Sessions Of Plasmapheresis Research Articles

Comparison of plasmapheresis efficacy and complex antioxidant therapy in patients with comorbid course of chronic pancreatitis and chronic obstructive pulmonary disease

60 patients with chronic obstructive pulmonary disease (COPD) and chronic pancreatitis (CP) were examined in the dynamics of treatment. The complex therapy of patients with COPD and CP including inhalation therapy with Thiotropium bromide, Serrathiopeptidase and Emoxypin promoted reduced intensity of oxidative stress, restoration of antioxidant protective components activity and natural detoxication system, intensified the activity of enzymatic, Hagemmandependant fibrinolysis and collagenosis, improving the processes of microcirculation, elimination of ischemia and swelling of the pancreatic tissue, quick removal of clinical exacerbation signs of the underlying disease and comorbid diseases. According to the correction degree of enzyme deviation syndrome in the blood, intensity of nitrositic stress and endogenic intoxication in patients with COPD and CP, the effect of 30-day intake of Serrathiopeptidase and 15-day intake of Emoxypin is equal to the efficacy of five plasmapheresis sessions.

Extreme hypercholesterolemia presenting with pseudohyponatremia - a case report and review of the literature

Pseudohyponatremia has been reported in association with severe hypertriglyceridemia and hyperparaproteinemia, but its association with severe hypercholesterolemia is not well-known. We report a 43-year-old woman with refractory primary biliary cirrhosis who presented with asymptomatic hyponatremia (121 mmol/L; normal range: 135-145 mmol/L). She was ultimately found to have a total serum cholesterol level of 2415 mg/dL (normal range: 120-199 mg/dL) — secondary to accumulation of lipoprotein-X—causing pseudohyponatremia. The diagnosis was confirmed by measurement of serum osmolality (296 mOsm/kg H2O; normal range: 270-300 mOsm/kg H2O) and serum sodium by direct potentiometry (141 mmol/L). Furthermore, following 16 sessions of plasmapheresis over a 4-month period, there was marked lowering of serum cholesterol to 200 mg/dL and normalization of serum sodium (139 mmol/L) as measured by indirect potentiometry. This case shows that extreme hypercholesterolemia from elevation of lipoprotein-X particles in cholestasis can be a rare cause of pseudohyponatremia. It highlights the need to measure serum sodium with direct potentiometry in the setting of extreme hypercholesterolemia and consider this possibility before initiating treatment of hyponatremia.

Giant cell arteritis: Relapsing disease is a nightmare in diabetics

cyclophosphamide pulses. He developed solitary ileal perforation requiring surgery with ileostomy on follow up. Despite being on monthly CYC pulses for four months, along with steroids, he developed new vasculitic skin lesions along with new onset upper and lower limb peripheral neuropathy. He was given methylprednisolone pulses for three days along with hiking up of cyclophosphamide to biweekly with a plan to increase the interval to three weeks. He did not tolerate first session of plasmapheresis. Thecasehighlights the therapeutic challengeand lackof consensus guidelines in management of such cases of relapsing PAN.

Fatal Late-Onset Pneumocystis Pneumonia After Rituximab: Administration for Posttransplantation Recurrence of Focal Segmental Glomerulosclerosis—Case Report

Recurrence of focal segmental glomerulosclerosis (FSGS) is an important cause of graft loss after kidney transplantation. The management of patients with recurrent FSGS is not well established because there are no prospective randomized studies with a view to the impact of FSGS on graft survival. Recent studies suggest that rituximab, an anti-B-CD20 monoclonal antibody, may be a therapeutic alternative in selected cases resistant to conventional therapy. Opportunistic infections with rituximab have not been studied extensively, but recent studies suggest an increased risk for Pneumocystis jirovecii pneumonia (PJP) after rituximab therapy. We report the case of a kidney transplant recipient with recurrence of FSGS in the graft, in whom fatal PJP developed subsequent to treatment with rituximab. Our patient was treated with plasmapheresis and a complex immunosuppressive drug scheme for the recurrence of FSGS in transplanted kidney. However, this treatment had no effect on the amount of proteinuria, which increased to a maximum of 15 g/d after 18 session of plasmapheresis. Thereafter, 500 mg intravenously (IV) of rituximab was administered at 4-week intervals. The number of CD19-positive B lymphocytes decreased from 9% to 0.57%. Two months after the second dose of rituximab, proteinuria decreased to 2.1 g/d. Ten months after transplantation and 5 months after the first dose of rituximab was administered, severe PJP pneumonia developed and the patient died despite all efforts with antibiotic therapy. It seems essential that all renal transplant recipients treated with rituximab should currently be considered at an increased risk for PJP. This case suggests that prolonged or restarted prophylaxis for PJP should be recommended not only after conventional treatment for acute rejection episodes but also after use of rituximab in combination with other immunosuppressive therapy as well.

