Clinical importance of renal calyceal microlithiasis in children.

BACKGROUND: Renal calyceal microlithiasis refers to a hyperechogenic spot in renal calyces <3 mm in diameter detected on renal sonography. These spots possibly represent the first step in calculus formation. The aim of this study was to analyze the clinical presentation, predisposing factors, prognosis and clinical importance of these hyperechogenic spots in renal calyces, renal calyceal microlithiasis, during childhood. METHODS: The data of 292 children (135 girls, 157 boys) with microlithiasis diagnosed between January 1998 and December 2010 were evaluated retrospectively. Demographic data, serum biochemistry, urinary metabolic factors, and renal sonography results were obtained from patient files. A total of 228 patients were re-evaluated at least 6 months after the first observation of renal calyceal microlithiasis and at 6-12 month intervals thereafter. RESULTS: Mean age was 16.8 ± 14.9 months, and mean follow-up duration was 14.6 ± 5.9 months. Presenting symptoms were abdominal or flank pain (41.1%), hematuria (35.6%), dysuria (24.7%) and urinary tract infection (34.6%). Previous ultrasounds were normal in 35% of the children. Metabolic and anatomic abnormalities were found in 55.5% and 17.8%, respectively. Hypercalciuria was the most common metabolic abnormality (88.9%). Among 228 patients who had been re-evaluated, microlithiasis disappeared in 37.7%; decreased in number or size in 23.7%; progressed to renal stone formation in 10.6%; increased in number of microlithiasis in 19.0%; and remained unchanged on radiology in 9.0%. CONCLUSION: Renal calyceal microlithiasis represents a spectrum of clinical situations and underlying metabolic abnormalities that need further investigation in children.

Comparison of recombinant human erythropoietin and darbepoetin alpha in children.

BACKGROUND: The aim was to compare the clinical efficacy of recombinant human erythropoietin (rHuEPO) and darbepoetin alpha (DA) in the treatment of anemia in children with chronic kidney disease (CKD). METHOD: Thirty-four (13 female, 21 male) CKD patients were enrolled in the study. Mean age was 11.42 ± 4.05 years. Nine patients were on hemodialysis, 18 were on peritoneal dialysis and seven patients were in CKD stage 4. RESULTS: Seventeen patients received rHuEPO and the remaining 17 patients received DA. Hemoglobin (Hb) was not significantly different between the two groups during monthly follow up and at the end of 6 months (P > 0.05), but there was a significant increase within each group at the end of 6 months (P = 0.01 for rHuEPO; P = 0.02 for DA). Hb was not different between the patients on and not on dialysis in both groups at the end of the study (P > 0.05). The efficacy of the s.c. and i.v. routes was similar within each group (P > 0.05). Systolic hypertension was observed in only one patient in the DA group, no other adverse effect was observed in either groups. CONCLUSION: DA is a reasonable alternative to rHuEPO in the treatment of anemia in pediatric CKD patients, due to its clinical efficacy, convenience of use, patient compliance and tolerability.

Matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in vesicoureteral reflux.

The aim of this study was to investigate whether urine levels of matrix metalloproteinase 9 (uMMP9) and tissue inhibitor of metalloproteinase 1 (uTIMP1) are novel biomarkers of vesicoureteral reflux (VUR) and to determine the optimal cut-off levels of these enzymes to predict VUR in children. The study group consisted of 67 children with VUR and 20 healthy children. Urine MMP9 and TIMP1 levels were measured by an enzyme-linked immunosorbent assay. Children with VUR had significantly higher uMMP9 (1,539.8 vs. 256.4 pg/mL; p = 0.0001) and uTIMP1 (182 vs. 32.6 pg/mL; p = 0.0001) levels than healthy children. For the prediction of VUR, the sensitivity of uMMP9 was 67%, with a specificity of 85% [cut-off value 1,054 pg/mL; area under the curve (AUC) 0.77], and the sensitivity of uTIMP1 was 74%, with a specificity of 65% (cut-off value 18.7 pg/mL; AUC 0.73). Both uMMP9 and uTIMP1 levels were significantly higher in patients with renal scar (uMMP9: 3,117.3 vs. 1,234.15 pg/mL; p = 0.0001; uTIMP1: 551.05 vs. 128.64 pg/mL; p = 0.0001). Urine MMP9 levels had a sensitivity of 81.2%, with a specificity of 85% to predict renal scar in the VUR group (cut-off 1,054 pg/mL; AUC 0.88). The sensitivity of uTIMP1 was 75%, with a specificity of 90% to predict renal scar (cut-off 243.7 pg/mL; AUC 0.82). Based on these results, we suggest that uTIMP1 may be a useful marker to predict renal scarring with a different cut-off value from VUR and a high specificity at this cut-off point. Although uMMP9 seemingly cannot distinguish renal scar from VUR, the simultaneous increase in the level of both markers may indicate ongoing renal injury due to VUR.

Ambulatory blood pressure monitoring and renal functions in term small-for-gestational age children.

The aim of this study was to investigate the relationship between birth weight and blood pressure (BP) by means of ambulatory BP monitoring (ABPM) and renal functions in non-obese children who were born small-for-gestational age (SGA) at term. The study group consisted of 39 (19 female, 20 male; mean age 8.8 ± 2.6 years) children born SGA. Their data were compared to those of 27 (13 female, 14 male; mean age 8.2 ± 2.9 years) children born appropriate-for-gestational age (AGA). No difference between SGA and AGA children was observed based on office BP measurements and daytime, nighttime and 24-h ABPM. Seventeen SGA (48.6%) and nine AGA (37.5%) children had a 24-h systolic BP (SBP) load over 25%, and seven of these (5 SGA, 2 AGA) were hypertensive according to mean SBP values. The prevalence of the non-dipping phenomenon in SGA and AGA children was similar. Renal functions were normal and similar in both groups. Three children (2 SGA, 1 AGA) with normal glomerular filtration rate had higher microalbumin excretion and one SGA child had systolic hypertension according to the office BP. Our findings demonstrate that the influence of intrauterine growth restriction on BP is not manifested during the childhood period, and they do not support the existence of a negative relationship between birth weight and BP in children.

Methylenetetrahydrofolate reductase C677T polymorphism in patients with Henoch-Schönlein purpura.

AIM: Associations between several vascular diseases such as Kawasaki disease, venous and arterial thromboembolism, cardiovascular disease, diabetic nephropathy, focal segmental glomerulosclerosis and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have been reported. This is a clinical study designed to investigate the possible effects of MTHFR C677T polymorphism on the development of Henoch-Schönlein purpura (HSP). METHODS: Forty-one patients with HSP (25 male/16 female) with a mean age of 7.8 ± 2.9 years were included in the study. The control group consisted of 50 healthy children. MTHFR genotypes were determined by polymerase chain reaction and by Hindf I restriction enzyme analysis and subsequent 3% agarose gel electrophoresis techniques. RESULTS: No significant differences were observed in the distribution of MTHFR genotypes or allele frequencies in the HSP cases versus controls. Plasma homocysteine levels and vitamin B(12) levels were almost comparable in the HSP patients and control group without a significant difference. Folic acid levels were within normal limits in the HSP cases and the control group, HSP patients' levels being significantly higher than the control group. No significant relationship was present with the MTHFR genotype and plasma homocysteine, vitamin B(12) and folic acid levels in HSP patients. CONCLUSION: No association with MTHFR gene polymorphism and homocysteine plasma levels could be found in patients with HSP. The results of this study indicate that other mechanisms should be operative in the development of HSP.

Effect of paraoxonase 1 gene polymorphisms on clinical course of Henoch-Schönlein purpura.

