Development of a tool for predicting HNF1B mutations in children and young adults with congenital anomalies of the kidneys and urinary tract.

BACKGROUND: We aimed to develop a tool for predicting HNF1B mutations in children with congenital abnormalities of the kidneys and urinary tract (CAKUT). METHODS: The clinical and laboratory data from 234 children and young adults with known HNF1B mutation status were collected and analyzed retrospectively. All subjects were randomly divided into a training (70%) and a validation set (30%). A random forest model was constructed to predict HNF1B mutations. The recursive feature elimination algorithm was used for feature selection for the model, and receiver operating characteristic curve statistics was used to verify its predictive effect. RESULTS: A total of 213 patients were analyzed, including HNF1B-positive (mut + , n = 109) and HNF1B-negative (mut - , n = 104) subjects. The majority of patients had mild chronic kidney disease. Kidney phenotype was similar between groups, but bilateral kidney anomalies were more frequent in the mut + group. Hypomagnesemia and hypermagnesuria were the most common abnormalities in mut + patients and were highly selective of HNF1B. Hypomagnesemia based on age-appropriate norms had a better discriminatory value than the age-independent cutoff of 0.7 mmol/l. Pancreatic anomalies were almost exclusively found in mut + patients. No subjects had hypokalemia; the mean serum potassium level was lower in the HNF1B cohort. The abovementioned, discriminative parameters were selected for the model, which showed a good performance (area under the curve: 0.85; sensitivity of 93.67%, specificity of 73.57%). A corresponding calculator was developed for use and validation. CONCLUSIONS: This study developed a simple tool for predicting HNF1B mutations in children and young adults with CAKUT.

X-linked variations in SHROOM4 are implicated in congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems.

BACKGROUND: SHROOM4 is thought to play an important role in cytoskeletal modification and development of the early nervous system. Previously, single-nucleotide variants (SNVs) or copy number variations (CNVs) in SHROOM4 have been associated with the neurodevelopmental disorder Stocco dos Santos syndrome, but not with congenital anomalies of the urinary tract and the visceral or the cardiovascular system. METHODS: Here, exome sequencing and CNV analyses besides expression studies in zebrafish and mouse and knockdown (KD) experiments using a splice blocking morpholino in zebrafish were performed to study the role of SHROOM4 during embryonic development. RESULTS: In this study, we identified putative disease-causing SNVs and CNVs in SHROOM4 in six individuals from four families with congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems (CNS). Embryonic mouse and zebrafish expression studies showed Shroom4 expression in the upper and lower urinary tract, the developing cloaca, the heart and the cerebral CNS. KD studies in zebrafish larvae revealed pronephric cysts, anomalies of the cloaca and the heart, decreased eye-to-head ratio and higher mortality compared with controls. These phenotypes could be rescued by co-injection of human wild-type SHROOM4 mRNA and morpholino. CONCLUSION: The identified SNVs and CNVs in affected individuals with congenital anomalies of the urinary tract, the anorectal, the cardiovascular and the central nervous systems, and subsequent embryonic mouse and zebrafish studies suggest SHROOM4 as a developmental gene for different organ systems.

Impaired Functional Status Increases Fracture Incidence in 10-year Follow-Up: The Results from RAC-OST-POL Study.

INTRODUCTION: The aim of study was to establish the influence of baseline functional status on fracture incidence. METHODOLOGY: In a prospective 10-years observation in epidemiological sample of postmenopausal women from RAC-OST-POL Study a thesis that affected functional status enhance fracture incidence was verified. At baseline, data were collected in 978 women at mean age 66.48±7.6 years and after 10 years of follow-up 640 subjects at mean age 75.04±6.95 years remained in the study. Functional status at baseline was established using Stand up and Go test (SAG) and Activity of Daily Living (IADL). Afterwards, annually data on fracture incidence were collected by phone interviews. RESULTS: In the period of observation 190 low-energy fractures in 129 women were noted. The whole group was divided into subgroups: without fracture (n=511), with one fracture (n=91) and those ones who had more than one fracture (n=38). In fractured and unfractured subgroup mean SAG results were 11.36±4.28 and 10.36±2.76, respectively and differed significantly (p<0.01). With increasing number of fractures the SAG time was longer - it was 11.15±4.49 in one fracture subgroup and 11.87±3.73 in multiple fractures subgroup, with both values significantly higher than in no fracture subjects. The mean value of IADL was 23.56±1.60. In 576 (90%) women IADL reached maximal value of 24 points. In the rest of them (n=64) IADL score was between 11 and 23 points. Mean value of IADL in fractured and unfractured subgroup were 23.27±1.97 and 23.64±1.47, respectively and differed significantly (p<0.01). CONCLUSION: The measures of functional status predict fractures in a prospective observation of representative epidemiological female sample.

