DNASE1L3 deficiency, new phenotypes, and evidence for a transient type I IFN signaling.

BACKGROUND: Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated with a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans. OBJECTIVES: To explore interferon signaling in DNASE1L3 deficient patients. To depict the characteristic features of DNASE1L3 deficiencies in human. METHODS: We identified, characterized, and analyzed five new patients carrying biallelic DNASE1L3 variations. Whole or targeted exome and/or Sanger sequencing was performed to detect pathogenic variations in five juvenile systemic erythematosus lupus (jSLE) patients. We measured interferon-stimulated gene (ISG) expression in all patients. We performed a systematic review of all published cases available from its first description in 2011 to March 24th 2022. RESULTS: We identified five new patients carrying biallelic DNASE1L3 pathogenic variations, including three previously unreported mutations. Contrary to canonical type I interferonopathies, we noticed a transient increase of ISGs in blood, which returned to normal with disease remission. Disease in one patient was characterized by lupus nephritis and skin lesions, while four others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented also with early-onset inflammatory bowel disease. Reviewing previous reports, we identified 35 additional patients with DNASE1L3 deficiency which was associated with a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Lung lesions were reported in 6/35 patients. CONCLUSIONS: DNASE1L3 deficiencies are associated with a broad phenotype including frequently lupus nephritis and hypocomplementemic urticarial vasculitis with positive ANCA and rarely, alveolar hemorrhages and inflammatory bowel disease. This report shows that interferon production is transient contrary to anomalies of intracellular DNA sensing and signaling observed in Aicardi-Goutières syndrome or STING-associated vasculitis in infancy (SAVI).

Psychosocial impact of structured transfer of adolescents with kidney transplants to adult services: An interventional national cohort study.

BACKGROUND: Pediatric kidney transplantation entails a well-timed transition from pediatric to adult medical care. We aimed to construct a structured transition protocol and evaluate its impact on transfer-related psychosocial problems in Slovenian patients with kidney transplants. METHODS: Individual transition-related perceptions of our patients and their parents were first assessed, and the gathered information was used to establish a country-specific transition protocol. Eleven kidney transplant patients qualified for actual transfer and were considered for further analysis. Comprehension and attitude towards transfer, coping strategies, personality resilience, behavioral, and emotional problems were assessed using questionnaires and established psychological tools before and after the completed transfer. The results were compared and analyzed. RESULTS: Ten of the eleven eligible patients were transferred to adult services between April 2020 and January 2021. The median age at enrollment was 19.7 years (range: 18.2-22.8 years). The most frequent concerns regarding upcoming health care were worse accessibility (50%), less supportive and less committed healthcare providers (40%), and deterioration of medical condition (10.0%). After the completed protocol-guided transfer, the patients declared to have no further concerns or worries. Before transfer, 28.9% of the patients' responses rated the amount and relevance of received information and counseling as "Adequate" or "Very adequate," whereas, after the transfer, the proportion of positive responses increased to 48.9%. Anxiety and withdrawn depressive symptoms were the predominant emotional problems before transfer. Their prevalence decreased after the completed transfer. CONCLUSIONS: Our results suggest that transfer-related anxieties and concerns can be significantly reduced by applying a structured transition protocol in transplant patients.

Clinical practice recommendations for recurrence of focal and segmental glomerulosclerosis/steroid-resistant nephrotic syndrome.

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence.

Peritonitis related to chronic peritoneal dialysis in Slovenian pediatric patients.

