Rescue therapy by immunoadsorption in combination with tacrolimus and mycophenolate mofetil for C4d-positive acute humoral renal allograft rejection

The aim of this study was to investigate the efficacy of immunoadsorption (IA) in combination with tacrolimus (TAC; 0.14 to 0.16 mg/kg/d) and mycophenolate mofetil (MMF; 1.5 to 2.0 g/d) rescue therapy for C4d-positive acute humoral rejection in nine cadaveric renal allograft recipients. Initial Panel reactive antibody (PRA-I and PRA-II levels were as high as 28.8% ± 16.2% and 15.3% ± 8.9%, IA therapy significantly decreased PRA-I and PRA-II levels to 5.9% ± 2.9% and 2.2% ± 0.6%, respectively. Total serum immunoglobulin levels were markedly decreased. Repeated allograft renal biopsy in nine patients revealed remission of acute humoral rejection (AHR), and the deposition of C4d disappeared and reduced. With a mean follow-up of 29.4 ± 5.4 months, patient and allograft survivals were 100%, and renal function remained stable with a mean serum creatinine of 1.1 ± 0.3 mg/dL. Our findings suggested that a therapeutic approach combining IA and TAC and MMF rescue improved the outcomes of AHR.     

C4d-positive acute humoral renal allograft rejection: rescue therapy by immunoadsorption in combination with tacrolimus and mycophenolate mofetil

OBJECTIVE: We investigated the efficacy of immunoadsorption (IA) in combination with tacrolimus (FK506) and mycophenolate mofetil (MMF) rescue therapy for C4d-positive acute humoral rejection (AHR) of renal transplants. METHODS: Six of 185 cadaveric renal allograft recipients developed AHR at a mean of 4.8 +/- 0.8 days after the operation. C4d deposits were observed in peritubular capillaries (PTC) with accumulation of granulocytes. IA with staphylococcal protein A and FK506-MMF combination therapy were administered. RESULTS: After treatment with IA for 6.3 +/- 1.03 sessions combined with FK506 (0.14 to 0.16 mg.kg(-1).d(-1)) and MMF (1.5 g/d) therapy, renal function recovered in all the patients. The mean duration of treatment to a serum creatinine decrease was 14 +/- 2.9 days. The pre-IA panel reactive antibody reactivity (PRA) peaked at 50.2% +/- 6.1%, and was significantly reduced to 8.3% +/- 2.9% after IA. In four of six patients repeat allograft biopsy revealed a remission of AHR. With a mean follow-up of 18.8 +/- 5.46 months, patient and allograft survival are 100% and renal function remains stable with a mean serum creatinine of 1.2 +/- 0.22 mg/dL. CONCLUSION: The optimal treatment for alloantibody-mediated AHR remains uncertain. Our findings suggest that a therapeutic approach combining IA and FK506-MMF rescue improves the outcome of AHR.     

Tacrolimus combined with mycophenolate mofetil can effectively reverse C4d-positive steroid-resistant acute rejection in Chinese renal allograft recipients.

BACKGROUND: Tacrolimus (TAC) combined with mycophenolate mofetil (MMF) has been suggested to play a critical role in the reversal of C4d-positive acute humoral rejection (AHR) in renal transplantation, but the efficacy of using only TAC-MMF without immunoadsorption or plasmapheresis has not been investigated. On the other hand, Chinese recipients of renal grafts usually need lower doses of immunosuppressants, and their optimal treatment for acute humoral rejection has not been established. METHODS: Since 1999, we have used TAC-MMF to treat steroid-resistant acute rejection (AR). C4d staining was retrospectively performed in 32 patients with steroid-resistant AR, and the treatments of 19 patients with C4d-positive steroid-resistant AR were investigated. RESULTS: Thirteen of 19 patients received TAC-MMF treatment only; 11 episodes of rejection in them were reversed (7 completely, 4 partially) and only 2 recipients lost their graft. Another 6 patients received immunoadsorption also. One of them failed to respond and lost her graft. Four of 5 patients treated with immunoadsorption and TAC-MMF recovered (3 completely, 1 partially), but 3 of them had severe pneumonia, a complication rate statistically higher than in patients treated with only TAC-MMF (P<0.05). AR occurring during the first two weeks after transplantation had a statistically better outcome than that occurring later (P = 0.003). CONCLUSION: Our study suggests that the combination of TAC and MMF is a potentially safe and economic treatment for most Chinese renal allograft recipients with C4d-positive steroid-resistant AR, especially for rejections developing within the first two weeks after transplantation.     

