Initial Experience With SARS-CoV-2-Neutralizing Monoclonal Antibodies in Kidney or Combined Kidney-Pancreas Transplant Recipients.

Background: Antiviral drugs have shown little impact in patient infected with acute respiratory coronavirus 2 (SARS-CoV-2). Especially for immunocompromised persons positive for SARS-CoV-2, novel treatments are warranted. Recently, the U.S. FDA has granted an emergency use authorization (EUA) to two monoclonal antibodies (mAb) targeting the viral spike protein: bamlanivimab and casivirimab and imdevimab. As per the EUA, all SARS-CoV-2 positive organ transplant recipients can receive mAb treatment. Patients and methods: We queried our center's transplant registry to identify SARS-CoV-2 infected recipients treated with single doses of either Bamlanivimab or casivirimab/imdevimab up to May 31, 2021. We analyzed clinical outcomes, renal function and virus-specific antibodies. The co-primary endpoints were hospitalization due to COVID-19 and SARS-CoV-2 RT-PCR negativity. Results: Thirteen patients at a median interval of 55 (IQR, 26-110) months from transplant were treated: 8 with bamlanivimab and 5 with casivirimab/imdevimab. In all, 4/13 (31%) patients were hospitalized at some time, while 11/13 (85%) achieved PCR negativity. 2/4 hospitalized patients received mAb as rescue treatment. Overall mortality was 23%, with one death attributable to transplant-associated lymphoma. All six patients infected with the B 1.1.7 variant were alive at last contact. Conclusion: mAb treatment appears effective when administered early to SARS-CoV-2-infected transplant recipients.

CT fluoroscopy-guided pancreas transplant biopsies: a retrospective evaluation of predictors of complications and success rates.

To identify predictors of biopsy success and complications in CT-guided pancreas transplant (PTX) core biopsy. We retrospectively identified all CT fluoroscopy-guided PTX biopsies performed at our institution (2000-2017) and included 187 biopsies in 99 patients. Potential predictors related to patient characteristics (age, gender, body mass index (BMI), PTX age, PTX volume) and procedure characteristics (biopsy depth, needle size, access path, number of samples, interventionalist's experience) were correlated with biopsy success (sufficient tissue for histologic diagnosis) and the occurrence of complications. Biopsy success (72.2%) was more likely to be obtained in men [+25.3% (10.9, 39.7)] and when the intervention was performed by an experienced interventionalist [+27.2% (8.1, 46.2)]. Complications (5.9%) occurred more frequently in patients with higher PTX age [OR: 1.014 (1.002, 1.026)] and when many (3-4) tissue samples were obtained [+8.7% (-2.3, 19.7)]. Multivariable regression analysis confirmed male gender [OR: 3.741 (1.736, 8.059)] and high experience [OR: 2.923 (1.255, 6.808)] (biopsy success) as well as older PTX age [OR: 1.019 (1.002, 1.035)] and obtaining many samples [OR: 4.880 (1.240, 19.203)] (complications) as independent predictors. Our results suggest that CT-guided PTX biopsy should be performed by an experienced interventionalist to achieve higher success rates, and not more than two tissue samples should be obtained to reduce complications. Caution is in order in patients with older transplants because of higher complication rates.

Thromboembolic complications in critically ill COVID-19 patients are associated with impaired fibrinolysis.

BACKGROUND: There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality. The mechanisms underlying this prothrombotic state remain enigmatic. Further data to guide anticoagulation strategies are urgently required. METHODS: We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients. RESULTS: Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found. Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications. Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction. CONCLUSIONS: The study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy. The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.

Microvascular inflammation is a risk factor in kidney transplant recipients with very late conversion from calcineurin inhibitor-based regimens to belatacept.

