Epidemiology of paediatric renal stone disease: a 22-year single centre experience in the UK

BACKGROUND: Whilst still rare, the incidence of paediatric stone disease is increasing in developed countries and it is important to evaluate the aetiology. We set up a dedicated renal stone service for children combining medical and surgical expertise in 1993 and now have a large case series of children to investigate the epidemiology. METHODS: A retrospective hospital note review of children presenting with kidney stones during the last 22 years (1993-2015) was conducted. All patients had a comprehensive infective and metabolic screen and were classified as metabolic, infective or idiopathic stone disease. RESULTS: Five hundred eleven patients (322 male) were reviewed. The median age of presentation was 4.4y for males (1 m-16.6y) and 7.3y (1-18.5y) for females with a median height and weight on the 25th centile for male and on 10th and 25th for female, respectively. One hundred seventy five (34%) had an underlying metabolic abnormality, 112 (22%) had infective stones and 224 (44%) were classified as idiopathic. Of the 175 patients with a metabolic abnormality: 91 (52%) had hypercalciuria (76 persistent and 15 transient), 37 (21%) hyperoxaluria, 38 (22%) cystinuria, 3 (2%) abnormalities in the purine metabolism and the remainder other metabolic abnormalities. Bilateral stones occurred in 27% of the metabolic group compared to 16% in the non-metabolic group (OR 0.2, p < 0.05). Urinary tract infection was a common complication (27%) in the metabolic group. CONCLUSIONS: In this paper, we present the largest cohort of paediatric stone disease reported from a developed country giving details on both, clinical and laboratory data. We show that in the majority of the patients there is an identifiable underlying metabolic and/or infective aetiology emphasizing the importance of a full work up to provide adequate treatment and prevent recurrence. Moreover, we show that stone disease in children, in contrast to the adult population, does not seem to be associated with obesity, as children have a weight below average at presentation

Fainting Fanconi syndrome clarified by proxy: a case report

BACKGROUND: Rare diseases may elude diagnosis due to unfamiliarity of the treating physicians with the specific disorder. Yet, advances in genetics have tremendously enhanced our ability to establish specific and sometimes surprising diagnoses. CASE PRESENTATION: We report a case of renal Fanconi syndrome associated with intermittent hypoglycemic episodes, the specific cause for which remained elusive for over 30 years, despite numerous investigations, including three kidney and one liver biopsy. The most recent kidney biopsy showed dysmorphic mitochondria, suggesting a mitochondrial disorder. When her son presented with hypoglycemia in the neonatal period, he underwent routine genetic testing for hyperinsulinemic hypoglycemia, which revealed a specific mutation in HNF4A. Subsequent testing of the mother confirmed the diagnosis also in her. CONCLUSION: Modern sequencing technologies that test multiple genes simultaneously enable specific diagnoses, even if the underlying disorder was not clinically suspected. The finding of mitochondrial dysmorphology provides a potential clue for the mechanism, by which the identified mutation causes renal Fanconi syndrome

Clinical and diagnostic features of Bartter and Gitelman syndromes

Background: Bartter and Gitelman syndromes are autosomal recessive disorders of renal tubular salt handling. Due to their rarity, limited long-term data are available to inform prognosis and management. / Methods: Long-term longitudinal data were analysed for 45 children with pathogenic variants in SLC12A1 (n = 8), KCNJ1 (n = 8), CLCNKB (n = 17), BSND (n = 2) and SLC12A3 (n = 10) seen at a single centre between 1984 and 2014. Median follow-up was 8.9 [interquartile range (IQR) 0.7–18.1] years. / Results: Polyhydramnios and prematurity were seen in children with SLC12A1 and KCNJ1 mutations. Patients with CLCNKB mutations had the lowest serum potassium and serum magnesium and the highest serum bicarbonate levels. Fractional excretion of chloride was >0.5% in all patients prior to supplementation. Nephrocalcinosis at presentation was present in the majority of patients with SLC12A1 and KCNJ1 mutations, while it was only present in one patient with CLCNKB and not in SLC12A3 or BSND mutations. Growth was impaired, but within the normal range (median height standard deviation score −1.2 at the last follow-up). Impaired estimated glomerular filtration rate (eGFR <90 mL/min/1.73 m2) at the last follow-up was seen predominantly with SLC12A1 [71 mL/min/1.73 m2 (IQR 46–74)] and KCNJ1 [62 mL/min/1.73 m2 (IQR 48–72)] mutations. Pathological albuminuria was detected in 31/45 children. / Conclusions: Patients with Bartter and Gitelman syndromes had a satisfactory prognosis during childhood. However, decreased eGFR and pathologic proteinuria was evident in a large number of these patients, highlighting the need to monitor glomerular as well as tubular function. Electrolyte abnormalities were most severe in CLCNKB mutations both at presentation and during follow-up. Fractional excretion of chloride prior to supplementation is a useful screening investigation in children with hypokalaemic alkalosis to establish renal salt wasting

Hypervitaminosis A is prevalent in children with CKD and contributes to hypercalcemia.

