mycophenolic-acid and Hemolytic-Uremic-Syndrome

Deficiency of complement factor H-related plasma proteins and complement factor H autoantibody-positive hemolytic uremic syndrome (DEAP-HUS), which is characterized by the deficiency of complement-factor H-related (CFHR) plasma proteins and the subsequent formation of autoantibodies against complement factor H (CFH), has been reported to have an adverse outcome in one third of patients. Therapy options include prompt removal of antibodies by plasma exchange and immunosuppressive therapy. Recently, restoration of complement control using the monoclonal antibody eculizumab has been shown to be effective as first- and as second-line therapy in cases of therapy resistance or severe side effects of the applied therapy.. Here, we report a 6-year-old girl with DEAP-HUS and first-line therapy with eculizumab under immunosuppressive therapy with glucocorticoids and mycophenolate mofetil (MMF). This therapy led to a prompt and sustained clinical recovery, to a stable reduction of complement activation, and to a rapid decline in autoantibody titer. A second increase in the autoantibody titer was successfully treated with methylprednisolone and the child remained in remission. After 8.3 months of sustained complement control and 4.5 months of stable antibody suppression, eculizumab was successfully discontinued without any sign of relapse.. To our knowledge, this is the first reported case of a child with DEAP-HUS treated with the combination of eculizumab and immunosuppression as first-line therapy avoiding any HUS- or therapy-related complications and resulting in prompt clinical recovery. Importantly, clinical remission is maintained after discontinuation of eculizumab under stable immunosuppression.

Topics: Antibodies, Monoclonal, Humanized; Autoantibodies; Child; Complement Activation; Complement C3b Inactivator Proteins; Complement Factor H; Drug Resistance; Drug Therapy, Combination; Female; Glucocorticoids; Hemolytic-Uremic Syndrome; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Mycophenolic Acid; Plasma Exchange; Withholding Treatment

Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are related conditions with similar clinical features of variable severity. Survival of patients with HUS and TTP has improved greatly over the past two decades with improved supportive care for patients with HUS and by the use of plasma exchange (PE) with fresh frozen plasma (FFP) for patients with TTP. Separate pathogenesis of these two disorders has become more evident, but management overlaps.. To evaluate the benefits and harms of different interventions for HUS and TTP separately, in patients of all ages.. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), conference proceedings, reference lists of articles and text books and contact with investigators were used to identify relevant studies.. Randomised controlled trials (RCTs) evaluating any interventions for HUS or TTP in patients of all ages.. Three authors independently extracted data and evaluated study reporting quality using standard Cochrane criteria. Analysis was undertaken using a random effects model and results expressed as risk ratio (RR) and 95% confidence intervals (CI).. For TTP, we found six RCTs (331 participants) evaluating PE with FFP as the control. Interventions tested included antiplatelet therapy (APT) plus PE with FFP, FFP transfusion and PE with cryosupernatant plasma (CSP). Two studies compared plasma infusion (PI) to PE with FFP and showed a significant increase in failure of remission at two weeks (RR 1.48, 95% 1.12 to 1.96) and all-cause mortality (RR 1.91, 95% 1.09 to 3.33) in the PI group. Seven RCTs were undertaken in children with HUS. None of the assessed interventions used (FFP transfusion, heparin with or without urokinase or dipyridamole, shiga toxin binding protein and steroids) were superior to supportive therapy alone, for all-cause mortality, neurological/extrarenal events, renal biopsy changes, proteinuria or hypertension at the last follow-up visit. Bleeding was significantly higher in those receiving anticoagulation therapy compared to supportive therapy alone (RR 25.89, 95% CI 3.67 to 182.83).. PE with FFP is still the most effective treatment available for TTP. For patients with HUS, supportive therapy including dialysis is still the most effective treatment. All studies in HUS have been conducted in the diarrhoeal form of the disease. There were no RCTs evaluating the effectiveness of any interventions on patients with atypical HUS who have a more chronic and relapsing course.

Topics: Cyclophosphamide; Hemolytic-Uremic Syndrome; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Mycophenolic Acid; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Randomized Controlled Trials as Topic

Topics: Adrenal Cortex Hormones; Calcineurin Inhibitors; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Disease Susceptibility; Drug Administration Schedule; Hemolytic-Uremic Syndrome; Humans; Hypertension; Immunocompromised Host; Immunosuppressive Agents; Incidence; Kidney Diseases; Kidney Transplantation; Mycophenolic Acid; Neoplasms; Postoperative Complications; Sirolimus