Glucocorticoids Increase Fracture Risk and Fracture Prevalence Independently from Bone Mineral Density and Clinical Risk Factors: Results from the Gliwice Osteoporosis (GO) Study.

The aim of the study was to establish the influence of glucocorticoids (GC) on fracture risk, probability, and prevalence. A set of 1548 postmenopausal women were divided into study group - treated with GC (n=114, age 66.48±7.6 years) and controls (n=1434, age 66.46±6.83 years). Data on clinical risk factors for osteoporosis and fractures were collected. Hip bone densitometry was performed using a device Prodigy (GE, USA). Fracture probability was established by FRAX, and fracture risk by Garvan algorithm and POL-RISK. Fracture risk and fracture probability were significantly greater for GC-treated women in comparison to controls. In the study group, there were 24, 3, 24, and 6 fractures noted at spine, hip, forearm, and arm, respectively. The respective numbers of fractures reported in controls at those skeletal sites were: 186, 23, 240, and 25. The use of GCs increased significantly prevalence of all major, spine and arm fractures. Also the number of all fractures was affected by GC use. Following factors significantly increased fracture probability: age (OR 1.04 per each year; 95% CI: 1.03-1.06), GC use (OR 1.54; 95% CI: 1.03-2.31), falls (OR 2.09; 95% CI: 1.60-2.73), and FN T-score (OR 0.62 per each unit; 95% CI: 0.54-0.71). In conclusion, in patients treated with GCs the fracture risk, probability, and prevalence were increased. This effect was evident regardless of whether GC therapy is included in the algorithm as a risk factor (FRAX, POL-RISK) or not taken into consideration (Garvan nomogram).

Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux.

BACKGROUND: Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood. METHODS: A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR. A GWAS was performed in 1395 patients and 5366 controls, of European ancestry. RESULTS: Altogether, 3% of VUR patients harbored an undiagnosed rare CNV disorder, such as the 1q21.1, 16p11.2, 22q11.21, and triple X syndromes ((OR, 3.12; 95% CI, 2.10 to 4.54; P=6.35×10-8) The GWAS identified three study-wide significant and five suggestive loci with large effects (ORs, 1.41-6.9), containing canonical developmental genes expressed in the developing urinary tract (WDPCP, OTX1, BMP5, VANGL1, and WNT5A). In particular, 3.3% of VUR patients were homozygous for an intronic variant in WDPCP (rs13013890; OR, 3.65; 95% CI, 2.39 to 5.56; P=1.86×10-9). This locus was associated with multiple genitourinary phenotypes in the UK Biobank and eMERGE studies. Analysis of Wnt5a mutant mice confirmed the role of Wnt5a signaling in bladder and ureteric morphogenesis. CONCLUSIONS: These data demonstrate the genetic heterogeneity of VUR. Altogether, 6% of patients with VUR harbored a rare CNV or a common variant genotype conferring an OR >3. Identification of these genetic risk factors has multiple implications for clinical care and for analysis of outcomes in VUR.

The significance of height loss in postmenopausal women. The results from GO Study.

