Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study

Bartter syndrome; Parathyroid hormone; PhosphateSíndrome de Bartter; Hormona paratiroidea; FosfatoSíndrome de Bartter; Hormona paratiroïdal; FosfatBackground Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. Methods Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). Results A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs −0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate—standard deviation score < −2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. Conclusions Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.This project has been supported by the European Reference Network for Rare Kidney Diseases (ERKNet), which is partly co-funded by the European Union within the framework of the Third Health Programme ‘ERN-2016-Framework Partnership Agreement 2017–2021’. This work is generated within the European Society for Paediatric Nephrology working group on inherited renal disorders. This work was supported by an Innovation Grant 19OI06 from the Dutch Kidney Foundation (to T.N.)

Upper urinary tract deterioration and possible etiologies in intractable voiding dysfunction: Role of occult spinal malformation

Objectives: To evaluate the presence of upper urinary tract deterioration (UUTD) and accompanying pathologies in children treated with the diagnosis of non-neurogenic bladder-sphincter dysfunction (NNBSD). Patients and Methods: We retrospectively reviewed the medical records of 316 consecutive patients with NNBSD who were treated. All cohort were grouped into two: Group I (Treatment success; n=284), Group II (Treatment failure with any form of occult spinal pathology; n=32). Thirty-four children with treatment-failure and normal magnetic resonance imaging (MRI) findings were excluded. Groups were compared for pre- and posttreatment pediatric lower urinary tract symptom score (PLUTSS), presence of UUTD and urodynamic findings. Results: The mean PLUTSS was significantly less in Group I compared with Group II at pre-treatment and 3 months thereafter the initial treatment (12.20 ± 5.90 and 5.20 ± 4.90 vs 20.3 ± 2.14 and 18 ± 3.4, respectively p<0.01). The mean cystometric capacities and detrusor leak point pressure (DLPP) of Group II prior to initial treatment and after 6 months of the untethering surgery were found to be 194, 267 mL and 28, 12cm H2O, respectively (p<0.05). Presence of UUTD was significantly correlated with DLPP >20 cm H2O and presence of vesicoureteral reflux (VUR)

COVID-19 in pediatric nephrology centers in Turkey

Background/aim: There is limited data on COVID-19 disease in children with kidney disease. We aimed to investigate the characteristics and prognosis of COVID-19 in pediatric nephrology patients in Turkey. Materials and methods: This was a national, multicenter, retrospective cohort study based on an online survey evaluating the data between 11th March 2020 and 11th March 2021 as an initial step of a detailed pediatric nephrology COVID-19 registry. Results: Two hundred and three patients (89 girls and 114 boys) were diagnosed with COVID-19. One-third of these patients (36.9%) were between 10–15 years old. Half of the patients were on kidney replacement therapy: kidney transplant (KTx) recipients (n = 56, 27.5%), patients receiving chronic hemodialysis (n = 33, 16.3%) and those on peritoneal dialysis (PD) (n = 18, 8.9%). Fifty-four (26.6%) children were asymptomatic. Eighty-two (40.3%) patients were hospitalized and 23 (28%) needed intensive care unit admission. Fifty-five percent of the patients were not treated, while the remaining was given favipiravir (20.7%), steroid (16.3%), and hydroxychloroquine (11.3%). Acute kidney injury developed in 19.5% of hospitalized patients. Five (2.4%) had MIS-C. Eighty-three percent of the patients were discharged without any apparent sequelae, while 7 (3.4%) died. One hundred and eight health care staff were infected during the study period. Conclusion: COVID-19 was most commonly seen in patients who underwent KTx and received HD. The combined immunosuppressive therapy and frequent exposure to the hospital setting may increase these patients’ susceptibility. Staff infections before vaccination era were alarming, various precautions should be taken for infection control, particularly optimal vaccination coverage

Schimke immunoosseous dysplasia: defining skeletal features

Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by prominent spondyloepiphyseal dysplasia, T cell deficiency, and focal segmental glomerulosclerosis. Biallelic mutations in swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD, but approximately half of patients referred for molecular studies do not have detectable mutations in SMARCAL1. We hypothesized that skeletal features distinguish between those with or without SMARCAL1 mutations. Therefore, we analyzed the skeletal radiographs of 22 patients with and 11 without detectable SMARCAL1 mutations. We found that patients with SMARCAL1 mutations have a spondyloepiphyseal dysplasia (SED) essentially limited to the spine, pelvis, capital femoral epiphyses, and possibly the sella turcica, whereas the hands and other long bones are basically normal. Additionally, we found that several of the adolescent and young adult patients developed osteoporosis and coxarthrosis. Of the 11 patients without detectable SMARCAL1 mutations, seven had a SED indistinguishable from patients with SMARCAL1 mutations. We conclude therefore that SED is a feature of patients with SMARCAL1 mutations and that skeletal features do not distinguish who of those with SED have SMARCAL1 mutations

Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease

Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m(2) and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression

Vascular access in children requiring maintenance haemodialysis: a consensus document by the European Society for Paediatric Nephrology Dialysis Working Group

Background. There are three principle forms of vascular access available for the treatment of children with end stage kidney disease (ESKD) by haemodialysis: tunnelled catheters placed in a central vein (central venous lines, CVLs), arteriovenous fistulas (AVF), and arteriovenous grafts (AVG) using prosthetic or biological material. Compared with the adult literature, there are few studies in children to provide evidence based guidelines for optimal vascular access type or its management and outcomes in children with ESKD. Methods. The European Society for Paediatric Nephrology Dialysis Working Group (ESPN Dialysis WG) have developed recommendations for the choice of access type, pre-operative evaluation, monitoring, and prevention and management of complications of different access types in children with ESKD. Results. For adults with ESKD on haemodialysis, the principle of Fistula First has been key to changing the attitude to vascular access for haemodialysis. However, data from multiple observational studies and the International Paediatric Haemodialysis Network registry suggest that CVLs are associated with a significantly higher rate of infections and access dysfunction, and need for access replacement. Despite this, AVFs are used in only similar to 25% of children on haemodialysis. It is important to provide the right access for the right patient at the right time in their life-course of renal replacement therapy, with an emphasis on venous preservation at all times. While AVFs may not be suitable in the very young or those with an anticipated short dialysis course before transplantation, many paediatric studies have shown that AVFs are superior to CVLs. Conclusions. Here we present clinical practice recommendations for AVFs and CVLs in children with ESKD. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system has been used to develop and GRADE the recommendations. In the absence of high quality evidence, the opinion of experts from the ESPN Dialysis WG is provided, but is clearly GRADE-ed as such and must be carefully considered by the treating physician, and adapted to local expertise and individual patient needs as appropriate

Microalbumin excretion and outcome in children with multicystic dysplastic kidney

Aim: To present the long-term follow-up results of children with multicystic dysplastic kidney (MCDK) and urinary microalbumin excretion levels in order to evaluate whether there is an increased risk of renal damage or not. Materials and methods: Thirty-three children with the diagnosis of MCDK who had been followed up by the nephrology outpatient clinic between 2002 and 2009 were invited to participate in the study. Twenty-six healthy children were investigated as a control group for microalbumin/creatinine ratio (mu g/g creatinine). The mean age at diagnosis, the duration of follow-up, accompanying urinary tract abnormalities, attacks of urinary tract infection (UTI), contralateral kidney size, and urinary microalbumin levels were investigated. Results: The mean age of the patients with MCDK and the mean duration of follow-up were 6.5 +/- 3.9 years and 35 months (range 2-96) months, respectively. The most common urinary tract abnormality was vesicoureteral reflux (VUR), with a rate of 34%. Thirty-nine percent of the children experienced UTI during follow-up. The compensatory renal hypertrophy of the contralateral kidney was 24% at 6 months and 68% at 12 months. Sixteen patients (59%) had an increased microalbumin/creatinine ratio (>30 mu g/mg creatinine). Microalbumin/creatinine ratio was higher in patients with MCDK than it was in the controls (P = 0.001). Conclusion: Microalbuminuria and VUR are not rare in children with MCDK. Systematic follow-up of these patients is recommended to identify those at risk of contralateral renal damage

Quality of life in children with chronic kidney disease (with child and parent assessments)

Herein the results of a multicenter study from the Turkish Pediatric Kidney Transplantation Study Group are reported. The aims of this study were to compare the quality of life (QoL) scores of Turkish children who are dialysis patients (DP), renal transplant recipients (TR), and age-matched healthy controls and to compare child-self and parent-proxy scores. The Turkish versions of the Kinder Lebensqualitat Fragebogen (KINDLA (R)) questionnaires were used as a QoL measure. The study group consisted of 211 children and adolescents with chronic kidney disease (CKD) (139 TR and 72 DP aged between 4-18 years; 13.7 A +/- 3.5 years) from 11 university hospitals, 129 parents of these patients, 232 age-matched healthy children and adolescents (aged between 4-18 years; 13.1 +/- 3.5 years) and 156 of their parents. Patients with CKD had lower scores in all subscales except for physical well-being than those in the control group. TR had higher scores in physical well-being, self-esteem, friends' subscales, and total scores than DP. Child-self scores were lower than parent-proxy scores, especially in CKD, DP, and control groups. Concordance between parent-proxy and child-self reports in the TR, DP, CKD, and control groups was only moderate for the majority of subscales (r = 0.41-0.61). It was concluded that parent-proxy scores on the QoL were not equivalent to child-self scores and that evaluating both children's and parents' perspectives were important. Additionally, psychosocial counseling is crucial not only for patients with CKD but also for their parents

Management of children with congenital nephrotic syndrome: challenging treatment paradigms

Background. Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective. Methods. We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS. Results. Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3-8) g/L (P< 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P< 0.001) were transplanted and 2 died. Conclusion. An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy