Non‐invasive differentiation of non‐rejection kidney injury from acute rejection in pediatric renal transplant recipients

Archdekin, Ben; Sharma, Atul; Gibson, Ian W.; Rush, David; Wishart, David S.; Blydt-Hansen, Tom

doi:10.1111/petr.13364

Cited by 9 publications

(9 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a single-center pediatric cohort study [ 64 ], Archdekin et al extended their previous work for detection of patterns related to allograft kidney injuries using the same set of quantified metabolites for identification of clinically relevant classifier of NRKI independent of acute rejection. Urine samples without rejection were split into NRKI, pre-NRKI, and no NRKI.…”

Section: Metabolomics In Kidney Transplantationmentioning

confidence: 99%

“…The NRKI discriminant score distinguished between NRKI from samples with no NRKI and pre-NRKI. In addition, the NRKI score sensitivity was found to significantly discriminate between NRKI and rejection (CMR, AMR, and mixed rejection): in the subset of all samples with elevated serum creatinine, the score was successfully tested for differentiating the two different conditions [ 64 ]. Regarding the NRKI score, some metabolites (such as Proline [ 65 ] or ADMA [ 65 , 66 ]) have been previously linked to reduced GFR [ 19 ].…”

Section: Metabolomics In Kidney Transplantationmentioning

confidence: 99%

“…Regarding the NRKI score, some metabolites (such as Proline [ 65 ] or ADMA [ 65 , 66 ]) have been previously linked to reduced GFR [ 19 ]. However, the patterned change in metabolism represented by the entire group of metabolites, rather than each metabolite, was found to be crucial [ 64 ].…”

Section: Metabolomics In Kidney Transplantationmentioning

confidence: 99%

See 2 more Smart Citations

New Insights from Metabolomics in Pediatric Renal Diseases

Riccio¹,

Valentino²,

Passaro³

et al. 2022

Children

View full text Add to dashboard Cite

Renal diseases in childhood form a spectrum of different conditions with potential long-term consequences. Given that, a great effort has been made by researchers to identify candidate biomarkers that are able to influence diagnosis and prognosis, in particular by using omics techniques (e.g., metabolomics, lipidomics, genomics, and transcriptomics). Over the past decades, metabolomics has added a promising number of ‘new’ biomarkers to the ‘old’ group through better physiopathological knowledge, paving the way for insightful perspectives on the management of different renal diseases. We aimed to summarize the most recent omics evidence in the main renal pediatric diseases (including acute renal injury, kidney transplantation, chronic kidney disease, renal dysplasia, vesicoureteral reflux, and lithiasis) in this narrative review.

show abstract

Section: Metabolomics In Kidney Transplantationmentioning

confidence: 99%

Section: Metabolomics In Kidney Transplantationmentioning

confidence: 99%

See 1 more Smart Citation

New Insights from Metabolomics in Pediatric Renal Diseases

Riccio¹,

Valentino²,

Passaro³

et al. 2022

Children

View full text Add to dashboard Cite

show abstract

“…The sample size determined for this study aligns with previously published drug metabolomic studies and cisplatin AKI incidence. [69][70][71][72][73] Metabolomics analysis. Metabolomics analyses of serum and urine for the discovery cohort will be done using a Waters Xevo G2-S quadrupole time-of-flight (QToF) mass spectrometer.…”

