Acute kidney injury requiring dialysis in children: a multicentric, emerging country perspective.

BACKGROUND: Acute kidney injury (AKI) is a life-threatening condition, especially in extreme age groups and when kidney replacement therapy (KRT) is necessary. Studies worldwide report mortality rates of 10-63% in pediatric patients undergoing KRT. METHODS: Over 13 years, this multicenter study analyzed data from 693 patients with AKI, all receiving KRT, across 74 hospitals and medical facilities in Rio de Janeiro, Brazil. RESULTS: The majority were male (59.5%), under one year old (55.6%), and treated in private hospitals (76.5%). Sixty-six percent had comorbidities. Pneumonia and congenital heart disease were the most common admission diagnoses (21.5% and 20.2%, respectively). The mortality rate was 65.2%, with lower rates in patients over 12 years (50%). Older age was protective (HR: 2.35, IQR [1.52-3.62] for neonates), and primary kidney disease had a three-fold lower mortality rate. ICU team experience (HR: 0.74, IQR [0.60-0.91]) correlated with lower mortality, particularly in hospitals treating 20 or more patients. Among the deceased, 40% died within 48 h of KRT initiation, suggesting possible late referral or treatment futility. CONCLUSIONS: This study confirms the high mortality in pediatric dialytic AKI in middle-income countries, underlining early mortality and offering critical insights for improving outcomes.

Renal angina index for early identification of risk of acute kidney injury in critically ill children.

BACKGROUND: The main objective was to test whether the Renal Angina Index (RAI), calculated on patient admission to the pediatric intensive care unit (PICU), is associated with the risk of acute kidney injury (AKI) based on the Kidney Disease: Improving Global Outcomes (KDIGO) (stage ≥ 2) in 72 h. The specific aim was to analyze the performance of the RAI at a specialized oncology PICU. METHODS: Retrospective cohort study involving two pediatric intensive care units located within a general hospital and an oncology hospital. Children aged ≥ 3 months to < 18 years admitted to the intensive care units in 2017 with a length of stay ≥ 72 h were included. RESULTS: The sample included 249 patients, of which 51% were male (127 patients), with median age of 77 months, and mean ICU stay of 5 days. Of the total admissions, 141 were clinical (57%) and 108 surgical. The rate of AKI was 15% and death rate within 30 days was 13%. Having a positive RAI on admission showed a statistically significant association with AKI at Day 3 (OR = 18.5, 95%CI = 4.3 - 78.9, p < 0.001) and with death (OR = 3.9, 95%CI = 1.6 - 9.9, p = 0.004). The accuracy of the RAI in the cancer population was 0.81 on the ROC curve (95%CI 0.74, 0.88). CONCLUSIONS: The RAI is a useful tool for predicting AKI and death in critically ill children, including in oncology units.

Symptoms for early diagnosis of chronic kidney disease in children - a machine learning-based score.

The objective of this study was to reveal the signs and symptoms for the classification of pediatric patients at risk of CKD using decision trees and extreme gradient boost models for predicting outcomes. A case-control study was carried out involving children with 376 chronic kidney disease (cases) and a control group of healthy children (n = 376). A family member responsible for the children answered a questionnaire with variables potentially associated with the disease. Decision tree and extreme gradient boost models were developed to test signs and symptoms for the classification of children. As a result, the decision tree model revealed 6 variables associated with CKD, whereas twelve variables that distinguish CKD from healthy children were found in the "XGBoost". The accuracy of the "XGBoost" model (ROC AUC = 0.939, 95%CI: 0.911 to 0.977) was the highest, while the decision tree model was a little lower (ROC AUC = 0.896, 95%CI: 0.850 to 0.942). The cross-validation of results showed that the accuracy of the evaluation database model was like that of the training. CONCLUSION: In conclusion, a dozen symptoms that are easy to be clinically verified emerged as risk indicators for chronic kidney disease. This information can contribute to increasing awareness of the diagnosis, mainly in primary care settings. Therefore, healthcare professionals can select patients for more detailed investigation, which will reduce the chance of wasting time and improve early disease detection. WHAT IS KNOWN: • Late diagnosis of chronic kidney disease in children is common, increasing morbidity. • Mass screening of the whole population is not cost-effective. WHAT IS NEW: • With two machine-learning methods, this study revealed 12 symptoms to aid early CKD diagnosis. • These symptoms are easily obtainable and can be useful mainly in primary care settings.