BACKGROUND: In de novo kidney transplant recipients (KTR) treatment with belatacept has been established as a comparable option as maintenance immunosuppression, preferably as a strategy to convert from calcineurin inhibitor (CNI)- to belatacept-based immunosuppression. Switch to belatacept demonstrated improved renal function in patients with CNI-induced nephrotoxicity, but risk of transplant rejection and the development of donor-specific antibodies (DSA) are still a matter of debate. Only few data are available in patients at increased immunological risk and late after transplantation. METHODS: We analyzed 30 long-term KTR (including 2 combined pancreas-KTR) converted from CNI to belatacept > 60 months after transplantation with moderate to severe graft dysfunction (GFR ≤ 45 mL/min). Biopsies were classified according to the Banff 2015 criteria. Group differences were assessed in a univariate analysis using Mann Whitney U or Chi square test, respectively. Multivariate analysis of risk factors for treatment failure was performed using a binary logistic regression model including significant predictors from univariate analysis. Fifty-six KTR matched for donor and recipient characteristics were used as a control cohort remaining under CNI-treatment. RESULTS: Patient survival in belatacept cohort at 12/24 months was 96.7%/90%, overall graft survival was 76.7 and 60.0%, while graft survival censored for death was 79.3%/66.7%. In patients with functioning grafts, median GFR improved from 22.5 mL/min to 24.5 mL/min at 24 months. Positivity for DSA at conversion was 46.7%. From univariate analysis of risk factors for graft loss, GFR < 25 mL/min (p = 0.042) and Banff microvascular inflammation (MVI) sum score ≥ 2 (p = 0.023) at conversion were significant at 24 months. In the analysis of risk factors for treatment failure, a MVI sum score ≥ 2 was significant univariately (p = 0.023) and in a bivariate (p = 0.037) logistic regression at 12 months. DSA-positivity was neither associated with graft loss nor treatment failure. The control cohort had comparable graft survival outcomes at 24 months, albeit without increase of mean GFR in patients with functioning grafts (ΔGFR of - 3.6 ± 8.5 mL/min). CONCLUSION: Rescue therapy with conversion to belatacept is feasible in patients with worsening renal function, even many years after transplantation. The benefit in patients with MVI and severe GFR impairment remains to be investigated.

Factors and outcomes in association with sepsis differ between simultaneous pancreas/kidney and single kidney transplant recipients.

BACKGROUND: As immunosuppressive therapy has improved in simultaneous pancreas/kidney transplant recipients (SPKTRs), infection has become the major limitation of disease-free survival. METHODS: We studied all SPKTRs and deceased-donor kidney transplant recipients (KTRs) between 2003 and 2015. Thirty-six of 134 SPKTRs (26.9%) were diagnosed with sepsis among which 13/36 SPKTRs (36.1%) developed severe sepsis/septic shock. A control group of 98 SPKTRs without sepsis and 61/538 KTRs (11.3%) with sepsis were used for comparison. RESULTS: Among SPKTRs, female sex, low BMI, CMV seronegativity, CMV disease, and acute cellular rejection increased the risk for sepsis (P < .05). Patient and allograft survival was comparable among SPKTRs with and without sepsis (P > .05), but showed inferior kidney allograft function (P < .05). While urosepsis was less common among SPKTRs (45%), pneumonia (33%) and peritonitis (15%) as site of infections were more frequent (P < .05). Here, gram-positive and fungal sepsis were more common among SPKTRs compared to KTRs (P < .05). SPKTRs showed a higher incidence and an earlier onset of sepsis compared to KTRs (P < .001). SPKTRs with severe sepsis/septic shock were more likely to show pneumonia as site of infection with gram-positive/polymicrobial bacteremia (P < .05). Mortality from severe sepsis was 29% among SPKTRs compared to 58% among KTRs (P < .05). CONCLUSION: Differences in incidence, site, causative pathogens, and onset of sepsis between SPKTRs and KTRs may be attributed to more intense immunosuppression, major surgery, and complications of diabetes among SPKTRs. Lower sepsis-related mortality may reflect younger age and more timely diagnosis, but also supports recent findings of less sepsis-related mortality among recipients of solid organ transplantation.

Simultaneous pancreas/kidney transplant recipients are predisposed to tissue-invasive cytomegalovirus disease and concomitant infectious complications.

