Health-related quality of life of children with X-linked hypophosphatemia in Germany.

BACKGROUND: X-linked hypophosphatemia (XLH) is a rare inherited phosphate-wasting disorder associated with bone and dental complications. Health-related quality of life (HRQoL) is reduced in XLH patients on conventional treatment with phosphate supplements and active vitamin D, while information on patients treated with burosumab is rare. METHODS: HRQoL was assessed in 63 pediatric XLH patients participating in a prospective, observational study and patient registry in Germany using the KIDSCREEN-52 survey instrument and standardized qualitative interviews. RESULTS: The median age of the XLH patients was 13.2 years (interquartile range 10.6 - 14.6). At the time of the survey, 55 (87%) patients received burosumab and 8 (13%) conventional treatment. Forty-six patients (84%) currently being treated with burosumab previously received conventional treatment. Overall, HRQoL was average compared to German reference values (mean ± SD: self-report, 53.36 ± 6.47; caregivers' proxy, 51.33 ± 7.15) and even slightly above average in some dimensions, including physical, mental, and social well-being. In general, XLH patients rated their own HRQoL higher than their caregivers. In qualitative interviews, patients and caregivers reported that, compared with conventional therapy, treatment with burosumab reduced stress, bone pain, and fatigue, improved physical health, and increased social acceptance by peers and the school environment. CONCLUSIONS: In this real-world study in pediatric XLH patients, HRQoL was average or even slightly above that of the general population, likely due to the fact that the vast majority of patients had their treatment modality switched from conventional treatment to burosumab resulting in improved physical health and well-being.

Intensive BP Control in Patients with CKD and Risk for Adverse Outcomes.

SIGNIFICANCE STATEMENT: Although most guidelines recommend tightly controlling BP in patients with CKD, individuals with advanced kidney disease or severe albuminuria were not well-represented in trials examining the effect of this intervention on kidney outcomes. To examine the effect of intensive BP control on the risk of kidney outcomes in patients with CKD, the authors pooled individual-level data from seven trials. They found that overall, intensive BP control was associated with a 13% lower, but not significant, risk of a kidney outcome. However, the intervention's effect on the kidney outcome differed depending on baseline eGFR. Data from this pooled analysis suggested a benefit of intensive BP control in delaying KRT onset in patients with stages 4-5 CKD, but not necessarily in those with stage 3 CKD. BACKGROUND: The effect of intensive BP lowering (to systolic BP of <120 mm Hg) on the risk of kidney failure requiring KRT remains unclear in patients with advanced CKD. Such patients were not well represented in trials evaluating intensive BP control. METHODS: To examine the effect of intensive BP lowering on KRT risk-or when not possible, trial-defined kidney outcomes-we pooled individual-level data from seven trials that included patients with eGFR<60 ml/min per 1.73 m 2 . We performed prespecified subgroup analyses to evaluate the effect of intensive BP control by baseline albuminuria and eGFR (CKD stages 4-5 versus stage 3). RESULTS: Of 5823 trial participants, 526 developed the kidney outcome and 382 died. Overall, intensive (versus usual) BP control was associated with a lower risk of kidney outcome and death in unadjusted analyses but these findings did not achieve statistical significance. However, the intervention's effect on the kidney outcome differed depending on baseline eGFR ( P interaction=0.05). By intention-to-treat analysis, intensive (versus usual) BP control was associated with a 20% lower risk of the primary kidney outcome in those with CKD GFR stages 4-5, but not in CKD GFR stage 3. There was no interaction between intensive BP control and the severity of albuminuria for kidney outcomes. CONCLUSIONS: Data from this pooled analysis of seven trials suggest a benefit of intensive BP control in delaying KRT onset in patients with stages 4-5 CKD but not necessarily with stage 3 CKD. These findings suggest no evidence of harm from intensive BP control, but also point to the need for future trials of BP targets focused on populations with advanced kidney disease. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_02_27_JASN0000000000000060.mp3.

Outcome of infantile nephropathic cystinosis depends on early intervention, not genotype: A multicenter sibling cohort study.

