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.

Biomarkers for acute kidney injury in children - where are we now?

PURPOSE OF REVIEW: Review the literature over the last 2 years on commonly evaluated biomarkers of acute kidney injury (AKI) and highlight the findings of these biomarkers. RECENT FINDINGS: Among several studied AKI biomarkers, urine neutrophil gelatinase-associated lipocalin (NGAL) and the combination of urine tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) have been recently studied most frequently as diagnostic biomarkers of AKI and for AKI risk stratification. Urine NGAL has continued to show good discriminative value to predict and diagnose AKI in childhood. Urine TIMP-2∗IGFBP7 can provide modest improvement to clinical models of AKI. SUMMARY: Prior research supports that AKI biomarkers may identify AKI at an earlier time point and indicate clinically meaningful tubular injury. More effort should be made to understand if AKI biomarkers can guide treatments and improve outcomes.

An initiative to improve pneumococcal immunization counseling in children with nephrotic syndrome.

BACKGROUND: Immunization is essential in preventing life-threatening pneumococcal infections in children with nephrotic syndrome. An additional 23-valent pneumococcal polysaccharide vaccine (PPSV23) series is required for children with nephrotic syndrome. Despite current practice guidelines, many children with nephrotic syndrome do not receive PPSV23. METHODS: Our nephrology clinic conducted a quality improvement project to improve the overall rate of PPSV23 counseling to more than 70% within a 12-month period by applying several targeted interventions to raise providers' awareness, improve communication with primary care providers, and increase provider adherence. Data was collected from the electronic health record (EHR), and monthly performance was tracked via monthly control charts and overall immunization counseling rate charts. RESULTS: We increased adherence to PPSV23 vaccination counseling from a baseline of 12 to 86%. The first intervention that effectively increased the vaccine counseling rate from 12 to 30% was improving a provider's awareness of the PPSV23 literature and vaccine guidelines. Other interventions included regular performance reviews at division meetings, creating an immunization protocol, posting performance charts on the office bulletin board, and unifying vaccine recommendation templates. Lastly, specific and timely EHR reminders improved the total counseling rate from 52 to 86% and maintained adherence until the completion of the project. CONCLUSION: Bridging the knowledge gap in provider awareness and using specific EHR reminders can improve adherence to PPSV23 counseling in children with nephrotic syndrome. Such interventions could be applied to similar groups of immunocompromised patients in whom additional vaccines are indicated. A higher resolution version of the Graphical abstract is available as Supplementary information.

A Time-Updated, Parsimonious Model to Predict AKI in Hospitalized Children.

BACKGROUND: Timely prediction of AKI in children can allow for targeted interventions, but the wealth of data in the electronic health record poses unique modeling challenges. METHODS: We retrospectively reviewed the electronic medical records of all children younger than 18 years old who had at least two creatinine values measured during a hospital admission from January 2014 through January 2018. We divided the study population into derivation, and internal and external validation cohorts, and used five feature selection techniques to select 10 of 720 potentially predictive variables from the electronic health records. Model performance was assessed by the area under the receiver operating characteristic curve in the validation cohorts. The primary outcome was development of AKI (per the Kidney Disease Improving Global Outcomes creatinine definition) within a moving 48-hour window. Secondary outcomes included severe AKI (stage 2 or 3), inpatient mortality, and length of stay. RESULTS: Among 8473 encounters studied, AKI occurred in 516 (10.2%), 207 (9%), and 27 (2.5%) encounters in the derivation, and internal and external validation cohorts, respectively. The highest-performing model used a machine learning-based genetic algorithm, with an overall receiver operating characteristic curve in the internal validation cohort of 0.76 [95% confidence interval (CI), 0.72 to 0.79] for AKI, 0.79 (95% CI, 0.74 to 0.83) for severe AKI, and 0.81 (95% CI, 0.77 to 0.86) for neonatal AKI. To translate this prediction model into a clinical risk-stratification tool, we identified high- and low-risk threshold points. CONCLUSIONS: Using various machine learning algorithms, we identified and validated a time-updated prediction model of ten readily available electronic health record variables to accurately predict imminent AKI in hospitalized children.