BACKGROUND: Infections have increased in simultaneous pancreas/kidney transplant recipients (SPKTRs) with cytomegalovirus (CMV) infection being the most important viral infection with adverse impact on patient and allograft outcomes. METHODS: We studied all primary SPKTRs and deceased-donor kidney transplant recipients (KTRs) between 2008 and 2015 for the development of CMV infection. A total of 21/62 SPKTRs (33.9%) and 90/335 KTRs (26.9%) were diagnosed with CMV infection. A control group of 41 SPKTRs without CMV infection was used for comparison. RESULTS: SPKTRs showed an increased incidence of CMV infection compared with KTRs. SPKTRs were more likely to develop CMV disease, CMV pneumonia, recurrent CMV infection, higher initial and peak CMV loads, and more need for intravenous antiviral therapy compared with KTRs (P<.05). High-risk CMV serostatus (D+R-) and 2 HLA-B/-DR mismatches increased the risk of CMV infection in SPKTRs (P<.05). No differences were observed for patient and allograft outcomes (P>.05). SPKTRs with CMV infection were more likely to show concomitant Epstein-Barr virus (EBV) viremia compared with SPKTRs without CMV infection (P<.05). SPKTRs with CMV infection showed higher incidences of concomitant BK polyomavirus-associated nephropathy, EBV viremia, and sepsis compared with KTRs with CMV infection (P<.05). CONCLUSION: Our results suggest a higher incidence and more severe course of CMV infection in SPKTRs compared with KTRs. The increased incidence of concomitant infectious complications among SPKTRs with CMV infection suggests an overall impaired immunity, and calls for more intense screening.

Simultaneous pancreas/kidney transplant recipients present with late-onset BK polyomavirus-associated nephropathy.

BACKGROUND: Infections have increased in simultaneous pancreas/kidney transplant recipients (SPKTRs) with BK polyomavirus (BKV)-associated nephropathy (BKVN) being the most important infectious cause of allograft loss. Comparisons of BKVN with kidney transplant recipients (KTRs), however, are lacking. METHODS: We studied all SPKTRs and KTRs at our transplant centre between 2003 and 2012. Eleven of 106 SPKTs (10.4%) and 21 of 1062 KTRs (2.0%) were diagnosed with BKVN with allograft loss in 1 SPKTR (9.1%) and 2 KTRs (9.5%). A control of 95 SPKTRs without BKVN was used for comparison. RESULTS: SPKTRs showed an increased incidence of BKVN compared with KTRs (P < 0.001). Onset of BKVN in SPKTRs was significantly later compared with KTRs (P = 0.033). While 67% of KTRs showed early-onset BKVN, 64% of SPKTRs developed late-onset BKVN. Older recipient age and male gender increased the risk of BKVN in SPKTRs (P < 0.05). No differences were observed for patient and allograft survival (P > 0.05). However, SPKTRs with BKVN showed inferior estimated glomerular filtration rate and a higher incidence of de novo donor-specific antibodies compared with SPKTRs without BKVN in long-term follow-up (P < 0.05). SPKTRs showed higher peak BKV loads, a need for more intense therapeutic intervention and were more likely not to recover to baseline creatinine after BKVN (P < 0.05). CONCLUSIONS: Our results suggest a higher incidence, more severe course and inferior outcome of BKVN in SPKTRs. An increased vulnerability of the allograft kidney due to inferior organ quality may predispose KTRs to early-onset BKVN. In contrast, SPKTRs present with late-onset BKVN in the presence of high-dose immunosuppression.

Body Mass Index Thresholds and the Use of Bariatric Surgery in the Field of Kidney Transplantation in Germany.

BACKGROUND: Obesity in the recipient is linked to inferior transplant outcome. Consequently, access to kidney transplantation (KT) is often restricted by body mass index (BMI) thresholds. Bariatric surgery (BS) has been established as a superior treatment for obesity compared to conservative measures, but it is unclear whether it is beneficial for patients on the waiting list. METHODS: A national survey consisting of 16 questions was sent to all heads of German KT centers. Current situation of KT candidates with obesity and the status of BS were queried. RESULTS: Center response rate was 100%. Obesity in KT candidates was considered an important issue (96.1%; n = 49/51) and 68.6% (n = 35/51) of departments responded to use absolute BMI thresholds for KT waiting list access with ≥ 35 kg/m2 (45.1%; n = 23/51) as the most common threshold. BS was considered an appropriate weight loss therapy (92.2%; n = 47/51), in particular before KT (88.2%; n = 45/51). Sleeve gastrectomy was the most favored procedure (77.1%; n = 37/51). Twenty-one (41.2%) departments responded to evaluate KT candidates with obesity by default but only 11 (21.6%) had experience with ≥ n = 5 transplants after BS. Concerns against BS were malabsorption of immunosuppressive therapy (39.2%; n = 20/51), perioperative morbidity (17.6%; n = 9/51), and malnutrition (13.7%; n = 7/51). CONCLUSIONS: Obesity is potentially limiting access for KT. Despite commonly used BMI limits, only few German centers consider BS for obesity treatment in KT candidates by default. A national multicenter study is desired by nearly all heads of German transplant centers to prospectively assess the potentials, risks, and safety of BS in KT waitlisted patients.

