Acute kidney injury in congenital cardiac surgery: Pediatric risk-injury-failure-loss-end-stage renal disease and Acute Kidney Injury Network.

BACKGROUND: Acute kidney injury (AKI) is associated with an increased risk of mortality, especially in pediatric intensive care units. The aim of this study was to determine the risk factors of AKI in children undergoing cardiac surgery for congenital heart disease and to compare two different classification systems: pediatric risk-injury-failure-loss-end-stage renal disease (pRIFLE) and Acute Kidney Injury Network (AKIN). METHODS: We retrospectively analyzed 145 patients undergoing pediatric congenital heart surgery who were between 1 month and 18 years of years, and treated at a cardiovascular surgery department from January 2009 to October 2011. RESULTS: One hundred and thirty-seven patients (mean age, 36.6 ± 43.3 months) were enrolled: 84 (61.3%) developed AKI according to the pRIFLE criteria (25.5%, risk; 20.4%, injury; 15.3%, failure); and 65 patients (47.4%) developed AKI according to the AKIN criteria (15.3%, stage I; 18.2%, stage II; and 13.9%, stage III). Children younger than 11 months were more likely to develop AKI (P < 0.005). Longer cardiopulmonary bypass time was associated with an increased risk of AKI (P < 0.05). pRIFLE identified AKI more frequently than AKIN (P < 0.0005). pRIFLE may help in the early identification of patient at risk for AKI and seems to be more sensitive in pediatric patients (P < 0.05). Any degree of AKI in both classifications was associated with increased mortality (pRIFLE: OR, 15.1; AKIN: OR, 11.2; P = 0.007). CONCLUSION: pRIFLE identified AKI more frequently than the AKIN criteria. pRIFLE identified patients at risk for AKI earlier, and was more sensitive in pediatric patients. Any degree of AKI in both classifications was associated with increased mortality. Both sets of criteria had the same association with mortality.

LRIG2 mutations cause urofacial syndrome.

Urofacial syndrome (UFS) (or Ochoa syndrome) is an autosomal-recessive disease characterized by congenital urinary bladder dysfunction, associated with a significant risk of kidney failure, and an abnormal facial expression upon smiling, laughing, and crying. We report that a subset of UFS-affected individuals have biallelic mutations in LRIG2, encoding leucine-rich repeats and immunoglobulin-like domains 2, a protein implicated in neural cell signaling and tumorigenesis. Importantly, we have demonstrated that rare variants in LRIG2 might be relevant to nonsyndromic bladder disease. We have previously shown that UFS is also caused by mutations in HPSE2, encoding heparanase-2. LRIG2 and heparanase-2 were immunodetected in nerve fascicles growing between muscle bundles within the human fetal bladder, directly implicating both molecules in neural development in the lower urinary tract.

Hypertension in children after renal transplantation.

BACKGROUND: Hypertension (HT) is a common and serious complication following renal transplantation in children, and an important risk factor for cardiovascular morbidity and mortality. This study evaluated the clinical characteristics of HT in children after renal transplantation. METHODS: Twenty-four children who were followed up at least 6 months after renal transplantation were enrolled in the study. From the clinical records, demographic and laboratory data, casual blood pressure (BP) measurement, ambulatory BP monitoring (ABPM), medication, and left ventricular mass index (LVMI) at echocardiogram were documented. RESULTS: Mean age at time of transplantation was 12.6 ± 3.0 years and mean follow-up period was 19.6 ± 15.8 months. HT was detected in 21 children (87.5%) after renal transplantation. Twelve patients (50%) had HT both before and after transplantation and nine (38%) had HT only after transplantation. HT developed in 67% within the first week and in 95% within the first month. All hypertensive children had night-time HT and no child had isolated daytime HT. The efficacy of HT control was 42%. Median LVMI in patients with HT after renal transplantation was 42.3 g/m(2.7). CONCLUSIONS: Severe HT, an important complication, was frequently seen in the early period after renal transplantation. Predominance of nocturnal HT and the lack of isolated daytime HT after transplantation underline the importance of ABPM. ABPM should be performed regularly in the first year after transplantation, not only for diagnosis but also for evaluation of HT control.

Mutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia.

