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.

Urinary oxalate to creatinine ratios in healthy Turkish schoolchildren.

AIM: we aimed to establish reference values for urinary oxalate to creatinine ratios in healthy children aged 6-15 years and to investigate the relationship between their nutritional habits and oxalate excretion. MATERIALS AND METHODS: Random urine specimens from 953 healthy children aged 6-15 years were obtained and analyzed for oxalate and creatinine. Additionally, a 24-h dietary recall form was prepared and given to them. The ingredient composition of the diet was calculated. The children were divided into three groups according to age: Group I (69 years, n = 353), Group II (10-12 years, n = 335), and Group III (13-15 years, n = 265). RESULTS: The 95th percentile of the oxalate to creatinine ratio for subjects aged 6-9, 10-12, and 13-15 years were 0.048, 0.042, and 0.042 mg/mg, respectively. The oxalate to creatinine ratio was significantly higher in Group 1 than in Group 2 and Group 3. Urinary oxalate excretion was positively correlated with increased protein intake and negatively correlated with age. A significant positive correlation was determined between urinary oxalate excretion and the proline, serine, protein, and glycine content of diet. Dietary proline intake showed a positive correlation with the urine oxalate to creatinine ratio and was found to be an independent predictor for urinary oxalate. CONCLUSIONS: These data lend support to the idea that every country should have its own normal reference values to determine the underlying metabolic risk factor for kidney stone disease since regional variation in the dietary intake of proteins and other nutrients can affect normal urinary excretion of oxalate.

Increased endothelial microparticles in obese and overweight children.

BACKGROUND: Obesity in children increases the risk of atherosclerosis. Endothelial dysfunction is an important factor in the pathogenesis of atherosclerosis, and endothelial microparticles (EMPs) are considered as markers of endothelial dysfunction. In this study, we aimed to evaluate circulating EMPs in obese and overweight children and to disclose the measure of obesity with the strongest relation with circulating microparticles and carotid atherosclerosis. METHODS: This prospective study included 55 obese and overweight children and 23 healthy controls. Insulin resistance was studied. Both in vivo and in vitro human umbilical vein endothelial cell evaluations were used for the study. Circulating EMPs (CD144 and CD146) were measured by flow cytometry. The carotid artery intima-media thickness (cIMT) and left ventricular mass index (LVMI) were measured using ultrasound and echocardiography, respectively. Study groups were compared for anthropometric measurement, insulin resistance, circulating EMP, cIMT, and LVMI. The relationship among overweight, obesity, and circulating EMPs were investigated. RESULTS: Blood pressure, CD144+EMP levels, and LVMI were statistically higher in the patients group than in the control group. The multiple logistic regression analysis and the backward elimination method showed that CD144+EMP and systolic blood pressure had a linear relationship with overweight and obesity. CONCLUSION: Our results suggest that endothelial damage starts in the early stage of childhood obesity and that obese and overweight children have increased circulating CD144+EMPs, showing that endothelial dysfunction and increased CD144+EMPs may be related to obesity.

Circulating endothelial microparticles in children with Henoch-Schönlein purpura; preliminary results.

The aim of this study was to investigate the levels of circulating endothelial microparticles (EMPs) in children with HSP and to determine whether there was a difference between patients with nephritis and those without nephritis. Twenty patients with HSP aged between 2.5 and 15 and 10 age-and sex-matched healthy controls were enrolled in the study. The HSP group was divided into two groups, including patients with nephritis (n = 9) and those without nephritis (n = 11). In all groups, circulating EMPs were enumerated by flow cytometry, after staining platelet-free plasma with PE-conjugated anti-CD144. At the same time, human umbilical vein endothelial cells (HUVEC) were incubated with the platelet-free plasma of patients with HSP and that of the control group. Then, circulating EMPs were counted in HUVEC supernatant incubated with the platelet-free plasma of patients and control groups, after staining the supernatant with PE-conjugated anti-CD146. Circulating EMPs were significantly higher in both the active and the remission period of the patient groups compared with the control subjects. In the patient group, there were no statistically significant differences in the level of circulating EMPs between patients with nephritis and those without nephritis. Both CD144 and 146+EMP in patients with HSP nephritis in the active period were substantially higher than in those remissions. CD144+EMP in the active period were substantially higher than in the remission period in patients without nephritis. We detected that circulating EMPs increased in patients with HSP in both active and remission periods. Although clinical and laboratory findings return to normal in the remission period, the increased circulating EMPs may show that the subclinical inflammatory process is continuous. We think that circulating EMPs could be used as a surrogate marker for subclinical inflammation in HSP.

