Single-Center Experience of Pediatric Cystic Kidney Disease and Literature Review.

INTRODUCTION: Pediatric cystic kidney disease (CyKD) includes conditions characterized by renal cysts. Despite extensive research in this field, there are no reliable genetics or other biomarkers to estimate the phenotypic consequences. Therefore, CyKD in children heavily relies on clinical and diagnostic testing to predict the long-term outcomes. AIM: A retrospective study aimed to provide a concise overview of this condition and analyze real-life data from a single-center pediatric CyKD cohort followed during a 12-year period. METHODS AND MATERIALS: Medical records were reviewed for extensive clinical, laboratory, and radiological data, treatment approaches, and long-term outcomes. RESULTS: During the study period, 112 patients received a diagnosis of pediatric CyKD. Male patients were more involved than female (1:0.93). Fifty-six patients had a multicystic dysplastic kidney; twenty-one of them had an autosomal dominant disorder; fifteen had an isolated renal cyst; ten had been diagnosed with autosomal recessive polycystic kidney disease; three had the tuberous sclerosis complex; two patients each had Bardet-Biedl, Joubert syndrome, and nephronophthisis; and one had been diagnosed with the trisomy 13 condition. Genetic testing was performed in 17.9% of the patients, revealing disease-causing mutations in three-quarters (75.0%) of the tested patients. The most commonly presenting symptoms were abdominal distension (21.4%), abdominal pain (15.2%), and oligohydramnios (12.5%). Recurrent urinary tract infections (UTI) were documented in one-quarter of the patients, while 20.5% of them developed hypertension during the long-term follow-up. Antibiotic prophylaxis and antihypertensive treatment were the most employed therapeutic modalities. Seventeen patients progressed to chronic kidney disease (CKD), with thirteen of them eventually reaching end-stage renal disease (ESRD). The time from the initial detection of cysts on an ultrasound (US) to the onset of CKD across the entire cohort was 59.0 (7.0-31124.0) months, whereas the duration from the detection of cysts on an US to the onset of ESRD across the whole cohort was 127.0 (33.0-141.0) months. The median follow-up duration in the cohort was 3.0 (1.0-7.0) years. The patients who progressed to ESRD had clinical symptoms at the time of initial clinical presentation. CONCLUSION: This study is the first large cohort of patients reported from Croatia. The most common CyKD was the multicystic dysplastic kidney disease. The most common clinical presentation was abdominal distention, abdominal pain, and oliguria. The most common long-term complications were recurrent UTIs, hypertension, CKD, and ESRD.

Determination of cystatin C reference interval for children in Croatia.

Introduction: Cystatin C is considered an early marker of kidney damage. The aim was to determine the reference interval in children since this information was not available from the test manufacturer. Materials and methods: Included were children aged 0 to 18 years undergoing routine check without history of any renal disease. Cystatin C was measured by the immunoturbidimetric method, and creatinine by the enzymatic method on a Cobas c501 analyzer (Roche Diagnostics, Manheim, Germany). Reference intervals were determined according to the CLSI C28-A3 guidelines using a robust method and a nonparametric percentile method, depending on the sample size. The Schwartz's formula was applied to estimate glomerular filtration (eGFR) from cystatin C. Results: The cystatin C reference interval for children aged 1-18 years (N = 204, median 8 years) was from 0.61 mg/L (90% CI: 0.53 to 0.64) to 1.08 mg/L (90% CI: 1.07 to 1.14). Differences according to sex were not found. For children aged 0-1 years (N = 29, median 5 months), the reference interval was from 0.60 mg/L (90% CI: 0.48 to 0.72) to 1.49 mg/L (90% CI: 1.36 to 1.61). The sample size was too small to test the difference according to sex. The eGFR was 76 (70-88) mL/min/1.73m2 for males and 83 (74-92) mL/min/1.73m2 for females. Conclusion: The cystatin C reference intervals for Croatian pediatric population according to age were determined. The cystatin C concentrations in children reach adulthood values after the first year. The cystatin C Schwartz's formula is applicable for eGFR calculation in children.

