Pediatric Chronic Kidney Disease Research Articles

#1984 Extracellular vesicles drive loss of endothelial homeostasis in pediatric chronic kidney disease

Abstract Background and Aims Cardiovascular disease (CVD) is the main cause of mortality in chronic kidney disease (CKD). However, the pathogenesis of CVD in CKD remains incompletely understood. Extracellular vesicles (EVs) emerged as mediators of inter-organ cross-talk and endothelial EVs (EC-EVs) were previously associated with CVD. We hypothesized that CKD drives endothelial EV release in CKD and that these EC-EVs drive CVD in CKD. Method A cohort of 94 children (mean age 10.9 years) at different stages of CKD (patients with or without dialysis and after kidney transplantation (KTx)) and age-matched healthy donors was recruited, offering the unique opportunity to analyze cardiovascular effects of CKD and EV dynamics in absence of age-related comorbidities. Thorough characterization of plasma EVs by electron microscopy, nanoparticle tracking analysis (NTA), flow cytometry and miRNA sequencing was carried out. Functional properties of patient EVs and CKD-specific EV release mechanisms were tested in vitro. Results EC-EVs were elevated in hemodialysis (HD) patients (as measured by flow cytometry) while total EV counts showed higher concentrations in peritoneal dialysis patients (according to NTA). Longitudinal follow-ups revealed that EC-EVs decreased after receiving KTx. EV small RNA sequencing showed lower abundance of 30 microRNAs in EVs from CKD patients, most pronounced in HD patients compared to both healthy donors and KTx recipients. Downregulation of let-7d-5p, miR-19a-3p, miR-24-3p, miR-103a-3p and miR-142-3p was confirmed using RT-qPCR. Gene enrichment analyses predicted angiogenesis and smooth muscle cell (SMC) proliferation as targets of differentially regulated miRNAs in CKD. In vitro, angiogenesis of Human Umbilical Vein Endothelial Cells (HUVECs) was decreased upon treatment with CKD EVs as indicated by decreased vascular tube formation, endothelial migration and proliferation while SMC proliferation remained unchanged. To assess the putative role of uremic toxins for EV release in CKD, we focused on tryptophan metabolites and performed targeted plasma metabolomics that showed stage-dependent increases of uremic toxins of indole and kynurenine pathways in children with CKD, with highest levels in dialysis patients and almost normal levels after KTx. Uremic toxins indoxyl sulfate, formylkynurenine and xanthurenic acid correlated positively with EC-EVs in our cohort, but were not sufficient to trigger EV release from aortic endothelial cells alone. However, high shear stress together with indoxyl sulfate increased EV release from venous endothelial cells corresponding to higher endothelial EV concentrations in HD patients with arterio-venous fistulas (AVF) and recapitulated EV miRNA changes in vitro observed in CKD in vivo (lower abundance of let-7d-5p and miR-24-3p). Conclusion Endothelial EV release and decreased EV miRNAs associate with advanced CKD while increased endothelial shear stress and indoxyl sulfate form potential causative factors of altered EV phenotype. CKD EVs inhibit angiogenesis in vitro, potentially caused by dysregulated EV miRNAs that could form novel therapeutical targets to reduce CVD burden in CKD.

#336 Early detection of vascular access complication in pediatric CKD hemodialysis patients