Infantile nephropathic cystinosis (INC) is an inheritable lysosomal storage disorder characterized by lysosomal cystine accumulation, progressive kidney disease, and multiple extrarenal complications (ERCs). Cysteamine postpones the onset of end-stage kidney disease (ESKD) and reduces the incidence of ERCs; however, cysteamine is generally initiated upon establishment of the renal Fanconi syndrome (FS) and partial loss of kidney function, whereas data on long-term effects of cysteamine administered from neonatal age are lacking. An international multicenter retrospective cohort study of siblings with INC was set up to investigate the outcome in relation to age at initiation of cysteamine versus CTNS genotype, with attention to patients treated with cysteamine from neonatal age. None of the siblings treated from neonatal age (n = 9; age 10 ± 6 years) had reached ESKD, while 22% of their index counterparts (n = 9; age 14 ± 5 years) had commenced renal replacement therapy. Siblings treated with cysteamine from the onset of symptoms at a younger age compared with their index counterparts, reached ESKD at a significant older age (13 ± 3 vs. 10 ± 3 years, p = 0.002). In contrast, no significant difference in ERCs was observed between sibling and index patients, independently from the age at initiation of cysteamine. The CTNS genotype had no impact on the overall outcome in this cohort. In INC, presymptomatic treatment with cysteamine results in a better renal outcome in comparison to treatment initiated from the onset of symptoms. This justifies including cystinosis into newborn screening programs. SYNOPSIS: In infantile nephropathic cystinosis, presymptomatic treatment with cysteamine improves the renal outcome which justifies the inclusion of cystinosis into newborn screening programs.

Role of hypertension in progression of pediatric CKD.

Hypertension is frequent in children with chronic kidney disease (CKD). Its prevalence varies according to CKD stage and cause. It is relatively uncommon in children with congenital kidney disease, while acquired kidney disease is associated with a higher prevalence of hypertension. Studies in children with CKD utilizing ambulatory blood pressure monitoring also showed a high prevalence of masked hypertension. Uncontrolled and longstanding hypertension in children is associated with progression of CKD. Aggressive treatment of high blood pressure should be an essential part of care to delay CKD progression in children.

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.

Relationship between age at initiation of cysteamine treatment, adherence with therapy, and glomerular kidney function in infantile nephropathic cystinosis.

Infantile nephropathic cystinosis, due to impaired transport of cystine out of lysosomes, occurs with an incidence of 1 in 100-200,000 live births. It is characterized by renal Fanconi syndrome in the first year of life and glomerular dysfunction progression to end-stage kidney disease by approximately 10 years of age. Treatment with oral cysteamine therapy helps preserve glomerular function, but affected individuals eventually require kidney replacement therapy. This is because glomerular damage had already occurred by the time a child is diagnosed with cystinosis, typically in the second year of life. We performed a retrospective multicenter study to investigate the impact of initiating cysteamine treatment within the first 2 months of life in some infants and comparing two different levels of adherence in patients diagnosed at the typical age. We collected 3983 data points from 55 patients born between 1997 and 2020; 52 patients with 1592 data points could be further evaluated. These data were first analyzed by dividing the patient cohort into three groups: (i) standard treatment start with good adherence, (ii) standard treatment start with less good adherence, and (iii) early treatment start. At every age, mean estimated glomerular filtration rate (eGFR) was higher in early-treated patients than in later-treated patients. Second, a generalized additive mixed model (GAMM) was applied showing that patients with initiation of treatment before 2 months of age are expected to have a 34 ml/min/1.73 m2 higher eGFR than patients with later treatment start while controlling for adherence and patients' age. These data strongly suggest that oral cysteamine treatment initiated within 2 months of birth preserves kidney function in infantile nephropathic cystinosis and provide evidence of the utility of newborn screening for this disease.

Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants.

