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Outcome after renal transplantation depends on patient compliance and adherence for early detection of complications and identification of intervention opportunities. Compliance describes the degree to which patients follow medical advice and take their medications. Adherence has been defined as the extent to which a patients' behavior coincides with clinical prescriptions.Patients were randomized 7 to 14 days after transplantation into groups with (n = 40) and without (n = 40) an electronic medication dispenser (EMD). The EMD, which was used for the 1-year study period, recorded the date and time the patient took their medications and was monitored via a web-based application. Patients were monitored for 1 year regarding outpatient follow-up visits, emergency hospitalizations, renal biopsies, rejection episodes, renal function, and blood concentration of medications.Compliance in the intervention group was 97.8% (the control group was not assessed). Number of missed doses varied significantly by weekday (P = 0.033); patients were most likely to miss doses on Saturdays and Thursdays. Patients missed a total of 11 follow-up visits. During the study, 92 biopsies were performed on 55 patients (intervention group: 32 [17]; control group, 60 [38]). Biopsy-verified rejection was three times more common among controls (13 patients vs. 4; P = 0.054, not significant). Average P-creatinine level was slightly lower in the intervention group than the control group (131 vs. 150 μmol/L, not significant), whereas mean tacrolimus was similar (7.32 vs. 7.22 ng/mL, n.s.).The EMD is associated with high compliance, and there are also indications of a lower rejection rate.

The presence of human leukocyte antigen (HLA) and non-HLA antibodies (Abs) in kidney transplant recipients is associated with graft rejections. This study reports the results of an endothelial precursor cell crossmatch (EPCXM) test for detection of non-HLA Abs and its correlation to lymphocyte crossmatch (LXM) test results, the degree and type of sensitization, and transplantation (Tx) outcome in patients evaluated for living donor (LD) kidney transplantation (KTx). Patients were tested before any pre-transplantation (pre-Tx) treatment and at Tx. Pre-Tx treatments included B cell depletion and Ab removal. Patient records were reviewed for assessment of renal graft function, results of biopsies, and identification of complications affecting the graft. Pre-Tx sera from 32% of the LD patients had IgG and/or IgM-binding donor EPCs. Twenty-five percent of the patients were EPCXM IgM+. Of the patients with negative LXM tests, 25% had EPC Abs mainly of IgM class not reactive with HLA. There was no difference in rejection frequency or serum creatinine levels between the EPCXM+ and EPCXM- groups. The pre-Tx EPCXM+ group had significantly more patients with delayed graft function. Prospective studies with appropriate control groups are needed to establish whether pre-treatments aiming at removing anti-endothelial cell antibodies, as detected by the EPCXM pre-Tx, have a beneficial effect on short-term and long-term graft survival.

There are still concerns about renal transplantation in small children. The aim of this study was to identify prenatal data, underlying diseases, patient and graft survival, graft function and growth in young renal transplant recipients at our center. A retrospective analysis was performed on 50 kidney transplants performed during the period 1981-2008 in children weighing13 kg. Their median age at transplantation was 1.4 (range 0.4-3.7) years and the median weight was 9.5 (3.4-12.1) kg. The underlying diseases were congenital in 88% of the patients and acquired in 12%. Ten-year patient survival was 88% (82% before 1998 and 95% since 1998). Ten-year graft survival was 82% (75 and 95%, respectively). Graft function (glomerular filtration rate) deteriorated from a mean of 75-48 ml/min/1.73 m(2) within 10 years. There was rapid catch-up growth within the first years post-transplant, from a median height of -2.44 standard deviation score (SDS) at transplantation to -0.74 SDS after 3 years. In small children, patient and graft survival were as good as those in older children. Renal function deteriorated during the first years post-transplant but stabilized within a few years. In most children, there was a substantial improvement in growth within the first years after transplantation.

Background. As antigen-specific immunoadsorption (IA) using the Glycosorb-ABO columns is becoming increasingly popular in ABO-incompatible (ABOi) transplantation, in this study, we retrospectively investigated the efficacy of Glycosorb-ABO IA in vivo and ex vivo .W e also assessed the risk of anti-A/B antibody (ABab) rebound before and after ABOi kidney transplantation. Methods. A protocol for ABOi living donor kidney transplantation was used, combining four preoperative and three preemptive postoperative Glycosorb-ABO IAs with rituximab and maintenance immunosuppression. ABabs were determined by a haemagglutination titration technique. Results. ABOi kidney transplantation was attempted 45 times and 43 transplantations were performed. Overall patient survival was 93% and graft survival was 91%. Mean followup was 4.5 years. Glycosorb-ABO IA significantly reduced the ABabs in the majority of patients (P < 0.0001). However, in three patients (6.8%), the antibody elimination was incomplete. Inadequate adsorption of core-chain-dependent ABabs may explain this finding, but further studies are needed. In five patients, the preconditioning was interrupted before transplantation, resulting in ABab rebound. Yet, when preconditioning was restarted, the antibodies could be removed as planned. After ABOi transplantation, rebound of ABabs was seen in two patients (5%). Conclusions. Glycosorb-ABO IA in combination with rituximab effectively depletes ABabs in most patients, but owing to core-chain-dependent ABabs, GlycosorbABO IA may be less effective than nonspecific techniques for antibody removal in some patients. Rebound before transplantation subsequent to interrupted preconditioning does not hamper a successful ABOi transplantation. Postoperatively, when this protocol for ABOi transplantation is followed, the risk of ABab rebound is small.

As the demand for kidney transplantation is constantly growing methods to expand the donor pool have become increasingly important. ABO-incompatibility has hitherto been regarded as an absolute contraindication to living donor donation. However, as ABO-incompatibility has accounted for the majority of living donor exclusions, efforts have been made to overcome this immunologic barrier. Successful desensitization protocols thus far, have combined plasmapheresis for antibody removal with splenectomy to reduce the antibody producing B-cell pool, in addition to quadruple immunosuppression. Although good graft function has been achieved, the high risks involved have been deterrent. We have developed a protocol for ABO-incompatible kidney transplantation based on antigen-specific immunoadsorption and rituximab, in combination with standard maintenance immunosuppression (tacrolimus, mycophenolate mofetil and corticosteroids). We hypothesized that the anti-A/B antibodies could be effectively eliminated and good graft function achieved, without the complications of coagulopathy and transfusion reactions associated with plasmapheresis. Furthermore, we hypothesized that the substitution of splenectomy with a single dose of the anti-CD20 antibody rituximab would further reduce surgical risk as well as the risk of infectious complications. In 2001 the program for ABO-incompatible kidney transplantation was started at our center. To date 50 ABO-incompatible kidney transplantations have been performed according to the protocol based on antigen-specific immunoadsorption and rituximab. Safety and efficacy of the protocol has been evaluated in several studies, all showing that the antigen-specific immunoadsorption is well tolerated and without any serious side effects. Patient and graft survival as well as kidney function have been comparable to that of ABO-compatible living donor kidney transplantation and the incidence of antibody-mediated rejection 0%. We conclude that AB0-incompatible kidney transplantation using a protocol based on antigen-specific immunoadsorption and rituximab, in combination with triple immunosuppressive therapy is safe and effective. ABO-incompatibility following this protocol does not have a negative impact on graft function. ABO-incompatible kidney transplantation is equivalent to standard ABO-compatible living donor kidney transplantation.