Time from kidney failure onset to transplantation and its impact on growth in pediatric patients.

BACKGROUND: In children with kidney failure, the longer the duration of dialysis the greater the impact on growth deficit, quality of life, and life expectancy. The aim of this research is to test whether there was a shortening of treatment time from kidney failure to transplantation in pediatric patients and whether this time interval impacted height. METHODS: Observational retrospective cohort study from 2005 to 2018. The first outcome variable was time to transplantation in years, while the second was height/age standard deviation score (SDS) at transplantation. Cox regression models were used to analyze time from disease to transplantation and linear regression was employed to test the association of the year of kidney failure onset with height. RESULTS: A total of 780 children were evaluated and 517 underwent kidney transplantation after a median time of 1.9 years (IQR = 1.0-4.0). The variables significantly associated with time to transplant were: year of kidney failure onset (HR = 1.07; 95% CI: 1.05-1.10; p < .001), age at kidney failure onset <12 years (HR = 0.59; 95% CI: 0.49-0.71; p < .001), living in different state as transplant center (HR = 0.63; 95% CI: 0.53-0.77; p < .001), and undergoing blood transfusion before transplantation (HR = 0.63; 95% CI: 0.53-0.75; p < .001). Regarding growth, for each 1-year increase in the epoch of kidney failure onset, a 0.05 SDS raise in height/age is expected (p < .001). CONCLUSION: Children with recent kidney failure onset had significantly lower time to the outcome and this reduction was associated with a less severe growth deficit.

Twenty-year Follow-up of Patients With Epidemic Glomerulonephritis due to Streptococcus zooepidemicus in Brazil.

Introduction: Post-streptococcal glomerulonephritis (PSGN) has a good prognosis in children, but few studies have evaluated the long-term renal outcomes in adults with PSGN. Methods: In a follow-up study, 47 predominantly adult patients with PSGN due to group C Streptococcus zooepidemicus were reassessed 20 years after an outbreak in Nova Serrana, Brazil. We evaluated clinical characteristics, renal outcomes, and the trajectory of the estimated glomerular filtration rate (eGFR) by the creatinine-based chronic kidney disease-epidemiology collaboration equation from 5 follow-up assessments. Logistic regression and mixed-effects regression were used in the analysis. Results: After 20 years, the participants' mean age was 56.6±15.1 years. Thirty-four (72%) patients had hypertension, 21 (44.7%) had eGFR <60 ml/min per 1.73 m2, 8 of 43 (18.6%) had urine protein-to-creatinine ratio >150 mg/g, and 25 (53%) had CKD (low eGFR and/or increased proteinuria). Increasing age was associated with CKD (odds ratio: 1.07; 95% confidence interval [CI]: 1.02-1.13; P = 0.011) in multivariate analysis. The mean eGFR decline in the last 11 years of follow-up was -3.2 ml/min per 1.73 m2 per year (95% CI: -3.7 to -2.7). Older age at baseline (coefficient -1.05 ml/min per 1.73 m2 per year; 95% CI -1.28 to -0.81; P < 0.001), and hypertension 5 years after the outbreak (coefficient -7.78 ml/min/1.73 m2; 95% CI -14.67 to -0.78; P = 0.027) were associated with lower eGFR during the whole study period. Conclusion: There was a marked worsening of renal function and a high prevalence of CKD and hypertension after 20 years of PSGN outbreak. Long-term follow-up is warranted after PSGN, especially among older patients.

Children on chronic hemodialysis before the first year of age in Brazil: A 3-year survival analysis.

INTRODUCTION: The limited data on survival rates of small children undergoing hemodialysis preclude comparison with other countries. The goal of this study was to determine the mortality rate and its risk factors in children starting hemodialysis during their first year of life. METHODS: We performed a retrospective cohort study, based on data from a reference dialysis center in São Paulo city. Data from 47 (8 females) children who underwent chronic hemodialysis before the first year of age were analyzed. Survival was characterized using Kaplan-Meier methods and log-rank tests, followed by a multivariable Cox regression model. RESULTS: The survival rates were 93%, 75%, and 64% at 1, 2, and 3 years, respectively. Only cardiovascular comorbidity was significantly associated with the mortality outcome (HR = 5.7, 95% CI = 1.7-19.6, p = 0.006). CONCLUSION: The survival rate among children who started hemodialysis in their first year of life was reasonable, similar to international standards.

Encouraging outcomes of using a small-donor single graft in pediatric kidney transplantation.

BACKGROUND: The use of small pediatric kidneys as single grafts for transplantation is controversial, due to the potential risk for graft thrombosis and insufficient nephron mass. METHODS: Aiming to test the benefits of transplanting these kidneys, 375 children who underwent kidney transplantation in a single center were evaluated: 49 (13.1%) received a single graft from a small pediatric donor (≤ 15 kg, SPD group), 244 (65.1%) from a bigger pediatric donor (> 15 kg, BPD group), and 82 (21.9%) from adult living donors (group ALD). RESULTS: Groups had similar baseline main characteristics. After 5 years of follow-up, children from the SPD group were comparable to children from BPD and ALD in patient survival (94%, 96%, and 98%, respectively, p = 0.423); graft survival (89%, 88%, and 93%, respectively, p = 0.426); the frequency of acute rejection (p = 0.998); the incidence of post-transplant lymphoproliferative disease (p = 0.671); the odds ratio for severely increased proteinuria (p = 0.357); the rates of vascular thrombosis (p = 0.846); and the necessity for post-transplant surgical intervention prior to discharge (p = 0.905). The longitudinal evolution of eGFR was not uniform among groups. The three groups presented a decrease in eGFR, but the slope of the curve was steeper in ALD children. At 5 years, the eGFR of the ALD group was 10 ml/min/1.73m2 inferior to the others. At that time, the eGFR from the SPD group was statistically similar to the BPD group (p = 0.952). CONCLUSION: In a specialized transplant center, the use of a single small pediatric donor kidney for transplantation is as successful as bigger pediatric or adult living donors, after 5 years of follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.

Copper Deficiency in Children With Intestinal Failure: Risk Factors and Influence on Hematological Cytopenias.

BACKGROUND: We investigated to what extent serum copper influences hemoglobin (Hb), neutrophil, and platelet counts and the factors associated with serum copper in children with intestinal failure (IF) who have their micronutrient status monitored according to a standard protocol. METHODS: Children with IF admitted to a pediatric intestinal rehabilitation program and receiving home parenteral nutrition (PN) were followed up prospectively. Patients received vitamins and multi-trace elements (TEs) as part of the PN. Copper, iron, zinc, vitamin A, and cobalamin serum levels were routinely monitored at 3-month intervals or monthly when a deficiency was detected. Complete blood counts were performed biweekly. Repeated-measures analyses were used to estimate the effect of explanatory variables on the outcomes. RESULTS: Thirteen children with a median time receiving PN of 16.6 months were included. An average of 7 copper measurements per patient were performed; 53.8% of patients had a low serum level at least twice during the follow-up. Eight patients with cholestasis had TEs of PN discontinued. In the multivariable analysis, copper was not associated with Hb levels; an increase of 10 µg/dL in serum copper resulted in an increase of 240/mm3 (95% confidence interval [CI], 18.0-30.1) neutrophils and of 8429/mm3 (95% CI, 466-1219) platelets (P < .001). Time of PN without copper, direct bilirubin levels, and ostomy were associated with lower serum copper. CONCLUSION: The increase in serum copper was associated with significant increases in neutrophil and platelet counts. Time without copper in PN, cholestasis, and having an ostomy negatively influenced copper status.

Acute rejection in pediatric renal transplantation: Retrospective study of epidemiology, risk factors, and impact on renal function.

