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Background: We prospectively evaluated whether serum cystatin C (CysC) detected acute kidney injury (AKI) earlier than basal serum creatinine (Cr)., Methods: In 107 pediatric patients at high risk of developing AKI, serum Cr and serum CysC were measured upon admission. Baseline estimated creatinine clearance (eCCl) was calculated using a CysC-based glomerular filtration rate (GFR) equation from a serum Cr measured at the pediatric intensive care unit (PICU) entrance., Results: The median age was 10 months (interquartile range, 3-36 months). Serum Cr, serum CysC, and eCCl (mean ± standard deviation [range]) were 0.5 ± 0.18 mg/dl (0.2-1.1 mg/dl), 0.53 ± 0.78 (0.01-3.7 mg/l), and 72.55 ± 28.72 (20.6-176.2) ml/min per 1.73 m(2), respectively. The serum CysC level in patients with AKI was significantly higher than children with normal renal function (p < 0.001). The values for the cut-off point, sensitivity, specificity, and the area under curve (AUC) were determined for CysC as 0.6 mg/l, 73.9 %, 78.9 %, and 0.92 [95 % confidence interval (0.82-1)], respectively, and for Cr the values were 0.4 mg/dl, 68 %, 46.2 %, and 0.39, [95 % confidence interval (0.24-0.54)], respectively. The receiver operating characteristics (ROC) curve analysis revealed that CysC had a significantly higher diagnostic accuracy than eCCl (p < 0.001)., Conclusions: Our results identify that the sensitivity of serum CysC for detecting AKI is higher than that of serum Cr in a heterogeneous pediatric intensive care unit (PICU) population.

Urolithiasis is relatively common in children, and identifiable predisposing factors for stone formation, including metabolic and structural derangements, can be established in most cases. Vesicoureteral reflux (VUR) is a common cause of kidney stone formation. The pathophysiological mechanism of urolithiasis in reflux is related to urinary tract infection and urinary stasis, both of which promote urinary crystal formation, but metabolic causes, such as crystallurias (mostly hypercalciuria), may also be involved in this process. However, few studies on urinary calcium and uric acid excretion in children with VUR have been conducted. We have studied the frequency of hypercalciuria and hyperuricosuria in children with VUR and compared the results with those from a control group. The VUR group comprised 108 children with VUR (19 boys, 89 girls; age range 3 months to 12 years), and the control group comprised 110 healthy children without any history of reflux or urinary tract infection (30 boys, 80 girls; age range 2 months to 12 years). Fasting urine was analyzed for the calcium/creatinine (Ca/Cr) and uric acid/creatinine (UA/Cr) ratios. Hypercalciuria was more frequently diagnosed in the VUR patients than in the control group (21.3 vs. 3.6%; P = 0.0001). Significant differences between the two groups were also found for the mean Ca/Cr and UA/Cr ratios (P = 0.0001 and P = 0.0001, respectively). No differences were found in the urinary Ca/Cr or UA/Cr ratios related to VUR grading or unilateral/bilateral VUR in the patient group, with the exception of those for hypercalciuria and mild VUR (P = 0.03). The association of urinary stones and microlithiasis in the VUR group was 29.6%. Our results demonstrate that the frequency of hypercalciuria and hyperuricosuria was higher in pediatric patients with VUR than in healthy children. Knowing this relationship, preventive and therapeutic interventions for stone formation in VUR could be greatly expanded.

We conducted a retrospective study on children with primary nephrotic syndrome (NS) to evaluate the clinical course and outcome of children with steroid-sensitive NS (SSNS). The medical records of 226 children, median 3.46 years (min 1.00, max 15.08) who referred to our clinics with SSNS between January 1978 and September 2005 were reviewed and entered into the study. Minimum duration of follow-up was 5 years and maximum 20 years (median 7.25 years). Of 226 patients who were treated with corticosteroids, 38 (16.8%) had no relapse but the remaining 188 (83.2%) patients experienced several relapses of which 128 patients (56.6%) required additional immunosuppressive agents for the remission. Of these, 122 (95%) were treated with levamisole, 22 (17%) with cyclosporine, 36 (28%) with cyclophosphamide, and ten (7.8 %) treated with mycophenolate mofetil. Several patients had to switch from one medication to others due to lack of response. On the last follow-up visit, 64(28.3%) patients were still under treatment, some patients had taken all of the above-mentioned drugs but still had multiple recurrences. Only 103 (45.5%) patients were in remission off the drug more than 3 years. This study shows that nearly one-third of pediatric patients with SSNS experience frequent relapses despite the combination of multiple immunosuppressive medications, which may continue until adulthood.

