Assessment of Urinary Kidney Injury Molecule-1 as an Indicator of Early Renal Insult in Children with Cystic Fibrosis

BACKGROUND: The risk of acute kidney injury in cystic fibrosis (CF) patients is due to renal tubular affection by CFTR gene. AIM: Our study aimed at early detection of renal impairment in CF patients, to enable careful monitoring and adjustment of nephrotoxic medications. METHODS: Fifty patients with CF were enrolled in our study; they were age- and sex-matched to 40 healthy control children. All subjects were screened by urine analysis, measurements of kidney function tests, fractional excretion of sodium, β2-microglobulin (beta-2-M) excretion, and renal ultrasound examination. Urinary kidney injury molecule-1 (KIM-1) was assayed using ELISA technique. RESULTS: Both urinary beta-2-M and KIM-1 concentrations were significantly higher in CF patients compared to the control group (p < 0.001). The duration of the disease was significantly positively correlated with the urinary beta-2-M and KIM-1 levels (r = 0.6 and 0.7, respectively; p < 0.01). CONCLUSIONS: Our results showed that urinary KIM-1 can be considered as a sensitive early indicator of acute renal injury.

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Anticoagulant Related Nephropathy Induced by Dabigatran

Case Reports in Nephrology ◽

10.1155/2018/7381505 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Nazia Sharfuddin ◽

Mahra Nourbakhsh ◽

Alan Box ◽

Hallgrimur Benediktsson ◽

Daniel A. Muruve

Keyword(s):

Acute Kidney Injury ◽

Iga Nephropathy ◽

Kidney Injury ◽

Volume Overload ◽

Fractional Excretion ◽

Bleeding Risk ◽

Renal Ultrasound ◽

Nonvalvular Atrial Fibrillation ◽

Fractional Excretion Of Sodium ◽

Ultrasound Findings

We describe a case of biopsy-proven dabigatran related nephropathy in a patient without underlying IgA nephropathy. To date, dabigatran related nephropathy was only reported in patients with concurrent or undiagnosed IgA nephropathy, suggesting that it may predispose patients to dabigatran associated injury. The patient is an 81-year-old woman with multiple medical comorbidities, including nonvalvular atrial fibrillation, who was anticoagulated with dabigatran. She presented to hospital with acute kidney injury in the setting of volume overload. Her estimated glomerular filtration rate decreased from a baseline of 57 mL/min/1.73 m2 to 4 mL/min/1.73 m2, necessitating hemodialysis. Renal ultrasound findings, fractional excretion of sodium, and urinalysis suggested acute kidney injury. Renal biopsy showed acute tubular injury, tubular red blood cell casts, and an absence of active glomerulonephritis, similar to the pathological findings of warfarin related nephropathy. A diagnosis of anticoagulant related nephropathy secondary to dabigatran was therefore established. This case demonstrates that dabigatran, like warfarin, may increase tubular bleeding risk in patients, irrespective of underlying kidney or glomerular disease.

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Equine urinary N-acetyl-β-D-glucosaminidase assay validation and correlation with other markers of kidney injury

Journal of Veterinary Diagnostic Investigation ◽

10.1177/1040638719867124 ◽

2019 ◽

Vol 31 (5) ◽

pp. 688-695 ◽

Cited By ~ 1

Author(s):

Rosemary L. Bayless ◽

A Russell Moore ◽

Diana M. Hassel ◽

Brittney J. Byer ◽

Gabriele A. Landolt ◽

...

Keyword(s):

Kidney Injury ◽

Standard Addition ◽

Fractional Excretion ◽

Reference Intervals ◽

Gamma Glutamyl Transferase ◽

Renal Tubular Epithelium ◽

Coefficients Of Variation ◽

Fractional Excretion Of Sodium ◽

Renal Tubular ◽

Glutamyl Transferase

Detection of equine acute kidney injury (AKI) is hindered by limited markers of early renal damage in horses. N-acetyl-β-D-glucosaminidase (NAG), a lysosomal enzyme in renal tubular epithelium released into urine during tubular insult, has shown promise for early identification of AKI in humans and other species. We validated an assay for NAG in equine urine and measured urinary NAG in 7 azotemic and 7 non-azotemic client-owned adult horses. The enzymatic NAG assay was validated using within- and between-run coefficients of variation (CVs), recovery following standard addition, and linearity of dilution. Intra- and inter-run CVs (21% and 3.2%, respectively), average recovery following standard addition (99–109%), and linearity under serial dilution ( R2 = 0.997) were satisfactory. Urine NAG index was significantly correlated with urinary fractional excretion of sodium (FENa; ρ = 0.76, p < 0.001) and plasma creatinine (ρ = 0.74, p = 0.001). Median urine NAG indices were higher in azotemic horses ( p = 0.006), in horses with increased urinary FENa ( p = 0.006), and in horses with increased urine gamma-glutamyl transferase index ( p = 0.032). Urine NAG can be measured in horses and shows positive correlation with 2 current renal biomarkers. Additional work is needed to establish normal equine reference intervals and characterize the increase of urine NAG index in horses in relation to tubular injury.