AR is a major relevant and challenging topic in pediatric kidney transplantation. Our objective was to evaluate cumulative incidence of AR in pediatric kidney transplant patient, risk factors for this outcome, and impact on allograft function and survival. A retrospective cohort including pediatric patients that underwent kidney transplantation between 2011 and 2015 was designed. Risk factors for AR were tested by competing risk analysis. To estimate its impact, graft survival and difference in GFR were evaluated. Two hundred thirty patients were included. As a whole, the incidence of AR episodes was 0.16 (95% CI = 0.12-0.20) per person-year of follow-up. And cumulative incidence of AR was 23% in 1 year and 39% in 5 years. Risk factors for AR were number of MM (SHR 1.36 CI 1.14-1.63 P = .001); ISS with CSA, PRED, and AZA (SHR 2.22 CI 1.14-4.33 P = .018); DGF (SHR 2.49 CI 1.57-3.93 P < .001); CMV infection (SHR 5.52 CI 2.27-11.0 P < .001); and poor adherence (SHR 2.28 CI 1.70-4.66 P < .001). Death-censored graft survival in 1 and 5 years was 92.5% and 72.1%. Risk factors for graft loss were number of MM (HR 1.51 CI 1.07-2.13 P = .01), >12 years (HR 2.66 CI 1.07-6.59 P = .03), and PRA 1%-50% (HR 2.67 CI 1.24-5.73 P = .01). Although occurrence of AR did not influence 5-year graft survival, it negatively impacted GFR. AR was frequent in patients assessed and associated with number of MM, ISS regimen, DGF, CMV infection, and poor adherence, and had deleterious effect on GFR.

Strategy to Enable and Accelerate Kidney Transplant in Small Children and Results of the First 130 Transplants in Children ≤15 kg in a Single Center.

BACKGROUND: Proper care of young children in need of kidney transplant (KT) requires many skilled professionals and an expensive hospital structure. Small children have lesser access to KT. METHODS: We describe a strategy performed in Brazil to enable and accelerate KT in children ≤15 kg based on the establishment of one specialized transplant center, focused on small children, and cooperating with distant centers throughout the country. Actions on 3 fronts were implemented: (a) providing excellent medical assistance, (b) coordinating educational activities to disseminate expertise and establish a professional network, and (c) fostering research to promote scientific knowledge. We presented the number and outcomes of small children KT as a result of this strategy. RESULTS: Three hundred forty-six pediatric KTs were performed in the specialized center from 2009 to 2017, being 130 in children ≤15 kg (38%, being 41 children ≤10 kg) and 216 in >15 kg (62%). Patient survival after 1 and 5 years of the transplant was 97% and 95% in the "small children" group, whereas, in the "heavier children" group, it was 99% and 96% (P = 0.923). Regarding graft survival, we observed in the "small children" group, 91% and 87%, whereas in the "heavier children" group, 94% and 87% (P = 0.873). These results are comparable to the literature data. Groups were similar in the incidence of reoperation, vascular thrombosis, posttransplant lymphoproliferative disease, and estimated glomerular filtration rate. CONCLUSIONS: The strategy allowed an improvement in the number of KT in small children with excellent results. We believe this experience may be useful in other locations.

Is Preoperative Preparation Time a Barrier to Small Children Being Ready for Kidney Transplantation?

BACKGROUND: Small children are less frequently transplanted when compared with older. The objective of the present study was to compare the preparation time for transplantation in children of different weights and to identify factors associated with a delay in the workup of small children. METHODS: We report on a retrospective cohort comprising all children referred for renal transplantation (RTx) workup between 2009 and 2017. The main outcome was transplantation workup time, defined as the time elapsed between the first consultation and when the child became ready for the surgery. RESULTS: A total of 389 children (63.5% males) were selected, with a median weight of 18 kg (interquartile range, 11-32). Patients were categorized into 2 groups: group A (study group): ≤15 kg (n = 165) and group B (control group): >15 kg (n = 224). The probability of being ready for RTx was comparable between groups A and B. The cumulative incidence rate difference between groups is -0.05 (95% confidence interval, -0.03 to 0.02). The median time for RTx workup was 5.4 (2.4-9.4) in group A and 4.3 (2.2-9.0) months in group B (P = 0.451). Moreover, the presence of urinary tract malformation was associated with the need for longer transplantation workup time (P < 0.001). CONCLUSIONS: In children >7 kg, the workup time for transplantation is not related to body weight. In a specialized center, children weighing 7-15 kg became ready within the same timeframe as children weighing >15 kg, despite the smaller children had greater difficulty being nourished, dialyzed, and a greater need for surgical correction of the urinary tract pretransplant.

