Jakub Zieg

Urinary transforming growth factor-β1 in children with obstructive uropathy.

Aim:  Obstructive uropathies (OU) in childhood constitute one of the major causes of chronic renal insufficiency. Transforming growth factor‐β1 (TGF‐β1) is considered to be the major fibrogenic growth factor. The aim of the present study was to investigate urinary TGF‐β1 levels in children with obstructive and non‐obstructive uropathies (NOU).

Evaluation and management of hyponatraemia in children.

Paediatric hyponatraemia is usually caused by an excess of antidiuretic hormone and may lead to serious neurological complications. It is challenging for clinicians to differentiate between conditions causing excess water and salt loss. This review analyses individual causes of hyponatraemia and focuses on optimal diagnostic algorithms and treatment strategies.

Rituximab resistant evans syndrome and autoimmunity in Schimke immuno-osseous dysplasia

Autoimmunity is often observed among individuals with primary immune deficiencies; however, the frequency and role of autoimmunity in Schimke immuno-osseous dysplasia (SIOD) has not been fully assessed. SIOD, which is caused by mutations of SMARCAL1, is a rare autosomal recessive disease with its prominent features being skeletal dysplasia, T cell deficiency, and renal failure. We present a child with severe SIOD who developed rituximab resistant Evans syndrome (ES). Consistent with observations in several other immunodeficiency disorders, a review of SIOD patients showed that approximately a fifth of SIOD patients have some features of autoimmune disease. To our best knowledge this case represents the first patient with SIOD and rituximab resistant ES and the first study of autoimmune disease in SIOD.

Fatal case of diarrhea-associated hemolytic uremic syndrome with severe neurologic involvement.

Jakub Zieg, Jiri Dusek, Monika Marejkova, Petra Limrova, Daniel Blazek, Petr Pavlicek, Marek Grega, Jan Janda and Kveta Blahova Departments of Pediatrics, Anesthesiology and Resuscitation, and Pathology and Molecular Medicine, Second Medical School, Charles University Prague, University Hospital Motol and National Institute of Public Health, National Reference Laboratory for Escherichia coli and Shigellas, Prague, Czech Republic

Current views on the diagnosis and management of hypokalaemia in children.

Hypokalaemia is a common electrolyte disorder in children, caused by decreased potassium intake, increased gastrointestinal and urinary losses or transcellular shift. Patients with severe hypokalaemia may suffer from symptoms such as life‐threatening cardiac arrhythmias. The aim of our study was to review the aetiology of hypokalaemia, suggest a diagnostic algorithm and discuss the management of patients with various aetiologies of hypokalaemia.

Pathophysiology of Hyponatremia in Children

Hyponatremia is a common electrolyte disorder in children. It is generally defined as plasma sodium of less than 135 mmol/l. Sodium homeostasis is essential for maintaining intravascular volume and is tightly linked to water balance. Plasma water volume is regulated mainly by the secretion of an antidiuretic hormone (ADH) and by the thirst mechanism. ADH is synthesized in the hypothalamus and stored in the posterior hypophysis. It binds to V2 receptors in the distal nephron and induces translocation of aquaporin water channels in the plasma membrane to retain water. There are two main types of receptors involved in the control of the body water balance—osmoreceptors and baroreceptors. Osmoreceptors reside in hypothalamus and respond to changes of extracellular fluid (ECF) osmolality. Baroreceptors are mechanoreceptors that sense blood pressure in the vessel wall. Response reflexes from baroreceptors influence sympathetic outflow, vessel tonus, and cardiac output. An increase of 1% of plasma osmolality may cause an increase in ADH levels, while the threshold of volume receptors for ADH secretion is higher. However, significant hypotension is a more potent stimulus for ADH secretion than increased osmolality. The main cause of pediatric hyponatremia is an abundance of free water. This may occur in hypovolemic children with low ECF volume, normovolemic patients with inappropriately increased ADH secretion, and also in hypervolemic individuals with decreased effective circulating volume and appropriately increased ADH levels. Proper understanding of the pathophysiology of hyponatremic states is essential for establishing the correct diagnosis and appropriate therapy.

