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Background: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy., Methods: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres., Results: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention., Conclusion: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies., (© 2020 The Authors. British Journal of Surgery published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Background: The clinical safety and efficacy of sirolimus plus reduced-dose tacrolimus was evaluated in de novo renal allograft recipients enrolled in a comparative, open-label study., Methods: One hundred twenty-eight renal allograft recipients were randomly assigned (1:1) to receive reduced-dose tacrolimus plus sirolimus (rTAC) or standard-dose tacrolimus and sirolimus (sTAC) for 6 months. The primary efficacy endpoint was calculated creatinine clearance values at 6 months., Results: Demographic variables were similar between groups. At 6 months, mean (± standard deviation) calculated creatinine clearance was significantly improved in the rTAC group (63.8 vs 52.7 mL/min, P = .005), although mean serum creatinine values were not significantly different. Patient survival (95.2% and 96.9%) and graft survival (93.7% and 98.5%) were similar between the rTAC and sTAC groups, respectively. Acute rejection rates were 17.5% with rTAC and 7.7% with sTAC (P = .095)., Conclusions: The rTAC regimen provided effective immunosuppression and was associated with improved creatinine clearance. Adequate immunosuppressant exposure must be achieved in the early postoperative period to minimize the risk of acute rejection., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Simultaneous pancreas and kidney transplantation (SPK) is associated with great postoperative morbidity, including the need for relaparotomy in up to 40% of cases. Because the pancreatic graft is known to be the major cause of the high morbidity, we examined the incidence and treatment of pancreatic fistula (PF) in this retrospective analysis., Methods: From January 2004 to July 2010, we transplanted 52 pancreas grafts, including 50 SPK, 1 pancreas after kidney, and 1 pancreas transplantation alone. There were 22 female and 30 male patients with an overall mean age of 42.4 ± 7.4 years. The mean duration of diabetes was 27.3 + 8.1 years, mean duration of dialysis was 24.2 ± 28.6 months, and 14 cases were pre-emptive transplantations. All procedures were performed using systemic venous and enteric drainage., Results: The incidence of clinically relevant PF was 16/52 (30.8%), including 11 (68.8%) that were treated conservatively with a drain. Five patients (31.2%) needed relaparotomy: 2 due to enteric leakage, 2 due to acute abdominal pain with graft pancreatitis observed at laparotomy, and 1 due to acute hemorrhage. In 3 cases, graft pancreatectomy was necessary. Comparing the patients with (PF+) versus without (PF-) fistulas, there was no significant difference in cold ischemia time (10.9 ± 2.6 hours vs 10.4 ± 4.4 hours; P = .633), donor age. We found a significantly higher peak C-reactive protein (CRP) level in the patients with pancreatic fistula (3661.4 ± 3474.8 U/L vs 821.8 ± 1293.7 U/L, P = .022). The lipase concentration measured in the drainage fluid postoperatively showed a significant difference between the 2 groups (3661.4 ± 3474.8 U/L vs 821.8 ± 1293.7 U/L; P = 0.006). Also, the amylase concentration was higher in the PF+ group (1747.3 ± 3346.7 U/L vs 265.3 ± 254.9 U/L; P = .097). Graft loss occurred in 4/16 cases (25.0%) of PF+ and 7/36 (19.4%) of PF- (P = .719)., Conclusion: The incidence of PF after pancreas transplantation is high and seems to be associated with ischemia-reperfusion injury reflected by peak-CRP. In most cases a conservative treatment is successful. The occurrence of a PF does not significantly impair graft survival., (Copyright © 2010 Elsevier Inc. All rights reserved.)

A 45-year-old man was admitted with fever and elevated pancreas enzymes 6 months after simultaneous pancreas-kidney transplantation (SPKT). Function of the allografts was normal. Bacterial and fungal infections were excluded, while Epstein-Barr virus (EBV)-polymerase chain reaction (PCR) was positive. However, screening for EBV-associated lymphoma was negative. EBV infection did not respond to antiviral therapy. After an 18F-Fluorodeoxyglucose positron emission tomography positive signal and an abnormal computed tomography scan of the pancreas transplant, a biopsy revealed a diffuse large monomorphic B-cell lymphoma, which was confined to the grafted organ. Its origin was assigned to the donor by microsatellite analysis. Reduction of immunosuppression and immunotherapy with rituximab was unsuccessful. After 10 weeks, the patient developed an acute hemolytic uremic syndrome which required explantation of the allografts. Subsequent to the intervention, fever disappeared, EBV DNA became undetectable and lymphoma screening remained negative. In posttransplant lymphoproliferative disorder of donor origin after SPKT, transplantectomy may be a curative therapy.

