Complement gene mutations in children with C3 glomerulopathy: do they affect the response to mycophenolate mofetil?

BACKGROUND: C3 glomerulopathy (C3G) is a complement-mediated disease. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to mycophenolate mofetil (MMF) treatment in pediatric C3G patients with and without mutations in complement-related genes. METHODS: Sixty pediatric C3G patients were included, divided into two groups based on complement-related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan-Meier analysis was performed for kidney survival. RESULTS: Out of the 60 patients, 17 had mutations. The most common mutation was in the CFH gene (47%). The mean age at diagnosis was higher in the group with mutation (12.9 ± 3.6 vs. 11.2 ± 4.1 years, p = 0.039). While the patients without mutation most frequently presented with nephritic syndrome (44.2%), the mutation group was most likely to have asymptomatic urinary abnormalities (47.1%, p = 0.043). Serum parameters and histopathological characteristics were similar, but hypoalbuminemia was more common in patients without mutation. During 45-month follow-up,10 patients progressed to chronic kidney disease stage 5 (CKD5), with 4 having genetic mutation. The time to develop CKD5 was longer in the mutation group but not significant. MMF treatment had no effect on progression in either group. CONCLUSIONS: This study is the largest pediatric C3G study examining the relationship between genotype and phenotype. We showed that the mutation group often presented with asymptomatic urinary abnormalities, was diagnosed relatively late but was not different from the without mutation group in terms of MMF treatment response and kidney survival.

The role of height and weight growth in spontaneous resolution of vesicoureteral reflux.

BACKGROUND: The aim of this study was to investigate the role of height and weight growth in the resolution of primary vesicoureteral reflux (VUR). METHODS: We retrospectively evaluated the data of 74 males and 135 females who were diagnosed with primary VUR. According to the vesicoureteral reflux resolution, patients were divided into two groups. Patients with complete or partial resolution of VUR were included in Group 1 and patients with no resolution of VUR were included in Group 2. Patients were evaluated for weight Z-score, height Z-score and body mass index at the diagnosis and in the follow-up. In addition, age, sex, grade of reflux and laterality were recorded. RESULTS: There were no significant differences between the two groups, according to height Z-score, weight Z-score and body mass index at the diagnosis, in the follow-up and also annual changes of these parameters. In addition, the same parameters did not significantly differ in Groups 1 and 2, between the initial and final evaluations. However, when we evaluate the patients older than 12 months old, weight Z-scores were significantly higher at the final evaluation than at the diagnosis, in Group 1. This significant difference was not detected in Group 2 at the same age. CONCLUSIONS: Although we could not detect the hectic pace of height growth as being important in the prediction of long-term outcomes of VUR, weight growth should be considered to predict the resolution of VUR.

Late onset Bartter syndrome: Bartter syndrome type 2 presenting with isolated nephrocalcinosis and high parathyroid hormone levels mimicking primary hyperparathyroidism.

OBJECTIVES: Nephrocalcinosis is associated with conditions that cause hypercalcemia and the increased urinary excretion of calcium, phosphate, and/or oxalate. A monogenic etiology is found in almost 30% of childhood-onset nephrocalcinosis which is also a common manifestation of primary hyperparathyroidism. We discuss a child with nephrocalcinosis and features mimicking primary hyperparathyroidism. CASE PRESENTATION: A 7-year-old girl presented with nephrocalcinosis. Hypercalciuria, hyperphosphaturia, mild hypercalcemia, hypophosphatemia and elevated parathyroid hormone levels along with normal serum creatinine and absence of hypokalemic alkalosis suggested primary hyperparathyroidism. However, she was ultimately diagnosed with Bartter syndrome type 2 based on the presence of homozygous pathogenic variation in KCNJ1gene. CONCLUSIONS: This is the second reported case of late-onset Bartter syndrome type 2 without hypokalemic alkalosis. Patients with Bartter syndrome may present with high parathyroid hormone levels and hypercalcemia in addition to hypercalciuria. Thus, the present case suggests that the KCNJ1 gene should be included in genetic analysis even in older children with isolated nephrocalcinosis.

Comparison of clinical, pathological and long-term renal outcomes of children with Henoch-Schonlein purpura nephritis and IgA nephropathy.

