Nadir Creatinine in Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): A Single-Center Experience.

BACKGROUND/OBJECTIVES: Congenital anomalies of the kidney and urinary tract (CAKUT) are the main cause of chronic kidney disease (CKD) requiring renal replacement therapy (RRT) in children, being the leading cause (50-70%) of end-stage renal disease (ESRD) in children and young adults. Our study aimed to assess the natural evolution of various antenatally diagnosed renal malformations and to identify potential prognostic factors to guide the therapeutic management of patients with CAKUT. METHODS: We conducted a retrospective study on 205 children with CAKUT. For each patient, analyzing their medical records, we established the nadir value of serum creatinine, defined as the lowest creatinine level during the first year of life. We assessed the value of nadir creatinine as a prognostic marker in patients with CAKUT, and using an ROC curve, we also determined a threshold value of nadir creatinine that predicted progression to ESRD. RESULTS: The male-to-female ratio was 2.8 to 1. The mean gestational age at detection was 29.85 weeks (±6.71). A total of 36 patients (17.6%) had impaired renal function, of which 8 (3.9% of the total) progressed to ESRD. The mean nadir creatinine in patients with ESRD was 1.39 mg/dL. A nadir creatinine cut-off of 0.98 mg/dL had high sensitivity and specificity in identifying patients with progression to ESRD, with an AUC of 0.95 and a 95% confidence interval between 0.86 and 1.05 mg/dL. CONCLUSIONS: Our results support the value of nadir creatinine in predicting progression to ESRD, consistent with previously published data.

The Utility of Noninvasive Urinary Biomarkers for the Evaluation of Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021-September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.

An Integrated Approach Using HLAMatchmaker and Pirche II for Epitopic Matching in Pediatric Kidney Transplant-A Romanian Single-Center Study.

(1) Background: Renal transplantation (KT) is the most efficient treatment for chronic kidney disease among pediatric patients. Antigenic matching and epitopic load should be the main criteria for choosing a renal graft in pediatric transplantation. Our study aims to compare the integration of new histocompatibility predictive algorithms with classical human leukocyte antigen (HLA) matching regarding different types of pediatric renal transplants. (2) Methods: We categorized our cohort of pediatric patients depending on their risk level, type of donor and type of transplantation, delving into discussions surrounding their mismatching values in relation to both the human leukocyte antigen Matchmaker software (versions 4.0. and 3.1.) and the most recent version of the predicted indirectly identifiable HLA epitopes (PIRCHE) II score. (3) Results: We determined that the higher the antigen mismatch, the higher the epitopic load for both algorithms. The HLAMatchmaker algorithm reveals a noticeable difference in eplet load between living and deceased donors, whereas PIRCHE II does not show the same distinction. Dialysis recipients have a higher count of eplet mismatches, which demonstrates a significant difference according to the transplantation type. Our results are similar to those of four similar studies available in the current literature. (4) Conclusions: We suggest that an integrated data approach employing PIRCHE II and HLAMatchmaker algorithms better predicts histocompatibility in KT than classical HLA matching.

Acute liver failure secondary to toxic exposure in children.

INTRODUCTION: Acute liver failure (ALF) is a syndrome defined by jaundice, coagulopathy (INR > 1.5) and hepatic encephalopathy in patients with no evidence of prior liver disease. Toxins and drugs are a frequent cause of ALF in children. MATERIAL AND METHODS: The aim of our study was to establish the causes of toxic ALF in children followed up in our hospital in the period of January 2000 to August 2018. We retrospectively studied all hospital records of patients who developed ALF after mushroom/drug exposure and had been admitted to our hospital, the main pediatric toxicology center in north-western Romania. RESULTS: In the last 18 years, 123 patients were admitted to our clinic with toxic ALF (89 patients secondary to mushroom ingestion and 34 patients after drug exposure). In the 2000-2012 period accidental mushroom poisoning was the leading cause of toxic ALF. Unfortunately, during the last years, voluntary drug ingestions have increased dramatically. The most commonly incriminated drug was acetaminophen (52.94%). CONCLUSIONS: ALF in mushroom poisoning is associated with a high mortality in children, despite optimal medical therapy. This etiology was one of the most important causes of death in our cohort. The difficulty in accessing emergency liver transplantation is an obstacle common to many Eastern European pediatric centers. Fortunately, in the last 5 years the incidence of mushroom intoxications has decreased in our area. It is worrying that over the last few years there has been an increased incidence of toxic ALF after drug exposure (for suicidal purposes or due to lenient regulations for prescribing hepatotoxic medications).