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Terlipressin Attenuates Hemorrhagic Shock-Induced Acute Kidney Injury in Rats

10.21203/rs.3.rs-1171115/v1 ◽

2022 ◽

Author(s):

Leticia Urbano Cardoso Castro ◽

Denise Aya Otsuki ◽

Talita Rojas Sanches ◽

Felipe Lima Souza ◽

Mirela Aparecida Rodrigues Santinho ◽

...

Keyword(s):

Acute Kidney Injury ◽

Body Weight ◽

Hemorrhagic Shock ◽

Fluid Resuscitation ◽

Kidney Injury ◽

Fractional Excretion ◽

Organ Damage ◽

Receptor Expression ◽

Control Group ◽

Fractional Excretion Of Sodium

Abstract Hemorrhagic shock (HS), a major cause of trauma-related mortality, is mainly treated by crystalloid fluid administration, typically with lactated Ringer’s (LR). Despite beneficial hemodynamic effects, such as the restoration of mean arterial pressure (MAP), LR administration has major side effects, including organ damage due to edema. One strategy to avoid such effects is pre-hospitalization intravenous administration of the potent vasoconstrictor terlipressin, which can restore hemodynamic stability/homeostasis and has anti-inflammatory effects. Wistar rats were subjected to HS for 60 min, at a target MAP of 30–40 mmHg, thereafter being allocated to receive LR infusion at 3 times the volume of the blood withdrawn; at 2 times the volume, plus terlipressin (10 µg/100 g body weight); and at an equal volume, plus terlipressin (10 µg/100 g body weight). A control group comprised rats not subjected to HS and receiving no fluid resuscitation or treatment. At 15 min after fluid resuscitation/treatment, the blood previously withdrawn was reinfused. At 24 h after HS, MAP was higher among the terlipressin-treated animals. Terlipressin also improved post-HS survival and provided significant improvements in glomerular/tubular function (creatinine clearance), neutrophil gelatinase-associated lipocalin expression, fractional excretion of sodium, aquaporin 2 expression, tubular injury, macrophage infiltration, IL-6 levels, IL-18 levels, and NF-κB expression. In terlipressin-treated animals, there was also significantly higher ANG II type 1 receptor expression and normalization of AVP 1a receptor expression. Terlipressin could be a viable therapy for HS-induced acute kidney injury, likely attenuating such injury by modulating the inflammatory response via the AVP 1a receptor.

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Risk Factors, Clinical Characteristics, and Prognosis of Acute Kidney Injury in Hospitalized COVID-19 Patients: A Retrospective Cohort Study

Medicines ◽

10.3390/medicines8010004 ◽

2021 ◽

Vol 8 (1) ◽

pp. 4

Author(s):

Panupong Hansrivijit ◽

Kinjal P. Gadhiya ◽

Mounika Gangireddy ◽

John D. Goldman

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Troponin I ◽

Urine Analysis ◽

Kidney Injury ◽

Fractional Excretion ◽

Positive Pressure ◽

St Segment ◽

Fractional Excretion Of Sodium ◽

Wave Change

Background: Acute kidney injury (AKI) is a serious complication of COVID-19. Methods: Records of hospitalized adult patients with confirmed SARS-CoV-2 infection from 1 March to 31 May 2020 were retrospectively reviewed. Results: Of 283 patients, AKI occurred in 40.6%. From multivariate analyses, the risk factors of AKI in COVID-19 can be divided into: (1) demographics/co-morbidities (male, increasing age, diabetes, chronic kidney disease); (2) other organ involvements (transaminitis, elevated troponin I, ST segment/T wave change on electrocardiography); (3) elevated biomarkers (ferritin, lactate dehydrogenase); (4) possible bacterial co-infection (leukocytosis, elevated procalcitonin); (5) need for advanced oxygen delivery (non-invasive positive pressure ventilation, mechanical ventilation); and (6) other critical features (ICU admission, need for vasopressors, acute respiratory distress syndrome). Most AKIs were due to pre-renal (70.4%) and intrinsic (34.8%) causes. Renal replacement therapy was more common in intrinsic AKI. Both pre-renal (HR 3.2; 95% CI 1.7–5.9) and intrinsic AKI (HR 7.7; 95% CI 3.6–16.3) were associated with higher mortality. Male, stage 3 AKI, higher baseline and peak serum creatinine and blood urea nitrogen were prevalent in intrinsic AKI. Urine analysis and the fractional excretion of sodium and urea were not helpful in distinguishing intrinsic AKI from other causes. Conclusions: AKI is very common in COVID-19 and is associated with higher mortality. Characterization of AKI is warranted due to its diverse nature and clinical outcome.