We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event. Results. We enrolled 140 patients (44 living donor and 96 deceased donor), and of those, 68 rituximab and 68 placebo patients fulfilled the study. In all the patients receiving rituximab, there was a complete depiction of CD 19/CD20 cells, whereas there was no change in the number of CD19/CD20 cells in the placebo group. There were 10 treatment failures in the rituximab group versus 14 in the placebo group (P=0.348). There were eight rejection episodes in the rituximab group versus 12 in the placebo group (P=0.317) Creatinine clearance was 66 +/- 22 mL/min in the study group and 67 +/- 23 mL/min in the placebo group. There was no difference in the number of bacterial infections, cytomegalovirus infections, and BK virus infections or fungal infections. Conclusion. We performed a placebo-controlled study of rituximab induction in renal transplantation. There was a tendency toward fewer and milder rejections during the first 6 months in the rituximab group. Although induction with one dose of rituximab induced a complete depletion B cells, there was no increase in the incidence of infectious complications or leukopenia and it seems safe, therefore, to conduct further studies on the use of rituximab in transplantation.

BACKGROUND.: Fixed-dose mycophenolate mofetil (MMF) reduces the incidence of acute rejection after solid organ transplantation. The Fixed-Dose Concentration Controlled trial assessed the feasibility and potential benefit of therapeutic drug monitoring in patients receiving MMF after de novo renal transplant. METHODS.: Patients were randomized to a concentration-controlled (n=452; target exposure 45 mg hr/L) or a fixed-dose (n=449) MMF-containing regimen. The primary endpoint was treatment failure (a composite of biopsy-proven acute rejection [BPAR], graft loss, death, or MMF discontinuation) by 12 months posttransplantation. RESULTS.: Mycophenolic acid (MPA) exposures for both groups were similar at most time points and were below 30 mg hr/L in 37.3% of patients at day 3. There was no difference in the incidence of treatment failure (25.6% vs. 25.7%, P=0.81) or BPAR (14.9% vs. 15.5%, P>0.05) between the concentration-controlled and the fixed-dose groups, respectively. We did find a significant relationship between MPA-area under the concentration-time curve on day 3 and the incidence of BPAR in the first month (P=0.009) or in the first year posttransplantation (P=0.006). For later time points (day 10, month 1) there was no significant relationship between area under the concentration-time curve and BPAR (0.2572 and 0.5588, respectively). CONCLUSIONS.: There was no difference in the incidence of treatment failure between the concentration-controlled and the fixed-dose groups. The applied protocol of MMF dose adjustments based on target MPA exposure was not successful, partly because physicians seemed reluctant to implement substantial dose changes. Current initial MMF doses underexpose more than 35% of patients early after transplantation, increasing the risk for BPAR.

ABO-incompatible (ABOi) kidney transplantation has gained a renewed interest during the past years. In 2001, a protocol for ABOi kidney transplantation based on antigen-specific immunoadsorption and rituximab was introduced at our center. In this study long-term graft function using this protocol was assessed. All ABOi kidney recipients with >1-year follow-up (n=15) were compared with all ABO-compatible (ABOc) living donor kidney recipients maintained on the same basic immunosuppression (n=27). Patient and graft survival as well as rejections and calculated glomerular filtration rate were analyzed. Mean follow-up was 3 years. There was no significant difference in patient and graft survival nor in rejection episodes. Mean glomerular filtration rate (79-83 ml/min) was equivalent at 1, 2, and 3 years in both groups. We conclude that ABOi kidney transplantation using antigen-specific immunoadsorption and rituximab is equivalent to standard ABOc living donor kidney transplantation. ABOi transplantation following this protocol does not have a negative impact on graft function long-term.

The anti-CD20 antibody rituximab has recently gained interest as a B-cell depleting agent in renal transplantation. However, little is known about the pharmacodynamics of rituximab in renal transplant recipients. We have therefore studied the effect of single-dose rituximab in combination with conventional triple immunosuppressive therapy on the B-cell population in peripheral blood as well as in tissues. A total of 49 renal transplant recipients received single-dose rituximab, as induction therapy (n = 36) or as anti-rejection therapy (n = 13). We counted B cells in peripheral blood and performed immunohistochemical staining on lymph nodes and kidney transplant tissue samples to assess the prevalence of B cells. In all but 6 patients (88%) complete depletion of B cells in peripheral blood was achieved. In adults, 15 months after treatment the CD19+ and CD20+ cell counts were still below 5 cells/muL in the majority of patients (78%). The immunohistochemical staining showed a complete elimination of B cells in kidney tissue and a reduction of B cells in lymph nodes. In conclusion, single-dose rituximab in kidney transplant recipients evokes a long-term elimination of B cells in peripheral blood as well as within the kidney transplant. The effect seems to extend beyond the expected 3-12 months observed in lymphoma patients.

This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with cyclosporin microemulsion (CyA) in pediatric renal recipients. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (

Background We have previously reported on our 10-year experience of renal transplantation in children in the cyclosporine era, that is, from December 1981 until December 1991. In this paper, we report on the same children observed for another 10 years. Methods Of 53 children who received a renal transplant between 1981 and 1991, 47 survived and were observed for 10 to 20 years. Immunosuppression consisted of cyclosporine, prednisolone, and azathioprine. Yearly clinical examinations were performed. Results Overall, actual patient survival is 91%, 89%, and 89%, and actual graft survival 85%, 77%, and 66% at 1, 5, and 10 years, respectively. No patients have died during the last 10 years. Twenty-six grafts were lost over 20 years. Thirteen of those were lost during the present follow-up (10-20 years): 11 in chronic rejection and 2 because of development of renal cell carcinoma. No other malignancies were noted. Mean glomerular filtration rate decreased from 58+/-19 at 1 year (n=42) to 44+/-16 mL/min/1.73 m2 body surface area at 10 (n=33) years. Hypertension was treated in 46%, 40%, and 66% of the children at 1, 5, and 10 years, respectively; two of them showed left ventricular hypertrophy 10 years after transplant. Minor cataracts without visual disturbance were found in 45% of patients. All children except three with mental retardation are, or have been, attending normal day care or normal school. Conclusion Social integration is good, and severe complications are scarce, even when renal transplantation occurred at a very young age.