P118 : HEART TRANSPLANT AFTER ANTIBODY REDUCTION WITH BORTEZOMIB AND PLASMAPHERESIS IN A HIGHLY SENSITIZED PATIENT

Aim To describe the case of a successful heart transplant in a highly sensitized individual by antibody reduction with bortezomib and plasmapheresis. Methods A 38 year old female patient with a pre-transplant cPRA of 81% (Class I & II) was desensitized with 5 sessions of plasmapheresis and two doses of bortezomib. The alloimmune status was determined by solid phase single antigen and phenotype bead based assays. Post transplant follow up included endocardial biopsies and DSA monitoring. Results The patient’s class I and class II PRAs decreased from 81% to 44% and 31% respectively by day 6 of desensitization. The overall strength of HLA antibodies was also reduced. A prospective crossmatch was performed with a local donor. The crossmatch was technically negative, but the Flow median Channel Shift (MCS) was closer to the positive cut off value. The patient underwent another PP and was tested and crossmatched again when the MCS was significantly below the positive cutoff value. The patient received the transplant and is doing well 18 months post transplant. Conclusions This case report demonstrates the potential efficacy of bortezomib therapy in addition to plasmapheresis to transplant highly sensitized patient awaiting heart transplant. Because of limitations with the prospective crossmatch for heart transplant candidates, desensitization of the potential recipient to increase the likelihood for an acceptable donor by depleting pre-existing antibodies against the unacceptable antigens is an attractive option. Plasmapheresis and IVIG in combination with rituximab has been utilized in kidney transplant recipients with a living donor; however, candidates awaiting a deceased donor represent a significant immunological and logistical challenge. Rituxan does not deplete circulating plasma cells that produce antibodies. Bortezomib has been shown to induce plasma cell apoptosis. However, its use prior to heart transplant has been limited. More studies are needed to evaluate the efficacy of bortezomib-based desensitization strategy in heart transplant set up. Patient is currently pursuing her degree as an echo technician.

P115 : PRIMARY GRAFT DYSFUNCTION AFTER 0 MM KIDNEY TRANSPLANTATION SECONDARY TO ACUTE CELL MEDIATED REJECTION

Aim To present a highly sensitized patient with end stage renal disease who received his third kidney transplant from HLA-A, -B, -DR zero mismatched (0 MM) deceased donor (DD) and developed early acute cellular rejection (ACR – BANFF 2A) in absence of DSA. Methods Donor and recipient were HLA typed by RSSOP Luminex assay for HLA loci A, B and C, DRB1, DRB3/4/5, DQB1, DQA1, DPB1, and DPA1. HLA antibody identification were performed with One Lambda Luminex single antigen bead assay. Sera were tested untreated, treated with heat inactivation (HI) and 1:8 dilutions. CDC (with and without HI) and flow XM for T and B cells were tested at the day of transplant. Results A 40 years old man, highly sensitized (CPRA 100%) with a history of two previous renal transplants (lost due to non-immunological cause) with multiple class II DP antibodies with high MFI. The patient received a local zero mismatched donor was offered and with confirmatory testing an antigen level match for all HLA including DP. CDC and flow XM for T and B cells were negative. No DSA was detected pre or post-transplant. In post-operative day 1, the patient presented with anuria and hyperkalemia that mandated dialysis, and underwent dialysis throughout the rest of hospitalization as needed. Due to delayed graft function, he had a biopsy on post-operative day 8 that showed ACR – BANFF 2A – with negative C4d, peritubular capillaritis, and DSA. Treatment with anti-thymo globulin (ATG) did not show improvement. Consequently the patient received 3 sessions of plasmapheresis plus IvIG but the patient remained dialysis dependent. In post-operative day 50, biopsy showed chronic active T cell mediated rejection with no DSA. The graft remained non-functioning and graft nephrectomy was performed. This case suggests that highly sensitized kidney transplant candidates are at increased risk of cell mediated rejection and graft loss even in the context of 0 MM, negative DSA and flow crossmatch.