The Role of Predictive Models in the Assessment of the Poor Outcomes in Pediatric Acute Liver Failure.

OBJECTIVES: In children, acute liver failure (ALF) is a severe condition with high mortality. As some patients need liver transplantation (LT), it is essential to predict the fatal evolution and to refer them early for LT if needed. Our study aimed to evaluate the prognostic criteria and scores for assessing the outcome in children with ALF. METHODS: Data of 161 children with ALF (54.66% female, mean age 7.66 ± 6.18 years) were analyzed based on final evolution (32.91% with fatal evolution or LT) and etiology. We calculated on the first day of hospitalization the PELD score (109 children), MELD, and MELD-Na score (52 children), and King's College Criteria (KCC) for all patients. The Nazer prognostic index and Wilson index for predicting mortality were calculated for nine patients with ALF in Wilson's disease (WD). RESULTS: PELD, MELD, and MELD-Na scores were significantly higher in patients with fatal evolution (21.04 ± 13.28 vs. 13.99 ± 10.07, p = 0.0023; 36.20 ± 19.51 vs. 20.08 ± 8.57, p < 0.0001; and 33.07 ± 8.29 vs. 20.08 ± 8.47, p < 0.0001, respectively). Moreover, age, bilirubin, albumin, INR, and hemoglobin significantly differed in children with fatal evolution. Function to etiology, PELD, MELD, MELD-Na, and KCC accurately predicted fatal evolution in toxic ALF (25.33 vs. 9.90, p = 0.0032; 37.29 vs. 18.79, p < 0.0001; 34.29 vs. 19.24, p = 0.0002, respectively; with positive predicting value 100%, negative predicting value 88.52%, and accuracy 89.23% for King's College criteria). The Wilson index for predicting mortality had an excellent predictive strength (100% sensibility and specificity), better than the Nazer prognostic index. CONCLUSIONS: Prognostic scores may be used to predict the fatal evolution of ALF in children in correlation with other parameters or criteria. Early estimation of the outcome of ALF is essential, mainly in countries where emergency LT is problematic, as the transfer to a specialized center could be delayed, affecting survival chances.

Case Report: Potocki-Lupski Syndrome in Five Siblings.

Potocki-Lupski syndrome (PTLS) is a rare developmental disorder resulting from the partial duplication of the short arm of chromosome 17. Affected children may have hypotonia, facial dysmorphism, or neurological abnormalities. PTLS is also frequently associated with failure to thrive due to swallowing difficulties or growth hormone deficiency. We report the first Romanian family (a mother and her five children) diagnosed with PTLS (17p11.2 microduplication). Fortunately, they present a less severe form of the disease. The neurological manifestations (speech delay, mild intellectual disability) are associated with craniofacial dysmorphism (microcephaly, micrognathia, triangular face, broad forehead, long chin, prominent ears, dolichocephaly, down slanting palpebral fissures). The diagnostic was established using a multiplex ligation-dependent probe amplification technique (MLPA) test, which detected the duplication of three regions of the 17p11.2 chromosome (RAI1, DRC3-6, LLGL1-4RA). Children with PTLS have specific phenotypes (craniofacial dysmorphism or neurological manifestations), which must draw the pediatrician's attention to a possible genetic condition. However, every child with this disease is unique and may have a different clinical presentation. A multi-disciplinary team is needed for the management of these patients. The parent's counseling and genetic advice are essential for a family with children with PTLS.

Etiology and Outcome of Acute Liver Failure in Children-The Experience of a Single Tertiary Care Hospital from Romania.

