Recent Renal Transplant Research Articles

Perforin A and granzyme B as non invasive markers in early acute rejection in pediatric renal transplantation

IntroductionIdentification of new non- invasive sensitive markers that can predict acute rejection (AR) will provide a better chance for early therapeutic intervention before full clinical picture of AR with its consequences had occurred. We aimed to measure perforin A and granzyme B mRNA levels in serum and urine of children underwent recent renal transplantation during the first three months after transplantation. MethodsThe study included 69 recently transplanted pediatric patients and 40 age and sex matched normal subjects. Quantification of perforin A and granzyme B expression using quantitative reverse transcriptase real time PCR, was done at 1 week, 1 month and 3 months after transplantation. Patients were followed up for development of AR during their first 3 months. ResultsTwelve patients developed AR (rejecters) and 57 patients did not develop AR (non-rejecters). Rejecters showed significantly elevated levels of perforin A and granzyme B expression in pre-rejection blood and urine samples (at 1st week and 1st month), compared to non-rejecter group (p < 0.001 for all comparisons). ROC curve analysis suggested that assessment of perforin A and granzyme B expression at 1 week and 1 month post-transplantation could be predictor markers for early AR with high discriminative power (AUC ranged between 0.79 and 0.98). ConclusionsEarly measurements of perforin A and granzyme B expression in blood and urine after renal transplantation could identify pediatric patients at risk of AR, suggesting these patients as candidates for biopsy or for initiation of anti-rejection therapy.

P1644SAPS AND EPTS SCORES AS PREDICTORS OF RENAL FUNCTION IN RECENT RENAL TRANSPLANTATION

Abstract Background and Aims The risk scores used in Critical Care Units estimate the severity and mortality of patients. The SAPS (Simplified Acute Physiologic Score) and its SAPS II and SAPS III variants calculate the severity by collecting the values recorded in the first 24 hours. The EPTS (Estimated Post-Transplant-Survival) is used as a reference for the allocation of organs in the US by the OPTN. The objective is to determine its use in recent renal transplant units as estimator of subsequent renal function, in services where patients move from the operating room to a nephrological intermediate care unit. Method The SAPS (II and III) and OPTN scores were applied in 87 (N = 87) consecutive renal transplanted patients. The point value of each of the scales was evaluated with the creatinine values at hospital discharge, and one month after the transplant. The scores obtained on the SAPS scales were divided as follows (SAPSIIA &amp;lt;20 points, SAPSIIB ≥20 points) (SAPSIII A &amp;lt;30 points, SAPSIIIB ≥30 points). In the EPTS scale, two cut-off points were used to divide the groups (20% Score; EPTS-IA ≤20%, EPTS-IB&amp;gt; 20%), (Score 40%; EPTS-IIA ≤40%, EPTS -IIB&amp;gt; 40). The sérum creatinine means of each of the groups were compared. Data were analyzed with SPSS 20.0.0 Results Significant differences were found in serum creatinine levels in renal function at the first month of transplantation in the SAPS II groups (SAPS IIA 1.38 mg / dl, SAPS IIB 1.79 mg / dl; P = 0.017 95% CI). With an area under the ROC curve of 0.65 (P = 0.017 95% CI). In the SAPS III groups no significant differences were found. In the EPTS scales, there were also significant differences in creatinine one month after the transplant in the group with a score of 40% (EPTS-IIA ≤40% 1.42 mg / dl, EPTS-IIB&amp;gt; 40 1.81 mg / dl; P = 0.024 95% CI) With an Area under the ROC curve of 0.64 (P = 0.037 95% CI). Conclusion The SAPSII and EPTS scores can be a useful tool in estimating renal function one month after renal transplantation, giving a prognosis of renal graft function. The combined use of these scales together with other functional graft tests could have an important relevance in the management and follow-up of recent renal transplantation. Other studies with larger sample sizes are necessary to establish the appropriate cut-off points for the scales.

