Hemolytic uremic syndrome in solid-organ transplant recipients

Post-transplant hemolytic uremic syndrome characterized by microangiopathic hemolysis, thrombocytopenia, and renal failure is an infrequent but potentially serious complication in organ transplant recipients. Hemolytic uremic syndrome developed in 2% (2/100) of our consecutive liver transplants. We report our patients and review a total of 91 cases of hemolytic uremic syndrome in adult solid organ transplant recipients reported in the literature. Ninety percent were observed in renal transplant recipients, 8% in liver, and 1% each in lung and heart transplant recipients. Eighty percent and 96% of cases occurred within 90 days and 1 year, respectively, post-transplantation. In renal transplant recipients, 23% of cases were due to post-transplant recurrence of hemolytic uremic syndrome. In 50% of renal transplant recipients and in all norenal solid-organ transplant recipients, hemolytic uremic syndrome was attributed to cyclosporin or tacrolimus therapy. Notably, infections were not a significant precipitating factor for post-transplant hemolytic uremic syndrome. Graft loss attributable to hemolytic uremic syndrome occurred in 43% of renal transplant recipients while renal transplantation and hemodialysis were required in the lung and heart transplant recipients due to hemolytic uremic syndrome induced renal failure. The overall mortality was 13% (12/91). Physicians caring for transplant recipients need to be aware of this potentially severe graft and life-threatening disorder since prompt recognition and removal of identifiable risk factors is critical in the management of post-transplant hemolytic uremic syndrome.     

Hemolytic uremic syndrome due to Capnocytophaga canimorsus bacteremia after a dog bite

The hemolytic uremic syndrome (HUS) is known to have several causes, including infectious diseases, drugs, pregnancy, and malignant disease. We report a patient who developed acute renal failure attributable to HUS in the course of Capnocytophaga canimorsus bacteremia. Acute tubular necrosis as well as HUS should be considered as a cause of acute renal failure in the setting of Capnocytophaga canimorsus bacteremia.     

Hemolytic uremic syndrome and thymic dysplasia in an infant

A 33-day-old male infant was admitted to the neonatal intensive care nursery because of respiratory distress, grunting, cyanosis, and radiological findings of bilateral bronchopneumonia. He responded well to intensive therapy, but 11 days later developed hemolytic uremic syndrome, which was treated conservatively with prednisone and plasma transfusions with good response. The hemolytic uremic syndrome resolved, but he subsequently developed severe recurrent infections of unknown etiology and died at the age of 78 days. Necropsy findings revealed necrotizing enterocolitis as well as dysplasia of the thymus and other lymphoid tissues, compatible with the diagnosis of immunodeficiency disorder. Received February 7, 1997; received in revised form November 12, 1997; accepted November 13, 1997     

Hemolytic uremic syndrome in small-bowel transplant recipients: the first two case reports

Post-transplant hemolytic uremic syndrome (HUS) is an uncommon but well-described complication in solid organ transplant recipients. Believed to be secondary to immunosuppressive therapy, it has been reported after kidney, liver, pancreas, heart, and lung transplants. In all reported cases, the primary organ affected was the kidney (transplant or native). But until now, no cases after small-bowel transplants and no cases in which the kidney was not the primary organ affected have been reported. We report two cases of HUS in small-bowel transplant recipients. In our first case, clinical presentation was with renal failure; biopsy of the native kidney demonstrated the typical histological changes seen with HUS, namely occlusion of the microcirculation by thrombi and platelet aggregation. Immunosuppression was changed from tacrolimus to cyclosporin, but with no improvement in renal function. In our second case, the transplanted bowel was the primary organ affected. This recipient presented with ulcers in the bowel mucosa, which were believed to be ischemic in origin, secondary to occlusive vascular lesions affecting the small vessels in the transplanted bowel. Her tacrolimus dose was decreased with resolution of ulcers and no evidence of rejection. These two cases represent the first reports of HUS after small-bowel transplants; in addition, our second case represents the first report of an extrarenal graft as the primary organ affected. When caring for small-bowel transplant recipients, physicians must be alert to the possibility of HUS and its various presentations. Received: 29 October 1998 Received after revision: 12 March 1999 Accepted: 3 May 1999     

Hemolytic uremic syndrome associated with group A beta-hemolytic streptococcus

Group A beta-hemolytic streptococcal (GABS) hemorrhagic colitis due to Streptococcus pyogenes is extremely rare and its association with hemolytic uremic syndrome (HUS) in children has not been described. We report a 9-year-old white male who developed biopsy-proven HUS while continuing to have GABS-positive bloody diarrhea. Renal function deteriorated rapidly requiring intermittent hemodialysis. Three months following discharge, his renal function is normal for age except for significant proteinuria.     

