Rapid Resolution of Proteinuria of Native Kidney Origin Following Live Donor Renal Transplantation

To assess the contribution of the protein content of urine from the native kidneys to post-transplant proteinuria, we prospectively studied 14 live donor transplant recipients with a pre-transplant random urine protein to creatinine ratio (UPr:Cr) >0.5. Seven patients received preemptive transplants, and seven patients were on dialysis pre-transplant (with residual urine output). Resolution of proteinuria was defined as UPr:Cr < 0.2. Immunosuppression consisted of tacrolimus, mycophenolate mofetil and corticosteroids. Anti-hypertensive drugs that might reduce proteinuria were avoided during the study. The serum creatinine was 8.7 +/- 0.7 mg/dL pre-transplant, and the nadir post-transplant serum creatinine was 1.4 +/- 0.1 mg/dL. The pre-transplant UPr:Cr ranged between 0.5 and 9.2 (mean = 2.9 +/- 0.6). The UPr:Cr decreased to <0.2 in all 14 patients at a mean of 4.5 weeks post-transplant (range 1-10 weeks). In conclusion, in live donor renal transplant recipients with immediate graft function, proteinuria of native kidney origin resolves in the early post-transplant period. After the immediate post-transplant period, proteinuria cannot be attributed to the native kidneys, and work up for proteinuria should focus on the allograft.     

Polyomavirus Nephropathy in Pediatric Kidney Transplant Recipients

Given the limited information regarding BK virus-associated nephropathy (BKVN) in pediatric kidney transplant recipients, we assessed the incidence, risk factors, clinical and virologic features of BKVN in pediatric renal transplant recipients at a single transplant center by means of a retrospective cohort study. Histologically confirmed BKVN developed in 6 of 173 (3.5%) kidney transplant recipients at a median of 15 months post-transplant (range: 4-47 months). At a median follow-up of 28 months (range: 5-32), all patients had functioning grafts with mean creatinine and GFR of 1.9 mg/dL and 58 mL/min/1.73 m2, respectively. At the time of diagnosis, all cases had viruria (median 6.1 x 10(6) copies/mL, range: 10(5) to 3.9 x 10(8) copies/mL) and viremia (median 21,000 copies/mL, range: 10,000-40,000 copies/mL). Recipient seronegativity for BKV was significantly associated with the development of BKVN (p = 0.01). BKVN is an important cause of late allograft dysfunction and is strongly associated with recipient seronegativity in pediatric kidney transplant recipients. Further studies to confirm this finding and to define the clinical utility of routine pre-transplant BKV serologic testing are warranted.     

Long-term bone mineral density changes and fractures in lung transplant recipients with cystic fibrosis

BackgroundLittle is known about long-term bone mineral density (BMD) changes and fractures in lung transplant recipients with cystic fibrosis (CF). We examined femur and lumbar spine (LS) BMD changes in men and women with CF up to 10 years post-transplant and documented post-transplant fracture prevalence.MethodsRetrospective study of individuals who had undergone a lung transplant (2000–2015) and had a pre-transplant and at least one BMD measurement after transplant. Vertebral fractures were assessed on chest computed tomography scans and other fractures abstracted from medical records.ResultsThe cohort consisted of 131 individuals; 53% males, median age: 28 years [interquartile range: 24–35] and 31% having pre-transplant low bone mass. Most recipients were given bisphosphonates after transplant with proportion reaching 94% at 10 years. Up to 10 years post-transplant, men experienced positive or little change in LS BMD, indicating minimal loss from pre-transplant values. In contrast, women displayed negative changes in BMD up to 5 years post-transplant before recovering pre-transplant BMD values by 10 years. Similar patterns were observed at the femur BMD where men demonstrated a lower bone loss and faster recovery towards pre-transplant values than women. After transplant, 88% of recipients maintained their pre-transplant bone status, 3% experienced an improvement, mostly progressing from low bone mass to normal status whereas 9% had a deterioration of their pre-transplant bone status. Twenty-seven recipients suffered fractures in the post-transplant period.ConclusionsThese findings underline that lung recipients with CF remain at risk of skeletal fragility despite prompt initiation of post-transplant anti-osteoporosis therapy.     