Abstract Background and Aims Vascular access (VA) dysfunction is a major clinical complication in the hemodialysis (HD) population and has a direct effect on dialysis outcome. Where in patients undergoing HD, neointimal hyperplasia results in vascular stenosis and subsequent thrombosis, which lead to vascular access failure. Interleukin-10 (IL-10), hs CRP, and tumor necrosis factor- (TNF–α) are inflammatory markers which are proved to be involved in the process neointimal hyperplasia & subsequent complications. We aimed to evaluate the value of these inflammatory markers in early detection of arterio-venous fistula (AVF) failure, in pediatric patients on regular HD, together with the clinical & radiological diagnoses, for proper intervention for correcting AVF failure according to guidelines. Method It was an prospective cohort study, where we included 59 pediatric chronic kidney disease patients’ stage 5, on regular HD (CKD5d), who were following up regularly with us for 1 year. Patients with nonfunctioning AVFs due to complications as thrombus occluding fistula, infections, or large aneurysm, were excluded from the beginning of the study. Monitoring of VA by pre-cannulation physical examination was performed to detect the physical signs of dysfunction, at least once per month according to KDOQI guidelines. Venous pressure (VP) and trans-membrane pressure (TMP) were recorded at each HD session, to detect any abnormalities and to record the pressure changes with the appearance of any AVF complications. Doppler ultrasound (DUS) was performed routinely every 3 months for all HD patients, & at the time of development AVF complications. Blood samples for measuring IL10, TNF, hs CRP were collected from the patients every 2 weeks for 12 months, prior to HD sessions, where we included the most recent samples prior to, and at the time of development complications, which were clinically and radiologically confirmed. Results The mean (±SD) age of our patients was 13.97 (±2.65) years, where we had 39 (56.5%) males, and 30 (43.5%) females, with a median (IQR) HD duration of 4.0 (5.0) years. On assessing the AVF complications, 33 patients (55.9%) had experienced complications, where thrombosis was the most common reported one (17 patients, 28.8%), followed by aneurysm formation in 14 patients (23.7%), while 6 patients (10%) had stenosed AVF, early VA failure in 2 patients (3.4%),1 patient (1.7%) had pseudoaneurysm, and another patient (1.7%) had perivascular hematoma. Mean serum levels of Hs-CRP, TNF-α, IL-10 were elevated at timing of early development of complication, in comparison to their baseline levels, meanwhile serum IL10, and TNF alpha were significantly higher among patients who developed AVF stenosis. The baseline hs-CRP had related positively with AVF diameter at the time of the development of the complications. Conclusion The inflammatory markers have no clinically applied role in early detection of AVF abnormalities, therefore, physical examination and DUS are deemed sufficient.

#331 Vascular and lipid profile interplays in pediatric CKD patients

Abstract Background and Aims Chronic kidney disease (CKD) is characterized by irreversible kidney damage and/or progressive loss of function. Children with CKD often have additional CVD risk factors, including hypertension and dyslipidemia. They may have myocardial abnormalities and early atherosclerosis evidence, such as coronary artery calcification, abnormal flow-mediated dilation, increased carotid intima-medial thickness (CIMT), and increased aortic stiffness. These abnormalities seem to be, in part, related to the degree of uremia. This study aimed at assessing the interrelationship between vascular status and lipid profile abnormalities in different stages of CKD in pediatric patients. Method This cross-sectional study was done on 99 patients: 33 with stage 5 CKD on regular hemodialysis & 33 pre-dialysis CKD stage 2-4 on conservative management & 33 age and sex matched controls. Anthropometric measures, blood pressure readings, and a lipid profile were done to all groups. Intima media thickness was measured using B-mode ultrasound doppler in both the common and internal carotid arteries (CCA, ICA). Which is a non-invasive way to measure the artery walls and track the early impacts of the atherosclerotic process. Results There was an obvious increase in blood pressure the percentiles in all CKD patients in relation to controls. The waist-to-hip ratio in CKD 2-4 patients was significantly higher than in CKD 5 patients, and both were higher than the controls, with means (±SD) of 1.01 (0.19), 0.88 (0.10), and 0.86 (0.05), respectively. Except for high-density lipoproteins (HDL), the lipid profile, including triglycerides, cholesterol, and low-density lipoproteins (LDL), were all significantly increased when comparing CKD 2-4 to CKD 5, and both higher than the controls: 170.45 (42.04), 166.00 (45.57), and 100.88 (26.19) for triglycerides (p 0.001). The right and left ICA and CCA showed a significant increase in the intimal thickness being higher in the CKD 5 group than the CKD 2-4 and both higher than the controls. On studying the correlation between the duration of CKD in years and other variables, we found a positive correlation with triglycerides (r = 0.409 & p = 0.001) and right CCA IMT (r = 0.271 & p = 0.028); however, the HDL (r = −0.326 & p = 0.007) revealed a negative correlation in all CKD patients. The HDL level showed an inverse correlation with right CCA and ICA. Conclusion Patients with CKD have an increased waist-to-hip ratio, dyslipidemia, and increased carotid IMT, which are factors that lead to the early development of atherosclerosis. Special care should be directed to CKD patients, especially those in stages 2-4, to control their lipid profile and postpone the development of atherosclerosis as much as possible.