ACUTE CONFUSIONAL STATES IN OLDER ADULTS WITH MAJOR NEUROCOGNITIVE DISORDER AND BACTERIURIA: IS ANTIBIOTIC TREATMENT WARRANTED?

Introduction Uncomplicated urinary tract infection (UTI)/acute simple cystitis (ASC) is defined as an infection confined to the bladder/lower urinary tract with the absence of signs and symptoms that would suggest an upper tract or systemic infection (such as fever, chills, rigors, significant fatigue or malaise beyond baseline, flank pain, costovertebral angle tenderness, pelvic or perineal pain in men). Presence of systemic symptoms suggests a complicated UTI. Symptoms of ASC include dysuria, urinary frequency or urgency, and/or suprapubic pain. The term asymptomatic bacteriuria refers to isolation of bacteria in an appropriately collected urine specimen from an individual without symptoms of UTI. Asymptomatic bacteriuria generally is not treated unless the patient is pregnant, undergoing urological procedure or has a history of recent renal transplant. However, it is recommended that ASC be treated empirically with antibiotics. Minimum criteria for the initiation of antibiotics for urinary tract infection in long-term care residents without indwelling catheter include acute dysuria or fever and at least one of the following: new or worsening urgency, frequency, suprapubic pain, gross hematuria, CVA tenderness, urinary incontinence. Acute change in mental status is not considered as a criterion to diagnose and treat UTI. However, it is known that infection in older patients may be associated with nonspecific symptoms such as increased confusion, falling, and anorexia besides other classic symptoms of infection. Diagnosis of ASC is based solely on the subjective complaints of patients. Cognitive impairment with reduced capacity to specifically communicate symptoms makes it challenging to rule out the diagnosis of ASC in older patients with major neurocognitive disorder (MNCD). Such patients may communicate the pain and discomfort from ASC by having increased confusion and behavioral disturbances. Under these circumstances, is bacteriuria a clinically significant condition that warrants antibiotic therapy? Guidelines to relate urinalysis findings to the diagnosis of ASC in older adults with MNCD with behavioral disturbance are not currently available. Establishing the diagnosis in older patients is further complicated due to the higher prevalence in this group, of asymptomatic bacteriuria and chronic urinary symptoms (such as chronic urinary nocturia, incontinence, and general sense of lack of well-being). The Infectious Diseases Society of American (IDSA) Guidelines of 2019 recommend against antibiotic “trials” as these may cause drug toxicity, drug-drug interactions, and antimicrobial resistance. Recommendation is not to routinely test urine in elderly or debilitated patients with nonspecific changes in mental or functional status in the absence of focal urinary tract symptoms, and instead hydrate, carefully observe, and assess other potential contributing factors.However, as a part of work-up for delirium/acute change in mental status ruling out UTI with UA is still standard practice despite the recommendation not to do so in the absence of specific genitourinary symptoms. This is possibly due to the failure of current guidelines to convince clinicians of its adequacy to rule out possibility of UTI in cognitively impaired patients. This diagnostic challenge often leads to dilemma in the treatment approach of these patients. Methods Case series, systematic literature review Results Case identification: Six cases of elderly patients with MNCD who presented to the emergency department with acute change in mental status and behavioral disturbance were identified. Initial work-up included abnormal urinanalysis results. In the absence of patients reporting genitourinary symptoms, a diagnosis of UTI was not considered and they were admitted to a geriatric psychiatric unit for evaluation and behavioral management.. Variation in the treatment approach for each case was evaluated which included either considering the mental status change to be a result of UTI and treating with antibiotics or managing them with psychotherapeutic interventions and psychotropic medications for behavioral stabilization if safety and well-being were concerns. Discrepancies were noted in the recommendations made by the consulting internist and geriatric psychiatrist regarding whether or not antibiotic therapy vs. psychotropic medication treatment was most appropriate for older adults with MNCD and acute confusional states who had bacteriuria >100,000?CFU/?ml. While internists were concerned about adding load of antibiotic resistance to the community, psychiatrists were worried about the adverse effects of antipsychotics including thromboembolic events and sudden deaths in elderly patients. Conclusions The cases described here illustrate the need for concrete specialized diagnostic criteria for early and accurate identification of uncomplicated UTI/ ACS in elderly population with MNCD along with an appropriate management protocol. This research was funded by: Not applicable

