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Deciphering molecular clues to paediatric urinary tract infection
Urinary tract infection (UTI) is one of the most common bacterial infections in children, and being able to identify patients with UTI who are at risk of kidney damage at an early stage is key to the development of better approaches to treatment and prevention, says A/Prof Chao Sing Ming.

Clinician researchers at KK Women’s and Children’s Hospital (KKH) are closing in on molecular clues found in urine, which may be able to help predict the risk of kidney damage in children with urinary tract infection (UTI) at an earlier stage.

“Kidney scarring is the ultimate morbidity associated with early childhood UTI, and is an implicating risk factor for hypertension, impaired kidney function and complications of pregnancy in later life,” says Principal Investigator, Associate Professor Chao Sing Ming, who is leading the research effort.

She added, “Being able to identify patients with UTI who are at risk of kidney damage at an early stage is key to helping us develop better approaches to treatment and prevention.”

Examining the innate immune response

UTI is one of the most common bacterial infections in children, and one of the leading causes of febrile illness necessitating hospital admission in infants and young children. While the majority of these patients will have limiting disease with no involvement of the kidneys, up to 25 percent will eventually develop kidney damage and scarring which permanently replaces functioning tissue.

To develop a more accurate and focused approach to management, KKH nephrologists A/Prof Chao Sing Ming, Dr Ng Yong Hong and Dr Indra Ganesan carried out a prospective cohort study, in collaboration with scientists and bioinformatics experts from the Agency for Science Technology and Research (A*STAR) and Lund University, Sweden. The study was supported by KKH’s Department of Diagnostic and Interventional Imaging and KK Research Centre, and funded by the Biomedical Research Council.

Using high throughput biotechnology with advanced multiplexing immunoassay, the team examined urine samples from 121 children with febrile UTI, looking for early urinary proteomic signatures that could be implicated in acute kidney infection – also known as acute pyelonephritis (APN) – and the development of kidney scarring.

“To the medical researcher, urine is liquid gold,” says A/Prof Chao.

“Obtainable without harming or distressing the patient – which is of utmost importance in young children. The analysis of urine also confers immense advantage in the study of renal diseases as urine is in direct contact with the kidney tissues where the disease occurs, and contains valuable downstream biomarkers that can be directly measured and studied,” she continued.

Of the 121 patients tested, 55 percent were diagnosed with APN, of which 43 percent went on to develop kidney scarring. The team further discovered distinguishing proteomic signatures in the urine samples of children with APN as well as proteomic signatures predictive of kidney scarring.

“Our study findings led us to conclude that urinary proteomic signatures could serve as early markers of kidney infection, and help to predict the risk of kidney scarring in a child with UTI,” says A/Prof Chao.

“These biomarkers could potentially be used as a non-invasive means to stratify the risk of children developing kidney damage following UTI, fuelling the development of more precise and targeted management, and sparing most patients’ unnecessary distress and costs of further investigations and management.”

Pursuing a deeper understanding of pathogenic dynamics

Already forging ahead, A/Prof Chao and the team have widened their research efforts in pursuit of a deeper understanding of the whole pathogenetic dynamics of UTI at a molecular level – including host genetic susceptibility and genetic polymorphism, uropathogen genomics, the longitudinal immune response and the resultant longitudinal clinical outcome.

“In order to harness the rapidly developing advanced technologies relevant to research, it is necessary for the clinicians to collaborate with biomedical scientists and bioinformatics experts,” asserts A/Prof Chao.

“KKH has in place well-established clinical pathways, a well-curated patient cohort and standardised management protocols, which are paramount for clinical data accuracy.”

“We are fortunate to have access to A*STAR’s expertise in biotechnology, enabling the simultaneous and accurate analysis of large batches of bio samples. With advancements in bioinformatics software, large amounts of raw multidimensional data that used to take years to be modelled and integrated can now be transformed into relevant information within a much shorter period of time that can help us better understand, anticipate and ultimately combat the disease.”

About the Author

Assoc. Prof. Chao Sing Ming
Senior Consultant, Nephrology Service, KKH

A/Prof Chao Sing Ming graduated with a MBBS and Master of Medicine (Paediatrics) from the National University of Singapore, specialising in Paediatric Nephrology. Her subspecialty interests include Childhood Urinary Tract Infection, Voiding Dysfunction, Nephrotic Syndrome, Childhood Lupus Nephritis and other general renal problems in children.

Source: Special Delivery Volume 65 Issue 4. Copyright © KK Women’s
and Children’s Hospital. Reproduced with permission.

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