Features Of Hemolytic Uremic Syndrome Research Articles

Acute Kidney Injury and Hemolytic Uremic Syndrome in Severe Pneumococcal Pneumonia—A Retrospective Analysis in Pediatric Intensive Care Unit

Abstract Objectives: This study aimed to evaluate the prevalence of acute kidney injury (AKI) and hemolytic uremic syndrome (HUS) in severe pediatric pneumonia due to Streptococcus pneumoniae and to identify factors associated with AKI and HUS in these patients. Methods: We retrospectively analyzed pediatric patients who were admitted to our pediatric intensive care unit due to severe pneumococcal pneumonia between 2013 and 2019. Results: Forty-two patients with a median age of 4.3 years were included. Among these patients, 14 (33.3%) developed AKI, including seven (16.7%) stage 1, two (4.8%) stage 2, and five (11.9%) stage 3 AKI. Features of HUS were present in all of the patients with stage 3 AKI, and four required renal replacement therapy (RRT), with a median duration of 10.5 days (range 3 to 16 days). All patients with HUS required mechanical ventilation and inotropic supports. Patients with lower leukocyte and platelet counts, serum sodium and bicarbonate levels, positive urine dipstick (heme or protein ≥ 2 + ), and presence of bacteremia were associated with stage 2 and 3 AKI. Conclusions: Pediatricians should be aware of the relatively high prevalence of kidney involvement in severe pneumococcal pneumonia, with one-third having AKI and 11.9% developing HUS. Majority (80%) of HUS patients required RRT. Positive urine dipstick, serum sodium, and bicarbonate at presentation, which can be measured in point-of-care tests, may potentially be useful as quick tests to stratify the risks of moderate-to-severe AKI.

Pathology findings in pediatric patients with COVID-19 and kidney dysfunction.

BackgroundAcute kidney injury (AKI) is seen in one-fifth of pediatric patients with COVID-19 requiring hospital admission, and is associated with increased morbidity, mortality, and residual kidney impairment. The majority of kidney pathology data in patients with COVID-19 is derived from adult case series and there is an overall lack of histologic data for most pediatric patients with COVID-19.MethodsWe assembled a multi-institutional cohort of five unvaccinated pediatric patients with COVID-19 and associated kidney dysfunction with available histology.ResultsThree complex patients with current or prior SARS-CoV-2 infection had multifactorial thrombotic microangiopathy with clinical features of hemolytic uremic syndrome (in two) or disseminated intravascular coagulation (in one); one died and another developed chronic kidney disease stage 5. Two with recently preceding SARS-CoV-2 infection presented with nephrotic syndrome; one had IgA vasculitis and one had minimal change disease. Within a short follow-up time, none has returned to baseline kidney function.ConclusionAlthough uncommon, COVID-19-associated kidney injury can have significant morbidity in the unvaccinated pediatric and adolescent population.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information. Supplementary InformationThe online version contains supplementary material available at 10.1007/s00467-022-05457-w.

Airway-Centered Granulomatous Fibrinous and Organizing Pneumonia as a Manifestation of Sirolimus-A Reversible Pulmonary Toxicity

Sirolimus is a potent immunosuppressant medication and is used in renal transplant patients to prevent acute graft rejection. Various pulmonary toxicities in patients treated with sirolimus include cough, desquamative interstitial pneumonia (DIP), diffuse interstitial pneumonia, diffuse alveolar damage (DAD), diffuse alveolar hemorrhage (DAH), alveolar phospholipoproteinosis and pulmonary hypertension with features of hemolytic uremic syndrome (HUS). We describe a case of a patient with an insidious development of chest X-ray (CXR), computed tomography of the chest (CT chest) and pulmonary function (PFT) (mainly the DLCO) abnormalities. When this progressed, an open lung biopsy was performed revealing granulomatous inflammation consistent with a hypersensitivity reaction. The abnormalities on imaging and pulmonary function testing improved after drug discontinuation. We suggest that patients using this drug have yearly DLCOs as their pulmonary symptoms may be few. If the DLCO declines significantly then a high resolution CT Chest should be performed. If abnormal, biopsy is warranted.