Nephrotic syndrome and acute kidney injury in a patient treated with lithium carbonate

Lithium carbonate has been used in psychiatry for decades for the treatment of depression and bipolar disorder. However, this medicine has several renal side effects such as nephrogenic diabetes insipidus, chronic tubulointerstitial nephritis, distal renal tubular acidosis and, rarely, nephrotic syndrome (NS).1 In addition, lithium intoxication can also lead to acute kidney injury (AKI).2 The pathogenesis of lithiuminduced NS is not fully understood, and underlying genetic predisposition or idiosyncratic causes are involved.3 The majority of patients recover after discontinuation of lithium treatment. Kidney biopsy usually shows minimal change disease (MCD), although focal segmental glomerulosclerosis has been seen.4

Genetic diagnosis of steroid-resistant nephrotic syndrome in a longitudinal collection of Czech and Slovak patients: a high proportion of causative variants in NUP93

BackgroundSteroid-resistant nephrotic syndrome (SRNS) has a heterogeneous spectrum of monogenic causes that substantially differ among populations. The aim of this study was to analyse the genetic aetiology of SRNS in Czech and Slovak paediatric patients.MethodsWe analysed clinical data from 74 patients (38 boys) with congenital (15%), infant (14%), and childhood-onset (71%) SRNS collected from the Czech Republic and Slovakia from 2000 to 2017 (inclusive). The DNA samples were first analysed by Sanger sequencing (genes NPHS2, NPHS1, and WT1) and then by next generation sequencing (NGS) using a targeted panel of 48 genes previously associated with SRNS. Family segregation of the causative variants was confirmed by Sanger sequencing when possible.ResultsGenetic diagnosis was established in 28/74 patients (38%) based on findings of pathogenic or likely pathogenic causative variants in genotypes conforming to the expected mode of inheritance. Sanger sequencing diagnosed 26% of patients, whereas second-tier testing by a targeted NGS panel diagnosed a further 12%. Frequent causative genes were NPHS2 (15%), WT1 (9.5%), and surprisingly NUP93 with four (5.4%) unrelated cases. Additional causative genes included COQ2 (two patients), NPHS1, INF2, DGKE, and LMX1B (one patient each).ConclusionsCompared with outright use of NGS, our tiered genetic testing strategy was considerably more rapid and marginally less expensive. Apart from a high aetiological fraction of NPHS2 and WT1 genes, our study has identified an unexpectedly high frequency of a limited set of presumably ancestral causative mutations in NUP93. The results may aid in tailoring testing strategies in Central European populations.

Urinary Neutrophil Gelatinase-Associated Lipocalin Does Not Distinguish Acute Rejection from Other Causes of Acute Kidney Injury in Pediatric Renal Transplant Recipients

BACKGROUND The aim of this prospective single center study was to investigate the ability of urinary neutrophil gelatinase-associated lipocalin (NGAL) to distinguish acute rejection from other causes of acute kidney injury (AKI) in children after renal transplantation. METHODS Fifteen children fulfilled the inclusion criteria (acute kidney injury (AKI) with allograft biopsy, at least 21 days after renal transplantation, no sepsis) during 2013 - 2014 in our pediatric transplantation center. The mean age was 14.8  2.8, median time after renal transplantation was 0.4 years (range 0.1 - 3.8). Urinary NGAL was measured in spot urine by Chemiluminescent Microparticle Immunoassay technology. RESULTS Four patients had biopsy proven acute rejection (rejection group), eleven children had AKI of other cause (non-rejection group). The median urinary NGAL concentration in the rejection group was not significantly different from NGAL in the non-rejection group (7.3 ng/mL, range 3.0 - 42.3 vs. 8.6 ng/mL, range 3.4 - 54.7, p = 0.48). There was a significant negative correlation between eGFR and urinary NGAL concentrations (r = -0.77, p < 0.001). CONCLUSIONS Our small study suggests that in children after renal transplantation, urinary NGAL cannot be used as a specific marker for distinguishing acute rejection from other non-rejection causes of AKI. Urinary NGAL was mainly associated with graft function but not with the etiology of AKI.

Oral penicillin-associated acute kidney injury in an infant with acute pyelonephritis.

Beta‐lactam‐associated acute tubulointerstitial nephritis (ATIN) is a rare condition in childhood. We report the case of an infant with penicillin‐associated ATIN and concomitant acute pyelonephritis resulting in the development of severe acute kidney injury (AKI). The treatment consisted of penicillin suspension and appropriate AKI management, which required a short period of dialysis. Finally, full recovery and normalization of laboratory parameters occurred. We present here the first case of oral penicillin‐associated ATIN in childhood.