Urinary uric acid : creatinine ratios in healthy Turkish children.

BACKGROUND: Determining uric acid : creatinine ratios in random urine samples may be useful to assess the excretion of uric acid in children. Because it was shown that urinary uric acid excretion varies with age and geographic area, it is important to have accurate reference values of uric acid excretion. The aim of the present study was therefore to obtain regional reference values for urinary uric acid : creatinine ratios in healthy Turkish children. METHODS: A total of 1306 children aged 1 month-15 years were analyzed for uric acid and creatinine, and urinary uric acid : creatinine ratios were determined from each sample. The second non-fasting morning urine samples were taken from all the children. Urine samples were analyzed for uric acid using the uricase method, and for creatinine with the Jaffe reaction. RESULTS: The mean +/- SD and 5th-95th percentiles of urinary uric acid : creatinine ratios (mg/mg) were 1.09 +/- 0.48 and 0.27-1.87 at 1-6 months, 0.86 +/- 0.41 and 0.19-1.64 at 7-12 months, 0.76 +/- 0.32 and 0.32-1.43 at 1-3 years, 0.63 +/- 0.29 and 0.20-1.23 at 4-6 years, 0.44 +/- 0.24 and 0.14-0.93 at 7-11 years, and 0.30 +/- 0.14 and 0.12-0.62 at 12-15 years. Uric acid : creatinine ratios were not significantly different between boys and the girls except at 12-15 years. Girls aged 12-15 years had higher urinary uric acid : creatinine ratio when compared with boys (P < 0.05). There was no correlation between urinary uric acid : creatinine ratio and protein intake. CONCLUSIONS: Urinary uric acid : creatinine ratio changes with age. When assessing urinary uric acid : creatinine ratio, the clinician should consider the age of the child.

Cytomegalovirus infection and haemophagocytosis in a patient with congenital nephrotic syndrome.

Congenital nephrotic syndrome is a rare clinical entity defined as massive proteinuria leading to symptoms within the infant's first 3 months of life. Although the association between congenital nephrotic syndrome and cytomegalovirus infection has been identified, association with haemophagocytosis has not been reported in the literature. In this case report we describe concomitant cytomegalovirus infection and haemophagocytosis in a 3-month-old girl with congenital nephrotic syndrome.

The relationship between circulating endothelial microparticles and arterial stiffness and atherosclerosis in children with chronic kidney disease.

BACKGROUND: Endothelial dysfunction is an important factor in the pathogenesis of atherosclerosis, and endothelial microparticles (EMPs) are considered as markers of endothelial dysfunction. In this study, we aimed to examine the relationship between EMPs and arterial stiffness and atherosclerosis in children with chronic kidney disease (CKD). METHODS: This cross-sectional study included 37 dialysis patients (12 haemodialysis, 25 peritoneal dialysis), 33 pre-dialysis patients and 18 healthy controls. Both in vivo and in vitro (HUVECs) evaluations were used for the study. Circulating EMPs were measured by flow cytometry. The carotid artery intima-media thickness (cIMT) and pulse wave velocity (PWV) were measured by using high-resolution ultrasound. Study groups were compared for circulating EMP, cIMT and PWV. The relationship between EMPs and arterial stiffness and atherosclerosis was evaluated. RESULTS: The levels of PWV, cIMT, CD144 + EMP and CD146 + EMP in the dialysis group were significantly higher than those in the pre-dialysis and control groups (P < 0.05). Additionally, the levels of cIMT, CD144 + EMP and CD146 + EMP in the pre-dialysis group were significantly higher than those in the control group (P < 0.05). In all CKD patients, the CD144 + EMP was significantly positively associated with blood pressures, age, known duration of disease, CRP and PTH, and was significantly negatively associated with haemoglobin, GFR and albumin. The CD146 + EMP was significantly positively associated with blood pressures, age and CRP. In a multiple linear regression analysis, in the CKD group, cIMT was independently related to mean blood pressure and dialysis duration. PWV was independently related to the CD144 + EMP and mean blood pressure. CONCLUSION: Our results suggest that endothelial damage starts in the early stage of CKD, that the endothelial dysfunction becomes overt with the increase of cardiovascular risk factors and that EMPs may be a reliable marker of the subclinical atherosclerosis and arterial stiffness.