#1801 Gut dysbiosis contributes to TMAO accumulation in CKD

Abstract Background and Aims Chronic kidney disease (CKD) patients face a substantial morbidity risk, especially related to cardiovascular complications. The imbalance of circulating metabolites influences inter-organ crosstalk and disease pathophysiology. In this regard, metabolites of microbial origin have gained increasing attention. Trimethylamine N-oxide (TMAO) originates from microbial Trimethylamine (TMA) metabolism and is found at high concentrations in the blood of CKD patients. A high TMAO concentration is known to be an independent risk factor for cardiovascular disease. This study aims to investigate the extent to which high concentrations of TMAO in the blood are due to increased bacterial production or are mainly a consequence of impaired renal clearance. Methods We used existing biomaterials and clinical data of a pediatric CKD cohort, consisting of patients enrolled at CKD stage G3-5, including G5 patients treated with hemodialysis (HD), as well as patients after kidney transplantation (KT) and individuals with normal kidney function. We analyzed TMAO in plasma and urine samples using LC-MS/MS and developed a novel gene targeting assay (GTA) that quantifies the abundance of the bacterial target genes (CutC, CntA) encoding for the key enzymes of microbial TMA synthesis in each fecal sample. Results Plasma TMAO levels were stage-dependently elevated in CKD, with HD patients showing the highest levels (75 ± 46 µmol/l). While urinary TMAO levels were lower in the CKD groups, TMAO/creatinine ratios and fractional excretion were not significantly different in CKD compared to controls. Fecal microbial gene abundance of both CutC and CntA genes was elevated across CKD stages and correlated with both plasma TMAO levels and eGFR. Although KT patients exhibited an eGFR range comparable to controls, they still showed higher plasma TMAO levels and elevated TMAO-associated gene abundances. In a regression analysis, this gene abundance was associated with plasma TMAO independent of eGFR in a model adjusted for age, sex, and BMI. Using a likelihood ratio test, we showed that adding fecal microbial gene abundance to the model provided a significantly better fit compared to only eGFR, age, sex, and BMI. Conclusion Our data indicate that the production of TMA by intestinal bacteria contributes significantly to the accumulation of TMAO in patients with CKD and after kidney transplantation. This finding opens the possibility for new potential interventions in the management of patients with CKD.

#332 Dermatological manifestations in pediatric CKD patients

Abstract Background and Aims Chronic kidney disease (CKD), regardless of its cause, may be accompanied by various skin lesions. The most common symptom in children suffering from CKD is pruritus however other signs that may be seen are xerosis, skin hyperpigmentation, ecchymoses, acquired perforating dermatoses, nail lesions, calcinosis cutis, as well as eczematous lesions at the site of an arteriovenous fistula and skin infections. Data on different skin lesions in children with CKD is very limited; only few reports have been published discussing xerosis in pediatric patients and most studies were conducted on a small number of patients who needed renal replacement therapy . This study aimed primarily to screen the different dermatological manifestations in pediatric patients with CKD, in addition to studying the relationship of dermatological manifestations with the CKD stage, types of dialysis, various clinical and metabolic parameters. Method This was a cross sectional study, that was conducted at Pediatric Dialysis and Nephrology unit, Children's Hospital, Faculty of Medicine, Ain Shams University Hospital, Cairo, Egypt, during the period from February 2023 to August 2023, where 70 patients were enrolled in our study being divided into two groups: group 1 including CKD patients stages (2-4) and group 2 including CKD patients with stage 5 on regular hemodialysis. Detailed dermatological & nail examination were conducted. Xerosis severity was assessed using a four-point xerosis assessment scale (0, normal skin, without any xerosis; 1, mild xerosis; 2, moderately dry skin with minimal flaking; 3, severe xerosis, heavy scaling visible), whereas pruritus was assessed using a visual analogue scale (VAS) on a scale of 1 (no itch) to 10 (worst possible itch). Laboratory data were withdrawn at the time of examination to correlate with different dermatological manifestation. Results In our study, xerosis was the most frequent dermatological manifestation (78.6%) following it pruritus (62.9%) then pallor (35.7%), hyperpigmentation (20%), hypertrichosis (10 %), nail and hair abnormalities (8.5%) & post inflammatory hyperpigmentation (4.3%). The prevalence of xerosis was not affected by clinico-demographic data, CKD duration & stage, type and duration of dialysis, the only significant relation was between efficacy of dialysis (Kt/V) and incidence of xerosis, where the higher dialysis efficacy rates were associated with low incidence rates of xerosis, in which effective hemodialysis contributes to better removal of uremic toxins, & hence decrease the xerosis. Leukocytosis was noticed in xerotic & pruritic patients, where xerosis & impaired skin barrier in children with CKD pose a risk for different cutaneous infections & inflammation, and hence pruritis. Conclusion Xerosis and pruritis are not uncommon dermatological manifestations among pediatric patients with chronic kidney disease, meanwhile the age of the patients and the underlying CKD etiology had no direct effect on skin changes. The most determinant factory affecting the xerosis was the hemodialysis efficacy, where higher efficacy was associated with less xerosis, meanwhile leukocytosis was associated with higher xerosis and pruritis. Further studies are needed to detect various skin manifestations in CKD patients with different CKD stages and correlate it with the used dialysis modalities.

