Acute kidney injury in children hospitalised for febrile urinary tract infection.

AIM: To determine (i) prevalence and the risk factors for acute kidney injury (AKI) in children hospitalised for febrile urinary tract infection (fUTI) and (ii) role of AKI as indicator of an underlying VUR. AKI, in fact, is favoured by a reduced nephron mass, often associated to VUR. METHODS: This retrospective Italian multicentre study enrolled children aged 18 years or younger (median age = 0.5 years) discharged with a primary diagnosis of fUTI. AKI was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. RESULTS: Of 849 children hospitalised for fUTI (44.2% females, median age 0.5 years; IQR = 1.8), 124 (14.6%) developed AKI. AKI prevalence rose to 30% in the presence of underlying congenital anomalies of the kidney and urinary tract (CAKUT). The strongest AKI predictors were presence of CAKUT (OR = 7.5; 95%CI: 3.8-15.2; p = 9.4e-09) and neutrophils levels (OR = 1.13; 95%CI: 1.08-1.2; p = 6.8e-07). At multiple logistic regression analysis, AKI during fUTI episode was a significant indicator of VUR (OR = 3.4; 95%CI: 1.7-6.9; p = 0.001) despite correction for the diagnostic covariates usually used to assess the risk of VUR after the first fUTI episode. Moreover, AKI showed the best positive likelihood ratio, positive predictive value, negative predictive value and specificity for VUR. CONCLUSION: AKI occurs in 14.6% of children hospitalised for fUTI and is a significant indicator of VUR.

Results of the PROPINE randomized controlled study suggest tapering of prednisone treatment for relapses of steroid sensitive nephrotic syndrome is not necessary in children.

Corticosteroid-related toxicity in children with steroid-sensitive nephrotic syndrome is primarily related to the cumulative dose of prednisone. To optimize treatment of relapses, we conducted the PROPINE study, a multicentric, open-label, randomized, superiority trial. Seventy-eight relapsing children aged 3-17 years who had not received steroid-sparing medications during the previous 12 months were randomized to receive, from day five after remission, either 18 doses of 40 mg/m2 of prednisone on alternate days (short arm), or the same cumulative dose tapered over double the time (long arm). Patients were monitored with an ad-hoc smartphone application, allowing daily reporting. The primary outcome was the six-month relapse rate at which time, 23/40 and 16/38 patients had relapsed in the long and short arms, respectively (no significant difference). Additionally, 40/78 patients were also enrolled in a secondary crossover study and were allocated to the opposite arm. Altogether, at six months, the relapse rate was 32/40 and 28/40 in the long and short arms, respectively (no significant difference). A post-hoc analysis excluding 30 patients treated with low-dose prednisone maintenance therapy failed to show significant differences between the two arms. No differences in adverse events, blood pressure and weight gain were observed. Thus, our data do not support the prescription of prolonged tapering schedules for relapses of steroid-sensitive nephrotic syndrome in children.

An Ex Vivo Test of Complement Activation on Endothelium for Individualized Eculizumab Therapy in Hemolytic Uremic Syndrome.

RATIONALE & OBJECTIVE: Although primary atypical hemolytic uremic syndrome (aHUS) is associated with abnormalities in complement genes and antibodies to complement factor H, the role of complement in secondary aHUS remains debatable. We evaluated the usefulness of an ex vivo test to: (1) detect complement activation within the endothelium in primary and secondary aHUS, (2) differentiate active disease from remission, (3) monitor the effectiveness of eculizumab therapy, and (4) identify relapses during eculizumab dosage tapering and after discontinuation of treatment. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 121 patients with primary aHUS and 28 with secondary aHUS. Serum samples were collected during acute episodes, following remission, and during eculizumab treatment and were assessed using a serum-induced ex vivo C5b-9 endothelial deposition test. RESULTS: Serum-induced C5b-9 deposition on cultured microvascular endothelium was quantified by calculating the endothelial area covered by C5b-9 staining; values were expressed as percentage of C5b-9 deposits induced by a serum pool from healthy controls. Testing with adenosine diphosphate-activated endothelium demonstrated elevated C5b-9 deposits for all untreated patients with aHUS independent of disease activity, while testing with unstimulated endothelium demonstrated deposits only in active disease. Similar findings were observed in secondary aHUS. Serum-induced C5b-9 deposits on activated and unstimulated endothelium normalized during eculizumab treatment. 96% (22/23) of patients receiving eculizumab at extended 3- or 4-week dosing intervals demonstrated normal C5b-9 deposits on activated endothelium, despite most patients having CH50Eq (serum complement activity) > 20 UEq/mL, indicating that adequate complement control was achieved even with incomplete blockade of circulating C5. During eculizumab dosage tapering or after treatment discontinuation, all patients experiencing relapses versus only 6% (1/17) of those in stable remission had elevated C5b-9 deposits on unstimulated endothelium. LIMITATIONS: The C5b-9 endothelial deposition test can be performed in only specialized laboratories. Findings on eculizumab dosage tapering need to be confirmed with longitudinal monitoring of C5b-9 deposition. CONCLUSIONS: The C5b-9 endothelial deposition assay may represent an advance in our ability to monitor aHUS activity and individualize therapy.

