High-risk Kidney Transplant Research Articles

Prevalence of Skin Cancer and Related Skin Tumors in High-Risk Kidney and Liver Transplant Recipients in Queensland, Australia

The increased skin cancer incidence in organ transplant recipients is well-known, but the skin cancer burden at any one time is unknown. Our objective was to estimate the period prevalence of untreated skin malignancy and actinic keratoses in high-risk kidney and liver transplant recipients and to assess associated factors. Organ transplant recipients underwent full skin examinations by dermatologically trained physicians. The proportion of examined organ transplant recipients with histopathologically confirmed skin cancer in the 3-month baseline period was estimated. Prevalence ratios with 95% confidence intervals indicated significant associations. Of 495 high-risk organ transplant recipients (average age= 54 years, time immunosuppressed= 8.9 years), 135 (27%) had basal cell carcinoma, squamous cell carcinoma or Bowen's disease (intraepidermal carcinoma) present and confirmed in the baseline period, with respective prevalence proportions of 10%, 11%, and 18% in kidney transplant recipients and 10%, 9%, and 13% in liver transplant recipients. Over 80% had actinic keratosis present, with approximately 30% having 5 or more actinic keratoses. Organ transplant recipients with the highest skin cancer burden were Australian born, were fair skinned (prevalence ratio= 1.61, 95% confidence interval= [1.07, 2.43]), reported past skin cancer (prevalence ratio=3.39, 95% confidence interval= [1.93, 5.95]), and were receiving the most frequent skin checks (prevalence ratio= 1.76, 95% confidence interval= [1.15, 2.70]). In conclusion, high-risk organ transplant recipients carry a substantial measurable skin cancer burden at any given time and require frequent review through easily accessible, specialized services.

Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.

Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR-GL (86 vs 0 vs 0%; log-rank P < 0.001) compared with post-transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant.

Effects of Ideal Versus Total Body Weight Dosage of Rabbit Antithymocyte Globulin on Outcomes of Kidney Transplant Patients With High Immunologic Risk.

The optimal dose of rabbit antithymocyte globulin induction therapy in kidney transplant recipients with high immunologic risk lacks consensus. The purpose of this study was to evaluate the effect of using ideal body weight rather than total body weight for the weight-based dose calculations in this patient population. Data were retrospectively collected on 89 adult patients who received rabbit antithymocyte globulin induction therapy for high immunologic risk kidney transplant. Hospital protocol changed from the use of cumulative rabbit antithymocyte globulin doses of 7.5 mg/kg total body weight to 7.5 mg/kg ideal body weight in 2009. Patients were separated into 2 cohorts based on the amount of rabbit antithymocyte globulin (in mg/kg total body weight) received. Rate of biopsy-proven acute rejection, patient survival, and allograft function were evaluated at 90 days and 1 year after transplant. Cost of induction therapy was also evaluated. Baseline demographics were predominantly similar between the 2 cohorts. No significant difference in maintenance immunosuppression was identified. Rates of biopsy-proven acute rejection at 90 days and 1 year were similar between ideal and total body weight cohorts (4.2% vs 0% at 90 days, P = .5; 8.7% vs 0% at 1 year, P = .13). Patient survival and allograft function were also similar. Median cost of rabbit antithymocyte globulin induction therapy per patient was lower in the ideal body weight cohort, but this difference was not statistically significant ($17 542 vs $19 934; P = .3). Our results suggest that use of ideal body weight for dose calculations of rabbit antithymocyte globulin induction therapy in high immunologic risk kidney transplant recipients at 7.5 mg/kg results in low rates of acute rejection with a safety profile similar to that shown with a total body weight dosage. Use of ideal body weight for lower cumulative doses may still need further evaluation in this patient population.

Effects of induction therapy with alemtuzumab versus antithymocyte globulin among highly sensitized kidney transplant candidates.