Early biochemical markers in the assessment of acute kidney injury in children after cardiac surgery.

Our aim was to evaluate biochemical markers in plasma (NGAL, CysC) and urine (NGAL, KIM-1) in children's early onset of acute kidney injury after congenital heart defect surgery using cardiopulmonary bypass. This study prospectively included 100 children with congenital heart defects who developed AKI. Patients with acute kidney injury had significantly higher CysC levels 6 and 12 h after cardiac surgery and plasma NGAL levels 2 and 6 h after cardiac surgery. The best predictive properties for the development of acute kidney injury are the combination (+CysCpl or +NGALu) after 12 h and a combination (+CysCpl and +NGALu) 6 and 24 h after cardiac surgery. We showed that plasma CysC and urinary NGAL could reliably predict the development of acute kidney injury. Measurement of early biochemical markers in plasma and urine, individually and combination, may predict the development of cardiac surgery-associated acute kidney injury in children.

Characteristics, Risk Factors and Predictors for Candidemia in the Pediatric Intensive Care Unit at the University Hospital Centre Zagreb in Croatia: A 9-Year Retrospective Study.

BACKGROUND: Candidemia is one of the leading causes of bloodstream infections in the pediatric intensive care unit (PICU). The aim of this study was to define characteristics and risk factors for candidemia in the PICU setting and propose a predictive model to identify the patients at risk. METHODS: This was a retrospective matched case-control study in the PICU during a 9-year period. Patients with candidemia were studied and matched with control patients without candidemia. Univariate analysis was performed for potential risk factors and multivariate analysis was conducted to determine the prediction score for candidemia. RESULTS: Forty-two cases of candidemia were matched with 84 control patients. Candida parapsilosis was the most common (71.4%) species. Risk factors independently associated with candidemia were: the use of >2 antibiotics in a maximum period of 4 weeks before the candidemia (odds ratio [OR]: 10.59; 95% confidence interval [CI]: 2.05-54.83), a previous bacterial infection in a maximum period of 4 weeks before the candidemia (OR: 5.56; 95% CI: 1.44-21.5) and the duration of PICU stay of >10 days (OR: 4.22; 95% CI: 1.02-17.41). The proposed predictive scoring system has a sensitivity of 95.24%, specificity of 76.12%, OR 64.0, 95% CI 14.2-288.6, the positive predictive value of 66.67% and the negative predictive value of 96.97%. CONCLUSIONS: Previously reported risk factors for candidemia have been confirmed and some new have been detected. The presented scoring system can help identify patients who would benefit from prophylactic antifungal therapy.

Rescue extracorporeal cardiopulmonary resuscitation in pediatric patients: a nine-year single-center experience in Zagreb, Croatia.

AIM: To investigate the risk factors and the outcomes of extracorporeal membrane oxygenation (ECMO) in pediatric patients treated at the University Hospital Center Zagreb, the largest center in Croatia providing pediatric ECMO. METHODS: This retrospective study enrolled all the pediatric patients who required E-CPR from 2011 to 2019. Demographic data, cardiac anatomy, ECMO indications, ECMO complications, and neurodevelopmental status at hospital discharge were analyzed. RESULTS: In the investigated period, E-CPR was used in 16 children, and the overall survival rate was 37.5%. Six patients were in the neonatal age group, 5 in the infant group, and 5 in the "older" group. There was no significant difference between the sexes. Four patients had an out-of-hospital arrest and 12 had an in-hospital arrest. Twelve out of 16 patients experienced renal failure and needed hemodialysis, with 4 out of 6 patients in the survivor group and 8 out of 10 in the non-survivor group. Survivors and non-survivors did not differ in E-CPR duration time, lactate levels before ECMO, time for lactate normalization, and pH levels before and after the start of ECMO. CONCLUSION: The similarity of our results to those obtained by other studies indicates that the ECMO program in our hospital should be maintained and improved.

