Perinatal asphyxia leads to acute kidney damage and increased renal susceptibility in adulthood.

Perinatal asphyxia (PA) poses a significant threat to multiple organs, particularly the kidneys. Diagnosing PA-associated kidney injury remains challenging and treatment options are inadequate. Furthermore, there is a lack of long-term follow-up data regarding the renal implications of PA. In this study, 7-day-old male Wistar rats were exposed to PA using a gas mixture (4% O2; 20% CO2 in N2 for 15 minutes) to investigate molecular pathways linked to renal tubular damage, hypoxia, angiogenesis, heat-shock response, inflammation, and fibrosis in the kidney. In a second experiment, adult rats with a history of PA were subjected to moderate renal ischemia-reperfusion (IR) injury to test the hypothesis that PA exacerbates renal susceptibility. Our results revealed an increased gene expression of renal injury markers (KIM-1, NGAL), hypoxic- and heat shock factors (HIF-1α, HSF-1, HSP-27), pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, MCP-1), and fibrotic markers (TGF-ß, CTGF, Fibronectin) promptly after PA. Moreover, a machine learning model was identified through Random Forest analysis, demonstrating an impressive classification accuracy (95.5%) for PA. Post-PA rats showed exacerbated functional decline and tubular injury and more intense hypoxic-, heat-shock-, pro-inflammatory-, and pro-fibrotic response after renal IRI compared to controls. In conclusion, PA leads to subclinical kidney injury, which may increase the susceptibility to subsequent renal damage later in life. Additionally, the parameters identified through Random Forest analysis provide a robust foundation for future biomarker research in the context of PA.

Effect of Urine Output on the Predictive Precision of NephroCheck in On-Pump Cardiac Surgery With Crystalloid Cardioplegia: Insights from the PrevAKI Study.

OBJECTIVES: Previous studies in other settings suggested that urine output (UO) might affect NephroCheck predictive value. We investigated the correlation between NephroCheck and UO in cardiac surgery patients. DESIGN: Post hoc analysis of a multicenter study. SETTING: University hospital. PARTICIPANTS: Patients who underwent cardiac surgery using cardiopulmonary bypass (CPB) and crystalloid cardioplegia. MEASUREMENTS AND MAIN RESULTS: All patients underwent NephroCheck testing 4 hours after CPB discontinuation. The primary outcome was the correlation between UO, NephroCheck results, and acute kidney injury (AKI, defined according to Kidney Disease: Improving Global Outcomes). Of 354 patients, 337 were included. Median NephroCheck values were 0.06 (ng/mL)2/1,000) for the overall population and 0.15 (ng/mL)2/1,000) for patients with moderate to severe AKI. NephroCheck showed a significant inverse correlation with UO (ρ = -0.17; p = 0.002) at the time of measurement. The area under the receiver characteristic curve (AUROC) for NephroCheck was 0.60 (95% confidence interval [CI], 0.54-0.65), whereas for serum creatinine was 0.82 (95% CI, 0.78-0.86; p < 0.001). When limiting the analysis to the prediction of moderate to severe AKI, NephroCheck had a AUROC of 0.82 (95% CI, 0.77 to 0.86; p<0.0001), while creatinine an AUROC of 0.83 (95% CI, 0.79-0.87; p = 0.001). CONCLUSIONS: NephroCheck measured 4 hours after the discontinuation from the CPB predicts moderate to severe AKI. However, a lower threshold may be necessary in patients undergoing cardiac surgery with CPB. Creatinine measured at the same time of the test remains a reliable marker of subsequent development of renal failure.

Naringin abrogates angiotensin-converting enzyme (ACE) activity and podocin signalling pathway in cobalt chloride-induced nephrotoxicity and hypertension.