Suppurative Thyroiditis due to Nocardia in An Immunocompromised Patient

Objective: Nocardia is an opportunistic organism that usually infects immunocompromised patients. However, suppurative thyroiditis is a rare complication of nocardiosis. Methods: We report a case of Nocardia thyroiditis in an immunosuppressed patient following renal transplant. Results: A 45-year-old man presented with worsening diffuse muscle pain, weakness, and subjective fever. He had a significant history of recent renal transplant with immunosuppression at the time of presentation. Mild swelling was noted in the right submandibular area, and multiple papules were noted on the skin. Although pulmonary exam revealed no abnormalities, computed tomography revealed numerous bilateral small pulmonary nodules and multiple hypodense thyroid nodules. A positron emission tomography scan showed hypermetabolic activity in the mediastinum, lungs, thyroid, and skeletal muscles. During a right-thyroid lobectomy to rule out post-transplant lymphoproliferative disease, purulent discharge from a ruptured cyst was iden...

Green inclusions in neutrophils—a case report and review of literature

Green refractile inclusions in neutrophils are a very rare peripheral smear finding with few reported cases in literature. They were thought to be a marker of impending death with a very high mortality rate in the immediate hospitalization period. They were often seen in critically ill patients and often related to liver injury. Clinical and pathophysiologic characterizations of these inclusions are limited due to the rarity of this finding. We describe the case of a 42-year-old woman with tuberous sclerosis and recent renal transplantation who was critically ill due to pneumonia and had elevation of liver enzymes. She was found to have green refractile inclusions on peripheral blood smear on the third day of hospitalization. The patient improved rapidly with treatment and was discharged in 5 days. It appears that prognostic value of these inclusion bodies is doubtful. We also highlight the need to conduct further studies to clarify the link between hepatic injury and the presence of these inclusions.

Disseminated Adenovirus Infection Without Infecting Allograft in Recent Renal Transplant

Disseminated Adenovirus Infection Without Infecting Allograft in Recent Renal Transplant

The Use of Everolimus for Renal-Transplant Patients with Nephrotoxicity by Calcineurin Inhibitors in our Center: Case Report

Introduction: Long-term renal-transplantation outcomes are reportedly impaired by acute and chronic nephrotoxicity caused by calcineurin inhibitors (CNI), while recent renal transplant results have improved remarkably due to progress in the development of immunosuppressive drugs. Everolimus (EVL) belongs to a novel class of immunosuppressive agents, known as mammalian target of rapamycin (mTOR) inhibitor or proliferation signal inhibitor, which allow dose reduction or even complete withdrawal of CNI. mTOR inhibitor, such as EVL appear to exacerbate pre-existing proteinuria and may ameliorate nephrotoxicity caused by CNI. We describe herein one patient showing histological improvement of CNI nephrotoxicity with EVL. Patient: A 53-year-old, female underwent her third living-donor transplantation. We used cyclosporine (CsA), mycophenolate mofetil (MMF), prednisolone (PSL) and basiliximab. Diuresis was obtained immediately, but on post-operative day 3 (POD 3), urine volume decreased and renal function gradually deteriorated. On POD 14, renal biopsy (BTx) revealed CsA-induced nephrotoxicity. Renal function improved with a reduction in the CsA dose, and the patient was subsequently discharged on POD 30 with a serum creatinine level (S-Cr) 1.07 (mg/dL). Acute r rejection occurred three times, but each time renal function was improved by anti-rejection therapy, and subsequently stabilized with S-Cr levels in the 1.4-1.6 range. S-Cr suddenly rose to 4.03 on POD 293. Histopathological examination showed CsA nephrotoxicity. Although we reduced the CsA dose, her renal function remained unstable. We changed CsA to EVL on POD 341, and renal function subsequently stabilized. On POD 420, her S-Cr level was 1.17, and BTx showed amelioration of nephrotoxicity findings. Conclusion: In this patient, we obtained improvement of renal dysfunction caused by CsA nephrotoxicity without rejection by switching CsA to EVL (EVL +MMF+PSL). EVL can be safely used as an alternative to CsA, and it is anticipated that EVL+MMF+PSL will become one of the choices for immunosuppressive therapy in the future.