Collaborative Brazilian pediatric renal transplant registry (CoBrazPed-RTx): A report from 2004 to 2018.

The Brazilian collaborative registry for pediatric renal transplantation began in 2004 as a multicenter initiative aimed at analyzing, reporting, and disseminating the results of pediatric renal transplantation in Brazil. Data from all pediatric renal transplants performed from January 2004 to May 2018 at the 13 participating centers were analyzed. A total of 2744 pediatric renal transplants were performed in the thirteen participating centers. The median age at transplantation was 12.2 years, with the majority being male recipients (56%). The main underlying diseases were CAKUT (40.5%) and glomerulopathy (28%). 1981 (72%) of the grafts were from deceased donors (DD). Graft survival at one year (censored by death) was 94% in the live donor group (LD) and 91% in the DD group (log-rank test P < 0.01). The patient's survival at one and 5 years was 97% and 95% for the LD group and 96% and 93% for the DD group (log-rank test P = 0.02). The graft loss rate was 19% (n = 517), more frequently caused by vascular thrombosis (n = 102) and chronic graft nephropathy (n = 90). DD recipients had 1.6 (1.0-2.2) times greater chance of death and 1.5 (1.2-1.8) times greater chance of graft loss compared to LD recipients. The mortality rate was 5.4% (n = 148), mainly due to infection (n = 69) and cardiovascular disease (n = 28). The results of this collaborative pediatric renal transplant record are comparable to other international registries, although we still have a high infection rate as a cause of death.

Management of Hypertension in CAKUT: Protective Factor for CKD.

Patients with congenital kidney and urinary tract abnormalities (CAKUT) will often develop end-stage renal disease at some point and the need for renal replacement therapy is associated with high rates of morbidity and mortality. Hence, efforts to slow the progression of the disease are essential. Hypertension has been proven to be an independent risk factor for faster decline of glomerular filtration rate in renal patients, but studies involving only children with CAKUT are scarce. We performed a literature review to explore the association of hypertension with faster chronic kidney disease progression in children with CAKUT and also treatment options in this condition. A recent study reported an annual decline in GFR of 1.8 ml/min/1.73 m2 among hypertensive patients with non-glomerular CKD, compared with 0.8 ml/min/1.73 m2 in normotensive children. A multicenter prospective cohort in Brazil showed that a 1-unit increase in systolic blood pressure Z-score was associated with a 1.5-fold higher risk of disease progression. Since renin-angiotensin-aldosterone system activation is the most important mechanism of hypertension in these children, the first-line therapy involves the use of inhibitors of this axis, including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers type I, which also promote an anti-fibrotic effect. Recent studies have shown a good safety profile for use in patients with chronic kidney disease and also in those with solitary kidneys. Hypertension is an independent risk factor for kidney disease progression and should be promptly managed for renal protection, especially among patients with CAKUT, the primary cause of chronic kidney disease in the pediatric population.

Cardiovascular risk in children and adolescents with end stage renal disease.

OBJECTIVES: To evaluate cardiovascular involvement in children and adolescents with End Stage Renal Disease (ESRD) and to characterize the main risk factors associated with this outcome. METHODS: Cross-sectional study of 69 children and adolescents at renal transplantation and 33 healthy individuals matched by age and gender. The study outcomes were left ventricular mass z-score (LVMZ) and carotid artery intima-media thickness (CIMT). The potential risk factors considered were age, gender, CKD etiology, use of oral vitamin D and calcium-based phosphate binders, systolic and diastolic blood pressure, body mass index z-score, time since diagnosis, dialysis duration, serum levels of ionic calcium, phosphorus, parathyroid hormone, fibroblast growth factor (FGF 23), uric acid, homocysteine, cholesterol, triglycerides, C-reactive protein (CRP), vitamin D and hemoglobin. RESULTS: In the multivariate analysis, the factors associated with LVMZ were dialysis duration, age, systolic blood pressure, serum hemoglobin and HDL cholesterol levels. Regarding CIMT, in the multivariate analysis, systolic blood pressure was the only factor associated with the outcome. CONCLUSION: Children exhibited important cardiovascular involvement at the time of the renal transplantation. Both of the studied outcomes were independently associated with systolic blood pressure. For this reason, controlling blood pressure seems to be the main therapy to minimize cardiovascular involvement in children with ESRD.

