P1828A PANEL OF URINE BIOMARKERS FOR EARLY KIDNEY INJURY DETECTION IN NEWBORNS

Abstract Background and Aims Neonatal kidney damage is a wide spread pathology, especially among preterm infants. Acute kidney injury (AKI) in newborns remains one of the most important problems because the features of neonatal nephrogenesis and physiology. The current clinical criteria for the diagnosis of AKI, including pediatric scales pRIFLE and nRIFLE, rely on glomerulal filtration rate (GFR), blood urea nitrogen (BUN), and serum creatinine (SCr), which are the late biomarkers detectable only within days or weeks after kidney damage occurred, and therefore have limitations when used within the first days after birth. Therefore, sensitive and specific tests for early diagnostics of kidney injury are extremely needed in neonatology. Urine biomarkers appear to be promising for early diagnosis of AKI. Quite often renal pathologies result in markedly increased (or decreased) urinary excretion of a number of protein biomarkers, indicating subclinical tubular injury while conventional AKI signs are not manifested yet. The aim of this study was to determine clinical value of urine molecular biomarkers for the prediction of acute kidney injury in newborns. Method Urine samples from newborns with congenital malformation were collected on the 1st day after born, and then once a week until the 21th postnatal day. Urine samples were centrifuged, aliquoted and stored at –80°С until testing. The next urinary biomarkers were analyzed: calbindin 1, clusterin, IL-18, KIM-1, GST-π, MCP-1 and NGAL. Quantitative determination was performed with immunoassay kit Bio-Plex Pro™ RBM Human Kidney Toxicity Panel 1 (Bio-Rad Inc., USA) and Human NGAL ELISA kit (Invitrogen, Germany). Control group included five age-matched healthy infants. Results 8 of 20 patients showed a direct correlation of increased NGAL levels in urine (50-fold compared to control group) with high levels of C-reactive protein in the blood (3-10-fold rise above the reference level). NGAL is the most sensitive marker for assessing AKI or tubular damage. These 8 patients were further investigated for other urine biomarkers. The IL-18 level in urine was slightly increased in 4 patients. IL-18 is proposed to be a predictor for AKI severity and mortality in children with critical illness. KIM-1 has low basal expression in the normal kidney but its appearance is highly specific and sensitive sign for nephrotoxicity in proximal tubules. We observed the increase of KIM-1 urinary excretion for 7 patients. However, we discover the equal occurrence of decrease or increase of urine MCP-1 through studied patients. Elevated levels of urine MCP-1 were earlier observed in experimental maleate induced azotemia, LPS injection and in model of unilateral ureteral obstruction (UUO). An increase of KIM-1 and/or MCP-1 urinary excretion is known to be associated with some risk of AKI development. We found 3-fold growth of urine clusterin in 7 children. It is noticed, that clusterin increased in damaged tubular cells during polycystic kidney disease and renal carcinoma. Additionally, we revealed 7-fold decrease of calbindin 1 in urine of 7 patients. Сalbindin 1 exclusively localized in the kidney distal nephron segment, and its decrease was discribed for models of UUO, glomerulonephritis and cisplatin nephropathy. GST-π protein is found in cells lining the lumen of the distal tubules and is elevated in the urine of patients with sepsis, independently of accompanied AKI. We also observed 10- to 20-fold rising of urine GST-π for all 8 NGAL-positive newborns. Conclusion The specificity, rate of increase, and non-invasive detection of urine markers studied in this work, make them indispensable in clinical practice. However, their use in neonatology is still experimental. We showed potential applicability of wide biomarker panel for early detection and prediction of AKI in newborns.