Acute Hemorrhagic Leukoencephalitis: Multimodal Diagnosis and Treatment

We report a case of a previously healthy 26-year-old male, admitted to the intensive care unit due to cerebral edema. The patient was admitted 3 days earlier to the neurological department because of sudden onset of headache and vision disturbances. Brain magnetic resonance imaging (MRI) on admission revealed an extended right parietooccipital lesion with marginal contrast enhancement and extension towards the corpus callosum. The patient quickly deteriorated, became comatose and was intubated and transferred to the intensive care unit. In order to control intracranial hypertension, decompressive craniectomy was decided which also allowed for a brain biopsy. According to clinical, radiological and laboratory data, acute disseminated encephalomyelitis was the working diagnosis. The patient was treated with high dose corticosteroids and plasmapheresis sessions and gradually improved and transferred to a rehabilitation center. Brain biopsy showed acute hemorrhagic leukoencephalitis or Hurst disease, a variant of acute disseminated encephalomyelitis. I N t r O D U c t I O N Acute fulminant brain dysfunction may derive from infectious, inflammatory, vessel-obstructive, vessel-inflammatory, demyelinating, neoplastic, metabolic or toxic processes. Causative spectrum is quite wide to be timely worked up when danger for life is present. Clinical evaluation, blood testing, brain computed tomography and lumbar puncture constitute the standard emergency diagnostic sequence. From the physician’s perspective, narrowing the differential diagnosis to subgroups of entities with common treatment plan is highly desirable. Early recruitment of detailed brain imaging, i.e., brain parenchyma magnetic resonance imaging (MRI) together with arteriography and venography protocols (MRA, MRV) should be viewed as mandatory in this context. On the contrary, specific laboratory investigations in blood and cerebrospinal fluid are often either not available or not informative in the early stage. In cases with ambiguous findings, targeted brain biopsy always remains an option. cAse repOrt Department of Critical Care Medicine and Pulmonary Services, Department of Neurology, Department of Neurosurgery, Laboratory of Pathology, Evagelismos Hospital, Athens, Greece HOSPITAL CHRONICLES 2014, 9(3): 202–207

SEVERE IMMUNE HEMOLYTIC ANEMIA AFTER LIVER TRANSPLANTATION

Clinical case of successful treatment of severe immune hemolytic anemia after liver transplantation is represen- ted in this article. The cause of complication was so-called passenger lymphocyte syndrome (a type of graft- versus-host disease). Two plasmapheresis sessions and Ig (0.5 g/kg) in combination with increased maintenance immunosuppression with a short course of oral methylprednisolone in a total dose of 150 mg during 12 days were effective. The patient was discharged from hospital 34 days after transplantation in a satisfactory condition with a stable hemoglobin level.

HOW TO IMPLEMENT IMMUNOADSORPTION IN A POLYVALENT DIALYSIS UNIT: A REVIEW

Many kidney-transplant candidates have anti-HLA alloantibodies (HLAi): these make transplantation difficult, even from a living kidney (LK) donor, because of the presence of donor-specific anti-HLA alloantibodies. Due to the shortage of deceased kidney donors, the number of LK transplants is increasing, but is potentially limited by ABO incompatibility (ABOi). To make ABOi and/or HLAi patients suitable for kidney transplantation they need to be desensitised: this strategy is mainly based on rituximab therapy combined with either plasmapheresis (PP) or immunoadsorption (IA). IA can be more efficient than PP because greater plasma volumes can be treated within a single session than a PP session (>4 vs. 1.5-2). IA can be specific (ABOi setting) or non-specific (HLAi). We describe how we designed and implemented a desensitisation programme based on IA. This was started in the first trimester of 2010 within the Acute Polyvalent Haemodialysis and Apheresis Unit in Toulouse University Hospital, France. So far, we have performed >200 IA sessions with good results. The IA sessions were associated with a net body-weight gain of ∼1 kg. Normally, IA is performed first and then haemodialysis on the same or next day; however, we have been able to, for the first time, couple IA with haemodialysis. Moreover, we can now carry out this procedure 24 hours a day, seven days a week. This procedure has improved patient care and reduced costs. The IA desensitisation programme has enabled successful transplantation in 24 patients to date.

