Cytomegalovirus prophylaxis with intravenous polyvalent immunoglobulin in high-risk renal transplant recipients

Cytomegalovirus (CMV) seronegative renal allograft recipients (R-), particularly those with a graft from a CMV-seropositive donor (D+), are at high risk for primary CMV infection. CMV resistance to antiviral oral therapy is an emerging problem in renal transplantation, prompting development of new prophylactic strategies. We retrospectively studied the 1-year posttransplantation incidence of CMV infection in high-risk renal transplant recipients, in whom polyvalent intravenous immunoglobulins (IVIg) were used as prophylaxis. Forty R- patients received immunoprophylaxis by polyvalent IVIg (0.25 g/kg weekly for 8 weeks, starting on the operative day). CMV serological tests remained negative in eight patients (20%). Eight patients (20%) had asymptomatic CMV infection while 24 (60%) developed CMV syndrome and were treated with gancyclovir (10 mg/kg/day intravenously for 3 weeks). None had CMV disease or opportunistic infection. Six patients (15%) had biopsy-proven acute rejection, which followed CMV syndrome in three cases. One-year renal allograft and patient survivals were 95% and 97.5%, respectively. Mean serum creatinine level was 124 +/- 33 micromol/L at 1 year. Clinical tolerance of IVIg was excellent, without any episode of acute renal failure. Polyvalent IVIg provides effective prophylaxis in renal transplant recipients at high risk for CMV infection and is associated with excellent 1-year allograft survival. Because of their immunomodulatory functions, IVIg may have a beneficial effect on the incidence of acute and chronic rejection and allograft survival. A randomized prospective study is required to evaluate long-term effects of CMV prophylaxis with polyvalent IVIg compared to antiviral agents in renal transplant recipients.     

Splenic Irradiation for the Treatment of Severe Antibody‐Mediated Rejection

Patients requiring desensitization prior to renal transplantation are at risk for developing severe antibody‐mediated rejection (AMR) refractory to treatment with plasmapheresis and intravenous immunoglobulin (PP/IVIg). We have previously reported success at graft salvage, long‐term graft survival and protection against transplant glomerulopathy with the use of eculizumab and splenectomy in addition to PP/IVIg. Splenectomy may be an important component of this combination therapy and is itself associated with a marked reduction in donor‐specific antibody (DSA) production. However, splenectomy represents a major operation, and some patients with severe AMR have comorbid conditions that substantially increase their risk of complications during and after surgery. In an effort to spare recipients the morbidity of a second operation, we used splenic irradiation in lieu of splenectomy in two incompatible live donor kidney transplant recipients with severe AMR in addition to PP/IVIg, rituximab and eculizumab. This novel approach to the treatment of severe AMR was associated with allograft salvage, excellent graft function and no short‐ or medium‐term adverse effects of the radiation therapy. One‐year surveillance biopsies did not show transplant glomerulopathy (tg) on light microscopy, but microcirculation inflammation and tg were present on electron microscopy.     

Therapy with plasmapheresis and intravenous immunoglobulin for acute humoral rejection in kidney transplantation

BACKGROUND: Acute humoral rejection (AHR) is characterized by acute graft dysfunction associated with de novo production of donor-specific alloantibodies (DSA) and C4d deposition in peritubular capillaries of the renal allograft. It has been reported the combination of plasmapheresis (PP) and intravenous gamma globulin (IVIG) as effective rescue therapy for established AHR. METHODS: Between 1999 and 2004, seven kidney allografts recipients suffered from AHR diagnosed by severe rejection and C4d staining in peritubular capillaries. All patients had a negative cross-match before renal transplantation. RESULTS: All patients were treated with daily sessions of PP and in four cases IVIG was added after the last PP session. Tacrolimus and mycophenolate mofetil were employed as maintenance immunosuppressive regimen. In one case, rituximab was added to PP and IVIG owing to refractory humoral rejection. At 1 year, patient survival was 100%, allograft survival was 70%, and the mean serum creatinine was 201 micromol/L. CONCLUSIONS: AHR is a severe form of rejection associated with a poor prognosis, but its early diagnosis and treatment with PP and IVIG allows reversal of AHR reaching a 70% graft survival at 1 year.     

