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

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.

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

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Irina Pevzner ◽  
Kirill Goryunov ◽  
Valentina Vtorushina ◽  
Vasily Popkov ◽  
Denis Silachev ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Urinary Excretion ◽  
Kidney Injury ◽  
Kidney Damage ◽  
Urine Samples ◽  
Reference Level ◽  
Control Group ◽  
Tubular Damage ◽  
Urine Biomarkers ◽  
Rate Of Increase

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.

scholarly journals Kidney Tubular Damage Secondary to Deferasirox: Systematic Literature Review

Children ◽  
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.

scholarly journals Renal function in premature infants in the neonatal period

2020 ◽  
Vol 10 (6) ◽  
pp. 19-25
Author(s):  
Anna N. Obukhova ◽  
Olga V. Khaletskaya ◽  
Elena V. Tush
Keyword(s):  
Acute Kidney Injury ◽  
Body Weight ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Preterm Infants ◽  
Gestational Age ◽  
Very Low Birth Weight ◽  
Kidney Injury ◽  
The Third ◽  
Group I

The aim of the investigation was to assess the functional state of the kidneys of preterm infants of various gestational ages with signs of acute kidney injury. Materials and Methods. The study included 30 preterm infants born at 29 to 36 weeks gestation with signs of acute kidney injury. Patients were divided into two groups: group I included children with low body weight, born at 3236 weeks of gestation; group II with very low birth weight, born at 2931 weeks of gestation. In the study of kidney function, the main markers were analyzed serum creatinine, urea, diuresis level, glomerular filtration rate (GFR) at the third week of life, as well as at discharge from the hospital when reaching the postconceptual gestational age of 36.0 [35.0; 39.0] weeks. Severity was assessed in both groups of patients. Results. In both groups of children, a slight degree of severity was recorded, the risk stage (Risk) according to the pRIFLE classification criteria (2007). The evaluation of the biochemical blood test did not show a statistically significant difference in creatinine, urea, GFR, and the rate of diuresis between groups of children with low body weight and very low birth weight. In both groups of patients, creatinine and urea levels in the third week of life exceeded the age standards. By the time the postconceptual gestational age was reached at 36.0 [35.0; 39.0] weeks, there was a statistically significant decrease in the level of these indicators in patients of both groups. In addition, it was found that premature children are at risk for the formation of hyperoxaluria (53% in the structure of crystalluria). Conclusion. Timely diagnosis of acute kidney injury in premature newborns will allow adequate therapy to prevent the progression and further formation of terminal renal failure. It is important to determine the level of excretion of oxalates in the urine to prevent the development of urolithiasis.

Acute kidney injury in preterm neonates with ≤30 weeks of gestational age and its risk factors

2019 ◽  
Vol 71 (5) ◽  
Author(s):  
Rita Ladeiras ◽  
Filipa Flor-De-Lima ◽  
Henrique Soares ◽  
Bárbara Oliveira ◽  
Hercília Guimarães
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Gestational Age ◽  
Kidney Injury ◽  
Preterm Neonates

scholarly journals AT1 and AT2 receptors modulate renal tubular cell necroptosis in angiotensin II-infused renal injury mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yongjun Zhu ◽  
Hongwang Cui ◽  
Jie Lv ◽  
Haiqin Liang ◽  
Yanping Zheng ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Injury ◽  
Critical Role ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Tubular Cell ◽  
Tubular Damage ◽  
Renal Tubular Cell ◽  
Ang Ii ◽  
Renal Tubular

