Decreased urinary uromodulin is potentially associated with acute kidney injury: a systematic review and meta-analysis

You, Ruilian; Zheng, Hua; Xu, Lubin; Ma, Tiantian; Chen, Gang; Xia, Peng; Fan, Xiaohong; Ji, Peili; Wang, Li; Chen, Limeng

doi:10.1186/s40560-021-00584-2

Cited by 12 publications

(6 citation statements)

References 57 publications

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“…Urinary TIMP-1 predicts AKI in pediatric ICU patients 55 , and urinary NAG predicts kidney impairment in cystic fibrosis patients 56 . In contrast to our findings, urinary NGAL may be less useful to predict kidney injury in critically-ill septic patients 57 , and a systematic review has reported decreasing urine Uromodulin is associated with AKI 58 .…”

Section: Discussioncontrasting

confidence: 99%

“…Moreover, with urinary biomarkers, there were positive correlations with kidney clearance (unlike plasma biomarkers, which only negatively correlated with kidney clearance). Uromodulin and EGF positively correlated with residual kidney clearance, raising the question of protective effects and supported by reports of a negative association between urine Uromodulin and kidney injury 58 . EGF receptor activation is associated with kidney recovery in AKI, via epithelial cell regeneration 78 .…”

Section: Discussionmentioning

confidence: 65%

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A novel multiplex biomarker panel for profiling human acute and chronic kidney disease

Van Nynatten,

Miller,

Patel

et al. 2023

Sci Rep

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Acute and chronic kidney disease continues to confer significant morbidity and mortality in the clinical setting. Despite high prevalence of these conditions, few validated biomarkers exist to predict kidney dysfunction. In this study, we utilized a novel kidney multiplex panel to measure 21 proteins in plasma and urine to characterize the spectrum of biomarker profiles in kidney disease. Blood and urine samples were obtained from age-/sex-matched healthy control subjects (HC), critically-ill COVID-19 patients with acute kidney injury (AKI), and patients with chronic or end-stage kidney disease (CKD/ESKD). Biomarkers were measured with a kidney multiplex panel, and results analyzed with conventional statistics and machine learning. Correlations were examined between biomarkers and patient clinical and laboratory variables. Median AKI subject age was 65.5 (IQR 58.5–73.0) and median CKD/ESKD age was 65.0 (IQR 50.0–71.5). Of the CKD/ESKD patients, 76.1% were on hemodialysis, 14.3% of patients had kidney transplant, and 9.5% had CKD without kidney replacement therapy. In plasma, 19 proteins were significantly different in titer between the HC versus AKI versus CKD/ESKD groups, while NAG and RBP4 were unchanged. TIMP-1 (PPV 1.0, NPV 1.0), best distinguished AKI from HC, and TFF3 (PPV 0.99, NPV 0.89) best distinguished CKD/ESKD from HC. In urine, 18 proteins were significantly different between groups except Calbindin, Osteopontin and TIMP-1. Osteoactivin (PPV 0.95, NPV 0.95) best distinguished AKI from HC, and β2-microglobulin (PPV 0.96, NPV 0.78) best distinguished CKD/ESKD from HC. A variety of correlations were noted between patient variables and either plasma or urine biomarkers. Using a novel kidney multiplex biomarker panel, together with conventional statistics and machine learning, we identified unique biomarker profiles in the plasma and urine of patients with AKI and CKD/ESKD. We demonstrated correlations between biomarker profiles and patient clinical variables. Our exploratory study provides biomarker data for future hypothesis driven research on kidney disease.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 65%

A novel multiplex biomarker panel for profiling human acute and chronic kidney disease

Van Nynatten,

Miller,

Patel

et al. 2023

Sci Rep

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“…Experiments from patients and animal studies proved the predictive value of urine UMOD in assessing the morbidity of AKI. Our previous study confirmed a negative correlation between uUMOD and AKI, particularly in pediatric and surgical patients [ 29 ]. Additionally, another study has confirmed the crucial role of circulating uromodulin in regulating systemic oxidative stress by inhibiting transient receptor potential cation channel, subfamily M, member 2 (TRPM2) activity in IRI-induced AKI [ 30 ].…”

Section: Adtkds and Akisupporting

confidence: 87%

From Rare Disorders of Kidney Tubules to Acute Renal Injury: Progress and Prospective