The main cause of death for diabetic patients and patients on dialysis is coronary artery disease (CAD). The most common cause of graft loss following simultaneous pancreas and kidney transplantation (SPK) is death with a functioning graft due to CAD. Therefore, careful pretransplantation evaluation of CAD is mandatory. In our series, every patient undergoes a noninvasive cardiac function test like dobutamine stress echocardiography (DSE) or myocardial thallium scintigraphy using adenosine to induce medical stress. Thirty patients were evaluated for SPK: 15 patients with myocardial scintigraphy and 8 with DSE. Seven investigations showed pathological findings and we performed coronary angiograms, none of which showed coronary artery stenosis. Seven primary coronary angiograms were performed: four due to a history of CAD and three as a primary diagnostic. Following SPK one patient died at 21 days after transplantation due to myocardial infarction. He had a history of CAD with angioplasty and stent implantation. Noninvasive cardiac function tests like DSE or myocardial scintigraphy are reliable methods to evaluate CAD in patients with diabetic nephropathy awaiting SPK. In case of a suspicious finding or a history of CAD, a coronary angiogram should be performed to assess the need for revascularization. Following this algorithm we may further reduce the mortality of SPK.

The outcome after live-donor kidney transplantation is influenced by many parameters. The aim of our study was to establish a multivariate prognostic model for calculating the recipient's creatinine clearance after transplantation. Basic immunological, donor-, recipient- and process-related variables were assessed in a series of 18 live-donor kidney transplant patients with an uncomplicated postoperative course. Multivariate analysis was carried out with automated forward and backward selection. The following four parameters were included in the predictive model: recipient age, recipient BMI, graft clearance and degree of relationship. The coefficient of determination (R(2)) was 0.67. It could be shown that a significant prediction of creatinine clearance after living related kidney transplantation can be made, based on simple variables. Therefore, this formula could help to detect early complications in the post-transplantation course if the recipient's creatinine clearance drops below the predicted result.

Background: Although pancreas graft-related complications are frequent after simultaneous pancreas-kidney transplantation (SPK), there are no parameters predicting the risk for these complications., Method: A two-center retrospective study was performed in 97 patients who underwent SPK to investigate the peak serum value of c-reactive protein (CRP) during the first 72 hr after SPK in view of graft-related complications and graft survival., Results: Mean peak CRP was 115.6 +/- 71.5 mg/L. Mean peak CRP was higher in patients needing relaparotomy (n=31) (136.4 vs. 105.8 mg/L, P=0.048), especially when postoperative bleeding was excluded (P=0.015); in patients with graft pancreatitis (P=0.03); and in patients with graft loss (n=19; P<0.001) compared with patients without these complications. With a cut-off of peak CRP at the level of mean plus 1 SD (187.05 mg/L), there was a significantly higher incidence of relaparotomies (P=0.01; bleedings excluded: P=0.003), graft pancreatitis (P=0.03), and pancreas graft loss (P<0.0001) in patients with high peak CRP compared with patients with low peak CRP. No differences were noticed with regard to rejection rate, mortality, and kidney graft loss., Conclusion: Our findings suggest that peak CRP is a helpful parameter in predicting pancreas graft-related complications and pancreas graft survival after SPK. Our results also stress the importance of early graft damage in pancreas transplantation.