AbstractAbnormal renin-angiotensin system (RAS) activation plays a critical role in the initiation and progression of chronic kidney disease (CKD) by directly mediating renal tubular cell apoptosis. Our previous study showed that necroptosis may play a more important role than apoptosis in mediating renal tubular cell loss in chronic renal injury rats, but the mechanism involved remains unknown. Here, we investigate whether blocking the angiotensin II type 1 receptor (AT1R) and/or angiotensin II type 2 receptor (AT2R) beneficially alleviates renal tubular cell necroptosis and chronic kidney injury. In an angiotensin II (Ang II)-induced renal injury mouse model, we found that blocking AT1R and AT2R effectively mitigates Ang II-induced increases in necroptotic tubular epithelial cell percentages, necroptosis-related RIP3 and MLKL protein expression, serum creatinine and blood urea nitrogen levels, and tubular damage scores. Furthermore, inhibition of AT1R and AT2R diminishes Ang II-induced necroptosis in HK-2 cells and the AT2 agonist CGP42112A increases the percentage of necroptotic HK-2 cells. In addition, the current study also demonstrates that Losartan and PD123319 effectively mitigated the Ang II-induced increases in Fas and FasL signaling molecule expression. Importantly, disruption of FasL significantly suppressed Ang II-induced increases in necroptotic HK-2 cell percentages, and necroptosis-related proteins. These results suggest that Fas and FasL, as subsequent signaling molecules of AT1R and AT2R, might involve in Ang II-induced necroptosis. Taken together, our results suggest that Ang II-induced necroptosis of renal tubular cell might be involved both AT1R and AT2R and the subsequent expression of Fas, FasL signaling. Thus, AT1R and AT2R might function as critical mediators.

scholarly journals Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 572
Author(s):  
Jung-Yeon Kim ◽  
Jungmin Jo ◽  
Jaechan Leem ◽  
Kwan-Kyu Park
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Renal Injury ◽  
Manganese Superoxide Dismutase ◽  
Immune Cell ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Kidney Injury ◽  
Pleiotropic Effects ◽  
Induced Apoptosis ◽  
Vascular Adhesion

Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity.

scholarly journals Biomarkers of Renal Injury in Cirrhosis: Association with Acute Kidney Injury and Recovery after Liver Transplantation

Nephron ◽  
2017 ◽  
Vol 138 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Ashwani K. Singal ◽  
Bradford Jackson ◽  
Glauber B. Pereira ◽  
Kirk B. Russ ◽  
Paul Stephen Fitzmorris ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Acute Kidney Injury ◽  
Renal Injury ◽  
Kidney Injury

scholarly journals Renalase and Biomarkers of Contrast-Induced Acute Kidney Injury

2015 ◽  
Vol 6 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Maciej T. Wybraniec ◽  
Katarzyna Mizia-Stec
Keyword(s):  
Acute Kidney Injury ◽  
Renal Injury ◽  
Amine Oxidase ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Creatinine Concentration ◽  
Invasive Cardiology ◽  
Proximal Tubular ◽  
Novel Biomarkers

Background: Contrast-induced acute kidney injury (CI-AKI) remains one of the crucial issues related to the development of invasive cardiology. The massive use of contrast media exposes patients to a great risk of contrast-induced nephropathy and chronic kidney disease development, and increases morbidity and mortality rates. The serum creatinine concentration does not allow for a timely and accurate CI-AKI diagnosis; hence numerous other biomarkers of renal injury have been proposed. Renalase, a novel catecholamine-metabolizing amine oxidase, is synthesized mainly in proximal tubular cells and secreted into urine and blood. It is primarily engaged in the degradation of circulating catecholamines. Notwithstanding its key role in blood pressure regulation, renalase remains a potential CI-AKI biomarker, which was shown to be markedly downregulated in the aftermath of renal injury. In this sense, renalase appears to be the first CI-AKI marker revealing an actual loss of renal function and indicating disease severity. Summary: The purpose of this review is to summarize the contemporary knowledge about the application of novel biomarkers of CI-AKI and to highlight the potential role of renalase as a functional marker of contrast-induced renal injury. Key Messages: Renalase may constitute a missing biochemical link in the mutual interplay between kidney and cardiac pathology known as the cardiorenal syndrome.

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

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

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

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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