Pre-conception preparation at the antiphospholipid syndrome as way to improve reproductive health.

IntroductionReproductive health is characterized by the condition of the woman in association with the course of pregnancy and childbirth. In this case, the absence of disease plays a fundamental role. Unfortunately, conditions that can negatively impact reproductive health and cause deterioration of pregnancy and delivery outcomes are frequent in women of reproductive age. Antiphospholipid syndrome (APS) is one of the leading conditions that can negatively affect reproductive health and lead to various complications in pregnancy including fetal loss.Materials and methodsWe assessed the effectiveness of pre-conception preparing, including traditional therapy of APS in conjunction with system enzyme therapy (SET) and plasmapheresis sessions. We conducted a study in two groups: women with APS and pre-conception preparing (n = 49) and the control group were women without pre-conception preparing (n = 46).ResultsThe effect of pre-conception preparing in women with APS was assessed by the course and outcome of pregnancy. The total number of women with complications of pregnancy were 39.1% lower in the study group compared to the control group. Risk of miscarriage in the basic group observed 68.7 % less frequently compared to the control group. The frequency of pre-eclampsia was 63.5 % less in the study group compared to the control group. We observed significantly lower rates of placental insufficiency in the study group and the difference in this parameter reached 65.2%. The risk of pre-term birth was 59.4 % lower in the study group compared to the control group.ConclusionWe concluded that pre-conception preparing in women with APS increases the possibility of physiological course pregnancy. Pre-conception preparing reduces the incidence of miscarriage, pre-term labor, and the development of pre-eclampsia, and placental insufficiency.

Gestational Severe, Nonfamilial Hypertriglyceridemia, Management with İnsulin and Metformin, A Case Report

Severe hypertriglyceridemia is a rare condition in pregnancy. We report a case of gestational, nonfamilial severe hypertriglyceridemia accompanied with gestational diabetes mellitus. Despite an intensive insulin regimen and dietary fat restriction plasma triglyceride levels were remained higher. After a plasmapheresis session, triglyceride levels were reduced nearly 40%. Since plasma glucose and triglyceride levels were higher, metformin therapy was administered. After two weeks of metformin therapy, plasma glucose levels were within target range and triglyceride level was reduced below 1000 mg/dl. She delivered at 38th week of pregnancy via elective cesarean section, a healthy female baby with normal birth weight. Serum triglyceride level decreased immediately to 280 mg/dl after delivery.

The use of ABO-incompatible grafts in living donor liver transplantation—First report from India

ABO incompatibility is the commonest reason for rejection of donors in living donor liver transplantation (LDLT). The donor pool could be expanded by 25 % to 35 % if the ABO barrier is overcome. In the absence of pre-conditioning, transplantation across the blood groups is fraught with the almost universal risk of antibody-mediated rejection (AMR) that rapidly leads to graft loss. However, AMR can be prevented by removal of preformed antibodies and reducing their production by B cells. We describe our initial experience of three cases of ABO-incompatible (ABO-i) LDLT: a 42-year-old male, an 8-month-old male and a 28-month-old female, all of blood group O+ who received blood group B + right lobe, B + left lateral segment, and A + left lateral segment liver grafts, respectively. Pre-LDLT conditioning included administration of anti-CD20 antibody (Rituximab(®)) to the adult 4 weeks prior, and four to seven sessions of double-filtration plasmapheresis to all, to remove preformed antibodies and achieve anti-donor blood group antibody (ADA) titers of ≤ 1:16 IgG and ≤ 1:8 IgM, respectively. In addition, cases 1 and 3 received mycophenolate mofetil for 7 days prior to LDLT. After LDLT, all three patients achieved normal graft function over 8-17 days with no evidence of AMR and without the need for further plasmapheresis. Postoperative complications included portal vein thrombosis (one successfully re-explored), CMV (one), Pseudomonas and Klebsiella sepsis (one each), and abdominal collection (one treated with percutaneous drainage). All are currently well with normal graft function and low ADA titers at 8, 16, and 19 months after ABO-i LDLT.