A Comparison of Plasmapheresis Versus High-Dose IVIG Desensitization in Renal Allograft Recipients with High Levels of Donor Specific Alloantibody

Several protocols allow for the successful transplantation of sensitized renal allograft recipients, yet no one best method has emerged. The aim of the current study was to compare the efficacy of high-dose IVIG with two different plasmapheresis (PP)-based regimens in kidney transplant recipients with high levels of donor specific alloantibody (DSA) defined as a positive T-cell cytotoxicity crossmatch. With the primary goal of achieving a negative crossmatch, we employed three protocols sequentially between April 2000 and May 2005: (i) PP, low-dose IVIG, anti-CD20 antibody (n = 32); (ii) high-dose IVIG (n = 13); and (iii) PP, low-dose IVIG, anti-CD20 antibody and pre-transplant Thymoglobulin combined with post-transplant DSA monitoring (n = 16). IVIG decreased DSA activity in all treated patient, yet only 38% (5/13) achieved a negative crossmatch. In contrast, a negative crossmatch was achieved in 84% in PP group and 88% in the PP/monitoring group (p < 0.01 vs. IVIG). Even with a negative crossmatch, the rejection rates were 80% (IVIG), 37% (PP) and 29% (PP/monitoring), respectively, (p < 0.05 IVIG vs. PP). We conclude that multiple PP treatments leads to more reproducible desensitization and lower humoral rejection rates than a single high-dose of IVIG, but that no regimen was completely effective in preventing humoral rejection.     

Alloantibody Levels and Acute Humoral Rejection Early After Positive Crossmatch Kidney Transplantation

We examined the course of donor ‐ specific alloantibody (DSA) levels early after transplant and their relationship with acute humoral rejection (AHR) in two groups of positive crossmatch (+XM) kidney transplant recipients: High DSA group—41 recipients with a baseline T‐ or B‐cell flow crossmatch (TFXM, BFXM) channel shift ≥300 (molecules of equivalent soluble fluorochrome units (MESF) of approximately 19 300) who underwent pretransplant plasmapheresis (PP), and Low DSA group—29 recipients with a baseline channel shift <300 who did not undergo PP. The incidence of AHR was 39% (16/41) in the High DSA group and 31% (9/29) in the Low DSA group. Overall, mean DSA levels decreased by day 4 posttransplant and remained low in patients who did not develop AHR. By day 10, DSA levels increased in patients developing AHR with 92% (23/25) of patients with a BFXM >359 (MESF of approximately 34 000) developing AHR. The BFXM and the total DSA measured by single antigen beads correlated well across a wide spectrum suggesting that either could be used for monitoring. We conclude that AHR is associated with the development of High DSA levels posttransplant and protocols aimed at maintaining DSA at lower levels may decrease the incidence of AHR.     

Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.     

Development of posttransplant antidonor HLA antibodies is associated with acute humoral rejection and early graft dysfunction

BACKGROUND: The goal of this study was to determine whether the production of posttransplant antibodies directed against donor HLA mismatches (donor specific antibody; DSA) is associated with renal allograft rejection and early graft dysfunction. METHODS: Forty-nine adult renal allograft recipients with increased risk of rejection were enrolled during the period of October 2001 through May 2003 and were prospectively monitored for the development of anti-HLA antibodies. RESULTS: Of 49 patients, eight (16.3 %) patients were diagnosed with acute humoral rejection (AHR) and 11/49 (22.4%) patients were diagnosed with acute cellular rejection (ACR). A strong association between pretransplant HLA sensitization and AHR was found (P=0.005). Of the eight patients diagnosed with AHR, the majority developed DSA before or concomitant with episodes of rejection (P<0.001). Only 3 of 41 patients (7.3%) without AHR developed DSA. The pathogenic role of alloantibodies was further substantiated by analyzing their association with graft function as measured by serum creatinine levels. The average serum creatinine after the third month posttransplantation in DSA producers was 2.24+/-1.01 mg/dL, while in non-DSA patients the average serum creatinine was 1.41+/-0.37 mg/dL (P<0.01). CONCLUSION: This study reveals a strong association between the production of DSA, AHR, and early graft dysfunction. Our findings indicate that prospective monitoring for anti-HLA antibodies following transplantation is a useful test for the diagnosis and classification of AHR for identifying patients at risk of early graft dysfunction.     