Neuromyelitis optica phenotype associated with therapy-responsive acute peripheral neuropathy.

A 51-year-old Hispanic woman with a history of Churg-Strauss syndrome (in remission for 20 years)–associated mesangial glomerulonephritis and end-stage renal disease with a recent renal transplant and previously cured cytomegalovirus (CMV) infection who was on a tapering dose of tacrolimus presented with sudden onset of lower extremity numbness. Symptoms progressed to complete paraplegia and sensory loss over 24 hours. The following day, ascending paresis extended to bilateral upper extremities, with high thoracic sensory level and complete blindness. Initial MRI revealed contrast enhancement of bilateral prechiasmatic optic nerve as well as T2 hyperintensities involving the central gray matter of the entire spinal cord with associated edema. CSF analysis documented neutrophilic pleocytosis (182 neutrophils per mm3) and increased total protein level (142 mg/dL) without oligoclonal banding. Bacterial, fungal, and mycobacterial cultures from the CSF were negative, as was PCR for CMV, Epstein-Barr virus, herpes simplex virus, human herpesvirus 6, and varicella-zoster virus. Serologic autoimmune assessment, including onconeuronal, anti-neutrophil cytoplasmic antibody, and other rheumatologic, Lyme, and aquaporin-4 (AQP4) antibody testing, was negative. Moreover, testing for sarcoidosis and HIV antibody was unrevealing. Nerve conduction studies (NCS) performed 2 weeks after symptom onset documented severe reduction in compound motor action potential amplitudes (worse in the lower extremities), <10% slowing of distal latencies but not conduction velocities, and mildly slowed upper extremity f-wave latencies. Sensory nerve action potentials were pathologically reduced in the lower extremities (table). Needle examination (EMG) showed active, severe denervation changes in lower extremity muscles and less severe changes in upper extremity muscles. Subsequent GM1, GM2, GD1a, GD1b, and GQ1b ganglioside antibody testing was negative. The patient was diagnosed with concurrent clinically definite neuromyelitis optica (NMO) phenotype1 and acute axonal polyradiculoneuropathy with primarily axonal features.

Nosocomial infective endocarditis in a renal transplant patient: culprit central venous line

Nosocomial infective endocarditis (IE) is a relatively uncommon but, a serious complication affecting critically ill hospitalized patients who are frequently exposed to life-saving invasive procedures. Immunosuppressive treatment in solid organ transplant recipients predisposes to infections, nevertheless, nonspecific symptoms of IE, such as fever, lassitude, weight loss, and signs of inflammation may often be misinterpreted as acute rejection episode or a common urinary tract infection. The case reported here was a recent renal transplant with methicillin-resistant Staphylococcus aureus IE. We believe the diagnoses of IE in her were missed at her first presentation due to her non-specific symptoms and lack of echocardiography and blood culture results. Septic procedure at insertion of central venous catheter (CVC) in the Intensive Care Unit with trauma to tricuspid valve (TV) at the time of CVC insertion was a possible source of infection for IE. The patient was managed effectively with intravenous antibiotics in spite of having hanging pedunculated vegetation on TV.