Long-term outcome of growth and final adult height (FH) are a major concern of children after a renal transplantation (Tx). We therefore studied the yearly measurements of height (Ht), expressed as the Z-score and bone age (BA), in 58 children (28 girls) transplanted in our departments and followed-up for 5–18 (mean 9.6) yr after the operation. Twenty-four children reached final adult height. Renal function was evaluated as the glomerular filtration rate (GFR), which is estimated from the clearance of inulin. The mean Ht Z-score at Tx was −1.3 in girls and −2.7 in boys and increased to −0.6 and −1.5, respectively, at 5 yr after Tx. The greatest increase, seen in the shortest children and those transplanted before 7 yr of age, occurred during the first 3 yr. Children aged 7–12 yr at Tx showed an increase in height during the first years after the transplant, while those transplanted at >12 yr of age were not growth-retarded and therefore did not change their Ht Z-score. The most growth-retarded were also the most BA retarded. The mean FH Z-score was −1.1. A direct correlation was seen between GFR at 1 yr after Tx and the increase in height Z-score from Tx to 1 and 5 yr after Tx. In summary, the increment in height following Tx was the greatest in the most growth-retarded children and most marked during the first 3 yr after the transplant. FH was within normal range in 75% of the children. A high Ht Z-score at Tx had a positive effect on FH. Thus, growth after Tx was affected by the degree of stunting at Tx and renal function after Tx.

Autotransplantation for renovascular hypertension in children with solitary functioning kidney

We designed a new protocol to enable safe ABO-incompatible kidney transplantation. The new protocol utilizes antigen-specific immunoadsorption rather than unspecific plasma exchange to remove existing anti A/B antibodies and rituximab rather than splenectomy to prevent rebound of antibodies. Sixty patients have so far been successfully transplanted with this protocol and 10 of those have been children. When compared with ABO-compatible transplantations, we could not find any differences in success rate, renal function, or adverse events.

BACKGROUND There is a lack of kidneys available for kidney transplantation, and living donors are increasingly used. It is important to examine the possible long-term adverse affect on the renal function and blood pressure of the donors. METHODS We have made a comprehensive follow-up of all living kidney donors at our center from 1964 to 1995. Of 402 donors still alive, we were able to get information about serum creatinine, urinary proteins, and blood cells in urine using reagent strips, and blood pressure from 87%. The glomerular filtration rate (GFR) was estimated using a formula and was measured with Iohexol clearance in 43 of the donors. Individual data on GFR and the prevalence of hypertension were compared with the age- and gender-expected values. RESULTS The mean age of the examined donors was 61 years (SD:13) at follow-up, and the time since donation was 12 years (SD:8). The average estimated GFR was 72% (SD:18) of the age-predicted value. The ratio of the estimated to the predicted GFR showed no correlation to the time since donation, indicating that there is no accelerated loss of renal function after donation. GFR below 30 ml/min was found in five donors. No donor died in uremia or had dialysis treatment before death. However, three donors developed renal disease, and one was in dialysis treatment. In two of these cases, hereditary factors were possibly involved. Hypertension was present in 38% of the donors but the age-adjusted prevalence of hypertension among donors was not higher than in the general population. Significant proteinuria (> or =1.0 g/L) was found in 3% and slight proteinuria (

BACKGROUND: Supplementation of immunosuppressive therapy with mycophenolate mofetil (MMF) has been found to reduce the rate of acute rejection in renal transplantation. We report a dose-finding study for MMF when administered in combination with low-dose tacrolimus and corticosteroid prophylaxis in cadaveric renal transplant recipients. METHODS: Two hundred thirty-two patients at 16 centers were enrolled in this randomized, parallel-group study. The three treatment groups were tacrolimus and corticosteroids (MMF-0 group, n=82); tacrolimus, corticosteroids, and 1 g of MMF daily (MMF-1 g group, n=79); and tacrolimus, corticosteroids, and 2 g of MMF daily (MMF-2 g group, n=71). Study duration was 6 months, and patients were followed up for patient and graft survival for 12 months. RESULTS: At 6 months posttransplantation, daily doses of 1 g and 2 g of MMF were associated with significantly lower rates of acute rejection compared with tacrolimus alone. The Kaplan-Meier rates were 48.5%, 24.9%, and 22.9%, respectively, for the three treatment groups when acute rejection was determined by clinical criteria (P=0.007). At month 12, patient survival rates were 100%, 97.5%, and 97.2% and graft survival rates were 90.2%, 92.4%, and 93.0% for the MMF-0 group, MMF-1 g group, and the MMF-2 g group, respectively. Gastrointestinal adverse events and leukopenia were higher in the MMF groups, especially in the MMF-2 g group (P

The purpose of this study was to find out whether prolonged normoglycemia, as achieved by a successful pancreas transplantation, can improve survival in patients with insulin-dependent diabetes mellitus. A retrospective analysis of actual 10-yr patient survival rates was done for all renal graft recipients who were given transplants more than 10 yr ago but within the cyclosporin era (i.e. 1981-1988). The actual 10-yr patient survival rate in non-diabetic renal graft recipients was 72%, In recipients of pancreas and kidney grafts and with prolonged function of the pancreas graft, the survival rate was 60%, whereas in patients subjected to simultaneous pancreas and kidney transplantation, but where the pancreatic grafts failed within 2 yr, the survival rate was 33%. In diabetic recipients of kidney transplants alone, the survival rate was 37%. The patient survival rate was substantially higher in non-diabetic patients and patients with functioning pancreas grafts compared with diabetic patients with kidney transplants alone or with failed pancreas grafts. We speculate that the decrease in mortality was due to the beneficial effect of long-term normoglycemia on diabetic late complications.

