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.

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.

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.

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.

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.

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.

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.

Unusual cause of acute neurologic deficit in childhood: primary central nervous system vasculitis presenting with basilar arterial occlusion.

INTRODUCTION: Primary central nervous system (CNS) vasculitis of childhood is a rare disorder. The most common signs and symptoms are acute severe headache and focal neurologic deficit. It should be suspected in children who have an acquired neurologic deficit that remains unexplained after an initial basic evaluation. Diagnosis usually depends on brain magnetic resonance imaging and conventional angiography of cerebral vasculature. Stenosis is the most common angiographic finding and it usually affects the middle cerebral artery and its branches. Anterior and posterior circulation is rarely involved. CASE REPORT: In this report, we describe an 8-year-old boy who presented with vertebrobasilar insufficiency symptoms and primary CNS vasculitis diagnosis was made later.

Case report: seizures in a child caused by a large venous angioma.

Cerebral venous angioma is a congenital anomaly of the medullary vein, the vessel that drains into the transparenchymal venous stem. This lesion is also referred to as a developmental venous anomaly. A few reports in the literature have documented developmental venous anomaly-related epilepsy, neurologic deficits, and intracranial hemorrhage. A 3-year-old boy was referred to our hospital after he sustained an afebrile, tonic-clonic, focal seizure of 15 minutes' duration that affected his right arm, leg, and eyebrow. Cerebral digital subtraction angiography showed a bilateral, large periventricular developmental venous anomaly. This report describes the clinical and radiologic findings for this large venous angioma that caused seizures in a child.

Full-house nephropathy in a patient with negative serology for lupus.

A 10-year-old girl presented with a complaint of recurrent abdominal pain. Physical examination findings were unremarkable. Laboratory investigations revealed BUN of 17 mg/dl and creatinine of 1 mg/dl, and complement levels were normal. She had neither hematuria nor proteinuria, and glomerular filtration rate was 60.9 ml/min/1.73 m(2). ANA, anti-DNA, p-ANCA and c-ANCA were all negative. Renal biopsy revealed findings of class III lupus nephritis in light, "full-house" nephropathy in immune fluorescent and tubuloreticular inclusions in electron microscopic examinations. After 17 months of treatment, her last creatinine is 2.5 mg/dl and GFR is 17.9 ml/min/1.73 m(2) and ANA and anti-DNA remain still negative. This case presents an example that decreased GFR can be the first presenting symptom of full-house nephropathy. Those patients who have negative lupus serology and renal biopsy findings of full-house nephropathy and tubuloreticular inclusions may behave and should be treated as lupus nephritis.

Endothelial nitric oxide synthase gene intron 4 a/b VNTR polymorphism in children with APSGN.

The role of endothelial nitric oxide synthase gene intron 4 a/b (eNOS4a/b) variable number of tandem repeats (VNTR) polymorphism in various renal diseases was investigated. We investigated whether the eNOS4a/b VNTR polymorphism is associated with susceptibility to acute poststreptococcal glomerulonephritis (APSGN) and its clinical features. Endothelial NOS4a/b VNTR polymorphism is determined by the polymerase chain reaction in 60 children with APSGN, and 66 healthy controls. The genotype distribution of eNOS4 does not differ between the patients and the controls (X(2)=5.1, p=0.079). However, the frequency of eNOS4a (eNOS4a/a and eNOS4a/b) genotype is higher in the patients than in the controls (X(2)=4.5, p=0.046). In the APSGN group we performed renal biopsy on eight patients because of nephrotic syndrome accompanies acute nephritic syndrome or glomerular filtration rate (GFR) is lower than 50% of normal, and found that to carry a/a and a/b genotypes were a significant risk factor for this type presentation (OR=17.3, 95% CI:1.95-152.67, p=0.03). Mean serum creatinine values are found statistically significantly higher in a/a and a/b genotypes when compared with b/b genotypes (p=0.022). Children carrying the "aa" and "ab" genotype or "a" allele of eNOS4 have a greater tendency to develop and clinical presentation of APSGN.