PURPOSE: To compare clinical, pathological, and long-term renal outcomes of children with Henoch-Schonlein purpura nephritis (HSPN) and IgA nephropathy (IgAN). METHODS: The medical records of patients diagnosed as HSPN and IgAN during childhood were evaluated retrospectively. HSPN and IgAN groups were compared in terms of gender, age, upper respiratory infection history, blood pressure; presence of nephrotic and/or nephritic syndrome; hemoglobin level, leukocyte count, C-reactive protein (CRP), serum albumin (sAlb), creatinine, complement 3 (sC3), complement 4 (sC4) and immunoglobulin A (sIgA) levels; estimated glomerular filtration rate (eGFR) and proteinuria levels; and renal pathology findings at the onset of disease; total follow-up time; and blood pressure, eGFR and proteinuria levels at the last visit. RESULTS: Fifty-four patients were enrolled in the study [38 (70%) HSPN and 16 (30%) IgAN]. The median follow-up time was 60.5 and 72.0 months in HSPN and IgAN groups, respectively (p > 0.05). The HSPN and IgAN groups were also not different in terms of gender, age at the onset; leukocyte count, eGFR, sC3-sC4-sIgA levels; and the presence of endocapillary, extracapillary and mesangial proliferation, tubular atrophy, interstitial fibrosis and IgA, IgM, C3 accumulation in renal tissue. Upper respiratory tract infection history was more common in children with IgAN (8/16 vs 8/38, p = 0.045). sAlb (3.96 ± 0.58 vs 4.40 ± 0.46 g/dL, p = 0.005), hemoglobin (12.1 ± 1.3 vs 13.3 ± 1.2 g/dL, p = 0.004,) and the incidence of mesangial IgG deposition (15/38 vs 11/16, p = 0.049) were lower, while CRP (16.3 ± 7.2 vs 7.8 ± 4.4 mg/L, p = 0.002) and proteinuria (72.1 ± 92.4 vs 34.2 ± 37.9 mg/m2/24 h, p = 0.041) was higher in HSPN group at the onset of disease. Proteinuria and eGFR were similar between the two groups at last visit. CONCLUSION: Children with HSPN and IgAN have little clinical and histological differences in our population. The most prominent difference at presentation with nephritis was higher proteinuria in HSPN probably associated with inflammation due to systemic vasculitis. Long-term renal outcome was good in both HSPN and IgAN.

IL-1ß blockade in periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome: case-based review.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are considered as inflammasome disorders associated with uncontrolled interleukin (IL)-1ß production. Anti-IL1 agents are used in colchicine-resistant cases of FMF. Increase in pro-inflammatory mediators even between febrile attacks in PFAPA suggests that anti-IL1 treatment might be beneficial in these patients. We describe a child presenting with recurrent, self-limited febrile attacks at 1 year of age who was diagnosed as FMF being heterozygous for M694 V mutation. Her clinical findings were only controlled by the addition of canakinumab (2 mg/kg/8 week) to colchicine treatment. However, she developed typical PFAPA attacks during this treatment at 3 years of age. We conducted a literature search focusing on English articles with keywords including PFAPA, anakinra, canakinumab, and rilonacept. Five children and one adult patient with PFAPA were found and evaluated. Anakinra was reported to abort PFAPA attacks in children, while the adult patient first responded and then became resistant to anakinra. Canakinumab was effective in preventing febrile attacks in this patient. Failure of canakinumab to prevent PFAPA attacks in our case may arise from the differences in the pathophysiology of PFAPA and FMF. Thus, further experience with higher doses or shorter intervals of canakinumab is needed in children with PFAPA.

Rhabdomyolysis with different etiologies in childhood.

AIM: To investigate different etiologies and management of the rhabdomyolysis in children. METHODS: Eight pediatric rhabdomyolysis cases who applied to the Dokuz Eylul University Faculty of Medicine Department of Pediatric Nephrology with different etiologies between January 2004 and January 2012 were evaluated in terms of age, gender, admission symptoms, physical examination findings, factors provoking rhabdomyolysis, number of rhabdomyolysis attacks, laboratory results, family history and the final diagnosis received after the treatment. RESULTS: Average diagnosis ages of eight cases were 129 (24-192) ± 75.5 mo and five of them were girls. All of them had applied with the complaint of muscle pain, calf pain, and dark color urination. Infection (pneumonia) and excessive physical activity were the most important provocative factors and excessive licorice consumption was observed in one case. In 5 cases, acute kidney injury was determined and two cases needed hemodialysis. As a result of the further examinations; the cases had received diagnoses of rhabdomyolysis associated with mycoplasma pneumoniae, sepsis associated rhabdomyolysis, licorice-induced hypokalemic rhabdomyolysis, carnitine palmitoyltransferase II deficiency, very long-chain acyl-CoA dehydrogenase deficiency, congenital muscular dystrophy and idiopathic paroxysmal rhabdomyolysis (Meyer-Betz syndrome). CONCLUSION: It is important to distinguish the sporadic and recurrent rhabdomyolysis cases from each other. Recurrent rhabdomyolysis cases should follow up more regardful and attentive.

