tacrolimus and Hemolytic-Uremic-Syndrome

Pulmonary alveolar proteinosis (PAP) has been associated with the immunosuppressant sirolimus in transplant patients. PAP is a progressive lung disease characterized by the accumulation of surfactant-like material in the lungs leading to decreased pulmonary function with shortness of breath and cough as common symptoms. We report a rare case of sirolimus-associated PAP in a kidney transplant recipient with a history of end-stage renal disease secondary to haemolytic uraemic syndrome (HUS) and review of the literature. Discontinuation of sirolimus and initiation of tacrolimus led to resolution of PAP without recurrence of HUS.

Topics: Female; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Pulmonary Alveolar Proteinosis; Recurrence; Sirolimus; Tacrolimus

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

Thrombotic microangiopathy (TMA) is a rare but potentially lethal complication encountered in solid organ and bone marrow transplant recipients, requiring rapid recognition, diagnosis, and initiation of therapy. Several potential causes have been identified in this setting, including viral infections and medications.. We report a case of TMA in a liver transplant recipient with active cytomegalovirus (CMV) gastritis. A 41-year-old female presented 3 months after liver transplantation with a 5-week history of nausea, vomiting, anorexia, and diarrhea. CMV serology was donor seropositive and recipient seronegative (D+/R-). The immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, and prednisone. Evaluation revealed CMV viremia with a high viral load and intravenous ganciclovir was started. A decline in hemoglobin and platelets with an increase in lactate dehydrogenase (LDH) warranted hematologic evaluation, which revealed findings consistent with microangiopathic hemolytic anemia. Ganciclovir and tacrolimus were discontinued. Intravenous immunoglobulin was administered and daily plasmapheresis was initiated. As the patient's blood counts and LDH started to improve, ganciclovir was cautiously reinstituted. The patient's gastrointestinal symptoms gradually resolved and her blood counts continued to improve with prolonged plasmapheresis (a total of 23 plasmapheresis sessions). Tacrolimus and possibly CMV infection were suspected to be the cause for her TMA, and cyclosporine was substituted.. TMA is an important entity in the differential diagnosis of acute hemolytic anemia in liver transplant recipients. Many cases seem to be medication-induced. However, in treatment-resistant or relapsing cases, a possibility of concomitant CMV infection should be considered.

Topics: Adult; Cytomegalovirus; Cytomegalovirus Infections; Female; Gastritis; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Liver Transplantation; Purpura, Thrombotic Thrombocytopenic; Tacrolimus

Hemolytic-uremic syndrome (HUS) is a rare, but well-described complication in organ transplant recipients maintained on cyclosporine immunosuppression. Tacrolimus is a newer agent with similar immunosuppressant efficacy. In cases of cyclosporine-related HUS in renal transplant recipients, tacrolimus has been used successfully without recurrence of HUS. Tacrolimus has been reported to cause HUS in renal and more recently in cardiac transplant patients. We report a case of HUS in a lung transplant recipient receiving tacrolimus who was subsequently converted to cyclosporine without recurrence of HUS.

Topics: Cyclosporine; Female; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Lung Transplantation; Middle Aged; Postoperative Complications; Tacrolimus

Topics: Cyclosporine; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Renal Circulation; Tacrolimus; Vasoconstriction

Acute and chronic nephrotoxicity frequently limits the therapeutic benefits of immunosuppressive therapy for transplant and autoimmune indications. The clinical aspects, pathophysiology, and relevant pharmacology of current and future immunosuppressive drugs are reviewed in this paper. Insights gained from experimental models of chronic nephrotoxicity associated with tubulointerstitial fibrosis are presented.

Topics: Acute Kidney Injury; Animals; Cyclosporins; Hemolytic-Uremic Syndrome; Humans; Hypertension; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Polyenes; Sirolimus; Tacrolimus

Several drugs including antineoplastic drugs and immunosuppressant can induce hemolytic uremic syndrome. Mitomycin C are well known to cause cancer associated HUS, and its frequency are reported to be 4-15%. Noncardiogenic pulmonary edema frequently ( > 50%) develops, especially after blood transfusion, among MMC induced HUS. Cancer associated HUS has a high mortality and no effective therapy has been established. Combination of vinblastin and bleomycin also induces HUS. Cisplatin, one of the most frequently used antineoplastic drugs, also induces HUS. Cyclosporin causes HUS, probably due to endothelial damage and/or an inhibition of prostacyclin synthesis. A case of FK506 induced HUS has been recently reported. Quinine and Cocaine also can induce HUS. Prognosis of cancer associated HUS is quite poor, whereas Quinine and Cocaine induced HUS may resolve.