AIMS: Peritonitis is the most significant complication of chronic peritoneal dialysis (PD). We aimed to define the frequency and country-specific characteristics of peritonitis in Slovenian pediatric patients. MATERIALS AND METHODS: All 23 children and adolescents treated with PD at our center between November 1995 and December 2019 were included in the study. There were 15 boys (65.2%) and 8 girls (34.8%). The median age at PD start was 4.8 years (range: 0 - 16.8 years). Patient demographic data, PD modality, treatment duration, and PD-related infections were collected retrospectively by reviewing the patients' medical records and the microbiology database. Data on the number of peritonitis episodes, microbiology results, and treatment outcomes were of prime interest. RESULTS: 30 peritonitis episodes were registered. The incidence rate was 1/33 patient-months (0.35/year). Twelve patients never experienced peritonitis (52.2%). Gram-positive organisms were isolated in 52.9% (Staphylococcus aureus (4/18), Staphylococcus epidermidis (4/18)). Gram-negative isolates were present in 32.4% (Escherichia coli (4/11), Pseudomonas species (2/11)). Fungal peritonitis occurred in 2.9% and negative culture peritonitis in 11.8%. Initial empirical treatment with vancomycin and ceftazidime was successful in 89.5%. PD was discontinued in 2 patients (8.7%) because of fungal peritonitis and refractory peritonitis. CONCLUSION: Our results compare favorably with the published literature. Awareness of local patient and microbial characteristics is crucial for the successful treatment and prevention of PD-associated infections.

Clinical characteristics of Slovenian pediatric patients with autosomal recessive polycystic kidney disease.

AIMS: Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited disease. We reviewed the clinical characteristics, management, and outcomes in Slovenian pediatric patients with ARPKD. MATERIALS AND METHODS: All patients with ARPKD who were treated at the Pediatric Nephrology Department of the University Children's Hospital in Ljubljana between 1980 and 2020 were included in the study. The data were assessed retrospectively by reviewing the patients' medical records and analyzed using descriptive statistics. RESULTS: We included 13 patients, 6 boys and 7 girls. A prenatal diagnosis was established in 3 (23%) patients. In 4 (31%) patients, the diagnosis was confirmed within the first few days of life, while in 6 (46%) patients the disease manifested later during childhood. Four babies (31%) needed ventilatory support after birth. Arterial hypertension developed in all patients. Liver function was affected in 12 (92%) patients and was the predominant clinical concern in 2 of them. Two (15%) patients presented with end-stage renal disease (ESRD). Portal hypertension was found in 7 (54%) patients. Initial sonography revealed enlarged kidneys in 12 (92%) patients, hyperechoic kidneys or poor cortico-medullary differentiation in 10 (77%), and liver abnormalities in 5 (38%) patients. Unilateral nephrectomy was necessary before dialysis in 1 patient. Six (46%) patients started maintenance dialysis at an average age of 15.3 years. Kidney transplantation was performed in 2 (15%) and liver transplantation in 1 (8%) patient. Two (15%) patients died because of sepsis or respiratory failure. CONCLUSION: ARPKD is a progressive disease leading to ESRD and renal replacement treatment in almost half of our patients. Our data confirm the phenotypic variability of ARPKD in Slovenian patients.

Results in the ESPN/ERA-EDTA Registry suggest disparities in access to kidney transplantation but little variation in graft survival of children across Europe.

One of the main objectives of the European health policy framework is to ensure equitable access to high-quality health services across Europe. Here we examined country-specific kidney transplantation and graft failure rates in children and explore their country- and patient-level determinants. Patients under 20 years of age initiating kidney replacement therapy from January 2007 through December 2015 in 37 European countries participating in the ESPN/ERA-EDTA Registry were included in the analyses. Countries were categorized as low-, middle-, and high-income based on gross domestic product. At five years of follow-up, 4326 of 6909 children on kidney replacement therapy received their first kidney transplant. Overall median time from kidney replacement therapy start to first kidney transplantation was 1.4 (inter quartile range 0.3-4.3) years. The five-year kidney transplantation probability was 48.8% (95% confidence interval: 45.9-51.7%) in low-income, 76.3% (72.8-79.5%) in middle-income and 92.3% (91.0-93.4%) in high-income countries and was strongly associated with macro-economic factors. Gross domestic product alone explained 67% of the international variation in transplantation rates. Compared with high-income countries, kidney transplantation was 76% less likely to be performed in low-income and 58% less likely in middle-income countries. Overall five-year graft survival in Europe was 88% and showed little variation across countries. Thus, despite large disparities transplantation access across Europe, graft failure rates were relatively similar. Hence, graft survival in low-risk transplant recipients from lower-income countries seems as good as graft survival among all (low-, medium-, and high-risk) graft recipients from high-income countries.

Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.

BACKGROUND: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment. METHODS: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias. RESULTS: The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings. CONCLUSIONS: We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.

Hemodialysis vascular access and subsequent transplantation: a report from the ESPN/ERA-EDTA Registry.

BACKGROUND: Current guidelines advocate use of arteriovenous fistula (AVF) over central venous catheter (CVC) for children starting hemodialysis (HD). European data on current practice, determinants of access choice and switches, patient survival, and access to transplantation are limited. METHODS: We included incident patients from 18 European countries who started HD from 2000 to 2013 for whom vascular access type was reported to the ESPN/ERA-EDTA Registry. Data were evaluated using descriptive statistics, logistic and Cox regression models, and cumulative incidence competing risk analysis. RESULTS: Three hundred ninety-three (55.1%) of 713 children started HD with a CVC and were more often females, younger, had more often an unknown diagnosis, glomerulonephritis, or vasculitis, and lower hemoglobin and height-SDS at HD initiation. AVF patients were 91% less likely to switch to a second access, and two-year patient survival was 99.6% (CVC, 97.2%). Children who started with an AVF were less likely to receive a living donor transplant (adjusted HR, 0.30; 95% CI, 0.16-0.54) and more likely to receive a deceased donor transplant (adjusted HR, 1.50; 95% CI, 1.17-1.93), even after excluding patients who died or were transplanted in the first 6 months. CONCLUSIONS: CVC remains the most frequent type of vascular access in European children commencing HD. Our results suggest that the choice for CVC is influenced by the time of referral, rapid onset of end-stage renal disease, young age, and an expected short time to transplantation. The role of vascular access type on the pattern between living and deceased donation in subsequent transplantation requires further study.

Anemia in children following renal transplantation-results from the ESPN/ERA-EDTA Registry.

BACKGROUND: Our aim was to determine the prevalence of sub-target hemoglobin (Hb) levels in children with a renal allograft and to identify potential determinants associated with these Hb levels. METHODS: Data from 3669 children with a functioning renal allograft, aged <18 years between 1 January 2000 and 31 December 2012, from 20 European countries were retrieved from the ESPN/ERA-EDTA Registry, providing 16,170 Hb measurements. RESULTS: According to the NKF/KDOQI classification and the UK-NICE guidelines, 49.8 and 7.8% of the patients, respectively, were anemic. Hb levels were strongly associated with graft function, with Hb levels of 12.6 g/dl in children with chronic kidney disease (CKD) stage 1, declining to 10.7 g/dl in children with CKD stage 5 (P < 0.001). Higher Hb levels were associated with the use of tacrolimus compared to ciclosporin (0.14 g/dl; 95% confidence interval 0.02-0.27; P = 0.002). Low Hb levels were associated with an increased risk of graft failure (P = 0.01) or combined graft failure and death (P < 0.01), but not with death alone (not significant). CONCLUSIONS: Anemia is present in a significant proportion of European pediatric kidney transplant recipients and is associated with renal allograft dysfunction and type of immunosuppressants used. In our patient cohort, higher Hb levels were associated with better graft and patient survival and less hypertension.

Contrast-Enhanced Ultrasound (CEUS) and Ultra-Microangiography (UMA) in Critically Ill Children with Acute Kidney Injury.

Acute kidney injury (AKI) is an acute condition of impaired kidney function with decreased glomerular filtration rate, which results in dysregulation in volume, electrolyte, and acid-base equilibrium. AKI can be a life-threatening condition and can also lead to chronic kidney disease. It is important to diagnose AKI early in the course of the disease or to predict its development, as this can influence therapeutic decisions, outcome, and, consequently, the prognosis. In clinical practice, an elevated serum creatinine concentration remains the most common laboratory indicator for diagnosing AKI. However, due to the delay in its rise, creatinine levels are often insensitive and inaccurate for early diagnosis. Novel biomarkers of kidney tubular injury and the renal angina index have shown promise in predicting AKI earlier and more accurately. Contrast-enhanced ultrasonography (CEUS) and ultra-microangiography (UMA) are radiological methods that can quantify renal microperfusion and may be able to predict the development of AKI. They have not yet been used for quantifying renal perfusion in children with risk factors for developing AKI. Further research is needed to compare these sonographic techniques with the renal angina index and emerging kidney injury biomarkers for predicting acute kidney injury (AKI) in both children and adults.