Basiliximab is associated with a lower incidence of De novo donor-specific HLA antibodies in kidney transplant recipients: A single-center experience

PurposeInduction immunosuppression has improved the long-term outcomes after kidney transplant. This study explores the association of different induction immunosuppression medications (Basiliximab vs. Alemtuzumab vs. rabbit Antithymocyte Globulin) used at the time of kidney transplant with the development of de novo donor-specific HLA antibodies (DSA) in the first 12 months post-transplant period.MethodsA total of 390 consecutive kidney transplant recipients (KTR), between 2016 and 2018, were included in the analysis. A 104 (26.6%) received Basiliximab, 186 (47.6%) received Alemtuzumab, and 100 (25.6%) received rabbit Antithymocyte Globulin (rATG) for induction. All recipients had a negative flow cytometry crossmatch before transplant. Serum samples at 4- and 12-months post-transplant were assessed for the presence of de novo HLA DSA. kidney allograft function was compared among the three groups with calculated Creatinine Clearance on 24 h urine collection.ResultsDe novo HLA DSA were detected in total of 81 (20.8%) patients within 12 months post-transplant. De novo HLA DSA were detected in 12/104 (11.5%), 43/186 (23.11%), and 26/100 (26%) KTR that received Basiliximab, Alemtuzumab, and rATG respectively (p = 0.006). KTR that received Basiliximab were significantly older, and the last follow-up creatinine clearance was significantly lower at 42 ml/min compared to KTR that received Alemtuzumab or rATG (p = 0.006).ConclusionInduction immunosuppression utilizing Basiliximab is associated with significant reduction in development of de novo DSA within the first 12-months post kidney transplant but had lower creatinine clearance with long-term follow up.     

New onset hyperglycemia and diabetes are associated with increased cardiovascular risk after kidney transplantation

BACKGROUND: Post-transplant diabetes (PTDM) is a common and serious complication of kidney transplantation. The implications of developing hyperglycemia of lesser severity are not well understood. METHODS: In this study we used American Diabetes Association (ADA) criteria to assess the incidence of abnormal glycemia post-transplant, the variables that relate to this complication, and the relationship between hyperglycemia and cardiovascular (CV) disease. Included in the study were 490 kidney recipients, transplanted from 1998 to 2003, without a history of diabetes, and with a pretransplant fasting glucose <126 mg/dL. RESULTS: Within one week post-transplant, 45% of recipients had impaired fasting glycemia (IFG, glucose 100-125 mg/dL), and 21% PTDM (glucose > or =126). One year post-transplant, 33% of patients had IFG, and 13% PTDM. Risk factors for hyperglycemia at one year included: older recipient, male gender, higher BMI, higher pretransplant glucose, and higher glucose one week post-transplant (all P < 0.002 by multivariable analyses). During a follow-up period of 40 +/- 14 months, 12% of recipients had CV events (cardiac, CVA, and/or peripheral). Increasing fasting glucose levels at one, four, and/or 12 months post-transplant were significantly related to CV events. Furthermore, these relationships were independent of other CV risk factors, including: older age, CV events pretransplant, male gender, dyslipidemia, and transplant year. Fasting glucose levels >100 mg/dL were associated with higher incidence of post-transplant cardiac (P= 0.001) and peripheral vascular disease events (P= 0.003). CONCLUSION: The incidence of post-transplant hyperglycemia and its CV impact have been underestimated. Pretransplant characteristics and, particularly, the glycemia during the first month post-transplant identified patients at risk of PTDM. Increasing glucose levels greater than 100 mg/dL, any time after the first month post-transplant, are associated with increasing CV risk. We postulate that aggressive detection and treatment of post-transplant hyperglycemia may significantly reduce CV morbidity and mortality after kidney transplantation.     