Treatment of a Hemodialysis Patient With Pulmonary Calcification–Associated Progressive Respiratory Failure With Sodium Thiosulfate

A 52-year-old man was admitted to the hospital with severe dyspnea. He had a history of mild chronic obstructive pulmonary disease, tertiary hyperparathyroidism, type II diabetes mellitus, and end-stage renal disease treated with hemodialysis for 4 years. He had stopped a 12-year habit of smoking 10 cigarettes per day 8 years previously. A living unrelated renal transplantation was performed 8 months before admission. It was complicated by massive intraoperative hemorrhage and required transfusion of approximately 40 U of packed red cells, and prolonged ventilatory and inotropic support. A thrombectomy to salvage a thrombosed arteriovenous fistula resulted in a large pulmonary embolus and cardiac arrest. He remained dialysis dependent throughout. Exertional dyspnea developed soon after discharge and 6 months before admission to our hospital. A chest radiograph and subsequent high-definition computed tomography scan of the thorax revealed focal calcification in the apices of both lungs. Laboratory data revealed a serum parathyroid hormone of 3373.33 pg/mL, phosphate of 5.14 mg/dL, and calcium of 10.56 mg/dL. Pulmonary function tests (PFTs) disclosed severe restrictive lung disease in association with severe reduction in oxygen diffusion capacity (Fig. 1). A transthoracic echocardiogram showed normal left ventricular systolic function. Nuclear bone scanning with single-photon emission computed tomography revealed advanced metabolic bone disease and large foci of uptake within the apices of both lungs. His dyspnea progressed despite therapy with home oxygen, corticosteroids, bronchodilators, and increased ultrafiltration at hemodialysis. He was admitted when rest-dyspnea ensued. He could speak in only one- or two-word sentences and was bed bound.FIGURE 1: Serial pulmonary function test results. STS, sodium thiosulfate; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; TLC, total lung capacity; DsbHb, diffusing capacity of the lung for carbon monoxide. The red line indicates the time when the patient was admitted to the hospital.Sodium thiosulfate (STS) 1250 mg administered intravenously after each thrice-weekly hemodialysis treatment was administered on admission. After 2 weeks, this was changed to STS 600 mg orally two times daily. Oral prednisone, cinacalcet, and lanthanum carbonate were continued. He began to notice improvement in his breathing and ability to weight-bear after 2 weeks. He then sustained a nontraumatic intratrochanteric fracture and required cemented bipolar hemiarthroplasty repair under spinal anesthesia. Two weeks later, he had a nontraumatic fracture of his contralateral intratronchanter and again required operative repair. STS was held when his fracture risk on bone scanning was found to be extreme (hip T score, –3.9; lumbar spine T score, –4.9), and resumed after a parathyroidectomy approximately 3 months later. One year later, he walked 252 m and maintained oxygen saturations of 97% during a 6-min walk test. Serial PFT results are shown in Figure 1. A follow-up computed tomography scan did not show evidence for radiographic improvement in the pulmonary calcification or nodules. Metastatic pulmonary calcification (MPC) occurs in 60% to 80% of patients receiving chronic hemodialysis and is usually asymptomatic being diagnosed incidentally on thoracic computed tomography or postmortem analysis (1). Occasionally, pulmonary calcification is associated with pulmonary restriction, respiratory failure, and death (1, 2). Risk factors for fulminant MPC-associated respiratory failure include recent renal transplantation (whether successful or not), corticosteroid use, elevated serum calcium and phosphate concentrations, and hyperparathyroidism (1–6). Outside of supportive care and attempts to improve these metabolic aberrations, there is no treatment currently available for respiratory failure in the setting of MPC. Pulmonary calciphylaxis is an exceedingly rare condition that is also characterized by abnormal alveolar septal wall deposits of calcium. It differs from MPC in that the deposits have been described as unstable, softer, and associated with diffuse infarcts (1–4). To our knowledge, all described cases were fatal. Our patient’s MPC-associated respiratory failure improved rapidly after administration of STS. STS is currently approved for the treatment of cyanide poisoning and to prophylax against cisplatin nephropathy. It is also increasingly used to treat patients with calcific uremic arteriolopathy (calciphylaxis), where it purportedly solubilizes tissue-bound calcium salts, scavenges local free oxygen radicals, and causes vasodilation by enhancing local nitric oxide formation (7, 8). We hypothesize that the use of STS solubilized unstable calcium deposits in the alveolar septal walls of our patient, leading to the improvement in lung compliance and volumes seen. The decline in PFT values when STS was held and the improvement when it was resumed support this (Fig. 1). However, without a lung biopsy, we are unable to comment on whether pulmonary calciphylaxis was present. Given its dismal prognosis, we propose to consider the use of STS in patients with MPC who develop otherwise unexplained progressive respiratory failure. Megan Christie 1 Janet Roscoe1,2 Jung Chee2 Miriam Inparajah2 Ted Vaughn-Neil2 Gordon Nagai1,2 Paul Ng1,2 Jason Fung1,2 Robert Ting1,2 Paul Tam1,2 Tabo Sikaneta1,2 1 Nephrology Associates, Scarborough Ontario, Canada 2 The Scarborough Hospital, Scarborough Ontario, Canada