PurposeThe persistent and alarming rates of increase in cardiovascular and renal diseases caused by chemicals such as cobalt chloride (CoCl2) in mammalian tissues have led to the use of various drugs for the treatment of these diseases. This study aims at evaluating the nephron-protective action of Naringin (NAR), a metal-chelating antioxidant against CoCl2-induced hypertension and nephrotoxicity.MethodsForty-two male Wistar rats were randomly distributed to seven rats of six groups and classified into Group A (Control), Group B (300 part per million; ppm CoCl2), Group C (300 ppm CoCl2 + 80 mg/kg NAR), Group D (300 ppm CoCl2 + 160 mg/kg NAR), Group E (80 mg/kg NAR), and Group F (160 mg/kg NAR). NAR and CoCl2 were administered via oral gavage for seven days. Biomarkers of renal damage, oxidative stress, antioxidant status, blood pressure parameters, immunohistochemistry of renal angiotensin-converting enzyme and podocin were determined.ResultsCobalt chloride intoxication precipitated hypertension, renal damage, and oxidative stress. Immunohistochemistry revealed higher expression of angiotensin-converting enzyme (ACE) and podocin in rats administered only CoCl2.ConclusionTaken together, the antioxidant and metal-chelating action of Naringin administration against cobalt chloride-induced renal damage and hypertension could be through abrogation of angiotensin-converting enzyme and podocin signalling pathway.

Drug induced nephrotoxicity- A mechanistic approach.

The main goal of the treatment of patients is its effectiveness and safety. However, all currently prescribed drugs being used also have certain adverse effects, which might be seen as an unavoidable but necessary cost of pharmacotherapy. The kidney is the primary organ for xenobiotics elimination, making it particularly susceptible to the harmful effects of drugs and their metabolites during their excretion from the body. Moreover, certain medications have a preferential nephrotoxicity potential, which means that using them increases the risk of kidney injury. Drug nephrotoxicity is, therefore, both a significant problem and a complication of pharmacotherapy. It should be noted that, there is presently no accepted definition of drug-induced nephrotoxicity and no established diagnostic criteria. The current review briefly describes the pathogenic mechanism of drug-induced nephrotoxicity, the various basic drugs with nephrotoxicity potential and the renal biomarkers for the treatment of the drug-related kidney damage.

Evaluation of Novel Urinary Biomarkers in Beagle Dogs With Amphotericin B-Induced Kidney Injury.

Next-generation urinary protein biomarkers have been qualified to enable monitoring for drug-induced kidney injury in toxicology studies conducted in rats. However, there is limited literature on the utility of these biomarkers in dogs. To add to the existing body of knowledge on the utility of the next-generation drug-induced kidney injury (DIKI) biomarkers, we evaluated the value of these biomarkers for the early detection of DIKI in Beagle dogs using a differentiated nephrotoxicant, Amphotericin B (AmpB). In dogs with AmpB-induced kidney injury, we monitored the response of urinary albumin, total protein, clusterin, kidney injury molecule 1, neutrophil gelatinase-associated lipocalin and N-acetyl-beta-D-glucosaminidase. We also measured blood urea nitrogen, serum creatinine and cystatin C. The results showed that urinary clusterin (up to ∼ 112x) was much more sensitive to AmpB-induced kidney injury relative to other biomarkers. Moreover, other than urinary clusterin and to a much lesser extent urinary albumin and total protein, none of the other biomarkers analyzed in this study were more sensitive than blood urea nitrogen and serum creatinine. The AmpB related tubular alterations were characterized by minimal to mild, multifocal necrosis, degeneration, regeneration, dilatation and mineralization. The mild nature of these histopathologic findings further attested to the sensitivity of urinary clusterin to AmpB-induced kidney injury in dogs. These results will help drug developers make informed decisions when selecting urinary biomarkers for monitoring DIKI in dogs for toxicology studies.

Biomarkers Associated with Organ-Specific Involvement in Juvenile Systemic Lupus Erythematosus.