Cerebral vasculitis and unilateral sixth-nerve palsy in acute post-streptococcal glomerulonephritis.

Cerebral vasculitis associated with acute post-streptococcal glomerulonephritis (APSGN) is rare. A 13-year-old girl presented with severe headache, vomiting, oedema and macroscopic haematuria. There was a history of upper respiratory infection 2 weeks previously. A diagnosis of APSGN was made. On admission, she was normotensive and biochemically well balanced. She experienced a tonic-clonic seizure 2 hours later. An MRI brain scan demonstrated multiple areas of abnormal signal intensity in the cerebral and cerebellar white matter, and subarachnoid haemorrhage consistent with vasculitis was diagnosed. A sixth-nerve palsy developed on the 6th day of admission. An elevated anti-streptolysin titre and low serum C3 complement level together with typical features on renal biopsy supported the diagnosis of APSGN. All clinical and laboratory abnormalities improved with corticosteroid therapy, pulse methyl-prednisolone. APSGN can present with central nervous system abnormalities without hypertension, uraemia and electrolyte disturbance.

Pediatric urolithiasis: an 8-year experience of single centre.

OBJECTIVE: The objective was to investigate the clinical features and metabolic and anatomic risk factors for kidney stone formation in our patient group. METHODS: Between 1998 and 2005, 179 children (94 girls, 85 boys) followed in our department because of urolithiasis were enrolled to participate in our study. Clinical presentation, urinary tract infection, stone localisation, positive family history, stone composition, presence of anatomic abnormalities and urinary metabolic risk factors, and treatment modality were evaluated retrospectively. RESULTS: The mean age at diagnosis of stone disease was 4.5 years (range 0.25-15.3 years). The mean follow-up duration was 8 months (range 1-98). The major clinical presentations of our patients were abdominal pain and/or flank pain in 100 children (55.9%) and macroscopic hematuria in 25 (14%). Urinary tract infection was detected in 20% of patients on admission. Forty-three children (24%) had a urinary tract abnormality and ureteropelvic junction obstruction was the most common abnormality. A family history of stone disease was recorded in 98 patients (54.7%). Stones were located within the renal parenchyma in 90 patients. Hypercalciuria and hyperuricosuria were detected in 42.3 and 54.8% respectively. Stone analysis was performed in 63 children and calcium oxalate was a major mineral. Surgical treatment was performed in 49 children and extracorporeal shock wave lithotripsy (ESWL) in 41 children. CONCLUSION: We think that urolithiasis remains a serious problem in children in our country. Family history of urolithiasis, urologic abnormalities (especially under the age of 5 years), metabolic disorders and urinary tract infections tend to indicate childhood urolithiasis.

Distal vaginal atresia resulting in obstructive uropathy accompanied by acute renal failure.

Children with hydrometrocolpos due to distal vaginal atresia may present with severe obstructive uropathy. Here we report a 27-day-old infant with a hydrometrocolpos causing life-threatening renal failure. Percutaneous drainage of the hydrometrocolpos resulted in dramatically improved clinical and laboratory findings in the patient.

Reno-vascular hypertension in childhood: a nationwide survey.