Vitamin A accumulates in renal failure, but the prevalence of hypervitaminosis A in children with predialysis chronic kidney disease (CKD) is not known. Hypervitaminosis A has been associated with hypercalcemia. In this study we compared dietary vitamin A intake with serum retinoid levels and their associations with hypercalcemia

Renal apnoea: extreme disturbance of homoeostasis in a child with Bartter syndrome type IV

A 2-week-old girl was transferred to our renal ward in February, 2014, from the neonatal intensive care unit of her local hospital with polyuria (200 mL/kg per day) and extreme acid–base and electrolyte disturbance that had been present from birth. She was born by spontaneous delivery at 32 weeks' gestation, after a pregnancy complicated by severe polyhydramnios necessitating two amnioreductions that had removed more than 6 L of fluid. She is the third child of consanguineous parents, with no relevant family history

Acidosis and Deafness in Patients with Recessive Mutations in FOXI1

Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of the kidney require an overlapping set of membrane transport proteins regulated by the forkhead transcription factor FOXI1. In two unrelated consanguineous families, we identified three patients with novel homozygous missense mutations in FOXI1 (p.L146F and p.R213P) predicted to affect the highly conserved DNA binding domain. Patients presented with early-onset sensorineural deafness and distal renal tubular acidosis. In cultured cells, the mutations reduced the DNA binding affinity of FOXI1, which hence, failed to adequately activate genes crucial for normal inner ear function and acidbase regulation in the kidney. A substantial proportion of patients with a clinical diagnosis of inherited distal renal tubular acidosis has no identified causative mutations in currently known disease genes. Our data suggest that recessive mutations in FOXI1 can explain the disease in a subset of these patients

Microbial soil respiration and its dependency on carbon inputs, soil temperature and moisture

This experiment was designed to study three determinant factors in decomposition patterns of soil organic matter (SOM): temperature, water and carbon (C) inputs. The study combined field measurements with soil lab incubations and ends with a modelling framework based on the results obtained. Soil respiration was periodically measured at an oak savanna woodland and a ponderosa pine plantation. Intact soils cores were collected at both ecosystems, including soils with most labile C burnt off, soils with some labile C gone and soils with fresh inputs of labile C. Two treatments, dry-field condition and field capacity, were applied to an incubation that lasted 111 days. Short-term temperature changes were applied to the soils periodically to quantify temperature responses. This was done to prevent confounding results associated with different pools of C that would result by exposing treatments chronically to different temperature regimes. This paper discusses the role of the above-defined environmental factors on the variability of soil C dynamics. At the seasonal scale, temperature and water were, respectively, the main limiting factors controlling soil CO2 efflux for the ponderosa pine and the oak savanna ecosystems. Spatial and seasonal variations in plant activity (root respiration and exudates production) exerted a strong influence over the seasonal and spatial variation of soil metabolic activity. Mean residence times of bulk SOM were significantly lower at the Nitrogen (N)-rich deciduous savanna than at the N-limited evergreen dominated pine ecosystem. At shorter time scales (daily), SOM decomposition was controlled primarily by temperature during wet periods and by the combined effect of water and temperature during dry periods. Secondary control was provided by the presence/absence of plant derived C inputs (exudation). Further analyses of SOM decomposition suggest that factors such as changes in the decomposer community, stress-induced changes in the metabolic activity of decomposers or SOM stabilization patterns remain unresolved, but should also be considered in future SOM decomposition studies. Observations and confounding factors associated with SOM decomposition patterns and its temperature sensitivity are summarized in the modeling framework

Disks and Outflows in the Intermediate-mass Star Forming Region NGC 2071 IR

We present ALMA band 6/7 (1.3 mm/0.87 mm) and VLA Ka band (9 mm) observations toward NGC 2071 IR, an intermediate-mass star forming region. We characterize the continuum and associated molecular line emission towards the most luminous protostars, i.e., IRS1 and IRS3, on ~100 au (0. 2") scales. IRS1 is partly resolved in millimeter and centimeter continuum, which shows a potential disk. IRS3 has a well resolved disk appearance in millimeter continuum and is further resolved into a close binary system separated by ~40 au at 9 mm. Both sources exhibit clear velocity gradients across their disk major axes in multiple spectral lines including C18O, H2CO, SO, SO2, and complex organic molecules like CH3OH, 13CH3OH and CH3OCHO. We use an analytic method to fit the Keplerian rotation of the disks, and give constraints on physical parameters with a MCMC routine. The IRS3 binary system is estimated to have a total mass of 1.4-1.5$M_\odot$. IRS1 has a central mass of 3-5$M_\odot$ based on both kinematic modeling and its spectral energy distribution, assuming that it is dominated by a single protostar. For both IRS1 and IRS3, the inferred ejection directions from different tracers, including radio jet, water maser, molecular outflow, and H2 emission, are not always consistent, and for IRS1, these can be misaligned by ~50$^{\circ}$. IRS3 is better explained by a single precessing jet. A similar mechanism may be present in IRS1 as well but an unresolved multiple system in IRS1 is also possible.Comment: 36 pages, 21 figures, accepted by Ap

Early Planet Formation in Embedded Disks (eDisk) X: Compact Disks, Extended Infall, and a Fossil Outburst in the Class I Oph IRS43 Binary

We present the first results from the Early Planet Formation in Embedded Disks (eDisk) ALMA Large Program toward Oph IRS43, a binary system of solar mass protostars. The 1.3 mm dust continuum observations resolve a compact disk, ~6au radius, around the northern component and show that the disk around the southern component is even smaller, <~3 au. CO, 13CO, and C18O maps reveal a large cavity in a low mass envelope that shows kinematic signatures of rotation and infall extending out to ~ 2000au. An expanding CO bubble centered on the extrapolated location of the source ~130 years ago suggests a recent outburst. Despite the small size of the disks, the overall picture is of a remarkably large and dynamically active region.Comment: Paper 10 of the ALMA eDisk Large Program. Accepted for publication in Ap