BACKGROUND A number of risk factors for chronic renal allograft rejection have been identified; in particular the number and severity of acute rejections, hypertension, hyperlipidemia, and insufficient immunosuppression. METHODS In a retrospective case control study, all histologically confirmed cases of chronic rejection (n=45) that occurred between 1985 and 1993 among patients transplanted at Huddinge Hospital were compared with twice as many controls. Determinants such as donor age and sex, HLA-mismatch, cold ischemia time, recipient age and sex, body mass index, cause of renal disease, time undergoing dialysis, condition of blood vessels at surgery, time of onset, number of acute rejection episodes during the first 3 months, area under the serum creatinine versus time curve (AUC(Creatinine)), blood pressure, blood lipids, and cyclosporine concentrations at various times after the transplantation were also compared. Additional data were obtained from a questionnaire, concerning 79% of the cases and controls. RESULTS Cases and controls were similar with regard to most determinants, that is, blood pressure, blood lipids, and average cyclosporine concentrations. The main outstanding risk factor for chronic rejection was the time-averaged creatinine (AUC(Creatinine)) value between day 22 and 3 months after transplantation. The adjusted odds ratio for chronic rejection increased stepwise from 1.1 to 9.2, when AUC(Creatinine) increased from 300 micromol/l. The number of acute rejection episodes and number of HLA-mismatches also had a significant effect on the risk of chronic rejection. CONCLUSIONS To reduce the risk of developing chronic rejection after renal transplantation acute rejection episodes during the first 3 months should be avoided as much as possible.

Background The purpose of pancreatic transplantation in insulin-dependent diabetic patients is to restore normoglycemia and thereby prevent the secondary complications of diabetes. However, uncertainty remains as to whether the mortality rate in diabetic patients can be affected by this procedure. Method We followed 14 patients with insulin-dependent diabetes mellitus (IDDM) and end-stage diabetic nephropathy for 10 years after successful combined kidney and pancreas transplantation. Fifteen diabetic patients subjected to kidney transplantation alone have served as controls. The glycemic control has been studied annually for 10 years and diabetic polyneuropathy has been assessed in both groups after 2, 4, and 8 years. Results In recipients of pancreas-kidney grafts, metabolic control was maintained throughout the observation period, with values of glycated hemoglobin in the normal range. In contrast, glucose metabolism was impaired in the control group, with glycated hemoglobin values around 10%. Nerve conduction and parasympathetic autonomic dysfunction improved in both groups after 2 years; there was no difference between the groups. After 4 years, we found a significant difference between the study group and the control group, and after 8 years it had widened. At the 4-year evaluation, there was no difference in mortality between the groups. At 8 years, however, a significant difference was noted, which was further substantiated at 10 years with a 20% mortality rate in the pancreas-kidney group versus an 80% mortality in the kidney alone group. Conclusions We found a substantial reduction in mortality in IDDM patients 10 years after successful combined pancreas and kidney transplantation. We speculate that the decrease in mortality was due to the beneficial effect of long-term normoglycemia on diabetic late complications and suggest therefore that combined pancreas and kidney transplantation, rather than kidney transplantation alone, should be offered to IDDM patients with end-stage diabetic nephropathy.

A new protocol for ABO-incompatible kidney transplantation has recently been introduced. We report here on the joint experience of the implementation in Stockholm and Uppsala, Sweden and Freiburg, Germany.The new protocol utilizes antigen-specific immunoadsorption to remove existing ABO-antibodies, rituximab, and intravenous immunoglobulin to prevent the rebound of antibodies, and conventional tacrolimus, mycophenolate-mofetil, and prednisolone immunosuppression. Sixty consecutive ABO-incompatible kidney transplantations were included in the study. The outcome is compared with the results of 274 ABO-compatible live donor transplantations performed during the same period.Two of the ABO-incompatible grafts have been lost (non-compliance and death with functioning graft). All the remaining 58 grafts had good renal function at a follow-up of up to 61 months. We did not observe any late rebound of antibodies and there were no humoral rejections. Graft survival was 97% for the ABO-incompatible compared with 95% for the ABO-compatible. Patient survival was 98% in both groups. There was a significant variation in preoperative A/B-antibody titer between the centers, with a median 1:8 in Uppsala, median 1:32 in Stockholm and median 1:128 in Freiburg. More preoperative antibody adsorptions were therefore needed in Freiburg than in Stockholm and Uppsala.The new protocol was easily implemented and there were no graft losses that could be related to ABO-incompatibility. A significant inter-institutional variation in the measurement of anti-AB-antibodies was found, having a substantial impact on the number of immunoadsorptions and consequently on the total cost for the procedure. A standardized fluorescence-activated cell sorting technique for antibody quantification is much needed.

Background: ABO-incompatible kidney transplantations have previously only been performed after several pre-operative sessions of plasmapheresis followed by splenectomy, and with the conventional triple-drug immunosuppressive protocol being reinforced with anti-lymphocyte globulin and B-cell-specific drugs. We have designed a protocol without splenectomy, based on antigen-specific immunoadsorption, rituximab and a conventional triple-drug immunosuppressive protocol. Methods: The protocol called for a 1-month pre-transplantation conditioning period, starting with one dosage of rituximab and followed by full-dose tacrolimus, mycophenolate mofetil and prednisolone. Antigen-specific immunoadsorption was performed on pre-transplantation days −6, −5, −2 and −1. After the last session, 0.5 g/kg of intravenous immunoglobulin (IVIG) was administered. Postoperatively, three more apheresis sessions were given every third day. Results: Twenty-one patients have received transplants with this protocol. The ABO-antibodies (Abs) were readily removed by the antigen-specific immunoadsorption and were kept at a low level post-transplantation by further adsorptions. There were no side effects, and all but one patient have normal renal transplant function. Conclusions: We conclude that after one infusion each of rituximab and IVIG, and antigen-specific immunoadsorption, blood-group incompatible renal transplantations can be performed with standard immunosuppression and without splenectomy, and with excellent short- and long-term results.

The immunological rejection of HLA-identical kidney transplants indicates that non-HLA antigens may also be targets for transplant rejection. Interest in the possible role of endothelial specific antigens has grown steadily over the years. Most of the studies published, regarding the association of such antibodies with rejection, have demonstrated the reactivity of endothelial antibodies also with monocytes and keratinocytes, but not with lymphocytes. Such antibodies escape detection in conventional crossmatch tests. In this paper, we present a case report of a 10-year-old girl, whose two consecutive kidney allografts, (one living and one cadaveric donor) were hyperacutely rejected in spite of the fact that she had neither been alloimmunized, nor had any HLA-specific antibodies. Endothelial cell specific antibodies were detected in vivo and in vitro after transplantation only 11 days apart, which were considered to be responsible for rejection. The third cadaveric kidney was lost within 1 week post-transplant. Immunopathological investigation of the three rejected grafts revealed deposition of IgM in the endothelium of arteries and in some glomeruli. No deposition of IgG antibodies was found. Antibodies from this patient did not react with lymphocytes, monocytes or keratinocytes. Patient serum had IgM antibodies that were specifically reactive with cultured endothelial cells, demonstrated by binding in vitro and by complement-dependent cytotoxicity of IL-β stimulated endothelial cells. No HLA antibodies were found following the first two transplantations, but were demonstrated 1 week after the third transplantation, at the time of an acute irreversible rejection. Western blots of proteins solubilized from endothelial cell membranes, indicated that the antibodies reacted with a 97–110 kD protein. Endothelial cell antigen preparations were made from several different umbilical cord veins. Some primary cell cultures, but not all, reacted with the patient's serum. Therefore, we suggest that the target determinant might be polymorphic. These findings imply that the non-HLA endothelial cell specific molecules may function as target(s) for hyperacute antibody-mediated destruction of kidney allografts.

Background. Adult donor grafts adapt to the smaller size of the child recipient by reducing their absolute glomerular filtration rate (GFR) (ml/min). The question arises whether these grafts can increase the absolute GFR when the child recipient grows or whether a child donor graft can better increase its function. The aim of this study was to evaluate the influence of donor and recipient ages and sex on renal function. Methods. Eighty-five children and adolescents, aged 0.4-20.5 years at transplantation, were monitored annually, by GFR and effective renal plasma flow (ERPF), determined by clearances of inulin and para-aminohippuric acid. The patients received 90 grafts from donors aged 3-67 years. Follow-up time was around 5 years. Results. Absolute GFR and ERPF (ml/min) of grafts from donors 20 years of age remained constant during follow-up, resulting in a significant decrease in relative values. Relative GFR and ERPF fell during follow-up in young recipients ( 12 years). Donor and recipient sex did not influence renal function. Conclusions. Child donor grafts seem better able to increase their function with the growth of the child recipient than adult grafts. However, the limited access to pediatric grafts and the fact that pediatric cadaveric grafts might involve technical problems in connection with grafting restrict their use.

Sirolimus is a new immunosuppressive drug that has been evaluated in animal experiments. The current study was conducted on humans with reformulated sirolimus in doses from 3 mg/m2 to 15 mg/m2. Sixteen renal transplant recipients were included in this phase I study to determine the safety, tolerance, and preliminary pharmacokinetics of increasing single doses of orally administered sirolimus. All 16 patients had stable renal graft function after a renal transplant at least 6 months before the study. Basal immunosuppression consisted of cyclosporine and prednisolone (n = 10) or cyclosporine, azathioprine, and prednisolone (n = 6). Four groups (I, 3 mg/m2; II, 5 mg/m2; III, 10 mg/m2; IV, 15 mg/m2) of four patients were assigned randomly to receive sirolimus (n = 3) or placebo (n = 1). Among the 12 patients who received sirolimus, five had mild transient study events such as headache, nausea, mild dizziness, hypoglycemia, epistaxis, and decrease in platelets. No serious adverse events occurred and no nephrotoxic effects could be related to the single dose administration of sirolimus. The only study event that was judged as probably related to sirolimus was the single case of thrombocytopenia. The other events were evaluated as possibly related. Thrombocytopenia occurred at the highest dose level (15 mg/m2 sirolimus). In two of the patients in the placebo group, slight elevations of liver enzymes and serum amylase were seen. Blood and plasma sirolimus concentrations were analyzed by an electrospray-high performance liquid/mass spectrophotometric (ESP-HPLC/MS) method Sirolimus showed an extensive red blood cell distribution with a mean blood/ plasma ratio of 49.1. The elimination half-life ranged from 43.8 to 86.5 hours (mean 56.9 hours). The Cmax and the area under the concentration versus time curves (AUC) correlated reasonably with doses from 3 to 15 mg/m2. The oral dose clearance ranged from 42 to 339 ml/h.kg. No clinically significant differences were seen in the trough concentrations of cyclosporine or the AUCs before and after the administration of sirolimus. Administration of single oral doses of sirolimus from 3 to 15 mg/m2 was safe and well tolerated in stable renal transplant recipients. Thrombocytopenia may be the dose-limiting toxicity. Additional phase II and phase III clinical trials will define the immunosuppressive efficacy of sirolimus.

Twenty-one infants, 2 years old or younger, received 21 renal transplants between 1983 and 1995. Six of the transplantations were performed from 1983 to 1989, and the remaining 15 were performed from 1990 to 1995. The median age at transplantation was 16.0 months and the median body weight was 9.0 kg. Living-related donor kidneys were used in 15 cases, an adult cadaveric donor kidney was used in one case, and pediatric cadaveric donor kidneys were used in five cases. All grafts were placed intra-abdominally. The immunosuppressive therapy consisted of cyclosporine, azathioprine, and prednisolone. No prophylactic antithymocyte globulins were used. Five infants have died, one with a functioning graft and four after loss of graft function. All graft losses and deaths occurred during the first 6 months after transplantation. The 5-year patient survival and graft survival rates were 87% for recipients of living donor grafts and 44% for recipients of cadaveric grafts. The median height SD score increased from -3.7 before operation to -1.9 at 1 year, -0.7 at 3 years, and -1.1 at 5 years. The glomerular filtration rate in absolute values remained stable in all infants, whereas a reduction in glomerular filtration rate related to body surface area was seen at follow-up, 5 years after transplantation. We conclude that renal transplantation can be performed with good long-term results in children less than 2 years old.

Acute rejection episodes still occur after kidney transplantation in spite of modern immunosuppressive protocols including combined tacrolimus, mycophenolate mofetil, and prednisolone. The authors present seven cases of biopsy-proven acute rejection after kidney transplantation refractory to conventional rejection therapy with repeated pulses of high-dose steroids followed by polyclonal or monoclonal antibodies that responded well to photopheresis treatment. Photopheresis is an atoxic immunomodulatory apheresis-based treatment with no generalized immunosuppressive action; rather, it is directed at suppressing donor-specific T-cell clones. At the last follow-up, 9 to 43 months after transplantation, all patients had functioning grafts, with serum creatinine levels ranging from 105 to 312 microM. The authors conclude that photopheresis treatment contributed to the favorable outcome. Therefore, the authors are presently designing a prospective, randomized trial to evaluate the effect of photopheresis as an adjuvant prophylactic treatment after renal transplantation.