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PERSPECTIVE URINARY BIOMARKERS ACCORDING TO PATHOGENETIC MECHANISMS OF ACUTE KIDNEY INJURY IN PRETERM-BORN CHILDREN

Neonatology surgery and perinatal medicine ◽

10.24061/2413-4260.xi.3.41.2021.4 ◽

2021 ◽

Vol 11 (3(41)) ◽

pp. 27-33

Author(s):

Y. Hodovanets ◽

A. Frunza

Keyword(s):

Acute Kidney Injury ◽

Body Weight ◽

Gestational Age ◽

Renal Injury ◽

Transient Receptor Potential ◽

Kidney Injury ◽

Transient Receptor Potential Channels ◽

Kidney Damage ◽

Tubular Damage ◽

Preterm Born

Technologies for nursing preterm-born babies have evolved significantly in recent years. However, we still have several unresolved issues, among which acute kidney injury remains one of the most urgent. This pathological clinical syndrome is associated with high rates of morbidity and mortality, especially in premature infants with severe perinatal pathology. Arrester diagnosis is based on the classification proposed in 2012 by the International Expert Group - Kidney Disease: Improving Global Outcomes. The main criteria for verifying the diagnosis of acute renal injury are an increase in serum creatinine levels and a decrease in urine output. The problem of diagnosis and differential diagnosis of acute renal failure in prematurely born children occupies a leading place, because it is still no consensus on the possibilities of using specific biomarkers of kidney damage, and no nomograms are taking into account the gestational age at birth, body weight and the severity of perinatal pathology.Plasma creatinine is still the most commonly used marker of impaired filtration function, but in recent years there have been numerous scientific discussions and new, highly sensitive, and highly specific markers of renal injury. In particular, it was proposed to consider functional biomarkers and markers of tubular damage as separate categories, since impaired renal function and the injury itself can coexist independently, simultaneously, or a transition of categories is observed. Plasma cystatin C, urinary and serum fractions of alpha-1-microglobulin and beta-2-microglobulin, lipocalin associated with neutrophil gelatinase, and others are promising biomarkers. Attention is focused on the importance of the epigenetic concept in the formation of kidney damage, blocking of the renin- angiotensin-aldosterone-antidiuretic hormone system, and the role of transient receptor potential channels in the modulation of basic renal functions. Metabolic urine profiles are widely studied taking into account gestational age and body weight.

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Kidney Tubular Damage Secondary to Deferasirox: Systematic Literature Review

Children ◽

10.3390/children8121104 ◽

2021 ◽

Vol 8 (12) ◽

pp. 1104

Author(s):

Martin Scoglio ◽

Maria Domenica Cappellini ◽

Emanuela D’Angelo ◽

Mario G. Bianchetti ◽

Sebastiano A. G. Lava ◽

...

Keyword(s):

Acute Kidney Injury ◽

Literature Review ◽

Systematic Literature Review ◽

Kidney Injury ◽

The United States ◽

Kidney Damage ◽

Tubular Damage ◽

Acid Base ◽

Electrolyte Disorders ◽

First Line Therapy

Deferasirox is a first-line therapy for iron overload that can sometimes cause kidney damage. To better define the pattern of tubular damage, a systematic literature review was conducted on the United States National Library of Medicine, Excerpta Medica, and Web of Science databases. Twenty-three reports describing 57 individual cases could be included. The majority (n = 35) of the 57 patients were ≤18 years of age and affected by thalassemia (n = 46). Abnormal urinary findings were noted in 54, electrolyte or acid–base abnormalities in 46, and acute kidney injury in 9 patients. Latent tubular damage was diagnosed in 11 (19%), overt kidney tubular damage in 37 (65%), and an acute kidney injury in the remaining nine (16%) patients. Out of the 117 acid–base and electrolyte disorders reported in 48 patients, normal-gap metabolic acidosis and hypophosphatemia were the most frequent. Further abnormalities were, in decreasing order of frequency, hypokalemia, hypouricemia, hypocalcemia, and hyponatremia. Out of the 81 abnormal urinary findings, renal glucosuria was the most frequent, followed by tubular proteinuria, total proteinuria, and aminoaciduria. In conclusion, a proximal tubulopathy pattern may be observed on treatment with deferasirox. Since deferasirox-associated kidney damage is dose-dependent, physicians should prescribe the lowest efficacious dose.