Primary caregivers' experience with the informed consent process in the paediatric emergency department: An interview-based qualitative study.

OBJECTIVE: This study aims to understand primary caregivers' (PCG) experience with the informed consent (IC) process. METHODS: We conducted in-depth interviews with PCGs of paediatric patients who underwent a procedure requiring IC in the paediatric emergency department (PED) of a tertiary care paediatric centre in the USA, between January and March 2013 and between September 2013 and January 2014. We triangulated the qualitative findings from the PCG interviews with Likert-scale responses from the PCGs and with results from surveyed physicians. RESULTS: We included 14 PCG-physician dyads. Our results show that PCGs understand the importance of the IC process. They appreciated the calm demeanor of providers, and the clarity of their wording. PCGs felt that IC can add to the stress, and that it could be made simpler and timelier. PCGs also had varying extents of retention of the information provided. CONCLUSION: This exploratory study suggests an overall positive IC experience of the PCGs while highlighting areas for improvement including a more thorough discussion of alternatives, a better assessment of knowledge transmission and retention by the PCG, and recognition of the PCG's discomfort during decision making in a stressful environment.

Novel biomarkers of acute kidney injury in children: an update on recent findings.

PURPOSE OF REVIEW: The clinical diagnosis of acute kidney injury (AKI) relies largely on changes in serum creatinine; a delayed biomarker. Research in children has been focused on developing novel AKI biomarkers, which can improve the prediction, early detection and diagnosis of kidney injury, as well as our understanding of AKI pathophysiology. In this review, we describe recently published studies on urine or blood biomarkers of AKI. The mechanistic relevance of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, interleukin (IL)-18, liver-type fatty acid binding protein, tissue inhibitor of metalloproteinase (TIMP)-2/insulin-like growth factor-binding protein (IGFBP)-7, uromodulin, as well as other inflammatory biomarkers are discussed in the context of AKI pathophysiology, as well as their performance predicting or diagnosing AKI. RECENT FINDINGS: Biomarkers of tubular injury, cell cycle arrest and inflammation are presented in this review. NGAL continues to be the most frequently studied biomarker and continues to have good performance in a variety of clinical settings, most notably after cardiopulmonary bypass. We also found promising results with less studied biomarkers for the prediction of AKI in children, including TIMP2, IGFBP7, uromodulin, tumor necrosis factor-α and IL-8. SUMMARY: Identifying new AKI biomarkers is a priority in pediatric nephrology research because of the morbidity associated with AKI, as well as the lack of therapies for AKI. Recent research suggests that novel AKI biomarkers have the potential to predict the development of AKI and diagnose AKI earlier than changes in serum creatinine. The diverse causes of AKI, the different settings where patients develop AKI and the changing biomarker reference ranges throughout childhood remain challenges in biomarker development.

Identification of novel mutations and phenotype in the steroid resistant nephrotic syndrome gene NUP93: a case report.

BACKGROUND: Monogenic mutations may be a significant cause of steroid-resistant nephrotic syndrome. NUP93 is a gene previously reported to cause isolated steroid-resistant nephrotic syndrome. CASE PRESENTATION: Here we describe a case of recessive, syndromic, steroid-resistant nephrotic syndrome caused by NUP93 mutation. CONCLUSIONS: NUP93 may convey a phenotype that has not only SRNS, but also other syndromic features.

Current and Novel Biomarkers of Progression Risk in Children with Chronic Kidney Disease.

