Neonatal atypical hemolytic uremic syndrome due to methylmalonic aciduria and homocystinuria

BACKGROUND: Inborn errors of cobalamin (Cbl) absorption and metabolism form a large group of rare diseases that include Cbl-C disorder. Among the renal complications of Cbl-C disorder, atypical hemolytic uremic syndrome (HUS) is the least common and has been described only in a small number of cases. CASE-DIAGNOSIS/TREATMENT: Four patients were admitted to our clinic after 15-30 days of life with vomiting associated with poor sucking, failure to thrive, lethargy and hypotonia. Examinations showed thrombocytopenia and microangiopathic hemolytic anemia associated with renal damage. The neonates had high blood homocysteine levels, increased urinary levels of both homocystine and methylmalonic acid, increased propionylcarnitine (C3) levels and an increased C3/acetylcarnitine ratio. Homozygosity for c.271-272dupA (p.Arg91LysfsX14) of the MMACHC gene was detected in three patients, and heterozygosity for c.271-272dupA and c.666C > A(p.Tyr222X) in one patient, which confirmed the diagnosis of Cbl-C disorder. Treatment with parenteral hydroxycobalamin in combination with folic acid and betaine gradually normalized the metabolic test findings and hematological and renal parameters after about 1 week. CONCLUSIONS: Atypical HUS in neonates with Cbl-C disorder may be associated with mild to moderate renal involvement also in early-onset disease, and early adequate therapy can reverse renal damage.     

Apparent recurrence of hemolytic uremic syndrome in azathioprine-treated allograft recipients

The present study describes 3 adult patients with hemolytic uremic syndrome (HUS) leading to chronic renal failure. Following renal transplantation, the 3 patients developed microangiopathic hemolytic anemia associated with acute rejection crises and graft failure. In 2 patients the renal histology of the transplanted kidney was consistent with HUS. It is concluded that, in adult patients, HUS may recur after renal transplantation and contribute to renal graft failure.     

Shiga toxin-associated hemolytic uremic syndrome: absence of recurrence after renal transplantation

We evaluated the relationship between the acute phase and the development of end-stage renal disease (ESRD) and the outcome of renal transplant in patients with Shiga toxin-associated hemolytic uremic syndrome (Stx-HUS). A 20-year retrospective study was performed of 66 renal transplants in 62 patients with Stx-HUS compared with 189 renal allografts in 178 children with other diseases. Of 62 patients, 61 had >7 days of oliguria during the acute phase. Stx-HUS patient survival was not different from controls (92% vs. 83% 15 years after renal transplantation). In the cyclosporine (CsA) era, survival of grafts from living related (LRD) and cadaver (CD) donors in Stx-HUS and control patients was 83% versus 70% ( P<0.03) and 77% versus 49% ( P<0.05) at 10 years. Graft survival in Stx-HUS and dysplasia/obstructive uropathy patients was 79% versus 76% ( P=NS), but it was different from that of other diseases (79% vs. 58%, P<0.001). There was no clinical or histopathological evidence of Stx-HUS recurrence. In conclusion, in Stx-HUS patients the duration of the acute oliguric period was a good predictor for the progression to ESRD. Use of CsA and the absence of recurrence of the disease influenced the excellent prognosis in Stx-HUS patients after renal transplantation. The development of ESRD in Stx-HUS could be mediated by non-immunological factors.     

Endotoxemia in hemolytic uremic syndrome

Hemolytic uremic syndrome (HUS) was diagnosed and confirmed by renal biopsy in an 18-year-old primigravida at the 13th week of pregnancy. Circulating endotoxin was detected and the endotoxemia was progressively reduced by hemodialysis (HD) performed daily from the 3rd to the 9th day of disease. Complete normalization of the renal function was observed on day 34. The authors emphasize the importance of detecting endotoxemia in HUS in order to initiate dialysis early; at the same time they also discuss the pathogenetic role of endotoxin in this disease.     

Tacrolimus-induced hemolytic uremic syndrome and end-stage renal failure after liver transplantation

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Despite steroid treatment, antihypertensive agents and fresh frozen plasma therapy, end-stage renal failure was observed and chronic hemodialysis treatment was required.     

The risk of recurrence of hemolytic uremic syndrome after renal transplantation in children

We reviewed the literature to analyze the risk of recurrence of hemolytic uremic syndrome (HUS) after renal transplantation in children. Among 118 children transplanted after post-diarrheal (D+) HUS, 1 (0.8%) had recurrence with graft loss. Among 63 children transplanted after HUS not associated with a prodrome of diarrhea (D–) of unknown mechanism, 13 (21%) had recurrence with graft loss. Of 11 patients with HUS associated with factor H deficiency who were transplanted, 5 lost the graft because of recurrence. Of 7 patients with HUS associated with normal factor H concentration but mutations in factor H gene who were transplanted, probably 2 had recurrence. Three patients with HUS associated with low serum C3, but no factor H deficiency or mutation lost their graft because of recurrence. The risk of recurrence in the autosomal recessive forms of HUS of unknown mechanism is not documented in children, but is around 60% in adults. A similar risk has been reported in the autosomal dominant forms. The only transplant patient with a constitutional deficiency of von Willebrand factor-cleaving protease had recurrence. Further efforts to document the post-transplant course of patients with D– HUS and progress in the understanding of the mechanisms and genetics of the disease are needed to allow more accurate prediction of the recurrence risk and to define therapeutic approaches.     