Haemodiafiltration use in children: data from the Italian Pediatric Dialysis Registry.

BACKGROUND: High volume haemodiafiltration (HDF) is associated with better survival than conventional haemodialysis (HD) in adults, but data concerning its use in children are lacking. The aim of this study was to assess the prevalence of paediatric HDF use and its associated factors in recent years in Italy. METHODS: We retrospectively reviewed the files of patients from the Italian Pediatric Dialysis Registry's database who were registered between January 1, 2004 and December 31, 2016 and treated with extracorporeal dialysis for at least 6 months, looking in particular at modality and its associated factors. RESULTS: One hundred forty-one out of 198 patients were treated exclusively with bicarbonate HD (71.2%), 57 with HDF (28.8%). Patients treated with HDF were younger (median 9.7 vs 13.2 years, p = 0.0008), were less often incident patients (52.6% vs 75.9%, p = 0.0031), had longer duration of the HD cycle (26.9 vs 20.8 months, p = 0.0036) and had a longer time to renal transplantation (32 vs 25 months, p = 0.0029) than those treated with bicarbonate HD only. The percentage of patients treated with HDF increased with dialysis vintage (16.9% at 6 months, 38.1% after more than 2 years of dialysis). The use of HDF was stable over time and was more common in the largest centres. CONCLUSIONS: Over the observation period, HDF use in Italy has been limited to roughly a quarter of patients on extracorporeal dialysis, in particular to those with high dialysis vintage, younger age or a long expected waiting time to renal transplantation.

Urine-derived podocytes-lineage cells: A promising tool for precision medicine in Alport Syndrome.

Alport Syndrome (ATS) is a rare genetic disorder caused by collagen IV genes mutations, leading to glomerular basement membrane damage up to end-stage renal disease. Podocytes, the main component of the glomerular structure, are the only cells able to produce all the three collagens IV alpha chains associated with ATS and thus, they are key players in ATS pathogenesis. However, podocytes-targeted therapeutic strategies have been hampered by the difficulty of non-invasively isolating them and transcripts-based diagnostic approaches are complicated by the inaccessibility of other COL4 chains-expressing cells. We firstly isolated podocyte-lineage cells from ATS patients' urine samples, in a non-invasive way. RT-PCR analysis revealed COL4A3, COL4A4, and COL4A5 expression. Transcripts analysis on RNA extracted from patient's urine derived podocyte-lineage cells allowed defining the pathogenic role of intronic variants, namely one mutation in COL4A3 (c.3882+5G>A), three mutations in COL4A4 (c.1623+2T>A, c.3699_3706+1del, c.2545+143T>A), and one mutation in COL4A5 (c.3454+2T>C). Therefore, our cellular model represents a novel tool, essential to unequivocally prove the effect of spliceogenic intronic variants on transcripts expressed exclusively at a glomerular level. This process is a key step for providing the patient with a definite molecular diagnosis and with a proper recurrence risk. The established system also opens up the possibility of testing personalized therapeutic approaches on disease-relevant cells.

Outcome of childhood-onset full-house nephropathy.

