Characteristics and predictors of chronic kidney disease in children with myelomeningocele: a nationwide cohort study.

BACKGROUND: Myelomeningocele (MMC) is highly prevalent in developing countries, and MMC-related neurogenic bladder is an important cause of childhood chronic kidney disease (CKD). This nationwide study aimed to evaluate demographic and clinical features of pediatric patients with MMC in Turkey and risk factors associated with CKD stage 5. METHODS: Data from children aged 0-19 years old, living with MMC in 2022, were retrospectively collected from 27 pediatric nephrology centers. Patients > 1 year of age without pre-existing kidney abnormalities were divided into five groups according to eGFR; CKD stages 1-5. Patients on dialysis, kidney transplant recipients, and those with eGFR < 15 ml/min/1.73 m2 but not on kidney replacement therapy at time of study constituted the CKD stage 5 group. RESULTS: A total of 911 (57.8% female) patients were enrolled, most of whom were expectantly managed. Stages 1-4 CKD were found in 34.3%, 4.2%, 4.1%, and 2.4%, respectively. CKD stage 5 was observed in 5.3% of patients at median 13 years old (range 2-18 years). Current age, age at first abnormal DMSA scan, moderate-to-severe trabeculated bladder on US and/or VCUG, and VUR history were independent risk factors for development of CKD stage 5 (OR 0.752; 95%; CI 0.658-0.859; p < 0.001; OR 1.187; 95% CI 1.031-1.367; p = 0.017; OR 10.031; 95% CI 2.210-45.544; p = 0.003; OR 2.722; 95% CI 1.215-6.102; p = 0.015, respectively). Only eight CKD stage 5 patients underwent surgery related to a hostile bladder between 1 and 15 years old. CONCLUSION: MMC-related CKD is common in childhood in Turkey. A proactive approach to neurogenic bladder management and early protective surgery in selected cases where conservative treatment has failed should be implemented to prevent progressive kidney failure in the pediatric MMC population in our country.

Is there a difference in fecal microbiota of children with and without voiding dysfunction?

OBJECTIVE: Voiding dysfunction (VD), which encompasses many urinary symptoms that are not caused by neurological or anatomical anomalies, is a frequently encountered functional urinary bladder disorder in children. It was reported that there was an association between lower urinary tract symptoms and fecal microbiota in adult patients. Therefore, we aimed to investigate the differences in fecal microbiota between children with or without VD. METHODS: Two patient groups, including 30 patients, were compared. Group 1 included patients with VD, while Group 2 consisted of healthy children. All study participants were asked to fill lower urinary tract and voiding dysfunction symptom score forms with the assistance of their parents. Subsequently, uroflowmetry tests and postvoiding residual urine measurements were performed. Fresh stool samples were collected from all children and analyzed by polymerase chain reaction. General bacterial load and presence of Roseburia intestinalis, Clostridium difficile, Fusobacterium nucleatum, and Bacteroides clarus were tested. RESULTS: The two groups were significantly different regarding general bacterial load; the presence of Fusobacterium nucleatum. Clostridium difficile and Bacteroides clarus was not detected in the fresh stool samples of the patients in Group 2; the counts of Roseburia intestinalis were less in Group 1 than in Group 2, although there was no statistically significant difference. There was a negative correlation between symptom scores, general bacterial load, and the presence of Fusobacterium nucleatum. However, there was no correlation between the presence of Roseburia intestinalis and symptom scores. CONCLUSIONS: There is a potential relationship between VD and a deviation in the fecal microbiota in the pediatric population.

The relationship between body mass index and renal length in obese children.

BACKGROUND: Obesity in the pediatric population is a severe public health problem and is associated with various comorbidities. Renal length is an important clinical parameter for the diagnosis and follow-up of renal diseases. The aim of this study was to determine the relationship between renal length (measured ultrasonographically) and body mass index (BMI) in obese children, and to develop nomograms for renal length according to BMI. METHODS: Renal ultrasound was performed in 368 children without renal disease. Each child's age, gender, weight, height, and BMI (kg/m2) were recorded. The children were divided into three groups according to BMI percentiles: obese group: BMI ≥ 95th percentile; overweight group: BMI 85th-94th percentile; normal weight group: BMI 5th-84th percentile. RESULTS: Weight, height, BMI, and right and left renal length differed significantly between the three groups (p = 0.001). There were significant correlations between renal length with age, weight, height, and BMI. Measurement of renal length was independently associated with BMI, age, and height. BMI was used to create renal length nomograms for obese children, based on multiple regression analysis (R2 = 0.32 and p = 0.0001). Mean renal length was highest in the obese group (96.9 ± 13.4 mm) and lowest in the normal weight group (88.3 ± 12.9 mm). CONCLUSIONS: Ultrasonographic measurement of the renal length according to BMI in children can be a useful method in evaluating these children. Smaller-than-normal kidneys can easily remain undiagnosed in obese and overweight children and this nomogram offers an additional method to evaluate the renal size in obese children.

Mutations in MAPKBP1 Cause Juvenile or Late-Onset Cilia-Independent Nephronophthisis.

Nephronophthisis (NPH), an autosomal-recessive tubulointerstitial nephritis, is the most common cause of hereditary end-stage renal disease in the first three decades of life. Since most NPH gene products (NPHP) function at the primary cilium, NPH is classified as a ciliopathy. We identified mutations in a candidate gene in eight individuals from five families presenting late-onset NPH with massive renal fibrosis. This gene encodes MAPKBP1, a poorly characterized scaffolding protein for JNK signaling. Immunofluorescence analyses showed that MAPKBP1 is not present at the primary cilium and that fibroblasts from affected individuals did not display ciliogenesis defects, indicating that MAPKBP1 may represent a new family of NPHP not involved in cilia-associated functions. Instead, MAPKBP1 is recruited to mitotic spindle poles (MSPs) during the early phases of mitosis where it colocalizes with its paralog WDR62, which plays a key role at MSP. Detected mutations compromise recruitment of MAPKBP1 to the MSP and/or its interaction with JNK2 or WDR62. Additionally, we show increased DNA damage response signaling in fibroblasts from affected individuals and upon knockdown of Mapkbp1 in murine cell lines, a phenotype previously associated with NPH. In conclusion, we identified mutations in MAPKBP1 as a genetic cause of juvenile or late-onset and cilia-independent NPH.

Allergic sensitization in kidney transplanted patients - Is it a result of immunosuppressive agents or the sensitization of living donor?

BACKGROUND: Allergic sensitization has been reported increasingly in organ transplant recipients. However, the pathogenesis of this sensitization has still not been clearly understood. OBJECTIVE: The aim of this study was to evaluate allergic sensitization in kidney transplanted children and adolescents under immunosuppressive treatment. METHODS: Twenty seven kidney-transplanted subjects were studied by standardized interviews from the International Study of Asthma and Allergies in Childhood criteria, skin prick test (SPT) and measurement of specific immunoglobulin E (s-IgE). Patients were considered to have allergic sensitization when presenting a positive SPT and/or s-IgE >0.35 kUA/l to at least one of the tested allergens. Patients with a history of allergic diseases accompanied by sensitization were accepted as allergic. We also performed SPT on the living donors of the allergic groups. RESULTS: Seven patients (25.9%) were found to be sensitized to ≥1 common inhalant and 3 subjects (11.1%) additionally reported a corresponding present history of allergic diseases. All of the living donors' sensitized patients were allergic. New-onset post-transplantation food allergy was not documented in any patients. CONCLUSIONS: This study supports the concept that not only immunosuppressant agents but also sensitization of living donors could be a significant contributor to allergic sensitization in kidney recipients.

Genotypic and phenotypic features of the cystinosis patients from the South Eastern part of Turkey.

We have conducted this study for the purposes of demonstrating the spectrum of mutations and of identifying their effects on the phenotype, with a particular focus on the clinical course, prognosis and response to treatment. A total of 25 patients from 20 families, who have been treated and followed up after being diagnosed with cystinosis. Nine patients were identified with mutations of homozygous c.451A > G, 7 patients with homozygous c.681G > A, 6 patients with homozygous c.834_842del, 2 patients with homozygous c.18_21delGACT and 1 patient with compound heterozygous for c.451A > G/ c.1015G > A. The c.834_842del mutation identified in six patients from four families has not been previously identified. Progression to renal failure occurred earlier in the patients identified with the new mutation, despite treatment. Larger patient series are required to demonstrate the genotypic properties of the patients with cystinosis and their relationship with the clinical course.

Role of new biomarkers for predicting renal scarring in vesicoureteral reflux: NGAL, KIM-1, and L-FABP.