肾移植术后急性体液性排斥反应的治疗

目的 总结肾移植术后急性体液性排斥反应中针对HLA抗体的检测和处理经验.方法 肾移植受者15例,术前行HLA分型、交叉配型和群体反应性抗体(PRA)的检测,术后采用他克莫司(或环孢素A)、霉酚酸酯和糖皮质激素预防排斥反应.15例于肾移植后1～14 d发生抗体介导的急性排斥反应(AMR),采用抗胸腺细胞球蛋白(100 mg/d,使用5 d)治疗,或将环孢素A转换为他克莫司,当PRA明显升高,且血清中出现供者特异性HLA抗体时,即行血浆置换(PP),共行1～5次,每次PP后静脉输注免疫球蛋白(IVIG)100～150 mg/kg,最后1次PP后给予WIG 200～500mg/kg.结果 术后出现抗供者特异性HLA Ⅰ类抗体者9例,抗HLAⅡ类抗体者4例,同时出现抗Ⅰ、Ⅱ类抗体者2例.14例的AMR逆转,1例术后发生移植肾功能恢复延迟,彩色多普勒超声波显示移植肾血流灌注差,于术后第10天切除移植肾.并行二行肾移植.2例AMR后并发急性肾小管坏死,透析后移植肾功能恢复正常.抗排斥反应治疗期间患者均未发生严重感染.随访12～52个月,1例因慢性移植肾肾病恢复血液透析治疗,1例死于心血管疾病,其余患者移植肾功能稳定.结论 将ATG、PP和IVIG联合应用能有效逆转AMR.     

Rituximab therapy for acute humoral rejection after kidney transplantation

A pilot study was performed on eight consecutive renal-transplant (RT) patients presenting with acute humoral rejection (AHR) to assess the efficacy of monoclonal anti-B cell antibodies, such as rituximab (375 mg/m weekly) for 3 to 5 consecutive weeks, in addition to plasma exchange (PE), steroids, mycophenolate mofetil, and tacrolimus. AHR was associated with increased serum creatinine, the appearance of donor-specific alloantibodies (DSA), and the presence of C4d in a transplant biopsy. After a follow-up of 10 months (range 7-23), patient and graft survivals were 100% and 75%, respectively. Renal function improved in six cases in which serum creatinine decreased from 297+/-140 to 156+/-53 micromol/L (P=0.015); graft loss occurred in two cases; and four patients had infectious complications. At last follow-up, DSA had disappeared or decreased in four cases. Rituximab therapy, in addition to PE, might be of benefit for RT patients presenting with AHR.     

Early steroid withdrawal therapy in renal transplant recipients: a steroid-free sirolimus and CellCept-based calcineurin inhibitor-minimization protocol

BACKGROUND: Maintenance steroid therapy is associated with significant morbidity and mortality in renal transplant recipients. Elimination of the many long-term side effects of corticosteroids, including those that impinge on cardiovascular risk, remains a laudable goal in designing immunosuppressive protocols. However, concern persists that prednisone-free maintenance immunotherapy in kidney transplant recipients will result in an increase incidence of acute rejections, renal dysfunction and ultimate graft loss. METHODS: From 24 March 2003 to 1 December 2004, 84 kidney transplant recipients (61 deceased donor, 23 living donors) discontinued prednisone on post-operative day 6. Immunotherapy consisted of polyclonal antibody induction (thymoglobulin) for five d and prednisone intraoperatively with a rapid taper over the next six d. Maintenance therapy consisted of a sirolimus and CellCept-based calcineurin inhibitor-minimization protocol. Tacrolimus and mycophenolate mofetil (CellCept) were initiated on day 0. Sirolimus immunotherpay was started on post-operative day 6 concomitant with the cessation of steroids. We compared outcomes with that of our historical controls, treated with sirolimus and tacrolimus, who did not discontinue steroids. In addition, we analyzed outcomes independently for recipients of living and deceased donors in the steroid-free protocol. RESULTS: The recipients on prednisone-free maintenance immunosuppression had excellent 2.5-yr actuarial patient survival (97%), graft survival (93%), and acceptable acute rejection-free graft survival (89%). The mean serum creatinine level (+/-SD) at one yr was 1.5 +/- 0.6 mg/dL and at two yr was 1.5 +/- 0.6 mg/dL. We noted that 5% of recipients developed cytomegalovirus (CMV) syndrome; 1%, polyoma nephropathy; 1%, post-transplant lymphoproliferative disorder (PTLD), and 5% developed post-transplant diabetes mellitus (PTDM). In all, 91% of kidney recipients with functioning grafts remain steroid-free as of 31 December 2005. When compared with historical controls, the recipients on the early steroid-withdrawal (ESW) protocol had comparable graft survival, acute rejection-free survival, graft function, but significantly better patient actuarial survival (p = 0.048). In addition, recipients on the steroid-free protocol had decreased prevalence of four risk factors for cardiovascular disease when compared with historical controls: hypertension (p = 0.008), hyperlipidemia (p = 0.003), weight gain (p = 0.024), and incidence of PTDM (p = 0.015). CONCLUSION: Early steroid-withdrawal in renal transplant recipients with a sirolimus and CellCept-based calcineurin inhibitor-minimimization protocol can effectively reduce many of the steroid-related side effects, decrease risk factors for cardiovascular disease, and is associated with improved recipient survival without compromising graft function.     

