Shiga toxin-producing
Escherichia coli
(STEC) hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury (AKI). The outcomes of STEC HUS have improved, and the acute mortality rate ...in children is 1–4 %. About 70 % of patients recover completely from the acute episode and the remainder have varying degrees of sequelae. Only a few retrospective studies have reviewed these patients over long periods. Methodological flaws include a lack of strict definitions, changing modes of treatment, ascertainment bias and loss of subjects to follow-up. The kidneys bear the brunt of the long-term damage: proteinuria (15–30 % of cases); hypertension (5–15 %); chronic kidney disease (CKD; 9–18 %); and end-stage kidney disease (ESKD; 3 %). A smaller number have extra-renal sequelae: colonic strictures, cholelithiasis, diabetes mellitus or brain injury. Most renal sequelae are minor abnormalities, such as treatable hypertension and/or variable proteinuria. Most of the patients who progress to ESKD do not recover normal renal function after the acute episode. Length of anuria (more than 10 days) and prolonged dialysis are the most important risk factors for a poor acute and long-term renal outcome. After the acute episode all patients must be followed for at least 5 years, and severely affected patients should be followed indefinitely if there is proteinuria, hypertension or a reduced glomerular filtration rate (GFR).
Background Neurocognitive dysfunction is a known complication in children with chronic kidney disease (CKD). However, less is known about putative mechanisms or modifiable risk factors. The objective ...of this study was to characterize and determine risk factors for cognitive dysfunction in children, adolescents, and young adults with CKD compared with controls. Study Design Cross-sectional study. Setting & Participants The Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults With Chronic Kidney Disease (NiCK) Study included 90 individuals aged 8 to 25 years with CKD compared with 70 controls. Predictors CKD versus control, estimated glomerular filtration rate (eGFR), ambulatory blood pressure. Outcomes Performance on neurocognitive assessment with relevant tests grouped into 11 domains defined a priori by expert opinion. Results of tests were converted to age-normalized z scores. Measurements Each neurocognitive domain was analyzed through linear regression, adjusting for eGFR and demographic and clinical variables. For domains defined by multiple tests, the median z score of tests in that domain was used. Results We found significantly poorer performance in multiple areas of neurocognitive function among individuals with CKD compared with controls. Particular deficits were seen in domains related to attention, memory, and inhibitory control. Adjusted for demographic and clinical factors, we found lower performance in multiple domains with decreasing eGFRs (attention: β = 0.053, P = 0.02; visual spatial: β = 0.062, P = 0.02; and visual working memory: β = 0.069, P = 0.04). Increased diastolic load and decreased diastolic nocturnal dipping on ambulatory blood pressure monitoring were independently associated with impairments in neurocognitive performance. Limitations Unable to assess changes in neurocognitive function over time, and neurocognitive tests were grouped into predetermined neurocognitive domains. Conclusions Lower eGFR in children, adolescents, and young adults is associated with poorer neurocognitive performance, particularly in areas of attention, memory, and inhibitory control. Hypertension identified on ambulatory blood pressure monitoring may be an important risk factor, illustrating that neurocognitive function is an area of target-organ damage in CKD.
Infections cause significant morbidity and mortality for children receiving maintenance hemodialysis (HD). The Standardizing Care to Improve Outcomes in Pediatric End-Stage Kidney Disease (SCOPE) ...Collaborative is a quality-improvement initiative aimed at reducing dialysis-associated infections by implementing standardized care practices. This study describes patient-level risk factors for catheter-associated bloodstream infections (CA-BSIs) and examines the association between dialysis center-level compliance with standardized practices and risk of CA-BSI.
Prospective cohort study.
Children enrolled in SCOPE between June 2013 and July 2019.
Data were collected on patient characteristics and center-level compliance with HD catheter care practices across the study period. Centers were categorized as consistent, dynamic (improved compliance over the study period), or inconsistent performers based on frequency of compliance audit submission and changes in compliance with HD care practices over time.
CA-BSIs.
Generalized linear mixed models were used to evaluate (1) patient-level risk factors for CA-BSI and (2) associations between change in center-level compliance and CA-BSIs.