Beneficial effect of plasmapheresis and intravenous immunoglobulin on renal allograft survival of patients with acute humoral rejection

BACKGROUND: Acute humoral rejection (AHR) has been associated with enhanced graft loss. Our study compared the renal allograft survival of patients with AHR treated with plasmapheresis (PP) and intravenous immunoglobulin (IVIG) with allograft survival in patients with acute cellular rejection (ACR). METHODS: We retrospectively analyzed all kidney transplants performed at our institution between January 1999 and August 2001 (n=286). Recipients were classified into three groups according to biopsy reports: AHR, ACR, or no rejection. The ACR group was further divided into early and late rejection (<90 and >90 days posttransplant, respectively). RESULTS: After a mean follow-up of 569+/-19 days, the incidence of AHR was 5.6% (n=16). Recipient presensitization, delayed graft function, early rejection, and higher creatinine at diagnosis were characteristic of AHR. Most AHR patients (14/16) were treated with PP and IVIG. One patient received only IVIG, whereas another received only PP. All AHR patients were given steroid pulses, but only four received antilymphocyte therapy because of concomitant severe ACR. The ACR group comprised 43 patients (15%). One patient with mild rejection received no therapy, 20 improved with steroids alone, and 22 required additional antilymphocyte therapy. One-year graft survival by Kaplan Meier analysis was 81% and 84% in the AHR and ACR groups, respectively (P=NS). Outcomes remained similar when AHR patients were compared with those with early ACR. CONCLUSIONS: We conclude that AHR, when diagnosed early and treated aggressively with PP and IVIG, carries a short-term prognosis that is similar to ACR.     

Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients

BACKGROUND: Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain recalcitrant conditions without effective treatments, and usually result in graft loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in many different clinical settings. Intravenous gamma globulin (IVIG) has been used to suppress alloantibody and modulate immune responses. Our hypothesis was that a combination of PP and IVIG could effectively and durably remove donor-specific, anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively desensitizing recipients who had positive crossmatches with a potential live donor. METHODS: The study patients consisted of seven live donor kidney transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one or more mismatched donor HLA antigens. The patients segregated into two groups: three patients were treated for established AHR (rescue group) and four cross-match-positive patients received therapy before transplantation (preemptive group). RESULTS: Using PP/IVIG we have successfully reversed established AHR in three patients. Four patients who were cross-match-positive (3 by flow cytometry and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal transplantation utilizing their live donor. The overall mean creatinine for both treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17-116 weeks). CONCLUSIONS: In this study, we present seven patients for whom the combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab specific for donor HLA antigens. Furthermore, this protocol shows promise for eliminating DSA preemptively among patients with low-titer positive antihuman globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches, allowing the successful transplantation of these patients using a live donor without any cases of HAR.     

The Utility of Splenectomy as Rescue Treatment for Severe Acute Antibody Mediated Rejection

Antibody-mediated rejection (AMR) after desensitization for a positive crossmatch (+XM) live donor renal transplant can be severe and result in sudden onset oliguria and loss of the allograft. Attempts to rescue these kidneys using plasmapheresis (PP) and IVIg may be ineffective due to the magnitude of antibody burden that must be controlled to prevent renal thrombosis or cortical necrosis. We review our experience using splenectomy combined with PP/IVIg as rescue therapy for patients experiencing an acute deterioration in renal function and a rise in donor-specific antibody within the first posttransplant week after desensitization for a +XM. Five patients underwent immediate splenectomy followed by PP/IVIg and had return of allograft function within 48 h of the procedure. Emergent splenectomy followed by PP/IVIg may be an effective treatment for reversing severe AMR.     

C4d-positive acute humoral renal allograft rejection: effective treatment by immunoadsorption.