儿童溶血尿毒综合征4例报道并文献回顾

溶血尿毒综合征(hemolytic uremic syndrome,HUS)是小儿急性肾衰竭常见原因之一,死亡率高。本文通过分析总结4例HUS患儿临床特点及诊治经过,为提高诊疗水平提供参考。方法将湖北省妇幼保健院PICU收治的4例HUS患儿临床表现、辅助检查、治疗及转归进行回顾性分析。结果4例患儿均进行血液净化治疗,2例患儿恢复良好;1例患儿出院后10个月复发,再次住院好转出院,随访5个月身体健康。1例患儿住院治疗68 d,间断透析治疗,因预后差放弃治疗后死亡。结论HUS为儿童致命性疾病,血浆置换能够缓解病情、改善预后,为HUS一线治疗。婴儿期发生非典型HUS可出现血浆置换治疗不敏感,建议尽早采用其他治疗如依库珠单抗。     

Hemolytic uremic syndrome in children in northern India

We observed 73 patients with the hemolytic uremic syndrome (HUS) in 9 years (1980–1988), comprising 34% of patients with acute renal failure treated over the same period. There were 53 boys and 20 girls; 59% were below the age of 2 years and 33% between 2 and 5 years. Acute, usually severe dysentery, responding poorly to various antibiotics, was the prodromal illness in 80%, whereas 12% had watery diarrhea. Most patients had severe renal involvement with anuria in 56% and oliguria in 30%. A polymorphonuclear leukocytosis was present in 85% of cases, but had no correlation with the highest levels of blood urea. Coagulation abnormalities suggesting consumption coagulopathy were found in 24 of 30 cases. The results of stool culture showedShigella species in 7 cases and nontyphoidalSalmonella in 9.Escherichia coli were isolated in 11 cases, but were not further characterized. Renal biopsy showed total or patchy cortical necrosis in 20 of 50 cases. The patients were managed with supportive care, including transfusion of fresh blood or plasma and dialysis as required. The mortality was 60%, being chiefly related to the duration of renal failure and presence of renal cortical necrosis, whereas persistent dysentery and infections were complicating factors. The presence of convulsions and coagulation defects had no relation to the outcome. Our observations indicate that HUS in children in northern India is mostly related to dysentery, likely to be shigellosis, and is usually associated with severe renal damage and a high death rate.     

Hemolytic uremic syndrome associated with Denys-Drash syndrome

The Denys-Drash syndrome is defined by the occurrence of combinations of pseudohermaphroditism, nephrotic syndrome with diffuse mesangial sclerosis, Wilms’ tumor, and constitutional mutations in the WT1 suppressor gene. Most patients develop end-stage renal failure. Atypical hemolytic uremic syndrome (HUS) is defined by onset of acute hemolytic anemia with fragmented erythrocytes, thrombocytopenia, and renal failure in the absence of a gastrointestinal prodromal illness of bloody diarrhea. The purpose of this report is to describe the occurrence of features of atypical HUS and Denys-Drash syndrome in two African-American boys aged 13 and 16 months. Each had nephrotic syndrome, diffuse mesangial sclerosis, and WT1 point mutations. Both had grade III hypospadias and undescended testes. They had normal serum creatinine concentrations and hematology a month before presenting with HUS. Stool cultures for Escherichia coli 0157:H7 were negative. Each patient has been transplanted with cadaver kidneys without recurrence of HUS. Received: 20 July 1999 / Revised: 22 February 2000 / Accepted: 17 March 2000     

Nephrotic syndrome associated with an Epstein-Barr virus infection

A 19-month-old child developed the nephrotic syndrome coincident with an Epstein-Barr virus (EBV) infection. This rare association was confirmed by EBV titers. There was a spontaneous resolution of the nephrotic syndrome temporally related to the abatement of the EBV infection. Received November 28, 1995; received in revised form February 19, 1996; accepted February 21, 1996     

Hemolytic uremic syndrome due to an altered factor H triggered by neonatal pertussis