Novel presentation of Plasmodium vivax malaria with acute kidney injury and hemolytic uremic syndrome

Abstract Background In India, epidemiologically, Plasmodium vivax predominates over Plasmodium falciparum malaria, and this produces a major public health problem due to the recent increase in severe vivax malaria. Malaria-related renal failure is usually ascribed to acute tubular necrosis (ATN) and interstitial nephritis, and rarely to cortical necrosis. Clinical features of hemolytic uremic syndrome (HUS) and thrombotic microangiopathy (TMA) on renal histology have not been described conclusively in relation to malaria. Methods This prospective observational study includes patients of vivax malaria with renal failure admitted to a tertiary care hospital during November 2011 to April 2012 with features of HUS (anemia, thrombocytopenia, and acute kidney injury). The diagnosis of P. vivax malaria monoinfection was established with detection of parasite in peripheral smear and malaria card test. Renal biopsies were performed after three weeks for nonrecovering renal failure and evaluated with light and immune-fluorescence microscopy. Results Five patients (2 males and 3 females) had clinical constellation of HUS associated with vivax malaria. All the patients required dialysis [1 peritoneal dialysis and 4 hemodialysis (HD)]. Renal biopsy performed in all the patients showed characteristic features of TMA like mucointimal proliferation, subintimal fibrin deposits with luminal thrombi along with ATN, and cortical necrosis. Three patients were dependent on dialysis [1 continuous ambulatory peritoneal dialysis (CAPD) and 2 HD]. The rest of the two patients had partial recovery at the end of 3 months. The patient on CAPD died due to pneumonia-related sepsis. Conclusion Clinical association of vivax malaria with TMA leading to HUS is novel and suggests parasite-related severe endothelial injury. Future studies are needed to demonstrate interaction of parasite with endothelium and factors related to it.

Haemolytic uraemic syndrome associated with Pseudomonas aeruginosa sepsis

Haemolytic uraemic syndrome (HUS) is a recognized complication of infection with Shiga toxin-producing Escherichia coli (STEC) and Shigella dysenteriae type 1. Infections with other micro-organisms, especially Streptococcus pneumoniae, have been cited as causes of HUS. In addition, influenza virus and other viruses may rarely be associated with this syndrome. A 2-year-old girl presented with severe Pseudomonas aeruginosa sepsis with renal failure and ecthyma gangrenosum. Further investigations revealed features of HUS. She was managed with antibiotics and other supportive measures including peritoneal dialysis, and subsequently made a full recovery. A possible role of neuraminidase in the pathogenesis of P. aeruginosa-associated HUS was proposed. This is the first reported case of P. aeruginosa sepsis leading to HUS.

Eculizumab therapy in a child with hemolytic uremic syndrome and CFI mutation

Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in childhood. It usually occurs after a prodromal episode of diarrhea and it leads to significant morbidity and mortality during the acute phase. However, cases that start as diarrhea-positive HUS whose renal function fail to recover should be screened for genetic disorders of the complement system, which is called atypical HUS (aHUS). We herein report a 10-year-old girl, who initially came with bloody diarrhea and had features of HUS with delayed renal and hematological recovery despite plasma therapy. Eculizumab (600 mg/week) was initiated on day 15 for atypical presentation and later a complement factor I (CFI) mutation was detected. The girl recovered diuresis within 24 h and after the third eculizumab infusion, hemoglobin, platelet, and C3 levels normalized; renal function improved; and proteinuria completely disappeared in 2 weeks. It is our belief that eculizumab can be the treatment of choice in children who have plasma exchange-refractory HUS with defective regulation of the alternative complement pathway.

Renal cortical necrosis in a live kidney donor

Renal cortical necrosis (RCN) is a rare cause of acute renal failure (ARF). There is no clinical case report of RCN in a live kidney donor. A 48-year-old female kidney donor developed sudden anuria five hours postnephrectomy and remained anuric for more than three months on maintenance hemodialysis. Laboratory investigations revealed the features of hemolytic uremic syndrome. Contrast-enhanced computed tomography scan of abdomen showed hypoattenuated subcapsular rim of renal cortex favoring diagnosis of RCN. To the best of our knowledge, this is the first clinical case report of RCN in a live kidney donor in world literature.

