Pretransplant blood transfusions with cyclosporine in pediatric renal transplantation

Pretransplant transfusions were repeatedly shown to be associated with improved graft survival in the ”pre-cyclosporine era,” and have recently been shown to be beneficial in patients on modern immunosuppressive regimes. In an attempt to improve this transfusion effect and minimize the potential development of cytotoxic antibodies, we have given these transfusions, with concomitant cyclosporine cover, prior to transplantation. Ninety-two renal transplantations were performed in 91 children in the study group (group 1) and all received pretransplant transfusions with cyclosporine cover. Results were compared with a preceding group of 102 children (104 transplantations) who had received pretransplant transfusions without cyclosporine cover (group 2). There were 70 cadaver and 22 living-related donor (LRD) transplants in group 1, and 88 cadaver and 16 LRD transplants in group 2. Graft survival rates (1- and 5-year) for cadaver transplantation were 96% and 90% in group 1 compared with 78% and 64% in group 2 (P=0.001). For LRD transplantation, these figures were 95% and 87% in group 1 and 81% and 69% in group 2. There was no difference between the two groups in terms of age at transplantation, sex, donor age, HLA-A, -B, -DR mismatches, or cold and warm ischemia times. All cadaver graft recipients received quadruple, sequential immunosuppression post transplant. However, 9 patients in group 1 were changed to tacrolimus for recurrent rejection episodes. No patient developed persistent lymphocytotoxic antibodies post transfusion or side effects of cyclosporine. Cyclosporine can be safely given with whole blood prior to transplantation with no adverse effect and no sensitization. Graft survival was significantly improved in this group of patients and graft loss due to rejection was exceptional. This effect should be further evaluated in prospective studies. Received: 10 June 1999 / Revised: 9 March 2000 / Accepted: 10 March 2000     

Perioperative blood transfusions after allogenic renal transplantation

The requirement of blood transfusions was evaluated in a two compartment (retrospective/prospective) study in our renal transplantation program. Between July 1st, 1993 and December 31st, 1994 (observation period I) we retrospectively investigated 110 patients with end stage renal disease and anemia undergoing kidney transplantation. Between January 1st, 1995 and December 31st, 1996 (observation period II) the requirement of blood transfusions was followed prospectively in 134 patients after allogenic renal transplantation. The amount of blood drawn for preoperative diagnostic investigations was in observation period I significantly higher (280 ml) than in observation period II (150 ml) (p = 0.02). For postoperative diagnostic tests in observation period II significantly less blood (240 ml) was needed than in observation period I (510 ml) (p = 0.01). The intraoperative bloodloss was similar in both periods (170 ml vs. 190 ml; p = 0.6). The need for closer graft observation was the reason for significantly increased amount of blood transfusions in patients with delayed graft function. The number of blood transfusions was significant lower in patients with primary graft function (p = 0.0001). There was no correlation between blood transfusions and the use of ATG/OKT3, surgical complications and reoperations. With an improved management of blood drawing for diagnostic tests after allogenic kidney transplantation the number of perioperative blood transfusions can be reduced significantly.     

Effect of blood transfusions on oncological outcomes of surgically treated localized renal cell carcinoma

Objective

To assess the associations between perioperative allogeneic blood transfusions (ABTs) and recurrence, overall and renal cell carcinoma (RCC)-specific survival in patients undergoing surgical treatment for clinically localized disease.

Disseminated tuberculosis after renal transplantation

Disseminated mycobacterial infections occurred in two female renal graft recipients late after transplantation. In the first patient, initially presenting with fever, diagnosis was made at autopsy. Temporary defervescence following antibiotic therapy with ofloxacin possibly contributed to the fatal diagnostic delay. In the second case, body temperature was normal throughout the protracted course of the patient's illness. Her presenting symptom was rapidly increasing ascites, attributed initially to chronic liver disease. These cases demonstrate that tuberculosis remains a serious complication after renal transplantation, in particular due to its sometimes atypical clinical manifestations. Response to antibacterial therapy has to be critically evaluated in order to avoid fatal diagnostic delay.     

Limits for organ-preserving surgery in renal cell carcinoma

Summary The indication for elective organ-preserving surgery in renal cell carcinoma is under discussion. The statements about the maximum tumor size, which could be considered for this surgical procedure, differ in the literature. In a serie of 281 consecutive radical tumornephrectomies we compaired the results of preoperative ultrasound and computerized tomography regarding to tumor size and multifocality with the results of the postoperative systematically section of the removed kidneys. Further we analysed the results of 14.793 autopsies regarding to tumor size and multifocality. Serial section of the 281 nephrectomy specimens revealed a total of 64 multifocal tumors in 48 kidneys ( = 17,1 %). The correlation between tumor size and multifocality showed only in tumors up to 20 mm no additional lesions, whereas in the higher tumor categories the incidence was up to 23 %. These clinical investigations were confirmed by the results of the autopsies. In summery of the results we conclude, that the elective organ-preserving surgery of renal cell carcinoma is only indicated in tumors with a maximum diameter of 20 mm.      