Renovascular disease accounts for 8-10% of all cases of paediatric hypertension, whereas, in adults, its incidence is approximately 1%. The Turkish Paediatric Hypertension Group aimed to create the first registry database for childhood renovascular hypertension in Turkey. Twenty of the 28 paediatric nephrology centres in Turkey responded to the survey and reported 45 patients (27 girls, 18 boys) with renovascular hypertension between 1990 and 2005. The age at presentation ranged from 20 days to 17 years. The mean blood pressure at the diagnosis was 169/110 mmHg. Chief complaints of symptomatic patients were headache (38%), seizure (18%), epistaxis (4%), growth retardation (4%), cognitive dysfunction (4%), polyuria (2%), palpitation (2%), and hemiplegia (2%). Renovascular hypertension was found incidentally in 11 children. The diagnosis of renovascular hypertension was established with conventional angiography in 39 patients, MR angiography in three, CT angiography in two, and captopril diethylene triamine penta-acetic acid (DTPA) scintigraphy in one patient. Twenty-one children had bilateral renal artery stenosis and 24 had unilateral renal artery stenosis. Of these, 14 (31%) had fibromuscular dysplasia; 12 (27%) Takayasu's arteritis; six (13%) neurofibromatosis; two (5%) Williams syndrome; one (2%) Kawasaki disease; one (2%) mid-aortic syndrome; one (2%) extrinsic compression to the renal artery, and eight (18%) unspecified bilateral renal artery stenosis. Hypertension was controlled with antihypertensive drugs in 17 patients. Percutaneous transluminal angioplasty (PTRA) or surgery had to be performed in 28 patients: PTRA in 16 patients, PTRA + surgery in one patient and surgery in 11 patients (four nephrectomies). The importance of vasculitic disease, especially Takayasu's arteritis, should not be underestimated in children with renovascular hypertension.

Carotid artery thickness in children and young adults with end stage renal disease.

Atherosclerosis is a major cause of morbidity and mortality for ESRD patients and we have little knowledge about the presence and risk factors of atherosclerosis in children with CRF. The measurement of carotid artery intima-media thickness (cIMT) using high-resolution ultrasonography is suggested as an excellent marker of subclinical atherosclerosis. In this study, we aimed to investigate the presence of atherosclerosis and to determine the relationship between atherosclerosis and some risk factors in children and young adults with ESRD. Thirty-four patients with ESRD and 20 controls were included in this study. The measurement of cIMT was performed by using a linear B-mode 7.5-MHz ultrasound transducer. We determined anemia, abnormal calcium/phosphate metabolism, hyperhomocysteinemia, hypertriglyceridemia and increased lipoprotein (a) levels in the ESRD group. The cIMT in the ESRD group was higher than in the control group (P<0.05). SBP, DBP, MAP, LVMI and LVH prevalence were statistically higher in the ESRD group (P<0.05). There were significant positive correlations between cIMT and LVMI, MBP, whereas a significant negative correlation was determined between cIMT and PTH in the ESRD group (P<0.05). When a multiple linear regression analysis was performed with cIMT as a dependent variable and LVMI, MBP, PTH, as independent variables, a significant positive correlation was determined between cIMT and LVMI (P<0.05). In conclusion, we think that arteriopathy occurs in children with ESRD. Left ventricular hypertrophy and hypertension may associate with vascular changes in children and young adults with ESRD. Further investigations are necessary to explain association of LVMI index with cIMT.

Stepwise shock wave lithotripsy: results of initial study for the treatment of urinary stones in childhood.

OBJECTIVE: To assess the effectiveness of stepwise extracorporeal shock wave lithotripsy in the treatment of upper urinary stones in childhood. PATIENTS AND METHODS: Between August 1998 and August 2003, 31 patients were treated for renal or ureteric stones. All treatments were performed with Dornier Compact Delta lithotripter. The number of shock wave was limited to maximum 3000 shock waves/session. The voltage was started at 10 kV and increased stepwise to 12.75 kV. Stone clearance was assessed at 3 months. The stone free state was defined as the absence of stone fragments. RESULTS: Total 31 stones (24 renal and 7 ureteral stones) were treated. The age of the patients was median 8 (min-max: 0.8-12) years. The length of the stones was median 1 (min-max: 0.5-1.5) cm for renal stones and median 0.5 (min-max: 0.5-1) cm for ureteral stones. As an auxiliary procedure, open pyelolithotomy was required for 1 patient. The overall stone free rates for renal and ureter stones were 79% and 100%, respectively. Post-treatment insignificant hematuria was observed in all cases. CONCLUSION: Stepwise shock wave lithotripsy was an effective procedure for the treatment of urinary calculi in childhood.

Incidence of nocturnal enuresis and nocturia in children with tuberculosis.