Background: Simultaneous pancreas-kidney transplantation (SPK) is still associated with the highest rate of morbidity among solid organ transplantations. Although improved long-term survival following SPK has been proven in IDDM patients, a further decrease in morbidity would be desirable., Methods: A retrospective, single-center study was performed to investigate the morbidity following SPK and to compare the results to kidney transplantation alone (KTA). Parameters included the rates of relaparotomies, septic complications (urinary tract infection, wound infection, pneumonia), and graft function., Results: Between September 2000 and August 2001, 99 patients underwent transplantation (34 SPK, 63 KTA, 2 pancreas transplants alone). Relaparotomies were performed in six SPK patients (17.6%), mostly due to complications related to the pancreatic graft (n=5). Three reoperations (4.8%) were necessary in KTA patients (p=0.085). Septic complications occurred more often in SPK than in KTA patients (55.9% vs 30.2%, p<0.05). This difference resulted from the high rate of wound infections in SPK patients (35.3%). No intra-abdominal infection or sepsis occurred in any patient. There was one hospital death in SPK and KTA patients, respectively. The rejection rate was similar in SPK (17.6%) and KTA (12.7%, p=0.72). At discharge 91.2% of SPK patients were insulin free and 97.1% free of dialysis. At discharge 96.8% of KTA patients were free of dialysis., Conclusion: SPK is still associated with a higher morbidity (relaparotomies, septic complications) than KTA, although life-threatening complications were rare. There was no increased mortality following SPK.

Background: Graft thrombosis is one of the main reasons of graft loss following simultaneous pancreas-kidney transplantation (SPK). Although antiphospholipid syndrome (APLS) is known as a high risk for graft thrombosis in kidney transplants alone, little is known about APLS in SPK., Methods: Between September 2000 and December 2001, 45 SPK were performed. The treatment and clinical course of 2 patients with APLS is presented., Results: In one patient, APLS was known before transplantation. After SPK, she was treated by systemic heparin followed by coumarin. Both grafts are doing well 5 months posttransplant. The second patient underwent SPK without knowledge of APLS. The patient developed a deep vein thrombosis 5 weeks posttransplant. Hypercoagulability screening revealed APLS. Treatment consisted of systemic anticoagulation. Grafts were not affected., Conclusion: SPK can successfully be performed in APLS patients if anticoagulation is performed consistently. To reduce the risk of graft thrombosis, a pretransplant screening for APLS would probably be of benefit.

Primary malignancy after solid organ transplantation has a more than three-fold incidence compared to the normal population. Causes are intensity and duration of immunosuppression, pre-operatively undetected, occult malignancy or pre-cancerous lesions in the recipient, direct or indirect tumor transmission via the transplant and environmental factors. Measures for prevention comprise antiviral treatment of individuals at risk for primary EBV-infection and prevention of sun exposure. Early detection follows general medical guidelines and, in addition, selective screening of certain risk groups of patients. Treatment of solid tumors follows established guidelines of professional working parties. Post-transplant lymphoproliferative disorders can often be treated with anti-CD antibody (rituximab). Antiproliferative immunosuppressants like rapamycin may seem promising with regard to a possibly reduced incidence of de-novo malignancy in the future.

Background: In contrast to kidney transplants a positive crossmatch is no contraindication for liver transplantation (OLT). In liver transplantation, antibody mediated rejections are rarely reported and a liver graft is suspected to have protective effects for kidney grafts when transplanted simultaneously. The aim of this study was to evaluate the effect of a positive crossmatch on outcome after OLT and combined liver and kidney transplantation (CLKTx)., Methods: We analyzed retrospectively the impact of a positive crossmatch on graft survival and rejection episodes after OLT (793pats) and CLKTx (18pats, 2.2%). Immunosuppression consisted of either Cyclosporine- or Tacrolimus-based regimens., Results: A total of 50/811 (6%) of patients had a positive crossmatch, 45/793 (5.6%) with liver transplantation alone and 5/18 (28%) of patients with CLKTx. Follow-up ranged from 1 to 122.5 months (median 45.8 months). One- and 5-year graft survival rates of liver transplants alone with a positive crossmatch were 89.6% and 75.3%, respectively and were 88% and 77.5% in crossmatch negative recipients. Additionally, the incidence of acute and steroid-resistant rejection (44% and 15.5%) was not significantly increased in patients with a positive crossmatch when compared with patients with a negative crossmatch (38% and 19%). None of the patients with a positive crossmatch and CLKTx underwent a hyperacute-rejection episode after transplantation, and kidney graft survival 100%., Conclusions: In conclusion, a positive crossmatch is no contraindication for OLT and CLKTx. Furthermore, not having to wait for results of donor/recipient crossmatching can shorten cold ischemia time and may improve the clinical outcome.