BACKGROUND: Patients with full-house nephropathy (FHN) present renal lesions that are indistinguishable from those of lupus nephritis (LN) but lack the systemic features necessary to meet diagnostic criteria for systemic lupus erithematosus (SLE). Some have been reported to develop a delayed SLE with time. The clinical outcome of children having FHN without SLE has never been reported. METHODS: Children with biopsy-proven FHN were selected after excluding SLE cases by the absence of America College of Rheumatology criteria. The proportion of patients with complete (proteinuria <0.5 g/day) or partial remission (proteinuria ≤50% from baseline), relapse (estimated glomerular filtration rate <25% and/or proteinuria ≥50% from baseline) and progression to Stage III chronic kidney disease (CKD) was described according to age and gender groups with the Kaplan-Meier curve and compared with the Log-rank test. Entity of treatment was summarized by a score at induction (0-6 months) and maintenance (6-18 months). Cox-regression model was performed to test predictors of remission, relapse and progression to CKD. RESULTS: Among 42 patients (28 pre-pubertal) who met the inclusion criteria, 39 (92.9%) achieved partial and 32 (76.2%) complete remission of nephropathy over 2.78 and 7.51 months of follow-up. At 10 years, the probability of progressing to CKD was 4.8%. Of those achieving remission, 18% had a renal flare mainly within 4 years after remission. Pre-pubertal males achieved complete remission more frequently than other patients but often relapsed; pre-pubertal females were treated more aggressively. Cox-regression analysis did not find independent predictors of remission or relapse. CONCLUSIONS: The outcome of the patients with FHN we investigated was encouraging. Recurrences are limited to the first 4 years following diagnosis, allowing progressive withdrawal of immunosuppression in patients achieving remission. Evaluation of risk factors for adverse outcome is necessary especially in pre-pubertal children.

Chronic haemodialysis in small children: a retrospective study of the Italian Pediatric Dialysis Registry.

BACKGROUND: Chronic haemodialysis (HD) in small children has not been adequately investigated. METHODS: This was a retrospective investigation of the use of chronic HD in 21 children aged <2 years (n = 12 aged <1 year) who were registered in the Italian Pediatric Dialysis Registry. Data collected over a period of >10 years were analysed. RESULTS: The median age of the 21 children at start of HD was 11.4 [interquartile range (IQR) 6.2-14.6] months, and HD consisted mainly of haemodiafiltration for 3-4 h in ≥4 sessions/week. A total of 51 central venous catheters were placed, and the median survival of tunnelled and temporary lines was 349 and 31 days, respectively (p < 0.001). Eight children (38 %) showed evidence of central vein thrombosis. Although 19 % of patients received growth hormone and 63.6 % received enteral feeding, the weight and height of these patients remained suboptimal. During the HD period the haemoglobin level increased in all patients, but not to normal levels (from 8.5 to 9.6 g/dl) despite erythropoietin administration (503-600 U/kg/week). The hospitalisation rate was 1.94/patient-year. Seventeen patients underwent renal transplantation at a median age of 3.0 years. Four patients, all affected by severe comorbidities, died during follow-up (in 2 cases due to absence of a vascular access). The 5- and 10-year cumulative survival was 82.4 and 68.7 %, respectively. CONCLUSIONS: Extracorporeal dialysis is feasible in children aged <2 years, but comorbidities, vascular access, growth and anaemia remain major concerns.

An international consensus approach to the management of atypical hemolytic uremic syndrome in children.

Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver-kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.

Treatment of Congenital Thrombotic Thrombocytopenic Purpura With Eculizumab.

A 12-year-old boy was hospitalized for hemolytic anemia, thrombocytopenia, acute kidney injury, and generalized seizures. The childhood onset, severely decreased kidney function, absence of prodromal diarrhea, negative test results for Shiga-like toxin-producing Escherichia coli, elevated plasma levels of the terminal complement complex sC5b-9, and ex vivo testing in endothelial cells showing serum-induced complement activation were all consistent with a diagnosis of complement-mediated atypical hemolytic uremic syndrome. Before plasma ADAMTS13 (von Willebrand factor protease) activity results were available, the patient was treated with the anti-C5 monoclonal antibody eculizumab, and treatment was followed by prompt disease remission. However, results of ADAMT13 activity level tests and gene screening revealed a severe deficiency associated with 2 heterozygous mutations in the ADAMTS13 gene, fully consistent with a diagnosis of congenital thrombotic thrombocytopenic purpura. Screening for atypical hemolytic uremic syndrome-associated genes failed to show a mutation and an assay for plasma anti-factor H antibodies gave negative results both before and after eculizumab treatment initiation. The patient's clinical evolution suggests that complement activation plays a role in the pathogenesis of thrombotic thrombocytopenic purpura and provides unexpected new insights into the treatment of this life-threatening disease.