Post-transplant hypertension impacts negatively on renal graft survival. Our primary objective was to analyze the effect of hypertension on the glomerular filtration rate (GFR) slope.All clinical charts of children who underwent renal transplantation since the introduction of the routine use of ambulatory blood pressure monitoring (ABPM) were reviewed. Eligibility criteria for inclusion were measurement of GFR at 3 months, at 1 year post-transplant, and thereafter at yearly intervals; ABPM performed annually after transplantation; and functioning graft for a minimum of 2 years.Sixty-eight (39 males) of 79 patients, aged 9.1±5.3 years, met the inclusion criteria. The mean follow-up was 6.2±2.8 years. Twenty-four patients had normotension or controlled hypertension throughout their follow-up (normotensive group). Forty-four patients had hypertension or noncontrolled hypertension at some point(s) during the follow-up period (hypertensive group). GFR slope was -1.6ml/min/1.73 m(2) per year (95% confidence interval (CI = -3.7 to 0.4) in the normotensive group and -2ml/min/1.73 m(2) per year (95% CI = -3 to -1.1) in the hypertensive group (P = 0.42). There was no difference between groups with regard to the change in GFR values from 3 months to 1 year and to last control (P = 0.87). At most recent control, the overall prevalence of controlled hypertension was 78.2% (95% CI = 63.6-89.1).Although the results of our study are encouraging, they need to be confirmed in a larger prospective study using the same post-transplant follow-up protocol.

A vasculopathy score (VP score) was designed in order to evaluate donor-related arteriosclerotic changes in kidney grafts. The four histopathological parameters that are semiquantitatively graded are glomerulosclerosis, stenosis and intimal hyperplasia of artery, and arteriolar hyalinization. The score of each parameter is weighted according to relative importance, and summed into a single parameter, the VP score. In order to evaluate the predictivity of the VP score on renal graft function, we applied this method to the first biopsy taken within 1 month after cadaveric kidney transplantation in 75 consecutive patients. The VP score was correlated to the following clinical data: graft survival at 3 months, 1 year, and 2 years after transplantation, graft function as reflected by need for hemodialysis within 1 week and 1 month, and serum creatinine level at 1 week, 1 year, and 2 years after transplantation. There was a significant correlation between VP score and donor age. In a particular case, however, age per se is not a good predictor of vascular status. Secondly, there was a significant correlation between short-term (3 months) graft survival and VP score, but none between 1 or 2 years graft survival and VP score. When two groups of patients with high and low VP scores, respectively, were compared, there were significant differences between graft function at 1 week and 1 year and graft survival at 3 months. Thus, our results show that the VP score is useful to predict short-term graft survival and graft function.

A randomized, double-blind, placebo-controlled study of single dose rituximab as induction in renal transplantation : a 3-year follow-up

Background In 2009, we started to screen all patients on the heart transplant waiting list for the presence of blood group anti-A or anti-B antibodies. From our experience with ABO-incompatible kidney transplantation, we know that transplantation can safely be performed if the antibody level is reduced to a titer of immunoglobulin G (IgG) 1:8. Methods We decided to accept all patients with anti-A or anti-B antibody titer≤1:8 for ABO-incompatible heart transplantation without any special pre-treatment and patients with antibody titers of IgG 1:16 and 1:32, provided 1 apheresis session could be performed immediately before transplantation. Results We found 6 of 13 patients were suitable for this program, and 2 ABO incompatible patients underwent successful transplantation with a follow-up of 1 year. Conclusion In heart transplant candidates where there are problems obtaining a compatible heart and who are not suitable for ventricular assist device support, ABO-incompatible heart transplantations can be considered using our protocol, provided that the levels of anti-A or anti-B antibodies are low.

Human Pancreas-Specific Protein (PASP) has been described as a useful serum marker for pancreatic graft rejection and acute pancreatitis. By molecular cloning PASP has recently been identified as procarboxypeptidase B (PCPB). By use of SDS-gel electrophoresis and Western blots, PASP isoforms (proteins interacting with PASP-antiserum) have now been explored in serum and pancreatic tissue and juice. In serum from healthy volunteers, six different isoforms could be visualised. Their MW varied as follows: > 100 K, about 100 K, 45 K, 35-40 K (two bands) about 30 K and 16 K. The 45 K band, corresponding to PASP purified from pancreatic tissue, was always the major band. In pancreatic cytosol and pancreatic juice, the major band corresponded to PASP (45 K) but weak bands were also seen at MW of 40, 30 and 16 K. In serum from 15 patients with acute pancreatitis, PASP was highly increased. Bands corresponding to PASP/PCPB as well as carboxypeptidase B (CPB) were seen simultaneously. During recovery PASP in serum was normalised and the CPB band disappeared. During 12 episodes of pancreatic graft rejection, PASP in serum was also increased but no changes of isoforms in serum were detected. However during these episodes isoforms in pancreatic juice changed dramatically. The band corresponding to PASP disappeared or became much weaker and only bands with lower MW were seen. We have thus observed changes in PASP/PCB serum isoforms during episodes of acute pancreatitis but not at graft rejection episodes although the total increase of PASP in serum was of the same magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)

In two kidney transplant patients, one of whom had panel-reactive antibodies (PRA) before transplantation, a pretransplant negative donor-recipient crossmatch became positive within the 1st week after transplantation. Simultaneously, good graft function deteriorated to a state of anuria. One patient graft biopsy showed a vascular rejection, whilst the other patient biopsy was unrevealing. Both patients were treated with plasmapheresis and a new immunosuppressive drug, 15-deoxyspergualin (DSG). Plasmapheresis was performed for 6 and 9 days, respectively, and DSG was given for 5 days in a dosage of 6 mg/kg body weight per day. One of the patients received methylprednisolone i.v. in addition. During treatment the cross-match became negative and has since remained that way. In both patients the graft function was restored. No adverse effects were seen from the treatment, except for a slight leukocytopenia and thrombocytopenia.