Psychotropic Medication Usage in Pediatric CKD: Reporting from the Chronic Kidney Disease in Children Cohort.

Mental health disorders (MHD) within the pediatric chronic kidney disease (CKD) population are prevalent. The frequency is unknown with which psychotropic medications that commonly treat these conditions are used in this population. Data from the Chronic Kidney Disease in Children (CKiD) cohort study were utilized to describe the use of psychotropic medications and patient-related characteristics of use. Medications were classified into 3 groups: antidepressants, CNS stimulants, and antipsychotic/mood stabilizing medications. Participant age, sex, CKD severity, and duration of medication use were ascertained. Medication use was evaluated in parallel with CKD disease type, presence of urological comorbidity, and hypertension. Chi-square tests compared subgroup medication use. Among 1074 CKiD participants (median baseline age 9.8 years), 6% (n=60) of participants used psychotropic medications at study entry with 11% reporting incident use of any medication category (n=120). CNS stimulants were most common at baseline. Antidepressants were more frequent among incident users at 7%. Use of two or more medications was rare (3%). Median eGFR at medication initiation was 45 ml/min|1.73m2. CNS stimulants were reported at a higher rate in males compared to females (p<0.05). 11% of CKiD patients report incident use of any psychotropic medication, with 7% reporting incident use of antidepressants. Future work is warranted to better ascertain the frequency, safety, and efficacy of psychotropic medication usage in relationship to formal MHD diagnoses in the pediatric CKD population.

Longitudinal plasma metabolome patterns and relation to kidney function and proteinuria in pediatric chronic kidney disease.

Understanding plasma metabolome patterns in relation to changing kidney function in pediatric chronic kidney disease (CKD) is important for continued research for identifying novel biomarkers, characterizing biochemical pathophysiology, and developing targeted interventions. There is a limited number of studies of longitudinal metabolomics, and virtually none in pediatric CKD. The Chronic Kidney Disease in Children (CKiD) study is a multi-institutional, prospective cohort that enrolled children aged six-months to 16-years with estimated glomerular filtration rate (eGFR) 30-90ml/min/1.73m2. Untargeted metabolomics profiling was performed on plasma samples from the baseline, two-, and four-year study visits. There were technologic updates in the metabolomic profiling platform used between the baseline and follow-up assays. Statistical approaches were adopted to avoid direct comparison of baseline and follow-up measurements.To identify metabolite associations with eGFR or urine protein:creatinine (UPCR) among all three timepoints, we applied linear mixed effects (LME) models. To identify metabolites associated with time, we applied LME models to the two- and four-year follow-up data. We applied linear regression analysis to examine associations between change in metabolite level over time (∆level) and change in eGFR (∆eGFR) and UPCR (∆UPCR). We reported significance based on both the False Discovery Rate (FDR) <0.05 and p<0.05. There were 1156 person-visits (N: baseline=626, 2-year=254, 4-year=276) included. There were 622 metabolites with standardized measurements at all three timepoints. In LME modeling, 406 and 343 metabolites associated with eGFR and UPCR at FDR<0.05 respectively. Among 530 follow-up person-visits, 158 metabolites showed differences over time at FDR<0.05. For participants with complete data at both follow-up visits (N=123), we report 35 metabolites with ∆level∼∆eGFR associations significant at FDR<0.05. There were no metabolites with significant ∆level∼∆UPCR associations at FDR<0.05. We report 16 metabolites with ∆level∼∆UPCR associations at p<0.05 and associations with UPCR in LME modeling at FDR<0.05. We characterized longitudinal plasma metabolomic patterns associated with eGFR and UPCR in a large pediatric CKD population. Many of these metabolite signals have been associated with CKD progression, etiology, and proteinuria in previous CKD Biomarkers Consortium studies. There were also novel metabolite associations with eGFR and proteinuria detected.