Autosomal recessive polycystic kidney disease (ARPKD) is a severe disease of early childhood that is clinically characterized by fibrocystic changes of the kidneys and the liver. The main cause of ARPKD are variants in the PKHD1 gene encoding the large transmembrane protein fibrocystin. The mechanisms underlying the observed clinical heterogeneity in ARPKD remain incompletely understood, partly due to the fact that genotype-phenotype correlations have been limited to the association of biallelic null variants in PKHD1 with the most severe phenotypes. In this observational study we analyzed a deep clinical dataset of 304 patients with ARPKD from two independent cohorts and identified novel genotype-phenotype correlations during childhood and adolescence. Biallelic null variants frequently show severe courses. Additionally, our data suggest that the affected region in PKHD1 is important in determining the phenotype. Patients with two missense variants affecting amino acids 709-1837 of fibrocystin or a missense variant in this region and a null variant less frequently developed chronic kidney failure, and patients with missense variants affecting amino acids 1838-2624 showed better hepatic outcome. Variants affecting amino acids 2625-4074 of fibrocystin were associated with poorer hepatic outcome. Thus, our data expand the understanding of genotype-phenotype correlations in pediatric ARPKD patients and can lay the foundation for more precise and personalized counselling and treatment approaches.

Sex and age as determinants for high blood pressure in pediatric renal transplant recipients: a longitudinal analysis of the CERTAIN Registry.

BACKGROUND: High prevalence of arterial hypertension is known in pediatric renal transplant patients, but how blood pressure (BP) distribution and control differ between age groups and whether sex and age interact and potentially impact BP after transplantation have not been investigated. METHODS: This retrospective analysis included 336 pediatric renal transplant recipients (62% males) from the Cooperative European Pediatric Renal Transplant Initiative Registry (CERTAIN) with complete BP measurement at discharge and 1, 2 and 3 years post-transplant. RESULTS: At discharge and 3 years post-transplant, arterial hypertension was highly prevalent (84% and 77%); antihypertensive drugs were used in 73% and 68% of the patients. 27% suffered from uncontrolled and 9% from untreated hypertension at 3 years post-transplant. Children transplanted at age < 5 years showed sustained high systolic BP z-score and received consistently less antihypertensive treatment over time. Younger age, shorter time since transplantation, male sex, higher body mass index (BMI), high cyclosporine A (CSA) trough levels, and a primary renal disease other than congenital anomalies of the kidney and urinary tract (CAKUT) were significantly associated with higher systolic BP z-score. Sex-stratified analysis revealed a significant association between high CSA and higher systolic BP in older girls that likely had started puberty already. An association between BP and estimated glomerular filtration rate was not detected. CONCLUSIONS: BP control during the first 3 years was poor in this large European cohort. The description of age- and sex-specific risk profiles identified certain recipient groups that may benefit from more frequent BP monitoring (i.e. young children) or different choices of immunosuppression (i.e. older girls).

Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children.

Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6-17 years with baseline estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m2. uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m2, and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m2, or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69-0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD.

Genetic associations of hemoglobin in children with chronic kidney disease in the PediGFR Consortium.

BACKGROUND: Genome-wide association studies (GWAS) in healthy populations have identified variants associated with erythrocyte traits, but genetic causes of hemoglobin variation in children with CKD are incompletely understood. METHODS: The Pediatric Investigation of Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE), and Cardiovascular Comorbidity in Children with CKD (4C). We performed cross-sectional and longitudinal association studies of single-nucleotide polymorphisms (SNPs) in 1125 patients. RESULTS: Children of European (n = 725) or Turkish (n = 400) ancestry (EA or TA) were included. In cross-sectional analysis, two SNPs (rs10758658 and rs12718597) previously associated with RBC traits were significantly associated with hemoglobin levels in children of EA and TA. In longitudinal analysis, SNP rs2540917 was nominally associated with hemoglobin in EA and TA children. CONCLUSIONS: SNPs associated with erythrocyte traits in healthy populations were marginally significant for an association with hemoglobin. Further analyses/replication studies are needed in larger CKD cohorts to investigate SNPs of unknown significance associated with hemoglobin. Functional studies will be required to confirm that the observed associations between SNPs and clinical phenotype are causal.

Treatment and long-term outcome in primary distal renal tubular acidosis.

BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome. METHODS: We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form. RESULTS: Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (±1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate. CONCLUSION: Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.