We retrospectively compared induction therapy utilizing alemtuzumab and antithymoglobulin (ATG) in high-risk kidney transplant recipients in our center. Two hundred and fifty-one patients underwent kidney transplantation between 2009 and 2012. The high-risk patients were defined as those who had two or more times kidney transplantation and/or more than 30% panel reactive antibody. We studied 130 high-risk kidney transplant candidate; 58 (44.6%) patients received induction immunosuppressive therapy with alemtuzumab, and 72 (55.4%) with ATG. Delayed graft function developed in 11 patients receiving alemtuzumab, against the 27 patients who receiving ATG (P = 0.021). Acute cellular rejection episodes were observed in five patients in the alemtuzumab group and 19 patients in the ATG group (P = 0.009). There were three graft failures in the alemtuzumab group and eight graft failures in the ATG group due to rejection episodes. We found immunosuppressive induction therapy with alemtuzumab a significantly less incidence of acute rejection and delayed graft function than induction therapy with ATG in the high-risk kidney transplant recipients.

Alemtuzumab (Campath-1H) experience in kidney transplantation what we have learned; current practices; and scope for the future?

Alemtuzumab (Campath) usage as a preconditioning agent in kidney transplantation has gained considerable interest in the recent future. Alemtuzumab is currently available only by special request from Sanofi through its Campath distribution program. It is restricted to transplant programs with prior and continued experience with the agent. There may be a resurgence of interest for the utilization of this agent because of its ease of administration, and less cost and comparable or improved outcome in comparison to other induction agents. Alemtuzumab when combined with standard calcineurin inhibitor and mycophenolate mofetil is well tolerated and efficacious as an induction therapy and allows for long-term steroid avoidance in high-risk renal transplant recipients. The transplant community has advanced through a learning curve with the use of alemtuzumab over time; starting from an agent that was tried out to induce proper tolerance, minimization of nephrotoxic calcineurin inhibitors, and currently as a comparable depletional therapy that can reduce acute rejection in high-risk kidney transplant recipients.

Safe Conversion From Tacrolimus to Belatacept in High Immunologic Risk Kidney Transplant Recipients With Allograft Dysfunction

There is no literature on the use of belatacept for sensitized patients or regrafts in kidney transplantation. We present our initial experience in high immunologic risk kidney transplant recipients who were converted from tacrolimus to belatacept for presumed acute calcineurin inhibitor (CNI) toxicity and/or interstitial fibrosis/tubular atrophy. Six (mean age = 40 years) patients were switched from tacrolimus to belatacept at a median of 4 months posttransplant. Renal function improved significantly from a peak mean estimated glomerular filtration rate (eGFR) of 23.8 ± 12.9 mL/min/1.73 m(2) prior to the switch to an eGFR of 42 ± 12.5 mL/min/1.73 m(2) (p = 0.03) at a mean follow-up of 16.5 months postconversion. No new rejection episodes were diagnosed despite a prior history of rejection in 2/6 (33%) patients. Surveillance biopsies performed in 5/6 patients did not show subclinical rejection. No development of donor-specific antibodies (DSA) was noted. In this preliminary investigation, we report improved kidney function without a concurrent increase in risk of rejection and DSA in six sensitized patients converted from tacrolimus to belatacept. Improvement in renal function was noted even in patients with chronic allograft fibrosis without evidence of acute CNI toxicity. Further studies with protocol biopsies are needed to ensure safety and wider applicability of this approach.

Geographic Variation in Cold Ischemia Time: Kidney vs. Liver Transplantation in the United States, 2003-2011.

BackgroundRegional variations in kidney and liver transplant outcomes have been reported, but their causes remain largely unknown. This study investigated variations in kidney and liver cold ischemia times (CITs) across organ procurement organizations (OPO) as potential causes of variations in transplant outcomes.MethodsThis retrospective study analyzed the Standard Transplant Analysis and Research data of deceased donor kidney (n = 61,335) and liver (n = 39,285) transplants performed between 2003 and 2011. The CIT variations between the 2 types of organs were examined and compared. Factors associated with CIT were explored using multivariable regressions. Spearman rank tests were used to associate CIT with graft failure at the OPO level.ResultsSignificant CIT variations were found across OPOs for both organs (P < 0.05). The variation was particularly large for kidney CIT. Those OPOs with longer average kidney CIT were likely to have a lower graft survival rate (P = 0.01). For liver, this association was insignificant (P = 0.23). The regression analysis revealed sharp contrasts between the factors associated with kidney and liver CITs. High-risk kidney transplant recipients and marginal kidneys were associated with longer average CIT. The reverse was true for liver transplants.ConclusionsLarge variations in kidney CIT compared to liver CIT may indicate that there is a room to reduce kidney CIT. Reducing kidney CIT through managerial improvements could be a cost-effective way to improve the current transplant system.