Simultaneous chemoradiation with cisplatin in a patient with recurrent cervical cancer undergoing hemodialysis: analysis of cisplatin concentrations in serum and dialysate and therapy-related acute toxicity.

PURPOSE: To prove the feasibility and toxicity of platinum-based chemoradiation in a patient with recurrent cervical cancer undergoing concomitant hemodialysis. PATIENT AND METHODS: We report a patient with a renal transplant because of chronic renal failure who then underwent radical hysterectomy and lymphadenectomy due to cervical cancer FIGO stage IB1. One year after primary therapy, a 53 × 54 × 68 mm vaginal stump recurrence was treated by total translevatoric exenteration with lymphadenectomy, explantation of the transplant, and the right residual kidney. Because of microscopically involved margins, chemoradiation was recommended. Radiation was performed to the tumor region and pelvic lymph nodes up to 50.4 Gy. A boost was given to the clip-marked region to 66.6 Gy. Neurological, gastrointestinal and genitourinary toxicity was evaluated once a week, while hematological toxicity twice per week. Samples to evaluate cisplatin concentrations were taken from blood and dialysate. RESULTS: The patient completed chemoradiation with 5 cisplatin applications with a decreased dose (20 mg/m(2)) without any high grade toxicity. Hemodialysis was performed three times a week. Within 30 min after cisplatin application, the cisplatin serum concentration reached the highest level with 1,179.6 µg/l and showed nearly stable concentrations over 120 min. There was an accumulation of cisplatin from week 1 (100%) to week 5 of application (219%). The corresponding concentration in the dialysate also showed a rapid increase within the first hour of hemodialysis and decreased to 50% within 2 h. CONCLUSION: Cisplatin application with a modified dose (20 mg/m(2)) is feasible and safe in a patient with cervical carcinoma undergoing chemoradiation and hemodialysis.

Viscoelastic testing reveals normalization of the coagulation profile 12 weeks after severe COVID-19.

COVID 19 is associated with a hypercoagulable state and frequent thromboembolic complications. For how long this acquired abnormality lasts potentially requiring preventive measures, such as anticoagulation remains to be delineated. We used viscoelastic rotational thrombelastometry (ROTEM) in a single center cohort of 13 critical ill patients and performed follow up examinations three months after discharge from ICU. We found clear signs of a hypercoagulable state due to severe hypofibrinolysis and a high rate of thromboembolic complications during the phase of acute illness. Three month follow up revealed normalization of the initial coagulation abnormality and no evidence of venous thrombosis in all thirteen patients. In our cohort the coagulation profile was completely normalized three months after COVID-19. Based on these findings, discontinuation of anticoagulation can be discussed in patients with complete venous reperfusion.

Impact of Early Pancreatic Graft Loss on Outcome after Simultaneous Pancreas-Kidney Transplantation (SPKT)-A Landmark Analysis.

(1) Background: Simultaneous pancreas-kidney transplantation (SPKT) is a standard therapeutic option for patients with diabetes mellitus type I and kidney failure. Early pancreas allograft failure is a complication potentially associated with worse outcomes. (2) Methods: We performed a landmark analysis to assess the impact of early pancreas graft loss within 3 months on mortality and kidney graft survival over 10 years. This retrospective single-center study included 114 adult patients who underwent an SPKT between 2005 and 2018. (3) Results: Pancreas graft survival rate was 85.1% at 3 months. The main causes of early pancreas graft loss were thrombosis (6.1%), necrosis (2.6%), and pancreatitis (2.6%). Early pancreas graft loss was not associated with reduced patient survival (p = 0.168) or major adverse cerebral or cardiovascular events over 10 years (p = 0.741) compared to patients with functioning pancreas, after 3 months. Moreover, kidney graft function (p = 0.494) and survival (p = 0.461) were not significantly influenced by early pancreas graft loss. (4) Conclusion: In this study, using the landmark analysis technique, early pancreas graft loss within 3 months did not significantly impact patient or kidney graft survival over 10 years.

