Advancements in diabetic kidney disease management: integrating innovative therapies and targeted drug development.

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and affects approximately 40% of individuals with diabetes . Cases of DKD continue to rise globally as the prevalence of diabetes mellitus increases, with an estimated 415 million people living with diabetes in 2015 and a projected 642 million by 2040. DKD is associated with significant morbidity and mortality, representing 34% and 36% of all chronic kidney disease deaths in men and women, respectively. Common comorbidities including hypertension and ageing-related nephron loss further complicate disease diagnosis and progression. The progression of DKD involves several mechanisms including glomerular endothelial cell dysfunction, inflammation, and fibrosis. Targeting these mechanisms has formed the basis of several therapeutic agents. Renin-angiotensin-aldosterone system (RAAS) blockers, specifically angiotensin receptor blockers (ARBs), demonstrate significant reductions in macroalbuminuria. Sodium-glucose transporter type 2 (SGLT-2) inhibitors demonstrate kidney protection independent of diabetes control while also decreasing the incidence of cardiovascular events. Emerging agents including glucagon-like peptide 1 (GLP-1) agonists, anti-inflammatory agents like bardoxolone, and mineralocorticoid receptor antagonists show promise in mitigating DKD progression. Many novel therapies including monoclonal antibodies CSL346, lixudebart, and tozorakimab; mesenchymal stem/stromal cell infusion; and cannabinoid-1 receptor inverse agonism via INV-202 are currently in clinical trials and present opportunities for further drug development.

Post-transplant recurrence of focal segmental glomerular sclerosis: consensus statements.

Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review.

Fluid management in children with volume depletion.

Volume depletion is a common condition and a frequent cause of hospitalization in children. Proper assessment of the patient includes a detailed history and a thorough physical examination. Biochemical tests may be useful in selected cases. Understanding the pathophysiology of fluid balance is necessary for appropriate management. A clinical dehydration scale assessing more physical findings may help to determine dehydration severity. Most dehydrated children can be treated orally; however, intravenous therapy may be indicated in patients with severe volume depletion, in those who have failed oral therapy, or in children with altered consciousness or significant metabolic abnormalities. Proper management consists of restoring circulatory volume and electrolyte balance. In this paper, we review clinical aspects, diagnosis, and management of children with volume depletion.

Navigating the microbial maze: unraveling the connection between gut microbiome and pediatric kidney and urinary tract disease.

The gut microbiome is made up of trillions of bacteria, viruses, archaea, and microbes that play a significant role in the maintenance of normal physiology in humans. Recent research has highlighted the effects of the microbiome and its dysbiosis in the pathogenesis and maintenance of kidney disease, especially chronic kidney disease (CKD) and its associated cardiovascular disease. While studies have addressed the kidney-microbiome axis in adults, how dysbiosis may uniquely impact pediatric kidney disease patients is not well-established. This narrative review highlights all relevant studies focusing on the microbiome and pediatric kidney disease that were published between 7/2015 and 7/2023. This review highlights pediatric-specific considerations including growth and bone health as well as emphasizing the need for increased pediatric research. Understanding microbiome-kidney interactions may allow for novel, less invasive interventions such as dietary changes and the use of probiotics to improve preventive care and ameliorate long-term morbidity and mortality in this vulnerable population.

Concurrent use of continuous kidney replacement therapy during extracorporeal membrane oxygenation: what pediatric nephrologists need to know-PCRRT-ICONIC practice points.