83 Serum BAFF levels and B cell subsets in secondary lymphoid organs after rituximab administration: Its association with clinical outcomes

INTRODUCTION AND OBJECTIVES: Rituximab (RIT), antiCD20 antibody, has been applied to kidney transplantation because of its potent B-cell depleting effect. Although CD20+ cells in peripheral blood (PB) and spleen are consistently depleted in patients receiving RIT, the clinical effects are heterogeneous, probably related to differences in the depleting effects of secondary lymphoid organs (SLOs), such as peripheral lymph nodes (LNs). Meanwhile, B cell activation factor of the TNF family (BAFF) promotes B cell development and antibody secretion, and also serum BAFF levels increase after RIT administration. The aim of this study was to investigate the relationship between serum BAFF levels and B cell subsets in different lymphoid organs after RIT administration and its association with clinical outcomes. METHODS: Since April 2005, 50 patients with immunological high risks [ABO-incompatible (ABOI) or donor specific anti-HLA antibody (DSA) positive or both] received a single dose of RIT with 200 mg/ body at 3 weeks before kidney transplantation. They received 3 to 4 sessions of apheresis prior to transplantation. The induction immunosuppressive therapy was consisted of tacrolimus, MMF, steroid, and basiliximab. In all patients, the several pelvic LNs were dissected at the time of transplantation. Of those, 2 ABOI (induction period of RIT) and 6 DSA positive patients received splenectomy concurrently with transplantation. Immunohistochemical intensity of B cell subsets (CD20, CD27, CD79a, and CD138) in both LN and spleen was scored. Serum BAFF levels at day -7, 7, and 28 post-transplant were measured by ELISA. RESULTS: Acute antibody-mediated rejection (AAMR) developed in 9 patients (19%) in this series. The intensity score of CD138 in LNs was significantly higher in AMR patients (p<0.01) than those in non-AMR patients. No significant difference was found in the intensity scores of all B cell subsets in spleen among the patients with or without AMR. The serum BAFF levels at day -7 (p<0.01), 7 (p<0.05), and 28 (p<0.01) post-transplantation were significantly lower in AMR patients than in non-AMR patients. The existence of DSA before transplant, the intensity score of CD138 in LNs, and low serum BAFF level at 7 days before transplant were significantly associated with the occurrence of AAMR. CONCLUSIONS: In immunological high risk kidney transplant recipients receiving RIT before transplant, the plasma cell intensity in LNs and low serum BAFF level were risk factors of AAMR.

Improvement in Renal Function in High Immunologic Risk Kidney Transplant Recipients Switched From Tacrolimus to Belatacept.

Improvement in Renal Function in High Immunologic Risk Kidney Transplant Recipients Switched From Tacrolimus to Belatacept.

Efficacy and Safety of Combination Therapy With Tacrolimus and Sirolimus in Immunological High Risk Kidney Transplant Recipients.

Objective: The aim of this study was to evaluate the efficacy and safety of combination therapy with tacrolimus and sirolimus in immunological high risk recipients. Methods: From January 2010 to December 2011, 28 immunological high risk patients were enrolled according to the following criteria: 1) retransplantation, 2) Class I or II PRA >50%, 3) 5 or 6 HLA mismatches The efficacy endpoints were incidence of biopsy-proven acute rejection reaction, graft loss, patient death and renal function. The safety was evaluated by analyzing the adverse effects. Results: Among 28 total patients, 8 (28.6%) were dropped due to acute rejection, infection, pneumonitis, or postoperative hemorrhage. One patient death occurred due to fungal infection. Acute rejection developed in 6 (21.4%) patients. The mean eGFR (MDRD) for the 1st year after transplantation was 52.0 ± 4.0 mL/min/1.73m2. Fifteen (53.6%) patients had infections and 3 (10.7%) patients experienced pneumonitis. Lymphocele developed in 4 (14.3%) patients. Conclusion: The combination therapy with tacrolimus and sirolimus must be considered with caution for immunological high risk recipients due to high incidence of adverse events. Special attention should be given to the target blood concentration levels of the two drugs in order to minimize adverse events.