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Impact of goal-directed hemodynamic management on the incidence of acute kidney injury in patients undergoing partial nephrectomy: a pilot randomized controlled trial

BMC Anesthesiology ◽

10.1186/s12871-021-01288-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qiong-Fang Wu ◽

Hao Kong ◽

Zhen-Zhen Xu ◽

Huai-Jin Li ◽

Dong-Liang Mu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Partial Nephrectomy ◽

Controlled Trial ◽

Intervention Group ◽

Kidney Injury ◽

Control Group ◽

Hemodynamic Management ◽

Randomized Controlled ◽

Renal Hilum ◽

Pilot Randomized Controlled Trial

Abstract Background The incidence of acute kidney injury (AKI) remains high after partial nephrectomy. Ischemia-reperfusion injury produced by renal hilum clamping during surgery might have contributed to the development of AKI. In this study we tested the hypothesis that goal-directed fluid and blood pressure management may reduce AKI in patients following partial nephrectomy. Methods This was a pilot randomized controlled trial. Adult patients who were scheduled to undergo partial nephrectomy were randomized into two groups. In the intervention group, goal-directed hemodynamic management was performed from renal hilum clamping until end of surgery; the target was to maintain stroke volume variation < 6%, cardiac index 3.0–4.0 L/min/m2 and mean arterial pressure > 95 mmHg with crystalloid fluids and infusion of dobutamine and/or norepinephrine. In the control group, hemodynamic management was performed according to routine practice. The primary outcome was the incidence of AKI within the first 3 postoperative days. Results From June 2016 to January 2017, 144 patients were enrolled and randomized (intervention group, n = 72; control group, n = 72). AKI developed in 12.5% of patients in the intervention group and in 20.8% of patients in the control group; the relative reduction of AKI was 39.9% in the intervention group but the difference was not statistically significant (relative risk 0.60, 95% confidence interval [CI] 0.28–1.28; P = 0.180). No significant differences were found regarding AKI classification, change of estimated glomerular filtration rate over time, incidence of postoperative 30-day complications, postoperative length of hospital stay, as well as 30-day and 6-month mortality between the two groups. Conclusion For patients undergoing partial nephrectomy, goal-directed circulatory management during surgery reduced postoperative AKI by about 40%, although not significantly so. The trial was underpowered. Large sample size randomized trials are needed to confirm our results. Trial registration Clinicaltrials.gov identifier: NCT02803372. Date of registration: June 6, 2016.

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Comparison of Effects of Different Statins on Contrast-Induced Acute Kidney Injury in Rats: Histopathological and Biochemical Findings

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/6282486 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Xiao-lei Wang ◽

Tuo Zhang ◽

Liu-hua Hu ◽

Shi-qun Sun ◽

Wei-feng Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Kidney Injury ◽

Lipid Lowering ◽

Control Group ◽

Sprague Dawley ◽

Atorvastatin Group ◽

New Strategy ◽

Ameliorative Effect ◽

Markers Of Oxidative Stress

Statins are a promising new strategy to prevent contrast-induced acute kidney injury (CI-AKI). In this study we compared the ameliorative effect of different statins in a rat model of CI-AKI. Sprague-Dawley rats were divided into five groups: control group; CI-AKI group; CI-AKI + rosuvastatin group (10 mg/kg/day); CI-AKI + simvastatin group (80 mg/kg/day); and CI-AKI + atorvastatin group (20 mg/kg/day). CI-AKI was induced by dehydration for 72 hours, followed by furosemide intramuscular injection 20 minutes before low-osmolar contrast media (CM) intravenous injection. Statins were administered by oral gavage once daily for 3 consecutive days before CM injection and once 4 hours after CM injection. Rats were sacrificed 24 hours after CM injection, and renal function, kidney histopathology, nitric oxide (NO) metabolites, and markers of oxidative stress, inflammation, and apoptosis were evaluated. The results showed that atorvastatin and rosuvastatin but not simvastatin ameliorated CM-induced serum creatinine elevation and histopathological alterations. Atorvastatin and rosuvastatin showed similar effectiveness against CM-induced oxidative stress, but simvastatin was less effective. Atorvastatin was most effective against NO system dysfunction and cell apoptosis, whereas rosuvastatin was most effective against inflammation. Our findings indicate that statins exhibit differential effects in preventing CI-AKI when given at equivalent lipid-lowering doses.

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Controlled Study of Decision-Making Algorithms for Kidney Replacement Therapy Initiation in Acute Kidney Injury

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.02060221 ◽

2021 ◽

pp. CJN.02060221

Author(s):

Yvelynne Kelly ◽

Kavita Mistry ◽

Salman Ahmed ◽

Shimon Shaykevich ◽

Sonali Desai ◽

...

Keyword(s):

Acute Kidney Injury ◽

Length Of Stay ◽

Kidney Injury ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Controlled Study ◽

Control Group ◽

Inpatient Mortality ◽

Icu Length Of Stay ◽

Kidney Replacement Therapy

Background: Acute kidney injury (AKI) requiring kidney replacement therapy (KRT) is associated with high mortality and utilization. We evaluated the use of an AKI-Standardized Clinical Assessment and Management Plan (SCAMP) on patient outcomes including mortality, hospital and ICU length of stay. Methods: We conducted a 12-month controlled study in the ICUs of a large academic tertiary medical center. We alternated use of the AKI-SCAMP with use of a "sham" control form in 4-6-week blocks. The primary outcome was risk of inpatient mortality. Pre-specified secondary outcomes included 30-day mortality, 60-day mortality and hospital and ICU length of stay. Generalized estimating equations were used to estimate the impact of the AKI-SCAMP on mortality and length of stay. Results: There were 122 patients in the AKI-SCAMP group and 102 patients in the control group. There was no significant difference in inpatient mortality associated with AKI-SCAMP use (41% vs 47% control). AKI-SCAMP use was associated with significantly reduced ICU length of stay (mean 8 (95% CI 8-9) vs 12 (95% CI 10-13) days; p = <0.0001) and hospital length of stay (mean 25 (95% CI 22-29) vs 30 (95% CI 27-34) days; p = 0.02). Patients in the AKI-SCAMP group less likely to receive KRT in the context of physician-perceived treatment futility than those in the control group (2% vs 7%, p=0.003). Conclusions: Use of the AKI-SCAMP tool for AKI-KRT was not significantly associated with inpatient mortality but was associated with reduced ICU and hospital length of stay and use of KRT in cases of physician-perceived treatment futility.

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Urine biomarkers for gentamicin-induced acute kidney injury in the neonatal ICU

Critical Care ◽

10.1186/cc9526 ◽

2011 ◽

Vol 15 (S1) ◽

Author(s):

D Jansen ◽

S Heemskerk ◽

L Koster-Kamphuis ◽

TP Bouw ◽

AF Heijst ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Urine Biomarkers ◽

Neonatal Icu

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A case of immersion‐induced acute kidney injury: did momentary hypoxia affect tubular damage?

Internal Medicine Journal ◽

10.1111/imj.14089 ◽

2018 ◽

Vol 48 (11) ◽

pp. 1410-1411

Author(s):

Kyung Min Kim ◽

Soon Kil Kwon ◽

Hye‐Young Kim ◽

Sun Moon Kim ◽

Do Hee Kim ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Tubular Damage

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Morphological and immunohistochemical predictors of renal response to therapy patients with myeloma cast nephropathy and dialysis-dependent acute kidney injury

Terapevticheskii arkhiv ◽

10.26442/00403660.2020.07.000776 ◽

2020 ◽

Vol 92 (7) ◽

pp. 63-69

Author(s):

I. G. Rekhtina ◽

E. V. Kazarina ◽

E. S. Stolyarevich ◽

A. M. Kovrigina ◽

V. N. Dvirnyk ◽

...

