the 1 month biopsy. In conclusion, 1 month biopsy may be valuable to determine borderline and subclinical rejection and to prognosticate the outcome of renal allograft function. Our findings suggest a greater susceptibility of histological deterioration among the older donor population. However, the presence of an untreated rejection in the younger donor pool leads to a rapid impairment of the graft function accelerating the process of chronic allograft nephropathy.     

Incidence, histological pattern, and clinical outcome of rejection episodes occurring in the late posttransplant period

We prospectively monitored clinical data and renal function at minimum monthly intervals in 220 patients who received kidney transplants at our institution between January 1, 1976 and December 31, 1982. All had functioning allografts for a year or longer. During a mean follow-up of 54.7 (14-96) months, 61 patients (28%) developed 74 late rejections, of which 23 (31%) were symptomatic and 51 (69%) were asymptomatic. Twenty-one rejections in 15 patients were diagnosed on clinical grounds (group A) and 53 rejections in 46 patients were diagnosed by renal histology (group B). Of this latter group, 26 biopsy specimens showed histological evidence of acute cellular rejection (ACR), 17 showed acute cellular rejection and chronic rejection (ACR + CR), and 10 showed chronic rejection (CR) only. Of the 26 ACRs, 10 (39%) responded fully to antirejection therapy, 14 (54%) responded partially, and 2 (7%) did not respond. Of the 17 ACR + CRs, the response to therapy was complete in 5 (29%), partial in 8 (47%), and none in 4 (24%). Of the 10 CRs, therapeutic response was none in 7 (70%) and partial in 3 (30%). During the period of our observation, 96% of patients with ACR had preservation of graft function (14% dead, 82% alive) and 4% had returned to dialysis. Among the patients with ACR + CR, 87% had preserved graft function (13% dead, 74% alive) and 13% returned to dialysis. Of the patients with CR, only 33% had preserved renal function (11% dead, 22% alive) and 67% returned to dialysis. Our observations indicate that (1) routine monitoring of renal function at minimum monthly intervals is essential to diagnose and treat these late rejections, which are often asymptomatic; (2) renal histology provides valuable diagnostic and prognostic information in the management of patients with late allograft rejection.     

Impact of banff borderline acute rejection among renal allograft recipients

OBJECTIVE: This study was performed to determine the incidence, treatment, and outcomes of Banff borderline acute rejection (AR) among renal transplant recipients. PATIENTS AND METHODS: We reviewed the courses of adult kidney transplant recipients with borderline AR on clinically indicated biopsies performed at our center from January 2003 to July 2006. Patients with complete transplant records and serum creatinine values at 6 and 12 months were included in this study. The primary outcome measures were serum creatinine values at 1 to 2 weeks after treatment, and at 6 and 12 months after graft biopsy. RESULTS: Among 428 renal graft biopsies, borderline AR was observed in 100 cases (23%). Patients were maintained on the same immunosuppression. The 86 who had complete data were included in the study. Seventy-eight percent of the patients received treatment with 3 days of methylprednisolone, while 22% were untreated. Mean serum creatinine values in the treated group were 2.9 +/- 1.0, 2.6 +/- 2.5, and 3.0 +/- 2.9 mg/dL at the time of biopsy, and at 6 and 12 months thereafter, respectively. In the untreated group, mean serum creatinine values were 2.2 +/- 1.0, 1.9 +/- 0.8, and 2.3 +/- 1.2 mg/dL during biopsy, and at 6 and 12 months thereafter, respectively. There was no significant difference in the serum creatinine at any of the measured time points between the 2 groups. Twelve patients had repeat renal graft biopsies which showed AR (6%), chronic allograft nephropathy (2.4%), and borderline changes (3.8%). Nine of the patients in the treated group eventually developed graft loss. CONCLUSIONS: Patients with borderline AR showed a progressive increase in serum creatinine over time. They should be followed closely; immunosuppression may need to be intensified.     