Renal cortical necrosis secondary to thrombotic microangiopathy in the context of acute promyelocytic leukaemia blast crisis.

A 37-year-old patient was transferred to Haematology from the ENT Emergency Department where he had been admitted due to tonsillitis. He displayed anaemia and leukopenia and had agranulocytosis in the study. A day later the patient had blast crisis, and was diagnosed with myeloid acute leukaemia. Due to blast crisis the patient experienced sudden back pain, with oliguria and renal function deterioration followed by anaemia, in the context of haemolysis consistent with thrombotic microangiopathy, and as such, we were consulted. We began treatment with plasmapheresis and on the following day we performed haemodialysis (we carried out a total of 12 sessions of plasmapheresis until haemolysis disappeared). Five days later there was respiratory failure, and the patient was consequently transferred to the Intensive Care Unit, where he continued treatment with plasmapheresis and haemodialysis. The patient remained anuric thereafter, requiring haemodialysis, with no sign of renal recovery. Once platelet levels normalised with haematology chemotherapy, a percutaneous renal biopsy was performed, which confirmed the diagnosis of cortical necrosis. Finally, the patient underwent renal replacement therapy by regular haemodialysis.

Miller–Fisher syndrome

Miller–Fisher syndrome is a rare variant of acute inflammatory demyelinating polyneuropathy. The paper describes a case of Miller–Fisher syndrome developing as ophthalmoplegia, ataxia, and areflexia one week after acute respiratory viral infection. Within 3 weeks, neurological disorders completely regressed due to a plasmapheresis session and intravenous immunoglobulin injection.

Population pharmacokinetics of rituximab with or without plasmapheresis in kidney patients with antibody‐mediated disease

Both rituximab and plasmapheresis can be associated in the treatment of immune-mediated kidney diseases. The real impact of plasmapheresis on rituximab pharmacokinetics is unknown. The aim of this study was to compare rituximab pharmacokinetics between patients requiring plasmapheresis and others without plasmapheresis. The study included 20 patients receiving one or several infusions of rituximab. In 10 patients, plasmapheresis sessions were also performed (between two and six sessions per patient). Rituximab concentrations were measured in blood samples in all patients and in discarded plasma obtained by plasmapheresis using an enzyme-linked immunosorbent assay method. Data were analysed according to a population pharmacokinetic approach. The mean percentage of rituximab removed during the first plasmapheresis session ranged between 47 and 54% when plasmapheresis was performed between 24 and 72 h after rituximab infusion. Rituximab pharmacokinetics was adequately described by a two-compartment model with first-order elimination. Plasmapheresis had a significant impact on rituximab pharmacokinetics, with an increase of rituximab clearance by a factor of 261 (95% confidence interval 146-376), i.e. from 6.64 to 1733 ml h(-1) . Plasmapheresis performed 24 h after rituximab infusion decreased the rituximab area under the curve by 26%. Plasmapheresis removed an important amount of rituximab when performed less than 3 days after infusion. The removal of rituximab led to a significant decrease of the area under the curve. This pharmacokinetic observation should be taken into account for rituximab dosing, e.g. an additional third rituximab infusion may be recommended when three plasmapheresis sessions are performed after the first rituximab infusion.

Guillain-Barré syndrome in a patient with diabetes mellitus

Introduction: Guillain-Barre syndrome (GBS) is a disorder of peripheral nervous system characterized by progressive, symmetrical, ascending paralysis. It is caused by inflammation and demyelination of peripheral nerves and roots of spinal nerves. Common features include absent muscle reflexes and loss of sensation. The aim of this case report is to delineate it from diabetic neuropathy on the basis of symptomatology, and to diagnose it earlier as it can lead to respiratory failure and cardiac arrhythmias in severe cases. Case presentation: A 40 years old female known case of diabetes mellitus for 4 years and hypertension for 2 years presented with paresthesias of both lower limbs which was progressive along with bilateral leg weakness and difficulty in walking without support and standing up from sitting position. Later, she also developed bilateral upper limb paresthesias and weakness. Two months before developing neurological symptoms, she had an episode of fever which lasted for about 7 days without associated symptoms of either respiratory or gastrointestinal tract. Considering her symptoms, GBS was suspected and multiple investigations were performed including lumbar puncture, ECG and NCV, all of which suggested GBS instead of diabetic neuropathy. Hence, sessions of plasmapheresis were started which improved her symptoms and she was discharged after 5 cycles of plasmapheresis as she had no complains of autonomic dysfunction or paralysis of any part of her body. Conclusion: Peripheral neuropathy in a diabetic patient is not always due to diabetes mellitus so other conditions should be considered as well. In such circumstances, specific investigations are required to make an accurate diagnosis.