Extracorporeal membrane oxygenation (ECMO) provides temporary cardiorespiratory support for neonatal, pediatric, and adult patients when traditional management has failed. This lifesaving therapy has intrinsic risks, including the development of a robust inflammatory response, acute kidney injury (AKI), fluid overload (FO), and blood loss via consumption and coagulopathy. Continuous kidney replacement therapy (CKRT) has been proposed to reduce these side effects by mitigating the host inflammatory response and controlling FO, improving outcomes in patients requiring ECMO. The Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup and the International Collaboration of Nephrologists and Intensivists for Critical Care Children (ICONIC) met to highlight current practice standards for ECMO use within the pediatric population. This review discusses ECMO modalities, the pathophysiology of inflammation during an ECMO run, its adverse effects, various anticoagulation strategies, and the technical aspects and outcomes of implementing CKRT during ECMO in neonatal and pediatric populations. Consensus practice points and guidelines are summarized. ECMO should be utilized in patients with severe acute respiratory failure despite the use of conventional treatment modalities. The Extracorporeal Life Support Organization (ELSO) offers guidelines for ECMO initiation and management while maintaining a clinical registry of over 195,000 patients to assess outcomes and complications. Monitoring and preventing fluid overload during ECMO and CKRT are imperative to reduce mortality risk. Clinical evidence, resources, and experience of the nephrologist and healthcare team should guide the selection of ECMO circuit.

Use of furosemide in preterm neonates with acute kidney injury is associated with increased mortality: results from the TINKER registry.

BACKGROUND: Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. METHODS: The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28 days) receiving intravenous fluids for at least 48 h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). RESULTS: A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational age with AKI who received furosemide compared to those who did not receive furosemide 3.78 [(1.60-8.94); p = 0.003; univariate analysis] and [3.30 (1.11-9.82); p = 0.03]; multivariate logistic regression]. CONCLUSIONS: In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses.

Insight into prevalence, etiology, and modalities of pediatric chronic dialysis: a comprehensive nationwide analysis.

BACKGROUND: This study aimed to determine the prevalence and etiology of kidney failure (KF) among children below 15 years of age receiving chronic dialysis in Saudi Arabia and describe their dialysis modalities. METHODS: This cross-sectional descriptive study was conducted on 8 August 2022, encompassing all 23 pediatric dialysis centers in Saudi Arabia. Data gathered comprised patient demographics, causes of KF, and the dialysis methods employed. Collected data underwent analysis to determine prevalence of children undergoing chronic dialysis, discern underlying causes of KF, and evaluate distribution of patients across different dialysis modalities. RESULTS: The prevalence of children on chronic dialysis is 77.6 per million children living in Saudi Arabia, equating to 419 children. The predominant underlying cause of KF was congenital anomalies of the kidneys and urinary tract (CAKUT), representing a substantial 41% of cases. Following this, others or unknown etiologies accounted for a noteworthy 25% of cases, with focal segmental glomerulosclerosis (FSGS) comprising 13%, glomerulonephritis at 11%, and congenital nephrotic syndrome contributing 10% to etiological distribution. Regarding dialysis modalities employed, 67% of patients were on peritoneal dialysis (PD), while the remaining 33% were on hemodialysis (HD). CONCLUSIONS: This first nationwide study of pediatric chronic dialysis in Saudi Arabia sheds light on the prevalence of children undergoing chronic dialysis and underlying causes of their KF, thereby contributing to our understanding of clinical management considerations. This research serves as a stepping stone for the development of national registries.

Electrolyte disorders related emergencies in children.

This article provides a comprehensive overview of electrolyte and water homeostasis in pediatric patients, focusing on some of the common serum electrolyte abnormalities encountered in clinical practice. Understanding pathophysiology, taking a detailed history, performing comprehensive physical examinations, and ordering basic laboratory investigations are essential for the timely proper management of these conditions. We will discuss the pathophysiology, clinical manifestations, diagnostic approaches, and treatment strategies for each electrolyte disorder. This article aims to enhance the clinical approach to pediatric patients with electrolyte imbalance-related emergencies, ultimately improving patient outcomes.Trial registration This manuscript does not include a clinical trial; instead, it provides an updated review of literature.

Utility of the Kidney Failure Risk Equation and Estimated GFR for Estimating Time to Kidney Failure in Advanced CKD.