BACKGROUND: The aim of the study was the assessment of clinical significance of height loss (HL) in female population. MATERIAL: The study cohort was recruited from GO Study. Data from 1735 postmenopausal women aged over 55 years (mean age 68.15 ± 8.16 years) were analysed. METHODS: Data on clinical risk factors for osteoporosis and fractures were collected. Bone densitometry at hip was performed using a device Prodigy (GE, USA). Height was established using stadiometer and was compared with maximal height in early adulthood. RESULTS: The mean HL was 3.9 ± 3.2 cm. HL was significantly higher in women with fractures in comparison with those without fracture (4.9 ± 3.6 cm vs 3.4 ± 2.8 cm; P < .0001). HL increased with the number of fractures, and was 4.1 ± 3.2 cm, 5.3 ± 3.5 cm and 6.7 ± 4.1 cm in women with one, two and three or more fractures respectively. Women with spine fractures presented with HL higher in comparison with all the other subjects (6.3 ± 4.0 vs 3.6 ± 2.9 cm, P < .0001) and women with all non-spine fractures (6.3 ± 4.0 vs 4.0 ± 3.0 cm, P < .0001). In women with steroid use and falls, HL was significantly greater than in subjects without this factor. HL correlated significantly with age and BMI (positively) and current height (negatively). Mean T-score for FN BMD was -1.75 ± 0.9 and correlate significantly with HL (r = -.21, P < .0001). For the HL threshold above 4 cm, the fracture incidence was above 50%. CONCLUSION: Height loss value is a simple and very informative measure describing fracture risk and functional status in postmenopausal women. HL exceeding 4 cm is related to fracture probability above 50%.

A rare complication of systemic lupus erythematosus in a 9-year-old girl: Questions.

Serious renal involvement in systemic diseases is common and generally constitutes a pivotal prognostic factor, making those pathology frequently seen in nephrology departments. Authors describe the case of a nine-year-old girl with lupus nephritis. After admission the patient's state deteriorated over a period of a few days, with an unremitting high-grade fever, significant weakness and drowsiness, generalized erythema, and decrease of the kidney function to eGFR nadir of 56 ml/min/1,73m 2. Treatment with pulsed methylprednisolone was started. After the first pulse the general state of the patient improved slightly, although laboratory tests showed an alarming evolution, with the exacerbation of anemia, leukopenia, neutropenia, increase of serum CRP concentration, extremely high D-dimer concentration and increase in activity of lactate dehydrogenase. The concentration of ferritin rose reaching the level of 540 µg/l, triglicerydes level was also high. Intravenous cyclophosphamide pulse therapy was added to the ongoing steroid treatment, and resulted in a radical patient improvement. Authors underline that it seems important to be aware of rare, non-renal, but potentially devastating complications of systemic diseases, like in this clinical case: the secondary hemophagocytic lymphohistiocytosis (HLH). When HLH complicates a rheumatic disease, it is also referred to as macrophage activation syndrome (MAS). Unfortunately treatment of MAS is still based on reports provided by individual centres and gathered own experiences so drawing up unambiguous diagnostic criteria will be valuable in future. The treatment should be individually tailored, and more specific evidence-based recommendations are needed.

Skeletal Status in Women With Carpal Tunnel Syndrome-A 1-Yr Prospective Study.

Functional deterioration due to carpal tunnel syndrome (CTS) may influence the bone status of the forearm and hand. The aim of this prospective study was to establish whether CTS has an impact on bone status at distal parts of the upper limb and to monitor the longitudinal changes of that status during a 1-yr follow-up after surgical treatment. Fifteen women with CTS at mean age of 55.13 ± 9.3 yr, mean weight of 79.18 ± 20.37 kg, and mean height of 157.8 ± 6.17 cm were enrolled into the study. All women had unilateral CTS that negatively affected upper limb function and were qualified to surgical treatment. Functional status was established at baseline using Levine's scale, motor latency, and nerve conduction velocity in electrophysiologic examinations. Bone status was established using densitometric measurements (Hologic Explorer, Bedford, MA) at the forearm, spine, and hip (bone mineral density [BMD], g/cm2) and with quantitative ultrasound measurements (amplitude-dependent speed of sound, m/s) at hand phalanges (DBM Sonic, IGEA, Carpi, Italy). Longitudinal changes were established for Levine's scale score and for forearm and phalanges measurements at 3, 6, and 12 mo after surgery. Levine's scale results improved significantly over a period of observation (p < 0.0001). Longitudinal BMD measurements for ultradistal forearm have shown a decrease only for measurement at 6 mo vs baseline result (0.386 ± 0.08 g/cm2 vs 0.375 ± 0.08 g/cm2, p < 0.05) with onward increase. Amplitude-dependent speed of sound did not differ over the period of observation. Correlation analysis has shown that functional status expressed by Levine's scale was most strongly related to the longitudinal BMD measurements for ultradistal forearm at 6 mo (r = -0.52, p < 0.05). Successful surgery in patients with CTS does not lead to permanent deterioration in bone status within the affected upper limb in a 1-yr longitudinal observation.

