Nykytyuk Svitlana^*, Martynyuk larysa, Martynyuk Lilya, Stelmakh Olena

Horbachevsky Medical University, Ternopil, Ukraine

*Corresponding Author: Nykytyuk Svitlana, Horbachevsky Ternopil National Medical University, Ternopil, Ukraine.

Abstract
Introduction: Hemolytic uremic syndrome (HUS) is one of the most common causes of acute kidney injury in children and is defined by the simultaneous occurrence of microangiopathic hemolytic anemia, thrombocytopenia when the small blood vessels in kidneys become damaged and inflamed.

Case presentation: A clinical case of post-diarrheal HUS in an 8-month-old child complicated by acute kidney injury. The analysis of the literary data from Medscape and Pubmed was carried out. During the examination, the diagnosis was specified. Postdiarrheal HUS. Acute renal failure, oligoanuria stage. Upon admission, the child's condition was severe, caused by impaired kidney function and, as a result, intoxication. The treatment was effective, and the patient's condition improved during the hospitalization period, although establishing the diagnosis required the cooperation of doctors of many specialties and many additional examinations.

Conclusions: This clinical case is a classic, "textbook" example of hemolytic-uremic syndrome in children, which is indicated by the presence of both a typical anamnesis (a clear connection with a previous infection) and a typical clinical picture ("triad"). There is a need to increase knowledge about this pathology among general practitioners and district pediatricians since managing patients with typical HUS in pediatrics requires a complex and multidisciplinary approach.

Keywords: hemolytic uremic syndrome, children, renal failure, acute kidney injury, AkI, Shiga toxin, Escherichia coli.

Introduction
Hemolytic uremic syndrome (HUS) is one of the most common causes of acute kidney injury in children. In Europe, the age category from 6 months up to 5 years is the most vulnerable [1]. The long-term consequences of this disease suffered in childhood are still being investigated. There is evidence that these children have a higher risk of developing CKD in adulthood, which correlates with the duration of the oligouric phase [2]. According to M.I. Burakovsky, the mortality rate in the USA and Western European countries is about 5- 7%, and the same number of children have serious consequences (CKD, hemorrhages, hypertensive disorders) [3]. Therefore, such patients require long-term observation and are often lost from the medical workers' field of view, making the study of pathology even more difficult [4,5].

Case Presentation
An 8-month-old child was admitted with complaints of decreased rate of diuresis, red color of urine, and discomfort during urination. According to the patient's mother's information, the child fell ill on 06.07.2021 when mushy stools appeared after eating fresh greens. There was no increased body temperature. He was treated on an outpatient basis (enterosorbents, diet). On 06.17.2021, multiple liquid stools and refused to eat, which the mother associates with introducing milk mixture into the diet. He was hospitalized at his residence (Kramatorsk) and received treatment - antibiotic therapy and infusion therapy. On 06.19.2021, the pink color of the urine appeared, and the child began to strain when urinating. On 06.20.2021, he was transferred to the intensive care unit, and later, on 06.21.2021, he was again transferred to the intensive care unit in the hospital of Sloviansk. During the treatment, increased azotemia, anemia, thrombocytopenia, and a decrease in the rate of diuresis, proteinuria, and microhematuria were observed. HUS and AKI are suspected. The child was transferred to Kyiv Children's Regional Hospital. He was discharged after treatment on the 15 days. Currently, he is under the observation of a hematologist in the oncology and hematology department of the Ternopil Regional Children's Clinical Hospital.

Anamnesis Vitae: The child is from 3rd pregnancy, 2nd childbirth. The pregnancy was uneventful; the labor was physiological. The child was born with a body weight of 3180 g, height of 56 cm, and 8.9 on the Apgar scale and vaccinated according to the calendar. There were no injuries or operations. Hereditary anamnesis is not burdensome. Allergological anamnesis is not overbearing.

Objective status upon admission: The general condition of the child is severe due to intoxication syndrome, oliguria, hyperazotemia, and anemia. The child is conscious, lethargic, and reacts to the examination by crying.