Section: Sample Size Considerationsmentioning

confidence: 99%

A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol

Jain

Huang

Lee

et al. 2021

Can J Kidney Health Dis

Self Cite

View full text Add to dashboard Cite

Background: Cisplatin, a chemotherapy used to treat solid tumors, causes acute kidney injury (AKI), a known risk factor for chronic kidney disease and mortality. AKI diagnosis relies on biomarkers which are only measurable after kidney damage has occurred and functional impairment is apparent; this prevents timely AKI diagnosis and treatment. Metabolomics seeks to identify metabolite patterns involved in cell tissue metabolism related to disease or patient factors. The A Canadian study of Cisplatin mEtabolomics and NephroToxicity (ACCENT) team was established to harness the power of metabolomics to identify novel biomarkers that predict risk and discriminate for presence of cisplatin nephrotoxicity, so that early intervention strategies to mitigate onset and severity of AKI can be implemented. Objective: Describe the design and methods of the ACCENT study which aims to identify and validate metabolomic profiles in urine and serum associated with risk for cisplatin-mediated nephrotoxicity in children and adults. Design: Observational prospective cohort study. Setting: Six Canadian oncology centers (3 pediatric, 1 adult and 2 both). Patients: Three hundred adults and 300 children planned to receive cisplatin therapy. Measurements: During two cisplatin infusion cycles, serum and urine will be measured for creatinine and electrolytes to ascertain AKI. Many patient and disease variables will be collected prospectively at baseline and throughout therapy. Metabolomic analyses of serum and urine will be done using mass spectrometry. An untargeted metabolomics approach will be used to analyze serum and urine samples before and after cisplatin infusions to identify candidate biomarkers of cisplatin AKI. Candidate metabolites will be validated using an independent cohort. Methods: Patients will be recruited before their first cycle of cisplatin. Blood and urine will be collected at specified time points before and after cisplatin during the first infusion and an infusion later during cancer treatment. The primary outcome is AKI, defined using a traditional serum creatinine-based definition and an electrolyte abnormality-based definition. Chart review 3 months after cisplatin therapy end will be conducted to document kidney health and survival. Limitations: It may not be possible to adjust for all measured and unmeasured confounders when evaluating prediction of AKI using metabolite profiles. Collection of data across multiple sites will be a challenge. Conclusions: ACCENT is the largest study of children and adults treated with cisplatin and aims to reimagine the current model for AKI diagnoses using metabolomics. The identification of biomarkers predicting and detecting AKI in children and adults treated with cisplatin can greatly inform future clinical investigations and practices.

show abstract

“…Characteristic urine NMR spectra were also demonstrated in murine renal ischemia-reperfusion injury models [17,18]. Archdekin et al using mass spectrometry of urine samples demonstrated the potential of a urine metabolite classifier to detect non-rejection kidney injury in pediatric kidney transplant patients and non-invasively discriminated non-rejection kidney injury from rejection [19]. While metabolomic profiles have been investigated in prematurity, low birth weight neonates, perinatal asphyxia, pediatric respiratory and neurological diseases, gastrointestinal diseases and inborn errors of metabolism, only very few clinical studies have been published that investigated the application of a metabolomic approach in pediatric AKI [20,21].…”

Section: Introductionmentioning

confidence: 99%

Urinary NMR Profiling in Pediatric Acute Kidney Injury—A Pilot Study

Muhle‐Goll

Eisenmann

Luy

et al. 2020

IJMS

View full text Add to dashboard Cite

Acute kidney injury (AKI) in critically ill children and adults is associated with significant short- and long-term morbidity and mortality. As serum creatinine- and urine output-based definitions of AKI have relevant limitations, there is a persistent need for better diagnostics of AKI. Nuclear magnetic resonance (NMR) spectroscopy allows for analysis of metabolic profiles without extensive sample manipulations. In the study reported here, we examined the diagnostic accuracy of NMR urine metabolite patterns for the diagnosis of neonatal and pediatric AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition. A cohort of 65 neonatal and pediatric patients (0–18 years) with established AKI of heterogeneous etiology was compared to both a group of apparently healthy children (n = 53) and a group of critically ill children without AKI (n = 31). Multivariate analysis identified a panel of four metabolites that allowed diagnosis of AKI with an area under the receiver operating characteristics curve (AUC-ROC) of 0.95 (95% confidence interval 0.86–1.00). Especially urinary citrate levels were significantly reduced whereas leucine and valine levels were elevated. Metabolomic differentiation of AKI causes appeared promising but these results need to be validated in larger studies. In conclusion, this study shows that NMR spectroscopy yields high diagnostic accuracy for AKI in pediatric patients.

show abstract

Non‐invasive differentiation of non‐rejection kidney injury from acute rejection in pediatric renal transplant recipients

Cited by 9 publications

References 50 publications

New Insights from Metabolomics in Pediatric Renal Diseases

New Insights from Metabolomics in Pediatric Renal Diseases

A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol

Urinary NMR Profiling in Pediatric Acute Kidney Injury—A Pilot Study

Contact Info

Product

Resources

About