There is increasing evidence for an important pathogenetic role of alloantibodies in acute renal allograft rejection. Acute humoral rejection (AHR) has been reported to be associated with a poor transplant survival. Although treatment modalities for cellular rejection are fairly well established, the optimal treatment for AHR remains undefined. Ten of 352 kidney allograft recipients transplanted at the authors' institution between November 1998 and September 2000 were diagnosed as having AHR, supported by severe graft dysfunction, C4d deposits in peritubular capillaries (PTC), and accumulation of granulocytes in PTC. AHR was diagnosed 18.9 +/- 17.5 d posttransplantation. All patients were subjected to immunoadsorption (IA) with protein A (median number of treatment sessions, 9; range, 3 to 17). Seven recipients with additional signs of cellular rejection (according to the Banff classification) received also antithymocyte globulin. In nine of ten patients, AHR was associated with an increase in panel reactive antibody reactivity. A pathogenetic role of alloantibodies was further supported by a positive posttransplant cytotoxic crossmatch in all tested recipients (n = 4). In nine of ten recipients, renal function recovered after initiation of anti-humoral therapy. One patient lost his graft shortly after initiation of specific therapy. Another recipient with partial reversal of AHR returned to dialysis 8 mo after transplantation. Mean serum creatinine in functioning grafts was 2.2 +/- 1.2 mg/dl after the last IA session (n = 9) and 1.5 +/- 0.5 mg/dl after a follow-up of 14.2 +/- 7.1 mo (n = 8). In conclusion, this study suggests that AHR, characterized by severe graft dysfunction, C4d staining, and peritubular granulocytes, can be effectively treated by timely IA. In the majority of patients, IA treatment can restore excellent graft function over a prolonged time period.     

Predicting factors of long-term results of OKT3 therapy for steroid resistant acute rejection following cadaveric renal transplantation

In this retrospective study, we evaluated the histological and biological predictors of long-term response of renal transplant (RT) patients treated with orthoclone OKT3 for steroid resistant acute rejection (AR). Seventy-three patients, aged 37 +/- 12 years, were included in this study between March 1987 and December 1996. All the patients but one had received sequential quadruple immunosuppression (polyclonal antilymphocyte globulins; steroids; azathioprine, and cyclosporin A). OKT3 (5 mg/day for 10 days) was administered for biopsy-proven steroid resistant AR i.e., after 3 consecutive pulses of methylprednisolone (10 mg/kg each). This was the first AR in 46 cases, the second AR in 22 cases and the third AR in 4 cases. Renal histology (Banff) showed borderline (BL) changes in 18 patients, grade I AR in 28 patients; grade II AR in 22 patients, and grade III AR in 5 patients. When treatment with OKT3 commenced (107 +/- 18 days post-transplantation) the mean serum creatinine (SCr) level was 325 +/- 195 micromol/l; this had decreased to 191 +/- 106 micromol/l by the end of OKT3 therapy. The immediate response to OKT3 therapy i. e., within the first month, was not dependent on the histological score. Twenty-six patients (35%) subsequently experienced at least one more AR episode of whom 4 were retreated with OKT3. The overall patient's survival was 94.5% at last follow-up. The overall cumulative graft survival was 64.5% at 2 years, 52.5% at 5 years, and 40.5% at 8 years. The graft survival (5 years) tended to depend on the initial histological score, i.e. BL 30%; grade I 66%; grades II and III 55.5% (p = 0.08). In a multiple logistic regression analysis we tried to identify independent factors that would predict that a graft would still be functioning at least 2 years after OKT3 therapy. We therefore analyzed the following parameters: donor and recipient's age; gender; cold ischemia time; HLA matching; panel reactive antibodies (PRA) prior to grafting; previous transplantation(s); total number of AR episodes; the time of onset of the AR treated by OKT3 compared to the other AR; the time of onset of the AR treated by OKT3; SCr levels at days 0, 10 and 30 after OKT3 therapy; histological score (Banff) i.e., the magnitude of AR and the presence or absence of chronic lesions. The only independent factors which would predict that a graft was still functioning 2 years after OKT3 therapy were: PRA <25% (Odds ratio (OR) 7.68 (1.15-51.3); p = 0.035); a grade I AR (OR 10.52 (1.18-93. 5); p = 0.035); SCr level 1 month after OKT3 therapy (OR 0.935 (0. 87-1.002); p = 0.05). HLA matching and the presence of histological chronic lesions were nearly significant (p = 0.06 and 0.09 respectively). In conclusion, this retrospective study shows that independent predictors of the long-term response to OKT3 therapy for AR in RT patients are the magnitude of pre-transplant PRA, the histological score, and the SCr level one month after OKT3 therapy. Copyright Copyright 1999 S. Karger AG, Basel     