Short-term survival of hyperammonemic neonates treated with dialysis.

BACKGROUND: In severe neonatal hyperammonemia, extracorporeal dialysis (ECD) provides higher ammonium clearance than peritoneal dialysis (PD). However, there are limited outcome data in relation to dialysis modality. METHODS: Data from infants with hyperammonemia secondary to inborn errors of metabolism (IEM) treated with dialysis were collected in six Italian centers and retrospectively analyzed. RESULTS: Forty-five neonates born between 1990 and 2011 were enrolled in the study. Of these, 23 were treated with PD and 22 with ECD (14 with continuous venovenous hemodialysis [CVVHD], 5 with continuous arteriovenous hemodialysis [CAVHD], 3 with hemodialysis [HD]). Patients treated with PD experienced a shorter duration of predialysis coma, while those treated with HD had a shorter ammonium decay time compared with all the other patients (p < 0.05). No difference in ammonium reduction rate was observed between patients treated with PD, CAVHD or CVVHD. Carbamoyl phosphate synthetase deficiency (CPS) was significantly associated with increased risk of death (OR: 9.37 [1.52-57.6], p = 0.016). Predialysis ammonium levels were significantly associated with a composite end-point of death or neurological sequelae (adjusted OR: 1.13 [1.02-1.27] per 100 µmol/l, p = 0.026). No association was found between outcome and dialysis modality. CONCLUSIONS: In this study, a delayed ECD treatment was not superior to PD in improving the short-term outcome of neonates with hyperammonemia secondary to IEM.

MYO1E mutations and childhood familial focal segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis is a kidney disease that is manifested as the nephrotic syndrome. It is often resistant to glucocorticoid therapy and progresses to end-stage renal disease in 50 to 70% of patients. Genetic studies have shown that familial focal segmental glomerulosclerosis is a disease of the podocytes, which are major components of the glomerular filtration barrier. However, the molecular cause in over half the cases of primary focal segmental glomerulosclerosis is unknown, and effective treatments have been elusive. METHODS: We performed whole-genome linkage analysis followed by high-throughput sequencing of the positive-linkage area in a family with autosomal recessive focal segmental glomerulosclerosis (index family) and sequenced a newly discovered gene in 52 unrelated patients with focal segmental glomerulosclerosis. Immunohistochemical studies were performed on human kidney-biopsy specimens and cultured podocytes. Expression studies in vitro were performed to characterize the functional consequences of the mutations identified. RESULTS: We identified two mutations (A159P and Y695X) in MYO1E, which encodes a nonmuscle class I myosin, myosin 1E (Myo1E). The mutations in MYO1E segregated with focal segmental glomerulosclerosis in two independent pedigrees (the index family and Family 2). Patients were homozygous for the mutations and did not have a response to glucocorticoid therapy. Electron microscopy showed thickening and disorganization of the glomerular basement membrane. Normal expression of Myo1E was documented in control human kidney-biopsy specimens in vivo and in glomerular podocytes in vitro. Transfection studies revealed abnormal subcellular localization and function of the A159P-Myo1E mutant. The Y695X mutation causes loss of calmodulin binding and of the tail domains of Myo1E. CONCLUSIONS: MYO1E mutations are associated with childhood-onset, glucocorticoid-resistant focal segmental glomerulosclerosis. Our data provide evidence of a role of Myo1E in podocyte function and the consequent integrity of the glomerular filtration barrier.

An audit analysis of a guideline for the investigation and initial therapy of diarrhea negative (atypical) hemolytic uremic syndrome.

BACKGROUND: In 2009, the European Paediatric Study Group for Haemolytic Uraemic Syndrome (HUS) published a clinical practice guideline for the investigation and initial therapy of diarrhea-negative HUS (now more widely referred to as atypical HUS, aHUS). The therapeutic component of the guideline (comprising early, high-volume plasmapheresis) was derived from anecdotal evidence and expert consensus, and the authors committed to auditing outcome. METHODS: Questionnaires were distributed to pediatric nephrologists across Europe, North America, and the Middle East, who were asked to complete one questionnaire per patient episode of aHUS between July 1, 2009 and December 31, 2010. Comprehensive, anonymous demographic and clinical data were collected. RESULTS: Seventy-one children were reported with an episode of aHUS during the audit period. Six cases occurred on a background of influenza A H1N1 infection. Of 71 patients, 59 (83 %) received plasma therapy within the first 33 days, of whom ten received plasma infusion only. Complications of central venous catheters occurred in 16 out of 51 patients with a catheter in-situ (31 %). Median time to enter hematological remission was 11.5 days, and eight of 71 (11 %) patients did not enter hematological remission by day 33. Twelve patients (17 %) remained dialysis dependent at day 33. CONCLUSIONS: This audit provides a snapshot of the early outcome of a group of children with aHUS in the months prior to more widespread use of eculizumab.

Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis.

BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. METHODS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. RESULTS: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. CONCLUSIONS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

Lupus nephritis in children and adolescents: results of the Italian Collaborative Study.

BACKGROUND: Lupus nephritis (LN) strongly affects the outcome in children with systemic lupus erythematosus (SLE). Many patients, however, have renal disease at onset, but lack a sufficient number of criteria to be diagnosed as SLE and develop delayed symptoms over time (d-SLE). Data on the clinical course, long-term outcome and predictors of disease progression in children with LN are scant. METHODS: The Italian Collaborative Study included 161 paediatric patients with LN who were followed up for a mean of 96 months (range 6-296) in seven paediatric nephrology units. Cox-Mantel regression models were used to identify predictors of disease remission, relapse and progression. RESULTS: At 1 year, the proportion of patients in remission was 83.2% (partial) and 53.5% (complete). Renal flares occurred in >50% of patients within 10 years. The intensity of induction treatment correlated significantly with the achievement of remission, while d-SLE, class IV LN and younger age were associated with poor response to treatment and/or with progression to chronic renal failure. CONCLUSIONS: The current study provides outcome data on a large paediatric population with LN and underlines the importance of prescribing appropriate induction treatment to all children, regardless of the presence of enough SLE criteria, which may develop several years after the initial diagnosis.

Encapsulating peritoneal sclerosis in paediatric peritoneal dialysis patients: the experience of the Italian Registry of Pediatric Chronic Dialysis.

BACKGROUND: Paediatric literature about encapsulating peritoneal sclerosis (EPS) is limited and comes primarily from anecdotic experiences. In this study, we described the incidence and characteristics of EPS in a large paediatric chronic peritoneal dialysis (CPD) patient population. METHODS: We reviewed files of patients starting CPD at <16 years of age, recorded from January 1986 to December 2011 by the Italian Registry of Pediatric Chronic Dialysis (n = 712). Moreover, in December 2011, a survey was performed involving all the Italian Pediatric Nephrology Units to report such EPS cases that occurred after CPD withdrawal. RESULTS: Fourteen EPS cases were reported, resulting in a prevalence of 1.9%. The median age of EPS cases was 4.8 years (range 0.6-14.4) at the start of CPD and 14.3 years (6.5-26.8) at EPS diagnosis. Eleven EPS cases received CPD for longer than 5 years. At diagnosis, nine patients were still on CPD, two were on haemodialysis and three were transplanted. In eight patients, the primary renal disease was represented by glomerulopathy, mainly focal segmental glomerulosclerosis (n = 5). In the last 6 months prior to CPD discontinuation, 10 patients were treated with solutions containing more than 2.27% glucose. Peritonitis incidence was 1:26.8 CPD-months, similar to that calculated in children >12 months of age from the same registry (1:28.3 CPD-months). The mortality rate was 43%. A more aggressive course and an association with calcineurin inhibitors were observed in transplanted patients. CONCLUSIONS: Surveillance for EPS should be maintained in high-risk children who received long-term PD even after years from CPD withdrawal.

De Novo Large Deletions in the PHEX Gene Caused X-Linked Hypophosphataemic Rickets in Two Italian Female Infants Successfully Treated with Burosumab.