BACKGROUND: Henoch-Schönlein purpura (HSP) is a systemic vasculitis; its pathogenesis is still unknown. Oxidative stress may play a role in the pathogenesis of HSP. Paraoxonase1 (PON1) is an antioxidant enzyme. Two polymorphisms have been defined in the coding region of the PON1 gene, Q/R192 and L/M55. In the present study, we aimed to investigate the effect of PON1 gene polymorphisms on the course and renal involvement of HSP in Turkish children. METHOD: Forty-six patients with HSP were compared with 34 healthy children regarding the distribution of PON1 polymorphisms. RESULTS: PON1 Q/R192 genotype distribution was 58.6% QQ, 32.6% QR and 8.8% RR in the HSP group and 14.3% QQ, 50% QR and 35.7% RR in the control group. The frequency of QQ genotype was higher in the HSP group, and the presence of QQ genotype increased the risk by 3.42-fold for developing HSP (p=0.000, Fisher exact test; odds ratio [OR] = 2.048; 95% confidence interval [95% CI], 1.396-3.00). PON1 L/M55 genotype distribution was 50% LL, 43.5% LM and 6.5% MM in the HSP group and 48% LL, 26% LM and 26% MM in the control group. The frequency of MM genotype was lower in the HSP group, and the presence of MM genotype decreased the risk by 7.38-fold for developing HSP (p=0.009, Fisher exact test; OR=7.380, 95% CI, 1.474-36.953). CONCLUSION: PON1 polymorphisms may contribute to the pathogenesis and course of HSP, but we suggest that further investigations with larger patient groups are required to confirm our results.

Takayasu arteritis in children.

OBJECTIVE: To retrospectively evaluate the clinical features, angiographic findings, and outcomes of children with Takayasu arteritis (TA) in Turkey. METHODS: Clinical, laboratory, and angiographic findings and outcomes of 19 children with TA were evaluated with a retrospective chart review. The criteria for inclusion were those proposed by the American College of Rheumatology. RESULTS: Mean followup period was 35.89 +/- 40.75 months (range 1-168, median 30). There were 14 girls and 5 boys. The mean age at diagnosis was 12.84 +/- 2.69 years (range 8-17, median 13). The most common complaints on admission were headache (84%), abdominal pain (37%), claudication of extremities (32%), fever (26%), and weight loss (10%). One patient presented with visual loss. Examination on admission revealed hypertension (89%), absent pulses (58%), and bruits (42%). Angiography revealed type I in 13 patients (aortic arch, descending thoracic, and abdominal aorta), type II in 4 (descending thoracic aorta and abdominal aorta), and type IV in 2 (diffuse aortic and pulmonary artery). The most commonly involved vessels were the renal, subclavian, and carotid arteries. All patients received corticosteroid therapy, and further immunosuppressive therapy was added in 15 patients. Fourteen of the 17 hypertensive patients had renal artery stenosis and 9 underwent surgery or interventional therapy. Thoraco-abdominal bypass graft was performed in 2 patients who had abdominal aortic stenosis. CONCLUSION: Hypertension is the most common clinical feature at presentation. Corticosteroid and immunosuppressive therapy was effective in the control of disease activity. Angioplasty or bypass grafting was successfully performed when needed.

Peritonitis in children who receive long-term peritoneal dialysis: a prospective evaluation of therapeutic guidelines.

In children who are on chronic peritoneal dialysis, peritonitis is the primary complication compromising technique survival, and the optimal therapy of peritonitis remains uncertain. An Internet-based International Pediatric Peritonitis Registry was established in 47 pediatric centers from 14 countries to evaluate the efficacy and safety of largely opinion-based peritonitis treatment guidelines in which empiric antibiotic therapy was stratified by disease severity. Among a total of 491 episodes of nonfungal peritonitis entered into the registry, Gram-positive organisms were cultured in 44%, Gram-negative organisms were cultured in 25%, and cultures remained negative in 31% of the episodes. In vitro evaluation revealed 69% sensitivity of Gram-positive organisms to a first-generation cephalosporin and 80% sensitivity of Gram-negative organisms to a third-generation cephalosporin. Neither the risk factors assumed by the guidelines nor the choice of empiric therapy was predictive of either the early treatment response or the final functional outcome of the peritonitis episodes. Overall, 89% of cases achieved full functional recovery, a portion after relapsing peritonitis (9%). These data serve as the basis for new evidence-based guidelines. Modification of empiric therapy to include aminoglycosides should be considered.