Successful rescue and maintenance of long-term remission of anti-HLA antibody-mediated acute allograft rejection by rituximab-containing therapy: case report

Abstract:  A 38-yr-old man with chronic renal failure received a second kidney transplantation from a cadaveric donor. Complement-dependent cytotoxicity cross-match (CDC) was negative against T cells, but positive with the B-cell warm test. Human leukocyte antigen (HLA)-typing showed a one haplo-identical match. The blood type was compatible. He was treated with tacrolimus, mycophenolate mofetil (MMF), methylpredonisolone (MP), and basiliximab as immunosuppressive therapy. A clinical episode graft biopsy and Flow-PRA on post-operative day (POD) 19 showed anti-HLA antibody-mediated acute rejection (AHR). The patient was treated with plasmapheresis (PP). Renal biopsy performed on POD 65 because of re-rise of serum creatinine level showed worsening of renal injury. The patient was treated with rituximab (100 mg/body) with PP and MP pulse therapy, followed by tacrolimus and MMF. Graft function thereafter improved. A renal allograft biopsy specimen on POD 300 and Flow-PRA showed the remission of AHR within one-yr after transplantation.     

MDRD-estimated GFR at one year post-renal transplant is a predictor of long-term graft function

Renal transplantation is the optimal mode of renal replacement. Improvements in graft survival and acute rejection rates have made these outcomes less useful for prognostication and as end-points in clinical trials; accurate surrogate markers of long-term graft outcome are therefore increasingly important. This study examines the relationship between both serum creatinine (SCr(1 yr)) and MDRD estimated glomerular filtration rate measured at one year (eGFR(MDRD)(1 yr)) as predictors of graft survival. Data on 1,110 patients who received a renal transplant between 1989 and 2005 were extracted from the Irish Renal Transplant Registry. The study group was divided into quartiles of patient numbers according to SCr(1 yr) and eGFR(MDRD)(1 yr). Kaplan-Meier estimates of the primary end-point graft survival were constructed for each quartile. Additionally, a Cox Regression restricted cubic spline model was performed for both eGFR(MDRD)(1 yr) and SCr(1 yr). Both overall graft outcome and outcome censored for death with a functioning graft (CDWFG) were used as endpoints. Cox regression analysis was performed along with tests for the proportionality assumption to compare the predictive value of eGFR(MDRD)(1 yr)and SCr(1 yr). Both eGFR(MDRD)(1yr) and SCr(1 yr) were independently associated with long-term renal transplant survival. eGFR(MDRD)(1 yr) and SCr(1 yr) had similarly strong associations with long-term outcome when the quartile variables were compared using the Bayesian Information Criterion method. The Cox regression restricted cubic spline modeling demonstrated that an eGFR(MDRD)(1 yr) value < 27 mLs/min/1.73 m(2) and a SCr(1 yr) value > 229 micromol/L were associated with poor graft survival.     

Importance of early adequate exposure to cyclosporine in renal transplant outcome: study of 1-year creatinine

INTRODUCTION: One-year serum creatinine (SCr) level has been used as a surrogate marker for graft survival in kidney transplantation. We evaluated the importance of different factors on this parameter, emphasizing the importance of adequate exposure to Cyclosporine (CyA). METHODS: Ninety-six consecutive renal transplant recipients who underwent transplantation between 1996 and 2002 were treated with CyA, steroids, and azathioprine. Univariate and multivariate regression analyses were performed for 1-year SCr, acute rejection episodes (ARE), and duration of delayed graft function (DGF). We considered adequate CyA levels within 1 week to be >250 ng/mL trough levels (38%) or 3 hour postdose level (C3) >1100 ng/mL (62%). RESULTS: Mean 1-year SCr was 1.52 +/- 0.5, ARE rate was 27%, and DGF rate was 31%. Overall, 53% of patients achieved adequate exposure to CyA at 1 week (68% on those monitored by C3). Univariate analysis identified female recipient gender, decreasing donor age, absence of ARE, and decreased DGF duration to yield lower 1-year SCr (P < .05). On multivariate analysis for donor age (lower), ARE rate, and duration of DGF (shorter) were the only factors considered to be significant for a lower 1-year SCr level. Multivariate analysis for ARE showed that adequate CyA exposure and lower HLA mismatch decreased ARE, whereas the ability to achieve adequate exposure to CyA and shorter cold ischemia time (CIT) correlated with a reduced incidence of DGF. CONCLUSIONS: One-year SCr level is affected primarily by the incidence of ARE, by donor age, and by duration of DGF. Adequate CyA exposure is related to lower ARE; however, its relation to DGF may be influenced by the reluctance to increase exposure on patients with a nonfunctioning graft.     