The cohort included 1,277 children from 35 pediatric dialysis centers; 1,018 (79.7%) had a catheter and 259 (20.3%) had an arteriovenous fistula or graft. Among children with a catheter, mupirocin use at the catheter exit site was associated with an increased rate of CA-BSIs (rate ratio RR, 4.45; P = 0.004); the use of no antibiotic agent at the catheter exit site was a risk factor of borderline statistical significance (RR, 1.79; P = 0.05). Overall median compliance with HD catheter care practices was 87.5% (IQR, 77.3%-94.0%). Dynamic performing centers showed a significant decrease in CA-BSI rates over time (from 2.71 to 0.71 per 100 patient-months; RR, 0.98; P < 0.001), whereas no significant change in CA-BSI rates was detected among consistent or inconsistent performers.
Lack of data on adherence to HD care practices on the individual patient level.
Improvement in compliance with standardized HD care practices over time may lead to a reduction in dialysis-associated infections.
Pediatric kidney transplant candidates often have multiple potential living donors (LDs); no evidence‐based tool exists to compare potential LDs, or to decide between marginal LDs and deceased donor ...(DD) kidney transplantation (KT). We developed a pediatric living kidney donor profile index (P‐LKDPI) on the same scale as the DD KDPI by using Cox regression to model the risk of all‐cause graft loss as a function of living donor characteristics and DD KDPI. HLA‐B mismatch (adjusted hazard ratio aHR per mismatch = 1.041.271.55), HLA‐DR mismatch (aHR per mismatch = 1.021.231.49), ABO incompatibility (aHR = 1.203.268.81), donor systolic blood pressure (aHR per 10 mm Hg = 1.011.071.18), and donor estimated GFR (eGFR; aHR per 10 mL/min/1.73 m2 = 0.880.940.99) were associated with graft loss after LDKT. Median (interquartile range IQR) P‐LKDPI was −25 (−56 to 12). 68% of donors had P‐LKDPI <0 (less risk than any DD kidney) and 25% of donors had P‐LKDPI >14 (more risk than median DD kidney among pediatric KT recipients during the study period). Strata of LDKT recipients of kidneys with higher P‐LKDPI had a higher cumulative incidence of graft loss (39% at 10 years for P‐LDKPI ≥20, 28% for 20> P‐LKDPI ≥−20, 23% for −20 > P‐LKDPI ≥−60, 19% for P‐LKDPI <−60 log rank P < .001). The P‐LKDPI can aid in organ selection for pediatric KT recipients by allowing comparison of potential LD and DD kidneys.
The authors propose a risk index for pediatric living donor kidney transplantation, which quantifies the risk of graft loss based on living donor characteristics on the same scale as the Kidney Profile Donor Index.
Streptococcus pneumoniae associated hemolytic uremic syndrome (SpHUS) is defined by the occurrence of acute hemolytic anemia, thrombocytopenia and acute kidney injury in a patient with a S. ...pneumoniae infection. We review the pathophysiology, clinical course, treatment and prognosis for SpHUS. We also describe an expanded classification system that uses additional diagnostic criteria to identify more patients with a high likelihood of having SpHUS.
SpHUS often may be underdiagnosed because of overlapping features with disseminated intravascular coagulation (DIC) and the lack of strict diagnostic criteria. The epidemiology has changed with the emergence of different pneumococcal serotypes as newer pneumococcal vaccines have been introduced.
SpHUS accounts for 5-15% of all HUS cases. The majority of SpHUS patients have pneumonia and a low mortality rate in contrast to those with meningitis, who have a more severe clinical course. Although the pathogenesis of SpHUS remains unknown, the Thomsen-Friedenreich antigen seems to play a central role. S. pneumoniae produces neuraminidase, thereby exposing the Thomsen-Friedenreich antigen on the surface of cell membranes. Thomsen-Friedenreich antigen exposure can result in hemolysis and direct endothelial injury leading to HUS phenotype. Early identification of these patients is critical so that fresh frozen plasma may be avoided.
The Fontan operation is a palliative procedure for congenital single ventricle heart disease. Long-term kidney function in this cohort is not well-known. Our aim was to evaluate renal function in ...long-term survivors post-Fontan palliation, and we hypothesize that this cohort will have a higher prevalence of chronic kidney disease (CKD) compared to controls.
We performed a retrospective cohort study of 68 subjects evaluated through the Single Ventricle Survivorship Program at the Children's Hospital of Philadelphia between July 2010 and December 2014 compared to 70 healthy children similar in age and sex. Primary outcome was CKD, defined as estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m
using creatinine and cystatin C-based estimating equations. Secondary outcomes included proteinuria and elevated intact parathyroid hormone.