ATP synthase deficiency due to m.8528T>C mutation - a novel cause of severe neonatal hyperammonemia requiring hemodialysis.

OBJECTIVES: Hyperammonemia in a newborn is a serious condition, which requires prompt intervention as it can lead to severe neurological impairment and death if left untreated. The most common causes of hyperammonemia in a newborn are acute liver failure and inherited metabolic disorders. Several mitochondrial disorders have been described as a cause of severe neonatal hyperammonemia. CASE PRESENTATION: Here we describe a new case of adenosine-triphosphate (ATP) synthase deficiency due to m.8528T>C mutation as a novel cause of severe neonatal hyperammonemia. So far six patients with this mutation have been described but none of them was reported to need hemodialysis in the first days of life. CONCLUSION: This broadens the so far known differential diagnosis of severe neonatal hyperammonemia requiring hemodialysis.

A case report of a child with sepsis induced multiorgan failure and massive complement consumption treated with a short course of Eculizumab: A case of crosstalk between coagulation and complement?

RATIONALE: This article describes a child with a life-threatening multiorgan failure with disseminated intravascular coagulation (DIC) and massive complement consumption. To our knowledge this therapeutic approach was for the first time effectively applied in a pediatric patient. PATIENT CONCERNS: A 14-month-old boy was presented with a severe, rapidly progressing, life-threatening disease because of sudden onset of fever, hemathemesis, hematuria, and bloody diarrhoea alongside fast spreading hematomas and general corporeal edema. DIAGNOSIS: The most plausible diagnosis in our patient is Clostridium difficile sepsis-induced thrombotic microangiopathy alongside with DIC and consumption coagulopathy. The diagnosis was confirmed by positive C difficile bacteria strain in coproculture, clinical, and laboratory tests affirming DIC and global complement activation and consumption. INTERVENTIONS: The patient was treated with antibiotics (Metronidazole, Vancomycin), plasmapheresis, dialysis, methylprednisolone, mycophenolate mofetil, and Eculizumab. OUTCOMES: The child is in fair overall condition in a 2 year follow-up with no complications save chronic renal failure. LESSONS: In rare cases of sepsis with massive complement consumption, a case-sensitive Eculizumab therapy may be at least considered after the resolution of life-threatening multiorgan failure. The application of this drug can be performed only after sepsis induced disease is put under control. A fast withdrawal of Eculizumab after control of massive complement consumption is recommended to prevent triggering of second sepsis reactivation.

ACUTE RESPIRATORY DISTRESS SYNDROME IN A FOUR-YEAR-OLD BOY WITH DIABETIC KETOACIDOSIS - CASE REPORT.

- Among many disease states as known initiators of acute respiratory distress syndrome (ARDS), diabetic ketoacidosis (DKA) is the rarest one. We present a 4-year-old boy with DKA as the first manifestation of insulin-dependent diabetes mellitus who developed ARDS, required tracheal intubation and mechanical ventilation, and survived without significant sequels. To improve survival of patients with ARDS as a complication of DKA, physicians should be aware of this rare pulmonary complication and its appropriate management.

Renal thromboembolism during treatment with recombinant activated factor VII (rFVIIa) in a child with hemophilia B with factor IX inhibitors.

BACKGROUND: Serious thromboembolic events connected with rFVIIa therapy in hemophilia patients are rare. Only three cases are reported in children, all of them with hemophilia A. CASE PRESENTATION: We present unique case of patient with hemophilia B and high titer inhibitors to coagulation FIX, who developed severe renal damage due to thromboembolic event during rFVIIa therapy, associated with unsuspected renovascular anomalies. CONCLUSION: Caution is necessary if hematuria B requires administration of rFVIIa. US color doppler renal imaging before and after drug administration should be sufficient as an early warning.