The skin is pale pink, warm, moist. The face is pasty; the limbs are swollen. T 36.8℃, BM – 10.4 kg. Respiratory rate - 38. min. During auscultation, it's puerile over the entire surface of the lungs without wheezing—SpO2 97-98%.

The tones of the heart are muffled and rhythmic. Heart rate – 117. min, blood pressure – 139.79 mmHg. Capillary filling - 2 s.

No neurological deficit was detected at the time of examination. Pupils D=S, photoreaction preserved.

The abdomen is soft, symmetrical, distended, and accessible to deep palpation. Auscultatively - the noise of peristalsis. There are traces of pink urine in the diaper. There are no stools at the time of inspection. The complete blood count revealed leukocytosis with a shift of the leukoformula to the left, which was observed only in the first days after admission, moderate anemia and thrombocytopenia, which persisted for about a week, increased ESR and reticulocytosis (Table 1). In the biochemical analysis of blood, a significant increase in urea and creatinine is noticeable, which indicates impaired kidney function (Table 2). The coagulogram showed hypofibrinogenemia and a slight rise in APTT, which were successfully corrected during treatment (Table 3).

Among the changes in urinalysis - macrohematuria and massive proteinuria (Table 4).

No changes were detected during instrumental examination and specific laboratory tests (Table 5-6).

Table 1. Complete blood count in dynamics.

Table 2. Biochemical profile in dynamics.

Table 3. Coagulogram in dynamics.

Table 4. Urinalysis in dynamics.

Table 5. Other lab tests.

Microbiological cultures
1. Nose 26.06 and 08.07 – growth of microflora was not detected.
2. Pharynx 26.06 – hemolytic streptococcus; 08.07 – Escherichia coli – III.
3. Blood 08.07 – Staphylococcus epidermidis.
4. Blood (vein) 08.07 - Acinetobacter baumannii, fungi not detected.
5. Blood (catheter)     08.07 - Acinetobacter baumannii, Staphylococcus epidermidis.
6. Blood, subclavian catheter 01.07 - Staphylococcus epidermidis; 09.07 – Staphylococcus epidermidis, no fungi detected.
7. Stomach contents 25.06 – C. Lusitarae.
8. Feces 26.06 – fungi of the genus Candida; 10.07 – pathogenic escherichia, salmonella, and shigella were not detected.
9. Urine 26.06 – C. Lusitarae; 08.07 – BI not detected
10. PD-liquid 08.07 – Acinetobacter baumannii, no fungi detected; 07.19 – microflora growth was not detected. Fungi were not detected.

Table 6. Instrumental examinations.

An ophthalmologist, neurologist, hematologist, and surgeon consulted the patient.
The prescribed treatment.
1. Antibacterial. Antimycotic therapy: Zivox, Ceftriaxone, Ceftum.
2. Efferent methods of detoxification: peritoneal dialysis, plasmapheresis, prolonged hemodiafiltration.
3. Infusion therapy and electrolyte solutions: NaCl 0.9%, NaCl 10%, glucose 5%.
4. Hypotensive therapy: Berlinpril, Amlodipine.
5. Blood components: erythrocyte mass, Albumin 20 %, platelet concentrate.
6. Symptomatic therapy.

Clinical diagnosis: Acute intestinal infection. Postdiarrheal hemolytic uremic syndrome. KDIGO-3, oligoanuria stage. Anemia of moderate severity. Mild thrombocytopenia. Dysmetabolic encephalopathy.

Discussion and Review of The Literature.
This clinical case illustrates the typical course of HUS - the presence of the classic triad – microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury [1,7]. This child is at increased risk of developing this disease (children under 5 years old) [3].

Usually, Escherichia coli, which is capable of Shiga toxin production, is the etiological factor in the development of the HUS8. The most common serotype is O157:H7, but there are cases caused by other serotypes, including O111:H8, O103:H2, O121, O145, O26, and O113, as well as other pathogens, such as bacteria of the Shigella spp. and Streptococcus pneumoniae [9,10,11].