Hepatitis C, acute humoral rejection, and renal allograft survival

The effect of recipient hepatitis C virus (HCV) infection on renal allograft loss and acute rejection in kidney transplantation remains controversial. We studied 354 renal allograft recipients transplanted during 1996 to 2001 who had HCV antibodies (Ab) measured before transplantation. The primary outcome was death-censored allograft loss and the secondary outcome was acute humoral rejection (AHR). Compared with HCV Ab-negative patients, those with positive HCV Ab had longer time on dialysis before transplantation, higher percentage of panel-reactive antibodies (PRA), were more likely to receive a cadaveric transplant, and were more likely to develop delayed graft function (DGF). In univariate analyses, predictors of renal allograft loss included HCV, cadaveric graft, PRA >20%, HLA mismatch > or =5, retransplantation, DGF, induction therapy, and AHR. When adjusted for PRA >20%, HLA mismatch > or =5, and multiple transplant status, HCV was not a statistically significant predictor of allograft loss. HCV was also associated with AHR but lost significance when adjusted for PRA >20%. HCV Ab-positive patients were more likely to have longer duration of dialysis before transplantation prior to kidney transplants, higher PRA, and to receive cadaveric transplants. These characteristics likely resulted in more DGF and AHR after transplantation. After adjusting for these confounding factors, the association between HCV Ab positivity and renal allograft loss was notably attenuated and no longer statistically significant.     

Intravenous Immunoglobulins in the Prevention of Rejection of a Second or Third Kidney Graft

Background

Intravenous immunoglobulin (IVIg) reduces acute rejection episodes in kidney transplantation, but adverse events (AEs) are common. The aim of this study was to assess whether human IVIg enhances immunosuppressive effects without increasing AEs in the prevention of acute kidney graft rejection.

AZA/Tacrolimus Is Associated with Similar Outcomes as MMF/Tacrolimus among Renal Transplant Recipients

There have been several retrospective studies indicating benefits associated with mycophenalate mofetil (MMF) compared to azathioprine (AZA) for renal transplant recipients. However, these analyses evaluated outcomes prior to changes in utilization patterns of concomitant immunosuppression. Recent prospective trials have indicated similar outcomes among patients treated with MMF and AZA. The aim of this study was to evaluate outcomes in a broad group of patients in the more recent era. We evaluated adult solitary renal transplant recipients from 1998 to 2006 with the national SRTR database. Primary outcomes were time to patient death and graft loss, complications and renal function. Models were adjusted for potential confounding factors, propensity scores and stratified between higher/lower risk transplants and concomitant immunosuppression. Adjusted models indicated a modest risk among AZA patients for graft loss (AHR = 1.14, 95% CI 1.07–1.20); however, this was not apparent among AZA patients also treated with tacrolimus (AHR = 0.97, 95% CI 0.85–1.11]. One-year acute rejection rates were reduced for patients on MMF versus AZA (10 vs. 13%, p < 0.01); there were no statistically significant differences of malignancies, renal function or BK virus at 1 year. The primary findings suggest the association of MMF with improved outcomes may not be apparent in patients also receiving tacrolimus.     