We report on a previously healthy newborn suffering from severe Bordetella pertussis infection who developed hemolytic uremic syndrome (HUS) a few weeks after the onset of whooping cough, with a fatal outcome. A factor H protein with abnormal mobility was found in the serum of the patient as analyzed by Western blotting, indicating that B. pertussis infection might have triggered HUS in a genetically predisposed patient. Received: 13 July 2000 / Revised: 3 October 2001 / Accepted: 9 October 2001     

Racial incidence of hemolytic uremic syndrome

Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children and is caused by infection with verotoxin-productingEscherichai coli. There is no consensus on the relative incidence of HUS in blacks and whites. An equal racial incidence has been reported by two centers with small black populations. A series from Washington D. C. reported a low incidence in blacks. The population of Alabama is 32% black and 66% white. The Children's Hospital of Alabama admission rate has a similar racial distribution (35% black, 65% white). A record review from 1980–1992 identified 45 patients with HUS; 43 (96%) were white and only 2 (4%) were black. Based on census data for Alabama in 1980 and 1990, this gives an average annual incidence of HUS of 0.45 per 100,000 in whites and of 0.043 per 100,000 in blacks (P<0.001, Fischer's exact test). Similar results were found in the group of patients with HUS and a history of diarrhea; whites 0.39 and blacks 0.02 (P<0.001). However, in those with no history of diarrhea there was no significant racial difference: whites 0.05 and blacks 0.02. There were too few blacks to compare clinical course and outcome. We conclude that typical diarrhea-associated HUS is a relatively rare disease in blacks compared with whites. The reasons are unclear.     

Hemolytic uremic syndrome induced by lipopolysaccharide and Shiga-like toxin

Induction of experimental hemolytic uremic syndrome (HUS) by simply administering Shiga-like toxin (Stx) to rodents has not yet been successful. Attention has been paid to the role of lipopolysaccharide (LPS) in the pathogenesis of HUS. In this study, we showed successful induction of an experimental HUS in LPS responder mice by administering Stx together with LPS. Intraperitoneal administration of 200 ng of Stx 2 for 2 days, followed by 250 g of LPS on the 2nd day of Stx administration, caused a significant decrease of thrombocytes and deterioration of renal function, with proteinuria and hematuria. Electron microscopy revealed alterations of glomerular endothelial cells. Administration of Stx alone or LPS alone caused neither hematological nor histopathological changes, as were observed with Stx and LPS co-administration. Interestingly, when LPS was administered before Stx, no hematological and histological changes were observed. The results showed that LPS was essential for the induction of HUS, but LPS pretreatment might protect against Stx toxicity. The order of LPS and Stx administration is important for the induction of experimental HUS.     

De novo hemolytic uremic syndrome following renal transplantation

We report a case of complete recovery of renal function in a patient with de novo hemolytic uremic syndrome (HUS) following renal transplantation. This 3-year-old girl had none of the factors known to contribute to the development of HUS in transplant recipients. This case illustrates the usefulness of renal biopsy in the accurate diagnosis and management of dysfunction in the allograft following renal transplantation.     

Cardiomyopathy: a late complication of hemolytic uremic syndrome

This report describes a child who presented with classic hemolytic uremic syndrome (HUS) and 4 months later developed a life-threatening but reversible cardiomyopathy with global cardiac dysfunction and a left ventricular ejection fraction of 14%. There was no evidence of electrolyte abnormalities, anemia, hypertension, severe fluid overload, or viral infection. Endomyocardial biopsies were consistent with a dilated cardiomyopathy. This paper highlights the importance of considering the diagnosis of associated cardiomyopathy when presenting with late-onset edema following HUS. Received February 12, 1996; received in revised form and accepted August 22, 1996     

Hemolytic uremic syndrome in families — an argentinian experience

Six hundred and thirty-one patients with hemolytic uremic syndrome (HUS) were treated from 1960 to 1992; 19 (3%) were familial cases, of which 9 were classified as concomitant (including twins), 6 as non-concomitant, and 4 as recurrent. In the recurrent group there were 15 HUS episodes, 10 being concomitant in 2 patients. Prodromal diarrhea was present only in concomitant and non-concomitant cases. Patients with recurrences were sisters from a single family. Concomitant and non-concomitant cases had clinical features, course, and age similar to typical endemoepidemic forms of HUS, in which an association with verocytotoxin-producingEscherichia coli has been reported. There may be a genetic determinant in concomitant cases; these occurred outside the season during which endemoepidemic forms are typically detected. In patients with recurrent disease a genetic factor which may lead to the development of the disease when triggered by viral infections is likely.     