Prevention strategies for cytomegalovirus disease and long-term outcomes in the high-risk transplant patient (D+/R-): experience from the RESITRA-REIPI cohort.

Cytomegalovirus (CMV)-negative recipients of a graft from a CMV-positive donor (D+/R-) are at high risk of CMV disease. Current preventive strategies include universal prophylaxis (UP) and preemptive therapy (PT). However, the best strategy to prevent CMV disease and achieve better long-term outcomes remains a matter of debate. We analyzed the incidence of CMV disease and long-term outcomes including graft dysfunction and patient mortality at 5 years after transplantation with both preventive strategies. High-risk (D+/R-) kidney and liver transplant recipients from the RESITRA cohort were included. Of 2410 kidney or liver transplant patients, 195 (8.3%) were D+/R-. The final cohort included 58 liver and 102 kidney recipients. UP was given in 92 patients and 68 received PT; 10.9% and 36.8% developed CMV disease, respectively (P < 0.01). The independent risk factors for CMV disease were PT strategy (hazard ratio [HR], 3.30; 95% confidence interval [CI], 1.6-6.9), kidney transplantation (HR, 3.8; 95% CI, 1.4-9.9), and cyclosporine immunosuppression (HR, 2.4; 95% CI, 1.2-4.7). PT strategy was also a risk factor for CMV disease in both liver transplantation (HR, 11.0; 95% CI, 1.2-98.7) and kidney transplantation (HR, 2.7; 95% CI, 1.3-6.0), independently. The development of CMV replication during the first 2 years after transplantation was a risk factor for graft dysfunction at 5 years after transplantation (odds ratio, 3.4; 95% CI, 1.3-9.0). Nevertheless, no significant differences were seen in either graft dysfunction or mortality between the 2 strategies. The study supports the benefit of the UP strategy to prevent CMV disease in D+/R- liver or kidney transplant patients. The development of CMV replication during the first 2 years after transplantation was associated with graft dysfunction at 5 years after transplantation.

MP72-03 SERUM BAFF LEVELS AND B CELL SUBSETS IN DIFFERENT LYMPHOID ORGANS AFTER RITUXIMAB ADMINISTRATION: ITS ASSOCIATION WITH CLINICAL OUTCOMES