RATIONALE & OBJECTIVE: The Kidney Failure Risk Equation (KFRE) predicts the 2-year risk of kidney failure for patients with chronic kidney disease (CKD). Translating KFRE-predicted risk or estimated glomerular filtration rate (eGFR) into time to kidney failure could inform decision making for patients approaching kidney failure. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: CKD Outcomes and Practice Patterns Study (CKDOPPS) cohort of patients with an eGFR<60mL/min/1.73m2 from 34 US nephrology practices (2013-2021). EXPOSURE: 2-year KFRE risk or eGFR. OUTCOME: Kidney failure defined as initiation of dialysis or kidney transplantation. ANALYTICAL APPROACH: Accelerated failure time (Weibull) models used to estimate the median, 25th, and 75th percentile times to kidney failure starting from KFRE values of 20%, 40%, and 50%, and from eGFR values of 20, 15, and 10mL/min/1.73m2. We examined variability in time to kidney failure by age, sex, race, diabetes status, albuminuria, and blood pressure. RESULTS: Overall, 1,641 participants were included (mean age 69±13 years; median eGFR of 28mL/min/1.73m2 [IQR 20-37mL/min/1.73 m2]). Over a median follow-up period of 19 months (IQR, 12-30 months), 268 participants developed kidney failure, and 180 died before reaching kidney failure. The median estimated time to kidney failure was widely variable across patient characteristics from an eGFR of 20mL/min/1.73m2 and was shorter for younger age, male sex, Black (versus non-Black), diabetes (vs no diabetes), higher albuminuria, and higher blood pressure. Estimated times to kidney failure were comparably less variable across these characteristics for KFRE thresholds and eGFR of 15 or 10mL/min/1.73m2. LIMITATIONS: Inability to account for competing risks when estimating time to kidney failure. CONCLUSIONS: Among those with eGFR<15mL/min/1.73m2 or KFRE risk>40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Our results demonstrate that estimating time to kidney failure in advanced CKD can inform clinical decisions and patient counseling on prognosis, regardless of whether estimates are based on eGFR or the KFRE. PLAIN-LANGUAGE SUMMARY: Clinicians often talk to patients with advanced chronic kidney disease about the level of kidney function expressed as the estimated glomerular filtration rate (eGFR) and about the risk of developing kidney failure, which can be estimated using the Kidney Failure Risk Equation (KFRE). In a cohort of patients with advanced chronic kidney disease, we examined how eGFR and KFRE risk predictions corresponded to the time patients had until reaching kidney failure. Among those with eGFR<15mL/min/1.73m2 or KFRE risk > 40%), both KFRE risk and eGFR showed similar relationships with time to kidney failure. Estimating time to kidney failure in advanced CKD using either eGFR or KFRE can inform clinical decisions and patient counseling on prognosis.

Epidemiology data on the cost and outcomes associated with pediatric acute kidney injury.

BACKGROUND: Hospitalized children with acute kidney injury (AKI) have not been extensively studied for clinical outcomes including hospital stay, the need for mechanical ventilation, mortality rates, and healthcare utilization. We hypothesize significant financial costs and increased morbidity and mortality associated with pediatric AKI. METHODS: This is a retrospective study of pediatric patients (age ≤18 years) included in the Kids' Inpatient Database (KID) between January 1, 2016, and December 31, 2021. The results of the data analysis were utilized for comparative testing between the AKI and non-AKI cohorts. RESULTS: The study included 4842 children [with AKI (n = 2424) and without AKI (n = 2418)]. The odds of mortality (p = 0.004) and mechanical ventilation (p < 0.001) were observed to be significantly higher among those with AKI as compared to those without AKI. Additionally, the median (IQR) duration of stay in the hospital (p < 0.001) and total cost (p < 0.001) were significantly higher among those with AKI vs. those without AKI. CONCLUSIONS: AKI in children was associated with higher odds of mortality, longer duration of hospital stay, increased requirement of mechanical ventilation, and increased hospital expenditure. The scientific community can utilize this information to better understand the outcomes associated with this disease process in this patient population. IMPACT: This article has thoroughly evaluated epidemiologic data associated with pediatric acute kidney injury (AKI) in hospitalized patients This study assesses mortality, hospital expenditure, and other factors to strengthen single-center and few multi-center studies and provides novel data regarding insurance and cost associated with pediatric AKI With increased knowledge of current epidemiology and risk factors, the scientific community can better understand prevention and outcomes in hospitalized children with AKI.