BACKGROUND: Acute liver failure (ALF) is a rare disease, associated with high mortality, despite optimal medical therapy without emergency liver transplantation. Knowing the possible cause of ALF plays a vital role in the management, as the child could benefit from effective specific therapies in emergencies. METHODS: We have analyzed the etiology and outcome of ALF in children followed-up in a tertiary care hospital between January 2012-December 2018. The patients were grouped into different age categories: neonates (0-1 month), infants (1-12 months), children (1-14 years), and teenagers (14-18 years). RESULTS: 97 children (46 males, 47.42%, the mean age of 7.66 ± 8.18 years) were admitted with ALF. The most important causes of ALF were in neonates and infants, infections (72.72%), and metabolic disorders (43.47%), in children and adolescents were the toxic causes (60% and 79.41%). The mortality rate was 31.95% (31 patients), mainly in ALF due to infections or metabolic disorders. CONCLUSIONS: In neonates and infants, the main causes of ALF were infections and metabolic diseases, while in older children and teenagers, were toxin-induced liver injuries. The mortality among neonates and infants was significantly higher than in other ages. Early recognition and immediate therapeutic intervention could improve the outcome of these patients.

Vitamin D-Binding Protein (Gc-Globulin) in Acute Liver Failure in Children.

This study aimed to analyse vitamin d-binding protein (Gc-globulin) serum levels in acute liver failure (ALF) in children in relation to disease outcomes and correlations with other known markers used to evaluate the severity of ALF. Our study included 34 children (mean age 4.87 ± 5.30 years) with ALF of different causes (metabolic, 26.47%; autoimmune, 23.53%; toxic, 20.59%; infection, 17.65%; unknown, 11.76%) and 30 children without any liver injury (mean age 6.11 ± 4.26 years). The outcome was poor in 14 patients (41.18%), including one child with liver transplantation (2.94%). Serum Gc-globulin levels were significantly lower in ALF patients compared to the control group (151.57 ± 171.8 mg/L vs. 498.63 ± 252.50 mg/L; p < 0.000001), with an optimum cut-off of 163.5 mg/L (Area Under the Curve, AUC, 0.8921; sensitivity, 76.50%; specificity, 100%). Levels were also lower in patients with poor outcomes compared to survivors (59.34 ± 33.73 mg/L vs. 216.12 ± 199.69 mg/L; p < 0.0001), with an optimum cut-off 115 mg/L (AUC, 0.7642; sensitivity, 100%; specificity, 50%). Gc-globulin serum levels were variable according to ALF aetiology, i.e., lower in metabolic, infectious, or unknown causes compared to autoimmune and toxic causes. Gc-globulin serum levels were decreased in children with ALF and lower in those with poor outcomes compared with survivors. Gc-globulin serum levels were correlated with other known parameters used to evaluate the severity of ALF and could help to identify patients at high risk for poor outcomes.

Long term follow-up in a patient with prune-belly syndrome - a care compliant case report.

RATIONALE: Malformative uropathies represent a major cause of Chronic Kidney Disease (CKD) in children. Genitourinary system is the most frequent and sever affected in Prune-Belly syndrome cases. That is why the findings of early diagnosis and vigilant monitoring for these situations remain a major challenge for the medical team. PATIENT CONCERNS: We present the clinical course of a 10 years old child with diagnosis of Prune-Belly syndrome. A urinary tract abnormality was suspected starting 25 weeks of gestation, when a routine ultrasound showed oligohydramnios, increased size urinary bladder, bilateral hydronephrosis and megaureters, thin abdominal wall. DIAGNOSIS: Prenatal suspicion of Prune-Belly syndrome plays a deciding role in renal disease progression. A detailed clinical exam at birth established the diagnosis of Prune-Belly syndrome. Renal ultrasound confirmed bilateral grade III hydronephrosis and megaureters, with empty bladder, suggesting an obstruction at this level. A persistent urachus was confirmed by catheterization. Later it was used for imaging study that showed bilateral high grade reflux. INTERVENTIONS: The main goal of any treatment is to preserve kidney function. Treatment options depend on the clinical picture. The pregnancy was closely monitorized, but fetal distress appeared so early labor was induced at 32 weeks. At beginning a temporary catheter was placed into the urachus which expressed urine. The urachus drain was left in place until the age of 6 weeks, when a bilateral ureterostomy was performed. Skeletal and genital malformations were present too; the child has undergone several surgeries to solve these abnormalities. OUTCOMES: At the age of 10 years, he is a well-adapted child. He has had fewer than 3 urinary tract infections per year. Long term follow-up showed a relatively slow decline in the estimated Glomerular Filtration Rate in our child (62 ml/1.73m/min). LESSONS: This case suggests that induced early labor could prove beneficial for early upper urinary tract decompression through earlier access to surgery. This is an option especially in situations or region where vesicoureteric or vesicoamniotic shunt placement is not available.