Outcome of immunosuppression in children with IgA vasculitis-related nephritis.

BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analyzed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow up. RESULTS: The median follow up was 3.7 years (IQR 2-6.2). At last follow up, 29% of patients had an eGFR < 90 ml/min/1.73m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second line immunosuppressive regimen to be superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

Calcineurin inhibitor-related hyperkalemia is caused by hyporeninemic hypoaldosteronism and fludrocortisone is an effective treatment: Report of a case series and review of the literature.

INTRODUCTION: Calcineurin inhibitors (CNIs) are widely used in transplantation. Although CNI-related hyperkalemia is common (10%-60.6%), the underlying pathogenetic mechanism is not well-elucidated and may lead to dose adjustment or treatment withdrawal. OBJECTIVE: The aim of this study is to describe CNI-related hyperkalemia due to hyporeninemic hypoaldosteronism in pediatric transplant recipients who were successfully treated with fludrocortisone. METHOD: In a total of 55 hematopoietic stem cell (HSCT) and 35 kidney transplant recipients followed according to institutional immunosuppression protocols, recipients diagnosed with CNI-related hyperkalemia were reviewed. Recipients who were receiving intravenous fluid, potassium, or were diagnosed with hemolysis, acute graft rejection, or had an eGFR < 30 mL/min/1.73m2, were excluded. A detailed analysis of clinical history as well as biochemical studies was carried out to reveal possible pathophysiology. RESULTS: Three pediatric transplant recipients (one HSCT, two kidney transplantation) with findings of hyperkalemia, hyponatremia, and a mild elevation in blood urea nitrogen while on CNIs were recruited. Urinary potassium excretion was diminished while sodium excretion was increased. Plasma aldosterone levels were low, and renin was not increased in response. Primary adrenal insufficiency was ruled out, and hyporeninemic hypoaldosteronism was diagnosed. CNI-related hyperkalemia was detected earlier in case 1, who had HSCT (22 days), than in the second and third cases, who had kidney transplantation (24 and 30 months post-transplantation, respectively). The discrepancy was hypothesized to be explained by higher overall CNI dose due to higher serum target CNI used in HSCT than kidney transplantation. Electrolyte imbalance was reversed upon administration of physiologic dose fludrocortisone (0.05 mg, daily), while fludrocortisone was ceased after CNI withdrawal in case 1, which is additional evidence for the etiological association of CNIs and hyporeninemic hypoaldosteronism. CONCLUSION: Our three cases strengthen the premise that CNI-related hyperkalemia may be due to hyporeninemic hypoaldosteronism, and the timing and severity may be related to CNI dose. Fludrocortisone is a safe and effective treatment in CNI-related hyperkalemia, providing maintenance of CNIs, which are one of the essential therapeutic agents for pediatric transplantation.

Acute kidney injury in children with moderate-severe COVID-19 and multisystem inflammatory syndrome in children: a referral center experience.

BACKGROUND: Data on the characteristics of acute kidney injury (AKI) in pediatric COVID-19 and MIS-C are limited. We aimed to define the frequency, associated factors and early outcome of AKI in moderate, severe or critical COVID-19 and MIS-C; and to present a tertiary referral center experience from Türkiye. METHODS: Hospitalized patients ≤ 18 years of age with confirmed COVID-19 or MIS-C at Ihsan Dogramaci Children's Hospital, Hacettepe University, between March 2020-December 2021 were enrolled. The characteristics of AKI in the COVID-19 group were investigated in moderate, severe and critically ill patients; patients with mild COVID-19 were excluded. RESULTS: The median (Q1-Q3) age in the COVID-19 (n = 66) and MIS-C (n = 111) groups was 10.7 years (3.9-15.2) and 8.7 years (4.5-12.7), respectively. The frequency of AKI was 22.7% (15/66) in COVID-19 and 15.3% (17/111) in MIS-C; all MIS-C patients with AKI and 73.3% (11/15) of COVID-19 patients with AKI had AKI at the time of admission. Multivariate analyses revealed need for vasoactive/inotropic agents [Odds ratio (OR) 19.233, p = 0.002] and presence of vomiting and/or diarrhea (OR 4.465, p = 0.036) as independent risk factors of AKI in COVID-19 patients; and need for vasoactive/inotropic agents (OR 22.542, p = 0.020), procalcitonin and ferritin levels as independent risk factors of AKI in the MIS-C group. Age was correlated with lymphocyte count (r = -0.513, p < 0.001) and troponin level (r = 0.518, p < 0.001) in MIS-C patients. Length of hospital stay was significantly longer in both groups with AKI, compared to those without AKI. Mortality was 9.1% in the COVID-19 group; and was associated with AKI (p = 0.021). There was no mortality in MIS-C patients. AKI recovery at discharge was 63.6% in COVID-19 survivors and 100% in MIS-C patients. CONCLUSIONS: Independent risk factors for AKI were need for vasoactive/inotropic agents and vomiting/diarrhea in moderate, severe or critical COVID-19 patients; and need for vasoactive/inotropic agents and severe inflammation in MIS-C patients. Our findings suggest that inflammation and cardiac dysfunction are associated with AKI in MIS-C patients; and the association with age in this group merits further studies in larger groups. Early outcome is favorable; long-term follow-up for kidney functions is needed.