The effects of COVID-19 on pediatric and adult solid organ transplant recipients and the emergence of telehealth.

BACKGROUND: The SARS-CoV-2 pandemic and corresponding acute respiratory syndrome have affected all populations and led to millions of deaths worldwide. The pandemic disproportionately affected immunocompromised and immunosuppressed adult patients who had received solid organ transplants (SOTs). With the onset of the pandemic, transplant societies across the world recommended reducing SOT activities to avoid exposing immunosuppressed recipients. Due to the risk of COVID-19-related outcomes, SOT providers adapted the way they deliver care to their patients, leading to a reliance on telehealth. Telehealth has helped organ transplant programs continue treatment regimens while protecting patients and physicians from COVID-19 transmission. This review highlights the adverse effects of COVID-19 on transplant activities and summarizes the increased role of telehealth in the management of solid organ transplant recipients (SOTRs) in both pediatric and adult populations. METHODS: A comprehensive systematic review and meta-analysis were conducted to accentuate the outcomes of COVID-19 and analyze the efficacy of telehealth on transplant activities. This in-depth examination summarizes extensive data on the clinical detriments of COVID-19 in transplant recipients, advantages, disadvantages, patient/physician perspectives, and effectiveness in transplant treatment plans via telehealth. RESULTS: COVID-19 has caused an increase in mortality, morbidity, hospitalization, and ICU admission in SOTRs. Telehealth efficacy and benefits to both patients and physicians have increasingly been reported. CONCLUSIONS: Developing effective systems of telehealth delivery has become a top priority for healthcare providers during the COVID-19 pandemic. Further research is necessary to validate the effectiveness of telehealth in other settings.

Point-of-care ultrasound in pediatric nephrology.

Point-of-care ultrasound (POCUS) has evolved in recent years in clinical practice, helping in early bedside diagnosis of important etiologies. Many medical schools and training programs are integrating POCUS into their curriculum. Especially with the technological advances of newer handheld ultrasound devices, POCUS has now become a component adjunct to clinical examination, in the clinic and bedside in critical care units. The diagnostic utility of POCUS lies both in early identification of critical kidney disease, and also extra-renal pathologies from a focused cardiac ultrasound, lung ultrasound, and integrated fluid assessment. There is a need to incorporate POCUS in training in pediatric nephrology and establish competency standard criteria. This review shall cover how POCUS helps in enhancing patient care in pediatric kidney disorders and critical children, and the recent advances.

Evidence of increased vascular stiffness and left ventricular hypertrophy in children with cystic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) is the most common cause of mortality in chronic kidney disease (CKD). Children with early-onset CKD arguably experience the greatest lifetime CVD burden. We utilized data from the Chronic Kidney Disease in Children Cohort Study (CKiD) to evaluate two pediatric CKD cohorts: congenital anomalies of the kidney and urinary tract (CAKUT) and cystic kidney disease for CVD risks and outcomes. METHODS: CVD risk factors and outcomes including blood pressures, left ventricular hypertrophy (LVH), left ventricular mass index (LVMI), and ambulatory arterial stiffness index (AASI) scores were evaluated. RESULTS: Forty-one patients in the cystic kidney disease group were compared to 294 patients in the CAKUT group. Cystic kidney disease patients had higher cystatin-C levels, despite similar iGFR. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) indexes were higher in the CAKUT group, but a significantly higher proportion of cystic kidney disease patients was on anti-hypertensive medications. Cystic kidney disease patients had increased AASI scores and a higher incidence of LVH. CONCLUSIONS: This study provides a nuanced analysis of CVD risk factors and outcomes including AASI and LVH in two pediatric CKD cohorts. Cystic kidney disease patients had increased AASI scores, higher incidence of LVH, and higher rates of anti-hypertensive medication use which could imply a greater burden of CVD despite similar GFR. Our work suggests that additional mechanisms may contribute to vascular dysfunction in cystic kidney disease, and that these patients may need additional interventions to prevent the development of CVD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Artificial intelligence in early detection and prediction of pediatric/neonatal acute kidney injury: current status and future directions.

