[Machine perfusion for conditioning liver and kidneys before transplantation]. / Maschinenperfusion zur Konditionierung der Leber und Niere vor Transplantation.

Machine perfusion will become established as the standard of care for solid organ transplantation in the near future. Ongoing studies are investigating the appropriate perfusion algorithms for each specific organ. Although it is neither proven which perfusion principle nor type of device is superior, it has already been sufficiently shown that the increasing number of marginal organs that are currently transplanted in Germany would benefit from machine perfusion for conditioning before transplantation. The addition of hypothermic and normothermic perfusion sequences opens up the possibility of conditioning of previously damaged organs as well as viability testing. Overall, machine perfusion increases the safety for the recipient and can counteract the increasingly more difficult scenario of working hour restrictions because solid organ transplantations in the future will be plannable and carried out during the day.

ABO-Incompatible Kidney Transplantation: Low Rates of Infectious Complications and Excellent Patient Survival.

BACKGROUND: A significant gap exists between demand and supply of organs for patients with end-stage renal disease. To increase the donor pool, kidney transplantation is performed across ABO- and HLA-incompatible barriers. ABO-incompatible kidney transplant (ABOi-KT) recipients are at increased risk of antibody-mediated rejection, infection, and mortality. Hypogammaglobulinemia secondary to immunosuppression is highly prevalent after solid organ transplantation, and intravenous immunoglobulin (IVIG) has been reported to reduce the risks of infections in various settings. We use high-dose IVIG in ABOi-KT recipients perioperatively. We aimed to determine the rate of infectious complications along with graft and patient survival in our ABOi-KT recipients. METHODS: We included all adult patients who underwent ABOi-KT from the year 2007 to 2016. Patients received rituximab, plasma exchange, and IVIG (2 g/kg body weight). Thymoglobulin and intravenous methylprednisolone were used as induction treatment. Oral prednisone, mycophenolate mofetil, and tacrolimus were used as maintenance therapy. RESULTS: A total of 77 ABOi-KTs were performed, and the recipients were followed up for a median of 1557 days. Two patients were diagnosed as having BK nephropathy. No patients were diagnosed as having pneumocystis infection, cytomegalovirus disease, herpes simplex, varicella zoster, or fungal infection. One-year graft and patient survival was 94.8% and 100%, respectively. CONCLUSIONS: In our series of ABOi-KTs, we observed a low risk of infectious complications and excellent patient survival. High-dose IVIG might have reduced infections.

Left-Sided Living Kidney Donation Leads to Transiently Reduced Adrenocortical Responsiveness.

Living kidney donation is safe and established, but can lead to long-term complications such as chronic fatigue. Since the adrenal vein is usually transected during left-sided donor nephrectomy-which is not necessary on the right-we hypothesized that venous congestion might lead to an impairment of adrenal function, offering a possible explanation. In this prospective open label, monocentric cohort study, adrenal function was compared in left- and right-sided living kidney donors. The primary endpoint was plasma cortisol response to low-dose adrenocorticotropic hormone (ACTH) stimulation. Secondary endpoints included plasma renin and ACTH concentration as well as adrenal volume in response to donor nephrectomy. A total of 30 healthy donors-20 left- and 10 right-sided donations-were included. On postoperative day 1, response to low-dose ACTH stimulation was intact, but significantly lower after left-sided donor nephrectomy. After 28 days, adrenal responsiveness to ACTH stimulation did not differ any longer. Magnetic resonance imaging volumetry showed no significant adrenal volume change over 4 weeks, neither after left- nor after right-sided nephrectomy. In conclusion, left-sided living kidney donation entails a transiently reduced adrenocortical responsiveness, which returns to baseline after 28 days.

Effect of Twice-Yearly Denosumab on Prevention of Bone Mineral Density Loss in De Novo Kidney Transplant Recipients: A Randomized Controlled Trial.

We conducted an open-label, prospective, randomized trial to assess the efficacy and safety of RANKL inhibition with denosumab to prevent the loss of bone mineral density (BMD) in the first year after kidney transplantation. Ninety kidney transplant recipients were randomized 1:1 2 weeks after surgery to receive denosumab (60 mg at baseline and 6 months) or no treatment. After 12 months, total lumbar spine areal BMD (aBMD) increased by 4.6% (95% confidence interval [CI] 3.3-5.9%) in 46 patients in the denosumab group and decreased by -0.5% (95% CI -1.8% to 0.9%) in 44 patients in the control group (between-group difference 5.1% [95% CI 3.1-7.0%], p < 0.0001). Denosumab also increased aBMD at the total hip by 1.9% (95% CI, 0.1-3.7%; p = 0.035) over that in the control group at 12 months. High-resolution peripheral quantitative computed tomography in a subgroup of 24 patients showed that denosumab increased volumetric BMD at the distal tibia and radius (all p < 0.05). Biomarkers of bone turnover (C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide) markedly decreased with denosumab (all p < 0.0001). Episodes of cystitis and asymptomatic hypocalcemia occurred more often with denosumab, whereas graft function, rate of rejections, and incidence of opportunistic infections were similar. In conclusion, denosumab increased BMD in the first year after kidney transplantation but was associated with more frequent episodes of urinary tract infection.