The Fontan cohort included 68 subjects with median age 13 years (IQR 9.0, 17.3) who were median 11.1 years (IQR 6.5, 15.7) post-Fontan palliation. This cohort was compared to 70 healthy individuals (median age 15.5 years (IQR 12.5, 18.3). Although median eGFRs were comparable: 102.6 vs. 101.9 mL/min/1.73 m
(P = .89) in Fontan vs. healthy subjects <18 years of age (Full CKiD equation), and 128.5 vs. 129.7 mL/min/1.73 m
(P = .56) in Fontan vs. healthy subjects ≥18 years of age (CKD-EPI creatinine and cystatin formula); 10% of Fontan subjects had an eGFR<90 mL/min/1.73 m
. Median intact parathyroid hormone level was higher at 59.4 pg/mL (IQR 43.0, 83.1) in the Fontan group compared to 23.4 pg/mL (IQR 16.7, 30.0) in controls (P ≤ .001). Proteinuria was present in 10% of the Fontan group compared to 4.7% in controls (P = .27).
Ten percent of long-term survivors post-Fontan palliation had eGFR <90 ml/min/1.73 m
, and higher median parathyroid hormone levels compared to controls. Taken together, these measures may indicate early kidney disease. Future studies will focus on longitudinal assessment of kidney function and evaluation of risk factors for CKD post-Fontan palliation.
Background
Environmental lead exposure is associated with cognitive impairment in healthy children, with deficits seen in intelligence quotient (IQ), attention, and behavior. Neurocognitive ...dysfunction is also a well-described complication among children with chronic kidney disease (CKD). The
o
bjective was to evaluate the association between blood lead levels (BLL) and performance on neurocognitive assessments in a cohort of children with CKD.
Methods
Cross-sectional study of children with mild to moderate CKD from the Chronic Kidney Disease in Children (CKiD) multicenter prospective cohort study. The primary exposure was BLL. The primary outcome was performance on age-specific neurocognitive assessments evaluating IQ, executive functioning, attention, hyperactivity, and behavior. Multivariable linear regression was used to evaluate the association between BLL and neurocognitive performance, adjusted for key sociodemographic and clinical variables.
Results
A total of 412 subjects were included with median age 15.4 years, median estimated GFR 39 mL/min/1.73
2
, median BLL 1.2 mcg/dL, and median IQ score 99. In multivariable linear regression, higher BLL was associated with significantly lower IQ score (− 2.1 IQ points for every 1-mcg/dL increase in BLL,
p
= 0.029). Higher BLL was associated with worse scores on the Conners’ Continuous Performance Test II Variability T-Score, a measure of inattention (+ 1.8 T-Score points for every 1-mcg/dL increase in BLL,
p
= 0.033).
Conclusions
Low-level lead exposure is associated with significantly lower IQ and more inattention in children with CKD, a population already at high risk for neurocognitive dysfunction. Universal screening for elevated BLL should be considered for all children with CKD at age 12–24 months.
Background
Children with chronic kidney disease (CKD) are at risk for abnormalities in pubertal development. We aimed to describe the timing of pubertal onset by luteinizing hormone (LH) levels and ...the association between hormonal onset of puberty with changes in GFR.
Methods
Data from the Chronic Kidney Disease in Children (CKiD) study were collected prospectively. GFR was estimated at annual visits and measured by iohexol clearance every other year. LH was measured from stored repository serum samples in a nested sample of 124 participants. Hormonal onset of puberty was defined as LH level greater than or equal to 0.3 IU/L. A mixed effects model with random intercepts and slopes was used to compare the slope of decline of GFR before and after hormonal onset of puberty. The model was adjusted for age, glomerular disease diagnosis, baseline proteinuria on the log scale, and BMI.
Results
Median age at hormonal onset of puberty was 9.9 years (IQR 8.1, 11.9) in girls and 10.2 years (IQR 9.2, 11.0) in boys. The mixed effects model showed faster decline in both estimated GFR and measured GFR in boys after hormonal onset of puberty (
p
< 0.001), and a similar but attenuated accelerated estimated GFR decline was observed for girls with no difference for measured GFR.
Conclusions
LH levels in the post-pubertal range were observed prior to clinical manifestations of puberty in children with CKD. Hormonal onset of puberty was associated with faster decline in GFR, particularly among boys with CKD.
Graphical abstract
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