Topics: Cisplatin; Cocaine; Cyclosporine; Hemolytic-Uremic Syndrome; Heparin; Humans; Mitomycin; Plasma Exchange; Platelet Aggregation Inhibitors; Quinine; Tacrolimus

Five patients with cyclosporin-related haemolytic uraemic syndrome (HUS) following cadaveric renal transplantation were converted from cyclosporin- to tacrolimus-based immunosuppression. All patients had biochemical, haematological and biopsy evidence of HUS at the time of conversion. Four of the patients showed complete resolution of the syndrome within 1 week of conversion with normalisation of haemoglobin, platelets and lactate dehydrogenase levels. In the fifth patient renal function stabilised with slow resolution of the haematological and biochemical parameters. Four of the five patients are still taking tacrolimus, one having converted back to cyclosporin due to marked hair loss. We conclude that conversion to tacrolimus appears to be an effective treatment for cyclosporin-related HUS following renal transplantation.

Topics: Adult; Cyclosporine; Female; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Tacrolimus

Topics: Adolescent; Adult; Child; Child, Preschool; Cyclosporine; Follow-Up Studies; Hemolytic-Uremic Syndrome; Humans; Infant; Kidney Transplantation; Tacrolimus; Time Factors; Treatment Outcome

HUS is a well-known entity primarily associated with bacterial infection and is characterized by a classic triad of anemia, thrombocytopenia, and kidney injury. Its atypical form has been associated with calcineurin inhibitors and has been extensively discussed in renal transplantation. We present a case of tacrolimus-associated HUS in a pediatric heart transplant recipient, which we believe to be previously unreported in the literature.

Topics: Child, Preschool; Female; Heart Transplantation; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Postoperative Complications; Tacrolimus

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

Renal transplantation is the optimal treatment for suitable patients with end-stage renal disease (ESRD). However, acute graft dysfunction occurs in 5%-35% of patients. This is commonly due to acute rejection, drug toxicity, ureteric obstruction, or infection. Atypical hemolytic uremic syndrome (aHUS), either recurrent or de novo, is uncommon after transplantation.. We highlight three cases of acute transplant dysfunction in which transplant biopsy revealed HUS without associated clinical or hematologic clues to the etiology. Two cases had recurrent HUS and 1 had de novo HUS secondary to tacrolimus therapy. Screenings for ADAMTS-13 and gene mutations of complement regulatory proteins were negative. Thrombocytopenia and red blood cell fragments on blood film appeared some days later.. Treatment comprised a combination of plasma exchange with fresh-frozen plasma and switching immunosuppressive therapy, which led to the recovery of the above hematologic features but salvaged graft function in only 1 case.. Classical hematologic findings of HUS appeared late in these cases. HUS should be considered in cases of allograft dysfunction where there is no obvious cause, and biopsy should be performed. This enables early initiation of therapy to gain rapid recovery of hematologic parameters and potentially of transplant function.

Topics: Adolescent; Adult; Female; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Tacrolimus

Topics: Adult; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Postoperative Complications; Tacrolimus

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

A 33-year-old woman with a history of chronic transplant dysfunction because of repeated bouts of haemolytic uraemic syndrome (HUS) was considered for a second transplant. Extensive genetic investigation of the complement system was executed to rule out known mutations prone to development of HUS. This case illustrates the importance of genetic screening in patients with recurrent HUS.

Topics: Adult; Atypical Hemolytic Uremic Syndrome; Complement Factor H; Disease Progression; Female; Hemolytic-Uremic Syndrome; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Plasma Exchange; Reoperation; Tacrolimus; Unrelated Donors