Steroid withdrawal improves blood pressure control and nocturnal dipping in pediatric renal transplant recipients: analysis of a prospective, randomized, controlled trial.

BACKGROUND: Variable effects of steroid minimization strategies on blood pressure in pediatric renal transplant recipients have been reported, but data on the effect of steroid withdrawal on ambulatory blood pressure and circadian blood pressure rhythm have not been published so far. METHODS: In a prospective, randomized, multicenter study on steroid withdrawal in pediatric renal transplant recipients (n = 42) on cyclosporine, mycophenolate mofetil, and methylprednisolone, we performed a substudy in 28 patients, aged 11.2 ± 3.8 years, for whom ambulatory blood pressure monitoring (ABPM) data were available. RESULTS: In the steroid-withdrawal group, the percentage of patients with arterial hypertension, defined as systolic and/or diastolic blood pressure values recorded by ABPM > 1.64 SDS and/or antihypertensive medication, at month 15 was significantly lower (35.7%, p = 0.002) than in controls (92.9%). The need of antihypertensive medication dropped significantly by 61.2% (p < 0.000 vs. control), while in controls, it even rose by 69.3%. One year after steroid withdrawal, no patient exhibited hypertensive blood pressure values above the 95th percentile, compared to 35.7% at baseline (p = 0.014) and to 14.3% of control (p = 0.142). The beneficial impact of steroid withdrawal was especially pronounced for nocturnal blood pressure, leading to a recovered circadian rhythm in 71.4% of patients vs. 14.3% at baseline (p = 0.002), while the percentage of controls with an abnormal circadian rhythm (35.7%) did not change. CONCLUSIONS: Steroid withdrawal in pediatric renal transplant recipients with well-preserved allograft function is associated with less arterial hypertension recorded by ABPM and recovery of circadian blood pressure rhythm by restoration of nocturnal blood pressure dipping.

Hypertension in childhood obesity.

AIM: The prevalence of childhood hypertension is rising in parallel with global increases in the prevalence of overweight and obesity. We looked at key papers and documents covering three decades. METHODS: This mini review examined a wide range of material published in English, with the main focus on 1993-2018, including clinical trials, meta-analyses, guidelines and data produced by the World Health Organization and the World Obesity Federation. RESULTS: The literature showed that body weight and blood pressure are closely correlated and obesity-related hypertension contributes further to the clustering of cardiovascular risk factors in obesity. Because the duration of hypertension affects the risk of end-organ damage, timely diagnosis and initiation of treatment are important. First-line interventions should aim for blood pressure control and weight reduction. However, lifestyle modifications are often not successful with regard to attaining and maintaining long-term blood pressure and weight control, despite a multidisciplinary approach. Antihypertensive treatment is recommended for all hypertensive children with failure of nonpharmacological treatment, diabetes, secondary hypertension, stage 2 hypertension or target organ damage. CONCLUSION: We found that obesity-related hypertension was associated with a significantly increased cardiovascular morbidity and mortality, and early diagnosis and treatment for blood pressure control and weight reduction is essential.

Early Proteinuria Lowering by Angiotensin-Converting Enzyme Inhibition Predicts Renal Survival in Children with CKD.

Background Although pharmacotherapeutic proteinuria lowering was found to be nephroprotective in adults, the predictive value of early drug-induced proteinuria reduction for long-term renal survival in pediatric CKD is unknown. We analyzed data from the ESCAPE Trial for a potential association between initial antiproteinuric effect of standardized angiotensin-converting enzyme (ACE) inhibition and renal disease progression in children with CKD.Methods In total, 280 eligible children with CKD stages 2-4 (mean age 11.7 years old, median eGFR 46 ml/min per 1.73 m2, 71% congenital renal malformations) received a fixed dose of ramipril (6 mg/m2 per day) and were subsequently randomized to conventional or intensified BP control. We assessed initial proteinuria reduction from baseline to first measurement on ramipril (at 2.5±1.3 months). We used multivariable Cox modeling to estimate the association between initial proteinuria reduction and the risk of reaching a renal end point (50% eGFR decline or ESRD), which occurred in 80 patients during 5 years of observation.Results Ramipril therapy lowered proteinuria by a mean of 43.5% (95% confidence interval, 36.3% to 49.9%). Relative to proteinuria reduction <30%, 30%-60% and >60% reduction resulted in hazard ratios (95% confidence intervals) of 0.70 (0.40 to 1.22) and 0.42 (0.22 to 0.79), respectively. This association was independent of age, sex, CKD diagnosis, baseline eGFR, baseline proteinuria, initial BP, and concomitant BP reduction.Conclusions The early antiproteinuric effect of ACE inhibition is associated with long-term preservation of renal function in children with CKD. Proteinuria lowering should be considered an important target in the management of pediatric CKD.