BACKGROUND: Reflux nephropathy is the most serious complication of vesicoureteral reflux (VUR). The aim of this study was to assess the role of urinary levels of neutrophil-gelatinase-associated lipocalin (NGAL),kidney injury molecule-1 (KIM-1), and liver-type fatty-acid-binding protein (L-FABP) in the early diagnosis of reflux nephropathy in patients with VUR. METHODS: This study assessed 123 patients with primary VUR and 30 healthy children as a control group. The children were divided into five groups: Group A, patients with VUR and renal parenchymal scarring (RPS); Group B, patients with VUR and without RPS; Group C, patients with RPS and resolved VUR; Group D, patients with resolved VUR and without RPS; Group E, healthy reference group. RESULTS: Median urinary NGAL (uNGAL)/Creatinine (Cr) was significantly higher in patients with than those without RPS and the control group (p = 0.0001). Median uKIM-1/Cr was similar in all groups (p = 0.417). Median uL-FABP/Cr was significantly higher in patients with RPS than in the reference group (p < 0.05). CONCLUSIONS: Urinary NGAL levels may be used as a noninvasive diagnostic marker for predicting renal scarring in reflux nephropathy.

Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity.

Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis, and allows identification of novel candidate genes.

Urinary NGAL, KIM-1 and L-FABP concentrations in antenatal hydronephrosis.

INTRODUCTION: The clinical tests currently in use for obstructive nephropathy (such as renal ultrasonography, differential radionuclide renal scans and urinary creatinine concentration data) are not efficient predictors of the subsequent clinical course. Novel and simple biomarkers are required which, if proven, could be clinically beneficial in determining if a patient is eligible for surgery or reno-protective therapy. More recently, the interest of clinicians has focused on the potential of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1) and urinary liver-type fatty acid-binding proteins (uL-FABP) as biomarkers for renal function in children with hydronephrosis (HN). OBJECTIVE: The purpose of this study was to investigate possible clinical applications of uNGAL, uKIM-1 and uL-FABP as beneficial non-invasive biomarkers to determine whether or not surgical intervention is required in children with HN. STUDY DESIGN: Renal ultrasonography and radionuclide renal scans were used as diagnostic tools to detect HN. Patients were divided into two groups based on the antero-posterior diameter of their renal pelvis and the presence of dysfunction. Group 1 included 26 children with severe HN (with dysfunction), and group 2 consisted of 36 children with mild HN (without dysfunction). Urine samples were collected from 62 children with HN and 20 healthy children. RESULTS: Hydronephrosis was more common in males than in females, with a male to female ratio of 9:1 in the study sample. The incidence of left kidney involvement (32 patients) was slightly higher than right kidney involvement (28 patients). Compared with controls and group 2, the ratio of uNGAL to creatinine was significantly higher in group 1 (p < 0.05). The biomarker uNGAL/Cr exhibited fairly good diagnostic accuracy, with an area under the curve of 0.68 [95% confidence interval 0.6-0.7] and an optimal cut-off value of 0.16 ng/mg Cr (sensitivity 58%, specificity 75%) (p < 0.05). There was a positive correlation between the uNGAL/Cr ratio and the uKIM-1/Cr ratio (r = 0.582, p < 0.05) and uL-FABP/Cr ratio (r = 0675, p < 0.05) in group 1. DISCUSSION: The results clearly demonstrated that children with hydronephrosis and dysfunction had significantly increased uNGAL, and uNGAL/Cr concentrations. However, uKIM-1, uKIM-1/Cr, uL-FABP and uL-FABP/Cr concentrations were not significantly different when compared with controls. These results support the use of uNGAL concentrations as an early marker for renal dysfunction in HN. CONCLUSIONS: The study clearly demonstrated that pediatric patients with hydronephrosis and dysfunction had significantly higher uNGAL to creatinine concentrations as compared with controls.

Value of sonographic anterior-posterior renal pelvis measurements before and after voiding for predicting vesicoureteral reflux in children.