Primary renal plasmacytoma. A case report

Summary We describe a patient with a primary renal plasmacytoma. In the literature available, only six clinical cases have been reported. A 64-year-old patient is presented who had the clinical signs of a renal cell carcinoma. Histological examination after nephrectomy, however, revealed a plasmacytoma. Based on this case, we discuss how one should proceed in this disease. Primary renal plasmacytoma can be tentatively diagnosed preoperatively only in the presence of paraproteinemia or Bence-Jones proteinuria, as it cannot be distinguished from other renal tumors by imaging procedures. Postoperatively, further staging procedures must rule out bone involvement (solitary myeloma or multiple myeloma). Nephrectomy is required in patients with plasmacytoma only if renal complications occur.      

Tertiary hyperparathyroidism after renal transplantation

.Tertiary hyperparathyroidism is considered as an autonomous proliferation state of the parathyroid glands with biological hyperfunction resistant to calcium/vitamin suppressor therapy. This phenomenon is thought to be secondary to monoclonal inactivation of tumoral growth suppression factor located on chromosome 11. Three patients, 13, 15, and 22 years of age, with chronic renal insufficiency of long evolution who presented with tertiary hyperparathyroidism following renal transplantation are described. The three patients underwent subtotal parathyroidectomy with consequent normalization of biochemical parameters of phospho-calcium metabolism in the first few weeks post surgery. Pathologic study showed adenoma in the affected glands with hyperplasia of the rest. We believe that in patients with long-term renal insufficiency an aggressive treatment, either medical or surgical, of secondary hyperparathyroidism which is continued after renal transplantation may be useful in preventing the development of tertiary hyperparathyroidism. Received April 13, 1995; received in revised form and accepted April 30, 1996     

Perioperative blood transfusion adversely affects prognosis after nephrectomy for renal cell carcinoma

Background

It has been previously suggested that perioperative blood transfusion (PBT) may induce adverse oncological outcomes following cancer surgery. The aim of the current study is to evaluate the effect of PBT on the prognosis of patients who underwent nephrectomy due to renal cell carcinoma (RCC).

Surgical treatment of metastases in patients with renal cell carcinoma

Summary The aim of the present study was to investigate the efficacy of surgical excision of metastases in patients with renal cell carcinoma (RCC). Eighteen patients with metastatic RCC underwent resection of metastases between 1988 and 1994 (pulmonary: n = 6; skeletal: n = 6; cerebral: n = 3; local relapse: n = 3). Two patients suffered from synchronous appearance of metastases, whereas in 16 cases a metachronous occurrence was observed. In 12 out of a total of 18 patients metastases were completely resected. These patients survived longer than patients in whom metastases were incompletely resected (30 vs. 12 months). Six out of these 12 patients with a complete resection of metastases are presently free of disease for a mean duration of 24 months (10–34 months). The resection of lung metastases seems to be associated with longer survival times. In conclusion, surgical resection of metastases – solitary or single organ site – especially in the lung appears to be justified in patients with RCC. The surgical excision of skeletal metastases at least improves quality of life.      

Experience with deflazacort in children and adolescents after renal transplantation

Deflazacort (DFZ) has been proposed as an alternative drug for immunosuppression after renal transplantation (TX), with fewer side effects than conventional glucocorticoids. We investigated renal function, body growth, body fat, and bone mineral density (BMD) after switching from oral methylprednisolone (MPR) to equivalent doses of DFZ 1–9 years after TX in 20 patients aged 5–20 years, selected because of severe adverse effects from previous steroid therapy. At conversion the patients received a mean dose of 7.4±2.4 mg DFZ/m² per day. The drug was continued for a mean of 3.7 (1.2–5.5) years. Under DFZ, the glomerular filtration rate dropped slightly (NS). A single rejection episode occurred. Growth velocity significantly improved in the 1st year on DFZ treatment and height standard deviation score (SDS) increased steadily after introduction of DFZ (from –2.64 to –1.96 after 4 years, P=0.06). However, in 10 prepubertal children the height gain (+0.20 SDS in 2 years on DFZ) was not significant and the overall mean annual growth rate after TX was similar to that in 10 matched prepubertal TX children on continued MPR treatment. Relative obesity, estimated from mean body mass index corrected for height, was reduced from +1.11 SDS at the start of DFZ to +0.71 SDS after 2 years (P=0.03) and to +0.39 SDS after 4 years (NS). BMD-SDS of the lumbar spine (L_2–4) increased after 1 year on DFZ (P=0.005). In conclusion, DFZ is well tolerated and safe in pediatric patients after TX. It improves relative obesity and bone mineralization. However, body growth is not significantly influenced pre puberty. Received: 19 October 1999 / Revised: 28 February 2000 / Accepted: 28 February 2000     

