Long-Term Outcomes of Immunosuppressed Renal Transplant Recipients with Malignancies

This study analyzes ten cases of malignancy in a cohort of 183 renal transplant recipients, examining surgical management, postoperative immunosuppressive therapy, and long-term outcome. One of these ten patients, who had malignant lymphoma of the jejunum, died of the neoplasm, but the other nine patients did not show any signs of tumor recurrence after removal. All of these nine patients, except for one who had transplant renal cell carcinoma (RCC), received the same dose of immunosuppressive agents after surgery for the malignant disease. Seven patients were still alive at the time of this report, six of whom had good transplant renal function. The findings of this study indicate that even if immunosuppressive agents predispose to the development of cancer, it is not necessary to reduce their dose after removal of the tumor. Received: April 17, 2000 / Accepted: November 20, 2000     

Does immunosuppressive pharmacotherapy affect isoagglutinin titers?

Objective

Preoperative reduction of isoagglutinins leads to successful ABO-incompatible (ABOi) renal transplantation. The strategy includes pretransplantation plasmapheresis, more potent immunosuppressive drugs, splenectomy, and anti-CD20 antibody. It has been reported that low isoagglutinin antibody titers posttransplant were observed among ABOi renal transplants with favorable outcome. The isoagglutinin titers may increase slightly when plasmapheresis is discontinued; however, it never returns to the pretreatment level under immunosuppressive therapy. This raises the question of what occurs to the isoagglutinin titer in ABO-compatible renal transplants under maintenance immunosuppressive pharmacotherapy.

Methods

We analyzed 10 renal transplant recipients, including seven living and three cadaveric donors. Patients were treated with basiliximab (20 mg) intravenously on day 0 and day 4. Maintenance immunosuppressive therapy involved a calcineurin inhibitor, mycophenolate mofetil, and steroid. Anti-human globulin isoagglutinin titers were routinely examined 1 day before and day 0 and 1, 2, 3, 4, 8, 12, and 24 weeks posttransplant. No ALG or intravenous immunoglobulin or plasmapheresis treatment was provided in the follow-up period.

Results

Our preliminary data showed nearly no influence on isoagglutinin titer levels in 6-month follow-up under maintenance immunosuppressive therapy. In addition, no significant difference in isoagglutinin titer was observed between tacrolimus and cyclosporine groups.

Conclusion

Maintenance immunosuppressive pharmacotherapy did not affect isoagglutinin titer levels in ABO-compatible kidney transplants. Further study is needed to investigate the mechanisms of persistent low-level isoagglutinin titers among successful ABOi renal transplantation patients.     

Simple cyst arising in a transplanted kidney: a case report.

A 17-year-old girl was hospitalized for evaluation of gradually decreasing function of a kidney transplanted 8 years earlier. A plain film of the abdomen showed a possible renal calculus. Excretory urography proved that this calcification was slightly anterior to the kidney but in the upper pole a well rounded mass was discovered. An echogram confirmed the diagnosis of benign renal cyst. Malignant cystic lesions obviously must be differentiated from those that are benign. Patients on immunosuppressive therapy are known to have a higher incidence of malignancy than the general population. A malignant tumor may require withdrawal of immunosuppressive therapy and removal of the transplanted organ, whereas a benign cyst would require no therapy unless it becomes infected or produces obstruction.     

Neuroblastoma in a renal transplanted child

A 3-year-old boy was diagnosed with neuroblastoma 2 years after a renal transplant that was complicated by acute and chronic rejection. Extensive immunosuppressive therapy may have contributed to the development or progression of this tumor which has not been described previously following organ transplantation.     

The predictive value of Oxford MEST-C classification to immunosuppressive therapy of IgA nephropathy

Purpose

To analyze the efficacy of immunosuppressive therapy in IgA nephropathy and investigate the value of all clinicopathologic indicators.