Acute kidney injury (AKI) has a significant impact on the short-term and long-term clinical outcomes of pediatric and neonatal patients, and it is imperative in these populations to mitigate the pathways leading to AKI and be prepared for early diagnosis and treatment intervention of established AKI. Recently, artificial intelligence (AI) has provided more advent predictive models for early detection/prediction of AKI utilizing machine learning (ML). By providing strong detail and evidence from risk scores and electronic alerts, this review outlines a comprehensive and holistic insight into the current state of AI in AKI in pediatric/neonatal patients. In the pediatric population, AI models including XGBoost, logistic regression, support vector machines, decision trees, naïve Bayes, and risk stratification scores (Renal Angina Index (RAI), Nephrotoxic Injury Negated by Just-in-time Action (NINJA)) have shown success in predicting AKI using variables like serum creatinine, urine output, and electronic health record (EHR) alerts. Similarly, in the neonatal population, using the "Baby NINJA" model showed a decrease in nephrotoxic medication exposure by 42%, the rate of AKI by 78%, and the number of days with AKI by 68%. Furthermore, the "STARZ" risk stratification AI model showed a predictive ability of AKI within 7 days of NICU admission of AUC 0.93 and AUC of 0.96 in the validation and derivation cohorts, respectively. Many studies have reported the superiority of using biomarkers to predict AKI in pediatric patients and neonates as well. Future directions include the application of AI along with biomarkers (NGAL, CysC, OPN, IL-18, B2M, etc.) in a Labelbox configuration to create a more robust and accurate model for predicting and detecting pediatric/neonatal AKI.

Cardiovascular implications of hypertensive autosomal dominant polycystic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is among the most common inherited kidney diseases. Hypertension is a frequent cardiovascular manifestation, especially in adults, but elevated blood pressure is also found in children and adolescents. Acknowledgment of pediatric hypertension early is critical, as it can result in serious complications long-term if left undiagnosed. OBJECTIVE: We aim to identify the influence of hypertension on cardiovascular outcomes, mainly left ventricular hypertrophy, carotid intima media thickness, and pulse wave velocity. METHODS: We performed an extensive search on Medline, Embase, CINAHL, and Web of Science databases through March 2021. Original studies with a mix of retrospective, prospective, case-control studies, cross sectional studies, and observational studies were included in the review. There was no restriction on age group. RESULTS: The preliminary search yielded 545 articles with 15 articles included after inclusion and exclusion criteria. In this meta-analysis, LVMI (SMD: 3.47 (95% CI: 0.53-6.41)) and PWV (SMD: 1.72 (95% CI: 0.08-3.36)) were found to be significantly higher in adults with ADPKD compared to non-ADPKD; however, CIMT was not found to be significantly different. Also, LVMI was observed to be significantly higher among hypertensive adults with ADPKD (n = 56) as compared to adults without ADPKD (SMD: 1.43 (95% CI: 1.08-1.79)). Fewer pediatric studies were available with heterogeneity among patient populations and results. CONCLUSIONS: Adult patients with ADPKD were found to have worse indicators of cardiovascular outcomes, including LVMI and PWV, as compared to non-ADPKD. This study demonstrates the importance of identifying and managing hypertension, especially early, in this population. Further research, particularly in younger patients, is necessary to further elucidate the relationship between hypertension in patients with ADPKD and cardiovascular disease. REGISTRATION NUMBER: PROSPERO REGISTRATION: 343,013.