Li,

Hou,

et al. 2024

Kidney Dis

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Background: Acute kidney injury (AKI) is a severe condition marked by rapid renal function deterioration and elevated mortality, with traditional biomarkers lacking sensitivity and specificity. Rare tubulointerstitial diseases encompass a spectrum of disorders, primarily including monogenic diseases, immune-related conditions, and drug-induced tubulointerstitial diseases. The clinical manifestations vary from the electrolyte and acid-base imbalance to kidney function insufficiency, which is associated with AKI in up to 20% of cases. Evidence indicated that rare tubulointerstitial diseases might provide new conceptual insights and perspectives for novel biomarkers and potential therapeutic strategies for AKI. Summary: Autosomal dominant tubulointerstitial kidney disease (ADTKD) and Fanconi syndrome (FS) are rare tubulointerstitial diseases. In ADTKD, UMOD and REN are closely related to AKI by affecting oxidative stress and tubuloglomerular feedback (TGF), which provide potential new biomarkers for AKI. Both rare tubulointerstitial diseases and AKI shared etiologies and treatment responses. From the mechanism standpoint, rare tubulointerstitial diseases and AKI involve tubular transporter injury, initially manifesting as tubular dysfunction in tubulointerstitial disorder and progressing to AKI because of the programmed cell death (PCD) with apoptosis, pyroptosis, or necroptosis of proximal tubule cells. Additionally, mitochondrial dysfunction has been identified as a common mechanism in both tubulointerstitial diseases and AKI induced by drugs, pSS, or monoclonal diseases. In the end, both AKI and FS patients and animal models responded well to the therapy of the primary diseases. Key messages: In this review, we describe an overview of ADTKD and FS to identify their associations with AKI. Mitochondrial dysfunction contributes to rare tubulointerstitial diseases and AKI, which might provide a potential therapeutic target.

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“…For instance, the role of uromodulin (UMOD) and urinary neutrophil gelatinase-associated lipocalin (NGAL) in acute kidney injury (AKI) [23][24][25]. Another biomarker that reflects the significant early steps in disease pathogenesis of necrotizing enterocolitis (NEC) is I-FABP [26][27][28][29].…”

Section: Significance Statementmentioning

confidence: 99%

A comparative proteomic analysis for non‐invasive early prediction of hypoxic‐ischemic injury in asphyxiated neonates

Gurtoo,

Karthikkeyan,

Behera

et al. 2023

Proteomics Clinical Apps

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AimHypoxic Ischemic Encephalopathy (HIE) is one of the principal causes of neonatal mortality and long‐term morbidity worldwide. The neonatal signs of mild cerebral injury are subtle, making an early precise diagnosis difficult. Delayed detection, poor prognosis, and lack of specific biomarkers for the disease are increasing mortality rates. In this study, we intended to identify specific biomarkers using comparative proteomic analysis to predict the severity of perinatal asphyxia so that its outcome can also be prevented.Experimental DesignA case‐control study was conducted on 38 neonates, and urine samples were collected within 24 and 72 h of life. A tandem mass spectrometry‐based quantitative proteomics approach, followed by validation via sandwich ELISA, was performed.ResultsThe LC‐MS/MS‐based proteomics analysis resulted in the identification of 1201 proteins in urine, with 229, 244, and 426 being differentially expressed in HIE‐1, HIE‐2, and HIE‐3, respectively. Axon guidance, Diseases of programmed cell death, and Detoxification of reactive oxygen species pathways were significantly enriched in mild HIE versus severe HIE. Among the differentially expressed proteins in various stages of HIE, we chose to validate four proteins – APP, AGT, FABP1, and FN1 – via sandwich ELISA. Individual and cumulative ROC curves were plotted. AGT and FABP1 together showed high sensitivity, specificity, and accuracy as potential biomarkers for early diagnosis of HIE.ConclusionEstablishing putative urinary biomarkers will facilitate clinicians to more accurately screen neonates for brain injury and monitor the disease progression. Prompt treatment of neonates may reduce mortality and neurodevelopmental impairment.

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Decreased urinary uromodulin is potentially associated with acute kidney injury: a systematic review and meta-analysis

Cited by 12 publications

References 57 publications

A novel multiplex biomarker panel for profiling human acute and chronic kidney disease

A novel multiplex biomarker panel for profiling human acute and chronic kidney disease

From Rare Disorders of Kidney Tubules to Acute Renal Injury: Progress and Prospective

A comparative proteomic analysis for non‐invasive early prediction of hypoxic‐ischemic injury in asphyxiated neonates

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