Anemia in children after renal transplantation is more common than previously appreciated. Multiple factors appear to play roles in the development of post-transplant anemia, the most common of which is absolute and/or functional iron deficiency anemia. Most experts recommend that iron limited anemias in transplant patients should be diagnosed using the same criteria as for chronic renal failure patients. Serum erythropoietin (EPO) levels are expected to normalize after a successful renal transplantation with a normal kidney function, yet both EPO deficiency and resistance have been reported. While no large controlled trials comparing the effect of different immunosuppressive agents on erythropoiesis after transplantation have been performed, generalized bone marrow suppression attributable to azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus, antithymocyte preparations has been reported. Pure red cell aplasia (PRCA) occurs rarely after transplantation and is characterized by the selective suppression of erythroid cells in the bone marrow. PRCA has been reported with the use of AZA, MMF, tacrolimus, angiotensin converting enzyme inhibitors (ACEI), but not with cyclosporine (CSA) use. Post-transplant hemolytic uremic syndrome has been reported with orthoclone anti T-cell antibody (OKT3), CSA and tacrolimus therapy. Viral infections including cytomegalovirus, Epstein-Barr virus and human parvovirus B19 have been reported to cause generalized marrow suppression. Management of severe anemia associated with immunosuppressive drugs generally requires lowering the dose, drug substitution or, when possible, discontinuation of the drug. Because this topic has been incompletely studied, our recommendation as to the best immunosuppressive protocol after renal transplantation remains largely dependent on the clinical response of the individual patient.

Topics: Anemia; Anemia, Iron-Deficiency; Azathioprine; Bone Marrow; Child; Erythropoiesis; Erythropoietin; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Tacrolimus

To explore the clinical characteristics, treatment protocol and prognosis of children with anti-complement factor H (CFH) autoantibody (Ab)-associated hemolytic uremic syndrome (HUS).. Clinical data of 8 patients with anti-CFH Ab-associated HUS who were admitted to Shandong Provincial Hospital from January 2011 to December 2020 were collected retrospectively.. The age at disease onset ranged between 5.83 and 13.5 years, with a male: female ratio of 1.67:1. The time of onset was distributed from May to June and November to December. Digestive and upper respiratory tract infections were common prodromal infections. Positivity for anti-CFH Ab and reduced C3 levels were observed among all patients. Heterozygous mutation of the CHFR5 gene (c.669del A) and homozygous loss of the CFHR1 gene [loss2(EXON:2-6)] were found in two patients. All patients received early treatment with plasma exchange and corticosteroid therapy. Six patients were given immunosuppressive agents (cyclophosphamide and/or mycophenolate mofetil) for persistent proteinuria. The follow-up period was 12-114 months. Four of 8 patients achieved complete remission, 3 achieved partial remission, and 1 died. Relapse occurred in two patients.. Children with anti-CFH Ab-associated HUS were mainly school-aged and predominantly male, with onset times of summer and winter. Digestive and upper respiratory tract infections were common prodromal infections. Plasma exchange combined with methylprednisolone pulse therapy in the acute phase and cyclophosphamide or mycophenolate mofetil treatment for maintenance can be utilized in children with anti-CFH Ab-associated HUS if eculizumab is not available.

Topics: Adolescent; Atypical Hemolytic Uremic Syndrome; Autoantibodies; Child; Child, Preschool; Complement Factor H; Cyclophosphamide; Female; Hemolytic-Uremic Syndrome; Humans; Immunologic Factors; Male; Mycophenolic Acid; Respiratory Tract Infections; Retrospective Studies

Antibodies to complement factor H are an uncommon cause of hemolytic uremic syndrome (HUS). Information on clinical features and outcomes in children is limited. In order to explore this we studied a multicenter cohort of 138 Indian children with anti-complement factor H antibody associated HUS, constituting 56% of patients with HUS. Antibody titers were high (mean 7054 AU/ml) and correlated inversely with levels of complement C3, but not complement factor H. Homozygous deletion of the CFHR1 gene was found in 60 of 68 patients. Therapies included dialysis in 119 children, 105 receiving plasma exchanges and 26 intravenous immunoglobulin. Induction immunosuppression consisted of 87 children receiving prednisolone with or without intravenous cyclophosphamide or rituximab. Antibody titers fell significantly following plasma exchanges and increased during relapses. Adverse outcome (stage 4-5 CKD or death) was seen in 36 at 3 months and 41 by last follow up, with relapse in 14 of 122 available children. Significant independent risk factors for adverse outcome were an antibody titer over 8000 AU/ml, low C3 and delay in plasma exchange. Combined plasma exchanges and induction immunosuppression resulted in significantly improved renal survival: one adverse outcome prevented for every 2.6 patients treated. Maintenance immunosuppressive therapy, of prednisolone with either mycophenolate mofetil or azathioprine, significantly reduced the risk of relapses. Thus, prompt use of immunosuppressive agents and plasma exchanges are useful for improving outcomes in pediatric patients with anti-complement factor H-associated HUS.