Lymphocyte transformation test (LTT) – a model for testing the cytokine-induced immunomodulatory capacity of renal cell carcinoma

Summary We investigated the immunomodulatory capacity of cytokines produced by renal cell carcinoma in vitro by analyzing their effects on mitogen-induced T-lymphocyte blast cell transformation. All of the tested 70 cell cultures, derived from 70 tumor areas in 33 patients, had immunomodulatory capacity. In addition to suppression in the lymphocyte transformation test (max. 44/70; 63 %) there was also superinduction (max. 37/70; 53 %). We found no significant correlation with the stage and grade of primary tumors. However, the suppression of mitogen-induced T-lymphocyte blast cell transformation was significant in multifocal tumors (0.08 % TCM, P < 0.001) and non-significant in metastatic tumors. The production of the assayed cytokines IL-6, IL-10, IL-11, and TGF beta 1 was variable and there was no significant correlation to the immunomodulatory capacity of the tumors.      

Prognostic value of intracaval neoplastic extension for patients with renal cell cancer

Summary The independent prognostic value of neoplastic extension of renal cell cancer (RCC) into the vena cava inferior has been the subject of several investigations reported to date. However, the use of vena cava thrombosis as an independent prognosticator of a patient's long-term survival is still debated. We have therefore correlated the clinical course of 53 patients with RCC and vena cava thrombosis with a control group consisting of 47 patients with renal cell tumors without vena cava thrombosis (follow-up: 1–154 months). The median long-term survival of patients with and without vena cava thrombosis was 32 and 35 months, respectively. Neither the propagation of the tumor into the vena cava (P = 0.391) nor the cranial extension of the thrombosis (P = 0.158) – even in case of propagation into the right atrium – could be identified as parameters of any prognostic value during univariate or multivariate statistical analysis.      

Risks of perioperative blood transfusions

It has been estimated that up to 40% of blood transfusions are given to surgical patients. Despite transfusion being safer than it ever has been, it still poses significant risk. These can be heightened in the perioperative period when identifying complications can also be more challenging. This article outlines the risks associated with perioperative transfusions and discusses the current recommendations for transfusion and use of alternatives to blood transfusion.     

Risks of perioperative blood transfusions

It has been estimated that up to 40% of blood transfusions are given to surgical patients. Despite transfusion being safer than it ever has been, it still poses significant risks. These can be enhanced in the perioperative period where identifying complications can also be more challenging. This article outlines the risks associated with perioperative transfusions and discusses the current recommendations for transfusion and use of alternatives to blood transfusion.     

Obstructive airway disease caused by Moraxella catarrhalis after renal transplantation

We report a case of severe acute obstructive airway disease 2 months after renal transplantation in a 16-year-old patient with Biedl-Bardet syndrome who was transplanted for end-stage renal failure secondary to cystic kidney disease. Symptoms of severe obstructive airway disease developed 2 months after transplantation under immunosuppression with prednisone, azathioprine, and tacrolimus. The patient did not develop signs of infection; progressive shortness of breath remained the only symptom for several weeks. After extensive diagnostic evaluation, bronchoalveolar lavage revealed Moraxella catarrhalis as the single infectious agent. After 3 weeks of appropriate antibiotic therapy, symptoms of obstructive airway disease were completely relieved. This atypical presentation of Moraxella infection in an immunocompromised host represents a rare complication of renal transplantation, especially in young patients. Special aspects such as frequency, diagnosis, differential diagnosis, and management of this rare complication of renal transplantation in a pediatric patient are discussed. Received: 22 July 1999 / Revised: 24 November 1999 / Accepted: 28 November 1999     