Activation of nuclear factor-kappa B and macrophage invasion in cyclosporin A-and tacrolimus-treated renal transplants

This retrospective study was designed to compare the efficacy of cyclosporin A (CyA) and tacrolimus (FK506) on chronic rejection (CR) associated with nuclear factor-kappa B (NF-kappaB) activation and macrophage invasion. Non-episodic day 50 protocol renal biopsy was performed in 63 consecutive patients with renal transplants from living donors, treated with either CyA or FK506. Southwestern histochemistry for NF-kappaB, immunostaining for CD68, and Banff classification were performed, and these findings were compared with outcome over 34 +/- 13 months. Compared with specimens from FK506-treated patients (n = 20), specimens from CyA-treated patients (n = 43) showed a significant increase in tubulointerstitial CD68-positive cells (1.5 +/- 0.9 vs. 0.9 +/- 0.8, p < 0.01), although no significant differences were observed in NF-kappaB activation. Specimens with Banff acute rejection (AR) grade > or = 1A (n = 20) showed increased macrophages (p < 0.01) compared with specimens with AR < 1A (n = 43). Specimens from patients with clinical AR prior to day 50 biopsy (n = 23) also showed increased macrophage invasion (p < 0.01) compared with specimens from patients without prior clinical AR (n = 40). The cumulative well-functioning (serum creatinine < 1.5 mg/dL) graft survival rate was significantly lower in patients with increased tubulointerstitial CD68-positive cells (n = 63, p < 0.05). Our findings suggest that tacrolimus is more effective than CyA against CR with respect to macrophage invasion and AR.     

移植肾的病理类型与肾功能及预后的关系——单中心十年经验回顾分析

目的 分析肾移植受者移植肾的病理类型和特征,及其与肾功能和预后的关系.方法 肾移植术后230例受者接受了移植肾穿刺病理活检,分析其病理表现类型和特征,比较不同病理类型和特征受者移植肾穿刺活检时的血肌酐(SCr)水平,随访受者穿刺活检后1年的移植肾功能情况,评价不同病理特征受者的预后.结果 移植术后3个月时接受了程序性肾活检的10例受者中,9例为正常肾组织,1例为移植后IgA肾病.有肾功能损害临床表现的220例受者中,病理表现为交界性改变33例,急性排斥反应(AR)45例,慢性排斥反应(CR)24例,慢性移植肾肾病(CAN)26例,移植后肾炎(PTGN)39例,以上共167例;另外,28例同时有前面两种或两种以上的病理类型表现,还有CNI肾毒性反应8例,BK病毒肾病7例,急性肾小管坏死5例.有5例受者因采集的移植肾组织过少而不能明确诊断.病理诊断为交界性改变、AR、CR、CAN和PTGN的受者,其穿刺活检时的SCr水平分别为(171±17)、(259±25)、(343±33)、(406±67)和(207±26)μmol/L,不同病理类型者的SCr水平两两比较,差异均有统计学意义(P＜0.01).穿刺活检后1年,随访到上述5种病理类型167例受者中的134例(80.2%),其中交界性改变23例、AR 36例、CR 20例、CAN 18例及PTGN37例,分别有1例(3.1%)、8例(18.2%)、8例(22.2%)、6例(33.3%)、5例(13.5%)发生移植肾功能丧失.穿刺活检后1年,上述5种病理类型移植肾功能异常受者的SCr水平与穿刺时SCr水平的差值(△SCr)分别为(-47±20.7)、(-37.3±36.9)、(25.5±24.3)、(13.5±27.7)和(25.2±17.1)μmol/L.结论 移植肾的病理改变复杂多样,结合移植肾穿刺病理活检结果和临床分析进行准确诊断,可以帮助临床选择合适的治疗方案,促进移植肾的长期存活.     