Evidence for a thromboembolic pathogenesis of lung cavitations in severely ill COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) induces lung injury of varying severity, potentially causing severe acute respiratory distress syndrome (ARDS). Pulmonary injury patterns in COVID-19 patients differ from those in patients with other causes of ARDS. We aimed to explore the frequency and pathogenesis of cavitary lung lesions in critically ill patients with COVID-19. Retrospective study in 39 critically ill adult patients hospitalized with severe acute respiratory syndrome coronavirus 2 including lung injury of varying severity in a tertiary care referral center during March and May 2020, Berlin/Germany. We observed lung cavitations in an unusually large proportion of 22/39 (56%) COVID-19 patients treated on intensive care units (ICU), including 3/5 patients without mechanical ventilation. Median interquartile range (IQR) time between onset of symptoms and ICU admission was 11.5 (6.25-17.75) days. In 15 patients, lung cavitations were already present on the first CT scan, performed after ICU admission; in seven patients they developed during a subsequent median (IQR) observation period of 48 (35-58) days. In seven patients we found at least one cavitation with a diameter > 2 cm (maximum 10 cm). Patients who developed cavitations were older and had a higher body mass index. Autopsy findings in three patients revealed that the cavitations reflected lung infarcts undergoing liquefaction, secondary to thrombotic pulmonary artery branch occlusions. Lung cavitations appear to be a frequent complication of severely ill COVID-19 patients, probably related to the prothrombotic state associated with COVID-19.

Influence of donor- and recipient-specific factors on the postoperative course after combined pancreas-kidney transplantation.

INTRODUCTION: Simultaneous pancreas-kidney (SPK) transplantation is state-of-the-art therapy for patients with type-1 diabetes mellitus and end-stage renal failure. Improvement of long-term organ function and long-term survival after transplantation is the main focus of current research, but improvement of the early postoperative course is very important for the patient. Pancreas transplantation is associated with postoperative complications. We defined and identified donor- and recipient-specific factors related to postoperative complications. PATIENTS AND METHODS: We carried out 210 SPKs from April 1995 to December 2007. The early postoperative course until first discharge from hospital was analyzed. Complications (pancreas-specific and surgical) were revisited. Donor-specific factors such as sex, age, body mass index (BMI), laboratory values, catecholamine administration, time in the intensive care unit, preprocurement blood substitution, and asystolic periods, as well as factors related to the organ donation procedure, were assessed. Recipient-specific factors such as age, sex, BMI, and blood group were correlated with the prevalence of complications and postoperative outcome. Donor-specific risk factors correlating with postoperative complications included donor age, BMI, and blood transfusion in the donor before organ donation. RESULTS: Graft preservation with histidine-tryptophan-ketoglutarate perfusion solution was related to a significantly higher number of surgical complications.When analyzing recipient-specific factors, pre-existing cardiac diseases influenced the prevalence of postoperative complications. The duration of the transplantation procedure was associated with significantly more complications. The anastomosis time was not significantly related to an increased prevalence of complications. The choice of immunosuppression had a significant effect on pancreas-specific complications, demonstrating that antithymocyte globulin instead of daclizumab had a negative effect. Initial immunosuppression with tacrolimus combined with mycophenolate mofetil (MMF) caused significantly fewer pancreas-related complications in comparison with tacrolimus combined with rapamycin as well as compared with cyclosporine combined with MMF. A high level of C-reactive protein within the first 7 days after transplantation was significantly related to an increased prevalence of complications. CONCLUSIONS: Early postoperative complications after combined pancreas-kidney transplantation have a considerable effect on short- and long-term outcomes. Several statistically relevant factors related to pancreas- or surgery-associated complications could be identified. These data may help to improve early outcome after SPK by consideration of relevant risk factors when choosing an organ and a recipient for transplantation.

Chronic renal dysfunction following liver transplantation.

With most of the immunosuppressive protocols consisting of calcineurin inhibitors (CI), nephrotoxicity has become a major long-term complication often compromising outcome. In a single-center retrospective study, we reviewed 1173 liver transplantations to identify variables indicative for the occurrence of chronic renal dysfunction (CRD) (defined as > or = 1 episode of serum creatinine increase > or = 1.8 mg/dL > or = 2 wk). Chronic renal dysfunction was found in 137 (11.7%) of all transplants [82 (7%) early (after 3-12 months), 55 (4.7%) late-onset (> 12 months)]. Compared to 5-/10-yr survival rates in non-CRD transplants (84/74%) survival was significantly decreased in early (66/46%), but unchanged in late-onset CRD (98/86%). Rates of alcoholic cirrhosis and prior renal dysfunction were significantly increased in patients with CRD. In a multivariate logistic regression analysis, only cyclosporine A (CyA) as immunosuppression remained an independent risk factor. No correlations to age, gender, rejection/retransplantation or diabetes were found. Surprisingly, renal function (creatinine) showed no difference between patients on CI monotherapy (FK/CyA) compared to those who had mycophenolate mofetil (MMF) added. In liver transplantation, early onset CRD significantly compromises survival. CyA-based immunosuppression appears to have a stronger impact than FK. The fact that patients with long-term severe chronic renal dysfunction failed to improve under MMF rescue therapy emphasizes the importance of new diagnostic strategies to earlier identify at-risk patients.

