losartan-potassium and Hemolytic-Uremic-Syndrome

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

Large and unusually large von Willebrand factor (vWf) multimers may be responsible for systemic platelet aggregation in thrombotic thrombocytopenic purpura (TTP). This possibility is supported by studies that show deficient vWf-cleaving metalloproteinase and increased platelet-vWf binding during TTP episodes. In acute idiopathic TTP, decreased vWf metalloproteinase is the result of autoantibodies against the enzyme. In familial and acquired hemolytic-uremic syndrome, vWf-cleaving metalloproteinase activity is normal. A deficiency or defect in factor H, which normally dampens the activation of C3 via the alternative complement pathway, has been seen in some patients with familial hemolytic-uremic syndrome. Ticlopidine therapy is an important risk factor for TTP.

Topics: Anti-Bacterial Agents; Child; Diagnosis, Differential; Erythropoietin; Hemolytic-Uremic Syndrome; Humans; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Survival Analysis; Ticlopidine

Topics: Adenosine Triphosphate; Biological Transport, Active; Blood Cells; Blood Platelets; Erythrocyte Aging; Erythrocytes; Erythropoietin; Glomerular Filtration Rate; Guanidines; Hemolysis; Hemolytic-Uremic Syndrome; Humans; Kidney; Kidney Glomerulus; Lymphocytes; Osmotic Fragility; Sodium; Succinates; Urea

The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) is uncertain.. We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events.. Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded.. In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted.. ClinicalTrials.gov identifier: NCT03776851. A higher resolution version of the Graphical abstract is available as Supplementary information.

Topics: Anemia; Child; Epoetin Alfa; Erythropoietin; Hemoglobins; Hemolytic-Uremic Syndrome; Humans; Pilot Projects; Recombinant Proteins; Renal Dialysis

Childhood hemolytic uremic syndrome (HUS) is most often caused by enterohemorrhagic Escherichia coli (EHEC). Due to severe hemolysis, red blood cell (RBC) transfusions are often necessary, and anemia is aggravated by low erythropoietin (EPO) levels caused by acute renal failure. In a single center, prospective study, we randomized ten children with EHEC-positive HUS into two therapeutic groups: one receiving EPO treatment (median age 2 years, age range 1-3 years) and the other receiving standard therapy (median age 2 years, age range 1-6 years). Red blood cell transfusions were performed when the hemoglobin level (Hb) fell below 5 mg/dl. The number of RBC transfusions was compared in both groups. The Hb level at admission was comparable between both groups (6.4 vs. 8.1 mg/dl, P > 0.05, t-test). However, children in the EPO group required a significantly lower mean number of RBCs than those in the non-EPO group (0.2 vs. 1.4, P < 0.04, t-test). Based on these results, we suggest that the early administration of EPO at the time of hemolytic anemia and beginning renal failure may attenuate renal anemia in children with EHEC-induced HUS and thereby reduce the number of RBC transfusions required. The results of this pilot study will have to be confirmed in a larger multicenter trial.

Topics: Anemia, Hemolytic; Child; Child, Preschool; Erythrocyte Transfusion; Erythropoietin; Hemolytic-Uremic Syndrome; Humans; Infant; Pilot Projects; Prospective Studies; Recombinant Proteins

Topics: Animals; Cytokine Receptor Common beta Subunit; Erythropoietin; Hemolytic-Uremic Syndrome; Humans; Mice; Oligopeptides; Receptors, Erythropoietin; Shiga Toxins; Shiga-Toxigenic Escherichia coli; Swine

Although erythropoietin (EPO) deficiency has been reported in children with post-diarrheal hemolytic uremic syndrome (D + HUS), very limited clinical data on EPO use in this disease are currently available. In this case-control study we examined whether EPO administration would reduce the number of red blood cell (RBC) transfusions in D + HUS patients under our care.. Data from children treated exclusively with RBC transfusions (controls; n = 21) were retrospectively compared with data on those who also received EPO for the treatment of anemia (cases; n = 21).. Both patient groups were similar in age (p = 0.9), gender (p = 0.12), weight (p = 1.00) and height (p = 0.66). Acute phase severity was also comparable, as inferred by the need for dialysis (p = 0.74), the duration of dialysis (p = 0.3), length of hospitalization (p = 0.81), presence of severe bowel (p = 1.00) or neurological injury (p = 0.69), arterial hypertension (p = 1.00) and death (p = 1.00). No differences in the hemoglobin level at admission (p = 0.51) and discharge (p = 0.28) were noted. Three children treated with EPO and two controls did not require any RBC transfusion (p = 1.00). Median number of RBC transfusions needed by cases and controls was 2 (p = 0.52).. Treatment with EPO did not reduce the number of RBC transfusions in D + HUS children. Assessment of EPO efficacy in D + HUS merits further studies.