Post-dysenteric hemolytic uremic syndrome in Bulawayo, Zimbabwe

An outbreak of dysentery in Zimbabwe was associated with a high mortality, especially in children who developed hemolytic uremic syndrome (HUS). To examine the causes of high mortality from HUS and to suggest measures that could reduce the case fatality rate, clinical and laboratory features of 91 children with dysentery were reviewed. Of these, 14 developed HUS; their findings were compared with age-matched controls with dysentery only. Persistent alteration of consciousness after rehydration, pallor, and oliguria were early clinical indicators of HUS. Leukocytosis and leukemoid reaction, microhematuria, and non-resolving hyponatremia distinguished children with HUS from those with dysentery. While Shigella dysenteriae type I was responsible for the dysentery outbreak in the community, most stool cultures of children with HUS were negative. Mortality from HUS was high. Late recognition of HUS and a lack of peritoneal dialysis could have contributed to the fatal outcome in some cases. Early recognition of HUS through close observation of children with dysentery and appropriate laboratory investigations with referral to a hospital, where peritoneal dialysis is available, should improve the outcome. Received: 24 August 2000 / Revised: 30 July 2001 / Accepted: 31 July 2001     

Immune complex disease associated with Epstein-Barr virus infectious mononucleosis

We describe a patient with immune complex-mediated glomerulonephritis and leukocytoclastic vasculitis associated with Epstein-Barr virus (EBV) infectious mononucleosis. The patient required hemodialysis and has residual hypertension. This case implicates acute EBV infection as a cause of immune complex-mediated glomerulonephitis. Received October 10, 1997; received in revised form January 20, 1998; accepted January 27, 1998     

Hemolytic uremic syndrome in Kuwaiti Arab children

Twenty-five children with hemolytic uremic syndrome (HUS) were diagnosed between January 1985 and January 2000 in the Pediatric Nephrology Unit at Mubarak Al-Kabeer Hospital. Fourteen patients (56%) had typical (D+) HUS whereas 11 (44%) had atypical (D–) HUS. No bacterial or viral pathogens could be isolated in the majority of cases. The atypical HUS group had more severe anemia (P=0.03), which was significantly more prolonged than in the typical HUS group (P=0.0028). There was no significant difference between the two groups in the mean maximum serum creatinine (P=0.1), blood urea nitrogen values (P=0.8) and severity of leukocytosis (P=0.4). Anuria and the need for dialysis were not significantly different between the two groups (P=0.1 and 0.05, respectively). Mortality was significantly higher in the D– HUS patients (P<0.0001). Recurrence of HUS was documented in 63.3% of the D– HUS group compared to 14.2% of the D+ HUS group (P=0.0053). Family history of HUS was reported in 72.7% of the atypical HUS group and 14.2% of the typical HUS group. There were no significant differences in chronic renal sequelae between the two groups. In conclusion, the pathogenesis of HUS in Kuwaiti children appears to be influenced by genetic factors rather than certain environmental pathogens. Atypical HUS has a higher mortality rate, a definite familial tendency and a high relapse rate. Received: 22 December 2000 / Revised: 8 August 2001 / Accepted: 8 August 2001     

8例溶血性尿毒症综合征临床分析

目的探讨溶血性尿毒症综合征（HUS）的临床特点和治疗方法。方法回顾性分析自1997年12月至2007年12月收治的8例HUS患者的临床特点及治疗方法。结果成人7例,儿童1例。诱因为产后3例,呼吸道感染2例,肠道感染1例,呼吸道合并肠道感染1例,无明显诱因1例。8例均表现为溶血性贫血、血小板减少和急性肾衰竭。病情属重型5例,轻型3例。肾损害表现为少尿1例,无尿2例,肉眼血尿3例,高血压8例,水肿6例。8例均采用综合治疗：抗感染、降压等一般治疗;血液透析、改善肾循环、血液灌流、血浆置换、新鲜冰冻血浆输注以及肾上腺皮质激素等。2例治愈,4例好转,2例病情恶化放弃治疗。治疗后血液系统及生化指标均有改善,血红蛋白（Hb）、血小板（PLT）、血肌酐（SCr）、总胆红素（TBIL）、血乳酸脱氢酶（LDH）与治疗前比较,差异有统计学意义（P〈0．05）。结论HUS较罕见,属临床急症,早期诊断、及时正确治疗有助于改善短期预后。