Parents' Perceptions of the Effectiveness of Music Therapy on Their Chronically Ill Children.

Chronic disease in a child, with the associated hospital stays, places considerable demands on the child and their family. The aim of this study was to investigate the parents' perceptions of the music therapy used with their child during a hospital stay and to determine whether they felt that it reduced the child's anxiety and stress generated by hospital admission. We hypothesized that the use of live music therapy from a music therapist would positively support these patients in everyday clinical practice, promote their wellbeing, and have positive impacts on their vital signs and blood pressure. Children with chronic gastroenterological and nephrological diseases included in this prospective study received live music therapy with a median duration of 41 min (range from 12 to 70 min) two to four times per week until discharged from the hospital. At the time of discharge, the parents were asked to complete a Likert-style questionnaire to evaluate the music therapy. Seven items were related to general questions about the patients and sessions, and eleven items evaluated the personal perceptions of the parents. Music therapy was conducted in 83 children, with a median age of 3 years (range from 1 month to 18 years). All parents (100%) completed the questionnaire at the time of discharge. Seventy-nine percent of the parents stated that their children were able to enjoy the music therapy sessions without being stressed. In addition, 98% of the respondents said that they were grateful for the music therapy their children received (97% fully agreed and 1% rather agreed). All parents considered music therapy to be beneficial for their child. The parents' responses reflected the view that music therapy is beneficial to patients. According to the parents, music therapy can be integrated effectively in the inpatient clinical setting and can support children with chronic illnesses during their hospital stay.

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.

Effects of Music Therapy on Vital Signs in Children with Chronic Disease.

BACKGROUND: Recent research found evidence supporting music therapy for hospitalized children with chronic diseases. The aim of this study was to investigate the effect of music therapy on hospitalized children's vital signs. METHODS: In this prospective study, children with chronic gastroenterological and nephrological diseases received active or receptive music therapy two to four times a week until discharge from hospital at the pediatric special care unit (SCU) and pediatric intensive care unit (ICU). Baseline and post-therapy heart rate, oxygen saturation and blood pressure were recorded and analyzed as control values at three points on the same day when the children were alone in their patient room at rest. RESULTS: A total of 83 children, median 3 age of years (range one month to eighteen years) received music therapy. In total, 377 music therapy sessions were treated: 200 receptive therapy (78 ICU, 122 SCU) and 177 with active therapy (0 ICU, 177 SCU). Music therapy interventions showed changes in vital signs during music therapy sessions. After music therapy, heart rates decreased by 18 beats per minute (95% confidence interval (CI), -19.4 to (-16.8)), oxygen saturation increased by 2.3% (95% CI, 2.2 to 2.5), systolic blood pressure decreased by 9.2 (95% CI, -10.6 to -7.7) and diastolic blood pressure decreased by 7.9 (95% CI, -9.6 to -6.3). When music therapy was applied at the SCU (ICU), heart rates significantly reduced by 17.9 (18.9) beats per min, oxygen saturation increased by 2.4% (2.1%) and blood pressure reduced by 9.2 (2.8) mmHg (systolic) and 7.9 (0.3) mmHg (diastolic). Almost all control values were better than directly before the intervention. However, after music therapy intervention, the children showed better values in vital signs compared to being alone in their patient room. CONCLUSION: Music therapy is an added value for children with kidney and liver/gastrointestinal diseases during their hospital stay.

The European Rare Kidney Disease Registry (ERKReg): objectives, design and initial results.

BACKGROUND: The European Rare Kidney Disease Reference Network (ERKNet) recently established ERKReg, a Web-based registry for all patients with rare kidney diseases. The main objectives of this core registry are to generate epidemiological information, identify current patient cohort for clinical research, explore diagnostic and therapeutic management practices, and monitor treatment performance and patient's outcomes. The registry has a modular design that allows to integrate comprehensive disease-specific registries as extensions to the core database. The diagnosis (Orphacode) and diagnostic information (clinical, imaging, histopathological, biochemical, immunological and genetic) are recorded. Anthropometric, kidney function, and disease-specific management and outcome items informing a set of 61 key performance indicators (KPIs) are obtained annually. Data quality is ensured by automated plausibility checks upon data entry and regular offline database checks prompting queries. Centre KPI statistics and benchmarking are calculated automatically. RESULTS: Within the first 24 months since its launch, 7607 patients were enrolled to the registry at 45 pediatric and 12 specialized adult nephrology units from 21 countries. A kidney disease diagnosis had been established in 97.1% of these patients at time of enrolment. While 199 individual disease entities were reported by Orphacode, 50% of the cohort could be classified with 11, 80% with 43 and 95% with 92 codes. Two kidney diagnoses were assigned in 6.5% of patients; 5.9% suffered from syndromic disease. Whereas glomerulopathies (54.8%) and ciliopathies including autosomal dominant polycystic kidney disease (ADPKD) (31.5%) were the predominant disease groups among adults, the pediatric disease spectrum encompassed congenital anomalies of the kidney and urinary tract (CAKUT) (33.7%), glomerulopathies (30.7%), ciliopathies (14.0%), tubulopathies (9.2%), thrombotic microangiopathies (5.6%), and metabolic nephropathies (4.1%). Genetically confirmed diagnoses were reported in 24% of all pediatric and 12% adult patients, whereas glomerulopathies had been confirmed by kidney biopsy in 80.4% adult versus 38.5% pediatric glomerulopathy cases. CONCLUSIONS: ERKReg is a rapidly growing source of epidemiological information and patient cohorts for clinical research, and an innovative tool to monitor management quality and patient outcomes.