Pathogenic variants in the PHEX gene cause rare and severe X-linked dominant hypophosphataemia (XLH), a form of heritable hypophosphatemic rickets (HR) characterized by renal phosphate wasting and elevated fibroblast growth factor 23 (FGF23) levels. Burosumab, the approved human monoclonal anti-FGF23 antibody, is the treatment of choice for XLH. The genetic and phenotypic heterogeneity of HR often delays XLH diagnoses, with critical effects on disease course and therapy. We herein report the clinical and genetic features of two Italian female infants with sporadic HR who successfully responded to burosumab. Their diagnoses were based on clinical and laboratory findings and physical examinations. Next-generation sequencing (NGS) of the genes associated with inherited HR and multiple ligation probe amplification (MLPA) analysis of the PHEX and FGF23 genes were performed. While a conventional analysis of the NGS data did not reveal pathogenic or likely pathogenic small nucleotide variants (SNVs) in the known HR-related genes, a quantitative analysis identified two different heterozygous de novo large intragenic deletions in PHEX, and this was confirmed by MLPA. Our molecular data indicated that deletions in the PHEX gene can be the cause of a significant fraction of XLH; hence, their presence should be evaluated in SNV-negative female patients. Our patients successfully responded to burosumab, demonstrating the efficacy of this drug in the treatment of XLH. In conclusion, the execution of a phenotype-oriented genetic test, guided by known types of variants, including the rarest ones, was crucial to reach the definitive diagnoses and ensure our patients of long-term therapy administration.

Peritoneal dialysis in infants: the experience of the Italian Registry of Paediatric Chronic Dialysis.

BACKGROUND: Although chronic peritoneal dialysis (CPD) is considered the replacement therapy of choice for infants with end-stage renal failure, many questions persist about treatment risks and outcomes. METHODS: We present data on 84 infants who started CPD at <1 year of age; these patients represent 12% of the total population of the Italian Registry of Paediatric Chronic Dialysis. We analysed patient records from all children consecutively treated with CPD between 1995 and 2007 in Italy. Growth data analysis was performed only in infants with complete auxological parameters at 0, 6 and 12 months of follow-up. RESULTS: Median age at the start of CPD was 6.9 months, weight was 6.1 kg and length 63.6 cm. In one-half of the study population diagnosis leading to renal failure was congenital nephrouropathy. Twenty-eight per cent of the children had at least one pre-existing comorbidity. The mean height standard deviation score was -1.65 at the start of CPD, -1.82 after 12 months and -1.53 after 24 months. Catch-up growth was documented in 50% of patients during dialysis. A positive correlation was observed between longitudinal growth and both exchange volume (R(2) = 0.36) and dialysis session length (R(2) = 0.35), while a negative association was found with the number of peritonitis cases (P = 0.003). Peritonitis incidence was 1:20.7 episode:CPD-months (1:28.3 in the older children from the same registry) and was significantly higher in children with oligoanuria (1:15.5 episode:CPD-months) compared to infants with residual renal function (1:37.4 episode:CPD-months). Catheter survival rate was 70% at 12 months and 51% at 24 months. Catheter-related complications were similar in infants and older children (1:20.5 versus 1:19.8 episode:CPD-months), while clinical complications were more frequent in children under 1 year of age (1:18.3 versus 1:25.2 episode:CPD-months; P < 0.05). During the follow-up period, 33 patients were transplanted (39.3%), 18 were shifted to haemodialysis (21.4%) and 8 died (9.5%). The mortality rate was 4-fold greater than in older children (2.3%). CONCLUSIONS: Our data confirm that infants on CPD represent a high-risk group; however, our experience demonstrated that growth was acceptable and a large portion was successfully transplanted. Increased efforts should be aimed at optimizing dialysis efficiency and preventing peritonitis. The higher mortality rate in infants was largely caused by comorbidities.

Pediatric Minimal Change Disease and AKI following the Pfizer-BioNTech COVID-19 Vaccine: causal or incidental correlation?

The global coronavirus 2019 (COVID-19) pandemic required vaccination even in children to reduce infection. We report on the development of acute kidney injury (AKI) and minimal change disease (MCD) nephrotic syndrome (NS), shortly after the first injection BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). A 12-year-old previously healthy boy was referred to our hospital with complaints of peripheral edema and nephrotic range proteinuria. Nine days earlier he had received his first injection BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). Seven days after injection, he developed leg edema, which rapidly progressed to anasarca with significant weight gain. On admission, serum creatinine was 1.3 mg/dL and 24-hour urinary protein excretion was 4 grams with fluid overload. As kidney function continued to decline over the next days, empirical steroid treatment and renal replacement therapy with ultrafiltration were started and kidney biopsy was performed. Seven days after steroid therapy, kidney function began to improve, gradually returning to normal. The association of MCD, nephrotic syndrome and AKI hasn't been previously described following the Pfizer-BioNTech COVID-19 vaccine in pediatric population, but this triad has been reported in adults. We need further similar case reports to establish the real incidence of this possible vaccine side effect.