Topics: Age Factors; Antibodies, Monoclonal, Murine-Derived; Autoantibodies; Azathioprine; Biomarkers; Blood Proteins; Case-Control Studies; Child; Child, Preschool; Combined Modality Therapy; Complement C3b Inactivator Proteins; Cyclophosphamide; Drug Therapy, Combination; Female; Gene Deletion; Hemolytic-Uremic Syndrome; Homozygote; Humans; Immunosuppressive Agents; India; Infant; Male; Mycophenolic Acid; Plasma Exchange; Prednisolone; Recurrence; Risk Factors; Rituximab; Time Factors; Time-to-Treatment; Treatment Outcome

To investigate the clinical characteristics, renal pathology, treatment and prognosis of children with atypical hemolytic uremic syndrome associated with H factor antibody.. Four children less than 18 yr of age admitted from Nov. 2010 to May 2011 in Peking University First Hospital were included. They all met the criteria for atypical hemolytic uremic syndrome and with positive serum anti factor H antibody. They aged from 5 to 11 yr. Data on clinical manifestations, renal pathology, treatment and prognosis were analyzed.. All of the 4 cases had gastrointestinal symptoms such as vomiting, abdominal pain, or abdominal distension. None of them had diarrhea. Two children had hypertension. One child had episodes of convulsion. One child had history of atypical hemolytic uremic syndrome. All of them had low serum complement C3. Three of them had low serum factor H (38.0, 88.4, 209.4 mg/L). All of them had serum antibody to factor H (1: 7 068, 1: 1 110, 1: 174, and 1: 869). Three of them received renal biopsy, all of them showed thrombotic microangiopathy. All of them were treated with steroid combined with mycophenolate mofetil. Two children received plasma exchange. They were followed up for 8 to 29 months. The renal function became normal and proteinuria relieved in all of them. The serum factor H concentration increased to 405.8, 155.8 and 438.4 mg/L, respectively. The titer of anti factor H antibody decreased to 1: 119, 1: 170, 1: 123, and 1: 674, respectively.. Gastrointestinal symptom is common in children with atypical hemolytic uremic syndrome associated with H factor antibody. Hypocomplementemia was observed in all of them. Steroid combined with mycophenolate mofetil seemed to be effective for them. The monitoring of serum factor H and antibody to factor H may help diagnosis and treatment.

Topics: Atypical Hemolytic Uremic Syndrome; Autoantibodies; Child; Child, Preschool; Complement Factor H; Creatinine; Female; Hemolytic-Uremic Syndrome; Humans; Kidney; Kidney Function Tests; Male; Mycophenolic Acid; Plasma Exchange; Prednisolone; Prognosis; Retrospective Studies

Dysregulation of complement activation is the most common cause of the atypical haemolytic uraemic syndrome (aHUS). Many patients with aHUS develop end-stage renal disease and consider kidney transplantation. However, the recurrence rate after transplantation ranges from 45-90% in patients with known abnormalities in circulating complement proteins. It was recently proposed that patients with aHUS should be treated prophylactically with plasma exchange or eculizumab to prevent recurrence after transplantation.. A case series describing the successful outcome of kidney transplantation without prophylactic therapy in four adult patients with aHUS and a high risk of disease recurrence. Patients received a living donor kidney and immunosuppression consisting of basiliximab induction, low-dose tacrolimus, prednisone and mycophenolate mofetil. Patients received a statin, and were targeted to a low blood pressure preferably using blockers of the renin-angiotensin system.. After a follow-up of 16-21 months, none of the patients developed recurrent aHUS. Also, no rejection was observed.. Kidney transplantation in adult patients with aHUS can be successful without prophylactic eculizumab, using a protocol that minimises cold ischaemia time, reduces the risk of rejection and provides endothelial protection. Our data suggest that in patients with aHUS, controlled trials are needed to demonstrate the optimal strategy.

Topics: Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Atypical Hemolytic Uremic Syndrome; Basiliximab; Cold Ischemia; Drug Therapy, Combination; Female; Hemolytic-Uremic Syndrome; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prednisone; Recombinant Fusion Proteins; Secondary Prevention; Tacrolimus; Young Adult

We report successful kidney transplantation in a 10-yr-old boy with aHUS and heterozygous factor H mutation using the terminal complement inhibitor eculizumab to avoid recurrence of aHUS in the renal graft. Vaccination against meningococcus C (Men C) is essential in patients with dysfunction of the complement system, as induced by eculizumab. In our patient, we report waning SBA titers but maintenance of protective SBA titers (≥1:8) after kidney transplantation under immunosuppressive therapy with mycophenolate mofetil, tacrolimus, steroids, and eculizumab over a 27-month observational period. Our case illustrates that a humoral immune response to conjugate Men C vaccination may be mounted and maintained despite chronic renal disease, kidney transplantation, immunosuppressive drugs, and immunomodulatory therapy with eculizumab. However, it remains unclear whether serologically defined protective SBA titers mediate true protection from invasive meningococcal disease in an immunocompromised patient, particularly under treatment with a complement inhibitor. Thus, close monitoring of SBA titers seems mandatory in this patient.