Keyword(s):

Acute Kidney Injury ◽

Prognostic Value ◽

Interstitial Fibrosis ◽

Kidney Injury ◽

Response To Therapy ◽

Tubular Damage ◽

Renal Response ◽

Cast Nephropathy ◽

Myeloma Cast Nephropathy ◽

E Cadherin

Aim.Reveal morphological and immunohistochemical predictors of reversibility of dialysis-dependent acute kidney injury (AKI) in patients with myeloma cast nephropathy (MCN) based on the study of kidney biopsy. Materials and methods.Renal pathological findings were studied in 36 patients with MCN and dialysis-dependent stage 3 AKI (AKIN, 2012). The study of biopsy samples was performed by a semi-quantitative and quantitative analysis using computer morphometry. The expression of E-cadherin, vimentin and-smooth muscle actin was determined immunohistochemically in the tubular cells and interstitium. Induction therapy for 26 patients was carried out to bortezomib-based programs; in 10 patients other schemes were used. A comparative analysis of morphological changes in nephrobiopathy depending on the renal response was performed in patients with achieved hematologic remission. Results.Improved renal function was observed only in patients with hematologic response to therapy. There were no differences in the number of sclerotic glomeruli, protein casts, the area of inflammatory interstitial infiltration, and the degree of acute tubular damage in patients with and without renal response. In patients with renal response compared with patients without improving renal function, the area of interstitial fibrosis was less (24.9% and 45.9%, respectively;p=0.001), and the area of E-cadherin expression was larger (15.9% and 7.1%, respectively;p=0.006). Interstitial fibrosis of 40% or more and/or the area of expression of E-cadherin less than 10% of the area of tubulo-interstitium have an unfavorable prognostic value in achieving a renal response in MCN. Conclusion.If the interstitial fibrosis area is 40% or more and the expression area of E-cadherin is less than 10%, the probability of the absence of a renal response is 93.3% (OR=24.5) even when a hematological response to induction therapy is achieved. The number of protein casts, the prevalence of acute tubular damage and inflammatory interstitial infiltration have not prognostic value.

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Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury

Biology Open ◽

10.1242/bio.058852 ◽

2021 ◽

Author(s):

Taro Miyagawa ◽

Yasunori Iwata ◽

Megumi Oshima ◽

Hisayuki Ogura ◽

Koichi Sato ◽

...

Keyword(s):

Acute Kidney Injury ◽

Advanced Glycation End Products ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Tubular Damage ◽

Advanced Glycation ◽

Renal Tubular Damage ◽

Glycation End Products ◽

End Products ◽

Renal Tubular

The full-length receptor for advanced glycation end products (RAGE) is a multiligand pattern recognition receptor. High-mobility group box 1 (HMGB1) is a RAGE ligand of damage-associated molecular patterns that elicits inflammatory reactions. The shedded isoform of RAGE and endogenous secretory RAGE (esRAGE), a splice variant, are soluble isoforms (sRAGE) that act as organ-protective decoys. However, the pathophysiologic roles of RAGE/sRAGE in acute kidney injury (AKI) remain unclear. We found that AKI was more severe, with enhanced renal tubular damage, macrophage infiltration, and fibrosis, in mice lacking both RAGE and sRAGE than in wild-type control mice. Using murine tubular epithelial cells (TECs), we demonstrated that hypoxia upregulated messenger RNA (mRNA) expression of HMGB1 and tumor necrosis factor α (TNF-α), whereas RAGE and esRAGE expressions were paradoxically decreased. Moreover, the addition of recombinant sRAGE canceled hypoxia-induced inflammation and promoted cell viability in cultured TECs. sRAGE administration prevented renal tubular damage in models of ischemia/reperfusion-induced AKI and of anti-glomerular basement membrane (anti-GBM) glomerulonephritis. These results suggest that sRAGE is a novel therapeutic option for AKI.

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