Pancreas transplantation is still the best option to achieve normoglycaemia and insulin independence in patients with type I diabetes. As a result of improvements in surgical techniques, immunosuppression and patient selection, one year survival rates of 95, 83, and 88% for patient, pancreas, and kidney survival, respectively, are reported for patients with simultaneous pancreas and kidney transplantation. The main goals for the future are to reduce postoperative morbidity, to identify the relevant indications for single pancreas transplantation, to adopt the best surgical technique for individual patients' needs (bladder versus enteric drainage with or without portal venous delivery of insulin), and to develop immunosuppressive strategies with low nephrotoxic and diabetogenic potential.

In a previous experiment we demonstrated the induction of tolerance by the allograft itself. In this model of weak histoincompatibility, second grafts of donor origin replacing chronically rejected first renal allografts were accepted long term. Additionally grafted donor-specific hearts functioned indefinitely while adoptive transfer experiments demonstrated the development of donor-specific transferable tolerance. In the current experiment we compared intragraft gene expression of chronically rejected first and tolerant second grafts by RT-PCR. Second renal allografts of donor origin (F-344) replaced first grafts 2, 4, 8, 12, and 16 weeks after the initial engraftment. No immunosuppression was used during second engraftment. Grafts were followed by serial proteinuria; morphological and immunohistological studies (APAAP/infiltrating cells, ICAM-1, MHC II expression) and competitive RT-PCR analyses (expressed as arbitary units AU/cDNA) for relevant cells and cytokines (CD-3, IFNgamma, IL-10, and IL-4) were assessed by the end of the observation period (16 weeks). Macrophages/monocytes (ED-1+) and T-cells (CD-5 and CD-4+) infiltrated first allografts in high numbers by 12 weeks associated with strong structural signs of chronic graft rejection (ca. 30% arterio- and glomerulosclerosis, tubular atrophy and interstitial fibrosis). Cellular infiltrates in second grafts were prominent, however significantly reduced, while histological changes were minor. At cDNA levels, CD-3 transcripts were elevated in second renal allografts performed 2, 4, and 8 weeks after the initial engraftment while comparable levels were observed when second engraftment was performed after 12 and 16 weeks. Analyses of relevant cytokines demonstrated a TH1/TH2 shift independent from the time interval between first and second engraftment. These results emphasize the role of alloresponsiveness for the development of chronic graft dysfunction. Mechanisms of tolerance induction in our model are associated with a distinct alloresponsive pattern. A crucial role for regulatory T-cells is suggested.

Background: The kind and intensity of immunosuppression as well as Epstein-Barr virus, a transforming herpes virus that selectively infects B lymphocytes and causes infectious mononucleosis, have been implicated in the development of posttransplantation lymph-proliferative disorders (PT-LPD), a life-threatening complication of solid organ transplantation. The morphologic spectrum of PT-LPD ranges from polymorphous hyperplasia to monomorphous B-non-Hodgkin lymphomas. Among different modalities of treatment, reduction of immunosuppression with or without co-administration of antiviral agents may result in PT-LPD regression especially in mononucleosis-like disease., Methods: Nonmononucleosis-like PT-LPD in a simultaneous heart and renal recipient was treated with Foscarnet, a potent inhibitor of different herpes viruses with a low profile of toxicity, although intensive immunosuppression therapy was maintained., Results and Conclusions: A 4-week course of Foscarnet resulted in relapse-free complete remission (follow-up 10+ months). Thus, antiviral treatment with Foscarnet, may induce prolonged remission in nonmononucleosis-like PT-LPD without reduction of immunosuppression.

The aim of the present study was to differentiate acute rejection, chronic rejection, and tacrolimus nephrotoxicity with color and power Doppler imaging of renal transplants. One hundred examinations were obtained from 45 patients. Pulsatility and resistive indices were calculated from color Doppler images. The grade of renal vascularization was quantified using computer-assisted pixel analysis in a rectangular region-of-interest. The percentage of vessel-covered renal parenchyma (POV) was calculated using a histogram that discriminated renal vessels from renal parenchyma via power Doppler images. Furthermore, the distance from the most peripherally located vessels to the renal capsule (PVD) was measured. A reduced POV < or = 55% proved to be the best discriminator when chronic rejection was suspected (sensitivity 79%, specificity 87%). Tacrolimus nephrotoxicity showed not only a moderate elevation of the Doppler signal but also an increased PVD > or = 3.9 mm and a normal POV. We conclude that the evaluation of renal vessels by power Doppler images improves diagnostic accuracy for patients with renal allografts.