PURPOSE: Voiding cystourethrography (VCUG) is the gold standard for diagnosing vesicoureteral reflux (VUR), but it is important to minimize the use of VCUG because of the urinary catheterization and radiation exposure required. Ultrasound (US) observations suggest that pelvicalyceal dilatation varies according to the degree of bladder fullness in children with urinary tract infection. The aim of this study was to assess whether anterior-posterior (AP) measurements of the renal pelvis on US before and after voiding can be used as a screening tool while predicting the presence of VUR in children. METHODS: The subjects were toilet-trained children older than 4 years who required VCUG. Two groups were established based on the VCUG results: a VUR group of 40 kidney units (each unit defined as calyces and ureter) that exhibited different severities of reflux, and a control group of 68 kidney units unaffected by VUR. Prior to VCUG, US AP measurements of the renal pelvis of each kidney unit were recorded when the urinary bladder was full and again after bladder emptying. The change in AP measurement from before to after voiding was compared between the two groups. RESULTS: The mean change in AP measurements from before to after voiding in the VUR group was significantly greater than that in the control group (p = 0.003). CONCLUSIONS: Comparing US AP measurements of the renal pelvis before and after voiding is useful for identifying children who are suspected to have VUR and thus require immediate VCUG.

The African variant of BKV in a Turkish renal transplant patient.

In renal transplant recipients, BK polyomavirus (BKV) is linked to nephropathy. BK virus genotypes have a strong geographic component. This paper presents the African variant of BKV in a Turkish renal transplant patient, which is a rare cause of infection in the Northern Hemisphere and, to our knowledge, the first case from Turkey.

Leptin and plasminogen activator inhibitor-1 levels in children on chronic dialysis.

PURPOSE: In this study, it is aimed to compare the serum leptin and PAI-1 levels and evaluate their relationship in children on hemodialysis (HD) and peritoneal dialysis (PD). METHOD: Thirty-six patients on HD (mean age: 15.0 ± 2.8 years), 19 patients on PD (mean age: 13.0 ± 3.5 years) and 15 healthy subjects (mean age: 14.5 ± 2.7 years) were included in the study. Laboratory investigations included blood count, biochemical parameters, serum iron, iron binding capacity, parathormone, erythrocyte sedimentation rate, C-reactive protein (CRP), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, serum leptin and PAI-1 levels. RESULTS: Serum leptin levels were significantly higher in HD group than in control group when the effects of BMI and sex were controlled, while PD and control groups had similar leptin levels. PAI-1 levels were also significantly higher in HD group than in control group, while there was no statistically significant difference in PAI-1 levels of PD and control group. PAI-1 levels and leptin levels were significantly correlated, which was independent of the effect of BMI in both HD and PD groups when they are evaluated separately. CONCLUSION: Results of our study showed that HD patients had higher leptin and PAI-1 levels and leptin and PAI-1 levels were correlated significantly in both patient groups. The effect of elevated serum leptin and PAI-1 levels on the cardiovascular complications remains to be established.

Association of eNOS gene intron 4 a/b VNTR polymorphisms in children with nephrotic syndrome.

To investigate the association of endothelial nitric oxide synthase gene intron 4 (eNOS4) polymorphisms with nephrotic syndrome, the eNOS4 genotypes were assessed in 161 children with nephrotic syndrome in comparison with 78 healthy subjects. We classified the children with nephritic syndrome into 2 groups: as steroid-sensitive nephrotic syndrome (SSNS) (n=125) and steroid-resistant nephrotic syndrome (SRNS) (n=36). The eNOS4 polymorphisms were analyzed by polymerase chain reaction. The frequencies of eNOS4 aa, ab and bb genotypes were 3%, 31%, and 66% in all the nephrotic syndrome groups, and 1%, 23%, and 76% in the control group (x(2)=2.87, p>0.05). In addition, the frequencies of eNOS4 aa, ab and bb genotypes were 2%, 33%, and 65% in SSNS group, and 5%, 28%, and 67% in the SRNS group (x(2)=1.13, p=0.567). The present study is the first to investigate eNOS4 gene polymorphisms in children with SSNS and SRNS. Our data show that the eNOS4 gene polymorphisms were not associated with the development, frequent relapse and response to steroid in nephritic syndrome.

Polyarteritis nodosa: a case presenting with renal mass.

An adolescent girl was hospitalized due to fever and abdominal flank pain. A left renal haematoma was detected on magnetic resonance imaging. Renal angiography demonstrated multiple microaneurysms at both hepatic arteries, intrarenal segments of the bilateral renal arteries, and inferior lobar segment of the left pulmonary artery, which is consistent with the diagnosis of polyarteritis nodosa. Vasculitic syndromes should be considered in patients with visceral haemorrhage.

Helicobacter pylori infection and gastroduodenal lesions in children with chronic kidney disease stage V.