Clinical predictors of exercise capacity 1 year after cardiac transplantation.

BACKGROUND: The exercise capacity of cardiac transplant recipients is reduced compared with normal controls. However, clinical variables predictive of post-transplant exercise capacity have not been well defined. The objective of the present study was to identify clinical features predictive of post-transplant exercise capacity. METHODS: Ninety-five cardiac transplant recipients underwent cardiopulmonary testing at 1 year after transplant. The exercise parameters were compared with both pre-transplant values and normal subjects. The relationships between exercise parameters and clinical characteristics were analyzed. RESULTS: Mean peak oxygen consumption (VO(2)) and exercise test duration at 1-year post-transplant improved significantly from 16.4 to 19.9 ml/kg/min and 5.5 to 7.6 minutes, respectively (p < 0.001), but were significantly lower than for normal controls (peak VO(2) 34.0 ml/kg/min; exercise duration 11.2 minutes; p < 0.001). Age- and gender-adjusted VO(2) was 54% of predicted. Pre-operative body weight correlated strongly with post-transplant weight (r = 0.80, p < 0.001). Significant recipient predictors of 1-year post-transplant peak VO(2) identified by multivariate regression analysis were age, male gender, body mass index, exercise peak heart rate and duration of post-operative intensive care. Donor variables did not contribute significantly to post-transplant peak VO(2). CONCLUSIONS: Peak VO(2) improved after cardiac transplantation but remained significantly impaired compared with normal subjects. In estimating the impact of cardiac transplantation on exercise capacity the most important pre-transplant factors to consider are age, gender and height and weight (or, alternatively, body mass index).     

Serum lipid pattern unifies following renal transplantation in children

Hyperlipidemia is a common problem in solid organ transplant recipients. In this study we evaluated the role of pre-transplant renal replacement therapy on early and late changes of serum lipid levels in children following renal transplantation. In 46 children with chronic renal failure (median age 10.3 years) and 12 children with heart failure (median age 5.0 years), cholesterol and triglycerides were measured before and during follow-up after transplantation. Children with renal failure had significantly higher serum lipids than controls (n=34, median age 9.2 years) and patients with heart failure. Pre transplantation, cholesterol and triglycerides were significantly lower in the hemodialysis than in the peritoneal dialysis population, whereas conservatively treated children had intermediate levels. After transplantation, serum cholesterol converged towards a mean level of 208 mg/dl and triglyceride levels converged towards a uniform level of 195 mg/dl at 9 months post transplant. The ratio of cholesterol/high-density lipoprotein significantly decreased from 4.7 to 3.8. The pattern of "post-transplant hyperlipidemia" was similar in both renal and cardiac allograft recipients. Hence, the early post-transplant changes of serum lipid pattern are markedly dependent on the mode of pre-transplant renal replacement therapy. Later, serum lipid levels were no longer influenced by prior renal replacement therapy and showed a new pattern of "post-transplant hyperlipidemia" in all children.     