Risk factors, outcomes, and predictors of resolution of acute kidney injury in children with diabetic ketoacidosis.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients with diabetic ketoacidosis (DKA) (incidence 35-77%). AKI evolution during DKA treatment/recovery is poorly understood. Our aim was to assess children with DKA for prevalence, short-term kidney outcomes, severity, and predictors of AKI development and resolution. METHODS: This retrospective cohort study included children aged 2-14 years admitted with DKA between January 2016 and May 2020 in a Saudi tertiary care hospital. We defined AKI as an increase in serum creatinine of > 1.5 times baseline or > 3 mg/dL (26 mmol/L) within 48 h. RESULTS: Of 213 patients admitted with DKA, 172 (80.75%) developed AKI: stage 1 in 83 (38.96%), stage 2 in 86 (40.37%), and stage 3 in 3 (1.4%). No patient required dialysis. Multivariate analysis showed an increased risk of developing AKI with male gender (OR = 2.85) and lower serum bicarbonate (OR = 0.83) when adjusted for initial heart rate, hematocrit, new onset diabetes, and recurrent AKI. The mean time to AKI resolution was 13.21 ± 6.78 h. Factors leading to prolonged recovery from AKI in linear regression analysis were older age (B coefficient = 0.44, p = 0.01), recurrent DKA episodes (B coefficient = 3.70, p value 0.003), increased acidosis severity (B coefficient = - 0.44, p = 0.04), increased time to anion gap normalization (B coefficient = 0.44, p = 0.019), and increased initial glucose (B coefficient = 0.01, p = 0.011). CONCLUSION: In our cohort, AKI is a common, but mostly transient complication in children presenting with DKA, and its severity is associated with longer intensive care stays and time for acidosis resolution. AKI was associated with male gender, and lower serum bicarbonate. Proper consideration of such risk factors is needed for AKI assessment and management in future DKA clinical practice guidelines. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinical and molecular characterization of a large primary hyperoxaluria cohort from Saudi Arabia: a retrospective study.

BACKGROUND: Primary hyperoxalurias (PHs) constitute rare disorders resulting in abnormal glyoxalate metabolism. PH-associated phenotypes range from progressive nephrocalcinosis and/or recurrent urolithiasis to early kidney failure. METHODS: A retrospective study was conducted for patients with confirmed PH diagnoses from three tertiary centers in Saudi Arabia. Detailed clinical molecular diagnosis was performed for 25 affected individuals. Whole exome sequencing (WES)-based molecular diagnosis was performed for all affected individuals. RESULTS: The male:female ratio was 52% male (n = 13) and 48% female (n = 12), and consanguinity was present in 88%. Nephrolithiasis and/or nephrocalcinosis were present in all patients. Kidney stones were present in 72%, nephrocalcinosis in 60%, hematuria in 32%, proteinuria in 16%, abdominal pain in 36%, developmental delay in 8%, and chronic kidney disease stage 5 (CKD stage 5) was observed in 28% of the patients. The most common PH disorder was type I caused by variants in the AGXT gene, accounting for 56%. The GRHPR gene variants were identified in 4 patients, 16% of the total cases. Seven patients did not reveal any associated variants. Missense variants were the most commonly observed variants (48%), followed by frame-shift duplication variants (28%). CONCLUSIONS: Characterization of the genetic and clinical aspects of PH in this unique population provides direction for improved patient management and further research. A higher resolution version of the Graphical abstract is available as Supplementary information.

High-Volume Hemodiafiltration with Step-Down Approach versus Standard-of-Care Continuous Renal Replacement Therapy Approach in Critically Ill Burn Patients.