Expanding the Spectrum of FAT1 Nephropathies by Novel Mutations That Affect Hippo Signaling.

INTRODUCTION: Disease-causing mutations in the protocadherin FAT1 have been recently described both in patients with a glomerulotubular nephropathy and in patients with a syndromic nephropathy. METHODS: We identified 4 patients with FAT1-associated disease, performed clinical and genetic characterization, and compared our findings to the previously published patients. Patient-derived primary urinary epithelial cells were analyzed by quantitative polymerase chain reaction (qPCR) and immunoblotting to identify possible alterations in Hippo signaling. RESULTS: Here we expand the spectrum of FAT1-associated disease with the identification of novel FAT1 mutations in 4 patients from 3 families (homozygous truncating variants in 3, compound heterozygous missense variants in 1 patient). All patients show an ophthalmologic phenotype together with heterogeneous renal phenotypes ranging from normal renal function to early-onset end-stage kidney failure. Molecular analysis of primary urine-derived urinary renal epithelial cells revealed alterations in the Hippo signaling cascade with a decreased phosphorylation of both the core kinase MST and the downstream effector YAP. Consistently, we found a transcriptional upregulation of bona fide YAP target genes. CONCLUSION: A comprehensive review of the here identified patients and those previously published indicates a highly diverse phenotype in patients with missense mutations but a more uniform and better recognizable phenotype in the patients with truncating mutations. Altered Hippo signaling and de-repressed YAP activity might be novel contributing factors to the pathomechanism in FAT1-associated renal disease.

Course of renal allograft function after diagnosis and treatment of post-transplant lymphoproliferative disorders in pediatric kidney transplant recipients.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication in renal transplant recipients. Immunomodulatory and chemotherapeutic treatment potentially affect allograft function. The aim of this study was to evaluate graft function of pediatric kidney transplant recipients following diagnosis and standardized treatment of PTLD. METHODS: Patients were identified from the German Ped-PTLD registry, and data on renal function were retrospectively retrieved from patient charts. For PTLD treatment, immunosuppressive therapy was reduced and all children received rituximab (375 mg/m2 ) for up to six doses. Two patients required additional low-dose chemotherapy. Renal allograft function was monitored by consecutive measurements of estimated glomerular filtration rate (eGFR) at defined time points. Follow-up was up to 60 months after PTLD. RESULTS: Twenty patients were included in this cohort analysis. Median time from transplantation to PTLD was 2.4 years. Histopathology showed monomorphic lesions in 16 and polymorphic in 4 patients. Two patients experienced PTLD relapse after 2 and 14 months. Range-based analysis of variance showed stable allograft function in 17 of 20 patients (85%). Mean eGFR increased during early treatment phase. One patient experienced graft rejection 5.3 years after diagnosis of PTLD. Another patient developed recurrence of primary renal disease (focal-segmental glomerulosclerosis) and lost his renal allograft 3.8 years post-transplant (2.0 years after PTLD diagnosis). CONCLUSION: Treatment of PTLD with rituximab with or without low-dose chemotherapy in combination with reduced immunosuppression, mostly comprising of an mTOR inhibitor-based, calcineurin inhibitor-free regimen, is associated with stable graft function and favorable graft survival in pediatric renal transplant patients.

Severe neurological outcomes after very early bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD).

To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (≤ 3 months; VEBNE) and early (4-15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset ≤ 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort.

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).

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.

Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies.

Identification of mutations in the HOGA1 gene as the cause of autosomal recessive primary hyperoxaluria (PH) type III has revitalized research in the field of PH and related stone disease. In contrast to the well-characterized entities of PH type I and type II, the pathophysiology and prevalence of type III is largely unknown. In this study, we analyzed a large cohort of subjects previously tested negative for type I/II by complete HOGA1 sequencing. Seven distinct mutations, among them four novel, were found in 15 patients. In patients of non-consanguineous European descent the previously reported c.700+5G>T splice-site mutation was predominant and represents a potential founder mutation, while in consanguineous families private homozygous mutations were identified throughout the gene. Furthermore, we identified a family where a homozygous mutation in HOGA1 (p.P190L) segregated in two siblings with an additional AGXT mutation (p.D201E). The two girls exhibiting triallelic inheritance presented a more severe phenotype than their only mildly affected p.P190L homozygous father. In silico analysis of five mutations reveals that HOGA1 deficiency is causing type III, yet reduced HOGA1 expression or aberrant subcellular protein targeting is unlikely to be the responsible pathomechanism. Our results strongly suggest HOGA1 as a major cause of PH, indicate a greater genetic heterogeneity of hyperoxaluria, and point to a favorable outcome of type III in the context of PH despite incomplete or absent biochemical remission. Multiallelic inheritance could have implications for genetic testing strategies and might represent an unrecognized mechanism for phenotype variability in PH.