Novel rescue therapy for C4d-positive acute humoral renal allograft rejection

OBJECTIVE: To investigate the efficacy of immunoadsorption (IA) in combination with tacrolimus (TAC) and mycophenolate mofetil (MMF) rescue therapy for C4d-positive acute humoral rejection (AHR) of renal transplants. METHODOLOGY: Six of 185 cadaveric renal allograft recipients transplanted at our institute developed AHR over a mean period of 4.8 +/- 0.8 d after operation. The ages ranged from 35 to 51 yr (mean 42.6 +/- 5.6 yr). C4d deposits in peritubular capillaries (PTC) and accumulation of granulocytes in PTC were observed. IA with staphylococcal protein A and TAC-MMF combination therapy were given. RESULTS: After subjected to IA for 6.3 +/- 1.03 sessions combined with TAC (0.14-0.16 mg/kg/d) and MMF (1.5 g/d) therapy, renal function recovered in all the patients. The mean duration of treatment when serum creatinine decreased was 14 +/- 2.9 d. The pre-IA panel reactive antibody reactivity was as high as 50.2 +/- 6.1%, and was significantly reduced to 8.3 +/- 2.9% after IA. Repeated allograft kidney biopsy in four of six patients revealed a favorable remission of AHR. With a mean follow-up of 18.8 +/- 5.46 months, patient and allograft survival are 100%, renal function remained stable with a mean serum creatinine of 1.2 +/- 0.22 mg/dL. CONCLUSION: The optimal treatment for alloantibody-mediated AHR remains undefined. Our findings suggest that a therapeutic approach combining IA and TAC-MMF rescue has excellence to improve the outcome of AHR.     

A case of acute vascular rejection after overseas deceased kidney transplantation

Abstract:  A 54-yr-old Japanese male received overseas deceased kidney transplantation in January 2006. His allograft functioned immediately and he received immunosuppression with cyclosporine A (CyA), mycophenolate mofetil (MMF), and prednisone (PR). On day 24 after transplantation, he came back to Japan. His serum creatinine level (s-Cr) was 1.39 mg/dL at two months after transplantation when he was admitted into Toda Central General Hospital on March 2006, for follow-up his renal allograft. He had taken only two immunosuppressive drugs, MMF and PR, and had not taken CyA at that time. His serum creatinine gradually rose after hospitalization. Allograft biopsy performed on April 6, 2006, showed acute vascular rejection (Banff 97 acute/active cellular rejection Grade III), together with suspicious for acute humoral rejection (Banff 97 antibody-mediated rejection Grade II). After treatment of two courses of steroid pulses and five d of gusperimus, acute vascular rejection and acute humoral rejection were relieved, which had been proven by the third allograft biopsy. In conclusion, this was a case of acute vascular rejection after overseas deceased kidney transplantation, resulted from non-compliance with immunosuppressive therapy.     

Treatment of early mixed cellular and humoral renal allograft rejection with tacrolimus and mycophenolate mofetil

This prospective study investigated the efficiency of the tacrolimus (Tac) combined with mycophenolate mofetil (MMF) alone without immunoadsorption (IA) or plasmapheresis (PPH) as treatment for early (within 2 weeks) acute humoral rejection (AHR) in non-sensitized renal allograft recipients. Of 160 patients enrolled in this prospective study, 11 patients had histologically and clinically confirmed early steroid-resistant acute rejection with an antibody response and received Tac-MMF therapy. No other aggressive rescue methods such as IA, PPH were used, according to the study design. Patients (n=11) were followed for 13.8+/-3.5 months; nine were females. The complement-dependent cytotoxicity crossmatch was negative before transplantation in all patients and only positive for panel-reactive antibody in one patient. Most of the rejection episodes were mixed with cellular rejection (four patients met Banff IIA criteria, five patients met Banff IIB, one patient met Banff IB, and one patient met Banff borderline). After 16.19+/-6.16 days of treatment, all rejection episodes were successfully reversed and all graft functions were stable, with a mean serum creatinine level of 1.12+/-0.32 mg/dl during follow-up. No patient suffered from severe infectious complications (except one case of urinary infection). Our investigation suggests that Tac combined with MMF alone is adequate to reverse early mixed cellular and humoral C4d-positive rejection in non-sensitized renal allograft recipients.     