INTRODUCTION: Acute kidney injury (AKI) is a common complication of severe burn injuries and contributes to morbidity and mortality. It is exacerbated in burn patients by elevated serum creatinine and pro-inflammatory cytokines, leading to immune dysregulation. Chronic renal replacement therapy is standard of care and removes cytokines to return the body to homeostasis. Continuous veno-venous hemodiafiltration (CVVHDF) is a high-filtration method to enhance cytokine clearance; we analyze a step-down approach for improved outcomes in burn patients. METHODS: This study reviewed 15 burn patients at Akron Children's Hospital stratified into 2 groups: high-flow CVVHDF with step-down approach versus standard CVVHDF. A normocarbia bicarbonate-based dialysate solution and citrate anticoagulation was applied, and blood flow rate was maintained greater than 200 mL/min. RESULTS: Fifteen burn patients at Akron Children's Hospital were separated into groups managed with high-flow CVVHDF (n = 9) and standard-flow CVVHDF (n = 6). All 15 developed AKI symptoms and diuretic-resistant fluid overload, with 4/15 displaying fluid overload greater than 40%. The most common indication for hemofiltration was acute tubular necrosis (11/15). Average time on CVVHDF was 20.2 days and length of admission was 58.6 days. Vasodepressor dependency index was significantly reduced in the high-flow group at 48 h, but no significant difference in mortality was identified. No significant difference was identified in adverse reactions, notably electrolyte imbalances. CONCLUSION: The literature on the efficacy of high-flow CVVHDF is limited. This study suggests improved mortality rates and length of stay with high flow compared to the literature. Further studies with multicenter involvement are necessary.

Challenges and unique considerations of adolescents with chronic kidney disease.

Chronic kidney disease (CKD) is an increasingly prevalent disease that burdens patients of all ages significantly. While much data have been gathered on adult and paediatric populations, there is a lack of data on the effects of CKD on young adults and adolescents. The aim of this review was to look at the prevalence and comorbidities of this patient population, considering the rapid biological growth and development during this time frame. We present this review to illustrate the need for further research into this special patient group.

Cardiovascular implications in adolescent and young adult hypertension.

Background: Hypertension is one of the most prevalent diseases in the United States, affecting an estimated 3.5% of children and adolescents. It can be adversely affect most organ systems but is particularly detrimental to the heart and vascular systems. The repercussions can be gauged through well-established measures of cardiovascular function including left ventricular mass index (LVMI), left ventricular hypertrophy (LVH), carotid intima media thickness (cIMT), and aortic stiffness. Cardiovascular function is also affected by underlying etiologies of hypertension including chronic kidney disease, polycystic kidney disease, coarctation of the aorta, adrenal disorders, renal artery stenosis, obstructive sleep apnea, as well as various drugs and medications (decongestants, stimulants, Non-steroidal Anti-inflammatory Drugs (NSAIDs), and steroids). Methods: An exhaustive literature search was conducted for clinical data regarding pediatric hypertension. Sixty-seven articles were incorporated with data on 189,477 subjects total. The data was then extracted and categorized as relating to hypertension incidence, LVMI, LVH, cIMT, and/or aortic stiffness. Results: The prevalence of pediatric ( < 18 years) hypertension extracted from 47 studies from 1994 to 2018 averaged 4%. The LVMI assessed over 7 studies (n = 661) averaged 39.3 g/ m 2.7 in the hypertensive cohort and 30.1 g/ m 2.7 in the control cohort. The cIMT assessed over 7 studies (n = 580) averaged 0.55 mm in the hypertensive cohort and 0.49 mm in the control cohort. Ambulatory arterial stiffness parameters assessed over 5 studies (n = 573) in the normotensive cohort averaged 99.73 mmHg, 69.81 mmHg, 76.85 mmHg, and 46.90 mmHg, for SBP, DBP, MAP, and PP respectively. Ambulatory arterial stiffness parameters assessed over 5 studies (n = 573) in the hypertensive cohort averaged 129.56 mmHg, 73.69 mmHg, 95.08 mmHg, and 56.80 mmHg, for SBP, DBP, MAP, and PP respectively. Conclusions: The significance of pediatric hypertension is emphasized by evidence of early cardiovascular disease as demonstrated by non-invasive measures including cIMT and arterial stiffness parameters, and target organ damage and including LVH and LVMI factors. Thus, early diagnosis and treatment of high blood pressure is paramount for improving long term cardiovascular health and preventing long term morbidity and mortality.