Prognostic value of serum carcinoembryonic antigen levels in patients who undergo lung transplantation

BACKGROUND: Potential candidates for lung transplantation undergo a rigorous evaluation before transplant. Serum carcinoembryonic antigen (CEA) levels are used as a screening tool for occult malignancy in many lung transplant centers. We reviewed the pre-transplant CEA levels in lung transplant recipients in our institution to determine their prognostic significance. MATERIALS AND METHODS: We performed a retrospective database review of the first 200 patients that had undergone lung or heart-lung transplant at our institution (dates were 1/20/92-7/25/98). Data extracted included CEA levels (in ng/ml) at the time of lung transplant evaluation, demographic data, and survival. Patients had one of the following diagnoses: alpha-1-anti-trypsin deficiency, cystic fibrosis, chronic obstructive pulmonary disease, Eisenmenger's syndrome, idiopathic pulmonary fibrosis, primary pulmonary hypertension, sarcoidosis, or other. RESULTS: After excluding re-transplants, CEA results were available for 174 of 193 (90.2%) patients. CEA levels were elevated in 85 patients (48.9%) with a mean value of 3.15 +/- 2.55 (normal < 2.5). Solid organ cancers developed in 6 patients, at a median follow-up of 27.5 months after transplant. Their mean pre-transplant CEA level was similar to the rest of the group (3.52 +/- 2.05). Pre-transplant CEA levels did not predict post-transplant survival. Patients with idiopathic pulmonary fibrosis had the highest pre-transplant CEA levels, whereas patients with primary pulmonary hypertension and Eisenmenger's syndrome had the lowest (5.36 +/- 4.59, 0.83 +/- 0.56, and 1.43 +/- 0.81, respectively; p = 0.0001). CONCLUSIONS: CEA levels are high in patients with end-stage lung disease, especially IPF. Their levels appear to be a marker of the underlying disease and do not predict the post-transplant survival or development of malignancy.     

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.     

Soluble CD30 concentrations in ESRD patients with and without panel reactive HLA antibodies

BACKGROUND: In this retrospective study we compared accuracy of panel reactive antibodies (PRA) with serum soluble CD30 (sCD30) contents in predicting acute rejection crisis post-renal transplant. METHODS: Pre-transplant sera from 115 patients were evaluated for their PRA and sCD30 concentrations. All patients received calcineurin inhibitor-based immunosuppressive therapy. Objective measurements for rejection were biopsy-proven acute rejection (AR) episodes within first six months of the transplant. Post-transplant sera of patients with AR were tested for the presence of donor-specific HLA antibodies (DSA). RESULTS: Overall AR rate was 16% (18/115). Patients positive for PRA and sCD30 tests were at significantly higher risk for AVR compared with those patients negative for both the tests (36% vs. 5%, p=0.01). Among negative PRA patients risk for AR was significantly elevated if they were also tested positive for sCD30 concentrations (21% vs. 5%, p=0.04). Of the 18 patients with AR, 14 were positive for sCD30, and 13 of them (93%) developed DSA post-transplant (p=0.001). CONCLUSION: These data showed that patients positive for sCD30 contents are at high risk for the development of DSA and AR post-transplant regardless of their pre-transplant PRA.     

Gastroparesis following kidney/pancreas transplant

This pilot study examined associations among patterns of gastric myoelectrical activity, symptoms of gastroparesis, years of diabetes, months of dialysis, and use of gastrointestinal medications in gastroparetic kidney-pancreas (KP) transplant recipients. Electrogastrography (EGG) and gastric symptom data were obtained from 42 transplant recipients before and after transplant (6, 12, and 24 months). Recipients were 38 +/- 7 yr of age, 88% Whites, and 60% male; 97% had hypertension. All had functioning grafts post-transplant (mean creatinine, 1.59 +/- 0.66 mg/dL, and serum glucose 91.97 +/- 24.92 mg/dL). Sixteen subjects had normal EGG (2.7-3.2 cycles per minute, cpm); two were tachygastric (>3.2 cpm) at all time points; one remained bradygastric (<2.7 cpm) throughout the study period. Following transplant, symptoms lessened and were associated with 6-month normalization of EGG (r = 0.41, p = 0.02). A small change in the percentage of patients with normal EGG was observed from baseline to 24 months (67% vs. 69% respectively); however, there was a shift from bradygastria (29% to 15% respectively) to tachygastria (5% to 15% respectively). Prescribed prokinetic and antisecretory medications use increased over the study period from 13 (31%) subjects at baseline to 32 (86%) at 6 months; 21 (78%) at 12 months; and 12 (92%) at 24 months. Although symptoms diminish following transplant, gastroparesis remains a significant problem for transplant patients. Normalization of EGG and shifts from bradygastria to tachygastria occur post-transplant. Our results suggest that serial EGGs and frequent assessment of symptoms can be used to follow gastroparesis in KP recipients.     