Clinical Significance of an Early Protocol Biopsy in Living-Donor Renal Transplantation: Ten-Year Experience at a Single Center

We report here our 10-year experience of a biopsy performed at day 14 after transplantation in 304 patients with stable graft function. The factors that may have influenced subclinical rejection were analyzed according to histology. The incidence of subclinical rejection was 13.2%. Addition of mycophenolate mofetile (MMF) as a primary immunosuppressant significantly decreased the incidence of subclinical rejection compared with patients without such treatment (odds ratio, 0.23; p < 0.05). On the other hand, HLA-DR antigen mismatch (odds ratio, 2.39) and unrelated donor (odds ratio, 2.10) were also significantly associated with decreased subclinical rejection (p < 0.05). The incidence of acute rejection in patients with normal findings was lower than in those with borderline changes or subclinical rejection (0.23 +/- 0.05 vs. 0.48 +/- 0.07 and 0.60 +/- 0.11, respectively; p < 0.05). The graft survival rates in patients with subclinical rejection were lower than in patients with normal or borderline changes at 1 (88.4% vs. 97.9% and 99.1%; p < 0.05), 5 (77.8% vs. 96.2% and 95.9%; p < 0.05) and 10 (62.3% vs. 96.2% and 93.7%; p < 0.05) years. Thus, a protocol biopsy performed on day 14 after transplantation is useful for predicting graft survival. Triple therapy including MMF, related donor and HLA-DR antigen match are important factors for reducing subclinical rejection in living-donor renal transplantation.     

Effect of increasing baseline immunosuppression on the prevalence of clinical and subclinical rejection: a pilot study.

This group has reported that treatment of subclinical rejection in the first 3 mo posttransplant with corticosteroids decreases late clinical rejections and improves graft function at 2 yr in renal transplant recipients. The current study was performed to determine whether an increase in baseline immunosuppression would decrease the prevalence of early subclinical rejections, as well as the incidence of early and late clinical rejections. Patients received mycophenolate mofetil (MMF) and Neoral cyclosporin A (CsA) posttransplant (n = 29), of which 17 underwent protocol biopsies at months 1, 2, 3, and 6 (Neoral + MMF Protocol Biopsy [Bx]), while 12 declined protocol biopsies (Neoral + MMF Control). These individuals were compared with 72 historical control patients treated with Sandimmune CsA and Imuran, of which 36 had undergone protocol biopsies at months 1, 2, 3, and 6 (Sandimmune + Azathioprine [AZA] Protocol Bx), and 36 had a protocol biopsy at month 6 (Sandimmune + AZA Control). Baseline immunosuppression with Neoral + MMF decreased the incidence of early clinical rejections (0 to 3 mo) and cumulative corticosteroid exposure, but had no impact on the prevalence of early subclinical rejection. Moreover, to maximally decrease the risk of developing late clinical rejections (months 7 to 12) in Neoral + MMF patients required that protocol biopsies be done and that subclinical rejection be treated. The paradoxical finding of recent clinical trials that a reduction in acute clinical rejection has not improved long-term graft outcome may be explained in part by the failure to control subclinical rejection.     

Randomized prospective trial of early steroid withdrawal compared with low-dose steroids in renal transplant recipients using serial protocol biopsies to assess efficacy and safety

BACKGROUND: Corticosteroid therapy after renal transplantation is associated with many adverse effects. Newer immunosuppressive agents may allow for safe and effective reductions in dose or early steroid withdrawal. METHODS: In this prospective, single-center clinical trial, 60 patients were randomized into 2 groups: control patients (n = 28), who received low doses of prednisone throughout, and study patients (n = 32), who were withdrawn from steroids 7 days posttransplant. Patients received a limited course of rabbit antilymphocyte globulin (rALG) induction therapy, tacrolimus (TAC), and mycophenolate mofetil (MMF). Patients were followed for clinical outcomes and renal function. Protocol biopsies were performed at 1, 6, and 12 months. RESULTS: Clinical rejections occurred in 11% of controls and 13% of study patients. Renal function was well maintained and equivalent in both groups. In all, 111 protocol biopsies were performed without complications. Subclinical rejection was noted in only 2 protocol biopsies, and borderline changes were seen in 12 biopsies, all of which were distributed equally between both groups. Unsuspected acute TAC toxicity was seen in 8 biopsies. Protocol biopsies led to changes in therapy in 10% of patients. In both groups, serial protocol biopsies demonstrated increased allograft fibrosis over time, which was significant at 1 year in the steroid withdrawal group. CONCLUSION: The immunosuppressive combination of rALG, TAC, and MMF prevents subclinical rejection and the need for high doses of steroids after transplantation. However, continual low-dose steroid therapy may aid in preventing chronic allograft fibrosis. Protocol biopsies help define the short-term and long-term risks of steroid withdrawal therapy.     