Absence of renal sequelae after childhood Escherichia coli O157:H7 gastroenteritis

Although a quarter of children who survive diarrhea-associated hemolytic uremic syndrome develop long-term renal sequelae, the prognosis of acute, self-limited Escherichia coli O157:H7 gastroenteritis has never been previously studied. Four years after a drinking water outbreak of E. coli O157:H7, we examined the risk of high blood pressure (>95th percentile expected for age, sex, and height), reduced kidney function, and microalbuminuria among previously healthy children and adolescents. Of the 951 participants, 313 were asymptomatic during the outbreak, 305 had moderate symptoms of acute gastroenteritis, and 333 had severe symptoms that necessitated medical attention. An additional 23 children who developed hemolytic uremic syndrome during the outbreak were excluded from this analysis. There were no differences in mean systolic blood pressure between those who had no, moderate, or severe symptoms of acute gastroenteritis during the outbreak (109, 110, and 107 mm Hg). Similarly, there were no group differences in diastolic blood pressure, estimated glomerular filtration rate, or random urine albumin to creatinine ratio (P ranged from 0.14 to 0.52), or in the adjusted relative risk of high blood pressure, a glomerular filtration rate <80 ml/min per 1.73 m(2), or microalbuminuria (P ranged from 0.23 to 0.89). Patients who presented to medical attention with gastroenteritis during this E. coli O157:H7 outbreak had an absence of renal sequelae 4 years later. With no existing data to support screening after self-limited E. coli O157:H7 gastroenteritis, we recommend that only those children who develop recognized features of hemolytic uremic syndrome be followed for long-term renal health.

Reduced Nitric Oxide Bioavailability In a Baboon Model of Shiga Toxin Mediated Hemolytic Uremic Syndrome (HUS)

Background. Although there is agreement that post-diarrheal hemolytic uremic syndrome (D + HUS) is caused by Shiga toxin (Stx)–producing E. coli, little is known about factors that mediate the host response to these toxins and potentially contribute to pathogenesis. Nitric oxide (NO) is a candidate mediator by virtue of its antiplatelet and renal vasodilatory properties. Methods. We used a baboon model of HUS to measure plasma and urinary NO metabolites and expression of NO synthase (eNOS and iNOS) in renal tissue following the intravenous administration of Stx-1. Results. Plasma concentrations through 60 hours of observation did not differ significantly from controls. Urinary values (indexed against urinary creatinine) tended, however, to rise during the initial 12 hours following administration of Stx-1. This was followed by a sustained reduction that coincided with the development of hemolytic anemia (schistocytosis) and other features of HUS. However, immunohistochemical staining for eNOS and iNOS in tissue obtained immediately after death at a median of 59 hours showed similar levels in control and Stx-treated animals, despite the presence of a florid thrombotic microangiopathy and tubular injury in the Stx-treated group. Conclusion. We propose that urinary NO metabolite reduction was due to NO inactivation subsequent to its avid binding to free hemoglobin released from lysed red blood cells, and that this contributed to the acute renal failure by facilitating vasoconstriction and platelet aggregation and adhesion within the renal microvasculature.

Response to single and divided doses of Shiga toxin-1 in a primate model of hemolytic uremic syndrome.

Postdiarrheal hemolytic uremic syndrome is caused by Shiga toxin (Stx)-producing Escherichia coli. It was shown previously that the baboon, like the human, has glycolipid receptors for Stx in the gut and the kidney and that a single 50- to 200-ng/kg intravenous dose of purified Stx-1 results in thrombocytopenia, hemolytic anemia, and renal thrombotic microangiopathy. For further characterization of factors that modulate disease expression, the baboon's response to the intravenous administration of 100 ng/kg Stx-1 given either rapidly as a single bolus or slowly as four 25-ng/kg doses at 12-h intervals was compared. Animals that received the Stx-1 as a single dose developed thrombocytopenia, schistocytosis, and acute renal failure. Urinary but not plasma tumor necrosis factor-alpha concentrations rose significantly by 6 h and then declined rapidly. Urinary and plasma interleukin-6 concentrations rose later. Glomeruli showed reduced patency of capillary loops, fragmented red blood cells, fibrin and platelet microthrombi, necrosis and detachment of endothelial cells, and accumulation of flocculent material in subendothelial spaces. Damage to tubular epithelium and peritubular capillary endothelium also was seen. Animals that received four divided doses of Stx-1 developed no clinical or histologic features of hemolytic uremic syndrome. It is concluded that in the primate model, disease expression is modulated by the rate of Stx administration, and it is speculated that in the human, the rate of Stx absorption from the gut is one determinant of disease severity.