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.

Is paraoxonase 192 gene polymorphism a risk factor for membranoproliferative glomerulonephritis in children?

We investigated the effects of paraoxonase (PON1) 192 polymorphism on serum PON1 activity and the impact of phenotypic expression on the risk and prognosis of Turkish children with membranoproliferative glomerulonephritis (MPGN). Eighteen children with biopsy-proven Type I MPGN (10 boys, 8 girls) and age-matched 53 healthy controls were included in the study. PCR (polymerase chain reaction), RFLP (restriction fragment length polymorphism) and agarose gel electrophoresis techniques were used to determine the PON1 192 genotype. PON1 activity was measured by spectrophotometric assay of p-nitrophenol production following addition of paraoxon. We found that PON1 192 genotype distribution (AA, AB, BB) in MPGN patients were 61.1%, 22.3%, 16.6% and 15.1%, 35.8%, 49.1% in controls, respectively. The frequency of AA genotypes was significantly higher in the MPGN group (0.611) compared with the healthy controls (0.151) (p < 0.001). Although the serum PON1 activity was lower in MPGN patients (103.3 +/- 55.2 U/l) than the healthy controls (130.9 +/- 71.2 U/mol), the difference was not statistically significant (p = 0.0563). In the genotypes of patients and controls classified according to PON1 A/B polymorphism; serum PON1 activities were significantly increased (p < 0.001, ANOVA) in the order of PON1 AA, AB and BB in both MPGN patients (82.4, 91.7 and 173.6 U/l) and healthy controls (85.9, 119.9 and 193.1 U/l), respectively. There was a significant relationship between the poor prognosis and having AA genotype and low PON1 activity. Of the 8 patients with poor prognosis, 7 had genotype AA and the remaining one was AB heterozygote. Our results suggest that homozygosity for the A allele might have an important role on the risk for developing MPGN and may also be associated with the poor prognosis of disease. In conclusion, we suggest that the PON1 activities are affected by PON1 genetic variability in Turkish patients with MPGN.

Brain calcification due to secondary hyperparathyroidism in a child with chronic renal failure.

Secondary hyperparathyroidism (SHPT) has been better treated over the last decades, but the rate of metastatic calcifications, which were rarely seen before, was significantly increased in dialysis patients. The presence of uncontrolled SHPT, disorders of calcium (Ca) and phosphorus homeostasis and the common usage of large doses of vitamin D and Ca- containing phosphate binders may all contribute to the metastatic calcifications of soft tissues and vasculature leading to some life-threatening complications. Although the metastatic lung, heart, kidney, intestinal wall, skin, eye and soft tissue calcifications have been commonly reported in adults and also in children undergoing dialysis, the central nervous system calcification is a very rare condition. We report here a pediatric hemodialysis patient who presented with severe neurological findings due to the metastatic brain calcification secondary to his uncontrolled hyperparathyroidism.

Central nervous system vasculitis secondary to parvovirus B19 infection in a pediatric renal transplant patient.