IL-17 expression as a possible predictive parameter for subclinical renal allograft rejection

In the present study we have tried to establish the role of IL-17 in subclinical renal allograft rejection. In this animal model, renal grafts from BN (RT1n) were transplanted heterotopically into LEW (RT1l) rats. As controls, LEW grafts were transplanted into LEW rats. The histopathological examination demonstrated that the changes in the allograft kidney on day 2 were similar to those ranked as borderline changes according to the Banff classification scale. On day 2, the serum level of blood urea nitrogen (BUN) and creatinine were the same as on day 1. The examination of allograft cytokines mRNA showed that IL-17 mRNA expressed earlier on the second postoperative day, peaked at day 5, and then declined, becoming almost undetectable at day 9, when most rats died. IL-17 antigen was also proven, by histochemical staining, to be expressed early, however we could not find the same early appearance on other Th1/Th2 cytokines. In human renal biopsy samples, the IL-17 antigen could be found scattered around in the borderline changed rejected renal allografts without evidence of a serum creatinine increase, but was undetectable both in normal controls and in renal transplant tissue without signs of rejection. IL-17 mRNA was detected in the mononuclear cells of the urinary sediment of patients suffering from borderline subclinical rejection. From the above results we can hypothesize that IL-17 could serve as a predictive parameter for borderline subclinical renal allograft rejection in the future.     

The significance of parenchymal changes of acute cellular rejection in predicting chronic liver graft rejection

BACKGROUND: Chronic rejection (CR) in liver allografts shows a rapid onset and progressive course, leading to graft failure within the first year after transplantation. Most cases are preceded by episodes of acute cellular rejection (AR), but histological features predictive for the transition toward CR are not well documented. METHODS: We assessed the predictive value of centrilobular necrosis, central vein endothelialitis (CVE), central vein fibrosis, and lobular inflammation in the development of CR. One-week and one-month biopsy specimens of 12 patients with CR were compared with those of a control group consisting of 17 patients, who experienced AR without developing CR. The progress of the histological changes was further evaluated in follow-up biopsy specimens of the CR group taken at 2 months and beyond 3 months after transplantation. RESULTS: Centrilobular necrosis, CVE, central vein fibrosis, and lobular inflammation were common features in both groups at 1 week. At 1 month, the incidence declined in the control group. The CR group showed an increased incidence and persistence of these features in the follow-up biopsy specimens. The incidence and median grade of severity of CVE was significantly higher in the CR group (P=0.04 and P<0.001). The severity of portal and lobular inflammation was also more pronounced in the CR group (P=0.01 and 0.068). Conversely, in the control group, the incidence of the lobular features decreased and the severity of CVE declined significantly (P=0.03). CONCLUSION: The shift from a predominantly portal-based process toward lobular graft damage represents the early transition of AR to CR, for which a modification of immunosuppression might be necessary to prevent graft loss.     

Protocol biopsies in pediatric renal transplant recipients on cyclosporine versus tacrolimus-based immunosuppression

Background

Protocol biopsies can detect subclinical rejection and early signs of calcineurin inhibitor-induced nephrotoxicity.