Method

One hundred and one eligible IgA nephropathy patients were retrospectively studied. All the patients received immunosuppressive treatment and were then grouped according to the treatment outcome. The endpoint was a composite outcome (halving eGFR, end-stage renal disease (ESRD) or death due to kidney disease). The outcomes of immunosuppressive therapy were evaluated, and the factors influencing the outcomes of immunosuppressive therapy were analyzed by logistics regression. The independent significance of clinicopathologic indicators on renal outcome was then analyzed by multivariable Cox regression.

Results

Multivariate logistic regression analysis showed that S1 and M1 were the risk factors for the immunosuppressive treatment effect in IgAN patients, and eGFR was the protective factor for the immunosuppressive treatment effect in IgAN patients. Kaplan–Meier analysis revealed that outcomes of immunosuppressive therapy were significantly associated with poor renal outcomes. Multiple Cox regression analysis further confirmed that M1, T2, and the initial level of eGFR were independent predictive factors for poor renal outcomes.

Conclusions

M, S scores and initial eGFR are independent predictors of outcomes of immunosuppressive therapy. Only M, T scores can effectively predict poor renal outcomes after immunosuppressive therapy. Nonetheless, stable eGFR and low proteinuria can protect renal outcomes.

     

肾移植术后并发泌尿系统肿瘤的相关因素与临床干预

目的:探讨肾移植术后并发泌尿系统肿瘤的相关因素与临床干预措施.方法:报告9例(10次)此种患者的临床资料.9例肾移植术后均行免疫抑制治疗.肿瘤均发生在自体肾、输尿管和膀胱:肾透明细胞癌、肾肉瘤和膀胱腺癌各1例,肾盂输尿管膀胱移行细胞癌6例,其中1例先发生膀胱腺癌后又发生肾盂输尿管移行细胞癌.肿瘤发生于移植术后8～146个月,且8例发生在应用新型免疫抑制剂之后.患者均有服用龙胆泻肝丸或冠心苏合丸史.8例接受了根治性手术,1例未能手术切除.结果:9例随访8～44个月,未能手术切除1例于术后5个月肝转移死亡.1例肉瘤复发后放弃治疗后死亡.1例膀胱肿瘤复发,行膀胱全切腹壁造瘘术,1例腺癌已出现肺和胸膜转移.另5例最后随访时存活良好.结论:肾移植术后并发泌尿系统肿瘤以移行细胞癌为多;可能与服用含马兜铃的中药和应用新型免疫抑制剂有关;根治性手术治疗、减少免疫抑制剂用量和更换免疫抑制剂种类是主要临床干预措施.     

肾移植后恶性肿瘤58例的治疗体会

目的 总结肾移植后并发恶性肿瘤的治疗体会.方法 同顾分析1812例肾移植后接受免疫抑制治疗6个月以上患者的资料.1812例中,58例发牛恶性肿瘤.患者发生恶性肿瘤时的年龄为31～67岁,平均为45岁,诊断时间为移植术后18～220个月,平均为98个月.58例中,44例经病理检查证实为恶性肿瘤,其中泌尿系统肿瘤19例,消化系统肿瘤14例,血液系统肿瘤5例,其他6例;6例临床诊断为恶性肿瘤,但未经病理证实;8例资料不全,不参与结果 统计.50例参与统计的患者接受以外科手术为主的综合治疗,其中10例停用免疫抑制剂,其余40例的免疫抑制剂用量减少1/3～1/2.结果 50例诊断肿瘤后的1年存活率为68.0%,其中19例泌尿系统肿瘤患者的1年存活率为73.7%,14例消化系统肿瘤患者的1年存活率为42.9%.同前存活的26例中,移植肾仍有功能者20例,维持性血液透析者2例,腹膜透析者4例.结论 完善的随访制度有利于肾移植后恶性肿瘤的早期诊断,此类患者的治疗以手术治疗为主,同时应合理减少免疫抑制剂的用量,并调整用药方案.     