Juvenile systemic lupus erythematosus (JSLE) is characterised by onset before 18 years of age and more severe disease phenotype, increased morbidity and mortality compared to adult-onset SLE. Management strategies in JSLE rely heavily on evidence derived from adult-onset SLE studies; therefore, identifying biomarkers associated with the disease pathogenesis and reflecting particularities of JSLE clinical phenotype holds promise for better patient management and improved outcomes. This narrative review summarises the evidence related to various traditional and novel biomarkers that have shown a promising role in identifying and predicting specific organ involvement in JSLE and appraises the evidence regarding their clinical utility, focusing in particular on renal biomarkers, while also emphasising the research into cardiovascular, haematological, neurological, skin and joint disease-related JSLE biomarkers, as well as genetic biomarkers with potential clinical applications.

Acute and chronic kidney disease after pediatric liver transplantation: An underestimated problem.

Acute and chronic kidney injuries represent critical issues after liver transplantation (LTx), but whereas renal dysfunction in adult transplant patients is well documented, little is known about its prevalence in childhood. It is a challenge to accurately evaluate renal function in patients with liver disease, due to several confounding factors. Creatinine-based equations estimating glomerular filtration rate, validated in nephropathic patients without hepatic issues, are frequently inaccurate in end-stage liver disease, underestimating the real impact of renal disease. Moreover, whereas renal issues observed within 1 year from LTx were often related to acute injuries, kidney damage observed after 5-7 years from LTx, is due to chronic, irreversible mechanisms. Most immunosuppression protocols are based on calcineurin inhibitors (CNIs) and corticosteroids, but mycophenolate mofetil or sirolimus could play significant roles, also in children. Early diagnosis and personalized treatment represent the bases of kidney disease management, in order to minimize its close relation with increased mortality. This review analyzed acute and chronic kidney damage after pediatric LTx, also discussing the impact of pre-existent renal disease. The main immunosuppressant strategies have been reviewed, highlighting their impact on kidney function. Different methods assessing renal function were reported, with the potential application of new renal biomarkers.

Role of the Furosemide Stress Test in Renal Injury Prognosis.

Risk stratification and accurate patient prognosis are pending issues in the management of patients with kidney disease. The furosemide stress test (FST) has been proposed as a low-cost, fast, safe, and easy-to-perform test to assess tubular integrity, especially when compared to novel plasma and urinary biomarkers. However, the findings regarding its clinical use published so far provide insufficient evidence to recommend the generalized application of the test in daily clinical routine. Dosage, timing, and clinical outcomes of the FST proposed thus far have been significantly different, which further accentuates the need for standardization in the application of the test in order to facilitate the comparison of results between series. This review will summarize published research regarding the usefulness of the FST in different settings, providing the reader some insights about the possible implications of FST in clinical decision-making in patients with kidney disease and the challenges that research will have to address in the near future before widely applying the FST.

Protein biomarkers for cardiorenal syndrome.

INTRODUCTION: The term cardiorenal syndrome (CRS) describes the progressive pathology and interactions that develop upon heart and kidney failure. The definition of CRS is not firmly established and has evolved gradually during the last decade. The main clinical challenges associated with CRS are the lack of tools for early disease diagnosis and the inability to predict the development of cardiorenal pathophysiology. Currently several biomarkers have been proposed for improving CRS patient management. However, validation studies are needed to implement these initial findings to the clinical setting. Areas covered: In this review the database PubMed was used for a literature search on the definition and classification of CRS as well as biomarkers for CRS diagnosis and prognosis. Expert opinion: A universally acceptable classification system for CRS is not available. Thus, acquiring mechanistic insights relative to the pathophysiology of the disease is challenging. Reported biomarkers include well-established markers for heart/renal dysfunction and inflammation. Some proteins expressed in both organs have also been associated with CRS, yet their link to disease pathophysiology and organ cross-talk is missing. Establishing the link between deregulated molecular pathways and CRS phenotypes is required to define biological relevance of existing findings and ultimately biology-driven markers and targets.

First-year profile of biomarkers for early detection of renal injury in infants with congenital urinary tract obstruction.