Even though Escherichia coli was not isolated from this child during stool culture, this is not an exclusion criterion. From the anamnesis, it is known that an extended period (12 days) passed between the appearance of symptoms of intestinal infection and kidney damage, which proportionally reduces the probability of identifying an ecotropic factor, according to the study of Mody R.K. et al., published in 2012 [12]. The previous administration of antibiotics is also essential.

When the diagnosis of HUS is established, it is essential to determine its clinical form - typical (associated with diarrhea) or atypical (not associated with infection, genetically induced), since the pathogenesis of both types is slightly different. This will help determine the treatment strategy. For a HUS, there is an orthotropic treatment - factor C5 inhibitor Eculizumab, but due to its high cost, it is not very accessible to patients [13].

In the case of the HUS, which is present in this patient, the basis of treatment is supportive therapy. The most critical points are the well-timed start of correction of blood system changes and early liquid resuscitation. However, the approach to infusion therapy must be individual and consider both the degree of renal dysfunction and the total blood volume loss since patients with HUS can be both hypovolemic (due to dehydration) and hypervolemic (due to fluid retention caused by renal dysfunction). In several independent studies (Poland, 2018; Germany, Hamburg, 2016), it has been proven that the early start of infusion contributes to a better prognosis of HUS, but in fluid-overloaded patients, it can cause heart failure, so all infusion solutions and blood products should be administered slowly and under constant monitoring of vital signs [14,15]. When correcting anemia, it is essential to balance the hemoglobin index and the volume of allocated blood components since the consequences of volemic overload for the myocardium are more dangerous than anemia itself. It was also crucial for this patient to start renal replacement therapy as soon as possible—the method of choice - peritoneal dialysis, which is the "gold standard" for children [18].

As for changes in the hemostasis system, both hyper- and hypocoagulation are possible for HUS. Hypercoagulation is more typical for the beginning of the disease, and hypercoagulation – is for the terminal phase due to the consumption of coagulation factors. However, options for the treatment of this syndrome are different. Currently, no advantages of therapy with heparin, streptokinase, or other anticoagulants over adequate supportive therapy have been found [16]. There is a hypocoagulation syndrome in this clinical case, but it was successfully corrected during the treatment with blood components. The duration of thrombocytopenia in this patient was 11 days, which is consistent with other researchers' data regarding the average time of this syndrome in children (13.7 days) [17].

Despite the typical clinical picture of HUS in a patient, diagnosis is still problematic at the primary and secondary level of medical care due to the low frequency of cases in the world (from 0.2 to 3.4 cases per 100,000 children) [3].

Therefore, we have found the necessity for a complex and multidisciplinary approach to managing patients with typical HUS in pediatrics and increasing knowledge about this pathology among general practitioners and district pediatricians.

Conclusions
1. This clinical case is a classic, "textbook" example of hemolytic-uremic syndrome in children, which is indicated by the presence of both a typical anamnesis (a clear connection with a previous infection) and a typical clinical picture ("triad").

2. There is a need to increase knowledge about this pathology among general practitioners and district pediatricians since managing patients with typical HUS in pediatrics requires a complex and multidisciplinary approach.

Author Contributions
S.O. and M.V. were responsible for the diagnostic procedures, clinical diagnosis, and treatment decisions. S.O. 

And O.Y. wrote the manuscript. A.I., I. A was responsible for the data acquisition. S.O., I.A., and O.Y.

They were responsible for collecting and assembling the articles/published data and their inclusion and interpretation. 

In this review. All authors contributed to the critical manuscript revision for valuable intellectual content. All authors have read and agreed to the published version of the manuscript.

Compliance with Ethics Requirements
"The authors declare no conflict of interest regarding this article. " "The authors declare that all the procedures and experiments of this study respect the ethical standards in the Helsinki Declaration of 1975, as revised in 2008(5), and the national law. Informed consent was obtained. from the patient included in the study. "No funding for this study. "

Acknowledgements: None

List of abbreviations
HUS- Hemolytic uremic syndrome
AKI-Acute kidney insufficiency
CKD - chronic kidney disease
KDIGO-3- kidney disease: Improving Global Outcomes
APTT- Activated partial Thromboplastin time
INR-international normalized ratio

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