KBG syndrome is characterized by intellectual disability associated with macrodontia of the upper central incisors as well as distinct craniofacial findings, short stature, and skeletal anomalies. Although believed to be genetic in origin, the specific underlying defect is unknown. Through whole-exome sequencing, we identified deleterious heterozygous mutations in ANKRD11 encoding ankyrin repeat domain 11, also known as ankyrin repeat-containing cofactor 1. A splice-site mutation, c.7570-1G>C (p.Glu2524_Lys2525del), cosegregated with the disease in a family with three affected members, whereas in a simplex case a de novo truncating mutation, c.2305delT (p.Ser769GlnfsX8), was detected. Sanger sequencing revealed additional de novo truncating ANKRD11 mutations in three other simplex cases. ANKRD11 is known to interact with nuclear receptor complexes to modify transcriptional activation. We demonstrated that ANKRD11 localizes mainly to the nuclei of neurons and accumulates in discrete inclusions when neurons are depolarized, suggesting that it plays a role in neural plasticity. Our results demonstrate that mutations in ANKRD11 cause KBG syndrome and outline a fundamental role of ANKRD11 in craniofacial, dental, skeletal, and central nervous system development and function.

Lower urinary tract dysfunction is frequently seen in urinary tract infections in children and is often associated with reduced quality of life.

AIM: Previous studies suggest that 6-46% of children suffer from lower urinary tract dysfunction (LUTD). This study evaluated the prevalence of LUTD in children with a urinary tract infection (UTI) and assessed the impact of standard urotherapy on patients with LUTD. METHODS: We enrolled 228 patients who were 4 years of age or older with at least one episode of UTI, together with a control group of 100 children. All the children were evaluated using the Pediatric Lower Urinary Tract Symptom Score (PLUTSS), and the intervention group were re-assessed after therapy to gauge their response. RESULTS: Lower urinary tract dysfunction was detected in 134 (59%) patients. Their mean PLUTSS was 15.9 ± 5.3, and 78% of these patients had a reduced quality of life (QOL). After 5 ± 2.7 months of behavioural therapy, 105 (78%) patients with LUTD were evaluated for the second time. This showed that LUTD was ameliorated in 69% of the patients and improved in 26%, with a mean post-treatment PLUTSS of 6.6 ± 5.6. Two control group children had LUTD. CONCLUSION: Lower urinary tract dysfunction was frequently seen in patients with UTIs, but standard urotherapy was usually successful. Most of the patients in our study with LUTD also had an impaired QOL.

Encapsulating peritoneal sclerosis in children on chronic PD: a survey from the European Paediatric Dialysis Working Group.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD) that is associated with significant morbidity and mortality in adults. There are scarce data for children. We performed a 10-year survey to determine the prevalence, risk factors and outcome for EPS in children. METHODS: Chronic PD patients in 14 dialysis units participating in the European Paediatric Dialysis Working Group between January 2001 and December 2010 were included in this study. RESULTS: Twenty-two cases of EPS were reported (prevalence 1.5%; 8.7 per 1000 patient-years on PD). Median PD vintage was 5.9 (1.6-10.2) in EPS and 1.7 (0.7-7.7) years in the remainder of the PD population (P<0.0001). EPS patients had a significantly higher peritonitis rate than non-EPS patients (P=0.2). EPS was diagnosed while the child was on PD in 17 (77%), after conversion to haemodialysis (HD) in 3 and after transplantation in 2. Fifteen of 17 (88%) developed ultrafiltration (UF) failure. The median interval between UF failure and presentation with bowel obstruction was 2.8 (0.02-5.8) months. Twenty (91%) had clinical and radiological signs of bowel obstruction. Enterolysis was performed in 14 and 19 received immunosuppression or tamoxifen. Nine required parenteral nutrition. At final follow-up 4.8 (1.3-8.7) years after EPS diagnosis, 3 patients died, 11 had a functioning transplant and 8 were on HD. CONCLUSIONS: The prevalence of EPS in European children on PD is comparable with that of adult PD patients, but mortality from paediatric EPS is significantly lower. A high index of suspicion is required for the diagnosis of EPS in children with longer dialysis duration, a high peritonitis rate and UF failure.