Methods

In a prospective study, protocol biopsies 3 and 12 months after transplant in transplanted children from two centers were studied. One center used cyclosporine (CsA)-based immunosuppression and the other center used tacrolimus. Patients were on CsA (n?=?26, group 1) or on tacrolimus (n?=?10, group 2). Patients received basiliximab induction, mycophenolate mofetil, and prednisone.

Results

In patients on CsA, 26 kidney biopsies were performed during the 6 months after transplantation. Eighteen protocol biopsies were performed at 3 months post transplant; 13 were normal and five showed rejection (two borderline and three Banff II rejections). Eight biopsies were motivated by an increase of serum creatinine; four were normal and four revealed signs of acute rejection (two borderline and two Banff II). Twelve protocol biopsies were performed after 12 months; all were normal. For patients on tacrolimus (n?=?10), ten protocol transplant biopsies were performed at 3 months post-transplant; none showed signs of rejection. No biopsy was performed for an increase of serum creatinine. There were no differences in patient age, number of human leukocyteantigen (HLA) incompatibilities, or other patient characteristics.

Conclusions

Patients on tacrolimus had less acute rejection episodes detected on protocol biopsies 3 months after transplant. Protocol biopsies seem to play an important role in the detection of subclinical rejection in patients on CsA.     

Can early liver biopsies predict long-term outcome of the graft?

Background: Chronic rejection (CR) in liver allografts show a rapid onset and progressive course, leading to graft failure within the first year after transplantation. Most cases are preceded by episodes of acute cellular rejection (AR), but histological features predictive for the transition toward CR are not well documented. Method: We assessed the predictive value of centrilobular necrosis, central vein endothelialitis (CVE), central vein fibrosis, and lobular inflammation in the development of CR. One-week and one-month biopsy specimens of 12 patients with CR were compared with those of a control group consisting of 17 patients, who experienced AR without developing CR. The progress of the histological changes was further evaluated in follow-up biopsy specimens of the CR group taken at 2 months and beyond 3 months after transplantation. Result: Centrilobular necrosis, CVE, central vein fibrosis, and lobular inflammation were common features in both groups at 1 week. At 1 month, the incidence declined in the control group. The CR group showed an increased incidence and persistence of these features in the follow-up specimens. The incidence and median grade of severity of CVE was significantly higher in the CR group (p=0.04, and P<0.001). The severity of portal and lobular inflammation was also more pronounced in the CR group (P+0.01 and 0.069). Conversely, in the control group the incidence of the lobular features decreased and the severity of CVE declined significantly (P=0.03). Conclusion: The shift from a predominantly portal-based process toward lobular graft damage represents the early transition of AR to CR, for which a modification of immunosuppression might be necessary to prevent graft loss.     

Clinical and Histopathologic Examination of Renal Allografts Treated with Tacrolimus (FK506) for at Least One Year

Background : We clinically and pathologically analyzed renal allografts from 19 renal transplant patients treated with tacrolimus (FK506) for more than 1 year.
Methods : Twenty-six renal allograft biopsy specimens from 19 renal transplant patients who underwent transplantations between 1991 and 1 993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy).
Results : The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR;n = 5), AR + CR(n=4), recurrent IgA nephropathy (n = 5), normal findings (n = 2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angio-degeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P < 0.001).
Conclusions : This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.     

The presence and prognostic importance of glomerular macrophage infiltration in renal allografts