Hepatitis B virus (HBV) core deletion variants with enhanced viral replication are associated with rapid deterioration of liver function in renal allograft recipients. Antiviral agents such as famciclovir and lamivudine offer new treatment strategies for these patients. Appearance, accumulation and persistence of HBV core deletion mutants were closely monitored in a kidney transplant recipient with liver cirrhosis before and after initiation of antiviral treatment. Under treatment with famciclovir HBV DNA concentration decreased by 50 %, HBV mutants persisted. After replacement of famciclovir by lamivudine HBV replication was reduced below the detection limit. Lamivudine was well tolerated and liver function improved. After successful combined kidney/liver transplantation the patient became HBsAg and HBV DNA (detected by PCR) negative under continuous hyperimmune globulin and lamivudine treatment. Antiviral therapy with lamivudine may be useful in treatment of progressive liver disease associated with HBV core deletion mutants in renal allograft recipients and may enable successful liver transplantation.

Chronic graft rejection represents the single most important risk factor for unsatisfactory long-term results after organ transplantation. In addition to various alloantigen dependent and independent factors, acute rejection episodes have been cited as a major immunological risk factor. However, the effects of acute rejection episodes on long-term graft outcome remains unknown. To examine the influence of a single early rejection event on ultimate graft outcome, acutely rejecting rat kidney grafts were retransplanted sequentially into syngeneic rats and their functional and structural behavior assessed over time. LEWxBNF1 kidney allografts and LEW isografts were removed from their LEW recipients after three, four, five and seven days (N = 12/group/time period) and retransplanted into donor strain hosts. The grafts were followed functionally and harvested four, eight, and 32 weeks later. Urinary protein excretion was measured weekly. Kidneys were examined morphologically and immunohistologically using monoclonal antibodies (mAbs) against macrophages (ED-1), T cells and their subsets (CD5, CD4, CD8), MHC class II expression (OX3) and adhesion molecules (ICAM-1 and LFA-1alpha). The mean standard time +/- SD of non-retransplanted allografts was 14.5 +/- two days; isografts functioned indefinitely. At five and seven days, acutely rejecting allografts showed massive cellular infiltrates associated with extensive necrosis. These changes could not be reversed by retransplantation and the syngeneic recipients later died of renal failure. In contrast, most allografts retransplanted earlier in the process recovered completely when retransplanted after three (12 of 12 allografts) and four (7 of 12 allografts) days. During the subsequent follow-up period, urinary protein excretion was comparable in retransplanted allografts and isografts. The increased mononuclear cell infiltration in non-retransplanted allografts seen at three and four days was only occasionally observed during the follow-up period after retransplantation. Only a few sclerosed glomeruli (approximately 15%), mild arterial changes and minimal cellular infiltrates were observed by 32 weeks, which were similar to that seen in retransplanted isografts. A single acute rejection episode was completely reversible and did not progress to chronic rejection if retransplanted into syngeneic donors when the inflammatory changes are still early. Those results demonstrate the critical effect of alloantigen-dependent events on chronic graft deterioration, and indicate that prompt and aggressive treatment of initial acute rejection episodes are beneficial to protect against late deleterious changes in the graft.

Acute rejection episodes have been cited as a major immunological risk factor for the development of chronic rejection. To examine the influence of a single rejection event on ultimate graft outcome, acutely rejection rat kidney grafts were retransplanted sequentially into syngeneic rats and their functional and structural behavior assessed over time Early structural changes (days 3 and 4) were completely reversible, while signs of chronic rejection did become obvious during the long-term follow up. More advanced deteriorated grafts (days 5 and 7) were irreversibly damaged and the rats died shortly after retransplantation. Those results indicate the critical impact of acute rejection episodes on chronic graft rejection. Immediate and aggressive treatment of acute rejection episodes may remove this event as a risk factor for late deteriorating changes.