High frequency of kidney and urinary tract anomalies in asymptomatic first-degree relatives of patients with CAKUT.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) commonly cause chronic kidney disease in children. While most CAKUT cases are sporadic, observed familial clustering suggests that the pathogenesis is influenced by genetic factors. METHODS: The purpose of the present study is to determine the frequency of the kidney and urinary tract anomalies in asymptomatic first-degree relatives of patients with CAKUT. A total of 218 index patients and their families followed at an academic hospital in Ankara, Turkey, were enrolled in the study. RESULTS: Family histories revealed at least one other member with a known kidney or urinary tract disease in 50% and CAKUT in 22.9% of the families. All asymptomatic first-degree relatives of 180 index patients were screened for kidney and urinary tract anomalies using ultrasound. New anomalies were diagnosed in 116 asymptomatic first-degree relatives (23%) in 87 families (48.3%). When family histories and ultrasound findings of 180 index patients were evaluated together, 129 first-degree relatives in 92 families (51.1%) had CAKUT. CONCLUSIONS: This study suggests that genetic mechanisms might be very important in the pathogenesis of apparently sporadic CAKUT. Identification of the underlying gene mutations will provide further insights into the knowledge of the kidney and urinary tract development and pathogenesis of CAKUT.

Hypocomplementemic urticarial vasculitis syndrome in three siblings.

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is relatively uncommon and generally seen in the fourth decade of life. There are very few pediatric cases with the diagnosis of HUVS in the literature. In this report, we describe the first familial cases of HUVS in three siblings. The disease onset was during childhood period in all patients. One of them developed severe renal involvement and died. The other two had ongoing skin and eye manifestations and the elder one developed lupus. Presence of these three patients is a strong evidence for the role of genetic factors in the pathogenesis of this rare vasculitis.

Acute kidney injury in a paediatric intensive care unit: comparison of the pRIFLE and AKIN criteria.

AIM: The purpose of our study was to evaluate and analyse the prevalence and association of acute kidney injury (AKI) as defined by paediatric Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease (pRIFLE) and Acute Kidney Injury Network (AKIN) classifications in a paediatric intensive care unit (PICU). METHODS: A prospective analysis of all patients that were admitted to our PICU between June 2009 and December 2010 was performed. Patients were classified according to AKIN and pRIFLE criteria. RESULTS: One hundred and eighty-nine patients (mean age 45.9 ± 54.7 months; 110 male, 79 female) were enrolled. Sixty-three (33.3%) patients developed AKI by AKIN criteria and 68 (35.9%) patients developed AKI by pRIFLE criteria. All patients that had AKI according to AKIN criteria also had this diagnosis with pRIFLE criteria. Five patients had developed AKI only according to pRIFLE classification, four of them owing to reduction in their estimated creatinine clearance and one of them owing to changes over 1-week period. The mean length of PICU stay was longer, need for mechanical ventilation and mortality rates were higher in patients with AKI when compared to patients without AKI. CONCLUSION: Although both pRIFLE and AKIN criteria were very helpful in the detection of patients with AKI even in the early stages of it, pRIFLE seems to be more sensitive in paediatric patients.

Urinary tract infections owing to ESBL-producing bacteria: microorganisms change--clinical pattern does not.

AIM: Urinary tract infections (UTIs) caused by extended-spectrum beta lactamase (ESBL)-producing bacteria have become a growing problem worldwide. The aim of this study was to investigate the clinical and radiological findings in patients with community-acquired UTIs owing to ESBL-producing bacteria. METHODS: Files of the patients that had UTI owing to ESBL-producing bacteria, between January 2008 and December 2009, were retrospectively evaluated. RESULTS: One hundred and eleven UTI episodes in 94 patients were included. Seventy-five per cent of the patients had recurrent UTIs. Ultrasound, dimercaptosuccinic acid (DMSA) scintigraphy and voiding cystourethrography (VCUG) were found abnormal in 36%, 46% and 31% of the patients, respectively. Overall, 68% of the patients had ≥1 underlying predisposing factor for UTI. Male patients and acute pyelonephritis (APN) episodes were more frequent at small ages. The rate of female patients and cystitis episodes predominated with increasing age. Ultrasound, DMSA scintigraphy, VSUG and UT abnormalities were more frequent in patients with APN, and lower UT disturbances were more frequent in patients with cystitis. CONCLUSION: UTIs owing to ESBL-producing bacteria begin to replace UTIs owing to non-ESBL-producing bacteria. However, the clinical pattern of these infections does not seem to be different. Thus, our aim should be to correct underlying predisposing factors in general in order to prevent infections owing to ESBL-producing bacteria.