No association between Helicobacter pylori infection and gastrointestinal complaints in a large cohort of symptomatic children.

AIM: This Polish study estimated the prevalence of the Helicobacter pylori infection in symptomatic children aged 3-18 and investigated its association with gastrointestinal complaints. METHODS: We prospectively enrolled 1984 children (54% female) with a mean age of 9.5 ± 4.1 years, from Silesia, Poland, for the Good Diagnosis Treatment Life screening programme from 2009 to 2016. They underwent a 13 C-isotope-labelled urea breath test (UBT) to assess their Helicobacter pylori status, making this the biggest Polish study to use this approach. Further analysis included parental-reported gastrointestinal symptoms and standard deviation scores (SDS) of anthropometric measurements. RESULTS: The Helicobacter pylori infection was identified in 220 (11%) children (48% female) and was independent of age and sex. The frequency of symptoms did not differ between Helicobacter positive and negative children (all p > 0.05). Children with a positive UBT result had a lower body mass SDS (-0.41 ± 0.98 versus -0.26 ± 1.01, p = 0.04) and height SDS (-0.45 ± 1.34 versus -0.23 ± 1.27, p = 0.02), but similar body mass index SDS. CONCLUSION: We found a low prevalence of Helicobacter pylori in symptomatic children, and positive UBT results were not associated with symptoms that suggested Helicobacter pylori infections. Our findings support the 2017 European and North American guidelines for Helicobacter infections in children.

ATP4A autoimmunity in pediatric patients with type 1 diabetes and its relationship to blood count, iron metabolism, and vitamin B12.

OBJECTIVE: We aimed to assess the prevalence of autoantibodies against the 4A subunit of the gastric proton pump (ATP4A) in pediatric type 1 diabetes (T1D) patients and explore the relationship between ATP4A positivity and blood cell count, iron turnover, and vitamin B12 concentration. SUBJECTS: The study included 94 (59% female) T1D children (aged 12.5 ± 4.1 years, T1D duration 4.2 ± 3.6 years, HbA1c 7.3 ± 1.5% (57 ± 12.6 mmol/mol) with no other autoimmune diseases. METHODS: ATP4A antibodies were measured in T1D patients using a radioimmunoprecipitation assay. Blood cell count, iron concentration, total iron binding capacity, ferritin, transferrin, hepcidin, and vitamin B12 concentration were measured in all the study participants. RESULTS: A total of 16 (17%) children were ATP4A positive. Serum concentrations of ferritin were significantly lower in ATP4A positive than in antibody negative subjects (P = .034). Overall the levels of ATP4A antibodies (ATP4A Index) correlated positively with the age at T1D diagnosis (r = 0.228, P = .026) and negatively with ferritin levels (r = -0.215, P = .037). In ATP4A positive patients, the ATP4A Index correlated positively with age at diagnosis (r = 0.544, P = .032) and negatively with vitamin B12 levels (r = -0.685, P = .004). CONCLUSIONS: ATP4A antibodies were present in a significant proportion of children with T1D. Higher ATP4A levels in T1D children are associated with lower, yet still fitting within the normal range, levels of vitamin B12, and ferritin. Routine screening of T1D children for gastric autoimmunity (ATP4A) should be considered with follow-up of those positive for vitamin B12 and iron deficiency.

Surgical treatment of adult patients with thalamic tumors with the aid of tractography, fMRI, transcranial electrical stimulation and direct electrical stimulation of the subcortical white matter.