Organ transplants do not escape paradoxical embolisms

Acute renal allograft dysfunction in the first weeks after transplantation primarily requires examination for acute rejection, drug-associated injury, pre-renal failure due to exsiccosis/dehydration, and post-renal problems such as urinary tract obstruction. In rare instances, main renal artery or vein thrombosis may be found, e.g. due to acute rejection of the vessels. Herein, we describe the clinical course of a patient with a recent renal transplantation who presented with an acute enigmatic renal allograft failure which, after intensive diagnostic efforts, emerged as paradoxical embolism with extensive allograft ischemia in consequence of a venous thrombosis and a patent foramen ovale - a so far unreported case.

Disseminated Mycobacterium kansasii infection with hepatic abscesses in a renal transplant recipient

Mycobacterium kansasii is the second most frequent cause of non-tuberculous mycobacterial disease in the United States after Mycobacterium avium complex. While primarily it is a pulmonary disease, extrapulmonary manifestations are common. This case report describes a recent renal transplant recipient with disseminated M. kansasii infection presenting with hepatic abscesses, with discussion of clinical management issues and strategies, and a review of the literature.

Arteriovenous thrombosis in chronic renal failure patients receiving renal replacement therapy.

To determine the frequency of thrombotic complications and to identify factors associated with arteriovenous thrombosis in patients of chronic renal failure receiving renal replacement therapy. A descriptive study. The study was carried out at Sindh Institute of Urology and Transplantation (SIUT), Karachi, from May 2003 to December 2003. Of the 3000 patients evaluated, 61 End Stage Renal Disease (ESRD) patients on regular dialysis, having recent renal transplant, were selected for the study after informed consent. These patients had arteriovenous thrombosis with temporary central lines thrombosis and vascular access problems. Cases of congenital or acquired thrombotic disorders, e.g. with malignancy, DIC, liver disease, systemic lupus erythematosus or other immunologic diseases, pregnancy or women using oral contraceptives, were excluded. Similarly, patients taking any type of anticoagulant therapy during the preceding one week were not included in the study. Findings were recorded in a structured questionnaire. Laboratory analysis was done after clinical and radiological evaluation. Thrombophilia screening included antithrombin, protein C, protein S deficiencies and lupus anticoagulant. Forty-seven out of 61 patients selected were positive for thrombophilia screening with protein C deficiency in 26.2%, protein S deficiency in 16.3%, antithrombin in 5%, lupus anticoagulant in 13.1% and combined deficiency was observed in 16.3%. Of the 3000 patients, 61 with frequency of 2% were found to be deficient in one or had combined deficiency of these. Thus, the study of ESRD patients presenting with arteriovenous thromboembolism emphasizes the need to reconsider the perception that this clinical entity is rare and requires further studies.

