Antibodies, Monoclonal, Humanized/therapeutic use* ; Atypical Hemolytic Uremic Syndrome/drug therapy* ; Humans

Hemolytic uremic syndrome (HUS) is clinically rare, with high mortality and case fatality rates. In recent years, the research on HUS has been intensified and the pathophysiological mechanism has been continuously improved. At present, the main mechanism of pathogenesis is the excessive activation of complement alternative pathways mediated by complement-related gene mutations or the existence of antibodies. The treatment methods and strategies are also constantly updated, mainly including complement-blocking drugs such as Eculizumab, Lavalizumab, and Ravulizumab. In this review, the new developments in the pathogenesis and treatment of HUS is summarized, and provide references for the clinical treatment of HUS.
Complement System Proteins/therapeutic use* ; Hemolytic-Uremic Syndrome/therapy* ; Humans ; Mutation

Antibodies, Monoclonal, Humanized ; therapeutic use ; Atypical Hemolytic Uremic Syndrome ; drug therapy ; surgery ; China ; Humans ; Kidney Transplantation ; Male

Streptococcus pneumoniae associated hemolytic uremic syndrome (SpHUS) is one of the causes of atypical hemolytic uremic syndrome, and increasingly reported. They are more severe and leave more long-term sequelae than more prevalent, typical hemolytic uremic syndrome. But it is not so easy to diagnose SpHUS for several reasons (below), and there was no diagnostic criteria of consensus. A 18 month-old-girl with sudden onset of oliguria and generalized edema was admitted through the emergency room. She had pneumonia with pleural effusion and laboratory findings of HUS, DIC, and positive direct Coombs' test. As DIC or SpHUS was suspected, we started to treat her with broad spectrum antibiotics, transfusion of washed RBC and replacement of antithrombin III. On the 3rd day, due to severe hyperkalemia and metabolic acidosis, continuous renal replacement therapy (CRRT) was started. She showed gradual improvement in 4 days on CRRT and discharged in 16 days of hospital care. At the follow up to one year, she has maintained normal renal function without proteinuria and hypertension. We report this case with review of articles including recently suggested diagnostic criteria of SpHUS.
Acidosis ; Anti-Bacterial Agents ; Antithrombin III ; Child ; Consensus ; Coombs Test ; Dacarbazine* ; Disseminated Intravascular Coagulation ; Edema ; Emergency Service, Hospital ; Follow-Up Studies ; Hemolytic-Uremic Syndrome* ; Humans ; Hyperkalemia ; Hypertension ; Oliguria ; Pleural Effusion ; Pneumonia ; Proteinuria ; Renal Replacement Therapy ; Streptococcus pneumoniae*

Streptococcus pneumoniae associated hemolytic uremic syndrome (SpHUS) is one of the causes of atypical hemolytic uremic syndrome, and increasingly reported. They are more severe and leave more long-term sequelae than more prevalent, typical hemolytic uremic syndrome. But it is not so easy to diagnose SpHUS for several reasons (below), and there was no diagnostic criteria of consensus. A 18 month-old-girl with sudden onset of oliguria and generalized edema was admitted through the emergency room. She had pneumonia with pleural effusion and laboratory findings of HUS, DIC, and positive direct Coombs' test. As DIC or SpHUS was suspected, we started to treat her with broad spectrum antibiotics, transfusion of washed RBC and replacement of antithrombin III. On the 3rd day, due to severe hyperkalemia and metabolic acidosis, continuous renal replacement therapy (CRRT) was started. She showed gradual improvement in 4 days on CRRT and discharged in 16 days of hospital care. At the follow up to one year, she has maintained normal renal function without proteinuria and hypertension. We report this case with review of articles including recently suggested diagnostic criteria of SpHUS.
Acidosis ; Anti-Bacterial Agents ; Antithrombin III ; Child ; Consensus ; Coombs Test ; Dacarbazine* ; Disseminated Intravascular Coagulation ; Edema ; Emergency Service, Hospital ; Follow-Up Studies ; Hemolytic-Uremic Syndrome* ; Humans ; Hyperkalemia ; Hypertension ; Oliguria ; Pleural Effusion ; Pneumonia ; Proteinuria ; Renal Replacement Therapy ; Streptococcus pneumoniae*

Hemolytic uremic syndrome (HUS) is a rare thrombotic complication characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS may be caused by several different conditions, including infection, malignancy, and chemotherapeutic agents, such as mitomycin, cisplatin, and most recently, gemcitabine. The outcome of gemcitabine-induced HUS is poor, and the disease has a high mortality rate. This study reports a case of gemcitabine-induced HUS in a patient with pancreatic cancer in Korea.
Antimetabolites, Antineoplastic/*adverse effects ; Deoxycytidine/adverse effects/*analogs & derivatives ; Hemolytic-Uremic Syndrome/*chemically induced ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/*drug therapy ; Treatment Outcome

OBJECTIVETo investigate the clinical characteristics, renal pathology, treatment and prognosis of children with atypical hemolytic uremic syndrome associated with H factor antibody.