To report our experience of a rather uncommon drug interaction, resulting in hemolytic uremic syndrome (HUS).. Two consecutive cases of hemolytic uremic syndrome were diagnosed in our service. In both patients the use of macrolides in patients taking Tacrolimus, resulted in high levels of Tacrolimus.. The first patient was a 48 years old female with Bilateral emphysema. She underwent Single Sequential Lung Transplantation. She developed reperfusion injury requiring prolonged stay. Tacrolimus introduced (Day 51). The patient remained well up till 5 months later; Erythromycin commenced for chest infection. High Tacrolimus levels and a clinical diagnosis of HUS were made. She was treated with plasmapheresis successfully. The second case was a 57 years old female with Emphysema & A1 Antithrypsin deficiency. She underwent Right Single Lung Transplantation. A2 rejection with mild Obliterative Bronchiolitis diagnosed 1 year later and she switched to Tacrolimus. She was admitted to her local Hospital two and a half years later with right middle lobe consolidation. The patient commenced on amoxicillin and clarithromycin. Worsening renal indices, high Tacrolimus levels, hemolytic anemia & low Platelets were detected. HUS diagnosed & treated with plasmapheresis.. There are 21 cases of HUS following lung transplantation in the literature that may have been induced by high tacrolimus levels. Macrolides in patients taking Cyclosporin or Tacrolimus lead to high levels. Mechanism of action could be glomeruloconstrictor effect with reduced GFR increased production of Endothelin-1 and increased Platelet aggregation.

Topics: Drug Interactions; Female; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Lung Transplantation; Macrolides; Middle Aged; Pulmonary Emphysema; Tacrolimus

Acute renal failure (ARF) is an uncommon complication in children with nephrotic syndrome. We report here the case of a 10-year-old male child with primary steroid-resistant nephrotic syndrome who was non-responsive to steroids and cyclophosphamide. A kidney biopsy revealed that he had focal segmental glomerulosclerosis. His treatment was initiated with tacrolimus (dose of 0.15 mg/kg/day) in two divided doses along with prednisolone 60 mg/m(2)/daily. After 1 month of treatment, he was diagnosed as having acute renal failure secondary to HUS. This was postulated to be due to the tacrolimus therapy, which was withdrawn. Two weeks after stopping the adminsitration of tacrolimus, his urine output improved, and the hemoglobin and serum creatinine normalized. Thus, tacrolimus-induced HUS is a rare cause of ARF in nephrotic syndrome. With the increasing use of tacrolimus in steroid-resistant nephrotic syndrome, the treating physicians need to be aware of this rare, but potentially life-threatening side effect.

Topics: Acute Kidney Injury; Biopsy; Child; Drug Resistance; Glomerulosclerosis, Focal Segmental; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney; Male; Nephrotic Syndrome; Steroids; Tacrolimus

Hemolytic uremic syndrome (HUS) is a rare complication following solid organ transplantation. We report on a patient who underwent renal transplantation using Campath-1H induction and tacrolimus maintenance therapy who developed HUS, which was managed by plasma exchange and switch to Rapamycin. However, graft function could not be restored.

Topics: Adult; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Plasma Exchange; Sirolimus; Tacrolimus

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

Thrombotic microangiopathy (TMA), a microvascular hemolytic disorder is a rare, but well described complication in organ transplant patients receiving immunosuppressant drugs. We report a 56-year-old female with a history of left lung transplant that presented to the hospital with microangiopathic hemolytic anemia and thrombocytopenia while receiving tacrolimus (FK 506) for 36 months. The patient was diagnosed with tacrolimus-induced TTP/HUS and started on daily plasmapheresis, and replacement of FK506 with cyclosporine. After thirteen plasmapheresis procedures, her platelet count, lactate dehydrogenase, and hematocrit were normalized. The ADAMTS-13 activity was subnormal and no inhibitory antibody was detected. The combination of daily plasmapheresis with fresh frozen plasma as a source of ADAMTS-13 and cyclosporine may be used as a rescue therapy in patients with FK506-induced TTP/HUS.

Topics: ADAM Proteins; ADAMTS13 Protein; Cyclosporine; Female; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Lung Transplantation; Middle Aged; Plasmapheresis; Purpura, Thrombotic Thrombocytopenic; Tacrolimus

Topics: Adult; Complement C4b; Diagnosis, Differential; Female; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Immunohistochemistry; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Peptide Fragments; Purpura, Thrombotic Thrombocytopenic; Tacrolimus; Transplantation, Homologous

Topics: Child; Cholangitis, Sclerosing; Escherichia coli Infections; Esophageal and Gastric Varices; Female; Gastritis; Gastrointestinal Hemorrhage; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Liver Failure; Liver Transplantation; Postoperative Complications; Tacrolimus