Is arterial calcification in children and adolescents with end-stage renal disease a rare finding?

AIM: To investigate if calcification and intimal media thickness (IMT) of arteries are present in children and adolescents with end-stage renal disease and to describe the risk factors associated with these alterations. METHODS: In an observational, cross-sectional prospective study, 68 patients were evaluated at the time of renal transplantation. A fragment of the inferior epigastric artery was removed during surgery for histopathological analysis to verify the presence or not of arterial calcification. Two outcomes were considered: the presence of calcium deposition and the measurement of the IMT of the artery. The potential exposure variables were: age, chronic kidney disease aetiology, diagnosis time, systolic blood pressure (SBP), use of oral active vitamin D, homocysteine and C-reactive protein. RESULTS: No arterial calcification was observed in the studied sample. The median value of the IMT of the inferior epigastric artery was 166 µm (interquartile range = 130-208). SBP standard deviation score and age were the only factors associated with this outcome. There was no statistical interaction between SBP and age with the IMT (P = 0.280). CONCLUSION: Arterial calcification is rare in children and adolescents with end-stage renal disease. The factors associated with IMT were age and SBP.

Exploring the consumption of ultra-processed foods and its association with food addiction in overweight children.

The present study explored the consumption of ultra-processed foods and its association with food addiction in overweight children. The prevalence of food addiction was investigated using the Yale Food Addiction Scale for Children in overweight 9-11 year-old children (BMI/age ≥1 Z score) of both sexes from two schools (n = 139). Food intake was estimated by a food frequency questionnaire and the food items were classified into 4 categories: minimally processed, culinary ingredients, processed foods and ultra-processed foods (UPF), based on their degree of processing. Among the children, 95% showed at least one of the seven symptoms of food addiction and 24% presented with a diagnosis of food addiction. In analysis of covariance adjusted for age and sex, a tendency of higher consumption of added sugar (refined sugar, honey, corn syrup) and UPF was found among those diagnosed with food addiction. Multiple logistic regression adjusted for sugar, sodium and fat ingestion showed that consumption of cookies/biscuits (OR = 4.19, p = 0.015) and sausages (OR = 11.77, p = 0.029) were independently associated with food addiction. The identification of foods that may be associated with addictive behavior is very important for correctly treating and preventing childhood obesity, which continues to be one of the greatest health problems in the world.

Cardiovascular risk in children and adolescents with end stage renal disease

OBJECTIVES: To evaluate cardiovascular involvement in children and adolescents with End Stage Renal Disease (ESRD) and to characterize the main risk factors associated with this outcome. METHODS: Cross-sectional study of 69 children and adolescents at renal transplantation and 33 healthy individuals matched by age and gender. The study outcomes were left ventricular mass z-score (LVMZ) and carotid artery intima-media thickness (CIMT). The potential risk factors considered were age, gender, CKD etiology, use of oral vitamin D and calcium-based phosphate binders, systolic and diastolic blood pressure, body mass index z-score, time since diagnosis, dialysis duration, serum levels of ionic calcium, phosphorus, parathyroid hormone, fibroblast growth factor (FGF 23), uric acid, homocysteine, cholesterol, triglycerides, C-reactive protein (CRP), vitamin D and hemoglobin. RESULTS: In the multivariate analysis, the factors associated with LVMZ were dialysis duration, age, systolic blood pressure, serum hemoglobin and HDL cholesterol levels. Regarding CIMT, in the multivariate analysis, systolic blood pressure was the only factor associated with the outcome. CONCLUSION: Children exhibited important cardiovascular involvement at the time of the renal transplantation. Both of the studied outcomes were independently associated with systolic blood pressure. For this reason, controlling blood pressure seems to be the main therapy to minimize cardiovascular involvement in children with ESRD.