Cardiac ischemia during hemolytic uremic syndrome

Increased thrombin generation and impaired fibrinolysis during Escherichia coli O157:H7-associated hemolytic uremic syndrome (HUS) plausibly diminish myocardial blood flow, but the frequency of cardiac ischemia during HUS is unknown. We identified a 9-year-old boy with HUS in whom myocardial diastolic dysfunction was demonstrated by echocardiography, who also had elevated serum troponin-I and creatine kinase MB mass. However, eight additional patients with HUS did not have elevated markers of cardiac injury. When present, elevated troponin-I should be considered to represent myocardial injury, and not attributed simply to renal insufficiency. It is possible that myocardial ischemia and secondary arrhythmias account for some sudden deaths that occur during acute HUS.     

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.     

Steroids in the hemolytic uremic syndrome

To determine whether steroids could be of clinical benefit in the treatment of the hemolytic uremic syndrome (HUS), we conducted a randomized, double-blinded, placebo-controlled trial of methylprednisone (5 mg/kg per day in four oral doses over 7 days), in children with HUS during the acute phase. Ninety-two patients with typical HUS (47 receiving placebo and 45 receiving steroids) were investigated for neurological, hematological, and nephrological variables. There were no differences between groups in the number of convulsive episodes or transfusion requirements during the hospital stay. Serum creatinine levels were slightly increased on day 10 in the placebo group compared with the steroid group (P = 0.06) and declined significantly between days 1 and 10 only in the steroid group (P = 0.001). In the 51 patients with anuria (24 placebo, 27 steroids), median serum creatinine levels were reduced in the steroid group compared with the placebo group on the 10th day (P = 0.01). Differences in median days of oliguria [11.5 versus 8 (P = 0.28)], anuria [5 versus 7 (P = 0.20)], and dialysis [12 versus 10 (P = 0.26)] for the placebo and the steroid group respectively were not significant. Our data suggest that oral steroids are not able to modify hematological, neurological, or nephrological clinical parameters during the acute phase of childhood HUS, even though they do seem to be associated with a more rapid decline in serum creatinine levels. Received April 9, 1997; received in revised form September 8, 1997, accepted September 10, 1997     

Troponin I levels in a hemolytic uremic syndrome patient with severe cardiac failure

Troponins are highly sensitive and specific biochemical markers of myocardial injury that are released into the circulation during myocardial ischemia. We describe changes in cardiac troponin I (cTnI) prior to and following clinical evidence of severe myocardial dysfunction in a child with hemolytic uremic syndrome (HUS). A previously healthy, 22-month-old girl presented with typical HUS and stool cultures positive for Escherichia coli O157:H7. She required dialysis, blood and platelet transfusions, and insulin for HUS-related diabetes mellitus. On the 6th hospital day she had sudden circulatory collapse with a blood pressure of 70/40 mmHg and an oxygen saturation of 88%. She responded rapidly to emergency resuscitation but had diminished left ventricular function (ejection fraction 18%). Four days after the acute event an echocardiogram showed normal ventricular size and contractility. She underwent hemodialysis for 22 days, and renal function was normal after 33 days. cTnI levels were measured with a microparticle enzyme immunoassay. cTnI was normal (>0.4 g/l) 32 h prior to cardiac collapse, mildly increased (2.1 g/l) 8 h before the cardiac collapse, severely elevated shortly after the cardiac event (43.1 g/l), and peaked (140.6 g/l) at 24 h. It then fell gradually and was normal at discharge. These results suggest that measurement of cTnI may be a useful predictor of cardiac involvement in severely affected children with HUS.     

Inherited hemolytic uremic syndrome in adults.

Familial hemolytic uremic syndrome (HUS) in children may be due to environmental factors or may be an inherited trait, usually with autosomal recessive inheritance. Familial HUS in adults is less well described, and can be associated with autosomal recessive or dominant inheritance. We report a family with autosomal dominant inheritance of HUS. The proband was an adult male. His adult sister developed HUS while taking oral contraceptives, and their mother developed HUS during the third trimester of pregnancy. The prognosis for these patients is poor. Pregnancy and oral contraceptive use may be risk factors for development of HUS in adult women with a family history of HUS or the related disorder thrombotic thrombocytopenic purpura (TTP).     

Rasburicase for hyperuricemia in hemolytic uremic syndrome

Background  

Acute kidney injury (AKI) with elevated serum uric acid (UA) levels has been reported in patients with hemolytic uremic syndrome (HUS). AKI is thought to result from tubular obstruction by UA crystals. Inducing a diuresis may ameliorate the oligoanuria in such patients. We describe a child with HUS in whom reducing UA with fluids and rasburicase appeared to accelerate the recovery of renal function.