Hemolytic-uremic syndrome (HUS) is a rare complication occurring in solid-organ and bone marrow transplant recipients treated with calcineurin inhibitors cyclosporine or tacrolimus. We report here about a 30-year-old female cadaveric renal transplant recipient receiving cyclosporine who developed HUS in the early post-transplant period. Renal allograft biopsy specimens showed the characteristic features of thrombotic microangiopathy and acute cyclosporine nephrotoxicity. Cyclosporine was discontinued and the patient was switched to tacrolimus in conjunction with plasma exchange. Unfortunately, plasma exchange was interrupted by bleeding complication resulting from placement of double-lumen catheter. Intravenous immunoglobulin (IVIG) was then administrated as an alternative therapy. Hematological resolution occurred promptly and renal function recovered uneventfully. Our presenting case suggests the beneficial effect of IVIG on cyclosporine-associated HUS.

Topics: Adult; Cyclosporine; Female; Hemolytic-Uremic Syndrome; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Transplantation; Plasma Exchange; Tacrolimus

Complement factor H (FH) deficiency is one of the causes of atypical hemolytic uremic syndrome (HUS). Most patients with FH deficiency associated HUS progress to end-stage renal disease despite plasma therapy. Moreover, the disease invariably recurs in the graft kidney and causes graft failure. We confirmed FH deficiency in a 30-month-old boy with recurrent HUS of 2 years duration, and attempted an auxiliary partial orthotopic liver transplantation (APOLT) to overcome the sustained intractable dependency on plasma therapy. APOLT restored the plasma FH level, without HUS recurrence, for 7 months. However, thereafter he suffered from serious infectious complications associated with immunosuppression and finally died 11 months after APOLT. In conclusion, although APOLT showed clinical and laboratory improvement for some period in this patient, the final fatal outcome suggests that liver transplantation should be cautiously applied to patients with HUS associated with FH deficiency.

Topics: Bacterial Infections; Blotting, Western; Child, Preschool; Complement Factor H; Epstein-Barr Virus Infections; Fatal Outcome; Hemolytic-Uremic Syndrome; Humans; Immunocompromised Host; Immunosuppressive Agents; Infant; Liver Failure; Liver Transplantation; Lymphoproliferative Disorders; Male; 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: Adult; Angiography; Angioplasty, Balloon; Cyclosporine; Female; Fibrinolytic Agents; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Recombinant Proteins; Renal Artery; Renal Artery Obstruction; Retreatment; Tacrolimus; Thrombosis; Tissue Plasminogen Activator

Topics: Blood Pressure; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Pulse; Tacrolimus

Defective plasma activity of Von Willebrand factor (VWF)-cleaving protease (CP) and/or the inhibitors against this protease has been shown to have a pathological role in several forms of thrombotic microangiopathy (TMA). This report describes a patient for whom a diagnosis of TMA was made immediately after living donor liver transplantation. In this patient, activity of VWF-CP and its inhibitor were analyzed serially. At the onset of the disease, VWF-CP activity was quantified as 17%. Inhibitor against this protease was positive, with a titer of 0.6 Bethesda U/mL, and its inhibitory activity was quantified as 3.8 Bethesda U/mg immunoglobulin G. Laboratory parameters and clinical features were significantly improved after induction of plasma exchange (PE) with fresh frozen plasma and concurrent cessation of tacrolimus therapy. The inhibitors disappeared after one session of PE. However, VWF-CP activity after a transient increase and again decreased to subnormal levels after completion of PE. Nevertheless, this did not result in disease recurrence. In view of sustained VWF-CP activity at disease onset and the absence of definite correlations between levels of this protease and clinical features, abnormality of this enzyme system had no essential role in the pathogenesis of TMA in this case. Clinical findings suggest that TMA was tacrolimus-induced.