[Vitamin B12 deficiency in children--underestimated danger in the light of new knowledge]. / Manjak vitamina B12 u djece --podcijenjena opasnost u svjetlu novih spoznaja.

Vitamin B12 (cobalamin) has two active forms, adenosylcobalamin and methylcobalamin which have a key role in two important metabolic pathways in humans and their deficiency is responsible for clinical problems. Cobalamin is essential during whole life, but its sufficient amount is extra important in fetal and neonatal period, when it is essential for normal child growth and development as well as for normal development of the central nervous system. Because of very complex transport and metabolism, its deficiency can be manifested in numerous congenital and acquired disorders. Vitamin B12 deficiency mostly has non-specific clinical features, it carries a great risk of permanent consequences, but most frequently it is easily curable if diagnosed on time. In Croatia cobalamin deficiency in children has been diagnosed too rarely. Accordingly, the aim of this paper is to point to the recently gained knowledge on cobalamin metabolism, present typical case reports and to provide guidelines for rapid and proper diagnostic and therapeutic approach.

Recombinant activated factor VII controls chemotherapy-related hemorrhage in patients with solid intra-abdominal tumors: a report of three pediatric cases.

Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) is used predominantly for the treatment of bleeding in patients with hemophilia and inhibitors, and in patients with traumatic injury. There are also literature reports of its use in chemotherapy-related bleeding in leukemia patients and intra- or postoperative bleeding in patients with solid tumors. We describe three pediatric patients where rFVIIa was successfully used to manage bleeding following the failure of conventional hemostatic treatments during chemotherapy for intra-abdominal tumors (hepatoblastoma, rhabdomyosarcoma and non-classified malignant sarcoma). Recombinant FVIIa proved effective and maintained hemostasis in two of three cases, with no evidence for toxic or adverse events in any of the treated patients.

The life-threatening hemodialysis catheter heparin lock caused bleeding in a child after peritoneal catheter removal.

Hemodialysis catheter patency is regularly maintained by high-concentration heparin filling, according to manufacturer's recommendation. Surprisingly, there are only few reports on serious bleeding complications in children on dialysis. A case of serious, life-threatening hemorrhage in a child after tunneled peritoneal catheter removal because of hemodialysis catheter heparin lock flushing is described. Discussion of the literature data is presented. Further investigations are needed to develop the guidelines for pediatric dialysis catheter care, including the optimal concentration for heparin lock as the possible heparin alternatives, but until that moment, previously suggested guidelines to prevent hemorrhagic complications in dialyzed children should be emphasized.

Fatal infant nasal seawater spray instillation.

UNLABELLED: The use of seawater nasal spray is considered safe and sold as a non-prescription medicine. However, it is well known that nasal manipulations can provoke vagal reaction leading to acute life-threatening events. A case of fatal seawater nasal spray application in an infant is presented. CONCLUSION: We do not consider the use of seawater nasal spray to be absolutely safe, especially among infants with disordered autonomic function.

Internal quality audit and quality standards as a method of quality improvement at the Department of Ophthalmology, University Hospital.

Quality assessment of clinical health care with the programme of quality standard is a method of health management, through which better efficiency and safety of health outcomes can be achieved. In the period from 2002 to 2004, a pilot program of quality has been carried out on the Department of Ophthalmology, University Hospital Center in Zagreb. Seven internal audit teams of hospital commission and teams of hospital departments were evaluating introducing practice for quality standards every three months. In the period of two years improvement in all standards of quality has been noticed (expressed in percent of progress towards the ideal result of 100%): personnel 20%, patient rights 15%, medical equipment 40%, quality of emergency service 60%, implementation of clinical guidelines and criteria for elective admission 55%, quality of risk prevention 70%, quality of medical records 60%. The two-years-improvement dynamics of about 46%, first year 24%.