Graft loss and acute coronary syndromes after renal transplantation in the United States

The impact of graft loss on acute coronary syndromes (ACS) after renal transplantation has not been studied in a national population. It was hypothesized that ACS might be more frequent after graft loss, as many of the benefits of a functioning allograft on metabolism and volume regulation would be lost. Data from the 2000 United States Renal Data System (USRDS) was used to conduct an historical cohort study of ACS in 14,237 patients who received renal transplants between April 1, 1995, and June 30, 1998, (followed until April 28, 2000) with valid information from CMS Form 2728, excluding patients with hospitalized ACS before renal transplant. Cox nonproportional regression models were used to calculate the time-dependent adjusted hazard ratio (AHR) of graft loss (censored for death) for time-to-first hospitalization for ACS (International Classification of Diseases 9th Modification Diagnosis Codes [ICD9] code 410.x or 411.x) occurring after transplant. The incidence of ACS was 12.1 per 1000 patient-years (PY) in patients after graft loss versus 6.5 per 1000 PY after transplantation (excluding patients with graft loss). As a time-dependent variable, graft loss had an AHR of 2.54 (95% confidence interval, 1.09 to 5.96; P = 0.031 by Cox regression). Other risk factors associated with ACS included diabetes, older recipient, and male recipient. Allograft rejection was NS. Renal transplant recipients share some of the risk factors for ACS with the general population. In addition, graft loss was identified as a unique risk factor for ACS in this population.     

Successful kidney transplantation from a cadaveric donor unsuitable for other centers due to acute renal failure: a case report

The demand for kidney transplantation due to improved recipient outcomes has stimulated surgeons to expand the criteria for usable donors, but still the use of organs from deceased donors with terminal acute renal failure is uncommon. We report 2 kidney transplant recipients from a cadaveric donor who was not accepted by other centers because of acute renal failure. The donor, a 24-year-old man with an intracerebral hemorrhage, displayed a serum creatinine (SCr) value of 0.6 mg/dL on hospital admission, which increased to 7.3 mg/dL on the fourth hospital day. After the diagnosis of brain death and refusal of the kidneys by other regional centers, we decided to transplant the 2 kidneys. Recipient 1, a 31-year-old man on an 11-year dialysis program, discontinued hemodialysis after 7 days of delayed graft function. The SCr level decreased gradually and was stable at 1.08 mg/dL on postoperative day (POD) 45. The contralateral graft was transplanted into a 30-year-old man (recipient 2) undergoing dialysis treatment for 7 years. After 10 days of delayed graft function, the SCr decreased gradually with continued hemodialysis until POD 24. The SCr level has been stable at 1.34 mg/dL on POD 52. At the end of the third month the SCr levels in recipients 1 and 2 were 1.1 mg/dL and 1.4 mg/dL, respectively. In conclusion, one may safely expand the donor pool with kidneys from deceased donors with acute renal failure (ARF) with good short-term outcomes.     

Desensitization and Subsequent Kidney Transplantation of Patients Using Intravenous Immunoglobulins (IVIg)

Transplantation of patients possessing antibodies against allo-HLA antigens can be delayed for years. We have shown that administration of intravenous immunoglobulins (IVIg) can induce a profound and sustained decrease in the titers of anti-HLA antibodies. We report here the first series of patients desensitized, then transplanted using IVIg therapy. Fifteen patients have been included and treated with IVIg, given as 3 monthly courses of 2g/kg body weight. Thirteen of those 15 patients (87%) were effectively desensitized and underwent immediate transplantation. Eleven were transplanted with a cadaveric donor, and two with a living donor against which the pretreatment cross-match was positive. One graft was lost from thrombosis and one from rejection. All other patients had uneventful courses, without any episodes of rejection, with a follow-up of more than 1 year. Thus, IVIg therapy allows safe and prompt kidney transplantation of immunized patients.     