Central nervous system (CNS) vasculitis secondary to chronic parvovirus B19 (B19) infection presenting with recurrent neurological findings is a very rare disorder during childhood. Here we report a 12-year-old boy with a renal transplant who had chronic B19 infection with skin eruptions and recurrent episodes of encephalopathy with focal neurological deficits. B19 DNA was detected in blood, bone marrow, and skin biopsy specimens. Repeat cranial magnetic resonance (MR) imaging during each episode of encephalopathy showed variable focal findings, and MR angiography revealed vasculitic changes with narrowing of the cerebral arteries. We hypothesized that the CNS vasculitis might be associated with the chronic B19 infection. At the time of his fourth presentation with the same clinical findings, we administered intravenous immunoglobulin (IVIG) (1 g/kg per day, 2 consecutive days), which we continued for 6 months, at monthly intervals. IVIG therapy resulted in remission and has been effective not only for the clearance of B19, but also for the improvement of clinical and radiological findings of CNS vasculitis. We suggest that chronic B19 infection should be considered in immunocompromised patients with suspected CNS vasculitis. IVIG should be considered as a part of the treatment.

Biochemical bone markers in nephrotic children.

In this study we evaluated the effects of high-dose corticosteroid (CS) therapy and the character of the nephrotic syndrome (NS) itself on bones in patients with normal glomerular filtration rate. We measured serum osteocalcin (OC), alkaline phosphatase (ALP), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, calcium (Ca), phosphorus (P), and magnesium (Mg) levels, and urinary Ca and protein excretion in nephrotic children during the active phase before (group Ia) and after CS treatment (group Ib). The results were compared with age-matched control subjects. A significant increase in urinary Ca excretion was observed after CS treatment. Serum ALP, OC, and iPTH levels were within normal limits at the time of study entry. However, both serum OC and ALP levels showed a significant decrease after the completion of CS treatment (OC from 13.6+/-9.2 ng/ml to 6.7+/-5.2 ng/ml and ALP from 151.8+/-60.2 U/l to 116+/-43.8 U/l). 25-Hydroxyvitamin D levels increased to 17.2+/-8.9 microg/l from 9.9+/-6.9 microg/l after CS treatment. The effects of recurrent use of CSs were assessed by dividing nephrotic patients into two subgroups: infrequent relapsers (IFR) and frequent relapsers (FR). The cumulative dose of CS was 28,125 mg/m(2) for IFR and 105,000 mg/m(2) for FR. The changes in OC, ALP, and 25-hydroxyvitamin D levels after CS treatment were significantly different between IFR and FR. We conclude that high-dose CS treatment causes a decrease in bone formation, as shown by the changes in OC and ALP levels. 25-Hydroxyvitamin D levels remained lower than control subjects after CS therapy. The higher the cumulative dose of CS used the more marked the changes in biochemical bone markers. The contribution of FR to baseline 25-hydroxyvitamin D levels needs further study.

ACE I/D gene polymorphism in primary FSGS and steroid-sensitive nephrotic syndrome.

The role of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism in various renal disorders has been investigated. We evaluated the association between the clinical characteristics and ACE genotypes of Turkish children with primary focal segmental glomerulosclerosis (FSGS) and steroid-sensitive nephrotic syndrome (SSNS). Patients with FSGS ( n=30) were classified into two groups: one with remission together with stable renal function ( n=22) and the other without remission and with impaired renal function ( n=8). We classified children with SSNS ( n=43) that were followed for at least 4 years into two subgroups as having more frequent ( n=19) and less frequent relapses ( n=11). The DD genotype was more frequent in the SSNS group than that in controls (37% vs. 17%, chi(2)=4.98, P=0.025). However, among SSNS subgroups, the frequency of the DD genotype was not different. The distribution of ACE genotype was similar among patients with FSGS and SSNS. There was no difference in the ACE I/D distribution between children with FSGS and normal controls (II 10%, ID 60%, DD 30% vs. II 13%, ID 70%, DD 17%). The frequency of the DD genotype was higher in FSGS patients with declining renal function (63%) than in those with stable renal function (18%) ( P=0.031). Progressive renal impairment was significantly more frequent in patients with FSGS with the homozygous D allele compared with FSGS patients with ID and II genotypes. Our results indicate that the DD genotype may be a risk factor for the development of progressive renal impairment in children with FSGS; however, larger studies are required to confirm this.