Alemtuzumab and sirolimus in renal transplantation: six-year results of a single-arm prospective pilot study.

mTOR inhibitors avoid calcineurin nephrotoxicity, but sirolimus de novo is associated with unacceptable side effects and higher rejection rates. We have investigated a modified strategy: alemtuzumab induction with tacrolimus and mycophenolate maintenance, switching from tacrolimus to sirolimus at 6 months and stopping mycophenolate at 12 months. Here, we report the 6-year follow-up of 30 patients prospectively recruited to this single-arm pilot study and compare outcomes to a matched contemporaneous control group of 30 patients who received standard induction and calcineurin-inhibitor-based immunosuppression.Six-year patient and graft survival were 83% and 80%(alemtuzumab) versus 77% and 70% (control). Rejection rates in the first 6 months were similar in alemtuzumab (6.6%) and control groups (10%). A higher than expected incidence of rejection in the alemtuzumab group following cessation of mycophenolate at 1 year (17%) was mitigated in later patients by retaining low dose mycophenolate. Mean eGFR was higher in the alemtuzumab group at all time points but not significantly (p»0.16). Tacrolimus levels in the first 6 months were significantly higher in the contemporaneous control group (p<0.001). Alemtuzumab induction with initial treatment with tacrolimus enables conversion to sirolimus without the side effects and incidence of acute rejection seen in earlier protocols.

Liver transplantation for hilar cholangiocarcinoma: a German survey.

BACKGROUND: The present study reports a German survey addressing outcomes in nonselected historical series of liver transplantation (OLT) for hilar cholangiocarcinoma (HL). PATIENTS AND METHODS: We sent to all 25 German transplant centers performing OLT a survey that addressed (1) the number of OLTs for HL and the period during which they were performed; (2) the incidence of HL diagnosed prior to OLT/rate of incidental HL (for example, in primary sclerosing cholangitis); (3) tumor stages according to Union Internationale Centre le Cancer; (4) patient survival; and (5) tumor recurrence rate. RESULTS: Eighty percent of centers responded, reporting 47 patients who were transplanted for HL. Tumors were classified as pT2 (25%), pT3 (73%), or pT4 (2%). HL was diagnosed incidentally in 10% of cases. A primary diagnosis of PSC was observed in 16% of patients. Overall median survival was 35.5 months. When in-hospital mortality (n = 12) was excluded, the median survival was 45.4 months, corresponding to 3- and 5-year survival rates of 42% and 31%, versus 31% and 22% when in-hospital mortality was included. HL recurred in 34% of cases. Three- and 5-year survivals for the 15 patients transplanted since 1998 was 57% and 48%, respectively. Median survival ranged from 20 to 42 months based on the time period (P = .014). CONCLUSIONS: The acceptable overall survival, the improved results after careful patient selection since 1998, and the encouraging outcomes from recent studies all suggest that OLT may be a potential treatment for selected cases of HL. Prospective multicenter randomized studies with strict selection criteria and multimodal treatments seem necessary.

Evaluation of rayon swab surface sample collection method for Bacillus spores from nonporous surfaces.

AIM: To evaluate US Centers for Disease Control and Prevention recommended swab surface sample collection method for recovery efficiency and limit of detection for powdered Bacillus spores from nonporous surfaces. METHODS AND RESULTS: Stainless steel and painted wallboard surface coupons were seeded with dry aerosolized Bacillus atrophaeus spores and surface concentrations determined. The observed mean rayon swab recovery efficiency from stainless steel was 0.41 with a standard deviation (SD) of +/-0.17 and for painted wallboard was 0.41 with an SD of +/-0.23. Evaluation of a sonication extraction method for the rayon swabs produced a mean extraction efficiency of 0.76 with an SD of +/-0.12. Swab recovery quantitative limits of detection were estimated at 25 colony forming units (CFU) per sample area for both stainless steel and painted wallboard. CONCLUSIONS: The swab sample collection method may be appropriate for small area sampling (10 -25 cm2) with a high agent concentration, but has limited value for large surface areas with a low agent concentration. The results of this study provide information necessary for the interpretation of swab environmental sample collection data, that is, positive swab samples are indicative of high surface concentrations and may imply a potential for exposure, whereas negative swab samples do not assure that organisms are absent from the surfaces sampled and may not assure the absence of the potential for exposure. SIGNIFICANCE AND IMPACT OF THE STUDY: It is critical from a public health perspective that the information obtained is accurate and reproducible. The consequence of an inappropriate public health response founded on information gathered using an ineffective or unreliable sample collection method has the potential for undesired social and economic impact.

Living donor kidney transplantation from the elderly donor.

PURPOSE: The organ shortage has led to increasing acceptance of living donation in all transplant centers. Although the risk of impaired long-term outcome seems to be greater using elderly donors, these organs are not generally refused for transplantation. We report our experience with 25 living donor kidney transplantations from donors older than 60 years. METHODS: Between 1995 and 2004, 124 living donor procedures were performed in our center from 83 related and 41 unrelated donors. Twenty-five donors (19 female, 6 male) were 60 years or older (mean, 65.3 +/- 3.9 years). The recipient included (10 females and 15 males) showed a higher degree of variance in age (46.1 +/- 14.6 years). The immunosuppressive protocol was cyclosporine (CyA)-based regimen in related cases and tacrolimus-based in unrelated cases. RESULTS: We transplanted 16 left and 9 right kidneys from older donors. The mean cold ischemia time was 171 +/- 64 minutes with a second warm ischemia time of 24 +/- 6 minutes. Severe arteriosclerosis made vascular reconstruction by graft interposition necessary in two recipients. The acute rejection rate was 20%. Two patients (8%) required dialysis in the early postoperative course, whereas initial function was excellent in 22 patients (88%). The mean serum creatinine concentration after 12 months was 1.6 +/- 0.3 mg/dL (n = 24) and 2.0 +/- 0.7 mg/dL (n = 16) at 4 years. In comparison, the mean creatinine concentration after 4 years in donors under 60 years was 1.6 +/- 0.9 mg/dL. Our analysis showed no significant difference in long-term graft function comparing young versus old donors in the setting of living donor transplants. CONCLUSION: Using living donors older than 60 years for transplantation is a feasible and safe option. The difference in long-term creatinine between young and old donors was not significant.

Kidney transplantation using donors with history of diabetes and hypertension.

PURPOSE: Due to the persistant organ shortage for kidney transplantation, donor selection has changed in the past years. Although hypertension and diabetes mellitus are known to be risk factors for renal insufficiency, kidneys from donors with these diagnoses in their history have been accepted for kidney transplantation even with an increased risk of poor graft function. Herein we have reported our experience with kidney transplantation using grafts from donors with both, a history of type II diabetes and hypertension. METHODS: Between 2000 and 2005, ten patients were grafted using donors with history of type II diabetes mellitus and hypertension. Mean donor age was 58 +/- 7.5 years and recipient age, 52.2 +/- 15.7 years. Mean HLA mismatch was 0.8 (A); 1.2 (B) and 0.9 (DR). Cold ischemia time was 17.4 +/- 4.1 hours. Immunosuppression was based on CyA (n = 7), tacrolimus (n = 2) or sirolimus (n = 1). RESULTS: Six patients (60%) showed good initial function, and four (40%) had delayed graft function (DGF). One patient died at ten weeks due to multiorgan failure. Two (20%) biopsy-proven rejections were diagnosed, one of which was resistant to therapy. Six months after kidney transplantation, 7 (77%, n = 9) showed good graft function (creatinine 1.3 to 2.4 mg/dL), but one patient displayed long-lasting DGF with poor function. CONCLUSION: Grafts from donors with a history of diabetes mellitus and hypertension are suitable for kidney transplantation. Elevated rate of DGF (40%) would justify allocation of these organs to local transplant centers to shorten ischemia time and thereby reduce DGF and achieve better long-term results. Identification and detailed evaluation of these donors prior to allocation (eg, HbAlc, biopsy) may help transplant centers to accept these kidneys.

Recurrent complicated colon diverticulitis in renal transplanted patient.

Colon perforation due to diverticulitis is a life-threatening complication in the postoperative course of kidney transplantation. In the immunocompromised patient a diagnosis of diverticulitis is difficult to make. We report a 53-year-old woman being kidney transplanted 14 years ago with known diverticulosis. She was admitted with acute severe pain in the lower left abdomen. Abdominal computed tomography (CT) scan indicated a diagnosis of intestinal abscess in the small pelvis. Laparotomy showed a covered sigma perforation with abscess located in the small pelvis (Hinchey-I). Because of the immunocompromised situation of the patient we performed a Hartmann procedure. Her postoperative course was uneventful. In a 6-month interval the intestinal continuity restoration was performed. Twelve days after discharge the patient was readmitted with reduced renal function and increased infection parameters. During physical examination the abdomen was tender. The patient complained of abdominal pain in the left upper abdomen and additional pain in the left shoulder. An antibiotic therapy using ciprofloxacin was already initiated owing to a urinary tract infection. An abdominal CT scan was performed and indicated an intestinal abscess in the left upper abdomen. Laparotomy showed an abscess involving transverse colon, distal jejunum, and proximal ileum (Hinchey-II). Segmental resection of the left colonic flexure, proximal jejunum, and ileum was performed. The postoperative course was uneventful and the patient was discharged on the 8th postoperative day. The present casuistry emphasizes that the immunocompromised patient can undergo diverticulitis twice, and that primary anastomosis is a feasible option for patients with localized peritonitis due to complicated diverticulitis.

Retrieval of abdominal organs for transplantation.

BACKGROUND: Organ retrieval and donor management are not yet standardized. Different transplant centres apply various techniques, such as single or dual organ perfusion, dissection in the cold or warm, and single or en bloc organ removal. These different approaches may cause inconvenience, especially when more than one organ retrieval team is involved. METHODS: Cochrane Library, Medline and PubMed were searched for publications on multiorgan donor/donation, retrieval technique and procurement. Levels of evidence and grades of recommendation were evaluated based on current advice from the Oxford Centre for Evidence-Based Medicine. RESULTS: Multiorgan donation itself does not compromise the outcome of individual organ transplants. Dissection of abdominal organs for transplantation is best performed after cold perfusion. Abdominal organs should be removed rapidly, en bloc, and separated during back-table dissection in the cold, particularly if pancreas or intestine is included. Perfusion itself should be carried out after single cannulation of the aorta with an increased pressure. CONCLUSION: Although the literature on organ retrieval is extensive, the level of evidence provided is mainly low. Nevertheless, optimized donor treatment and organ retrieval should increase the number and quality of cadaveric donor organs and improve graft function and survival.

Alemtuzumab induction and sirolimus plus mycophenolate mofetil maintenance for CNI and steroid-free kidney transplant immunosuppression.

We performed a pilot study in which 22 kidney recipients (14 LD: 8 DCD) were given alemtuzumab induction (30 mg day 0 and 1), steroids (500 mg mp day 0 and 1, none thereafter), mycophenolate mofetil (MMF) maintenance (500 mg b.i.d) and sirolimus (concentration controlled 8-12 ng/mL). With a mean follow-up of 15.9 months, patient survival is (21/22) 96% and graft survival (19/22) 87%. Acute rejections occurred in (8) 36.3% (two humoral). Of 19 surviving grafts, 18 (95%) remain steroid and 15 (79%) CNI-free. At 1 year, mean creatinine was 1.43 mg/dL. Overall infection rates were low, but 2 patients developed severe acute respiratory distress syndrome (ARDS) at month 3 and 7, respectively, resulting in mortality in one and a graft loss in the other. No cancer or PTLD was observed. Leukopenia was common and MMF dose was reduced or eliminated in 6/22 (27%) patients. The reported higher than expected rate of acute rejection, leukopenia and possible pulmonary toxicity suggests excessive morbidity. Modifications such as an initial period of CNI use should be considered.

Living donor kidney transplantation: impact of differentiated immunosuppressive regimen.

INTRODUCTION: Recipients of related (R) and unrelated (NR) living donor kidney transplantations (LDKTX) receive immunosuppressive (IS) therapy 5 days in advance in order to achieve low rates of acute rejection episodes. We herein report the different IS regimens for R and NR transplants as well as acute rejection and primary function rates. METHODS: Ninety-five LDKTX (69% R, 31% NR) were performed with mean cold ischemia time (CIT) of 145 +/- 32 minutes. In R-LDKTX mean age of recipients was 31 +/- 12.5 years. This cohort included 41 men and 25 women whose mean age was 50 +/- 11.1 years. The therapeutic regimen for R-LDKTX included CyA/MMF/prednisone; for NR-LDKTX, FK/MMF/prednisone. Among the recipients of NR grafts the mean recipient age was 51 +/- 8.5 years. This cohort included 23 men and 6 women whose donor mean age was 50 +/- 8.8 years. The mean HLA mismatch among R-LDKTX (2.3) was significantly less than that in the NR-LDKTX cohort (3.51). RESULTS: At a mean follow-up of 35 months, 94.7% of grafts were functioning. DGF was seen in only one recipient (1%). Three grafts were lost due to acute (R) or chronic (NR) rejection or to multiorgan failures. Two recipients died with functioning grafts. Biopsy-proven rejection episodes were observed in 17.2% of NR-LDKTX and 9% of R-LDKTX. In R-LDKTX 50% of rejection episodes were corticoid-sensitive, while 33% needed ATG, and 16% were treated by a switch to FK. In NR-LDKTX 20% of rejections were corticoid-sensitive, 40% needed ATG, and 40% were treated with rapamycin rescue therapy. CONCLUSION: Although HLA mismatching is significantly different between R- and NR-LDKTX, no difference in outcome was observed, which may be due to the specific therapeutic regimen and short CIT.