BACKGROUND: Diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. Use of renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and prevention or minimization of definitive renal damage. METHODS: This longitudinal, prospective study analyzed the first-year profile of two serum renal biomarkers: creatinine (sCr) and cystatin C (sCyC); and six urinary renal biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-ß1), retinol-binding protein (RBP), cystatin C (uCyC), and microalbuminuria (µALB) in a cohort of 37 infants with UTO divided into three subgroups: 14/37 with unilateral hydro(uretero)nephrosis, 13/37 with bilateral hydro(uretero)nephrosis, and 10/37 patients with lower urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. RESULTS: All urine biomarkers showed significantly higher values at the first month of life (p ≤ 0.009), while NGAL (p = 0.005), TGF-ß1 (p < 0.001), and µALB (p < 0.001) were high since birth compared to controls. Best single biomarker performances were RBP in bilateral hydronephrosis and LUTO subgroups and KIM-1 in unilateral hydronephrosis subgroup. Best biomarker combination results for all subgroups were obtained by matching RBP with TGF-ß1 or KIM-1 and NGAL with CyC ([AUC] ≤ 0.934; sensitivity ≤ 92.4%; specificity ≤ 92.8%). CONCLUSIONS: RBP, NGAL, KIM-1, TGF-ß1, and CyC, alone and especially in combination, are relatively efficient in identifying surgically amenable congenital UTO and could be of practical use in indicating on-time surgery.

Acute toxic kidney injury.

Substances toxic to the kidney are legion in the modern world. The sheer number and variety, their mutual interactions and, metabolism within the body are a challenge to research. Moreover, the kidney is especially prone to injury owing to its physiology. Acute kidney injury (AKI) induced by poisonous or primarily nephrotoxic substances, may be community acquired with ingestion or inhalation or nosocomial. Many nephrotoxic plants, animal poisons, medications, chemicals and illicit drugs can induce AKI by varying pathophysiological pathways. Moreover, the epidemiology of toxic AKI varies depending on country, regions within countries, socioeconomic status and health care facilities. In this review, we have selected nephrotoxic insults due to medication, plants, animal including snake venom toxicity, environmental, (agri)chemicals and also illicit drugs. We conclude with a section on diagnosis, clinical presentation and management of poisoning accompanied by various organ dysfunction and AKI.

Evaluation of sedative, analgesic, physiological, and laboratory effects of two doses off medetomidine and xylazine in dromedary calves.

The present study aims to comparatively evaluate the effects of different doses of intravenous xylazine and medetomidine on sedation and antinociception scores, and physiological and laboratory parameters in dromedary calves. Thirty clinically healthy male dromedary calves 15 ± 2 weeks old and weighing 95 ± 5.5 kg were studied. Two groups received xylazine at low (0.2 mg/kg) and high (0.4 mg/kg) doses. Two groups received medetomidine at low (10 µg/kg) and high (20 µg/kg) doses. One group received normal saline. Sedation signs were scored using a 3-point scale. Analgesic effect was analyzed using pinpricks. Data were analyzed by one-way ANOVA and Mann-Whitney U-tests. Sedation and antinociception scores of the animals 1 hr after receiving the higher dose of xylazine and medetomidine were significantly higher than that of other groups. Compared with other studied groups, the animals receiving the higher dose of xylazine showed significantly higher potassium and creatinine serum levels after 24 hr. Doses as high as 0.4 mg/kg for xylazine and 20 µg/kg for medetomidine can be considered safe and useful for procedures associated with mild pain in dromedary calves.

Estimating glomerular filtration rate for the full age spectrum from serum creatinine and cystatin C.