Clearance of C4d deposition after successful treatment of acute humoral rejection in follow-up biopsies: a report of three cases

Acute humoral rejection (AHR) is currently perceived as an immunological reaction against donor antigens mediated by complement-binding antibodies. C4d, a split product of complement activation and bound to endothelial cells of the peritubular capillaries, is used as a diagnostic marker for AHR. We report on three patients with biopsy-proven acute humoral rejection who were treated initially with plasmapheresis (PS). As two of the patients did not recover renal function, and biopsy showed persistent C4d staining after PS, immunoadsorption (IAS) was additionally performed on them. In all patients, renal function recovered, and follow-up biopsies in two patients showed complete disappearance of C4d, 29 days and 58 days after transplantation and only minimal residual C4d deposits in one patient 48 days after transplantation. We conclude that successful treatment of AHR is followed by complete resolution of serological and histological markers of AHR, displayed by the disappearance of C4d.     

Randomised open clinical trial of conversion from mycophenolate mofetil to azathioprine in cadaveric renal transplantation

Abstract Mycophenolate mofetil (MMF) is a powerful immunosuppressive drug with established efficacy and safety. The search for a less expensive immunosuppressive protocol has led to an open randomised clinical trial of conversion from MMF to azathioprine (Aza). A total of 28 renal allograft recipients treated with prednisone, cyclosporine, and MMF was randomised into two groups: converted (early conversion) and control (late conversion). Conversion from MMF to Aza was conducted at the end of the 4th post‐transplant month in the converted group and after the 12th month in the control. During the 20‐month observation period, biopsy‐proven acute rejection occurred more frequently in the converted than in the control group, although the difference was not statistically significant. Early conversion from MMF to Aza increased the risk of subsequent rejection in those patients who underwent at least one episode of acute rejection prior to conversion.     

Treatment of C4d-positive acute humoral rejection with plasmapheresis and rabbit polyclonal antithymocyte globulin

BACKGROUND: Alloantibody-mediated acute rejection is a major cause of renal allograft loss despite aggressive therapy. Patients with humoral rejection can be identified with high sensitivity and specificity by the presence of peritubular capillary C4d staining on renal biopsy and donor-specific anti-human leukocyte antigen antibodies. Standard therapy for acute humoral rejection (AHR) has been removal of donor-specific antibodies by plasmapheresis (PPH) in conjunction with intravenous immunoglobulin therapy. We describe a series of seven patients with C4d positive AHR who received combined therapy with PPH and polyclonal rabbit antithymocyte globulin (rATG). METHODS: PPH (1.4 volume exchange) was initiated on diagnosis of AHR on an alternate day basis for a mean number of 6.8 treatments, in conjunction with rATG (0.75 mg/kg/day 5-10 days) until the serum creatinine returned to 120% of nadir. RESULTS: The nadir posttreatment creatinine was significantly lower than pretreatment creatinine (1.0+/-1.2 vs. 2+/-1.4, P <0.007) with only one episode of graft loss. On follow-up there was no difference in renal allograft survival between the AHR group and the 60 patients without AHR who underwent transplantation during the same period. We describe the ability of rATG to induce apoptosis in vitro peripheral blood and activated B cells. CONCLUSION: Combination therapy using PPH and rATG is an effective means of reversing AHR in renal allografts.     

Assessment of the risk of chronic allograft dysfunction after renal transplantation in a randomized cyclosporine withdrawal trial