Citrate-induced local ionized calcium decrease in pediatric hemodialysis settings: An in-vitro study.

BACKGROUND: Citrate is instilled into the dialysis catheter to prevent clotting and to maintain patency between dialysis sessions. A significant amount of citrate leaks from the catheter at the injection time, which decreases the blood ionized calcium concentration (Ca2+) due to chelation. We aimed to evaluate the local impact of concentrated (i.e. 30%) citrate spilling on Ca2+ at the catheter tip in real-time pediatric conditions. METHODS: An in-vitro model was constructed, involving an ion-selective electrode (Ca-ISE). A pre-curved catheter and the Ca-ISE were submerged in a glass vessel with the tips positioned adjacent to each other. The vessel was filled with 30 and 80 ml of normal saline with added calcium to simulate normal right atrium size in children and adults, respectively, and normal blood Ca2+. The amount of instilled citrate matched the filling volume of the catheter. Measurements were performed with 4% and 30% citrate solutions. RESULTS: The mean Ca2+ measured at the tip of the catheter was 0.457 and 0.058 mmol/l when using 4% and 30% citrate, respectively (p < 0.001). The mean Ca2+ recorded in 30 and 80 ml after instilling 30 % citrate was 0.058 and 0.055 mmol/l, respectively (p = 0.878). CONCLUSIONS: The spilling of 30% citrate caused a strikingly greater decrease of Ca2+ at the catheter tip than the standard 4% citrate. The atrial volume did not influence the test results implying similar safety concerns for pediatric and adult patients. The used static experimental setting might have overestimated the spilling effect.

Demographics of blood pressure and hypertension in children on renal replacement therapy in Europe.

Hypertension is a well-known complication in children on renal replacement therapy and an important risk factor for cardiovascular disease in later life. In order to define the prevalence of and risk factors for hypertension among children, we enrolled 3337 pediatric patients from 15 countries in the ESPN/ERA-EDTA Registry of whom 464 were on hemodialysis, 851 on peritoneal dialysis, and 2023 had received a renal allograft. Hypertension was defined as either systolic or diastolic blood pressures in the 95th percentile or greater for age, height, and gender or use of antihypertensive medication. Analyses were adjusted for age, gender, duration, and modality of renal replacement therapy. In 10 countries in which information on the use of antihypertensive medication was available, hypertension was present in over two-thirds of hemodialysis, peritoneal dialysis, or transplant patients. Blood pressure values above the 95th percentile were significantly more prevalent in very young patients (under 3 years) compared to 13- to 17-year olds (odds ratio 2.47), during the first year compared to over 5 years of renal replacement therapy (odds ratio 1.80), and in patients on hemodialysis compared to transplant recipients or those on peritoneal dialysis (odds ratios of 2.48 and 1.59, respectively). Over time, mean blood pressures decreased in both hemodialysis and transplant patients, but not in peritoneal dialysis patients. Hence, our findings highlight the extent of the problem of hypertension in children with end-stage renal disease in Europe.

Ultrasound detection of vesicoureteral reflux in children.

PURPOSE: We present different ultrasound techniques to detect vesicoureteral reflux in children with special emphasis on voiding urosonography. MATERIALS AND METHODS: Urinary tract infection is a common problem in children that may be related to vesicoureteral reflux. Currently there is no consensus on investigations in children after the first urinary tract infection. The least invasive imaging with the smallest radiation burden should be used in children. Ultrasound to detect reflux meets several of these criteria. The development of echo enhancing agents has markedly improved reflux visualization by ultrasound. RESULTS: We discuss the clinical relevance of voiding urosonography. We reviewed the currently available literature and the results of our studies of this issue. We also describe our endeavors to avoid catheterization and detect vesicoureteral reflux based on various sonomorphological features, ie indirect voiding urosonography and ureteral jet Doppler waveform analysis, to avoid applying any substance into the bladder. CONCLUSIONS: Voiding urosonography is safe and reliable to detect vesicoureteral reflux. When indicated, considerably decreased radiation exposure can be achieved by voiding urosonography instead of established cystography methods. Indirect voiding urosonography and ureteral jet Doppler waveform analysis could be an alternative to invasive voiding cystography, at least in children older than 3 years.