Outcome Measures of Clinical Trials in Pediatric Chronic Kidney Disease

Outcome Measures of Clinical Trials in Pediatric Chronic Kidney Disease

Role of Nutrients in Pediatric Non-Dialysis Chronic Kidney Disease: From Pathogenesis to Correct Supplementation.

Nutrition management is fundamental for children with chronic kidney disease (CKD). Fluid balance and low-protein and low-sodium diets are the more stressed fields from a nutritional point of view. At the same time, the role of micronutrients is often underestimated. Starting from the causes that could lead to potential micronutrient deficiencies in these patients, this review considers all micronutrients that could be administered in CKD to improve the prognosis of this disease.

Growth after pediatric kidney transplantation: a 25-year study in a pediatric kidney transplant center.

Growth failure is one of the major complications of pediatric chronic kidney disease. Even after a kidney transplant (KT), up to 50 % of patients fail to achieve the expected final height. This study aimed to assess longitudinal growth after KT and identify factors influencing it. A retrospective observational study was performed. We reviewed the clinical records of all patients who underwent KT for 25 years in a single center (n=149) and performed telephone interviews. Height-for-age and body mass index (BMI)-for-age were examined at KT, 3months, 6months, 1 year, and 5 years post-transplant and at the transition to adult care. We evaluated target height, disease duration before KT, need and type of dialysis, recombinant human growth hormone pretransplant use, nutritional support, glomerular filtration rate (GFR), and cumulative corticosteroid dose. At transplant, the average height z-score was-1.38, and height z-scores showed catch-up growth at 6months (z-score-1.26, p=0.006), 1 year (z-score-1.15, p<0.001), 5 years after KT (z-score-1.08, p<0.001), and on transition to adult care (z-score-1.22, p=0.012). Regarding BMI z-scores, a significant increase was also detected at all time points (p<0.001). After KT, GFR was significantly associated with height z-score (p=0.006) and BMI z-score (p=0.006). The height in transition to adult care was-1.28 SD compared to the target height. Despite the encouraging results regarding catch-up growth after KT in this cohort, results remain far from optimum, with a lower-than-expected height at the time of transition.

Is mild dehydration a risk for progression of childhood chronic kidney disease?

Children with chronic kidney disease (CKD) can have an inherent vulnerability to dehydration. Younger children are unable to freely access water, and CKD aetiology and stage can associate with reduced kidney concentrating capacity, which can also impact risk. This article aims to review the risk factors and consequences of mild dehydration and underhydration in CKD, with a particular focus on evidence for risk of CKD progression. We discuss that assessment of dehydration in the CKD population is more challenging than in the healthy population, thus complicating the definition of adequate hydration and clinical research in this field. We review pathophysiologic studies that suggest mild dehydration and underhydration may cause hyperfiltration injury and impact renal function, with arginine vasopressin as a key mediator. Randomised controlled trials in adults have not shown an impact of improved hydration in CKD outcomes, but more vulnerable populations with baseline low fluid intake or poor kidney concentrating capacity need to be studied. There is little published data on the frequency of dehydration, and risk of complications, acute or chronic, in children with CKD. Despite conflicting evidence and the need for more research, we propose that paediatric CKD management should routinely include an assessment of individual dehydration risk along with a treatment plan, and we provide a framework that could be used in outpatient settings.

Growth hormone in pediatric chronic kidney disease: more than just height.

Recombinant human growth hormone therapy, which was introduced in the 1980s, is now routine for children with advanced chronic kidney disease (CKD) who are exhibiting growth impairment. Growth hormone usage remains variable across different centers, with some showing low uptake. Much of the focus on growth hormone supplementation has been on increasing height because of social and psychological effects of short stature. There are, however, numerous other changes that occur in CKD that have not received as much attention but are biologically important for pediatric growth and development. This article reviews the current knowledge about the multisystem effects of growth hormone therapy in pediatric patients with CKD and highlights areas where additional clinical research is needed. We also included clinical data on children and adults who had received growth hormone for other indications apart from CKD. Ultimately, having robust clinical studies which examine these effects will allow children and their families to make more informed decisions about this therapy.