BACKGROUND: We report the two-year follow-up of a trial comparing the three-month postgraft discontinuation of either cyclosporine (CsA) or mycophenolate mofetil (MMF) from a triple-drug regimen after de novo renal transplantation. METHODS: One hundred and eight patients were enrolled in this study and randomized to be withdrawn from CsA (MMF group, n=54) or MMF (CsA group, n=54). RESULTS: Despite an increased risk of acute rejection and a lower, but nonsignificant, two-year graft survival, CsA withdrawal induced a sustained improvement of the renal function. At one year, the chronic allograft damage index was similar in both the MMF and CsA groups. However, CsA elimination resulted in a higher incidence of C4d deposits, irrespective of the occurrence of a prior acute rejection. While this finding could suggest a risk of chronic rejection in the MMF group, the outcome did not appear to be related to the C4d status. Moreover, logistic regression analysis showed that only two factors, acute rejection and the one-year glomerular filtration rate level, were predictive of a significant decline of the renal function at two years. CONCLUSIONS: These results point out the need to secure the minimization of the calcineurin inhibitors after renal transplantation, in order to reduce the risk of acute rejection in these patients, because this strategy allows the improvement of the one-year renal function which is predictive of a chronic allograft dysfunction.     

A case of allograft dysfunction with antibody-mediated rejection developing 13 yr after kidney transplantation

Abstract:  Antibody-mediated rejection is an important cause of chronic allograft dysfunction. We report a case of chronic antibody-mediated rejection 13 yr after transplantation. This patient is a 19-yr-old man who had renal insufficiency since infancy because of bilateral polycystic kidneys. Peritoneal dialysis was started when he was four yr old and he received a renal allograft from his mother at the age of six yr. Donor and recipient were ABO compatible and immunosuppressive treatment was started with cyclosporine, mizoribine, and methylprednisolone. No acute rejection was experienced and histological acute rejection was not proven on any subsequent protocol biopsies. Ten yr after transplantation, a protocol biopsy revealed moderate chronic allograft nephropathy and severe cyclosporine-associated arteriolopathy. His allograft function was preserved at this time and the cyclosporine dose was tapered to 125 mg/d. His renal function gradually deteriorated starting 12 yr after transplantation. Although mizoribine was changed to mycophenolate mofetil, he required dialysis one yr later. A diagnosis of antibody-mediated rejection was made based upon the renal biopsy findings (including C4d staining) and circulating anti-human leukocyte antigen (HLA) antibody levels (12 yr after transplantation). We conclude that it is necessary to pay attention to antibody-mediated rejection, even in allograft cases with good function for over 10 yr and no risk factors for the development of de novo anti-HLA antibodies.     

Peritubular capillary C4d staining in late acute renal allograft rejection – is it relevant?

Abstract: Background: In the early post-transplant period, renal allograft rejection with diffuse peritubular capillary (PTC) C4d deposition predicts poor graft survival. In the late post-transplant setting, that is, one or more yr after transplantation, the implication of diffuse PTC C4d deposition is still a topic of debate. The purpose of our study was to see if diffuse PTC C4d deposition, in late acute rejection (LAR), occurring more than one yr post-transplant, has any impact on graft survival and function. Methods: We selected cases, both cadaveric as well as living donor renal transplant recipients, in whom acute rejection with PTC C4d deposition was first detected after the first year post-transplant. Recipients with multiple acute rejection episodes during the first year post-transplant were excluded from the study. The first biopsy diagnosed with LAR was considered the index biopsy (n = 40). We formed two groups: group 1, C4d-positive LAR (n = 20), and group 2, C4d-negative LAR (n = 20). Groups were matched for maintenance and post-rejection immunosuppressive therapy, baseline serum creatinine levels before the time of the index biopsy, time from transplant to index biopsy, as well as chronic allograft damage index (CADI) score in the index biopsies. We compared the rate of graft loss, and the graft function of the surviving grafts at the end of the study period, as well as histologic parameters in the index biopsy specimens between the two groups. The mean follow-up period was 20 months. Results: No significant differences in the rate of graft loss or graft function were found between groups 1 and 2 at the end of the follow-up period. Histologically, PTC margination and transplant glomerulopathy were more common in the C4d-positive group, and this difference was statistically significant. There was no statistically significant difference in the degree of plasma cell infiltrates. Conclusions: Unlike in the acute setting, the presence or absence of PTC C4d staining in renal allografts with LAR may not have a predictive value regarding graft outcome.     