Background: We recently published and validated the new serum creatinine (Scr)-based full-age-spectrum equation (FAS crea ) for estimating the glomerular filtration rate (GFR) for healthy and kidney-diseased subjects of all ages. The equation was based on the concept of normalized Scr and shows equivalent to superior prediction performance to the currently recommended equations for children, adolescents, adults and older adults. Methods: Based on an evaluation of the serum cystatin C (ScysC) distribution, we defined normalization constants for ScysC ( Q cysC = 0.82 mg/L for ages <70 years and Q cysC = 0.95 mg/L for ages ≥70 years). By replacing Scr/ Q crea in the FAS crea equation with ScysC/ Q cysC , or with the average of both normalized biomarkers, we obtained new ScysC-based (FAS cysC ) and combined Scr-/ScysC-based FAS equations (FAS combi ). To validate the new FAS cysC and FAS combi we collected data on measured GFR, Scr, ScysC, age, gender, height and weight from 11 different cohorts including n = 6132 unique white subjects (368 children, aged ≤18 years, 4295 adults and 1469 older adults, aged ≥70 years). Results: In children and adolescents, the new FAS cysC equation showed significantly better performance [percentage of patients within 30% of mGFR (P30) = 86.1%] than the Caucasian Asian Paediatric Adult Cohort equation (P30 = 76.6%; P < 0.0001), or the ScysC-based Schwartz equation (P30 = 68.8%; P < 0.0001) and the FAS combi equation outperformed all equations with P30 = 92.1% (P < 0.0001). In adults, the FAS cysC equation (P30 = 82.6%) performed equally as well as the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI cysC ) (P30 = 80.4%) and the FAS combi equation (P30 = 89.9%) was also equal to the combined CKD-EPI equation (P30 = 88.2%). In older adults, FAS cysC was superior (P30 = 88.2%) to CKD-EPI cysC (P30 = 84.4%; P < 0.0001) and the FAS combi equation (P30 = 91.2%) showed significantly higher performance than the combined CKD-EPI equation (P30 = 85.6%) (P < 0.0001). Conclusion: The FAS equation is not only applicable to all ages, but also for all recommended renal biomarkers and their combinations.

Increased urinary neutrophil gelatinase-associated lipocalin in very-low-birth-weight infants with oliguria and normal serum creatinine.

BACKGROUND: In infants, oliguria is defined as a urine output of <1.5 mL/kg/h. The aim of our study was to assess the impact of oliguria on urinary neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C (CysC) levels in very-low-birth-weight infants (VLBWIs) with a normal serum creatinine (Cr) level. METHODS: Fifty-seven VLBWIs were enrolled in the study. Urinary NGAL, serum CysC and Cr levels and urinary NGAL/Cr ratios were measured. Infants with Apgar scores of >5 at 5 min and/or a serum Cr level of >1.5 mg/dL or those treated for patent ductus arteriosus were excluded. In case of antibiotic treatment, blood and urine samples were collected at ≥48 h after discontinuation of antibiotic treatment. RESULTS: There was a significant difference in gestational age between infants with oliguric episodes during hospitalization and those without, but not in birth weight, perinatal or postnatal factors. Gestational age was negatively correlated with urinary NGAL and serum CysC levels and urinary NGAL/Cr ratio (p < 0.05), whereas postnatal age was negatively correlated with serum Cr level and urinary NGAL/Cr ratio (p < 0.05). Of the 117 urine and blood samples collected, 25 (21.4%) were obtained from neonates with oliguric episodes. After adjusting for gestational age and postnatal age, comparison of samples collected in infants with and without oliguric episodes revealed significant differences in the mean level of urinary NGAL and in the urinary NGAL/Cr ratio, but not in mean serum CysC or serum Cr levels. The urinary NGAL level [area under the curve (AUC) 0.886, 95% confidence interval (CI) 0.814-0.937] and urinary NGAL/Cr ratio (AUC 0.853, 95% CI 0.775-0.911) showed significantly greater discrimination for oliguria than serum CysC (AUC 0.610, 95% CI: 0.515-0.699) or serum Cr (AUC 0.747, 95%CI 0.659-0.823) levels. CONCLUSIONS: Urinary NGAL level and urinary NGAL/Cr ratio were more sensitive markers for the presence of oliguria in VLBWIs with normal serum Cr levels than serum CysC level.

Cardiorenal Interactions.