Peginterferon alfa-2b plus ribavirin for the treatment of hepatitis C recurrence following combined liver and kidney transplantation.

BACKGROUND: Several studies have demonstrated safety and efficacy of treatment protocols using pegylated interferon alfa-2b (PegIntron) and ribavirin in hepatitis C (HCV) recurrence and liver transplantation but no data exists about antiviral treatment following combined liver and kidney transplantation. PATIENTS: Six patients with recurrent HCV (genotype 1 [n = 5] and 4 [n = 1]) received peginter-feron alfa-2b (1 ug/kg/weekly) and ribavirin (600 mg) for 48 weeks. Sustained virologic response was defined as undetectable HCV-RNA 24 weeks after termination of therapy. All patients underwent liver biopsies prior to treatment and after 72 weeks and liver enzymes (ASAT) and serum creatinine levels were obtained regularly. RESULTS: In 4/6 patients, viral load prior to treatment was below 1,000,000 (IU/mL). SVR was achieved in 3/6 (50%) patients. None of the patients developed signs of deteriorating kidney function or rejection. One patient without SVR had HCV related liver graft failure and died 13 months later. Side effects like neutropenia (50%) and anemia (50%) were treated with G-CSF, erythropoietin, and dose reduction of peginterferon and ribavirin. CONCLUSIONS: In a small group of patients with combined kidney and liver transplantation, peginterferon-alfa2b is safe and effective to achieve SVR in HCV recurrence. Larger scale studies are warranted to further validate our results.

Monitoring of human cytomegalovirus, HHV-6 and HHV-7 infection in kidney transplant recipients by molecular methods to predict HCMV disease after transplantation: a prospective study.

OBJECTIVES: Recently, highly sensitive molecular assays to detect HCMV, HHV-6 and HHV-7 have been developed but their ability to detect patients at high risk for disease is unclear. METHODS: The positive predictive values (PPV) of pp65-antigenemia, quantitative plasma DNA and pp67-mRNA for CMV-disease were prospectively compared in 82 transplant recipients (72 renal, 10 pancreas-kidney) without CMV-prophylaxis. In addition, the prevalence of HHV-6 and HHV-7 infection were assessed using qualitative PCR. The assays were performed weekly. RESULTS: Three patients (3,7%) developed CMV-disease and were effectively treated. They were positive in all three CMV-assays. The PPVs of pp65-Ag, DNA viral load and pp67-mRNA were 33%, 20% and 25% in CMV-positive and 100%, 67% and 50% in seronegative recipients. Sensitivity and negative predictive value were 100% for all assays. Using cut-offs, PPVs were 75% (pp65-Ag > or = 20/200.000 cells) and 100% (PCR > or =30.000 copies/ml). Transfusion of >2 packed red cells, rejection and non-functioning graft were risk factors for CMV Five patients and one patient were positive for HHV-6 and HHV-7 resp.; both were symptomless and did not have a HCMV infection. CONCLUSIONS: Therefore, pp65-antigenemia and plasma PCR with a cut-off could be useful for monitoring preemptive therapy.