Body composition with bioelectrical impedance analysis and body growth in late-diagnosed vesicoureteral reflux.

BACKGROUND: This study aimed to evaluate together body composition and growth in children with vesicoureteral reflux (VUR). METHODS: The study was performed in children presenting with recurrent urinary tract infection. The patients were grouped as VUR(+) (Group 1) and VUR(-) (Group 2). A group of healthy cases formed the control group (Group 3). The patients and control cases were evaluated from respect to age, gender, body weight, height, Z-scores of weight (WZ) and height (HZ), and Weight-for-Height Index (WHI). In addition, Body Mass Index, lean body mass, body fat mass, fat-free mass, and body cell mass were measured with bioimpedance analyzer. The parameters compared among groups. RESULTS: There were 53 patients in Group 1, 27 patients in Group 2, and 20 subjects in Group 3. While age, sex, weight, and height were not different among groups, WZ and HZ score were lower in the Group 1 than Group 2 and 3 (P=0.002 and P=0.012 to WZ score, P=0.003 and P=0.016 to HZ score, respectively). WHI was lower Group 1 than Group 2 (P=0.036). Among body composition values, only body cell mass was lower in Group 1 than Group 2 and 3 (P=0.015 and P=0.009, respectively). However, there was no difference between the Group 2 and Group 3. CONCLUSIONS: Deficit of body cell mass with body growth evident in patients with VUR in compared with other groups. Therefore, early evolution and treatment in terms of VUR of children with recurrent urinary tract infections may be important.

Unilateral multicystic dysplastic kidney in children.

This study was performed to evaluate the clinical course and renal outcome of patients with unilateral multicystic dysplastic kidney (MCDK). We retrospectively reviewed the medical records of 59 cases with MCDK followed at Sanliurfa Children's Hospital between January 2009 and February 2013. The median age of the patients (boys 52.5%) was 31 months (range: 6-197) and the median follow-up period was 23 months (range: 6-111). Forty-two (71.2%) patients were diagnosed antenatally. The MCDKs were found more often on the right side (55.9%). The most frequently associated urological abnormality was contralateral vesicoureteral reflux (VUR) (26.6%). A total of 3 (5%) patients developed chronic renal insufficiency (CRI), 2 of whom had grade IV and V VUR; the other patient with CRI had a small and hyperechogenic contralateral kidney, suggesting dysplasia-hypoplasia, without any urological anomalies on imaging studies. The size of MCDK was unchanged in 20 (34%), had regressed in 26 (44%), and had increased in 9 (15.3%) patients. Total involution was documented in 4 (6.7%) patients. Compensatory hypertrophy occurred in 36/45 (80%) patients, with a mean age of 19.2±8.3 months. Proteinuria and hypertension were detected in 1 (1.7 %) patient each. In conclusion, abnormalities in the contralateral kidney in patients with MCDK increase the risk of renal failure. An initial investigation for associated urinary tract malformations should be done and the growth and function of the contralateral kidney, hypertension, and proteinuria should be monitored in all children with MCDK.

Acute tubulointerstitial nephritis-uveitis (TINU) syndrome developed secondary to paracetamol and codeine phosphate use: two case reports.

Tubulointerstitial nephritis (TIN) refers to a group of heterogeneous diseases affecting the interstitial compartment of the kidney. It might be primary or can develop secondary to many urinary systemic diseases. Primary TIN develops mainly following drug usage, exposure to toxins, and also infections and humoral and cell-mediated immune reactions. In some patients, signs of systemic inflammatory reactions can be the first presenting symptoms. Histopathological evaluation reveals mononuclear cells and lymphocytes in the interstitium and tubuli. Acute and chronic TIN can resolve after elimination of the culprit destructive factors, as drugs, toxins and immune reaction. Combination of tubulointerstitial inflammation and uveitis is termed as tubulointerstitial nephritis-uveitis (TINU) syndrome. Uveitis might occur before, after, and also concomitantly with TIN. Herein, two adolescent cases of TIN and TINU, seemingly developed secondary to paracetamol and codeine phosphate use, are presented.

The relationship between renal P-glycoprotein expression and response to steroid therapy in childhood nephrotic syndrome.