The diagnostic efficacy of diffusion tensor imaging in children with chronic kidney disease: correlation with histopathology and serum biomarkers

BackgroundChildren with chronic kidney disease (CKD) usually present with disease impact on growth besides cardiovascular problems that not only impact the patient's health during childhood but also affect their adult life. We aimed to identify the diagnostic role of diffusion tensor imaging (DTI) in CKD in pediatric using its metrics: apparent diffusion coefficient (ADC) and fraction anisotropy (FA).ResultsThis prospective study was performed on thirty-five CKD patients (16 girls, 19 boys; mean age 12.3 ± 2.6 years) and 19 sex- and age-matched controls. Both groups underwent renal DTI and renal function tests. Based on renal biopsy, patients with CKD were further categorized into sclerotic CKD (n = 25) and non-sclerotic CKD (n = 10). Mean FA renal medulla/cortex in CKD (0.18 ± 0.18 and 0.20 ± 0.17) was lower significantly (p = 0.001) than volunteers' (0.31 ± 0.19, 0.27 ± 0.18). The cutoff FA of renal medulla/cortex used for CKD diagnosis was 0.22 and 0.23 with AUC of 0.828, 0.838 and accuracy of 80.8%, 82.8%. Mean of renal medulla/cortex ADC in CKD (2.13 ± 0.23 and 1.93 ± 0.22 × 10−3 mm2/s) was higher significantly (p = 0.001) than that of volunteers' (1.67 ± 0.15 and 1.64 ± 0.133 × 10−3 mm2/s. ADC cutoff value of renal medulla/cortex used for CKD diagnosis was 1.86 and 1.74 × 10−3 mm2/s with AUC of 0.827, 0.82, 0.827, and 0.911, and accuracy of 80.6%, 79.6%, 82.8%, and 84.2%. Renal medulla/cortex FA in sclerotic CKD was significantly different (p = 0.001) from non-sclerotic CKD (0.25 ± 0.07 and 0.26 ± 0.08). Cortical and medullary FA in CKD patients correlated with e-GFR (r = 0.363, r = 0.317) and serum creatinine (r = − 0.467, r = − 0.383).ConclusionsRenal cortical/medullary FA can assist in diagnosing pediatric CKD, predict sclerotic CKD, and correlate with some serum biomarkers.

Surgical treatment of secondary hyperparathyroidism in children with chronic kidney disease. Experience in 19 patients.

Secondary hyperparathyroidism (sHPT) is an important contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). When conservative measures are ineffective, parathyroidectomy is indicated. The aim of our study was to evaluate the efficacy and safety of subtotal parathyroidectomy (sPTX) in pediatric and adolescent patients, and to provide a rationale for considering this aggressive treatment in CKD patients with uncontrolled sHPT. We retrospectively analyzed the medical records of 19 pediatric CKD patients on dialysis with refractory sHPT who underwent sPTX at our institution between 2010 and 2020. All patients had clinical, radiological, and biochemical signs of renal osteodystrophy. One year after sPTX, parathyroid hormone (PTH) levels (median and interquartile range (IQR)) dropped from 2073 (1339-2484) to 164 (93-252) pg/mL (p=0.0001), alkaline phosphatase (ALP) levels from 1166 (764-2373) to 410 (126-421) IU/L (p=0.002), and the mean (±SDS) calcium-phosphate (Ca*P) product from 51±11 to 41±13mg2/dL2 (p=0.07). Postoperatively, all patients presented with severe hungry bone syndrome (HBS) and required intravenous and oral calcium and calcitriol supplementation. None of them had other postoperative complication. Histological findings had a good correlation with preoperative parathyroid ultrasound imaging (n: 15) in 100 % and with technetium-99m (99mTc) sestamibi scintigraphy (n: 15) in 86.6 %. Clinical and radiological signs of bone disease improved in all patients. Pediatric sPTX is effective and safe to control sHPT and calcium-phosphate metabolism in children with CKD on dialysis and may mitigate irreversible bone deformities and progression of cardiovascular disease.

Common mental health conditions and considerations in pediatric chronic kidney disease.

The mental health of youth with chronic kidney disease (CKD) has been increasingly recognized as an area of clinical need. The development of mental health concerns is influenced by a range of physiological, psychological, and environmental factors. Some of these factors are common across child development, but some are more unique to youth with CKD. Mental health concerns are associated with increased risk for a range of poor medical outcomes (e.g., adherence, risk of transplant rejection) and quality of life concerns. In this educational review, we discuss the current evidence base regarding the development of mental health concerns in youth with CKD. The review covers multiple domains including mood and anxiety disorders, traumatic stress, and neurodevelopmental disorders. Estimated prevalence and hypothesized risk factors are outlined, and the potential impact of mental health on medical care and functional outcomes are reviewed. Finally, we introduce options for intervention to support positive mental health and offer recommendations for building access to mental health care and improving the mental health education/training of medical professionals.