Topics: Antibodies; Antibodies, Monoclonal, Humanized; Atypical Hemolytic Uremic Syndrome; Child; Complement Factor H; Complement Inactivating Agents; Hemolytic-Uremic Syndrome; Heterozygote; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Meningococcal Infections; Meningococcal Vaccines; Mutation; Mycophenolic Acid; Neisseria meningitidis; Peritoneal Dialysis; Recurrence; Renal Insufficiency; Steroids; Tacrolimus; Time Factors

Systemic lupus erythematosus (SLE) has been described as a cause of thrombotic microangiopathy, especially thrombotic thrombocytopenic purpura (TTP). Haemolytic-uraemic syndrome (HUS) is less frequent in SLE. We report a case of such an association during an episode of severe lupus nephritis in a young woman, who was successfully treated with steroids, cyclophosphamide and especially plasma exchange with plasma replacement. This report highlights the importance of recognising atypical HUS in SLE patients by looking for schistocytes in case of haemolytic anemia with a negative antiglobulin test, in order to begin plasma exchange.

Topics: Acute Kidney Injury; Adult; Biopsy; Combined Modality Therapy; Cyclophosphamide; Drug Therapy, Combination; Erythrocytes, Abnormal; Female; Hemolytic-Uremic Syndrome; Humans; Hydroxychloroquine; Immunosuppressive Agents; Kidney; Lupus Nephritis; Methylprednisolone; Models, Immunological; Mycophenolic Acid; Plasma Exchange; Prednisone

A 34-year old male renal transplant recipient developed thrombotic microangiopathy (Hemolytic Uremic Syndrome) in the early post-transplant period following combined immuno-suppressive therapy with tacrolimus and everolimus. The management consisted of discontinuation of tacrolimus and substitution with mycophenolate mofetil. His renal functions improved, the hematological abnormalities reversed and he continues to have good graft function one year later.

Topics: Adult; Biopsy; Drug Therapy, Combination; Everolimus; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Prodrugs; Sirolimus; Tacrolimus

Among the numeruos adverse side effects of tacrolimus (TAC), de novo thrombotic microangiopathy stands out as an infrecuente but severe complication. Renal dysfunction is the only alteration that should lead to suspicion of thrombotic microangiopathy, because the clinical features of intravascular hemolysis are not always found. The definitive diagnosis can usually be made with kidney biopsy. Patientes with TAC induced thrombotic microangiopathy usually promptly recover after treatment withdrawal or reduction in the dose of TAC and a short course of plasma therapy, but the risk of rejection increases. Switching from TAC to cyclosporine has also been tried with resolution of the hemolysis but thrombotic microangiopathy has been noted with both and this condition may later recur. We present a 29-year-old man who received a kidney-pancreas transplant for end-stage diabetic nephropathy. After initial induction with basiliximab, the immunosuppression consisted of prednisone, tacrolimus and mycophenolate mofetil. Twenty four days posttransplantation his renal function declined with a peak creatine level of 2.35 mg/dl. Laboratory studies showed thrombocytopenia and features of intravascular hemolysis. TAC associated hemolytic uremic syndrome was suspected and drug was immediately stopped and converted to sirolimus. Also he was treated with plasma infusion. The allograft biopsy showed focal glomerular and arteriolar acute thrombosis without evidence of rejection. Our experience demostrate that switching from tacrolimus to sirolimus could be an adecuate strategy for patients who develop FK506-associated de novo thrombotic microangiopathy without increase risk of acute rejection.

Topics: Adult; Antibodies, Monoclonal; Basiliximab; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Drug Therapy, Combination; Duodenostomy; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Jejunostomy; Kidney Failure, Chronic; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Male; Mycophenolic Acid; Pancreas Transplantation; Pancreatic Fistula; Plasma; Postoperative Complications; Prednisone; Recombinant Fusion Proteins; Sirolimus; Tacrolimus

Topics: Child; Cyclosporine; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Postoperative Complications

Topics: Child, Preschool; Drug Therapy, Combination; Female; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Recurrence; Transplantation, Homologous

Topics: Adult; Biopsy; Creatinine; Cyclosporine; Female; Graft Rejection; Hemoglobins; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Platelet Count; Postoperative Complications

Topics: Adult; Creatinine; Cyclosporine; Edema; Female; Follow-Up Studies; Hemolytic-Uremic Syndrome; Hemorrhage; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Optic Nerve; Time Factors

Topics: Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid