Case Report

Complete Renal Recovery in Pediatric Patient with Streptococcus pneumoniae-Associated HUS: A Case Report and Literature Review

Elizabeth Mancuso1, Jeanvieve Cannon1, Bree C. Kramer2, Michael Bowler2, Oscar G. Gómez-Duarte3, Beverly Schaefer4, Wayne R. Waz5, Xiaoyan Wu5*

1Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

2Division of Pediatric Critical Care, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

3Division of Pediatric Infectious disease, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

4Division of Pediatric Hematology and Oncology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

5Division of Nephrology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

*Corresponding author: Xiaoyan Wu, Department of PediatricNephrology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, 1001 Main Street, Buffalo, NY 14203, USA

Received Date: 31 May 2023

Accepted Date: 05 June 2023

Published Date: 08 June 2023

Citation: Mancuso E, Cannon J, Kramer BC, Bowler M, Gómez-Duarte OG, et al. (2023) Complete Renal Recovery in Pediatric Patient with Streptococcus pneumoniae-Associated HUS: A Case Report and Literature Review. J Urol Ren Dis 08: 1334. https://doi.org/10.29011/2575-7903.001334.

Abstract

Hemolytic uremic syndrome caused by invasive pneumococcal disease (Sp-HUS) is rare in children and adolescents, has a high mortality in the acute phase and is often complicated by long term renal sequelae. Here we report a 22-month-old female with no significant past medical history who was initially admitted for severe streptococcal pneumonia, which ultimately progressed to acute kidney injury and hemolytic anemia. Broad functional complement analysis showed low C3 and C4, and genetic complement analyses were negative. Coagulation studies were examined at the time of HUS diagnosis. The presence of normal fibrinogen levels associated with findings consistent with HUS was used to rule out disseminated intravascular coagulopathy (DIC). The patient required hemodialysis and received plasmapheresis. The patient did not receive C5 blockade. During a follow up time of 12 months, the patient showed no signs of renal sequelae.

Keywords: Acute kidney injury; Hemodialysis; Hemolytic Uremic Syndrome (HUS); Pediatrics; Plasmapheresis; Thrombotic Microangiopathy (TMA); Streptococcal pneumoniae-associated HUS (Sp-HUS); Thomsen-Friedenreich (T) antigen (T-antigen)

Introduction

Thrombotic Microangiopathy (TMA) is a clinicalpathological syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. Hemolytic Uremic Syndrome (HUS) is a heterogeneous group of diseases that result in a common feature of TMA. While most cases of HUS in the pediatric population are associated with an antecedent diarrheal illness caused by Shiga-toxin producing Escherichia coli (STEC), there are other, non-diarrheal, infections that lead to HUS. [1-3] One such infection is Streptococcus pneumoniae, which can lead to pneumococcal HUS (Sp-HUS). Pneumococcal HUS accounts for approximately 5% of the total cases of HUS in the pediatric population, with the highest prevalence found in children less than two years of age. [1-4] The incidence of HUS complicating invasive pneumococcal infections is estimated to be 0.4 to 0.6%. [3,5,6] The clinical features typically occur 3 to 13 days after the onset of the acute pneumococcal infection. [6,7] When compared with STEC HUS, patients with Sp-HUS are typically younger and usually have higher morbidity and mortality. Historically, Sp-HUS has been characterized with a severe acute disease course resulting in prolonged hospital admissions, with patients requiring frequent hemodialysis and multiple transfusions of platelets and Packed Red Blood Cells (pRBCs). Additionally, there is a higher incidence of long-term kidney and liver injury associated with Sp-HUS [8].

The exact pathophysiology of Sp-HUS has not yet been determined, however, the Thomsen-Friedenreich (T) antigen is known to play a crucial role. [9-11] The T-antigen is a component of the surface structure of erythrocytes, platelets and glomerular endothelial cells and is normally hidden by neuraminic acid. Neuraminidase, produced by S pneumoniae, cleaves N-acetylneuraminic acid from glycoproteins on the plasma membranes resulting in exposure of the T-antigen on these cells. Preformed anti-T antigen IgM antibodies can subsequently interact with the exposed T-antigen, initiating the cascade of events that leads to Sp-HUS. Additionally, abnormalities in the alternative complement pathway may contribute to the course of Sp-HUS. [12,13] Evidence demonstrates that pneumococcal neuraminidase can also disrupt Factor H (an important inhibitor of the alternative complement pathway) and impair its ability to effectively bind to host cells. This loss of function can then lead to indiscriminate complement activation and host cell injury. [14] In fact, complement (C3) and factor H have been found to be lower in patients with Sp-HUS. Further evidence to support the role of the complement system in HUS can be based on the effectiveness of the complement C5 inhibitor, eculizumab, as a treatment modality in some cases. [12]Here we report one case of Sp-HUS in a female patient who was diagnosed at age of 22 months. Her primary organ manifestations were respiratory failure due to pneumonia and acute kidney injury. Her invasive pneumococcal infection was treated with IV antibiotics and HUS was managed with hemodialysis and plasmapheresis. Broad functional and genetic complement analyses were negative, and she did not receive anti-complement treatment. Ultimately, she survived the acute phase of Sp-HUS and had complete renal recovery.

Case Presentation

A previously healthy 22-month-old female presented to the emergency department of a hospital in the northeastern United States with respiratory distress. Four days prior to presentation, she presented to the same emergency department for one day of fever and rash and was discharged on the same day with a diagnosis of viral upper respiratory infection. The patient was up-to-date on her vaccinations and had no history of sick contacts. In the emergency department, her temperature was 38.9°C, pulse was 212 beats per minute, blood pressure was 83/44 mmHg, respiratory rate was 68 breaths per minute, and oxygen saturation was 98% on room air. Her physical examination was remarkable for tachypnea with accessory muscle use and diminished breath sounds on the left side. CXR demonstrated left sided pneumonia with effusion as well as consolidation of the right upper lobe (Figure 1A). Blood cultures were obtained and the patient received IV ceftriaxone and vancomycin for community acquired pneumonia. High flow nasal cannula was initiated due to moderate respiratory distress. She had decreased urine output despite fluid resuscitation. She had no signs of active bleeding. She subsequently progressed to respiratory failure within hours and was intubated before being admitted to the Pediatric Intensive Care Unit (PICU) for management of acute respiratory failure and sepsis in the setting of bilateral pneumonia. On admission labs were significant for hemolytic anemia with a hemoglobin of 5.8 g/dL, LDH of 4,906 unit/L (nl 155-345 unit/L), haptoglobin of 12mg/dL (nl 30-200 mg/dL) (Figure 2, upper); thrombocytopenia with platelets of 10 x 109/L (Figure 2, left lower), and acute kidney injury with a serum creatinine of 1.68mg/ dL, BUN of 59mg/dL (Figure 3). Of note, the patient had a white count of 8.5 x 109/L and moderate schistocytes on peripheral smear (data not shown). Her UA was significant for 1+ protein (30mg/ dL) without gross hematuria. DIC panel was significant for a prolonged PT of 17.3 sec (nl 11-15 sec), prolonged aPTT of 71.1 sec. (nl 25-34 sec), elevated fibrinogen of 573mg/dL (nl 200-470 mg/dL), and D-Dimer of 5.31mcg/mL (Figure 2, right lower).


Figure 1: CXR on admission (A) and day 15 (B) of the hospitalization. A. There are bilateral infiltratesand left pleural effusion (red errors). B. There is a large cavitary lesion in left lower lobe of the lung indicating necrotizing pneumonia in the setting of Streptococcus pneumoniae infection (blood culture was positive on admission & tracheal aspirate was positive on hospital day 2) (red errors). Antibiotics (Azithromycin, vancomycin and ceftriaxone) were initiated on admission; azithromycin was given one dose, and vancomycin was discontinued on hospital day 4. Ceftriaxone was continued until hospital day 18 at which time the patient was started on amoxicillin. The S. pneumoniae  strain was susceptible to all antibiotics tested including penicillin, clindamycin and erythromycin. Patient remained on amoxicillin for approximately 2 weeks to complete one month of antibiotics therapy.