You have accessJournal of UrologyTransplantation & Vascular Surgery II1 Apr 2014MP72-03 SERUM BAFF LEVELS AND B CELL SUBSETS IN DIFFERENT LYMPHOID ORGANS AFTER RITUXIMAB ADMINISTRATION: ITS ASSOCIATION WITH CLINICAL OUTCOMES Mitsuru Saito, Shigeru Satoh, Kazuyuki Numakura, Mingguo Huang, Hiroshi Tsuruta, Susumu Akihama, Takamitsu Inoue, Shintaro Narita, Norihiko Tsuchiya, and Tomonori Habuchi Mitsuru SaitoMitsuru Saito More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Mingguo HuangMingguo Huang More articles by this author , Hiroshi TsurutaHiroshi Tsuruta More articles by this author , Susumu AkihamaSusumu Akihama More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2242AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Rituximab (RIT), anti-CD20 antibody, has been applied to kidney transplantation because of its potent B-cell depleting effect. Although CD20+ cells in peripheral blood (PB) and spleen are consistently depleted in patients receiving RIT, the clinical effects are heterogeneous, probably related to differences in the depleting effects of secondary lymphoid organs (SLOs), such as peripheral lymph nodes (LNs). Meanwhile, B cell activation factor of the TNF family (BAFF) promotes B cell development and antibody secretion, and also serum BAFF levels increase after RIT administration. The aim of this study was to investigate the relationship between serum BAFF levels and B cell subsets in different lymphoid organs after RIT administration and its association with clinical outcomes. METHODS Since April 2005, 50 patients with immunological high risks [ABO-incompatible (ABOI) or donor specific anti-HLA antibody (DSA) positive or both] received a single dose of RIT with 200 mg/body at 3 weeks before kidney transplantation. They received 3 to 4 sessions of apheresis prior to transplantation. The induction immunosuppressive therapy was consisted of tacrolimus, MMF, steroid, and basiliximab. In all patients, the several pelvic LNs were dissected at the time of transplantation. Of those, 2 ABOI (induction period of RIT) and 6 DSA positive patients received splenectomy concurrently with transplantation. Immunohistochemical intensity of B cell subsets (CD20, CD27, CD79a, and CD138) in both LN and spleen was scored. Serum BAFF levels at day -7, 7, and 28 post-transplant were measured by ELISA. RESULTS Acute antibody-mediated rejection (AAMR) developed in 9 patients (19%) in this series. The intensity score of CD138 in LNs was significantly higher in AMR patients (p<0.01) than those in non-AMR patients. No significant difference was found in the intensity scores of all B cell subsets in spleen among the patients with or without AMR. The serum BAFF levels at day -7 (p<0.01), 7 (p<0.05), and 28 (p<0.01) post-transplantation were significantly lower in AMR patients than in non-AMR patients. The existence of DSA before transplant, the intensity score of CD138 in LNs, and low serum BAFF level at 7 days before transplant were significantly associated with the occurrence of AAMR. CONCLUSIONS In immunological high risk kidney transplant recipients receiving RIT before transplant, the plasma cell intensity in LNs and low serum BAFF level were risk factors of AAMR. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e824 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Mitsuru Saito More articles by this author Shigeru Satoh More articles by this author Kazuyuki Numakura More articles by this author Mingguo Huang More articles by this author Hiroshi Tsuruta More articles by this author Susumu Akihama More articles by this author Takamitsu Inoue More articles by this author Shintaro Narita More articles by this author Norihiko Tsuchiya More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Resolution of Mild Ganciclovir-Resistant Cytomegalovirus Disease with Reduced-Dose Cidofovir and CMV-Hyperimmune Globulin.

Ganciclovir-resistant cytomegalovirus (CMV) is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by “indirect” viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative) kidney transplant patients diagnosed with ganciclovir-resistant CMV disease. All patients initially developed “breakthrough” viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2 mg/kg) cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV.

Solid phase detection of C4d-fixing HLA antibodies to predict rejection in high immunological risk kidney transplant recipients

Protocols for recipient desensitization may allow for successful kidney transplantation across major immunological barriers. Desensitized recipients, however, still face a considerable risk of antibody-mediated rejection (AMR), which underscores the need for risk stratification tools to individually tailor treatment. Here, we investigated whether solid phase detection of complement-fixing donor-specific antibodies (DSA) has the potential to improve AMR prediction in high-risk transplants. The study included 68 sensitized recipients of deceased donor kidney allografts who underwent peritransplant immunoadsorption for alloantibody depletion (median cytotoxic panel reactivity: 73%; crossmatch conversion: n=21). Pre and post-transplant sera were subjected to detection of DSA-triggered C4d deposition ([C4d]DSA) applying single-antigen bead (SAB) technology. While standard crossmatch and [IgG]SAB testing failed to predict outcomes in our desensitized patients, detection of preformed [C4d]DSA (n=44) was tightly associated with C4d-positive AMR [36% vs. 8%, P=0.01; binary logistic regression: odds ratio: 10.1 (95% confidence interval: 1.6-64.2), P=0.01]. Moreover, long-term death-censored graft survival tended to be worse among [C4d]DSA-positive recipients (P=0.07). There were no associations with C4d-negative AMR or cellular rejection. [C4d]DSA detected 6months post-transplantation were not related to clinical outcomes. Our data suggest that pretransplant SAB-based detection of complement-fixing DSA may be a valuable tool for risk stratification.