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease.

OBJECTIVE: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis. STUDY DESIGN: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life. RESULTS: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys. CONCLUSIONS: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD.

Estimating Time to ESRD in Children With CKD.

RATIONALE & OBJECTIVE: The KDIGO (Kidney Disease: Improving Global Outcomes) guideline for chronic kidney disease (CKD) presented an international classification system that ranks patients' risk for CKD progression. Few data for children informed guideline development. STUDY DESIGN: Observational cohort study. SETTINGS & PARTICIPANTS: Children aged 1 to 18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. PREDICTOR: Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio [UPCR]) at study entry. OUTCOME: A composite event of renal replacement therapy, 50% reduction in eGFR, or eGFR<15mL/min/1.73m2. eGFR was estimated using the CKiD-derived "bedside" equation. ANALYTICAL APPROACH: Accelerated failure time models of the composite outcome using a conventional generalized gamma distribution. Likelihood ratio statistics of nested models were used to amalgamate levels of similar risk. RESULTS: Among 1,232 children, median age was 12 (IQR, 8-15) years, median eGFR was 47 (IQR, 33-62) mL/min/1.73m2, 60% were males, and 13% had UPCRs>2.0mg/mg at study entry. 6 ordered stages with varying combinations of eGFR categories (60-89, 45-59, 30-44, and 15-29mL/min/1.73m2) and UPCR categories (<0.5, 0.5-2.0, and >2.0mg/mg) described the risk continuum. Median times to event ranged from longer than 10 years for eGFRs of 45 to 90mL/min/1.73m2 and UPCRs<0.5mg/mg to 0.8 years for eGFRs of 15 to 30mL/min/1.73m2 and UPCRs>2mg/mg. Children with glomerular disease were estimated to have a 43% shorter time to event than children with nonglomerular disease. Cross-validation demonstrated risk patterns that were consistent across the 10 subsample validation models. LIMITATIONS: Observational study, used cross-validation rather than external validation. CONCLUSIONS: CKD staged by level of eGFR and proteinuria characterizes the timeline of progression and can guide management strategies in children.

Effects of growth hormone treatment on adult height in severely short children with X-linked hypophosphatemic rickets.

BACKGROUND: We recently showed that a 3-year growth hormone (GH) treatment improves linear growth in severely short children with X-linked hypophosphatemic rickets (XLH). It is unknown if GH therapy increases adult height in XLH patients. METHODS: We carried out a follow-up analysis of a randomized controlled open-label GH study in short prepubertal children with XLH on phosphate and active vitamin D treatment. The changes in SD scores (SDS) of height, sitting height, leg and arm length, and sitting height index (i.e., the ratio between sitting height and height) were analyzed in 11 out of 16 patients followed-up until adult height. RESULTS: At baseline, XLH patients showed disproportionately short stature with reduced standardized height (-3.2 ± 0.6), sitting height (-1.7 ± 0.6), leg (-3.7 ± 0.7) and arm (-2.5 ± 0.8) length, and markedly elevated sitting height index (3.3 ± 0.6; each p < 0.01 versus healthy children). In GH-treated patients, adult height, sitting height, leg length, and arm length exceeded baseline values by 0.7 SDS, 1.7 SDS, 0.7 SDS, and 1.2 SDS respectively, although this was only significant for sitting height. In controls, no significant changes in linear body dimensions were noted. Adult height did not statistically differ between groups (-2.4 ± 0.7 vs -3.3 ± 1.2, p = 0.082). GH did not exaggerate body disproportion. CONCLUSIONS: Growth hormone treatment did not significantly increase adult height in this group of short children with XLH, which may be at least partly due to the small number of patients included in our study.