Dyslipidemia in children with chronic kidney disease-findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study.

BACKGROUND: Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. METHODS: In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3-5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. RESULTS: A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. CONCLUSIONS: Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors.

Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study.

BACKGROUND: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. METHODS: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. RESULTS: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). CONCLUSIONS: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Variable phenotype and genotype of pediatric patients with HNF1B nephropathy.

AIMS: Hepatocyte nuclear factor 1ß (HNF1B) mutations are the most common monogenic cause of congenital anomalies of the kidney and urinary tract (CAKUT). We aimed to investigate clinical and genetic characteristics of patients with HNF1B nephropathy to expand its phenotypic and genetic spectrum. MATERIALS AND METHODS: This retrospective cohort study included 16 unrelated pediatric patients (6 females, 10 males) from 13 families with genetically confirmed HNF1B-related nephropathy. RESULTS: Abnormal prenatal kidney abnormalities were present in 13 patients (81.3%). The most common antenatal kidney abnormality was kidney cysts, which were observed in 8 patients (61.5%). Urinary system abnormalities (vesicoureteral reflux (VUR) and ureteropelvic junction obstruction (UPJO)) were present in 4 patients (25%). HNF1B analysis uncovered missense variants in 4 families (30.8%) as the most common genetic abnormality. In addition, 4 novel pathological variations have been defined. During follow-up, hypomagnesemia and hyperuricemia were observed in 7 (43.8%) and 5 patients (31.3%), respectively. None of the patients with a missense variant had hypomagnesemia. However, 7 out of 12 patients (58.3%) with a non-missense variant had hypomagnesemia (p = 0.09). None of the patients had an HNF1B score below 8, and the mean score was 15.3 ± 4.4. The mean follow-up period was 7.4 ± 5.0 years. While 100% of patients (n = 4) with missense variants were in various stages of CKD (CKD2: 2 patients, CKD3: 2 patients), 25% of those with non-missense variants had CKD (CKD2, 3, and 5; 1 patient, respectively) (p = 0.026). CONCLUSION: Patients with HNF1B-associated disease have concomitant urinary system abnormalities such as VUR or UPJO. Missense variants seem to be the most common pathological variations in HNF1B gene and have higher risk of CKD.

Adolescence-onset atypical hemolytic uremic syndrome: is it different from infant-onset?

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare, mostly complement-mediated thrombotic microangiopathy. The majority of patients are infants. In contrast to infantile-onset aHUS, the clinical and genetic characteristics of adolescence-onset aHUS have not been sufficiently addressed to date. METHODS: A total of 28 patients (21 girls, 7 boys) who were diagnosed as aHUS between the ages of ≥10 years and <18 years were included in this study. All available data in the Turkish Pediatric aHUS registry were collected and analyzed. RESULTS: The mean age at diagnosis was 12.8±2.3 years. Extra-renal involvement was noted in 13 patients (46.4%); neurological involvement was the most common (32%). A total of 21 patients (75%) required kidney replacement therapy. Five patients (17.8%) received only plasma therapy and 23 (82%) of the patients received eculizumab. Hematologic remission and renal remission were achieved in 25 (89.3%) and 17 (60.7%) of the patients, respectively. Compared with the infantile-onset aHUS patients, adolescent patients had a lower complete remission rate during the first episode (p = 0.002). Genetic analyses were performed in all and a genetic variant was detected in 39.3% of the patients. The mean follow-up duration was 4.9±2.6 years. At the last visit, adolescent patients had lower eGFR levels (p = 0.03) and higher rates of chronic kidney disease stage 5 when compared to infantile-onset aHUS patients (p = 0.04). CONCLUSIONS: Adolescence-onset aHUS is a rare disease but tends to cause more permanent renal dysfunction than infantile-onset aHUS. These results may modify the management approaches in these patients.