Dietary Phosphate Educational Materials for Pediatric Chronic Kidney Disease: Are Confused Messages Reducing Their Impact?

ObjectiveThis study aimed to review the quality and content of phosphate educational materials used in pediatric chronic kidney disease. MethodsThe quality of text-based pediatric phosphate educational materials was assessed using validated instruments for health literacy demands (Suitability Assessment of Materials [SAM] and Patient Education Material Assessment Tool [PEMAT-P]) and readability (Flesch Reading Ease [FRE] and Flesch-Kincaid [FK] Grade Level). Codes were inductively derived to analyse format, appearance, target audience, resource type and content, aiming for an intercoder reliability (ICR) >80%. The content was compared to Paediatric Renal Nutrition Taskforce (PRNT) recommendations. ResultsSixty-five phosphate educational materials were obtained, 37 were pediatric-focused including 28 text-based. Thirty-two percent of text-based materials were directed at caregivers, 25% children and 43% unspecified. Most (75%) included a production date with 75% produced >2 years ago. The median FRE test-score was 68.2 (interquartile range [IQR] 61.1-75.3) and FK Grade Level 5.6 (IQR 4.5-7.7). Using SAM, 54% rated “superior” (≥70), 38% “adequate” (40-69) and 8% “not suitable” (≤39). Low scoring materials lacked a summary (12%), cover graphics (35%) or included irrelevant illustrations (50%). PEMAT-P scores were 70% (IQR 50-82) for understandability and 50% (IQR 33-67) for actionability. An ICR of 87% was achieved. Over half limited foods in agreement with PRNT (including 89% suggesting avoiding phosphate additives). Recommendations conflicting with PRNT included reducing legumes and wholegrains. Over a third contained inaccuracies and over two thirds included no practical advice. ConclusionsText-based pediatric phosphate educational materials are pitched at an appropriate level for caregivers, but this may be too high for children under 10 years. The inclusion of relevant illustrations may improve this. Three quarters of materials scored low for actionability. The advice does not always align with the PRNT, which (together with the inaccuracies reported) could result in conflicting messages to patients and their families.

Longitudinal progression trajectory of estimated glomerular filtration rate in children with chronic kidney disease: results from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease).

The natural course of chronic kidney disease (CKD) progression in children varies according to their underlying conditions. This study aims to identify different patterns of subsequent decline in kidney function and investigate factors associated with different patterns of estimated glomerular filtration rate (eGFR) trajectories. We analyzed data from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease), which is a longitudinal, prospective cohort study. A latent class linear mixed model was applied to identify the trajectory groups. In a total of 287 patients, the median baseline eGFR (mL/min/1.73 m2) was 63.3, and the median age was 11.5 years. The eGFR decline rate was -1.54 during a 6.0-year follow-up. The eGFR trajectory over time was classified into four groups. Classes 1 (n = 103) and 2 (n = 11) had a slightly reduced eGFR at enrollment with a stable trend (ΔeGFR, 0.2/year) and a rapid decline eGFR over time (ΔeGFR, -10.5/year), respectively. Class 3 had a normal eGFR (n = 16), and class 4 had a moderately reduced eGFR (n = 157); both these chasses showed a linear decline in eGFR over time (ΔeGFR, -4.1 and -2.4/year). In comparison with classes 1 and 2, after adjusting for age, causes of primary renal disease, and baseline eGFR, nephrotic-range proteinuria was associated with a rapid decline in eGFR (odds ratio, 8.13). We identified four clinically relevant subgroups of kidney function trajectories in children with CKD. Most children showed a linear decline in eGFR; however, there are different patterns of eGFR trajectories.

Pediatric chronic kidney disease mortality in Brazil-A time trend analysis.