Determinants of eGFR at start of renal replacement therapy in paediatric patients.

BACKGROUND: Few studies have investigated the determinants of glomerular filtration rate (GFR) in paediatric patients starting on dialysis or with a transplant. METHODS: Data were collected as part of the European Society of Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association registry from 14 European countries and referred to incident paediatric patients starting on renal replacement therapy (RRT) between 2002 and 2007 under the age of 18 years. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula. Data were adjusted for age, gender, treatment modality at start, primary cause of renal failure (PRD) and regions in Europe (eGFR(adj)). RESULTS: Median eGFR in the 938 patients starting RRT was 10.4 mL/min/1.73 m(2) (5th and 95th percentile: 4.0-26.9). Twenty-six patients (2.8%), mainly infants with Finnish-type nephropathy, started with eGFR levels >50 mL/min/1.73 m(2). Younger age, female gender, starting on dialysis and having a short time between the first visit to a paediatric nephrologist (PN) and start of RRT were associated with lower eGFR at start of RRT. Gender differences were only present during adolescent age and disappeared when using the same K value for both genders. The various PRDs showed large differences in the rate of decline in eGFR between the first visit to a PN and start of RRT; however, this did not result in differences in eGFR(adj) at start of RRT. CONCLUSIONS: The main determinants of eGFR at start of RRT were age, gender, treatment modality at start, and the time between the first visit to a PN and start of RRT. Research is needed to determine the consequences of these differences.

Catheter-free methods for vesicoureteric reflux detection: our experience and a critical appraisal of existing data.

In recent years, the exact role of vesicoureteric reflux (VUR) in general has become controversial, though in some groups of children the knowledge of the existence or non-existence of VUR is still a very important issue. The number of techniques available for the assessment of VUR is increasing, and a new classification taking into account their real characteristics (direct/indirect, catheter-using/catheter-free, radiation-giving/radiation-free) has been proposed. The purpose of the following review is to evaluate the currently available evidence supporting the use of various catheter-free methods for VUR detection. We believe that as the clinical role of VUR has been questioned, it is even more important for the method of its detection to be user-friendly as regards catheterisation, radiation and availability. There is still no evidence supporting the assertion that any of the catheter-free methods of VUR detection might be the optimal one for any child. However, there are some groups of children who would benefit from using them. New studies using new, catheter-free methods of VUR detection or a combination of two or more of the methods described may prove useful in improving sensitivity and providing additional data on this important issue.

Does Guidewire Exchange Influence Infection Rate Related to Catheters Used for Vascular Access in Children on Chronic Hemodialysis?

A central venous catheter (CVC) can either be inserted "de novo" or placed by guidewire exchange (GWE). From September 1998 to September 2015, 32 children (19 boys, 13 girls) were hemodialyzed in our unit by using a CVC. The mean age at CVC insertion was 12.6 ± 0.5 years. A total of 121 uncuffed catheters were placed, either "de novo" or by GWE in 64 (52.9%) and 57 (47.1%) cases, respectively. The most frequent cause for line revision was catheter dysfunction in 40/121 (33.1%) patients. The overall incidence of bacteremia was 1.5/1000 catheter-days. The incidence in newly inserted and GWE catheters was 1.4 and 1.7/1000 catheter-days, respectively. The difference did not reach statistical significance (P = 0.939). The infection rate correlated with patient age, and was higher in younger children (P = 0.006). GWE is an effective option of line revision, and did not influence the infection rate in our study.

Chronic Hemodialysis in Small Children.