COVID-19 vaccination among adolescents and young adults with chronic kidney conditions: a single-center experience.

BACKGROUND: Following the pandemic of COVID-19, the main focus has been on COVID-19 vaccines and herd immunity. Although the safety of the COVID-19 vaccines has been shown in clinical trials, children with chronic diseases were not included. We investigated the side effect profile and safety of the COVID-19 vaccines in adolescents with kidney disease. METHODS: A questionnaire including demographic information, history of COVID-19, vaccination status, and vaccine-related side effects was administered to the patients with chronic kidney disease (CKD) stage 2-5, glomerular disease treated with immunosuppression, and kidney transplant recipients. RESULTS: Ninety-eight patients were vaccinated with CoronaVac-inactivated SARS-CoV-2 (n=16) or BNT162b2 messenger RNA (mRNA) COVID-19 (n=82) vaccine. The mean age was 16.90±2.36 years. The most common side effects were local pain, fatigue, and fever. No serious side effects or renal disease flare were observed. There was no significant difference in the side effects reported after the BNT162b2 mRNA-RNA as compared to the Corona Vac-inactivated SARS-CoV-2 vaccine. No significant relationship was found between the frequency of side effects according to age, glomerular filtration rate, immunosuppressive treatments, CKD stage, and the underlying disease. CONCLUSION: Although the reported data are subjective because they were obtained through a questionnaire and studies with long-term follow-up are needed, our early experience suggests that the vaccine is safe and adolescents and young adults should be encouraged to be vaccinated.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The risk of cardiovascular comorbidity in children with Behçet's disease.

OBJECTIVE: Patients with Behcet disease (BD) may experience long term morbidity caused by different forms of cardiovascular diseases. This study aimed to assess the risk for cardiovascular comorbidity in pediatric BD patients with and without vascular involvement, independent of the contribution of traditional risk factors. METHODS: Pediatric patients classified as BD according to the 2015 International Pediatric BD criteria were included in the study. Twenty-four-h ambulatory blood pressure monitoring (ABPM), transthoracic echocardiography, and carotid intima media thickness (cIMT) measurements were performed. Patients with an active disease and have other known risk factors for cardiovascular disease were not included in the study. RESULTS: Thirty-one children and adolescents with pediatric BD (16 female, 51.6%; F/M: 1.06) were enrolled in the study. Among all BD patients 10 patients (34.4%) had abnormal ABPM. Carotid IMT values, mean arterial pressure, systolic and diastolic blood pressure by ABPM and the prevalence of abnormal ABPM, non-dipping, and ambulatory hypertension were similar between patients with and without vascular involvement. The echocardiography measurements showed that BD patients with vascular involvement had significantly higher velocity and velocity time integral of the left ventricle outflow tract which may point out increased stiffness of the aorta. CONCLUSION: Pediatric BD patients with vascular involvement may tend to have more cardiovascular risk factors. However, cardiovascular assessment should be considered in all BD patients regardless of the involved systems. We suggest that ABPM may accurately define hypertension and cardiovascular risk in BD.

Hearing Loss Related to Gene Mutations in Distal Renal Tubular Acidosis.