BACKGROUND: This study aimed to investigate the dyspeptic symptoms, endoscopic findings, and frequency of Helicobacter pylori (Hp) infection in children with chronic kidney disease (CKD) stage V, and to compare findings in peritoneal dialysis (PD) and hemodialysis (HD) patients. METHODS: Sixty-five patients on PD (n = 36) or HD (n = 29) were included. Age, gender, duration and type of dialysis, and dyspeptic complaints were recorded. All patients underwent endoscopy. Rapid urease tests were performed in all patients and antral biopsy examinations done in suitable patients to investigate presence of Hp infection. RESULTS: The mean age of patients (55 % male) was 13.9 ± 3.6 years. Frequency of dyspepsia was 43 % and was similar in HD and PD groups. The most frequent dyspeptic symptoms were early satiety (21.5 %) and bloating (17 %). Abnormal endoscopic findings were present in 81.5 % of patients (similar in both groups), and the most common lesion was gastritis (35.5 %). Hp positivity was determined in 37 % of the patients, which was similar in both groups. No significant relationship was found between dyspeptic symptoms and Hp infection. Hp infection was found to be significantly higher in 41.5 % of the patients with gastroduodenal lesions. Abnormal endoscopic findings were significantly higher in severely dyspeptic patients (88.9 %). CONCLUSIONS: We think performing an upper gastrointestinal tract examination and Hp screening may be helpful in renal transplant candidates with severe dyspeptic symptoms.

Etiology and outcome of acute kidney injury in children.

The aim of this prospective, multicenter study was to define the etiology and clinical features of acute kidney injury (AKI) in a pediatric patient cohort and to determine prognostic factors. Pediatric-modified RIFLE (pRIFLE) criteria were used to classify AKI. The patient cohort comprised 472 pediatric patients (264 males, 208 females), of whom 32.6% were newborns (median age 3 days, range 1-24 days), and 67.4% were children aged >1 month (median 2.99 years, range 1 month-18 years). The most common medical conditions were prematurity (42.2%) and congenital heart disease (CHD, 11.7%) in newborns, and malignancy (12.9%) and CHD (12.3%) in children aged >1 month. Hypoxic/ischemic injury and sepsis were the leading causes of AKI in both age groups. Dialysis was performed in 30.3% of newborns and 33.6% of children aged >1 month. Mortality was higher in the newborns (42.6 vs. 27.9%; p < 0.005). Stepwise multiple regression analysis revealed the major independent risk factors to be mechanical ventilation [relative risk (RR) 17.31, 95% confidence interval (95% CI) 4.88-61.42], hypervolemia (RR 12.90, 95% CI 1.97-84.37), CHD (RR 9.85, 95% CI 2.08-46.60), and metabolic acidosis (RR 7.64, 95% CI 2.90-20.15) in newborns and mechanical ventilation (RR 8.73, 95% CI 3.95-19.29), hypoxia (RR 5.35, 95% CI 2.26-12.67), and intrinsic AKI (RR 4.91, 95% CI 2.04-11.78) in children aged >1 month.

Parvovirus B19-induced multisystemic vasculitis and acute endocapillary proliferative glomerulonephritis in a child.

A 10-year-old girl was admitted with fever, cough, maculopapular rash, hemoptysis, dark-colored urine, edema, multiple lymphadenopathies, and hepatosplenomegaly. She developed acute glomerulonephritis during the course of these complex clinical features. Laboratory data showed hematuria, proteinuria, and hypocomplementemia. Serological tests showed positive human parvovirus B19 (HPVB19)-specific immunoglobin M (IgM) and HPVB19 DNA was detected in the patient's serum using polymerase chain reaction (PCR). Renal biopsy revealed acute endocapillary proliferative glomerulonephritis (AEPGN) with coarse granular C3 depositions in a "starry sky pattern," which is more peculiar to poststreptococcal glomerulonephritis. Electron microscopy showed subendothelial and small hump-shaped subepithelial electron-dense deposits in glomerular capillary walls. There was no evidence of either any mycobacterial, staphylococcal, or streptococcal infection, and the diagnosis of Goodpasture syndrome and connective tissue disorders was excluded during clinical and laboratory investigations. A diagnosis of HPVB19-induced pleuropneumonitis and glomerulonephritis was made. Through a literature search there was no documented pediatric case of AEPGN induced by HPVB19, and this case represents, to our knowledge, the first time that a direct relationship between parvovirus infection and AEPGN has been demonstrated in a child.