Chronic kidney disease (CKD) is defined based on structural or functional abnormalities of the kidneys, or a glomerular filtration rate (GFR) below the threshold of 60 ml/min per 1.73 m2 for more than 3 months. It is an important noncommunicable disease with a rising worldwide, becoming a global public health problem. There are few studies about this problem, especially in low- and middle-income countries (LMIC), including Brazil, an upper-middle-income country. The objective of the study was to determine the cause-specific mortality rates for pediatric CKD patients (CKDMR) from 0 to 19 years old, based on the 10th revision of the International Classification of Diseases (ICD-10) and the Global Burden of Diseases Injuries and Risk Factors Study's (GBD) list. We calculated the impact of the annual human development indexes (HDI) in CKDMR in Brazil and its regions at two different times and compared it with the literature results. We obtained data from the Department of Informatics of the Brazilian Unified Health System (DATASUS) from 1996 to 2017. The Joinpoint regression analyses estimated the average annual percentage changes (AAPCs). The correlation between the HDI values and the number of deaths from each age group in Brazil and its different regions were assessed using the time series autoregressive integrated moving average (ARIMA) models. There were 8838 deaths in a pediatric and adolescent population of about 1.485 x 109 person-years observed in Brazil from 1996 to 2017. Our results demonstrated a significant increase in the AAPC in Brazil's less than 1-year-old age group and a decrease in children from 5 to 19 years old. We observed a positive correlation between CKDMR and HDI among children under 1 year of age. Conversely, there is a negative association in the age groups ranging from 5 to 19 years, indicating an inverse relationship between CKDMR and HDI.

COVID-19 in Children with Chronic Kidney Disease; Does it Differ Much?

COVID-19 is known to have a mild course in children, however more data on pediatric chronic kidney disease (CKD) is needed. We aimed to assess the incidence and severity of COVID-19 in pediatric CKD patients. A questionnaire including demographics, COVID-19 history, symptoms, and vaccination status was applied to patients with CKD. We also retrospectively reviewed the presentation and outcomes of SARS-CoV-2 infection in this patient group from March 2020 to December 2021. 220 patients were included, 48 were found to have experienced COVID-19. There was no significant difference regarding age, gender, underlying kidney disease, CKD stage, dialysis status, type or number of immunosuppressive medications, and glomerular filtration rate between patients with and without COVID-19. Most were infected by a household member (43.8%) and during outpatient or inpatient care (18.8%). Four (8.3%) were asymptomatic, and 43 (89.6%) had mild infection. Severe COVID-19 was observed in only one patient. Eleven (22.9%) patients with COVID-19 were previously vaccinated. Acute kidney injury was detected in 4 (8.3%); as stage 1 in all. Median follow-up after COVID-19 was 4.6 months. All patients fully recovered, and no renal disease flare or death was observed. Although the vaccination rate was low in our cohort, the majority of the children with COVID-19 showed a mild course. Along with the vaccination, general precautions seemed to be successful for this population.

Objectified kidney ultrasound echogenicity and size metrics as potential predictors for kidney function in children.

Kidney echogenicity is typicallydetermined subjectively but may have a quantifiable relationship to kidney function. Similarly, kidney length has been shown to correlate with kidney function. This study sought to quantify echogenicity using readily available software. Secondarily, we aimed to evaluate the correlation between quantified echogenicity and kidney length to the estimated glomerular filtration rate (eGFR) in children with acute kidney injury (AKI) and chronic kidney disease (CKD). In a single-center retrospective observational study, echogenicity index (EI) was determined using a ratio of right kidney to liver mean pixel density. The kidney length ratio (KLR) was determined by the actual to predicted lengths of both kidneys. Both variables were correlated to eGFR using correlation analyses and predictive capacity was determined with receiver operating characteristic curve (ROC) analysis. Of 94 subjects, 46% (43/94) had AKI, 28% (26/95) had CKD and 26% (25/95) were controls. The higher the EI the lower the eGFR (r = -0.46, p < 0.0001). EI between 1.0 and 1.1 predicted an eGFR < 90ml/min/1.73m2 with an AUC of 0.71-0.78 while an EI between 1.1 and 1.2 predicted an eGFR < 60ml/min/1.73m2 with AUC of 0.75-0.80. Overall, the larger the KLR the lower the eGFR (r = -0.25, p 0.018). We have developed an accessible methodology to quantify kidney echogenicity. Overall, there was an inverse correlation between EI and eGFR in pediatric CKD and AKI. However, these correlations did not persist within subgroups which could be due to small sample size and heterogeneity of etiologies. Overall, KLR had a weaker correlation to eGFR, compared to EI. Despite these correlations, both EI and KLR had "fair" to "good" performance as a biomarker for an eGFR < 60ml/min/1.73m2.