A prospective randomized study for prevention of postrenal transplantation bone loss

We aimed to investigate different treatment drugs for the prevention of post-transplant bone loss. Sixty adult male recent renal transplant recipients were enrolled into the study. Patients were randomized into 4 groups: group I received daily alfacalcidol 0.5 microg PO; group II received oral alendronate 5 mg/day; group III received intranasal salmon calcitonin 200 IU every other day; and group IV was considered a control group. Every patient was supplemented with daily 500 mg oral calcium carbonate. Parameters of bone metabolism were measured before and at 12 months after starting treatment. Bone mineral density (BMD) was measured by (DEXA) at lumber spine, femoral neck, and forearm before and after treatment period. BMD was increased at lumber spine by 2.1%, 0.8%, 1.7%, by 1.8%, 0.6%, 1.6% at femoral neck, and by 3.2%, 1.9%, 2.6% at forearm in groups I, II, and III, respectively, while it decreased by 3.2%, 3.8%, and 1.8% at the same sites, respectively, in control group (P= <0.05). iPTH level decreased significantly in group I, while the decrease was insignificant in other groups (P= 0.003). All other parameters were not statistically significant between treatment groups. Apart from transient hypocalcaemia in 3 patients in group II, and 2 patients in group III, no other significant adverse effects were noted. This study proves that early bone loss that occurs during the first 12 months after renal transplantation could be prevented by alfacalcidol, calcitonin, or alendronate. Among the treatment groups, alfacalcidol significantly improved the hyperparathyroidism. All treatment drugs are safe and tolerable.

SEQUENTIAL BLOOD LEVEL MONITORING OF BASILIXIMAB DURING MULTISESSION PLASMAPHERESIS IN A KIDNEY TRANSPLANTATION PATIENT

P761 Aims: Basiliximab is a chimeric monoclonal antibody against the alpha chain of interleukin-2 receptors (IL-2R). It has been used with either tacrolimus or cyclosporine and other immunosupressants, for recent renal transplant cases at our institute since 2002. The blood concentration of this agent may be critical when plasmapheresis is performed in antibody mediated rejection cases. We present sequential blood concentrations of Basiliximab in a case of kidney transplantation with Basiliximab-based immunosuppression who received multisession plasmapheresis for its treatment. Methods: Case: Thirty-four year-old male received living-related kidney transplantation with induction immunosuppression of tacrolimus, mycophenolate, methylprednisolone and Basiliximab. Severe antibody-mediated acute rejection (Banff grade 2B) suddenly occurred on day 7 and the patient required hemodialysis. The rejection was confirmed by biopsy and anitibody was confirmed by flow-cytometry cross-match. Pulse therapy of methylprednisolone was done without any obvious effect and deoxyspergualin was given for 10 days at daily dose of 5 mg/ kg combined with double filtration plasmapheresis (DFPP). Eight sessions of DFPP within 15 days allowed this patient to be free from HD. Current serum creatinine level was 0.95 mg/ dL. Basiliximab blood level monitoring: Sequential Basiliximab blood levels were monitored on the daily blood stock samples after transplantation. The analyses were performed at the laboratory of Novartis Basel AG. Serum basiliximab concentrations were determined by a valiated, idiotype-specific enzyme-linked immunosorbent assay (ELISA) method. Results: Serum basiliximab concentration were 5.53 ug/mL on day 5 after two basiliximab infusions, 2.04 ug/mL on day 12 before DFPP, 0.56 ug/mL on day 18 after five consecutive DFPP and 0.25 ug/mL on day 24 after further three DFPP which means the eighth session. The elimination rate of basiliximab concentration (▵BLX) was 5.7% before DFPP. The mean of ▵BLX increased to 19.1% over eight DFPP. Serum basiliximab concentration declined to 0.16 ug/ml on day 33, which is under IL-2R saturated concentration (0.2 ug/mL), and fell below the limitation of detection level on day 40. The ratio of CD25 positive T cell per CD3 positive T cell were 0.65% on day 13 and 0.33% on day 19, which means basiliximab saturated CD25. Conclusions: Multisession plasmapheresis enhance to eliminate serum basiliximab and its average elimination rate was 19.1% over DFPP. Serum basiliximab concentration fell below 0.2ug/mL which needs to saturate IL-2R within one month posttransplant. The second rejection was not observed in this case. Additional basiliximab infusion should be considered in case of more than three session plasmapheresis.