In this study, we aimed to investigate the relationship between renal P-glycoprotein (rP-gp) expression and response to corticosteroid therapy in childhood nephrotic syndrome (NS). Expression of rP-gp was evaluated prior to non-steroid immunosuppressive therapy in children with NS (Group 1), prior to any treatment in children with immunoglobulin (Ig)A nephropathy (Group 2), and during renal donation in healthy adults (Group 3); mesangial proliferation was evaluated in Groups 1 and 2. Total dosage of steroid was calculated in Group 1. The ratio of rP-gp (+) glomeruli was higher in Group 1 than Group 3 (33.8 ± 27.1% vs 4.7 ± 4.6%, p=0.000). There were no rP-gp (+) glomeruli in Group 2. The rate of mesangial proliferation was similar in Groups 1 and 2. There was no statistically significant correlation between rP-gp expression and total steroid dosage (r=0.455, p=0.160). Our findings showed that rP-gp expression is increased in patients receiving steroid therapy for NS regardless of the cumulative steroid dosage and mesangial cell proliferation.

Is Imaging Time Between two Tc 99m DMSA Scans Sufficient for Reporting as Renal Parenchymal Scarring? Healed Parenchymal Renal Defect After 6 Years.

UNLABELLED: We aimed to report a healed renal parenchymal defect after 6 years in a 9-year-old girl who was being followed for recurrent urinary tract infection (UTI). The first UTI was at the age of two. She was being followed with ultrasonography, urine analysis and urine culture since the first UTI. Technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy was repeated four times up to the present day. She had a renal parenchymal defect reported as parenchymal scarring, which healed 6 years after the first DMSA scintigraphy. CONFLICT OF INTEREST: None declared.

Renal outcome of children with unilateral renal agenesis.

The aim of this study was to evaluate associated urological anomalies and renal outcome in children with unilateral renal agenesis (URA). Medical records of 51 cases of URA followed at Sanliurfa Children 's Hospital between January 2009 and December 2012 were reviewed retrospectively. In all patients, diagnosis was made by abdominal ultrasound (US) and confirmed by a radionuclide scan. The children were between 3 months and 17 years of age (median age: 5 years). There were 31 males (60.8%) and 20 females (39.2%). In 33 patients (67.3%), the left kidney was absent. Urological anomalies were found in 12/51 patients (23.5%), including ureterovesical junction obstruction in 4 (7.8%), bladder dysfunction in 2 (3.9%), and vesicoureteral reflux (VUR), ureteropelvic junction obstruction, ureterovesical and ureteropelvic junction obstruction, duplicated collecting system plus grade IV VUR, ectopic kidney plus grade V VUR, and ectopic kidney in 1 patient (2%) each. Chronic renal insufficiency (CRI) developed in 5/51 patients (9.8%) (stage III in 3 patients and stage IV in 2), 4 of whom had additional urological anomaly; in the remaining 1 patient, a 17-year-old female, imaging studies were normal except for a small and hyperechogenic solitary kidney determined on US. A total of 3 patients (5.8%) developed hypertension, and all except one had an associated urological anomaly. Proteinuria was seen in 2 patients (3.8%) with stage IV CRI, one of whom was also hypertensive. In conclusion, urological anomalies usually accompany URA and should be followed closely to decrease the risk of renal failure.

Chronic kidney disease in an adolescent with hyperuricemia: familial juvenile hyperuricemic nephropathy.

Chronic kidney disease (CKD) is a life-long condition associated with substantial morbidity and premature death due to complications from a progressive decrease in kidney function. Especially in children, early diagnosis and detection of the etiologic factors are important to improve their health outcomes. Familial juvenile hyperuricemic nephropathy (FJHN) is a rare autosomal-dominant disorder characterized by hyperuricemia with renal uric acid under-excretion and CKD. Genetic studies have revealed mutations in the uromodulin (UMOD) gene. Highlighting the importance of CKD in children, a 14-year-old girl with the rare diagnosis of FJHN is reported herein.

Secondary pseudohypoaldosteronism caused by urinary tract infection associated with urinary tract anomalies: case reports.

Secondary pseudohypoaldosteronism type 1 develops due to transient aldosterone resistance in renal tubules and is characterized by renal sodium loss, hyponatremia, hyperkalemia and high plasma aldosterone levels. Although many reasons are described, urinary tract infections and/or urinary tract anomalies are the most common causes. Although the cause of the tubular resistance is not known exactly, renal scar development due to obstruction and reduced sensitivity of mineralocorticoid receptors due to cytokines such as transforming growth factor (TGF)-beta are the possible mechanisms. It is seen especially within the first three months of life and the frequency decreases with age. The treatment is usually elimination of the underlying cause. In this article, we present four patients with several urinary tract anomalies and concomitant urinary tract infection who developed transient secondary pseudohypoaldosteronism.