Histological analysis of late renal allografts of antidonor antibody positive patients with C4d deposits in peritubular capillaries

Abstract:  The association of humoral immunity with late renal allograft dysfunction has recently been recognized, and many reports have revealed C4d deposits in peritubular capillaries (C4d in PTC), and the presence of serum antidonor HLA antibody in patients suffering from graft dysfunction, long time after transplantation. In this study, morphological changes in renal allograft biopsies more than 1 year after transplantation in 14 patients with C4d in PTC and serum antidonor antibody were investigated for the presence of chronic rejection (CR). In addition to the light microscope study, an electron microscope study was done to evaluate the multilayering of the peritubular capillary basement membrane (MLPTC). Histologically, only seven of 14 patients met the criteria of CR, and 71.4% (5/7) of CR patients had episodes of acute humoral rejection (AHR), coexisting with acute tubulointerstitial rejection. Peritubular capillaritis was observed in all patients, although it differed in severity. Transplant glomerulitis and interstitial inflammation were also observed in many patients: 71.4% (10/14) and 92.9% (13/14) respectively. MLPTC was observed in 12 patients (85.7%), but the severity of the MLPTC did not reflect the severity of peritubular capillaritis or any other histological features. The long-term outcomes of the patients CR, especially those with episodes of AHR, were poor, and two of them lost their graft functions. On the other hand, patients without CR had relatively favourable outcomes. In conclusion, we confirmed the diverse morphological changes of late renal allografts, which cannot be categorized as chronic humoral rejection (CHR), and such patients who do not have typical morphological changes such as CHR, should be followed-up on a long-term basis in order to clarify the significance of C4d on PTC in late renal allografts.     

移植肝内C4d沉积在肝移植急性和慢性排斥反应诊断和治疗中的意义

目的 观察移植肝组织中补体C4的裂解片断CAd沉积情况,探讨其与排斥反应的关系,为临床诊断和治疗排斥反应提供思路和依据.方法 25例肝移植患者术后共行移植肝穿刺36次,取34次肝脏穿刺样本入组研究.穿刺时间为移植后7 d至25个月,所有供肝移植前均留取样本.穿刺所得移植肝组织进行HE染色和免疫组织化学染色,观察CAd的沉积情况.结果 34次病理检查中,诊断为急性排斥反应16次,慢性排斥反应9次,非排斥反应9次(包括胆道并发症3次,药物性肝损害5次,乙型肝炎复发1次).移植前供肝组织中均未见CAd沉积.发生急性排斥反应者中,9例(9/16)移植肝组织中可见到C4d沉积,发生慢性排斥反应者中,5例(5/9)移植肝组织中可见到CAd沉积,非排斥反应者中,仅1例(1/9)非吻合口胆管狭窄患者的肝组织中有CAd沉积.排斥者和非排斥者的CAd沉积部位无明显差异.急性排斥反应者和慢性排斥反应者的C4d阳性率均高于非排斥反应者(P<0.05,P<0.05);CAd阳性率与肝损伤程度无明显相关性.CAd阳性者激素冲击有效率为35.7%(5/14),远低于CAd阴性者的63.6%(7/11).结论 CAd沉积可提示体液性排斥反应,可作为肝移植后肝损害时病理检查的常规免疫组织化学项目,有利于监测和预警体液性排斥反应的发生.并为选择冲击治疗方案提供依据.     

Risk factors for capillary C4d deposition in kidney allografts: evaluation of a large study cohort

BACKGROUND: Capillary deposition of the complement split product C4d has turned out to be a valuable marker of antibody-mediated rejection. The impact of pre- and posttransplant variables including particular immunosuppressive regimens on the frequency of C4d deposition has not yet been systematically investigated in a large multivariate analysis. METHODS: In this retrospective study, the authors evaluated the incidence of C4d deposition in 388 kidney transplant recipients subjected to diagnostic biopsy within the first 6 months and analyzed the influence of potential confounders on the rate of C4d-positive graft dysfunction by applying multivariate logistic regression. RESULTS: Sixty-six recipients (17%) developed linear C4d deposits in at least a quarter of peritubular capillaries, a finding associated with inferior 1-year allograft survival (73% vs. 88% in C4d-negative patients, P=0.0003). A 50% reduction in the odds of C4d-positive graft dysfunction was found if calcineurin inhibitor or mycophenolate mofetil (MMF) therapy was started 2 to 4 hr before transplantation when compared with initiation after surgery (adjusted odds ratio [OR], 0.5; P=0.03). No differences with respect to C4d staining results were found for the use of tacrolimus, MMF, or sirolimus, or for cyclosporine C2 monitoring. Retransplantation (OR, 3.6; P<0.001) and presensitization (OR, 3.1; P=0.002) turned out to be strong independent risk factors for C4d deposition. CONCLUSIONS: The authors' results suggest a reduced risk of C4d-positive graft dysfunction for patients receiving immunosuppression before transplantation. Apart from first dose timing, no influence of particular immunosuppressive strategies on C4d staining results was found.     