Measurement of hepatic and intestinal CYP3A4 and PGP activity by combined po + iv [14C]erythromycin breath and urine test.

The aim of the present study was to develop a test for measuring hepatic and intestinal removal of cytochrome p-450 3A4 (CYP3A4)- and P-glycoprotein (PGP)-dependent xenobiotics that would be applicable for clinical use in humans. Orally and intravenously administered [N-methyl-14C]erythromycin was used for evaluation of 14C-labeled excretion dynamics in breath and urine. Simultaneous breath and urine test measurements were performed in 32 healthy volunteers and in 23 renal transplant recipients. Mathematical analysis of the excretion rate of labeled CO2 in breath and labeled carbon in urine resulted in 1). separation of both CYP3A4 and PGP activity in the liver and the intestinal mucosa and 2). numerical calculation of the dynamics of the different processes. The test was sufficiently sensitive to detect theoretically predicted process-specific pharmacological modulations by different drugs in healthy volunteers and after recent renal transplantation. It is concluded that the combined oral and intravenous erythromycin breath and urine test is a reliable and noninvasive test to measure phenotypic intestinal and hepatic CYP3A4 and PGP activity and may be a promising tool for prediction of drug interactions and dose adjustment of many pharmacotherapeutics in clinical practice, e.g., immunosuppressive agents after renal transplantation.

Pulmonary granulocyte kinetics in relation to endothelial and granulocyte activation

The aim of the study was to measure the peripheral blood levels of soluble E-selectin in patients with systemic inflammation and compare them with in vivo granulocyte activation, pulmonary intravascular granulocyte pooling, pulmonary extravascular granulocyte migration and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) aerosol clearance, an index of lung injury. The level of soluble E-selectin was measured by capture ELISA. Granulocytes were labelled with 111In and 99mTc for quantification of pulmonary granulocyte kinetics. The pulmonary vascular granulocyte pool (PGP) was expressed as a fraction of the total blood granulocyte pool. Pulmonary granulocyte migration was quantified on 24-h images using the 111In signal. Granulocyte activation was quantified as the percentage of circulating cells showing shape change ('primed'). Lung injury was assessed from the clearance rate of inhaled 99mTc-DTPA aerosol. Eighteen patients with systemic inflammation were studied: five with inflammatory bowel disease, eight with systemic vasculitis, four with graft versus host disease and one with a recent renal transplant. The peripheral blood levels of soluble E-selectin were significantly elevated in patients with systemic inflammation. The level of soluble E-selectin showed a significant association with granulocyte migration (Spearman rank correlation coefficient, Rs=0.53; P<0.05) but not with PGP or with the percentage of cells showing shape change (P>0.05 for both). Granulocyte migration was bimodal: patients were therefore subdivided into 'migrators' and 'non-migrators'. Soluble E-selectin level, 99mTc-DTPA clearance and PGP, but not the percentage of cells showing shape change, were significantly higher in migrators than in non-migrators. We conclude that pulmonary intravascular granulocyte pooling is increased in the presence of increased numbers of circulating primed granulocytes but increased pooling does not by itself promote granulocyte migration into the lung interstitium. Insofar as an elevated level of E-selectin in peripheral blood reflects vascular endothelial activation, the data are consistent with the notion that pulmonary endothelial activation is required, in addition to granulocyte activation and an expanded PGP, for granulocyte migration into lung parenchyma and, therefore, for lung injury to occur.

Nutritional management in a child on chronic peritoneal dialysis: a team approach

The nutritional management of a child on chronic peritoneal dialysis (CPD) requires considerable dietetic input as frequent adjustments are necessary to account for growth and changes in biochemical parameters. The progress is described of a 6‐year‐old boy with chronic renal failure (CRF) from birth due to renal dysplasia. In contrast to the relative ease of overnight dialysis, feeding problems have been the major source of stress for the family. Management involves constant support using a multidisciplinary team approach. A recent renal transplant has resolved many of the problems.