INTRODUCTION: Distal renal tubular acidosis (dRTA) is a disease that may develop either primarily or secondarily, resulting from urinary acidification defects in distal tubules. Hearing loss may accompany primary forms of dRTA. This study aims to determine the characteristics of hearing loss due to different gene mutations in patients with dRTA. METHODS: Behavioral and electrophysiological audiological evaluations were performed after otolaryngology examination in 21 patients with clinically diagnosed dRTA. Radiological imaging of the inner ear (n = 9) was conducted and results of genetic analyses using next-generation sequencing method (n = 16) were included. RESULTS: Twenty-one patients with dRTA from 20 unrelated families, aged between 8 months and 33 years (median = 12, interquartile range = 20), participated. All patients with ATP6V1B1 mutations (n = 9) had different degrees of hearing loss. There was one patient with hearing loss in patients with ATP6V0A4 mutations (n = 6). One patient with the WDR72 mutation had normal hearing. Large vestibular aqueduct syndrome (LVAS) was detected in 6 (67%) of 9 patients whose radiological evaluation results were available. CONCLUSIONS: LVAS is common in patients with dRTA and may influence the type and severity of hearing loss in these patients. The possibility of both congenital and late-onset and progressive hearing loss should be considered in dRTA patients. A regular audiological follow-up is essential for the early detection of a possible late-onset or progressive hearing loss in these patients.

Predictors of kidney complications and analysis of hypertension in children with allogeneic hematopoietic stem cell transplantation.

BACKGROUND: This study aimed to determine incidence of kidney complications in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) patients. METHODS: Pediatric allogeneic HSCT patients were included. Post-transplantation urinary system complications were collected from medical records and glomerular filtration rates at last visit compared with clinical parameters. Additionally, 24-h ambulatory blood pressure monitoring was performed. RESULTS: The study included 165 pediatric patients. Acute kidney injury (AKI) developed in 125 (75.8%) patients of whom 54 (43.2%) had stage 1, 36 (28.8%) stage 2, and 35 (28%) stage 3 AKI. Primary malignant disease and viral infection post-HSCT were associated with increased risk of AKI (OR: 4; 95%CI: 1.2-13, p = 0.022 and OR: 2.9; 95%CI: 1.2-6.8, p = 0.014, respectively). Mean duration of post-HSCT follow-up was 4.4 ± 2.5 years, during which time 8 patients had chronic kidney disease (CKD) (stage 1, 4 patients; stage 2, 3 patients; stage 3, 1 patient). CKD incidence was higher in patients in whom stem cell product was bone marrow + cord blood and mobilized peripheral blood, compared to bone marrow alone (40-37.5% versus 5.1%, p = 0.002). Based on 24-h ABPM, 14.7% and 7.4% of patients with normal office blood pressure had pre-hypertension and hypertension, respectively. In patients with albuminuria/severe albuminuria, daytime and nighttime systolic SDS scores were higher than those without albuminuria/severe albuminuria (p = 0.010 and p = 0.004, respectively). CONCLUSIONS: Incidence of AKI is higher in pediatric HSCT patients with primary malignant disease and those with documented viral infection. Our study highlights the beneficial role of 24-h ABPM as a routine part of standard care of pediatric HSCT recipients.

Long-term kidney follow-up after pediatric acute kidney support therapy for children less than 15 kg.

BACKGROUND: In small children, acute dialysis (pediatric acute kidney support therapy (paKST)) is increasingly used; however, it is challenging for many reasons. We compared clinical characteristics and predictors of long-term outcomes of patients < 15 kg on peritoneal dialysis (PD), hemodialysis (HD), and continuous kidney replacement therapy (CKRT). METHODS: Patients with history of paKST (CKRT, HD, PD) weighing < 15 kg and ≥ 6 months of follow-up at Hacettepe University were included. Surviving patients were evaluated at last visit. RESULTS: 109 patients (57 females) were included. Median age at paKST was 10.1 months (IQR: 2-27 months). In total, 43 (39.4%) patients received HD, 37 (34%) PD, and 29 (26.6%) CKRT. 64 (58.7%) patients died a median 3 days (IQR: 2-9.5 days) after paKST. Percentages of patients using vasopressor agents, with sepsis, and undergoing mechanical ventilation were lower in those who survived. After mean follow-up of 2.9 ± 2.1 years, 34 patients were evaluated at mean age 4.7 ± 2.4 years. Median spot urine protein/creatinine was 0.19 (IQR: 0.13-0.37) and 12 patients (35.3%) had non-nephrotic proteinuria. Three patients had estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 and 2 (6%) had hyperfiltration. In total 22 patients (64.7%) had ≥ 1 kidney risk factor (elevated blood pressure/hypertension, hyperfiltration, eGFR < 90 ml/min/1.73m2, and/or proteinuria) at last visit. Among 28 patients on paKST < 32 months, 21 had ≥ 1 risk factor (75%), whereas among 6 patients who had paKST ≥ 32 months, one patient had ≥ 1 risk factor (16.7%), (p = 0.014). CONCLUSIONS: Patients on paKST who undergo mechanical ventilation and vasopressor treatment should be followed-up more closely. After surviving the acute period, patients on paKST need to be followed-up closely during the chronic stage. A higher resolution version of the Graphical abstract is available as Supplementary information.

Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study.

BACKGROUND: The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI. METHODS: A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI. RESULTS: Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48 ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive. CONCLUSIONS: Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Nutritional and Anthropometric Indices in Children Receiving Haemodiafiltration vs Conventional Haemodialysis - The HDF, Heart and Height (3H) Study.

BACKGROUND: The "HDF-Heart-Height" study showed that haemodiafiltration (HDF) is associated with improved growth compared to conventional haemodialysis (HD). We report a post-hoc analysis of this study assessing the effect of extracorporeal dialysis therapies on nutritional indices. METHODS: 107 children were included in the baseline cross-sectional analysis, of whom 79 (43 HD, 36 HDF) completed the 12-month follow-up. Height (Ht), optimal 'dry' weight (Wt), and body mass index (BMI) standard deviations scores (SDS), waist-to-hip ratio, des-acyl ghrelin (DAG), adiponectin, leptin, insulin-like growth factor-1 (IGF-1)-SDS and insulin were measured. RESULTS: The levels of nutritional indices were comparable between HDF and HD patients at baseline and 12-month. On univariable analyses Wt-SDS positively correlated with leptin and IGF-1-SDS, and negatively with DAG, while Ht-SDS of the overall cohort positively correlated with IGF1-SDS and inversely with DAG and adiponectin. On multivariable analyses, higher 12-month Ht-SDS was inversely associated with baseline DAG (beta = -0.13 per 500 higher; 95%CI -0.22, -0.04; P = .004). Higher Wt-SDS at 12-month was positively associated with HDF modality (beta = 0.47 vs HD; 95%CI 0.12-0.83; P = .01) and inversely with baseline DAG (beta = -0.18 per 500 higher; 95%CI -0.32, -0.05; P = .006). Growth Hormone (GH) treated patients receiving HDF had higher annualized increase in Ht SDS compared to those on HD. CONCLUSIONS: In children on HD and HDF both Wt- and Ht-SDS independently correlated with lower baseline levels of the anorexygenic hormone DAG. HDF may attenuate the resistance to GH, but further studies are required to examine the mechanisms linking HDF to improved growth.

Findings from 4C-T Study demonstrate an increased cardiovascular burden in girls with end stage kidney disease and kidney transplantation.

Mortality in children with kidney failure is higher in girls than boys with cardiovascular complications representing the most common causes of death. Pulse wave velocity (PWV), a measure of vascular stiffness, predicts cardiovascular mortality in adults. Here, PWV in children with kidney failure undergoing kidney replacement therapy was investigated to determine sex differences and potential contributing factors. Two-hundred thirty-five children (80 girls; 34%) undergoing transplantation (150 pre-emptive, 85 with prior dialysis) having at least one PWV measurement pre- and/or post-transplantation from a prospective cohort were analyzed. Longitudinal analyses (median/maximum follow-up time of 6/9 years) were performed for PWV z-scores (PWVz) using linear mixed regression models and further stratified by the categories of time: pre-kidney replacement therapy and post-transplantation. PWVz significantly increased by 0.094 per year and was significantly higher in girls (PWVz +0.295) compared to boys, independent of the underlying kidney disease. During pre-kidney replacement therapy, an average estimated GFR decline of 4 ml/min/1.73 m2 per year was associated with a PWVz increase of 0.16 in girls only. Higher diastolic blood pressure and low density lipoprotein were independently associated with higher PWVz during pre-kidney replacement therapy in both sexes. In girls post-transplantation, an estimated GFR decline of 4ml/min/1.73m2 per year pre-kidney replacement therapy and a longer time (over 12 months) to transplantation were significantly associated with higher PWVz of 0.22 and of 0.57, respectively. PWVz increased further after transplantation and was positively associated with time on dialysis and diastolic blood pressure in both sexes. Thus, our findings demonstrate that girls with advanced chronic kidney disease are more susceptible to develop vascular stiffening compared to boys, this difference persist after transplantation and might contribute to higher mortality rates seen in girls with kidney failure.