METHODFour 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.

RESULTAll 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.

CONCLUSIONGastrointestinal 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.

Atypical Hemolytic Uremic Syndrome ; Autoantibodies ; blood ; immunology ; Child ; Child, Preschool ; Complement Factor H ; immunology ; Creatinine ; blood ; Female ; Hemolytic-Uremic Syndrome ; drug therapy ; immunology ; pathology ; Humans ; Kidney ; pathology ; physiopathology ; Kidney Function Tests ; Male ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; therapeutic use ; Plasma Exchange ; Prednisolone ; administration & dosage ; therapeutic use ; Prognosis ; Retrospective Studies

Hemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in childhood and is primarily diagnosed in up to 4.5% of children who undergo chronic renal replacement therapy. Escherichia coli serotype O157:H7 is the predominant bacterial strain identified in patients with HUS; more than 100 types of Shiga toxin-producing enterohemorrhagic E. coli (EHEC) subtypes have also been isolated. The typical HUS manifestations are microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency. In typical HUS cases, more serious EHEC manifestations include severe hemorrhagic colitis, bowel necrosis and perforation, rectal prolapse, peritonitis, and intussusceptions. Colonic perforation, which has an incidence of 1%-2%, can be a fatal complication. In this study, we report a typical Shiga toxin-associated HUS case complicated by small intestinal perforation with refractory peritonitis that was possibly because of ischemic enteritis. Although the degree of renal damage is the main concern in HUS, extrarenal complications should also be considered in severe cases, as presented in our case.
Acute Kidney Injury ; Anemia, Hemolytic ; Child* ; Colitis ; Colon ; Enteritis ; Enterohemorrhagic Escherichia coli ; Escherichia coli ; Hemolytic-Uremic Syndrome* ; Humans ; Incidence ; Intestinal Perforation* ; Intussusception ; Necrosis ; Peritonitis ; Rectal Prolapse ; Renal Insufficiency ; Renal Replacement Therapy ; Shiga Toxin ; Thrombocytopenia

Hemolytic uremic syndrome (HUS) is a rare disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. These characteristics are related to the formation of platelet-rich microthrombi in the microvasculature. HUS is associated with a variety of etiologies, including cisplatin. Previously reported HUS cases after cisplatin administration were almost always related to systemic combination chemotherapy that included cisplatin. Transarterial chemoembolization (TACE) is commonly used in treatment of hepatocellular carcinoma, and most centers in Korea use cisplatin. A 70-year-old female with hepatocellular carcinoma was treated with TACE including cisplatin and subsequently developed clinical and laboratory findings compatible with HUS.
Acute Kidney Injury ; Anemia, Hemolytic ; Carcinoma, Hepatocellular ; Chemoembolization, Therapeutic ; Cisplatin ; Drug Therapy, Combination ; Female ; Hemolytic-Uremic Syndrome ; Humans ; Korea ; Microvessels ; Thrombocytopenia

OBJECTIVETo observe the therapeutic effect of continuous blood purification (CBP) combined with hemoperfusion (HP) in children with hemolytic-uremic syndrome (HUS) and to investigate its possible mechanism.

METHODSEight children with HUS received CBP combined with HP on the basis of internal medicine treatment in the acute stage. Before and after treatment, serum levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) were measured by chemiluminescence method, and levels of blood urea nitrogen (BUN), serum creatinine (SCr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase MB (CKMB), hemoglobin (Hb), platelet (PLT) and C-reactive protein (CRP) were measured. Eight healthy children undergoing physical examination were used as controls.

RESULTSThe 8 children with HUS all survived after CBP combined with HP and showed improved conditions. They had increased Hb and PLT levels and decreased serum levels of IL-6, IL-8, TNF-α, BUN, SCr, ALT, CK and CRP after treatment (P<0.05).

CONCLUSIONSCBP combined with HP can quickly remove pathogenic factors, continually eliminate inflammatory mediators and toxins, and reverse multiple organ dysfunction, and is one of effective methods for treating HUS in children.

Child ; Child, Preschool ; Female ; Hemofiltration ; Hemolytic-Uremic Syndrome ; therapy ; Hemoperfusion ; Humans ; Infant ; Male