The effect of colchicine on physical growth in children with familial mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disease, characterized by recurrent, self-limited attacks of fever with serositis involving the peritoneum, pleura, and joints. There is very scarce information on physical growth of affected children. The aim of this study was to determine whether there is significant improvement in growth parameters in FMF patients after colchicine treatment. Patient files were retrospectively evaluated and patients that used colchicine for more than 1 year were included in the study. Demographic features, clinical findings before and after colchicine therapy, duration and dosage of therapy, weight, height, parentally adjusted height, and body mass index before and after colchicine therapy were noted and transformed into standard deviation scores (SDS). The study group consisted of 50 FMF (25 male and 25 female) patients. Median age at the time of diagnosis was 6.5 years. Median follow-up period was 3.6 (1-12.5) years. Mean height SDS increased from -0.19 +/- 1.01 to 0.13 +/- 0.99 (p = 0.026), and mean parentally adjusted height increased from -0.18 +/- 1.23 to 0.13 +/- 1.24 (p = 0.027), and both of them were found to be statistically significant. Mean body mass index SDS increased from -0.61 +/- 1.32 to -0.32 +/- 1.33, but this improvement was statistically insignificant (p = 0.18). In this study, we found that colchicine significantly improved height development in FMF patients.

Antibiotic resistance of urinary tract pathogens and evaluation of empirical treatment in Turkish children with urinary tract infections.

The changing pattern of antimicrobial resistance in the causative microorganisms of urinary tract infection (UTI) in childhood is a growing problem. The aims of this study were to assess the resistance patterns of urinary isolates to commonly used antimicrobials and to evaluate the options for empirical treatment of UTI. A prospective cross-sectional analysis of bacteria isolated from children with UTI was performed between January 2003 and January 2004. Resistance to antibiotics was analysed in three age groups: Group I, < or =12 months; Group II, 13-60 months; and Group III, >60 months. A total of 165 urinary pathogens were isolated from 131 patients. Mean patient age was 63.7+/-49.8 months. The most common causative agent was Escherichia coli (87% of cases) followed by Klebsiella pneumoniae (10%). Resistance to ampicillin (74.2%) and co-trimoxazole (61.3%) was significant in all isolates. Nitrofurantoin was the most active agent against E. coli (2.2% resistant isolates), followed by amikacin (4.9%), ceftriaxone (7.5%) and ciprofloxacin (12%). None of the isolates from Group I patients were resistant to ciprofloxacin and a low resistance rate (7.1%) was noted for amikacin. In Group II patients, none of the isolates were resistant to amikacin, and ceftriaxone was the second most suitable antibiotic (resistance rate 2.2%). In Group III patients, the lowest resistance rate was against nitrofurantoin (2.7%). In conclusion, we observed that the use of ampicillin and co-trimoxazole as a single agent for empirical treatment of a suspected UTI would not cover the majority of urinary pathogens in our region. Whilst amikacin, with a negligible resistance rate, was suitable in all age groups, gentamicin might still be useful as an empirical treatment of UTI in children aged >1 year. Nitrofurantoin could be included as a reasonable alternative in the empirical treatment of lower UTI in older children.

Mechanical ventilation in children.

Mechanical ventilation can be lifesaving, but > 50% of complications in conditions that require intensive care are related to ventilatory support, particularly if it is prolonged. We retrospectively evaluated the medical records of patients who had mechanical ventilation in the Pediatric Intensive Care Unit (PICU) during a follow-up period between January 2002-May 2005. Medical records of 407 patients were reviewed. Ninety-one patients (22.3%) were treated with mechanical ventilation. Ages of all patients were between 1-180 (median: 8) months. The mechanical ventilation time was 18.8 +/- 14.1 days. Indication of mechanical ventilation could be divided into four groups as respiratory failure (64.8%), cardiovascular failure (19.7%), central nervous system disease (9.8%) and safety airway (5.4%). Tracheostomy was performed in four patients. The complication ratio of mechanically ventilated children was 42.8%, and diversity of complications was as follows: 26.3% atelectasia, 17.5% ventilator-associated pneumonia, 13.1% pneumothorax, 5.4% bleeding, 4.3% tracheal edema, and 2.1% chronic lung disease. The mortality rate of mechanically ventilated patients was 58.3%, but the overall mortality rate in the PICU was 12.2%. In conclusion, there are few published epidemiological data on the follow-up results and mortality in infants and children who are mechanically ventilated.

Vesicoureteral Reflux and Renal Scarring Risk in Children after the First Febrile Urinary Tract Infection.