When peritoneal dialysis is inapplicable, chronic hemodialysis (HD) becomes the only available treatment option in small children. Due to small patient size, central venous catheters (CVC) are mainly used for vascular access. Over the past 4 years, four children weighing less than 15 kg received chronic HD in our unit. A total of 848 dialysis sessions were performed. Altogether, 21 catheters were inserted. In all but one occasion, uncuffed catheters were used. Catheter revision was performed 15 times during the study period, either due to infection or catheter malfunction. The median number of catheter revisions and the median line survival was 3.0/patient-year and 53 days (range; 6-373 days), respectively. There were 14 episodes of catheter related infections requiring 11 CVC revisions (78.6%). The median rate of line infections was 2.8/patient-year. Chronic HD in small children is demanding and labor intensive. Issues pertain mainly to CVCs and limit its long-term use.

Fate of Central Venous Catheters Used for Acute Extracorporeal Treatment in Critically Ill Pediatric Patients: A Single Center Experience.

Renal replacement treatment (RRT) is required in severe acute kidney injury, and a functioning central venous catheter (CVC) is crucial. Twenty-eight children younger than 16 years have been treated at the University Medical Centre Ljubljana between 2003 and 2012 with either acute hemodialysis (HD) and/or plasma exchange (PE), and were included in our study. The age of the patients ranged from 2 days to 14.1 years. Sixty-six CVCs were inserted (52% de novo, 48% guide wire). The sites of insertion were the jugular vein in 20% and the femoral vein in 80%. Catheters were in function from 1 day to 27 days. The most common cause for CVC removal or exchange was catheter dysfunction (50%). CVCs were mostly inserted in the femoral vein, which is the preferred site of insertion in acute HD/PE because of the smaller number of complications.

Post-Transplant Recurrence of Focal Segmental Glomerulosclerosis in a Child With Heterozygous Mutations in NPHS1 and NPHS2.

Renal transplantation is the optimal renal replacement therapy (RRT) in children, but some primary diseases can recur after transplantation, and recurrence accounts for a significant proportion of graft losses, being second only to acute rejection. The risk of disease recurrence is highest among patients with idiopathic focal segmental glomerulosclerosis (FSGS), presumably due to a circulating permeability factor. Less is clear about the genetic forms of FSGS, where the data regarding the frequency of recurrence are rather conflicting. We present a 12-year-old girl with rapidly progressive FSGS and end-stage renal disease in her native kidneys associated with heterozygous mutations in NPHS1 and in NPHS2, suffering from early post-transplant recurrence. On the basis of reviewed literature, and until further and more conclusive evidence considering pathogenicity is provided, we propose that FSGS patients with heterozygous mutations in NPHS1 or NPHS2 should be considered as having idiopathic FSGS, and post-transplant recurrence should be anticipated.

End-Stage Renal Disease in an Infant With Hajdu-Cheney Syndrome.

Hajdu-Cheney syndrome (HJCYS) is a rare, autosomal dominant, skeletal disorder caused by mutations in the NOTCH2 signaling pathway for which genetic testing has recently become available. Renal abnormalities are associated in at least 10% of cases. We present an 8-year-old Caucasian boy, born with multiple dysmorphic features consistent with HJCYS. Imaging of the urinary tract revealed bilateral cystic dysplastic kidneys with associated vesicoureteral reflux. Renal function has been impaired since birth and deteriorated progressively to end-stage renal disease (ESRD) by the age of two and a half years, when peritoneal dialysis was initiated and only recently renal transplantation was performed. Additional congenital abnormalities and multisystem involvement in HJCYS further complicated management, and he developed refractory anemia. Molecular diagnosis was confirmed by identification of a truncating mutation in exon 34 of NOTCH2. Although, renal abnormalities are considered an integral part of the HJCYS, published reports on ESRD are scarce. In those few published cases, where ESRD was recognized, renal failure developed either in late adolescence or adulthood. This is the first report of early ESRD occurring in a child. Patients with HJCYS may need chronic renal replacement therapy even in early childhood. The management of these children can be challenging given the multisystemic manifestations of HJCYS.