Podocyte Effacement Closely Links to suPAR Levels at Time of Posttransplantation Focal Segmental Glomerulosclerosis Occurrence and Improves With Therapy

Focal segmental glomerulosclerosis (FSGS) recurs after kidney transplantation in more than 30% of cases and can lead to allograft loss. Serum soluble urokinase-type plasminogen activator receptor (suPAR) is implicated in the pathogenesis of native and recurrent FSGS. We conducted a retrospective study of 25 adults with posttransplantation FSGS. We investigated the relationship between suPAR levels and podocyte changes and the impact of therapy on podocyte structure. We assessed response to therapy by improvement in proteinuria, allograft function, and resolution of histologic changes. A median (interquartile range) of 15 (10-23) plasmapheresis sessions was administered; 13 of the subjects also received rituximab. Median pretreatment suPAR levels were higher among those with severe (≥75%) versus those with mild (≤25%) podocyte foot process effacement (13,030 vs. 4806 pg/mL; P=0.02). Overall, mean±SD of proteinuria improved from 5.1±3.8 to 2.1±2.8 mg/dL (P=0.003), mean podocyte effacement decreased from 57%±33% to 22%±22% (P=0.0001), estimated glomerular filtration rates increased from median (interquartile range) of 32.9 (20.6-44.2) to 39.3 (28.8-63.4; P<0.0001), and suPAR levels decreased from a median of 6.781 to 4.129 pg/mL (P=0.02) with therapy. Podocyte effacement is the first pathologic manifestation of FSGS after transplantation. The degree of podocyte effacement correlates with suPAR levels at time of diagnosis. Response to therapy results in significant reduction of suPAR levels and complete or significant improvement of podocyte effacement.

Antibody-Mediated Rejection and Treatment in Pediatric Patients: One Center’s Experience

Antibody-mediated rejection is a rare complication that often results in the loss of the kidney graft. Treatment options include plasmapheresis, intravenous immunoglobulin, and use of rituximab. We retrospectively evaluated the data files from 86 pediatric renal transplant patients over the last 5 years. A biopsy was taken for each rejection episode. Seven patients (7.7%) developed antibody-mediated rejection. All patients with antibody-mediated rejection had histologic evidence of severe acute humoral rejection and extensive C4d staining in peritubular capillaries. Staining was diffuse (involving > 50% of peritubular capillaries) for 4 biopsies, and it was focal (involving < 50% of peritubular capillaries) for 3 biopsies. Twelve biopsies demonstrated at least 1 histologic feature associated with acute humoral rejection. Donor-specific antibodies were evaluated in recipients. The mean peak panel reactive antibody class 1 was 7.16% (range, 0%-86%). The mean time between rejection episodes and the transplant was 16.9 ± 13.5 months. All patients were treated with high-dose intravenous methylprednisolone and intravenous immunoglobulin. Three patients recovered renal function rapidly after this treatment. Donor-specific antibodies were negative in these patients. Five sessions of plasmapheresis were used simultaneously in these 4 patients. In 3 resistant patients, rituximab was prescribed after plasmapheresis and intravenous immunoglobulin. The presence of donor-specific antibodies was demonstrated in 4 patients. Two patients were refractory to antibody-mediated rejection treatment and lost their transplants. One patient had interstitial fibrosis and tubular atrophy during the 16th month after her antibody-mediated rejection. Graft survival in patients with antibody-mediated rejection at the end of 1 year was 71.4%. Early diagnosis and treatment with plasmapheresis, intravenous immunoglobulin, and rituximab may resolve antibody-mediated rejection. Although effective therapy is available for acute antibody-mediated rejection, the allograft remains at risk for chronic antibody-mediated rejection and shortened survival.

