Evaluation of Tubular Dysfunction Using Urine Biomarkers in Children with COVID-19

Background: : Drug-induced Acute Kidney Injury (AKI) develops in 10-15% of patients who receive nephrotoxic medications. Urinary biomarkers of renal tubular dysfunction may detect nephrotoxicity early and predict AKI. Methods:: We prospectively studied patients who received aminoglycosides, vancomycin, amphotericin, or calcineurin inhibitors, and collected their serial urine while on therapy. Patients who developed drug-induced AKI (fulfilling KDIGO criteria) were matched with non-AKI controls in a 1:2 ratio. Their urine samples were batch-analyzed at time-intervals leading up to AKI onset; the latter benchmarked against the final day of nephrotoxic therapy in non- AKI controls. Biomarkers examined include clusterin, beta-2-microglobulin, KIM1, MCP1, cystatin-C, trefoil-factor- 3, NGAL, interleukin-18, GST-Pi, calbindin, and osteopontin; biomarkers were normalized with corresponding urine creatinine. Results:: Nine of 84 (11%) patients developed drug-induced AKI. Biomarkers from 7 AKI cases with pre-AKI samples were compared with those from 14 non-AKI controls. Corresponding mean ages were 55(±17) and 52(±16) years; baseline eGFR were 99(±21) and 101(±24) mL/min/1.73m2 (all p=NS). Most biomarker levels peaked before the onset of AKI. Median levels of 5 biomarkers were significantly higher in AKI cases than controls at 1-3 days before AKI onset (all µg/mmol): clusterin [58(8-411) versus 7(3-17)], beta-2-microglobulin [1632(913-3823) versus 253(61-791)], KIM1 [0.16(0.13-0.76) versus 0.07(0.05-0.15)], MCP1 [0.40(0.16-1.90) versus 0.07(0.04-0.17)], and cystatin-C [33(27-2990) versus 11(7-19)], all p<0.05; their AUROC for AKI prediction were >0.80 (confidence intervals >0.50), with average accuracy highest for clusterin (86%), followed by beta-2-microglobulin, cystatin-C, MCP1, and KIM1 (57%) after cross-validation. Conclusion: : Serial surveillance of these biomarkers could improve the lead time for nephrotoxicity detection by days.

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Urine biomarkers of renal renin–angiotensin system activity: Exploratory analysis in humans with and without obstructive sleep apnea

Physiological Reports ◽

10.14814/phy2.14376 ◽

2020 ◽

Vol 8 (6) ◽

Cited By ~ 1

Author(s):

Patrick J. Hanly ◽

Sofia Ahmed ◽

Chris D. Fjell ◽

George B. Handley ◽

Darlene Sola ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Renin Angiotensin System ◽

Exploratory Analysis ◽

Angiotensin System ◽

System Activity ◽

Renin Angiotensin ◽

Urine Biomarkers ◽

Obstructive Sleep

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Acute kidney injury, metabolic acidosis, and hypercalcemia with proximal tubular dysfunction—a diagnostic challenge: Answers

Pediatric Nephrology ◽

10.1007/s00467-021-05033-8 ◽

2021 ◽

Author(s):

Adem Yasin Köksoy

Keyword(s):

Acute Kidney Injury ◽

Metabolic Acidosis ◽

Kidney Injury ◽

Tubular Dysfunction ◽

Diagnostic Challenge ◽

Proximal Tubular Dysfunction ◽

Proximal Tubular

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Validity and Cost-Effectiveness of Pediatric Home Respiratory Polygraphy for the Diagnosis of Obstructive Sleep Apnea in Children: Rationale, Study Design, and Methodology

Methods and Protocols ◽

10.3390/mps4010009 ◽

2021 ◽

Vol 4 (1) ◽

pp. 9

Author(s):

Esther Oceja ◽

Paula Rodríguez ◽

María Jurado ◽

Maria Luz Alonso ◽

Genoveva del Río ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Cost Effectiveness ◽

Sleep Apnea ◽

Therapeutic Interventions ◽

Diagnostic Process ◽

Urine Biomarkers ◽

Obstructive Sleep ◽

Respiratory Polygraphy ◽

The Cost ◽

The Impact

Obstructive sleep apnea (OSA) in children is a prevalent, albeit largely undiagnosed disease associated with a large spectrum of morbidities. Overnight in-lab polysomnography remains the gold standard diagnostic approach, but is time-consuming, inconvenient, and expensive, and not readily available in many places. Simplified Home Respiratory Polygraphy (HRP) approaches have been proposed to reduce costs and facilitate the diagnostic process. However, evidence supporting the validity of HRP is still scarce, hampering its implementation in routine clinical use. The objectives were: Primary; to establish the diagnostic and therapeutic decision validity of a simplified HRP approach compared to PSG among children at risk of OSA. Secondary: (a) Analyze the cost-effectiveness of the HRP versus in-lab PSG in evaluation and treatment of pediatric OSA; (b) Evaluate the impact of therapeutic interventions based on HRP versus PSG findings six months after treatment using sleep and health parameters and quality of life instruments; (c) Discovery and validity of the urine biomarkers to establish the diagnosis of OSA and changes after treatment.

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Functional tests to guide management in an adult with loss of function of type-1 angiotensin II receptor

Pediatric Nephrology ◽

10.1007/s00467-021-05018-7 ◽

2021 ◽

Author(s):

Daan H. H. M. Viering ◽

Anneke P. Bech ◽

Jeroen H. F. de Baaij ◽

Eric J. Steenbergen ◽

A. H. Jan Danser ◽

...

Keyword(s):

Angiotensin Ii ◽

Collecting Duct ◽

Perinatal Period ◽

Tubular Dysfunction ◽

Loss Of Function ◽

Angiotensin Ii Receptor ◽

Salt Wasting ◽

Truncating Mutation ◽

Urinary Potassium

AbstractBackgroundGenetic loss of function ofAGT(angiotensinogen),REN(renin),ACE(angiotensin-converting enzyme), orAGTR1(type-1 angiotensin II receptor) leads to renal tubular dysgenesis (RTD). This syndrome is almost invariably lethal. Most surviving patients reach stage 5 chronic kidney disease at a young age.MethodsHere, we report a 28-year-old male with a homozygous truncating mutation inAGTR1(p.Arg216*), who survived the perinatal period with a mildly impaired kidney function. In contrast to classic RTD, kidney biopsy showed proximal tubules that were mostly normal. During the subsequent three decades, we observed evidence of both tubular dysfunction (hyperkalemia, metabolic acidosis, salt-wasting and a urinary concentrating defect) and glomerular dysfunction (reduced glomerular filtration rate, currently ~30 mL/min/1.73 m2, accompanied by proteinuria). To investigate the recurrent and severe hyperkalemia, we performed a patient-tailored functional test and showed that high doses of fludrocortisone induced renal potassium excretion by 155%. Furthermore, fludrocortisone lowered renal sodium excretion by 39%, which would have a mitigating effect on salt-wasting. In addition, urinary pH decreased in response to fludrocortisone. Opposite effects on urinary potassium and pH occurred with administration of amiloride, further supporting the notion that a collecting duct is present and able to react to fludrocortisone.ConclusionsThis report provides living proof that even truncating loss-of-function mutations inAGTR1are compatible with life and relatively good GFR and provides evidence for the prescription of fludrocortisone to treat hyperkalemia and salt-wasting in such patients.

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