移植肾功能丧失受者的临床管理策略

随着肾移植手术技术的成熟和新型免疫抑制药的引入以及免疫抑制方案的改进,肾移植受者的短期生存率已显著提高,但长期生存并未得到显著改善。肾移植受者通常可能面临移植肾功能丧失。移植肾功能丧失后的医疗管理较为复杂,包括免疫抑制药的调整、移植肾的处理以及后续肾脏替代治疗方式的选择。这些医疗管理直接影响移植肾功能丧失患者的预后,但目前仍缺少相关指南或共识,往往根据临床医师的自身经验决定。本文对目前移植肾功能丧失后免疫抑制药的调整、移植肾的处理和后续肾脏替代治疗方式的选择等进行综述,旨在为延长患者的生存期和提高生活质量提供参考。     

Graves' disease in a renal transplant

The occurrence of hyperthyroidism and/or Graves' disease (GD) in transplant recipients receiving immunosuppressive therapy is extremely rare. A 47-year-old man developed GD after renal transplantation while he was under adequate immunosuppressive therapy. To our knowledge, the case presented here is the second case report of GD developed in a renal transplant recipient under adequate immunosuppressive therapy. The patient had undergone a renal transplantation 2 years before, and since then, he had been receiving continuous immunosuppressive therapy with cyclosporine A and prednisone. He presented with 3 months' history of palpitation, excessive sweating, weakness, heat intolerance and weight loss. Thyroid ultrasonography and scan revealed diffusely enlarged thyroid gland without nodules. The finding of elevated serum levels of thyroid hormones and suppressed TSH level subsequently confirmed hyperthyroidism. A diagnosis of GD was made after the demonstration of elevated thyroid autoantibodies. Although the mechanisms involved in transplant rejection and human autoimmunity are thought to be similar, the development of GD in a patient receiving therapeutic immunosupression suggests that different immunologic processes may be involved in GD. Further studies seem to be needed since the pathogenetic mechanisms suggested in the literature so far are not satisfactory to explain the development of GD in transplant patients under adequate immunosuppressive therapy.     

Double endocrine neoplasia in a renal transplant recipient: case report and review of the literature

Introduction

The incidence of cancer compared for age groups is 3-4 times higher in transplant recipients than the general population. The increased risk is related to immunosuppressive therapy as well as the use of increasingly older donors and recipients. Although cardiovascular disease with a functioning transplant is the leading cause of death (47%), cancer mortality is significant especially among older patients. However, the most frequent posttransplantation cancers relate to hemolymphopoietic organs and skin, whereas the occurrence of solid tumors elsewhere is rare. Herein we have described a rare case of synchronous double malignancy of endocrine organs (thyroid-adrenal) in a young woman who underwent renal transplantation.

Case Report

A 37-year-old woman with end-stage renal disease for 18 years underwent transplantation when she was 30 years old with a 17-year-old standard cadaveric donor receiving immunosuppressive therapy with mycophenolate mofetil, cyclosporine, and steroids. Follow-up demonstrated good indices of renal function with negative tumor pathology at 79 months when, at an annual ultrasound monitoring, we found a lesion in the right lobe of the thyroid and left adrenal neoplasm of dubious interpretation. The cytology for the thyroid was highly suspicious of papillary carcinoma, whereas the histological examination after surgery diagnosed a thyroid multifocal papillary microcarcinoma (mpT1NxMx) and an oxyphil cell adrenocortical carcinoma (pT2, N0).

Results

Six months after total thyroidectomy with central lymphadenectomy and left kidney and adrenal gland removal the patient showed no evidence of recurrent lesions and stable graft function.

Conclusions

The rare occurrence of solid tumors after transplantation has no known etiopathogenetic relation. Despite the young age of the patient and the double neoplasm that could have produced an unfavorable outcome for the patient and the graft, careful follow-up for tumor pathologies and multidisciplinary management achieved an early diagnosis of both tumors with a surgical eradication without adjuvant therapy, preserving the life of the patient and the function of the graft.     