The aim of investigation was to assess treatment outcomes in adult patients with thalamic tumors, operated on with the aid of tractography (DTI) and monitoring of motor evoked potentials (MEPs) generated due to transcranial electrical stimulation (TES) and direct electrical stimulation (DES) of the subcortical white matter. 38 subsequent patients with thalamic tumors were operated on using tractography (DTI)-integrated neuronavigation, transcranial electrical stimulation (TES) and direct electrical stimulation (DES). The volumetric method was used to calculate pre- and postoperative tumor volume. Total tumor resection (100%) was performed in 18 (47%) patients, subtotal in 9 (24%) (mean extent of resection -89.4%) and partial in 11 (29%) patients (mean extent of resection -77.18%). The mean extent of resection for all surgical patients was 86.5%. Two (5.2%) patients died postoperatively. Preoperative hemiparesis was present in 18 (47%) patients. Postoperative hemiparesis was observed in 11 (29%) patients of whom only in 5 (13%) new paresis was noted due to surgical intervention. In patients with hemiparesis significantly more frequently larger tumor volume was detected preoperatively. Low mean normal fractional anisotropy (nFA) values in the internal capsule were observed statistically significantly more frequently in patients with preoperative hemiparesis as compared to the internal capsule of the unaffected hemisphere. Transcranial electrical stimulation helps to predict postoperative paresis of extremities. Direct electrical stimulation is an effective tool for intraoperative localization of the internal capsule thus helping to avoid postoperative deficit. In patients with tumor grade I and II the median time to tumor progression was 36 months. In the case of patients with grades III and IV it was 14 months. The median survival time in patients with grades I and II it was 60 months. In patients with grades III and IV it was 18 months. Basing on our results, patients with glioma grade I/II according to WHO classification are the best candidates for surgical treatment of thalamic tumors. In this group of the patients more often resection is radical, median time to progression and survival time are longer than in patients with gliomas grade III and IV. Within a 7-year follow-up none of the patients with GI/GII grade glioma died.

Total anomalous pulmonary vein drainage in a 60-year-old woman diagnosed in an ECG-gated multidetector computed tomography - a case report and review of literature.

PURPOSE: Total anomalous pulmonary vein drainage (TAPVD) is a congenital cardiac defect in which there is no connection between pulmonary veins and the left atrium. Pulmonary veins form a confluence independent of the left atrium and drain to a systemic vein. TAPVD types are: supracardiac, cardiac, infracardiac, and mixed. TAPVD accounts for approximately 1.5-2.2% of all congenital heart diseases. This anomaly is usually diagnosed in the neonatal period, and it coexists with atrial septal defect. Adult cases of TAPVD are rarely reported. CASE REPORT: We report a rare case of a 60-year-old woman with incidentally found, uncorrected TAPVD in ECG-gated multidetector computed tomography. In previous echocardiographic examinations partial anomalous pulmonary venous return and atrial septal defect were diagnosed. CONCLUSIONS: ECG-gated multidetector computed tomography is a valuable diagnostic method for adults with congenital heart disease. It enables evaluation of coronary arteries and simultaneously provides detailed anatomy of great vessels.

Rare case of nephrocalcinosis in a 14-year-old girl: Questions.

A 14-year-old Caucasian girl with a history of primary hypoparathyroidism and unstable calcium and phosphorus levels and on ongoing treatment was admitted to the Department of Pediatric Nephrology because of the onset of nephrocalcinosis and difficulties achieving normocalcemia. Coexistence of hypoparathyroidism, oral candidiasis, dental enamel hypoplasia, and subclinical Hashimoto's disease was strongly suggestive for autoimmune polyglandular syndrome (APS) type I. One of the clinical implications of this diagnosis is the high probability of future occurrence of adrenal insufficiency and hence the importance of maintaining a high level of suspicion in case of the onset of symptoms like weakness, fainting, hypotonia, or hyperkaliemia. Addison's disease would, in fact, be quite challenging for the future management of this patient.This clinical quiz highlighted the importance of careful evaluation of all multiorgan symptoms occurring in a patient to prevent further complications.

Quantitative Ultrasound Measurement at the Hand Phalanges Does Not Reveal Skeletal Disturbances in Children With Bronchial Asthma: A Longitudinal Observation.