Previous studies on pathophysiological mechanisms of chronic graft rejection demonstrated the impact of both alloresponsiveness and nonspecific immunological events on the process. To study the role of alloantigen-specific factors further, we hypothesized an acceleration of chronic graft rejection after presensitization. Chronically rejected renal allografts in the established Fischer 344 --> Lewis rat model were replaced sequentially by native allografts of donor origin. Grafting of second allografts was performed 2, 4, 8, and 12 weeks after the original transplantation and followed long term. Second allografts demonstrated significantly ameliorated functional and structural alterations with few cellular infiltrates. These changes were independent from the time interval between first and second engraftment (2-12 weeks); immunosuppressive treatment after the second engraftment was not influential. The nonresponsiveness was not restricted to the second kidney allografts, as heart allografts of donor origin in these recipients also functioned indefinitely, whereas third-party grafts (Lewis x Brown Norway F1) and Fischer 344 heart grafts in untreated Lewis control rats were acutely rejected. Thus, donor-specific and tissue-nonspecific graft acceptance is achieved by second engraftment of donor-specific allografts in a model of chronic graft rejection. Those observations demonstrate the synergistic effects of alloresponsiveness and of the injured graft itself for the development of chronic graft failure.

As part of a European multicenter study to investigate the potency of FK506 in primary immunosuppression after liver transplantation, this comparison with our conventional cyclosporine-based quadruple regimen was carried out as a controlled, prospective, randomized trial. The 121 patients entering the study were randomly assigned to receive immunosuppressive regimens consisting either of FK506 and prednisolone (FK/n = 61) or of cyclosporine, prednisolone, azathioprine, and a 7-day course of rabbit antithymocyte globulin (CsA/n = 60). Rejection was suspected in the case of scant production of light bile or biochemical graft dysfunction, without evidence of vascular, biliary, or infectious complications. A liver biopsy for confirmation of the diagnosis was obtained each time. Initial therapy entailed a 3-d course of high-dose methyl-prednisolone. Steroid resistant rejections were treated with OKT3 monoclonal antibody or, in the group of primary CsA administration, conversion to FK506 as another treatment option. One-year patient (FK: 90.2%; CsA: 96.7%) and graft survival (FK: 88.5%; CsA: 91.7%) did not differ significantly. Overall, 41 patients (33.9%) experienced 50 acute, cellular rejection episodes (RE) [FK: 25 RE in 21 patients (34.4%); CsA: 25 RE in 20 patients (33.3%)]. The histological grading ranged from mild (FK: 14/25; CsA: 8/25) to moderate (FK: 9/25; CsA: 16/25) and severe (FK: 2/25; CsA: 1/25): not significantly different between the two groups. In the CsA-based group, three additional rejection episodes were classified as early chronic (n = 1) and chronic rejection (n = 2).(ABSTRACT TRUNCATED AT 250 WORDS)

RS-61443 is a noncompetitive allosteric inhibitor of inosine monophosphate dehydrogenase. It blocks the proliferative response of T and B lymphocytes, prevents the generation of cytotoxic T cells, and inhibits antibody formation. This study was conducted to see whether or not RS-61443 can reverse acute renal allograft rejection in dogs. It was possible to reverse this process.

RS-61443, a morpholinoethyl ester of mycophenolic acid, has been shown to prevent renal allograft rejection in dogs when administered in combination with low-dose cyclosporine and prednisolone. The purpose of this study was to test whether high-dose RS-61443 can reverse acute renal allograft rejection. Mongrel dogs receiving a renal allograft were treated with baseline immunosuppression consisting of RS-61443 10 mg/kg, cyclosporine 5 mg/kg, and prednisolone 0.1 mg/kg. All animals developed acute allograft rejection. Dogs in group I (n = 11) received 14, 7, and 3.5 mg/kg methylprednisolone intravenously on 3 consecutive days after the diagnosis of rejection. Dogs in group II (n = 16) were given RS-61443 80 mg/kg twice daily. After rejection treatment, RS-61443 was increased to 20 mg/kg in all animals; cyclosporine and prednisolone were continued as before. In group I, five of 11 dogs developed uncontrollable rejection; in six of 11 dogs only a temporary reversal occurred. None of the dogs in group I survived for more than 20 days after the diagnosis of rejection. In group II rejection was completely reversed in 14 of 16 dogs (87.5%), resulting in a return of serum creatinine to prerejection levels. Thus, high-dose therapy with RS-61443 can successfully reverse acute kidney allograft rejection in dogs in a high proportion of cases.