AIM: The purpose of this study was to analyze the role of intraglomerular macrophage infiltration in human renal allografts by examining biopsies from kidney grafts that were dysfunctional after transplantation. METHODS: Eighty-three patients (58 men, 25 women) of a mean age of 30.2 +/- 1.4 years were evaluated. In all cases, biopsy specimens were examined for the presence of macrophage infiltration in the glomeruli. The infiltration of these cells was evaluated immunohistochemically using monoclonal antibody CD68, which labels macrophage cytoplasm. 10 renal allograft biopsies with normal histopathology were used as control group. The CD68-positive macrophages in all glomeruli were counted and the glomerular macrophage index (GMI) was calculated. RESULTS: Of the 83 patients, 40 showed acute rejection (AR), 33 showed chronic rejection (CR) and 10 showed cyclosporin A (CsA) toxicity. Only the biopsies of 28 patients stained positive for CD68 in the glomeruli. Neither patients with CsA toxicity nor controls showed intraglomerular macrophages. The CD68-positive group consisted of 7/33 CR and 21/40 AR patients. We observed intraglomerular macrophages in only 6 of the 20 AR cases that responded to steroid therapy (mean GMI 0.3 +/- 0.1) and in 15 of the 20 steroid-resistant AR cases (mean GMI 1.7 +/- 1.2; p < 0.01). The outcome of grafts that contained intraglomerular macrophages was significantly worse than the outcomes of other grafts noticed during the follow-up. CONCLUSION: We conclude that the presence of glomerular macrophages can be considered a marker for rejection and is a valuable additional criterion of rejection in the histological examination of renal allograft biopsies. The presence of intraglomerular macrophages indicates that the outcome of the graft will be significantly worse than that of grafts without intraglomerular macrophage infiltration.     

Clinical significance of protocol biopsy at one month posttransplantation in deceased-donor renal transplantation

BACKGROUND: Protocol biopsy was used to detect pathologic changes in recipients with stable allograft function. With our 5-year practice, we reviewed protocol biopsies performed at 1 month posttransplantation in Chinese renal transplantation to analyze the impact of pathologic changes on allograft survival and to evaluate the clinical significance of protocol biopsy. METHODS: 227 patients who received biopsy at 1 month posttransplantation during Aug 2000 to Feb 2005 with stable graft function were enrolled. Patients were divided into normal group (NM), borderline change group (BL) and subclinical rejection group (SCR) based on pathology in protocol biopsy. Their clinical data were all reviewed. RESULTS: In the 227 patients with stable graft function, there were 173 patients (76.2%), 37 patients (16.3%) and 17 patients (7.5%) in the NM, BL, SCR group respectively. The incidence of acute rejection in the following period was significantly higher in the BL and SCR groups than that in the NM group (21.6%, 29.4% vs 7.5%, P<0.01). There was a significant difference of graft survival between the BL, SCR group and NM group (P<0.01). CONCLUSIONS: Borderline changes and subclinical rejection detected in protocol biopsy were associated with poor allograft survival. Protocol biopsy performed at 1 month posttransplantation is of great significance and can predict graft survival.     

Clonality analysis of T cells mediating acute and chronic rejection in kidney allografts

The clonality of T-cell populations mediating acute and chronic rejection (AR and CR, respectively) of kidney allografts was ascertained by investigating the diversity of TCRBV genes expressed by allograft-infiltrating T cells. Both oligoclonality and polyclonality cases were found in biopsy specimens of AR as well as CR. These results indicated that the T-cell clonality in each specimen did not correlate directly with the mode of rejection. When AR and CR specimens were compared, however, the CR specimen group was significantly more polyclonal (or less oligoclonal) than the AR group. This result may reflect the higher chance of epitope spreading in the more slowly progressing CR than in AR.     

Study of Liver Transplant Rejection in Alcoholism-Induced Cirrhosis

Rejection is the most usual cause of primary dysfunction of hepatic allograft transplants. Acute rejection (AR) often occurs in the early post-transplantation weeks, with an incidence of 12%–19%. Chronic rejection (CR) is less usual (2.5%–17%) and irreversible. Our aim was to determine the incidence of AR and CR in patients who underwent transplantaton due to alcoholism-induced cirrhosis and the survival of these groups. We undertook a retrospective study of the 93 patients who received a liver transplant due to hepatic cirrhosis between 2005 and 2012. AR occurred in 23.7% of cases, and CR in 11.8%. The median time from implantation to the appearance of AR was 34.5 days, and for CR it was 334 days. The survival of the patients with AR and CR showed no significant differences as compared with the control group (P = .77). From our clinical appraisal, symptoms of previous AR may lead to CR, although the relationship was not significant.