Influence of plasma exchange on rituximab pharmacokinetics

Rituximab, an anti CD20 monoclonal antibody is approved for the treatment of B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukaemia and rheumatoid arthritis [1]. It is also used off label for the treatment of lymphomas induced by the Epstein–Barr virus (EBV) after bone marrow or organ transplant [2], in particular forms of organ transplant rejection (acute humoral rejection) [3] and in a number of autoimmune diseases. Plasma exchange (PEx) is an extracorporeal blood purification technique allowing the removal of large molecular weight substances from the plasma and hence is used in various diseases including cryoglobulinaemia. In this last condition, its aim is to eliminate pathogenic antibodies involved in vascular and glomerular lesions. Because PEx is not selective, it also leads to the elimination of any circulating therapeutic antibody. An impact of PEx on plasma concentrations of basiliximab and rituximab [4, 5] was reported but its influence of monoclonal antibody pharmacokinetics was not studied. We report the use of compartmental pharmacokinetic modelling to quantify the impact of multiple PEx sessions on exposure to rituximab in two patients. Two patients with non-Hodgkin's lymphoma (MALT-type lymphoma and lymphoma following liver transplantation) treated with rituximab underwent multisession PEx for cryoglobulinaemia associated with membranoproliferative glomerulonephritis. Rituximab was administered intravenously at a dose of 350 mg m−2 weekly for 4 weeks to a 49 kg, 52-year-old woman (patient 1) and as six injections of 375 mg m−2 over 6 months to a 80 kg, 56-year-old man (patient 2). Patient 1 underwent weekly plasmapheresis sessions. Patient 2 underwent plasmapheresis twice a month during rituximab treatment, followed by weekly sessions. In both cases, plasmapheresis sessions were performed before rituximab injections, except for one plasmapheresis session (patient 1), performed 14 h after the infusion. Blood samples were collected 2 h after rituximab injections and before, immediately and 6 h after plasmapheresis sessions, in accordance with the policy of the local Ethics Committee. Serum rituximab concentrations were measured by enzyme-linked immunosorbent assay [6] and rituximab pharmacokinetics were described using a two compartment model with two elimination clearances, a ‘physiological’ clearance (CL) and a ‘PEx’ clearance (CLP) taking place only during the sessions. Estimated parameters were 0.2 and 0.5 l day−1 for CL, 28 and 20 l day−1 for CLP, 1.9 and 3.2 l for central compartment volume, 3.2 and 3.3 l for peripheral compartment volume and 5.2 and 4.5 l day−1 for intercompartment clearance, for patients 1 and 2, respectively. The model was used to simulate cumulated rituximab areas under the concentration vs. time curves (AUC) with and without plasmapheresis (Figure 1). This simulation showed a decrease in exposure to rituximab of 38% at day 54 and 10% at day 274 for patients 1 and 2, respectively (Figure 1). Figure 1 Observed (circles), model-predicted rituximab serum concentrations (black lines) and cumulated AUC (grey lines) as a function of time in the two patients. Predicted concentrations and cumulated AUC (* – dashed lines) in the absence of PEx (without ... Our model is the first to describe the pharmacokinetics of rituximab when it is associated with PEx. This procedure had a marked impact on patients' exposure to rituximab. The pharmacokinetic model may also be used to predict the consequences of alterations in rituximab dose or in interval between infusion and PEx. However, the pharmacokinetic consequences of PEx can be minimized by applying PEx sessions at the end of dosing intervals. Alternatively, patients given repeated infusions of rituximab in association with PEx may benefit from an individual dose adjustment based on the monitoring of rituximab serum concentrations.

Recurrence of focal segmental glomerulosclerosis in a renal allograft recipient

A 22-year girl, diagnosed to have primary focal segmental glomerulosclerosis in 2009, underwent live related donor renal transplantation in May 2011. Her immunosuppressive regimen included Tacrolimus, Mycophenolate Mofetil and Prednisolone. For next three months graft function remained normal. In August 2011 she developed massive proteinuria with mild graft dysfunction and graft biopsy showed recurrence of focal segmental glomerulosclerosis. She underwent nine sessions of plasmapheresis followed by two doses of Rituximab. She attained remission of proteinuria and normal graft function after treatment. She continues to be in remission at one year and six months.