Validating the use of bioimpedance spectroscopy for assessment of fluid status in children.

BACKGROUND: Bioimpedance spectroscopy (BIS) with a whole-body model to distinguish excess fluid from major body tissue hydration can provide objective assessment of fluid status. BIS is integrated into the Body Composition Monitor (BCM) and is validated in adults, but not children. This study aimed to (1) assess agreement between BCM-measured total body water (TBW) and a gold standard technique in healthy children, (2) compare TBW_BCM with TBW from Urea Kinetic Modelling (UKM) in haemodialysis children and (3) investigate systematic deviation from zero in measured excess fluid in healthy children across paediatric age range. METHODS: TBW_BCM and excess fluid was determined from standard wrist-to-ankle BCM measurement. TBW_D2O was determined from deuterium concentration decline in serial urine samples over 5 days in healthy children. UKM was used to measure body water in children receiving haemodialysis. Agreement between methods was analysed using paired t test and Bland-Altman method comparison. RESULTS: In 61 healthy children (6-14 years, 32 male), mean TBW_BCM and TBW_D2O were 21.1 ± 5.6 and 20.5 ± 5.8 L respectively. There was good agreement between TBW_BCM and TBW_D2O (R2 = 0.97). In six haemodialysis children (4-13 years, 4 male), 45 concomitant measurements over 8 months showed good TBW_BCM and TBW_UKM agreement (mean difference - 0.4 L, 2SD = ± 3.0 L). In 634 healthy children (2-17 years, 300 male), BCM-measured overhydration was - 0.1 ± 0.7 L (10-90th percentile - 0.8 to + 0.6 L). There was no correlation between age and OH (p = 0.28). CONCLUSIONS: These results suggest BCM can be used in children as young as 2 years to measure normally hydrated weight and assess fluid status.

Presentation of pediatric Henoch-Schönlein purpura nephritis changes with age and renal histology depends on biopsy timing.

BACKGROUND: This study correlates the clinical presentation of Henoch-Schönlein purpura nephritis (HSPN) with findings on initial renal biopsy. METHODS: Data from 202 pediatric patients enrolled in the HSPN registry of the German Society of Pediatric Nephrology reported by 26 centers between 2008 and 2014 were analyzed. All biopsy reports were re-evaluated for the presence of cellular crescents or chronic pathological lesions (fibrous crescents, glomerular sclerosis, tubular atrophy >5%, and interstitial fibrosis >5%). RESULTS: Patients with HSPN with cellular glomerular crescents were biopsied earlier after onset of nephritis (median 24 vs 36 days, p = 0.04) than those without, whereas patients with chronic lesions were biopsied later (57 vs 19 days, p < 0.001) and were older (10.3 vs 8.6 years, p = 0.01) than those without. Patients biopsied more than 30 days after the onset of HSPN had significantly more chronic lesions (52 vs 22%, p < 0.001), lower eGFR (88 vs 102 ml/min/1.73m2, p = 0.01), but lower proteinuria (2.3 vs 4.5 g/g, p < 0.0001) than patients biopsied earlier. Children above 10 years of age had lower proteinuria (1.98 vs 4.58 g/g, p < 0.001), lower eGFR (86 vs 101 ml/min/1.73m2, p = 0.002) and were biopsied significantly later after onset of nephritis (44 vs 22 days, p < 0.001) showing more chronic lesions (45 vs 30%, p = 0.03). Proteinuria and renal function at presentation decreased with age. CONCLUSIONS: In summary, we find an age-dependent presentation of HSPN with a more insidious onset of non-nephrotic proteinuria, impaired renal function, longer delay to biopsy, and more chronic histopathological lesions in children above the age of 10 years. Thus, HSPN presents more like Immunoglobulin A (IgA) nephritis in older than in younger children.