Topics: ADAM Proteins; ADAMTS13 Protein; Adult; Female; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Liver Failure; Liver Transplantation; Living Donors; Metalloendopeptidases; Plasma Exchange; Postoperative Period; Purpura, Thrombotic Thrombocytopenic; Tacrolimus; von Willebrand Factor

Topics: Adult; Cytomegalovirus Infections; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Sirolimus; Tacrolimus

Hemolytic uremic syndrome (HUS) is a rare complication in solid organ transplantation. It can be associated with severe hypertension. Several risk factors have been identified including immunosuppressive drugs such as cyclosporin A and, more recently, tacrolimus.. Here we report a case of tacrolimus-induced HUS in a 61-yr-old woman after liver transplantation. Hypertension, microangiopathic anemia and end-stage renal failure occurred 2 yr after liver transplantation.. At admission, she had malignant hypertension with a severe hypertensive retinopathy, renal failure (creatininemia: 800 micromol/L) and microangiopathic anemia (Hb: 7.3 g/dL, a low platelet count and elevated lactate dehydrogenase). At renal biopsy, histologic findings were ischemic and sclerotic glomeruli with hyaline thrombi, severe mesangiolysis and interstitial fibrosis.. Despite steroid treatment, antihypertensive agents and fresh frozen plasma therapy, end-stage renal failure was observed and chronic hemodialysis treatment was required.

Topics: Female; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Liver Transplantation; Middle Aged; Tacrolimus

This retrospective study describes the outcome in 53 patients who had immunosuppressive treatment changed from cyclosporine (CSP) to tacrolimus for resistant acute GVHD (n = 23), hemolytic uremic syndrome (HUS) (n = 13) or CSP-associated neurotoxicity (n = 17). Tacrolimus was administered at doses of 0.03 mg/kg/day intravenously or 0.12 mg/kg/day orally in divided doses, as tolerated. Median time of conversion to tacrolimus after transplant was day 47. Nineteen patients had treatment changed to tacrolimus for resistant acute GVHD grades III or IV, with the median day of conversion being day 49 after transplant. Two of 20 evaluable patients had a complete resolution of GVHD after changing treatment to tacrolimus, with 18 showing no improvement. Eleven evaluable patients had therapy changed to tacrolimus for CSP-associated neurotoxicity at a median of 36 days after transplant. Eight patients had resolution of neurotoxicity and three had partial improvement. Eleven evaluable patients had therapy changed to tacrolimus for HUS at a median of 46 days after transplant. One patient had complete resolution of HUS and 10 showed no response. Side-effects related to tacrolimus included renal toxicity (34%), neurotoxicity (15%) and HUS (9%). Nine (17%) patients remain alive, including six patients who had therapy changed to tacrolimus for CSP-associated neurotoxicity. While often successful for dealing with neurotoxicity, only a rare patient improved after therapy was changed from CSP to tacrolimus for HUS or resistant acute GVHD.

Topics: Acute Disease; Adolescent; Adult; Bone Marrow Transplantation; Child; Child, Preschool; Cyclosporine; Drug Resistance; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney Diseases; Male; Middle Aged; Peripheral Nervous System Diseases; Retrospective Studies; Tacrolimus; Transplantation, Homologous; Treatment Outcome

Hemolytic-uremic syndrome (HUS) is a well-recognized complication of cyclosporine (CyA) therapy. Transplant recipients with this complication are frequently switched to tacrolimus, although this drug has also been implicated. We report a case of a renal transplant recipient who developed severe graft dysfunction due to biopsy-proven HUS after receiving CyA. Renal function and hemolytic parameters improved with discontinuation of the drug, but they deteriorated again after commencement of tacrolimus 15 days later. A second transplant biopsy demonstrated fresh lesions diagnostic of HUS. Hemolytic parameters resolved with discontinuation of tacrolimus. This is the first report of metachronous HUS being caused in a renal transplant by both CyA and tacrolimus. We therefore believe that caution should be exercised when using tacrolimus as rescue therapy in patients with CyA-induced HUS.

Topics: Biopsy; Cyclosporine; Endothelium, Vascular; Epoprostenol; Female; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Interleukin-2; Kidney; Kidney Transplantation; Middle Aged; Phosphoric Monoester Hydrolases; Polycystic Kidney, Autosomal Dominant; Postoperative Complications; Recurrence; Tacrolimus

Topics: Acute Kidney Injury; Administration, Oral; Adult; Anti-Inflammatory Agents; Cortisone; Drug Resistance; Female; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Tacrolimus; Transplantation, Homologous

Topics: Animals; Hemolytic-Uremic Syndrome; Immunosuppressive Agents; Insulin; Islets of Langerhans; Kidney; Macaca mulatta; Pancreas; Tacrolimus; Tremor

A case of tacrolimus (FK 506)-induced hemolytic uremic syndrome is reported. The direct implication of tacrolimus, an alternative immunosuppressant to cyclosporine, was strongly supported by the recurrence of the syndrome after a second exposure to the treatment.