Recently, there has been increased appreciation of the identification and management of comorbidities in heart failure patients, and for therapies targeting conventional heart failure signs and symptoms. Renal dysfunction is common in patients with heart failure and is associated with high morbidity and mortality. Early identification of renal damage through novel biomarkers and the use of new pharmacological strategies aimed at preserving renal function may represent an important objective in the treatment. This article reviews the epidemiology and pathophysiology of cardiorenal syndrome in heart failure, and highlights novel biomarkers and improved therapies targeting renal dysfunction.

A comprehensive analysis of albuminuria in canine chronic kidney disease.

BACKGROUND: Albuminuria, an important marker of decreased kidney function in chronic kidney disease (CKD), is not routinely used for CKD detection or proteinuria appearance. Its relationships with biochemical parameters and blood pressure in dogs are poorly understood. OBJECTIVES: This study aimed to evaluate the relationship of albuminuria with various CKD markers, its correlation with the urinary protein to creatinine ratio (UPC), and hypertension in dogs with early stages of CKD. It also sought to determine the usability of the urinary albumin to creatinine ratio (UAC) for CKD screening. METHODS: The study reviewed records of 102 dogs, categorising them into four groups based on disease status. UAC and UPC ratio, biochemistry and haematology variables, age, and systolic blood pressure were determined. RESULTS: The Pearson's correlation coefficient between log-transformed values of UPC and UAC was r = 0.902 (95% CI: 0.87 to 0.93). Median UAC ratio values were 2.1 mg/g for the Healthy control group (n = 17), 54.2 mg/g for early stages CKD (n = 42), 5.8 mg/g for Acute sick control (n = 30), and 104 mg/g for Chronic sick control (n = 13). Thresholding UAC ratio as an indicator for impaired kidney function with the threshold of 10 mg/g (established based on the receiver operating characteristic curve) had a sensitivity 81.8%, specificity of 89.4%, positive predictive value (PPV) 90%, and negative predictive value (NPV) 80.1%. The correlation of UAC with biochemistry and haematology variables was statistically significant; for SDMA (µg/L), it was r = 0.566 and for other variables, it was weak to moderate. UAC was markedly elevated in cases of severe hypertension. CONCLUSIONS: UAC ratio was significantly different among dogs with impaired and not impaired kidney function. The correlation strength for the UAC and UPC ratios was high. UAC ratio may be a promising marker for proteinuria analysis in dogs with CKD or other kidney function alterations.

Association between echocardiographic indexes and urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in dogs with myxomatous mitral valve disease.

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of tubular damage, and its elevation has been described in human and canine cardiorenal syndrome. The aim was to evaluate the association between echocardiographic indexes and urine NGAL (uNGAL) and uNGAL normalized to urine creatinine (uNGALC) in dogs with MMVD. This is a multicentric prospective cross-sectional study. A total of 77 dogs with MMVD at different ACVIM stages were included. All dogs underwent echocardiography, serum chemistry, and urinalysis. Echocardiographic data analyzed were shortening fraction (SF), left ventricular diastolic (LVIDDn) and systolic (LVIDSn) diameters normalized for body weight, left atrium to aortic root ratio (LA/Ao), maximal (LAVMax) and minimal (LAVMin) left atrial volumes, LA stroke volume (LASV), early diastolic mitral peak velocity (EVmax), EVmax to tissue Doppler E' wave (E/E'), aortic (VTIAo) and mitralic (VTIMit) velocity time integrals and their ratio (VTIMit/VTIAo), and tricuspid regurgitation velocity (TRVmax). In the univariate analysis LASV, TRVmax, LAVMax, LVIDDn, and VTIMit/VTIAo were independent predictors of increased uNGAL and uNGALC; however, only LASV [(OR: 1.96, 95% CI: 1.16 to 3.31) P = 0.01 for NGAL, and (OR: 2.79, 95% CI: 1.50 to 5.17) P < 0.001 for NGALC] and TRVmax [(OR: 1.73, 95% CI: 1.20-2.51) P = 0.002 for NGAL, and (OR: 1.50, 95% CI: 10.07-2.10) P = 0.015 for NGALC] remained statistically significant in the multivariable analysis. Based on our results, LASV and TRVmax are associated with increased uNGAL and uNGALC. These parameters might detect dogs with MMVD at higher risk of developing kidney damage.