The Monitoring of Serum Fibrinogen in Patients with End Stage Renal Disease Undergoing Plasma Exchange for High Risk Kidney Transplantation

Background: Plasma exchange is being increasingly used in the antibody reduction for high risk kidney transplantation. There were some reports of post-transplant bleeding in patients who had a large number of plasma exchange. In addition, wide variation in technique is reported, thereby adding to the confusion that exists about both efficacy and safety. Since changes in coagulation factors are known to occur to following plasmapheresis, we studied serial changes of serum fibrinogen in patients undergoing plasma exchange for antibody reduction before high risk kidney transplantation. Methods: Eighty eight times of plasma exchange were carried out at every other day in 18 patients before kidney transplantation, using the COBE® Spectra™ apheresis system. Sixteen patients were received ABO incompatible living donor kidney transplantation and 2 patients were received cross matching positive living donor kidney transplantation in our hospital from 2009 to 2011. The levels of serum fibrinogen were measured at pre-exchange, post-exchange one day and two days. In procedure, 1.0 time the calculated plasma volume was replaced with an electrolyte solution containing 5% salt-free human albumin or fresh frozen plasma (FFP). Anticoagulation was achieved using a whole venous blood to acid-citrate dextrose ratio of 15 to 1. Median flow rates, plasma collection, and procedure times were respectively 80 ml/minute, 20 ml/ minute, 80 minutes in cases of 5% albumin solution replacement and 40 ml/minute, 20 ml/minute, 150 minutes in cases of FFP replacement. Results: The cases with 5% albumin solution replacement were 55, and with FFP were 28. In cases of 5% albumin solution replacement, the mean serum fibrinogen level was 230.35 mg/dL, 138.93 mg/dL and 167.07 mg/dL at pre-exchage, post-exchage 1 day and post exchage 2 days. And in case of FFP replacement, the mean serum fibrinogen level was 168.68 mg/dL, 178.25 mg/dL and 181.18 mg/dL at the same time as before. The serum fibrinogen levels were markedly reduced immediately following the procedure and did not have returned to prior levels within 48 hours in cases of 5% albumin solution replacement. But the serum fibrinogen levels were increased in cases of FFP replacement.Table: [The serum fibrinogen levels in subjects(mg/dL).]Conclusion: In spite of every other day schedule, consecutive plasma exchange with 5% albumin solution replacement has a decrease of serum fibrinogen in patients with end stage renal disease before high risk kidney transplantation. And it may be associated with decrease coagulation and post-transplant bleeding. It is useful to prevent post-transplant bleeding that the use of FFP as replacement fluid or the use of cryoprecipitate containing fibrinogen and other coagulation factors.

The Monitoring of Serum Fibrinogen in Patients with End Stage Renal Disease Undergoing Plasma Exchange for High Risk Kidney Transplantation

The Monitoring of Serum Fibrinogen in Patients with End Stage Renal Disease Undergoing Plasma Exchange for High Risk Kidney Transplantation

Results of Immunosuppressive Switch in Polyoma Virus Nephropathy in Immunologically High Risk Kidney Transplant Recipients

Introduction: Polyoma virus nephropathy is one of the most dreadful complications after kidney transplantation and usually results in graft lost and jeopardizes the future possibility of re-transplantation. Here we present the results of five kidney transplant recipients (KTRs) who developed polyoma virus nephropathy (BKVN) within the first six months after living-related kidney transplantation (LRKT) and were switched to a new immunosuppressive regimen consisting of: low dose cyclosporin, low dose everolimus and reduced dose of antimetabolites. Methods: Four KTRs were men and one was a woman with an average age of 46 years. All were immunologically high risk KTRs with an average HLA mismatch of 4 and were transplanted their first grafts from living-related donors. All of them had received ATG (Fresenius S) and methylprednisolone (500 mg/day) as an induction therapy. The maintenance immunosuppressive treatment consisted of tacrolimus, mycophenolate mofetil (2 gm/day) and prednisolone (tapered from 40 mg/day to 5 mg/day within 6 weeks). Tacrolimus trough levels were monitored in all patients. All patients also received valganciclovir (900 mg/day) and TMP-SMX (400 mg/day) for prophylaxis. None of the recipients were diabetic but two of them developed NODAT and were receiving insulin treatment (HbA1C's %7.1 and 6.7). Results: Average time for BKVN after transplantation was 164 days. The initial presentation of the BKVN was an increase in serum creatinine levels (average increment from the baseline = 0.7 mg/dL) and CRP levels (average increment rate % 18). Mild proteinuria (< 500 mg/L) was detected in two patients. Average trough tacrolimus level was 9.8 mg/mL). The patients underwent graft biopsy and the biopsy samples were analyzed by a nephropathologist with light microscopy and immunofluorescent stainings. After receiving the initial pathology results, urine and plasma BKV PCRs were measured. Biopsies revealed BKVN with varying degrees of tubulointerstitial inflammation and all stained for SV40. Average plasma BKV copies were 800.000 copies/mL and urinary BKV copies were 160 million/mL. The average serum creatinine level was 1.8 mg/dL at the time of diagnosis. Tacrolimus was discontinued, MMF dose reduced to 1 gm/day and prednisolone dose was reduced to 5 mg/day immediately after diagnosis. Treatment with ciclosporin-A neoral 75 mg b.id. and everolimus 0.5 mg bid was initiated. Conclusion: Average follow-up period after this immunosupressive switch was 4 months. There was an initial increase in CRP and serum creatinine levels (average increase 0.3 mg/dL) after new regimen. The serum creatinine levels didn't return to baseline value but remained stable for four months for all of the patients. The average serum creatinine levels were 1.96 mg/dL at the end of four months. There was no graft loss and evidence of systemic polyoma virus infection. Although the follow-up period is brief and the number of patients in the study are insufficient, these preliminary findings suggest that low dose ciclosporin A and everolimus combination may prevent graft loss and rejection in immunologically high risk KTRs who develop BKVN in the early course after transplantation.