BACKGROUND/AIMS: There are many controversies regarding the best approach for evaluating children after their first febrile urinary tract infection (UTI). The aim of this study was to define the clinical, laboratory, and radiological features of patients with their first febrile UTI and to investigate the factors that might predict the presence of vesicoureteral reflux (VUR) and renal scarring. METHODS: The files of patients who were followed due to their first febrile UTI between 2008 and 2013 were retrospectively reviewed (n = 300). Patients were divided into groups based on their age, the resistance state of microorganisms, the presence of VUR, and scarring on Tc99m dimercaptosuccinic acid scintigraphy. The chi-square test and Mann-Whitney U test were used for analysis. RESULTS: The median age at the first febrile UTI was 11 months and girls constituted 77% of the patient population. VUR and renal scarring were detected in 30.9 and 19.4% of the patients, respectively. C-reactive protein levels and the presence of renal scarring were significantly higher in patients with VUR (p < 0.05). Abnormal ultrasonography findings, VUR and recurrent UTIs were significantly higher in patients with renal scars (p < 0.001). In multivariate analysis, we did not detect any factor that might predict the presence of VUR and renal scarring. CONCLUSION: A majority of children had their first febrile UTI at a young age. Although we could not find any factor that might predict the VUR and scar risk in patients with their first febrile UTI, an abnormal renal scan at 6 months after infection was closely related with the presence of VUR and recurrent UTIs.

HPSE2 mutations in urofacial syndrome, non-neurogenic neurogenic bladder and lower urinary tract dysfunction.

BACKGROUND: Urofacial syndrome (UFS) is characterised by congenital bladder dysfunction accompanied by a characteristic abnormal grimace upon smiling and crying. In recent years, biallelic mutations of HPSE2 and LRIG2 have been reported in UFS patients. Non-neurogenic neurogenic bladder (NNNB) has a bladder identical to UFS without typical facial features. The aim of this study was to analyse HPSE2 mutations in patients with UFS and NNNB or severe lower urinary tract dysfunction (LUTD) without abnormal facial expression. METHODS: Patients with UFS, NNNB and severe LUTD were enrolled in the study. We examined a total of 35 patients from 33 families. There were seven UFS patients from five different families, 21 patients with NNNB and seven with LUTD. HPSE2 gene mutation analysis was performed using the polymerase chain reaction protocol followed by Sanger sequencing in these patients. RESULTS: A twin pair with UFS was found to be homozygous for c.457C>T (p.Arg153*) mutation. No other pathogenetic variant was detected. CONCLUSION: HPSE2 mutations were found in one UFS family but not detected in patients with NNNB and severe LUTD. Considering the increasingly recognised cases of NNNB that were diagnosed in early childhood period, genetic factors appear to be responsible. Thus, further genetic studies are needed to discover novel associated gene variants in these bladder anomalies.

Renal replacement therapies in pediatric intensive care patients: experiences of one center in Turkey.

BACKGROUND: Despite constant improvements in caring for critically ill neonates and infants with congenital cardiac disease, sepsis, bone marrow and solid organ transplantation, acute renal failure (ARF) is an important problem in these children. ARF, severe fluid overload and inborn errors of metabolism are some of the indications for acute dialysis in infants and children. METHODS: The authors had retrospectively evaluated the medical records of Pediatric Intensive Care Unit, Ankara University School of Medicine, Ankara, Turkey patients who had required acute renal replacement therapy between the dates of January 2002 to February 2005. RESULTS: Medical records of 332 patients were reviewed. Acute renal replacement therapy was performed in 21 patients (6.3%; mean age, 9.6 +/- 7.4 years). Dialysis modalities were peritoneal dialysis in 15 patients (71.4%; mean age, 3.9 +/- 5.6 years) and hemodialysis in six patients (28.6%; mean age, 12.1 +/- 3.2 years). A total of 90% of patients had severe systemic disease leading to ARF. A total of 95% of patients had multiple organ dysfunction syndrome. The most common cause of ARF was refractory shock. At the beginning of renal replacement therapy, 10 patients were anuric, nine patients had volume overload, seven patients had decompensated metabolic acidosis and nine patients had hypotension. The average dialysis period was 4.7 +/- 6.4 days. Mortality rate was 66.7%. Eight patients recovered from ARF and chronic renal failure had developed in one patient. CONCLUSION: In the Pediatric Intensive Care Unit, ARF is frequently seen together with multiple organ dysfunction syndrome and the mortality rate is high. Both peritoneal dialysis and hemodialysis are important renal replacement treatment modalities in patients with ARF. The age and hemodynamic status of the patients are important when choosing treatment modality; generally peritoneal dialysis is preferred in infants and toddler, while hemodialysis is preferred in older children.