Seasonality and other Epidemiological Features of Haemolytic Uraemic Syndrome and E. ColiO157 Isolates in Scotland

The main objective was to determine whether there was seasonality in presentation of haemolytic uraemic syndrome (HUS) in children and adults, and compare this with the reporting of E. coli O157. The data came from Scotland, examining admissions during 1980-95 and E. coli isolates 1984-95. Seasonality was sought by fitting a sine curve to monthly or four-weekly data throughout the year. Seasonality was present for HUS and E. coli isolates in patients under 15 years of age but not in those above that age. The highest point of the sine curve was in July/August but there was a high plateau from June to September. The timing was similar to other diarrhoeal disease. This is an epidemiological study, the purpose being to clarify the seasonal features of HUS. E. coli infection is an important food hazard and a sound knowledge of the epidemiology, could lead to optimal control. The Scottish geographic distribution is illustrated.

The Etiology and Clinical Features of Hemolytic Uremic Syndrome

The Etiology and Clinical Features of Hemolytic Uremic Syndrome

Acute renal failure and severe hypertension in children with renal thrombotic microangiopathy.

We observed 12 boys and 1 girl, 5-15 years old, presenting with acute renal failure (ARF) and severe hypertension. They constituted 4.9% of all patients with ARF. There was no preceding diarrheal or respiratory prodrome. Clinical and laboratory findings were indicative of hemolytic uremic syndrome (HUS) in 4, but obscure in 9 others. Renal biopsies revealed variably severe occlusive thrombotic microangiopathy (TMA) affecting predominantly interlobular arteries in 8 and both arteries and glomeruli in 5 cases. Glomerular crescents and cortical necrosis were not seen. Following supportive therapy, 8 progressed to or died of uremia; 2 showed persistent proteinuria, 1 moderate hypertension and 2 complete recovery. Our observations indicate that renal TMA without a prodromal illness and typical features of HUS may present with ARF, proteinuria and severe hypertension, and is associated with high mortality.

Urinary excretion of platelet-activating factor in haemolytic uraemic syndrome

Since some of the features of haemolytic uraemic syndrome (HUS), such as platelet activation and glomerular injury, could be brought about by platelet-activating factor (PAF), we have studied the urinary excretion of PAF in 10 children with HUS and in 10 healthy age-matched controls. Urinary PAF concentrations, measured by radioimmunoassay, were significantly higher in acute-phase H US patients than in controls (mean 2·04 [SD 1·66] vs 0·72 [0·43] ng/mg creatinine, p < 0·05) but were similar to those in controls in samples taken after recovery. High PAF concentrations during the acute phase of HUS may reflect platelet activation and glomerular injury; the lower values after recovery suggest that urinary PAF may be a marker of disease activity.

Long-term prognosis of haemolytic-uraemic syndrome in children.

Haemolytic-uraemic syndrome (HUS) is the most frequent cause of acute renal failure in children. Geographical surveys have demonstrated occurrence of HUS in both an epidemic and endemic manner (1) and familial occurrences have been reported (2). The clinical and histopathologi= cal features of HUS are well-known,while aetiology and physiopathology are not completely understood. The long-term evolution of renal function in children is incompletely documented. The recognition that HUS is not a conseq uence of a single clinico-pathologic entity may explain the conflicting results regarding prognosis.

Hemorrhagic Colitis With Escherichia coli 0157:H7 Preceding Adult Hemolytic Uremic Syndrome

Escherichia coli serotype O157:H7 is a rarely identified organism that has recently been associated with hemorrhagic colitis in all age groups and with the hemolytic uremic syndrome (HUS) in children. We now report the development of HUS in two young women following enteric infection with E coli O157:H7. Both patients were hospitalized because of the severity of their colitis. They later developed major hemolysis requiring transfusion and significant renal failure requiring, in one case, hemodialysis. One patient underwent laparotomy, where sterile ascites, marked right colonic edema, and intraserosal hemorrhage were noted. Both women survived and are currently improving. Fecal E coli serotype O157:H7 was sought only after routine cultures were negative and features of HUS were recognized. The search for the E coli was facilitated by the continued availability of stool cultures obtained early in the course of the illness. The source of infection was not ascertained, but ingestion of untreated water was a feature of both cases. The HUS is a potential complication of the hemorrhagic colitis associated with E coli serotype O157:H7 and may develop in adults as well as children following enteric infection with this organism.