Efficacy and safety of tacrolimus compared with cyclosporine microemulsion in primary simultaneous pancreas-kidney transplantation: 1-year results of a large multicenter trial.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) transplantation has become an accepted therapy for type 1 diabetic patients with end-stage renal disease. This open-label, multicenter study compared the efficacy and safety of tacrolimus with the microemulsion (ME) formulation of cyclosporine in a clinical setting. The 1-year results are reported here. METHODS: The study was conducted in 10 European centers and one center in Israel. One hundred three patients were randomly assigned to tacrolimus and 102 to cyclosporine-ME. All patients received concomitant rabbit anti-T-cell globulin induction therapy, mycophenolate mofetil (MMF), and short-term cortico-steroids. The initial daily oral doses were 0.2 mg/kg for tacrolimus, 7 mg/kg for cyclosporine-ME, and 2 to 3 g for MMF. RESULTS: The 1-year incidence of biopsy-proven kidney or pancreas acute rejection was lower with tacrolimus (27.2%) than with cyclosporine-ME (38.2%; P = 0.09). Pancreas graft survival at 1 year was 91.3% with tacrolimus and 74.5% with cyclosporine-ME (P <0.0005). Renal graft survival was similar in the two study groups. There were no significant treatment-related differences in pancreatic or renal graft function. In total, 34 patients switched treatment from cyclosporine-ME to tacrolimus, but only 6 patients receiving tacrolimus required alternative therapy. Mean doses of MMF at 1 year were also lower in the tacrolimus group (1.36 vs. 1.67 g/day; P = 0.007). CONCLUSION: These findings support the use of tacrolimus therapy for uremic patients with type 1 diabetes who are undergoing SPK transplantation.

Anti-human leukocyte antigen and donor-specific antibodies detected by luminex posttransplant serve as biomarkers for chronic rejection of renal allografts.

BACKGROUND: Although the incidence of early acute rejection could have been diminished in the past, the long-term renal allograft survival could not benefit from the introduction of more effective immunosuppressive regimens mainly aiming at cellular rejection mechanisms. The cause of chronic rejection is still discussed controversially. Here, we demonstrate to what extent human leukocyte antigen (HLA) antibodies (HLAab) posttransplant contribute to late graft outcome. METHODS: A total of 1014 deceased kidney transplant recipients transplanted at the Charité hospital were monitored in a cross-sectional manner for the development of HLAab using Luminex Single Antigen beads. Patients with stable kidney function at a median of 5-years posttransplant were tested once for HLAab and monitored for 5.5 years after testing. RESULTS: Thirty percent of recipients showed HLAab. Donor-specific antibodies (DSA) were found in 31% of antibody positive patients. The presence of DSA was associated with a significantly lower graft survival of 49% vs. 83% in the HLAab negative group (P< or =0.0001). Non-DSAs also had an adverse effect on graft survival (70% vs. 83%; P=0.0001). In a prospective analysis of 195 patients with repeatedly no detectable HLAab, the survival probability was 94% as opposed to 79% survival among patients who developed HLAab de novo after the first testing (P=0.05). CONCLUSIONS: We confirmed that HLAab produced even late after transplantation are detrimental to graft outcome. DSA were proven to have a strong adverse impact on graft survival. The results indicate that a posttransplant HLAab monitoring routine could be appropriate to improve long-term results.

Long-term results of subtotal vs total parathyroidectomy without autotransplantation in kidney transplant recipients.

HYPOTHESIS: Total parathyroidectomy without autotransplantation in kidney transplant recipients leads to reduced recurrence rates and similar improvement of clinical symptoms compared with subtotal parathyroidectomy. DESIGN: A retrospective cohort study. SETTING: University clinic. PATIENTS: Thirty-three patients with functioning renal grafts who underwent primary total (n = 17; group 1) or subtotal (n = 16; group 2) parathyroidectomy for renal hyperparathyroidism. MAIN OUTCOME MEASURES: Long-term levels of intact parathyroid hormone, serum calcium, phosphate, alkaline phosphatase, creatinine, and vitamin D; bone pain; use of medication; and incidence of persistent or recurrent hyperparathyroidism. RESULTS: The mean length of follow-up was 31 months in group 1 and 41 months in group 2. In all patients, postoperative serum calcium and phosphate levels normalized and bone pain markedly decreased. Persistent hypocalcemia was not observed. Serum creatinine levels intermittently increased in both groups but returned to preoperative levels in most of the patients. In group 1, all patients had undetectable intact parathyroid hormone levels throughout the study period. In group 2, 2 patients had persistent and 3 patients developed recurrent hyperparathyroidism (31%) that required therapy with cinacalcet hydrochloride in 3 cases. In 4 of these 5 patients, intact parathyroid hormone levels were greater than 54 ng/L directly after operation. In all, 27 of 33 patients (82%) received cholecalciferol therapy. Additional calcium supplementation was used by 12 group 1 patients (71%) and 3 group 2 patients (19%). CONCLUSIONS: Total parathyroidectomy in kidney transplant recipients appears to be safe and protective against persistent and recurrent disease. If subtotal parathyroidectomy is performed, the remnant should be small.