BACKGROUND: Due to the complexity of chronic kidney disease (CKD) pathophysiology, biomarkers representing different mechanistic pathways have been targeted for the study and development of novel biomarkers. The discovery of clinically useful CKD biomarkers would allow for the identification of those children at the highest risk of kidney function decline for timely interventions and enrollment in clinical trials. SUMMARY: Glomerular filtration rate and proteinuria are traditional biomarkers to classify and prognosticate CKD progression in clinical practice but have several limitations. Over the recent decades, novel biomarkers have been identified from blood or urine with metabolomic screening studies, proteomic screening studies, and an improved knowledge of CKD pathophysiology. This review highlights promising biomarkers associated with the progression of CKD that could potentially serve as future prognostic markers in children with CKD. KEY MESSAGES: Further studies are needed in children with CKD to validate putative biomarkers, particularly candidate proteins and metabolites, for improving clinical management.

Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines.

Background: Kidney transplant recipients (KTRs) commonly suffer from impaired immunity. KTRs' compromised immune response to COVID-19 vaccines indicates urgent revision of immunisation policies. Methods: A cross-sectional study was conducted in Madinah, Saudi Arabia of 84 KTRs who had received at least one dose of a COVID-19 vaccine. ELISA was used to evaluate anti-spike SARS-CoV-2 IgG and IgM antibody levels in blood samples obtained one month and seven months after vaccination. Univariate and multivariate analyses were performed to identify associations between seropositive status and factors such as the number of vaccine doses, transplant age, and immunosuppressive therapies. Results: The mean age of KTRs was 44.3 ± 14.7 years. The IgG antibody seropositivity rate (n=66, 78.5%) was significantly higher than the seronegativity rate (n=18, 21.4%) in the whole cohort (p<0.001). In KTRs seroconverting after one month (n=66), anti-SARS-CoV-2 IgG levels declined significantly between one month (median [IQR]:3 [3-3]) and seven months (2.4 [1.7-2.6]) after vaccination (p<0.01). In KTRs with hypertension, IgG levels significantly decreased between one and seven months after vaccination (p<0.01). IgG levels also decreased significantly in KTRs with a transplant of >10 years (p=0.02). Maintenance immunosuppressive regimens (triple immunosuppressive therapy and steroid-based and antimetabolite-based regimens) led to a significant decrease in IgG levels between the first and second sample (p<0.01). KTRs receiving three vaccine doses showed higher antibody levels than those receiving a single dose or two doses, but the levels decreased significantly between one (median [IQR]: 3 [3-3]) and seven months (2.4 [1.9-2.6]) after vaccination (p<0.01). Conclusion: KTRs' humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of >10 years.

Plasma and Urine Biomarkers of CKD: A Review of Findings in the CKiD Study.

Serum creatinine and level of proteinuria, as biomarkers of chronic kidney disease (CKD) progression, inadequately explain the variability of glomerular filtration rate decline, and are late markers of glomerular filtration rate decline. Recent studies have identified plasma and urine biomarkers at higher levels in children with CKD and also associate independently with CKD progression, even after adjustment for serum creatinine and proteinuria. These novel biomarkers represent diverse biologic pathways of tubular injury, tubular dysfunction, inflammation, and tubular health, and can be used as a liquid biopsy to better characterize CKD in children. In this review, we highlight the biomarker findings from the Chronic Kidney Disease in Children cohort, a large longitudinal study of children with CKD, and compare results with those from other pediatric CKD cohorts. The biomarkers in focus in this review include plasma kidney injury molecule-1, monocyte chemoattractant protein-1, fibroblast growth factor-23, tumor necrosis factor receptor-1, tumor necrosis factor receptor-2, soluble urokinase plasminogen activator receptor, and chitinase-3-like protein 1, as well as urine epidermal growth factor, α-1 microglobulin, kidney injury molecule-1, monocyte chemoattractant protein-1, and chitinase-3-like protein 1. Blood and urine biomarkers improve our ability to prognosticate CKD progression and may improve our understanding of CKD pathophysiology. Further research is required to establish how these biomarkers can be used in the clinical setting to improve the clinical management of CKD.