Efficacy and cardiovascular safety of daclizumab, mycophenolate mofetil, tacrolimus, and early steroid withdrawal in renal transplant recipients: a multicenter, prospective, pilot trial

This single-arm, open-label, pilot study was designed to assess the efficacy and cardiovascular safety profile of daclizumab, a humanized monoclonal interleukin (IL)-2Ralpha antibody, in combination with mycophenolate mofetil (MMF), tacrolimus, and early corticosteroid withdrawal in renal transplant recipients. Seventy-nine renal allograft recipients were treated with daclizumab (1 mg/kg; five doses starting on the day before transplant and then every two weeks), MMF (1 g b.i.d.), tacrolimus (0.2 mg/kg/d), and low-dose prednisolone, which was withdrawn at day 150 after transplant. The rate of acute rejection was determined at 12 months. Lipid profile, oral glucose tolerance, and adverse events were monitored. Of the 76 patients eligible for analysis, eight (10.5%) developed biopsy-proven acute rejection (BPAR). Ten (13.2%) experienced clinical and/or BPAR. Corticosteroids were withdrawn completely in 91% of patients at 12 months. Graft and patient survival were 97.5% and 98.7% respectively. Mean total cholesterol and triglycerides were significantly lower at 12 months post-transplant than at baseline (201 +/- 47.5 vs. 190.8 +/- 43.6 mg/dL, p = 0.005 and 196.2 +/- 133.2 vs. 144.5 +/- 76.8 mg/dL, p < 0.001, respectively). Mean hemoglobin A1c levels did not differ between baseline (5.54%) and 12 months (5.48%). New-onset post-transplant diabetes mellitus occurred in 6.6% of the non-diabetic transplanted patients. The proportion of patients with abnormal oral glucose tolerance test (OGTT) was 47% at 3 months and 39% at 12 months (p = NS). Daclizumab induction in combination with MMF, tacrolimus, and low-dose (followed by withdrawal) prednisolone appears to be effective and safe in patients receiving renal allografts. The regimen appears to be associated with a favorable cardiovascular profile.     

Tuberculosis in Egyptian kidney transplant recipients: study of clinical course and outcome

BACKGROUND: Tuberculosis (TB) is an important infection encountered post-transplantation especially in developing countries, with high incidences of morbidity and mortality. In this report, we study the risk factors and impact of TB on the outcome of kidney transplantation. METHODS: Of 1200 live-donor Egyptian kidney transplantations, 45 (3.8%) patients developed post-transplant TB. Of these, five had had TB pre-transplantation and 40 were male. The mean age was 32.6 +/- 10.5 years. Primary immunosuppression treatment for 39 (86.7%) patients was cyclosporine (CsA). RESULTS: The mean time interval between transplantation and TB diagnosis was 49.8 +/- 41.5 (range 2-180) months. In 86.7% of patients, TB was diagnosed one year post-transplantation. Urinary TB was the most common form (53%), while pleuropulmonary TB accounted for 38%. All post-transplant TB patients received a triple anti-tuberculous therapy (rifampicin, ethambutol and INH) with a favorable response in all but two patients who needed another 24-month course. Hepatotoxicity was seen in 11 patients, eight were mild with normalization after temporary withdrawal of rifampicin, and three cases were severe, but mortality was not attributable to hepatocellular failure. Twelve patients died, 11 of them due to unrelated causes. Chronic rejection occurred in more than half of the patients (55.6%), of whom 24 (96%) were CsA-treated, which can be attributed to rifampicin/CsA interaction. More than 35% of TB patients lost their graft as a result. Pre-transplant tuberculosis patients had a comparable post-transplant course. CONCLUSIONS: TB is a common infection in renal transplant recipients with a peak incidence occurring one year post-transplant. Chronic rejection is a serious complication that had a negative impact on the graft survival, especially in CsA-treated recipients. INH prophylaxis is safe in pre-transplant TB. The post-transplantation outcome in the pre-transplant tuberculosis patients is no different from non-TB patients.