Topics: Cardiomyopathy, Dilated; Graft Rejection; Heart Transplantation; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Male; Middle Aged; Postoperative Complications; Recurrence; Tacrolimus

Posttransplant hemolytic uremic syndrome (pHUS) is a rare but severe disorder that confers a poor prognosis on an allograft due to thrombotic microangiopathy. Immunosuppression with cyclosporine (CsA) is implicated as a significant risk factor for the development of pHUS. In early reports, it was hypothesized that immunosuppression with FK506 (tacrolimus) would avoid the development of pHUS. However, this initially supposed beneficial effect remains controversial, because pHUS associated with tacrolimus therapy has been published in some later case reports. This article aims to further evaluate FK506 with respect to the development and resolution of pHUS.. We describe the course of seven adult kidney graft recipients with pHUS, treated with FK506 either as initial immunosuppression for retransplantation or after discontinuation of CsA for resolution of pHUS. Work-up for pHUS was initiated when certain clinical features, such as hemolytic anemia, thrombocytopenia, and deterioration of graft function, were found. The diagnosis was confirmed by histologic examination of a renal allograft biopsy specimen (thrombotic microangiopathy). With the onset of pHUS, additional plasma exchange was performed in all patients.. Two patients suffered from end-stage renal disease due to primary HUS and had a history of recurrent pHUS in previous renal transplants. In both patients, the attempt to regraft was only made because of the early optimistic reports using FK506. Despite initial FK506 therapy, both recipients developed pHUS again, leading to loss of graft function. Two additional kidney graft recipients with primary renal failure other than HUS also received FK506 as initial immunosuppression. One of them (loss of the first kidney graft due to CsA-induced pHUS) was successfully treated with FK506 for his second renal transplant. The other recipient, a patient in whom de novo pHUS had occurred in the first graft despite initial therapy with FK506, was treated with CsA for his second graft and again developed pHUS. The latter process, however, could be reversed by a switch to steroids and azathioprine. In all three patients regrafted for reasons other than pHUS, development of de novo pHUS was treated by CsA withdrawal and a switch to FK506; this approach was effective in two patients.. Our results demonstrate that three of seven renal allograft recipients benefited from FK506 therapy for prevention or resolution of pHUS. Treatment or prophylaxis with FK506 can be considered advantageous in some patients with de novo pHUS, but FK506 fails to prevent recurrent pHUS in patients with primary HUS.

Topics: Adult; Biopsy; Creatinine; Female; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Middle Aged; Reoperation; Tacrolimus

Topics: Female; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Ischemia; Kidney; Kidney Transplantation; Middle Aged; Muromonab-CD3; Postoperative Complications; Tacrolimus

Topics: Creatinine; Cyclosporine; Female; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Kidney Transplantation; Middle Aged; Tacrolimus

Topics: Adult; Cyclosporine; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Kidney Transplantation; Male; Pancreas Transplantation; Tacrolimus

We describe a patient who received a living related kidney transplant that worked very well initially but developed oliguria and renal failure within 1 week and required dialysis. Clinical and hemological changes, as well as renal biopsy, confirmed the diagnosis of cyclosporin-induced hemolytic uremic syndrome. The patient did not respond to antirejection therapy or plasma exchange but did respond to the withdrawal of cyclosporin A and the commencement of FK 506.

Topics: Adult; Cyclosporine; Female; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Kidney Failure, Chronic; Kidney Transplantation; Tacrolimus

Topics: Adult; Bone Marrow Transplantation; Female; Graft vs Host Disease; Hemolytic-Uremic Syndrome; Humans; Tacrolimus

Topics: Adult; Child; Child, Preschool; Cyclosporine; Female; Hemolytic-Uremic Syndrome; Humans; Infant; Kidney; Kidney Transplantation; Tacrolimus; Thrombocytopenia; Treatment Outcome

Topics: Adult; Azathioprine; Biopsy; Creatinine; Female; Ganciclovir; Hemolytic-Uremic Syndrome; Humans; Kidney Transplantation; Prednisone; Tacrolimus

Topics: Anti-Bacterial Agents; Drug Evaluation; Hemolytic-Uremic Syndrome; Humans; Immunosuppressive Agents; Tacrolimus