Eighteen patients with long-standing insulin-dependent (type 1) diabetes mellitus and polyneuropathy were studied after combined pancreatic and renal transplantation. Repeated tests were performed on peripheral nerve function (electroneurography) and on autonomic function (R-R test) 6 mo and 1, 2, and 4 yr after the transplantation. Eighteen diabetic patients with only a kidney graft served as controls. After initial improvement of nerve conduction in both groups, probably caused by the elimination of uremia, further improvement was seen only in the euglycemic pancreas-graft recipients. Improvement of autonomic (parasympathetic) function was slight after 48 mo and was similar in both groups.

We retrospectively examined the effectiveness of prophylaxis with cotrimoxazole in preventing Pneumocystis carinii pneumonia in recipients of kidney and combined kidney-pancreas transplants between 1985 and 1989. Cotrimoxazole prophylaxis (480 mg daily or 300 mg/m2), when used, was started within 2 months after transplantation and usually continued until 6 months after surgery. Eight (3.7%) of the 214 patients who were not given prophylaxis were infected with Pneumocystis carinii, and there were 4 fatalities (50% mortality). There were no cases among the 161 patients given prophylaxis (P less than or equal to 0.03). No serious adverse effects were noted in the prophylaxis group. It is concluded that prophylaxis against Pneumocystis carinii infection is well tolerated and should be given as soon as possible to all organ transplant recipients for at least 6 months.

Thirty-one pancreas transplant recipients were monitored by pancreatic juice cytology in the early post-operative period. An increase in the total amount of cells and, in particular, signs of immunoactivation with the appearance of two or more blast-transformed cells per specimen were taken as evidence of acute rejection. According to these criteria a total of 38 rejection episodes were diagnosed. The first positive cytology appeared after 9 days (mean) and lasted for 2 days (mean). Immunocytochemical analysis of the juice showed increased amounts of CD3+ cells during rejection. When rejection occurred during prophylaxis with antithymocyte globulin, neutrophils were preponderant in the pancreatic juice while during OKT-3 prophylaxis a high percentage of monocytes was a characteristic finding. Antirejection treatment was started when the cytology became positive and all rejection episodes except one were reversed. A decrease in the pancreatic juice amylase activity occurred in 66% of the rejection episodes, but in only 5 of the 38 episodes was the decrease highly significant. No correlation was found between graft rejection and volume excretion of pancreatic juice. There were no persistent or characteristic changes in serum amylase or peripheral white blood cell count at the time of rejection. Graft pancreatitis was diagnosed cytologically in 7 patients, in 5 of whom the grafts were eventually lost.

Background. Although development of malignancies after transplantation is well recognized, de novo development of cancer in renal transplants is a rare phenomenon.We describe two cases of de novo development of renal cell carcinoma in two living donor grafts. Background. Materials and results. Background. The recipients were 45 and 4 years, respectively, at transplantation and their fathers were donors. Because of failure to grow, they were both treated with human growth hormone. Over the years a number of cysts developed in the grafts and after 8 and 7 years the echogenecity of some of the cysts changed. Biopsy confirmed the diagnosis renal cell carcinoma 9 and 11 years after transplantation. The grafts were removed and the immunosuppressive therapy discontinued. The two fathers are well with normal function of the native kidney and no signs of cyst formation or cancer. Conclusion. Two cases of de novo development of cancer in living donor kidney transplants are described. Because a stimulatory effect of growth hormone on tumor genesis has been described, this treatment may have been of importance in the tumor development. The findings emphasize the importance of annual ultrasonographic surveillance of renal grafts, especially in the pediatric population.

Background. Despite their clinical importance, clinical routine tests to detect anti-endothelial cell antibodies (AECA) in organ transplantation have not been readily available. This multicenter prospective kidney transplantation trial evaluates the efficacy of a novel endothelial cell crossmatch (ECXM) test to detect donor-reactive AECA associated with kidney allograft rejection. Methods. Pretransplant serum samples from 147 patients were tested for AECA by a novel flow cytometric crossmatch technique (XM-ONE) using peripheral blood endothelial progenitor cells as targets. Patient enrolment was based on acceptance for transplantation determined by donor lymphocyte crossmatch results. Results. Donor-reactive AECA were found in 35 of 147 (24%) patients. A significantly higher proportion of patients with a positive ECXM had rejections (16 of 35, 46%) during the follow-up of at least 3 months compared with those without AECA (13 of 112, 12%; P

Pancreatic transplantation was performed in three patients with insulin-dependent diabetes mellitus in whom recurrent and severe episodes of hypoglycaemia had been found to be due to defective glucose counterregulation. Thus in these patients the spontaneous blood glucose recovery after insulin-induced hypoglycaemia (0.1 U kg−1 h−1 i.v. insulin until blood glucose levels fell below 2.8 mmol l−1) was delayed, and the responses of glucagon, epinephrine and growth hormone (GH) were absent or diminished. After pancreas transplantation the patients exhibited essentially normal blood glucose control. When the insulin infusion test was repeated 3 months after the transplantation, the blood glucose level recovered rapidly after insulin withdrawal. The glucagon response was restored, and the responses of epinephrine and GH were improved. Plasma C-peptide was suppressed by approximately 50%, which is less than is observed in normal subjects. It is concluded that glucose counterregulation improves after pancreas transplantation. This appears to be mainly due to an improvement in the hypoglycaemia-induced glucagon response, but an amelioration of sympatho-adrenal and hypothalamic-pituitary regulatory mechanisms may also be involved. The apparent failure to suppress completely the insulin release from the denervated pancreas transplant indicates that inhibition of beta-cell secretion during insulin-induced hypoglycaemia may be partly under neural control.

Long-term metabolic control after pancreatic transplantation with enteric exocrine diversion was evaluated in 42 Type I (insulin-dependent) diabetic pancreas recipients with functioning grafts for 1 to 7 years. Glycaemic control (fasting blood glucose, glycosylated haemoglobin A1c, oral and intravenous glucose tolerance tests) was normal or near-normal in most patients, and showed no deterioration with time. In ten patients with functioning grafts for 5 years there was a small, but significant, improvement in the glucose control at 3 to 5 years as compared with that at 6 months post-operatively. In the latter recipients the number of acute rejection episodes correlated negatively with the intravenous glucose tolerance at 6 months (r=−0.64, p

Background. In 2001 a protocol for ABO-incompatible (ABOi) kidney transplantation based on antigen-specific immunoadsorption and rituximab was introduced at our center, short-term results being comparable with those of ABO-compatible (ABOc) living donor kidney transplantation. Of greater importance, however, is long-term graft function, thus far not evaluated. The aim of this study was therefore to assess long-term results of this protocol. Methods. Twenty ABOi kidney recipients with more than 12-month follow-up were included in the study: all adult crossmatch negative ABOi kidney recipients (n15) were compared with an adult ABOc living donor recipient control group (n30), and all pediatric ABOi kidney recipients (16 years of age) (n5) were compared with a group of pediatric ABOc kidney recipients (n18). Results. Mean follow-up was three years. There was no significant difference in patient survival, nor in graft survival or in the incidence of acute rejection in any of the groups. In the adult kidney recipients mean glomerular filtration rate was equivalent at all time points (79 – 83 mL/min), as was s-creatinine. In the pediatric groups, s-creatinine was similar but glomerular filtration rate lower among the ABOi kidney recipients. There was a significant reduction (P0.0001) without rebound in A/B antibody titers after transplantation (median IgG 1:2 and median IgM 1:11 year posttransplant) compared with pretransplant levels (median IgG 1:32 and IgM 1:16). Conclusion. We conclude that ABOi kidney transplantation using antigen-specific immunoadsorption and rituximab is equivalent to ABOc living donor kidney transplantation. ABOi transplantation after this protocol does not have a negative impact on long-term graft function.

We describe a female patient who, despite negative conventional cross-matches, lost her first kidney graft in an acute humoral rejection. Prior to the second, AB0-incompatible (A1B to A1) living-donor kidney transplant, the patient had negative T- and B-cell cross-matches but had a positive donor-reactive endothelial cell cross-match. Following pre-transplant protein A and GlycoSorb-ABO immunoadsorptions to remove blood group B and anti-endothelial cell antibodies, Mabthera, and IVIG administrations, she was successfully transplanted. By the second post-operative day, creatinine levels were down to 96 micromol/L from 611 micromol/L pre-operatively. On day 9 creatinine rose again, and on the same day the endothelial cell crossmatch became positive for IgG, whereas the T-cell cross-match remained negative and the anti-A1B titers remained low. A kidney biopsy taken on day 10 post-transplant showed a picture of an acute vascular, antibody-mediated rejection. Following rejection treatment and repeated protein A and Glyco-Sorb-ABO immunoadsorptions, the patient's kidney function was again normalized. The use of a recently developed kit (XM-ONE) for the detection of anti-endothelial cell antibodies allowed us to identify a patient at risk for developing acute antibody-mediated rejection as well as to monitor treatment efficacy and post-transplant complications.

In ABO-incompatible kidney transplantation, only a few studies have addressed the necessity, duration, and content of immunosuppressive induction therapy. At our center (Karolinska Institute, Stockholm, Sweden), using a preconditioning regimen consisting of 13 days of tacrolimus, mycophenolate mofetil, and prednisolone, we have investigated both short- and long-term renal allograft function (up to 28 days and 1 year after transplantation, respectively) and correlated them to tacrolimus 12-hr trough levels. In summary, during the first 28 days after transplantation, renal allograft function in the ABO-incompatible group was impaired when compared with that observed in the ABO-compatible group. One possible explanation for this finding is the prolonged pretransplantation exposure to tacrolimus in the ABO-incompatible group, resulting in tacrolimus-associated renal toxicity, which slows the reduction in plasma creatinine. In fact, the day before, and also immediately after, the transplantation (for the first 3-4 postoperative days), the tacrolimus 12-hr trough levels in the ABO-incompatible group were greater than in the ABO-compatible group. Possibly, a shorter pretreatment period with tacrolimus or a reduced target tacrolimus trough level could eliminate this difference in postoperative renal allograft function. However, 1 year after transplantation, kidney allograft function in the two study groups was similar.

Renal transplantation into a patient with a positive cytotoxic cross-match or with an incompatible blood group inevitably results in acute humoral rejection, unless the HLA or anti-A/B antibodies have been removed before transplantation. Although there are several procedures to remove HLA and anti-A/B antibodies, plasmapheresis and immunoadsorption are the most commonly used. In this report, presently available techniques for antibody removal are briefly reviewed.

The B-cell depleting anti-CD20 antibody rituximab has become a therapeutic alternative in renal transplantation. However, understanding of the pharmacodynamics is limited. We have therefore studied the effect of single-dose rituximab, in combination with conventional triple immunosuppressive therapy, on the B-cell population in peripheral blood as well as in tissues, in kidney transplant recipients. Forty-nine kidney recipients received single-dose rituximab. The prevalence of B cells was assessed in peripheral blood, kidney transplant tissue, and in lymph nodes. In 88%, complete depletion of B cells in peripheral blood was observed and, 15 months after treatment, B cells were still undetectable in the majority of patients. In kidney tissue, B cells were also completely eliminated. In contrast, the B cells were not eliminated in lymph nodes, although a reduction was observed. In conclusion, single-dose rituximab in kidney transplant recipients evokes a long-term elimination of B-cells in peripheral blood as well as within the kidney transplant.

A new protocol for ABO-incompatible kidney transplantation was introduced in 2001. In this protocol, antigen-specific immunoadsorption to remove existing AB antibodies is used in addition to rituximab to prevent rebound of antibodies and conventional immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). This protocol has successively been implemented in many European centers, primarily in Sweden and Germany but also in the UK, Switzerland, the Netherlands, Norway, Denmark, Greece and Spain, and almost 200 ABO-incompatible transplantations have now been performed. In a recent 3-center pooled analysis of 60 consecutive ABO-incompatible living-donor transplantations, there were no graft losses that could be related to the ABO incompatibility and, when compared with ABO-compatible transplantations, no difference in graft or patient survival was found.

Data from 60 consecutive ABO-incompatible kidney transplantations performed in Stockholm, Sweden; Freiburg, Germany; and Uppsala, Sweden, revealed significant variation in preoperative A/B antibody levels, with median titers of 1:32, 1:128, and 1:8, respectively. We wanted to investigate whether these differences were method-related. The same samples from 21 healthy blood donors were analyzed in the three centers using current local methods. Results confirmed method-related differences, with higher A/B titers in Freiburg and lower titers in Uppsala compared with Stockholm. Results for the same sample differed by a median of three (range 0 to 6) titer steps. When the same number of samples were analyzed in the three centers using the same gel method and the same test erythrocytes, results differed by a median of one titer step (range 0 to 4) for the same sample. In conclusion, gel hemagglutination technique significantly decreases intercenter variation compared with tube technique.