Hyperleptinemia and its relation with peripheral C34(+)CD7(+) stem cells in renal transplant recipients.

OBJECTIVES: Leptin, the Ob gene product, centrally regulates weight control. Transplant recipients are exposed to many factors affecting body mass. Leptin has been reported to activate the peripheral immune system. In this study, we evaluated serum leptin levels and factors contributing to hyperleptinemia; the relationship between serum leptin levels and lymphoid stem and mature cells; and their role in the rejection process in renal transplant recipients. MATERIALS AND METHODS: Sixty-three renal transplant recipients were included in the study. Patients were grouped according to serum leptin percentiles as hypoleptinemic (n=17), normoleptinemic (n=32), and hyperleptinemic (n=14). We determined serum leptin levels by radioimmunoassay and absolute number of CD34(+), CD7(+), CD34(+)CD7(+) lymphoid stem cells, CD4(+) and CD8(+) lymphocytes in peripheral blood by flow cytometry. RESULTS: The hyperleptinemic patients constituted 22.3% of the transplant patient. The mean peripheral blood CD34(+)CD7(+) lymphocyte count was significantly higher in hyperleptinemic patients than in normo- or hypoleptinemic patients (6.9, 6.1, and 44.3 cells/mm(3), respectively, P<0.05). There were no significant differences in the mean CD34(+), CD7(+), CD8(+), and CD4(+) lymphocyte count and CD4/CD8 ratio among the groups with respect to serum leptin levels. CD34(+)CD7(+) lymphocyte count was positively correlated with serum leptin levels (r=0.416, P<0.05). CONCLUSIONS: Hyperleptinemia is not rare during the posttransplant period. Our data support the results of previous experimental studies that have demonstrated the effect of the leptin hormone on lymphoid stem cells. The central and peripheral effects of leptin may differ on lymphoid stem cells and a serum threshold level may apply for the central effects.

Unusual presentation of IgA nephropathy in childhood: a case report.

Immunoglobulin A (IgA) nephropathy is the most common form of primary glomerulonephritis worldwide, and approximately 20% to 30% of adult patients with the disorder develop chronic renal failure within 20 years. This type of nephropathy is also an important risk factor for chronic renal failure in children. The pathogenesis of IgA nephropathy is still unknown, and treatment remains controversial. Microscopic hematuria and recurrent episodes of macroscopic hematuria are the most common clinical manifestations of this condition in children. This article describes the case of a young girl who presented with steroid-resistant nephrotic syndrome unaccompanied by hematuria. Renal biopsy findings were consistent with IgA nephropathy. The patient's condition was a rare clinical manifestation of IgA nephropathy.

Autoimmune thyroiditis with associated proteinuria: report of two patients.

The association of renal disease and autoimmune thyroid disorders has been reported previously. Renal findings associated with autoimmune thyroiditis present more commonly as proteinuria ranging from mild to nephrotic levels. We report here two adolescent girls with hyperthyroidism associated with transient proteinuria correlated with thyroid hormone levels. They had positive antithyroid peroxidase and antithyroglobulin antibodies. Ultrasonographic and scintigraphic findings of the thyroid gland were consistent with Graves' disease in both. Their renal functions were normal except proteinuria (daily protein excretion of 13.5 mg/m2/h in patient 1 and 11 mg/m2/h in patient 2). When they became euthyroid on antithyroid treatment, proteinuria decreased without associated hematuria and/or hypertension. In conclusion, patients with autoimmune thyroid disease should be assessed for the possibility of proteinuria and the etiological investigation of proteinuria should include evaluation of thyroid functions.

Bilateral calcifications in the basal ganglia, and frontal and parietal lobes of a patient with coeliac disease.

Previous authors have described a specific syndrome of coeliac disease, bilateral cerebral calcifications and epileptic seizures. We report a 4-year-old boy with coeliac disease who had bilateral calcifications in the basal ganglia and frontal and parietal lobes, but did not exhibit epileptic seizures.