The treatment of glomerulonephritis in children

The results of treatment of glomerulonephritis (GN) in childhood with oral corticosteroids, immunosuppressive drugs, anticoagulants and the newer regimens of pulsed, high-dose intravenous methylprednisolone and plasma exchange are reviewed and compared with the natural history of the untreated condition. Poststreptococcal GN and the nephritis of Schönlein-Henoch purpura need no specific treatment unless extensive glomerular crescents are present. The progression of mesangiocapillary GN can probably be slowed or even reversed with long-term, alternate-day steroid therapy. As in adults, recovery of renal function in GN due to antibody to glomerular basement membrane can be achieved in some patients using plasma exchange, but only those in whom some renal function is still present when treatment is started. In rapidly progressive (extracapillary) GN with crescents, traditional therapy with oral steroids, immunosuppressive drugs and anticoagulants reduces renal mortality from 85%–90% to about 50%, while pulsed methylprednisolone and plasma exchange improve the outcome further, mortality falling to about 25%. It is recommended that children with crescentic GN and deteriorating function be treated initially with pulsed methylprednisolone, followed by plasma exchange in those who fail to respond or who deteriorate following temporary response to pulse therapy. Treatment must be given early in the course of the illness if good results are to be obtained.     

个体化免疫抑制治疗在肾移植的疗效观察

目的：探讨个体化免疫抑制治疗对肾移植患者的临床价值。方法：将肾移植患者分为个体化组(42例)和常规组(50例),分别采用个体化免疫抑制治疗和常规免疫抑制治疗,并对术后两组的临床指标进行比较。结果：个体化组比较常规组,术后肝功能损害、高血糖、胃肠功能紊乱、呼吸系统感染、急性排斥反应发生率均明显降低(P＜0．05);而巨细胞病毒感染发生率及移植肾切除人数无差异(P＞0．05)。结论：个体化免疫抑制治疗既能维持免疫抑制效果,又能最大限度减少药物不良反应,对肾移植患者有较好治疗价值。     

Sirolimus and mycophenolate mofetil as calcineurin inhibitor-free immunosuppression in a cardiac transplant patient with chronic renal failure.

Chronic renal failure triggered by calcineurin inhibitor (CNI)-based immunosuppression is a common complication after cardiac transplantation. Sirolimus and mycophenolate mofetil (MMF) are 2 newer immunosuppressive agents with no documented nephrotoxic side effects. This case report describes a patient with ongoing chronic renal failure 10 months after cardiac transplantation on cyclosporine-based immunosuppressive therapy. Conversion of the immunosuppressive regimen from cyclosporine to sirolimus and MMF resulted in freedom from acute rejection, excellent cardiac graft function and consistently improved renal function. This case illustrates the beneficial potential of sirolimus and MMF as CNI-free and safe long-term immunosuppression in a patient with chronic renal failure after heart transplantation.     

Induction of regulatory T cells after prophylactic treatment with photopheresis in renal transplant recipients

Extracorporeal photopheresis (ECP), originally used to treat cutaneous T-cell lymphoma, also has been applied to the therapy of transplant rejection. Our aim was to investigate the biologic response in two children who underwent kidney transplantation with ECP as prophylactic treatment. They received conventional immunosuppressive therapy and ECP immediately after transplantation: six applications over the course of 3 weeks. During a 12-month follow-up, the clinical course was favorable in both patients; renal histology was normal 6 months after transplantation. When compared with four transplanted controls, the ECP-treated patients showed lower tumor necrosis factor-alpha serum levels in the short-term and a marked increase of Foxp3-positive T-regulatory cells. T-regulatory cells were still higher than in the controls 1 year after transplantation. These preliminary results suggest that the addition of ECP to standard immunosuppressive therapy induces a tolerogenic shift in the immune system of kidney transplanted patients and may pave the way to preventing chronic rejection.     

Ocular findings in patients with successful renal transplantation

Successful renal transplantation has a favourable effect on the development of ocular disorders in periodic haemodialysis patients [4]. Certain complications arise in the eyes of the recipients and are attributed mainly to the immunosuppressive medication [2, 3, 6]. The purpose of our study was the recording of the ocular complications in patients with successful renal transplants after long-term stabilization of renal function and immunosuppressive therapy.     

BK virus nephritis after renal transplantation

BK viremia and nephritis are increasing problems in renal transplant recipients. The exact cause of the increasing prevalence of this condition remains poorly understood. Increasing prevalence has been correlated with newer immunosuppressive agents and the decline in acute rejection rates in recent years. The clinical manifestation varies from the asymptomatic state of viremia and nephritis to clinical renal dysfunction. The diagnosis of this infection is based on the combination of the presence of urinary decoy cells, virus in the urine/blood, and typical renal histological findings of interstitial nephritis. Routine post-transplant screening for BK viremia and viruria prior to the occurrence of nephritis and the reduction in immunosuppressive therapy for subjects with viremia appear to be attractive approaches. The treatment of BKV nephritis (BKVN) consists of reduction in immunosuppressive therapy and antiviral therapy with cidofovir or leflunomide or a combination of both. Approximately 30-60% of subjects with BKVN experienced irreversible graft failure. However, in recent years, the combinations of early detection, prompt diagnosis, and appropriate reduction in immunosuppressive therapy have been associated with better outcome. The pathogenesis of BK virus infection in renal transplant recipients needs to be explored. The source of BKV infection (donor as opposed to recipient), the role of host humoral, and cellular immunity to BKV, and the role of alloimmune activation in renal graft to the occurrence of nephritis are discussed in this review.     

Complete Clinical Remission of Psoriasis 6 Months After Renal Transplantation

Background

Psoriasis, one of the most common immune-mediated inflammatory diseases of the skin is mediated by activated effector T cells.

Case Report

We report a case of a 56-year-old white man with a 22-year history of severe psoriasis vulgaris with plaque and joint involvement, who experienced a complete clinical remission after renal transplantation. The patient had been on hemodialysis for 6 years because of chronic renal failure caused by an undetermined chronic nephropathy. Psoriasis, which worsened over the years, was symmetrically distributed as erythematous scaly plaques that had increased until they covered about 50% of the body surface, involving mainly the abdomen, legs, back, and arms. The patient also complained of severe itching an responsive to drugs. He had been treated with topical and systemic corticosteroids and phototherapy several times without benefit. After renal transplantation he underwent immunosuppressive therapy with corticosteroids, mycophenolate mofetil (MMF), and tacrolimus (Advagraf, beginning starting dose 1 mg/kg/day, C0 10 ng/mL).

Results

From the early days post-surgery the patient reported a fast improvement in the itching with progressive reduction of the skin lesions. After 4 months follow-up the psoriasis had completely regressed, presumably due to the immunosuppressive regimen.

Conclusion

This finding suggests that systemic immunosuppressive drugs may be useful for psoriasis an responsive to conventional therapy.     

Reduced intensity stem cell transplantation for metastatic renal cell carcinoma

PURPOSE: We reviewed reduced intensity stem cell transplantation (RIST) in metastatic renal cell cancer (RCC). PATIENTS AND METHODS: Two cases of lung metastasis of immunotherapy invalidity. Six days of fludarabine 30 mg/m2 and 2 days of busulfan 4 mg/kg were given as conditioning for mini-SCT. CyA and short-term MTX were used as immunosuppressive agents. RESULTS: Size reduction of tumor was observed with dose reduction of CyA. Following steroid therapy for the treatment of GVHD, the tumor progressed. No serious complications except for GVHD. CONCLUSION: These results suggested that RIST might be considered as salvage therapy in patients metastatic RCC.     

Overlapping presentation of fungal tubulointerstitial nephritis in an immunosuppressed pediatric patient

With the expanding use of immunosuppressive therapies and broad-spectrum antibiotics, Candida species has become an increasingly important cause of infections, particularly in the presence of anti-tumor necrosis factor-α therapy. We report the case of a 17-year-old female with ulcerative colitis who developed oliguric renal failure following immunosuppressive and nephrotoxic therapy. Although urine cultures and urinary tract imaging were negative in the face of fungemia, renal biopsy was the key to establishing the diagnosis of fungal tubulo-interstitial nephritis as the primary reversible cause of the renal failure.