OBJECTIVES: To assess the skeletal status in asthmatic children treated with inhaled corticosteroids in a longitudinal observation by quantitative ultrasound (US) measurement at the hand phalanges. METHODS: Thirty-four children were studied prospectively. Quantitative US measurements were performed at baseline and after a mean ± SD of 2.35 ± 0.20 years. The obtained results were compared to age-, sex-, and body size-matched control participants selected from a database of previously examined healthy children. Individual changes in the amplitude-dependent speed of sound (Ad-SoS) during the follow-up period were also analyzed. RESULTS: The mean age of the asthmatic children was 10.6 ± 2.5 years. The mean Ad-SoS in the asthmatic children at baseline was 1940.5 ± 49.6 m/s, and the mean Z score was -0.26 ± 0.80. Corresponding values at the follow-up examination were 1976.2 ± 63.6 m/s and -0.18 ± 1.16. The results did not differ significantly in comparison to the healthy controls. The analysis of individual changes in Ad-SoS revealed that 18 participants had a significant increase in this parameter (ie, exceeding the least significant change threshold), and 16 did not have a significant change in their values. No one had a significant decrease in Ad-SoS. CONCLUSIONS: Quantitative US at the hand phalanges applied as a diagnostic tool revealed no essential differences in the pattern of skeletal development between asthmatic children treated with inhaled glucocorticosteroids and healthy controls.

Non-dipping status and selected adipokines concentration in children with primary arterial hypertension.

High blood pressure (BP) in children and adolescents is associated with increased risk of persistent hypertension (HT) in adulthood and, consequently, cardiovascular disease and target organ damage. AIM: The values of selected anthropometric parameters and laboratory test results including leptin and apelin concentration were evaluated with regard to averaged values of office BP measurements and 24-hour ABPM. MATERIAL AND METHODS: The study included 55 children: 23-with primary HT and coexisting overweight or obese (HT-OB), 16-with primary HT and normal weight (HT-NW), and 16 healthy children (C). RESULTS: The concentration of leptin and apelin in HT-OB children was significantly higher than in the C and HT-NW group. A similar finding for leptin level was demonstrated in comparison of HT-NW with C group. In children with HT-OB, the lack of decline in nocturnal DBP was associated with significantly higher BMI and the Cole's Index value. Children with HT-OB and lack of decline in nocturnal SBP showed lower leptin and insulin concentrations, and lower values of HOMA-IR as compared with dipping children. Positive correlation in the whole study group was found between adipokines levels and BP measurements. In conclusion, children with primary HT show higher concentration of adipokines compared with their healthy peers. The data on relationship of serum adipokines levels with anthropometric and BP parameters in children may be helpful to clarify the sequence of disturbances in the cardiovascular system in adults, which requires further examination.

What has changed in the prevalence of hypertension in dialyzed children during the last decade?

BACKGROUND: Hypertension very often accompanies progression of chronic kidney disease (CKD) in children. A cross-sectional analysis of hypertension prevalence in dialyzed children in Poland was designed with a comparison with the data previously recorded 10 years earlier. METHODS: Two cohorts of children were analyzed: 59 subjects dialyzed in 2013, and 134 children from the previous study performed in 2003 that were reevaluated according to the current methodology. The incidence of hypertension (defined by SDS of sBP or dBP >1.64), clinical data, medical history, dialysis modalities and selected biochemical parameters of dialysis adequacy were analyzed. RESULTS: The prevalence of hypertension increased from 64% in 2003 to 78% in 2013. The efficacy of antihypertensive treatment remained unsatisfactory (61% proper BP control). Preservation of residual urine output and strict fluid balance may prevent development of hypertension in children on dialysis. CONCLUSIONS: Despite the higher awareness of hypertension and its complications in dialyzed children, the incidence of this entity has increased during the last decade, with the percentage of undertreated patients comparable to that observed 10 years ago. Thus, more attention should be paid to therapy efficacy in this population to prevent further damage to the cardiovascular system and to decrease morbidity.

Familial juvenile hyperuricemic nephropathy as rare cause of dialysis-dependent chronic kidney disease-a series of cases in two families.

Hyperuricemia is a common symptom in adult population. It usually accompanies the chronic kidney disease. Less frequently, it is a primary phenomenon causing later serious clinical consequences. Familial juvenile hyperuricemic nephropathy (FJHN) is one of the hereditary conditions associated with high levels of serum uric acid and leading to dialysis in young adult age. It results from mutation in the UMOD gene, encoding the uromodulin protein, that is, Tamm-Horsfall protein. The aim of this paper was to present two families (7 affected members) with FJHN, in whom standard nephrological diagnostics did not provide clear cause of dialysis-dependent chronic kidney disease, until genetic testing was performed.