Effects of growth hormone on growth factors after renal transplantation

Growth retardation occurs frequently in renal transplanted children (RTx) and can be improved by growth hormone (GH) treatment. This study retrospectively examines the insulin-like growth factor-1 (IGF-1) and IGF binding protein (IGFBP) profile of ten growth-retarded children previously given renal allografts, after 1 year of GH treatment period. Ten prepubertal patients (nine boys and one girl) were investigated. They had a mean chronological age (CA) of 11.4±1.1 years and a mean bone age (BA) of 7.3±0.9 years. Mean height was –3.9±0.4 SD units below the mean for CA. The mean body mass index (BMI) was 16.9±0.6 and the mean inulin clearance was 36.5±4.9 ml/min/1.73 m². Recombinant hGH was given at 4 IU/m²/day. Plasma GH, total and free IGF-1, IGFBP-2 and -3 were measured by specific radioimmunoassay (RIA). IGFBPs were characterized by SDS PAGE techniques and ligand and immunoblot analyses. Mean velocity was markedly increased (P<0.01) after 1 year of GH therapy, expressed as SD score for BA. The range of growth response was wide. The total and free plasma IGF-1 increased (P<0.01) by about 100% (mean values after GH therapy: 95.9± 2.1 nM and 165±29 pM, respectively). Plasma IGFBP-3 concentrations increased by about 40% (mean value: 148±18 pM, P<0.01), with a concomitant increase in both intact IGFBP-3 and its 30-kDa proteolytic fragment. There was no change in plasma IGFBP-2 concentration. Both mean values of inulin clearance and BMI were unchanged during the treatment. In view of the IGF-1/IGFBP concentration changes, there should have been an even better growth response to GH therapy in these patients. This strongly suggests IGF-1 insensitivity, probably as a result of corticosteroid therapy. Received: 12 April 2000 / Revised: 31 July 2000 / Accepted: 1 August 2000     

Hypertension after renal transplantation

Hypertension is a common and serious complication after renal transplantation. It is an important risk factor for graft loss and morbidity and mortality of transplanted children. The etiology of posttransplant hypertension is multifactorial: native kidneys, immunosuppressive therapy, renal-graft artery stenosis, and chronic allograft nephropathy are the most common causes. Blood pressure (BP) in transplanted children should be measured not only by casual BP (CBP) measurement but also regularly by ambulatory BP monitoring (ABPM). The prevalence of posttransplant hypertension ranges between 60% and 90% depending on the method of BP measurement and definition. Left ventricular hypertrophy is a frequent type of end-organ damage in hypertensive children after transplantation (50–80%). All classes of antihypertensive drugs can be used in the treatment of posttransplant hypertension. Hypertension control in transplanted children is poor; only 20–50% of treated children reach normal BP. The reason for this poor control seems to be inadequate antihypertensive therapy, which can be improved by increasing the number of antihypertensive drugs. Improved hypertension control leads to improved long-term graft and patient survival in adults. In children, there is a great potential for antihypertensive treatment that could also result in improved graft and patient survival.     

Diabetes mellitus in patients with infantile cystinosis after renal transplantation

Diabetes mellitus is a frequent long-term complication of infantile nephropathic cystinosis. We studied 44 cystinotic patients, aged 22.1±5.4 years, transplanted at a mean age of 11.3±2.5 years; 25% were treated with insulin at 20 years of age or 10 years after transplantation, and over half required insulin at latest follow-up. In comparison, diabetes mellitus occurred in only 1% of non-cystinotic transplanted patients. Sequential oral glucose tolerance tests (OGTTs) in these patients showed the progressive deterioration of glucose metabolism. All but 2 patients had an abnormal response at latest follow-up. The high doses of corticosteroid given after transplantation or during rejection episodes were responsible for transient insulin dependency. However, the development of impaired glucose tolerance and diabetes mellitus depended mainly on the cystinotic process, which developed slowly with time. The deterioration of glucose tolerance was correlated with a decreased early phase of insulin secretion, estimated from the plasma insulin level at 30 min of the OGTT, while there was no evidence of insulin resistance. The occurrence of diabetes mellitus correlated with a worsening of the vital prognosis. Received: 28 July 1998 / Revised: 22 September 1998 / Accepted: 23 September 1998     

肾移植术中及术后液体和药物的使用

目的　探讨肾移植术中及术后液体和药物的使用方法 ,以使肾移植受者达到良好的肾功能。方法　 3 0例肾移植受者术中采取扩张血容量和肾动脉内注射血管扩张剂的方法 ,术中输液5 0 0～ 10 0 0m1/h ,白蛋白 1～ 1.5g/kg ,吻合血管开通后 ,立刻从肾动脉内注入异搏定 (Isoptin) 5～ 10mg。 结果　肾脏供血后全部受者 5min内有大量尿液从输尿管涌出 ,术后 2～ 5d血肌酐正常。结论　肾移植术中扩张血容量和肾动脉内注射血管扩张剂可保证植入的肾脏有良好血液供应 ,术后功能恢复良好。