Control of antidonor antibody production with tacrolimus and mycophenolate mofetil in renal allograft recipients with chronic rejection

BACKGROUND: In renal transplantation, chronic rejection is a major cause of late allograft loss. Recent studies indicate that a subset of chronic rejection is associated with anti-HLA donor specific antibodies (DSA) and complement C4d deposition in peritubular capillaries (PTC). Since rescue therapy with tacrolimus and mycophenolate mofetil has been found to limit antidonor B-cell responses in recipients with acute humoral rejection, we sought to determine whether a similar immunosuppressive regimen might be effective in patients with 'chronic humoral rejection'. METHODS: Four renal allograft recipients with 'chronic humoral rejection' were prospectively identified. The diagnosis was based on: (1) progressive rise in serum creatinine over 12 months; (2) typical pathologic features by light microscopy (transplant arteriopathy and glomerulopathy); (3) widespread C4d deposits in PTC by immunofluorescence; (4) detection of 'de novo' DSA at the time of biopsy. Maintenance immunosuppression was CsA, prednisone and azathioprine (n=3) or prednisone and azathioprine (n=1). Rescue therapy with tacrolimus and mycophenolate mofetil was initiated in all patients, 12 hr after cyclosporine and azathioprine discontinuation. RESULTS: At diagnosis, the mean serum creatinine was 3.9 mg/dl (range: 3.3 to 5.4 mg/dl). DSA was an IgG directed against HLA class II (n=3) or class I (n=2), that is one patient had both anti-HLA class I and class II antibodies. Pretreatment antibody titers varied between 1:8 and 1:128. Rescue therapy was associated with a rapid and sustained decrease in antibody titers. In two patients, DSA became undetectable after 9 months and a repeat biopsy performed after 12 months revealed a decrease in C4d deposition in PTC. CONCLUSION: These results suggest that a decrease in DSA production can be induced in renal allograft recipients with 'chronic humoral rejection' by using an immunosuppressive regimen that combines tacrolimus and mycophenolate mofetil. Limitation of antidonor antibody synthesis may be important for the treatment or the prevention of chronic rejection in organ transplantation.     

Clinical experience of mycophenolate mofetil in the treatment of chronic allograft nephropathy in kidney transplantation: three-year follow-up

BACKGROUND: Mycophenolate mofetil (MMF) in conjunction with calcineura antagonists has been shown to prevent acute rejection in renal allograft recipients. Its role in treatment of chronic rejection or allograft nephropathy is still controversial. We initiated the study to investigate the effect of adding MMF to a cyclosporine plus prednisolone regimen in renal recipients with chronic allograft nephropathy. MATERIALS AND METHODS: We retrospectively studied 36 patients with chronic allograft nephropathy, defined clinically as increased of serum creatinine, proteinuria, and hypertension. Renal function, cyclosporine level, renal biopsy, and renal scan were regularly done as indicated. MMF was added to 20 recipients after initial treatment with cyclosporine and prednisolone. The other 16 recipients were managed without adding MMF. Serum creatinine was monitored for 3 years. RESULTS: The demographic characteristics of the patients in the two groups were comparable. The average dose of prednisolone was unchanged throughout the study and the trough level of cyclosporine was maintained in the range of 100 to 150 ng/mL. The serum creatinine decreased initially in the group on MMF, but renal function deteriorated progressively after 6 months. There was a difference in serum creatinine between the two groups but this did not reach statistical significance. CONCLUSION: MMF therapy tender to improve renal function initially but did not attenuate significantly the impairment in chronic allograft nephropathy.     