Nocturnal enuresis is a common problem and occurs in 15 to 20 percent of 5-year-old children. The etiology of nocturnal enuresis remains unknown and is probably multifactorial. In this study 52 children aged between 6-17 years with tuberculosis were questioned for nocturia and nocturnal enuresis, retrospectively. Nocturnal, enuresis was found in 12 (23%) and nocturia in 22 (42%) of the children, respectively. After specific treatment with antituberculosis drugs nocturnal enuresis and nocturia were improved in 5 and 21 children, respectively. However, it could not be explained why these disorders were much higher in children with tuberculosis than healthy children. The findings suggest that nocturnal enuresis and nocturia may be in a high frequency in children with tuberculosis; however, the authors think that prospective and more extensive studies should be performed to clarify these preliminary findings.

Antibody response to influenza A vaccination in children with nephrotic syndrome.

The aim of this study was to determine the antibody response to influenza vaccination in children with nephrotic syndrome (NS). Nineteen children with NS and 10 healthy controls were vaccinated with a 1999-2000 influenza vaccine. A dose of 0.25 ml was used for those under 6 years and 0.5 ml for those over 6 years. All children were given two doses with a month between each dose. Antibody titers were measured before vaccination and 1 month after vaccination in both groups and 6 months after vaccination in 8 patients with NS. The proportion of subjects in the nephrotic group with protective antibody titers before immunization (10.5%) was significantly lower than the proportion at 1 (78.9%) and 6 months (87.5%) post vaccination. The mean concentration of specific IgG antibodies to influenza A in the NS group increased 6-fold at 1 month and approximately 14-fold at 6 months. These results suggest that pediatric patients with NS have an adequate antibody response to influenza A vaccine. Protective antibody titers to influenza A were maintained at 6 months after immunization in 8 patients with NS.

Homocysteine and left ventricular hypertrophy in children with chronic renal failure.

Hyperhomocysteinemia is recognized as an independent risk factor for cardiovascular disease, especially atherosclerosis, in adult patients with chronic renal failure (CRF). However, there is little information about the relationship between plasma homocysteine levels and left ventricular hypertrophy. The aim of this study was to determine plasma homocysteine levels and risk factors for left ventricular hypertrophy and to investigate the relationship between plasma homocysteine concentration and left ventricular mass index (LVMI) in children with CRF. The homocysteine level was measured by high-performance liquid chromatography and LVMI was calculated using echocardiographic findings in 27 children with CRF and 16 healthy controls. The mean LVMI and mean plasma homocysteine concentration in the CRF group, especially in patients with end-stage renal disease, were statistically higher than the control group ( P<0.05). There was no correlation between LVMI and plasma homocysteine concentration. There was a positive correlation between plasma homocysteine concentration and serum creatinine level. There was a positive correlation of LVMI with creatinine and blood pressures (systolic, diastolic, and mean arterial pressure). There was a negative correlation of LVMI with hemoglobin level in multiple linear regression analysis. In our view homocysteine does not have a direct effect on left ventricular structure and left ventricular hypertrophy is the end organ damage associated with hypertension, anemia, and CRF. More prospective studies are needed to better clarify the inter-relationships of plasma homocysteine level and left ventricular structure in children with CRF.

Acute hemorrhagic edema of infancy.

BACKGROUND: Acute hemorrhagic edema of infancy (AHEI) is a leukocytoclastic vasculitis of infants. Even though the cutaneous findings are dramatic in both appearance and rapidity of onset, the prognosis is benign. METHODS: We report on eight patients with AHEI evaluated from the viewpoints of age, sex, history of infection, drug administration or immunization before the onset of skin lesions, laboratory findings, cutaneous findings, cutaneous biopsy and treatment. RESULTS: The ages of the patients, six of whom were male, ranged between 7 and 27 months. Five episodes in our patients occurred in winter. Six patients (75%) had a history of recent infection, drug administration or immunization. All patients had fever, peripheral edema and large, purpuric, annular or targetoid plaques on the face and extremities. Two patients had mucosal involvement (conjunctiva and palatum molle). One patient with severe genital involvement had trunk involvement. Hematologic and immunologic tests were not diagnostic in any patient. Leukocytoclastic vasculitis was demonstrated in four patients for whom a cutaneous biopsy was performed. Complete recovery time ranged between 4 and 7 days. CONCLUSIONS: We believe that AHEI is a benign disorder, despite its dramatic appearance. We want to point out that mucosal and trunk involvement may also occur in AHEI.