Posttransplant Prophylactic Intravenous Immunoglobulin in Kidney Transplant Patients at High Immunological Risk: A Pilot Study

The effects of posttransplant prophylactic intravenous immunoglobulin (IVIg) were investigated in renal transplant recipients at high immunological risk. Thirty-eight deceased-donor kidney transplant recipients with previous positive complement-dependent cytotoxicity crossmatch (n=30), and/or donor-specific anti-HLA antibodies (n=14) were recruited. IVIg (2 g/kg) was administrated on days 0, 21, 42 and 63 with quadruple immunosuppression. Biopsy-proven acute cellular and humoral rejection rates at month 12 were 18% and 10%, respectively. Glomerulitis was observed in 31% and 60% of patients at months 3 and 12, respectively, while allograft glomerulopathy rose from 3% at month 3 to 28% at 12 months. Interstitial fibrosis/tubular atrophy increased from 18% at day 0 to 51% and 72% at months 3 and 12 (p<0.0001). GFR was 50 +/- 17 mL/min/1.73 m(2) and 48 +/- 17 mL/min/1.73 m(2) at 3 and 12 months. PRA decreased significantly after IVIg (class I: from 18 +/- 27% to 5 +/- 12%, p<0.01; class II: from 25 +/- 30% to 7 +/- 16%, p<0.001). Patient and graft survival were 97% and 95%, respectively and no graft was lost due to rejection (mean follow-up 25 months). In conclusion, prophylactic IVIg in high-immunological risk patients is associated with good one-year outcomes, with adequate GFR and a profound decrease in PRA level, but a significant increase in allograft nephropathy.     

高致敏尿毒症患者肾移植术前的脱敏治疗及效果

目的 探讨高致敏尿毒症患者肾移植术前脱敏治疗的可行性和效果.方法 等待肾移植的群体反应性抗体(PRA,抗HLA Ⅰ类抗体)＞50%的尿毒症患者35例,27例的T淋巴细胞和(或)B淋巴细胞毒交叉配合试验阳性,8例T淋巴细胞和B淋巴细胞毒交叉配合试验为阴性.移植前接受血浆置换(PP)联合静脉注射小剂量免疫球蛋白(IVIG)进行脱敏治疗.采用美国One Lambda公司抗原板检测PRA,并用相应电脑软件分析抗HLA抗体特异性.当淋巴细胞毒交叉配合试验为阴性时接受肾移植.结果 淋巴细胞毒交叉配合试验阳性的27例中,25例(92.6%,25/27)在PP+IVIG治疗(6.2±2.1)次后转为阴性,其抗HLA Ⅰ类抗体从治疗前的(77±14)%下降至(36±17)%(P＜0.01),抗HLA Ⅱ类抗体从治疗前的(52±33)%降至(37±30)%(P＜0.01),最终接受了肾移植;另2例因淋巴细胞毒交叉配合试验持续阳性而放弃肾移植.接受肾移植的25例中,有8例(32.0%,8/25)发生急性排斥反应,其中5例(62.5%,5/8)为急性体液性排斥反应(AHR),均经治疗后逆转.随访(52±26)个月,受者术后1年和2年时的血肌酐分别为(112±18)μmol/L和(130±38)μmol/L.移植肾1年和3年存活率分别为96.0%和80.0%.结论 肾移植前采用PP+IVIG能有效地对高致敏患者进行脱敏治疗,但术后AHR发生率较高,其近期效果可以接受,远期效果还有待观察.

Abstract：

Objective To explore the feasibility and efficacy of desensitization protocol for highly sensitized renal transplant patients (HSP). Methods Thirty-five HSPs ( HLA class-Ⅰ panel reactive antibody ＞50 %), including 27 patients with a positive T and/or B cell cytotoxicity crossmatch (XM) and 8 patients with a negative T and B cell XM, received plasmapheresis plus intravenous immunoglobulin (PP-IVIG)treatment. Results The positive XM was rendered negative by PP-IVIG treatment in 25 of 27 (92.6 %)HSPs, and subsequent transplantation was performed. Two patients did not receive renal transplants due to persistent positive XM. In 25 patients receiving renal transplants, no hyperacute rejection occurred. There were 8 cases of acute rejection, including 5 cases of acute humoral rejection (AHR). All rejection episodes were reversed. During a follow-up period of 52 ± 26 months, the serum creatinine levels at 12th and 24th month were 112± 18 and 130 ± 38 mol/L respectively. The 1- and 3-year graft survival rate was 96. 0 %and 80. 0 % respectively. Conclusion The desensitization therapy by PP-IVIG is effective for HSP. High rate of AHR is the major defect of this protocol. The short-term graft survival rate after this protocol is acceptable but the long-term survival rate needs to be defined.