Differential Effect of CMV Prophylaxis in Relation to Anti-Rejection Induction Therapy on Graft Outcomes in High-Risk Kidney Transplant Patients in the United States

Differential Effect of CMV Prophylaxis in Relation to Anti-Rejection Induction Therapy on Graft Outcomes in High-Risk Kidney Transplant Patients in the United States

Cytomegalovirus Viremia After Kidney Transplantation in Thailand: Predictors of Symptomatic Infection and Outcome

BackgroundWhile prevention of cytomegalovirus (CMV) infection after kidney transplantation (KT) has become a standard practice in Western countries, this approach is not always feasible in Thailand. In order to argue for the need for CMV prevention, the knowledge on the incidence and impact of the CMV infection following KT is highly desirable. MethodsWe retrospectively reviewed medical records of adult patients who underwent KT at our transplant center between January 2006 and December 2010. Patients who developed CMV viremia within 1 year after transplantation were studied for the incidence, risk factors, and outcome of symptomatic infection. The threshold value of blood CMV DNA load indicating symptomatic infection was also analyzed. ResultsSymptomatic CMV infection occurred in 18 (4.6%) patients within a median time of 12.1 (range, 3–30) weeks after KT. At initial presentation, coexisting opportunistic infection was common (44%) and gastrointestinal tract was the major type of organ involvement (44%). Between groups of patients with symptomatic and asymptomatic CMV infection, the mean (±standard deviation) level of blood viral load were significantly higher in the first group [4.2 (±0.5) vs 3.3 (±0.4) log copies/mL]. From multivariate analysis, associated factors of symptomatic infection included acute rejection [odds ratio (OR) 7.32, P = 0.001], and acute tubular necrosis (OR 3.44, P = .019). Death (13%) and graft failure (13%) were significantly higher among the symptomatic infection group than those in the no-infection group (P = .005 and .03, respectively). ConclusionDespite a low incidence rate, symptomatic CMV infection clearly resulted in significant morbidity following KT. In Thailand, the prevention of CMV infection should be prioritized among high-risk KT populations.

Studium 3 przypadków kwasicy nieoddechowej u pacjentów po przeszczepieniu nerki otrzymujących leczenie p/CMV

To preserve kidney graft function it is necessary to use ganciclovir or valganciclovir as a therapy for fresh CMV infection or prophylaxis in high-risk kidney transplant recipients. Ganciclovir-induced lactic acidosis has thus far not been reported. Three cases of nonrespiratory acidosis in kidney transplant recipients receiving ganciclovir or valganciclovir as anti-CMV therapy or prophylaxis are presented. Lactic acidosis developed in 2 patients, and the other patient had nonrespiratory acidosis of unknown origin. The possible mechanism of the development of lactic acidosis in presented cases is explored. The analysis of the described cases cannot eliminate the potential negative influence of anti-CMV therapy on acid-base equilibrium, especially with coexisting active viral infection.