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Renal Involvement in Children with Type 2 Diabetes Mellitus Onset: A Pilot Study

Children ◽

10.3390/children8080627 ◽

2021 ◽

Vol 8 (8) ◽

pp. 627

Author(s):

Pierluigi Marzuillo ◽

Anna Di Sessa ◽

Pier Luigi Palma ◽

Giuseppina Rosaria Umano ◽

Cesare Polito ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Involvement ◽

Kidney Injury ◽

Fractional Excretion ◽

Tubular Damage ◽

Beta 2 ◽

Beta 2 Microglobulin

Type 2 Diabetes Mellitus (T2DM) is a main cause of chronic kidney disease (CKD) in adulthood. No studies have examined the occurrence of acute kidney injury (AKI)—that enhances the risk of later CKD—and renal tubular damage (RTD)—that can evolve to AKI—in children with onset of T2DM. We aimed to evaluate the prevalence and possible features of AKI and RTD in a prospectively enrolled population of children with onset of T2DM. We consecutively enrolled 10 children aged 12.9 ± 2.3 years with newly diagnosed T2DM. AKI was defined according to the KDIGO criteria. RTD was defined by abnormal urinary beta-2-microglobulin and/or tubular reabsorption of phosphate (TRP) < 85% and/or fractional excretion of Na > 2%. None of the patients developed AKI, whereas 3/10 developed RTD with high beta-2-microglobulin levels (range: 0.6–1.06 mg/L). One of these three patients also presented with reduced TRP levels (TRP = 70%). Proteinuria was observed in two out of three patients with RTD, while none of patients without RTD had proteinuria. Patients with RTD presented higher beta-2-microglobulin, acute creatinine/estimated basal creatinine ratio, and serum ketones levels compared with patients without RTD. In conclusion, in our pilot observation, we found that none of the 10 children with T2DM onset developed AKI, whereas three of them developed RTD.

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Fractional excretion of magnesium as an early indicator of renal tubular damage in normotensive diabetic nephropathy

Turkish Journal of Biochemistry ◽

10.1515/tjb-2019-0232 ◽

2020 ◽

Vol 45 (5) ◽

pp. 543-551

Author(s):

Fatih Ozcelik ◽

Serif Kactas ◽

Halime Hanim Pence ◽

Saadet Kurcenli ◽

Erdim Sertoglu ◽

...

Keyword(s):

Fractional Excretion ◽

Study Patient ◽

Control Group ◽

Tubular Damage ◽

Renal Tubular Damage ◽

Renal Tubular ◽

Excretion Rates ◽

Urine And Serum ◽

Diagnostic And Prognostic Value

AbstractObjectivesThe aim of the present study is to evaluate the diagnostic powers of fractional magnesium, sodium and potassium as markers of renal tubular damage in normotensive type 2 diabetes mellitus (T2DM) patients with respect to microalbuminuria and estimated glomerular filtration rate (eGFR).Materials and methodsForty healthy volunteers and 91 normotensive T2DM patients were included in the study. Patient group was divided into two according to albuminuria level; 49 were normoalbuminuric and 42 were microalbuminuric. In addition to albumin in urine, urine and serum Na, K, Mg and creatinine values were measured to calculate fractional electrolyte excretion rates.ResultsIn normoalbuminuric and microalbuminuric groups, fractional excretion of magnesium (FEMg) values were found to be significantly higher than the control group (p < 0.05). There was a moderate correlation between FEMg and albümin to cratinin ratio (ACR) (Spearman r = 0.3215, p < 0.05). In the ROC analysis for eGFR and FEMg based on microalbuminuria, the areas under the curve were 0.625 and 0.732, respectively (diagnostic sensitivity 59.52% and 66.67%; specificity 70.79% and 77.53%, p < 0.05).ConclusionFor renal tubular damage predicted by microalbuminuria, FEMg could be accepted as a candidate biochemical marker with diagnostic and prognostic value.

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Urinary Measurement of Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 Helps Diagnose Acute Pyelonephritis in a Preclinical Model

Journal of Biomarkers ◽

10.1155/2013/413853 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Hahn-Ey Lee ◽

Sun Hee Lee ◽

Minki Baek ◽

Hwang Choi ◽

Kwanjin Park

Keyword(s):

Acute Pyelonephritis ◽

Time Course ◽

Kidney Injury ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Preclinical Model ◽

Urinary Ngal ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Kidney Injury Molecule 1 ◽

Neutrophil Gelatinase

Background. The study assessed whether measurement of urinary biomarkers of acute kidney injury could be helpful in diagnosing acute pyelonephritis and subsequent scarring. Method. Escherichia coli J96 (0.3 mL inoculum containing 1×109/mL) was directly injected into the renal cortex of 3-week-old female Sprague Dawley rats (n=20), with saline substituted in a control group (n=10). Following the injection, urine was collected 2, 7, 14, 28, and 42 days after injection. Urinary neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and interleukin-18 were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The levels of the biomarkers were adjusted for creatinine. Time course changes within a group or between the groups were compared. Correlation analysis was performed to understand the relationship between urinary levels and histological scarring. Results. Significantly elevated urinary NGAL was evident at two and seven days after injection, and Kim-1 was elevated at two days after injection. Receiver operating characteristic analyses confirmed the sensitivity of these markers at these times. No urinary marker at acute stage of APN was correlated with the amount of future scarring, negating their predictive value. Conclusion. Urinary NGAL and Kim-1 could be helpful in diagnosing febrile urinary tract infection in children.

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