肾移植一年后急性排斥反应时移植肾组织中C4d表达阳性的临床研究

目的 观察肾移植1年后发生急性排斥反应时移植肾组织中补体片段C4d的表达情况,分析其对移植肾功能及预后的影响.方法 选择肾移植时间超过1年,临床诊断为急性排斥反应并经病理穿刺活检证实的肾移植受者36例为研究对象.以第1例受者移植肾组织穿刺时间为观察起点(2006年3月),以此项研究结束时间为观察终点(2010年4月).应用C4d多克隆抗体对移植肾穿刺组织行免疫组织化学染色,检测C4d在移植肾组织中的表达情况;根据检测结果,分为C4d阳性组和阴性组,分析和比较两组在观察时间段内移植肾功能的变化及存活时间.结果 在36例受者的移植肾穿刺标本中,C4d阳性16例(44.4%),C4d阴性20例(55.6%);C4d阳性组和阴性组移植肾组织中嗜酸性粒细胞浸润数量分别为(9.4±4.5)个和(2.6±1.8)个,两组比较,差异有统计学意义(P＜0.05).在观察时间段内,所有受者血清肌酐均有不同程度上升,但C4d阳性组上升幅度与C4d阴性组比较,差异无统计学意义(P＞0.05);C4d阳性组和C4d阴性组受者移植肾功能丧失率分别为31.3%(5/16)和30.0%(6/20),两组比较,差异无统计学意义(P＞0.05).C4d阳性组和C4d阴性组受者移植肾穿刺后的巾位存活时间分别为(19.3±5.3)个月和(22.5±7.4)个月,两组比较,差异无统计学意义(P＞0.05).结论 肾移植1年后发生急性排斥反应时,移植肾组织中C4d表达阳性对其功能及存活时间无明显影响.     

Prevalence and association of post-renal transplant anemia

In some renal allograft recipients, anemia persists or develops following transplantation. Anemia is associated with pre-operative blood loss and allograft dysfunction, including delayed graft function, acute rejection and chronic allograft dysfunction. To study the prevalence and association of post-renal transplant anemia, we studied 200 renal transplant recipients; 131 (65.5%) patients were males and 69 (34.5%) patients were females, and age ranged from 17 to 67 years, with a mean of 37.7 ± 10.8 years. All patients were receiving cyclosporine, prednisolone and mycophenolate mofetil (MMF). Complete blood count was done at two times: three and six months post-renal transplant. There were 74% anemic patients three months after renal transplantation and 45% anemic patients six months after renal transplantation. High creatinine value, female gender, delayed graft function, episodes of acute rejection, perioperative blood loss and infections were the only significant independent risk factors for prevalence of anemia post-renal transplant. In our study, we did not find an association between MMF and cyclosporine nor angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptors blocker (ARBs) with anemia. This study demonstrates that anemia is a common complication during the first six months after kidney transplantation, with several risk factors precipitating this complication.     

Late cytomegalovirus disease with atypical presentation in renal transplant patients: case reports

Cytomegalovirus (CMV) disease typically occurs 1 to 4 months (median 35 days) after solid organ transplantation. Recent reports documented that the natural history of CMV disease associated with solid organ transplantation has been modified as a result of the widespread use of potent immunosuppressents and antiviral prophylaxis. We herein report three pretransplant CMV seropositive recipients (with unknown donor status) who were diagnosed recently to display late and atypical CMV disease. Two men and one woman included two patients who presented with allograft dysfunction at 12 years and at 3 years after transplantation. Both patients showed increased serum creatinine approximately from baseline 200 to >400 micromol/L over 3 months in the absence of features of rejection or cyclosporine toxicity. A renal biopsy was refused by both patients. Two of the three patients presented with symptoms of enterocolitis (diarrhea, nausea, weight loss), which had persisted for more than 6 months. Other symptoms and signs of overt CMV disease (fever, leukopenia) were absent. None had pulmonary, hepatic, or other major organ involvement. In all patients IgG antibodies and CMV DNA by polymerase chain reaction were positive with negative IgM antibodies. The immunosuppressive regimen consisted of mycophenolate mofetil (MMF), steroids, and calcineurin inhibitors. The kidney function significantly improved in both patients with renal dysfunction. Gastrointestinal symptoms resolved completely with gradual weight gain. The recognition and early diagnosis of late atypical CMV disease in kidney transplant patients presenting with allograft dysfunction and/or other organ systems is important. The MMF has a red herring effect in our cases due to its GI side effects.