Topics: Case-Control Studies; Child; Child, Preschool; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemolytic-Uremic Syndrome; Humans; Infant; Male; Recombinant Proteins; Retrospective Studies

Topics: Aged; Anemia, Hemolytic; Antibodies, Monoclonal, Murine-Derived; Darbepoetin alfa; Delayed Graft Function; Diagnosis, Differential; Erythropoietin; Female; Graft vs Host Disease; Hematinics; Hemolysis; Hemolytic-Uremic Syndrome; Humans; Immunologic Factors; Kidney Failure, Chronic; Kidney Transplantation; Rituximab

Topics: Aged; Anemia; Antimetabolites, Antineoplastic; Chronic Disease; Deoxycytidine; Erythropoietin; Gemcitabine; Hemolytic-Uremic Syndrome; Humans; Liver Neoplasms; Male; Pancreatic Neoplasms; Treatment Failure

Topics: Adenocarcinoma; Adult; Antibiotics, Antineoplastic; Antigens, CD34; Biomarkers; Burkitt Lymphoma; Calcineurin; Endothelium, Vascular; Erythropoietin; Female; Hemolytic-Uremic Syndrome; Humans; Male; Mitomycin; Renal Dialysis; Stomach Neoplasms

Topics: Blood Platelet Disorders; Blood Platelets; Calpain; Caspases; Dialysis; Erythropoietin; Hemolytic-Uremic Syndrome; Humans; Phosphatidylserines; Platelet Activation; Platelet Aggregation; Renal Dialysis; Thrombophilia; Thrombopoiesis; Uremia

Mitomycin C is a powerful antineoplastic agent. If used at high dosage, it may cause a secondary form of adult hemolytic-uremic syndrome (HUS). Blood transfusions worsen the evolution of this peculiar form of HUS. We describe a patient who developed HUS after treatment with mitomycin C (total dose 144 mg/m2) due to a carcinoma of the ascending colon. Repeated blood transfusions were associated with rapidly evolving renal failure coupled with anemia and thrombocytopenia. Haptoglobin was undetectable. Soon after starting subcutaneous erythropoietin, the velocity of progression of renal failure slowed whilst no more blood transfusions were required and haptoglobin levels returned to normal. Thereafter, the patient's renal function slowly worsened and she started chronic hemodialysis 5 years later. Up to now, all investigations have failed to show a relapse of her adenocarcinoma. A possible explanation of these data is that erythropoietin permitted the termination of blood transfusions which both triggered and perpetuated the syndrome. However, we cannot exclude a primitive effect of erythropoietin on the endothelium or on the platelets.

Topics: Antibiotics, Antineoplastic; Colonic Neoplasms; Erythropoietin; Female; Hemolytic-Uremic Syndrome; Humans; Middle Aged; Mitomycin

Serum erythropoietin (EPO) levels were measured in ten previously non-transfused children with hemolytic uremic syndrome (HUS). Complete blood cell count, serum EPO, and renal function tests were carried out upon admission and weekly thereafter. Blood samples were obtained: (1) prior to the first transfusion; (2) after the first transfusion but before recovery from renal failure; (3) during the recovery stage. All patients required transfusions (mean 1.8+/-0.8 per child). Absolute values of EPO correlated positively with the hematocrit during the three stages (r = 0.53, 0.36, and 0.12, respectively) which is opposite to expected results. The observed EPO logarithm/predicted EPO logarithm upon admission was low (0.70+/-0.08), falling further during stage 2 (0.57+/-0.03), but increasing thereafter (0.78+/-0.07) without reaching normal values. The reticulocyte production rate followed a parallel course (0.74+/-0.14, 0.54+/-0.11, and 0.60+/-0.10, respectively). On comparing the observed serum EPO levels with those expected, 9 of 11 pre-transfusion samples showed low values; in stage 2, all samples were below normal; in the recovery phase most (77.8%) were still low. Our results show an inadequate EPO synthesis in children with HUS, which could play an important pathogenic role, since it aggravates the severity of the existing hemolytic anemia; the secondary inhibitory effect of repeated transfusions exacerbates this inadequate synthesis.

Topics: Blood Transfusion; Child, Preschool; Erythropoietin; Hemolytic-Uremic Syndrome; Humans; Infant

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Erythropoietin; Female; Hemolytic-Uremic Syndrome; Humans; Middle Aged; Mitomycin; Tamoxifen

The effect of 6-methylprednisolone (GCC) was studied on erythropoietin (ESF) levels and on the metabolic functions of erythrocytes (RBC). GCC (U mg/kg/day for 15 days) was administered to 6 patients with the haemolytic-uraemic syndrome (group B) and to 6 patients with non-spherocytic haemolytic anaemia due to hereditary pyruvate kinase enzyme deficiency (group C). 6 healthy persons served as control (group A). The metabolic functions of RBC were investigated by assaying HMPS activity, GSH/GSSG and lactate/pyruvate ratios, relevant glycolytic intermediates, 2,3-DPG, ATP, and key enzymes. A significant increase in ESF was observed in group B patients after GCC therapy, correlating with an improvement in the haemolytic state, and consequent rectification of the secondary disturbances of RBC metabolism. Group C patients already had raised ESF levels before GCC therapy; no further increase occured in response to treatment and no other clinical or haematological change was recorded. Hence, no harmonal influence of GCC on the disturbed RBC metabolic process was detectable in the cases.

Topics: Adult; Anemia, Hemolytic, Congenital Nonspherocytic; Deficiency Diseases; Erythrocytes; Erythropoietin; Female; Hemolytic-Uremic Syndrome; Humans; Male; Methylprednisolone; Pyruvate Kinase

Topics: Animals; Erythropoietin; Hemolytic-Uremic Syndrome; Humans; Rabbits; Toxins, Biological; Uremia

Topics: Adolescent; Adult; Anemia, Hemolytic; Erythropoietin; Female; Hemolytic-Uremic Syndrome; Humans; Kidney Failure, Chronic; Male; Methenolone; Middle Aged; Renal Dialysis; Uremia