Acute Kidney Injury in Neonatal Intensive Care Unit: Epidemiology, Diagnosis and Risk Factors.

Acute kidney injury (AKI) is associated with long-term consequences and poor outcomes in the neonatal intensive care unit. Its precocious diagnosis represents one of the hardest challenges in clinical practice due to the lack of sensitive and specific biomarkers. Currently, neonatal AKI is defined with urinary markers and serum creatinine (sCr), with limitations in early detection and individual treatment. Biomarkers and risk factor scores were studied to predict neonatal AKI, to early identify the stage of injury and not the damage and to anticipate late increases in sCr levels, which occurred when the renal function already began to decline. Sepsis is the leading cause of AKI, and sepsis-related AKI is one of the main causes of high mortality. Moreover, preterm neonates, as well as patients with post-neonatal asphyxia or after cardiac surgery, are at a high risk for AKI. Critical patients are frequently exposed to nephrotoxic medications, representing a potentially preventable cause of AKI. This review highlights the definition of neonatal AKI, its diagnosis and new biomarkers available in clinical practice and in the near future. We analyze the risk factors involving patients with AKI, their outcomes and the risk for the transition from acute damage to chronic kidney disease.

Comparison of diagnostic accuracy of models combining the renal biomarkers in predicting renal scarring in pediatric population with vesicoureteral reflux (VUR).

INTRODUCTION: Renal scarring is prominently observed in children with vesicoureteral reflux (VUR) and can lead to complicated renal outcomes. Although biopsy is the gold standard to detect renal scarring, it is an invasive procedure. There are established renal biomarkers which can help detect renal scarring. Individual biomarkers have not shown to have extensively good discriminatory ability for this. AIM: This paper aims at combining the values of multiple biomarkers in models to detect renal scarring. METHODOLOGY: Secondary data with the values of renal biomarkers like kidney injury molecule-1, neutrophil gelatinase-associated lipocalin (NGAL), and urinary creatinine along with the renal scarring status was considered. Logistic regression, discriminant analysis, Bayesian logistic regression, Naïve Bayes, and decision tree models were developed with these markers. The discriminatory ability of individual biomarkers along with the models was assessed using the area under the curve from ROC curve. Sensitivity, specificity, and misclassification rates were estimated and compared. RESULTS: NGAL was the most predominant renal biomarker in classifying the patients with renal scarring (AUC: 0.77 (0.67, 0.87); p value < 0.001). Each of the model performed better than individual biomarkers. Decision tree (AUC: 0.83 (0.74, 0.91); p value < 0.001) and Naïve Bayes model (misclassification rate = 20.2%) performed the best amongst the models. CONCLUSION: Combining the values of renal biomarkers through a statistical or machine learning model to detect renal scarring is a better approach as compared to considering individual renal biomarkers.

Renal Assessment in Acute Cardiorenal Syndrome.

Cardiorenal syndrome (CRS) is a complex, heterogeneous spectrum of symptoms that has kept cardiologists awake for decades. The heart failure (HF) population being burdened with multimorbidity poses diagnostic and therapeutic challenges even for experienced clinicians. Adding deteriorated renal function to the equation, which is one of the strongest predictors of adverse outcome, we measure ourselves against possibly the biggest problem in modern cardiology. With the rapid development of new renal assessment methods, we can treat CRS more effectively than ever. The presented review focuses on explaining the pathophysiology, recent advances and current practices of monitoring renal function in patients with acute CRS. Understanding the dynamic interaction between the heart and the kidney may improve patient care and support the selection of an effective and nephroprotective treatment strategy.