Long-term renal survival of paediatric patients with lupus nephritis.

BACKGROUND: Childhood-onset systemic lupus erythematosus (SLE) is more severe than adult-onset disease, including more frequent kidney involvement. This study aimed to investigate baseline clinical features, treatment modalities and short- and long-term renal outcomes of paediatric patients with lupus nephritis (LN). MATERIALS AND METHODS: This study enrolled 53 LN patients out of 102 childhood-onset SLE patients followed at Hacettepe University between 2000 and 2020. The demographic and clinical data were reviewed retrospectively from the medical charts and electronic records. All SLE patients with renal involvement underwent renal biopsy either at the time of diagnosis or during follow-up. RESULTS: The median age at onset of SLE was 13.3 years [interquartile range (IQR) 10.4-15.8]. The median follow-up duration was 43.1 months (IQR 24.3-69.3). Of the 102 SLE patients, 53 (52%) had LN. The most frequent histopathological class was Class IV LN (54.7%), followed by Class III (22.6%). The proportion of patients who achieved either complete or partial remission was 77.3% and 73% at 6 and 12 months, respectively. In the overall LN cohort, 5- and 10-year renal survival rates were 92% and 85.7%, respectively. The remission rate at Month 6 was significantly higher in mycophenolate mofetil (MMF)- and cyclophosphamide (CYC)-treated groups than other combination therapies (P = 0.02). Although no difference was found between the CYC and MMF response rates (P = 0.57) in proliferative LN (Classes III and IV), the majority of Class IV patients (79%) received CYC as induction therapy. There was no difference between the response rates in any treatment regimens at Month 12 (P = 0.56). In the multivariate analysis, male gender, requiring dialysis at the time of LN diagnosis and failure to achieve remission at 6 and 12 months were found to be associated with poor renal outcome. CONCLUSIONS: Our study demonstrated that male gender, failure to achieve remission at 6 and 12 months and requiring dialysis at the time of diagnosis were the best predictors of poor renal outcome. Therefore appropriate and aggressive management of paediatric LN is essential to achieve and maintain remission.

Long-term follow-up of patients after acute kidney injury in the neonatal period: abnormal ambulatory blood pressure findings.

BACKGROUND: Data on the long-term effects of neonatal acute kidney injury (AKI) are limited. METHODS: We invited 302 children who had neonatal AKI and survived to hospital discharge; out of 95 patients who agreed to participate in the study, 23 cases were excluded due to primary kidney, cardiac, or metabolic diseases. KDIGO definition was used to define AKI. When a newborn had no previous serum creatinine, AKI was defined as serum creatinine above the mean plus two standard deviations (SD) (or above 97.5th percentile) according to gestational age, weight, and postnatal age. Clinical and laboratory features in the neonatal AKI period were recorded for 72 cases; at long-term evaluation (2-12 years), kidney function tests with glomerular filtration rate (eGFR) by the Schwartz formula, microalbuminuria, office and 24-h ambulatory blood pressure monitoring (ABPM), and kidney ultrasonography were performed. RESULTS: Forty-two patients (58%) had stage I AKI during the neonatal period. Mean age at long-term evaluation was 6.8 ± 2.9 years (range: 2.3-12.0); mean eGFR was 152.3 ± 26.5 ml/min/1.73 m2. Office hypertension (systolic and/or diastolic BP ≥ 95th percentile), microalbuminuria (> 30 mg/g creatinine), and hyperfiltration (> 187 ml/min/1.73 m2) were present in 13.0%, 12.7%, and 9.7% of patients, respectively. ABPM was performed on 27 patients, 18.5% had hypertension, and 40.7% were non-dippers; 48.1% had abnormal findings. Female sex was associated with microalbuminuria; low birth weight (< 1,500 g) and low gestational age (< 32 weeks) were associated with hypertension by ABPM. Twenty-three patients (33.8%) had at least one sign of microalbuminuria, office hypertension, or hyperfiltration. Among 27 patients who had ABPM, 16 (59.3%) had at least one sign of microalbuminuria, abnormal ABPM (hypertension and/or non-dipping), or hyperfiltration. CONCLUSION: Even children who experienced stage 1 and 2 neonatal AKI are at risk for subclinical kidney dysfunction. Non-dipping is seen in four out of 10 children. Long-term follow-up of these patients is necessary.

Association of urine phthalate metabolites, bisphenol A levels and serum electrolytes with 24-h blood pressure profile in adolescents.

BACKGROUND: Among the possible causes of hypertension in adolescence, electrolyte imbalances and environmental pollutants are drawing increasing attention. We aimed to examine the relationship between bisphenol A (BPA), phthalate metabolites, and serum electrolytes and blood pressure. METHODS: Eighty-six participants aged 12-15 years were included in the study. Body mass index (BMI), office blood pressure and 24-h ambulatory blood pressure measurements (ABPM), and carotid intima-media thickness were determined. Blood samples were taken for hemogram, renal function tests, and serum electrolytes. Free- and total-BPA and phthalate metabolites were analyzed from urine samples. RESULTS: Of the participants, 34 were evaluated as normal blood pressure profile, 33 as white-coat hypertension (WCHT), and 19 as ABPM-hypertension. Adolescents in ABPM- hypertension groups had higher BMI-standard deviation score (SDS), leucocyte, platelet count; but lower serum chloride, compared to the normal blood pressure profile group. The percentage of adolescents with detectable urinary mono-benzyl phthalate (MBzP) was higher in ABPM-hypertension (42.1%) and WCHT groups (33.3%), compared to the normal blood pressure profile group (5.9%, p = 0.004). Associations between MBzP and ABPM- hypertension and WCHT were remained after confounding factor adjustment. Adolescents with detectable MBzP levels had also higher "albumin-corrected calcium" and lower serum phosphate and "albumin-corrected calcium x phosphate product" compared to others. Adolescents with detectable urinary MBzP levels had higher blood pressure profiles in some 24-h (mean arterial pressure-SDS, systolic blood pressure-SDS), daytime (systolic blood pressure-SDS), and night-time (mean arterial pressure-SDS, systolic blood pressure-SDS, and diastolic blood pressure-SDS) measurements, compared to others. WCHT was found to be associated negatively with monomethyl phthalate and the sum of dibutyl phthalate metabolites and ABPM-HT with MCPP. There was no significant association between blood pressure profiles and free- and total-BPA status. CONCLUSION: MBzP was associated with adverse blood pressure profiles in adolescence. Additive follow-up studies are necessary for cause-effect relations.

Importance of clinical practice guidelines to practicing pediatric nephrologists and IPNA survey.

Clinical practice guidelines (CPGs) are systematically developed statements backed by scientific evidence to assist practitioners in management in clinical practice. An international cross-sectional survey was conducted by the IPNA to examine the perceptions of pediatric nephrologists on guidelines and their usage and to identify important diseases for future clinical practice guidelines (CPGs). The survey found that the majority of pediatric nephrologists find CPGs useful in clinical practice and admitted to using them most of the time. Developing CPGs is challenging and there are standards available to develop trustworthy guidelines. While evidence-based global guidelines are ideal, pediatric nephrologists expressed the desire that they address regional differences. Most respondents (89.2%) to the survey agreed that adult guidelines did not cover the pediatric perspective adequately and 71.4% opined that consensus-based pediatric guidelines can be developed when evidence for the pediatric population is lacking. The development of high-quality practice guidelines requires substantial resources and may not be feasible in resource-poor countries. Adaptation of an existing guideline has been suggested as an alternative and the ADAPTE collaboration provides a systematic approach to adapting guidelines. Several diseases where pediatric guidelines are needed as a priority including IgA and C3 glomerulopathy were identified in the survey. Implementation of guideline-based care is challenging and the survey found that lack of availability of guidelines (43%) and resources (22.8%) are important reasons for poor implementation in lower-middle and low-income countries. Perceived complexity of guidelines, physician attitudes, and lack of training also contribute to non-adherence to guidelines.