Fractional excretion of sodium (FENa) has been said to be the most sensitive index for differentiating prerenal failure (PRF) from intrinsic renal failure (IRF). However, there are several instances of high FENa (>2%) in cases of PRF and low FENa (<1%) in IRF patients. In contrast, the fractional excretion of urea nitrogen (FEUN) is primarily dependent on passive forces, and many confounding variables that affect FENa have little effect on FEUN, if any. To compare FEUN with FENa, pediatric patients with acute kidney injury (AKI) were prospectively evaluated by history, physical examination, and obtaining appropriate laboratory data during a 1-year interval. Diagnosis of PRF or IRF was made in each patient, and renal failure indices were compared between two groups using chi-square and t test, as appropriate. Probability value (P value) <0.05 was considered significant. Receiver operating characteristic (ROC) plots for FEUN and FENa were drawn to compare the discriminative power of each index. Forty-three patients were enrolled in the study. There were 27 patients in the PRF and 16 in the IRF group. FENa was 2+/-0.4 in PRF and 4.5+/- 1% in IRF patients (P<0.05), and low FENa (<1%) was only seen in 44.4% of PRF patients, which was not statistically different from those with IRF (P>0.05). FEUN was 23.6+/- 4.9% in PRF and 41.6+/-4.8% in IRF patients (P<0.05), and low FEUN (<35%) was seen in 77.8% of the PRF group (P<0.05). Cutoff values of 30% and 1.6% were reached for FEUN and FENa, respectively. In conclusion, FEUN <35% had higher sensitivity and specificity than FENa <1% for differentiation of PRF from IRF.

The objective of this study was to determine the clinical and histopathological features and outcome of children with lupus nephritis (LN). Of 84 children with systemic lupus erythematosus (SLE), we retrospectively studied 58 children (69%) under 15 years of age with biopsy-proven LN who had been followed between October 1989 and January 2005. The mean age at diagnosis or initial referral was 10.6 +/- 2.25 years, and the mean follow-up was 5.3 +/- 4.1 years. Class IV LN was observed in 34 (58.6%) patients. The 5-year patient and renal survival rates were 82.5 and 78.5%, respectively, in the total group, and 75 and 85.8%, respectively, in patients with Class IV LN. No independent predictor of unfavorable outcome, including renal histology, was detected by multivariate analysis. The mid-term patient and the renal survival rates of Iranian children with biopsy-proven LN are high. Within 5 years of follow-up, renal histology was not a predictor for survival.

Unlabelled: We evaluated changes in serum zinc (Zn) and copper (Cu) levels in two groups of children with chronic renal failure (CRF)--children with CRF who were on regular hemodialysis (Group 1, n=40) and children with CRF who were on conservative management (Group 2, n=31)--and in one group of healthy children (Group 3, n=30). All of the participants in the study were between 5-18 years old, and the composition of the three groups was almost identical with respect to age and sex. The length of time the children in Group 1 had been on hemodialysis varied between 3 and 52 months (mean: 20.97+/-14.8 months). To evaluate the impact of the duration of dialysis on serum levels of Zn, we further sub-divided Group 1 patients into two subgroups: Subgroup A patients (n=20) had been on hemodialysis therapy for less than 18 months (mean: 8.85+/-4.83 months); Subgroup B patients (n=20) had been on hemodialysis therapy for longer than 18 months (mean: 33.1+/-10.86 months). The PIXE (proton-induced X-ray emission) was used for measuring the trace elements., Results: The mean serum level of Zn was lower in the Group 1 (hemodialysis group) children than in the children of Group 2 (on conservative management) and group 3 (healthy children) (p<0.001), but the difference was not significant between Groups 2 and 3. No significant differences in serum levels of Cu were found among the three groups. The serum level of Zn was lower in Subgroup B than in Subgroup A (p<0.001). The correlation test showed that there was an inverse linear relation between the length of time the child was on the hemodialysis regimen and serum Zn levels., Conclusion: Chronic hemodialysis may lead to abnormalities in the serum levels of some trace elements in children with CRF that increase in severity with increasing duration of hemodialysis. Deficiencies of these trace elements--zinc in particular--may contribute to various conditions and symptoms in children undergoing chronic hemodialysis.

It is generally believed that infants are more susceptible to development of renal scarring after pyelonephritis than children over 5 years old. This view has led to differences in investigations and treatment according to age. The aim of this prospective study was to assess the occurrence of renal parenchymal lesion in children over 5 years admitted with a first-time symptomatic urinary tract infection (UTI). Between October 2000 and April 2002, 52 children aged over 5 years who were admitted to our department with probable acute pyelonephritis (APN) and a positive urine culture were included in this study. All children received antibiotics for 14 days. During the acute phase of infection, scintigraphy with technetium-99m-labeled dimercaptosuccinic acid (DMSA) and ultrasonography (US) were done. Voiding cystourethrography (VCUG) was performed in all children early in the course of the illness, generally within 5-7 days of hospitalization. When scintigraphy showed renal parenchymal changes, repeat scintigraphy was done after at least 3 months to assess the progression of renal abnormalities. Of the 52 children with a first-time documented pyelonephritis, cortical scintigraphy showed renal lesion in 41 children (78.8%). US was normal in all children with normal renal scintigraphy, while it detected renal abnormalities in 16 of the 41 (39 %) with abnormal scintigraphy (p <0.0001). Topographic analysis of the 165 focal lesions showed that 42.4% were localized to the upper poles, 17.5% to the middle third, and 40% to the lower poles of the kidneys. Repeat scintigraphy showed persistent lesions corresponding to those on the initial scan in nine (28.2%) of the 32 children. Renal lesions had partly regressed in 23 (71.8%) of the patients who underwent repeat scintigraphy. Vesicoureteral reflux was observed in 13.4% of kidneys and renal parenchymal abnormalities were identified in 71.4% and 72.2% of renal units, respectively, with and without reflux ( p >0.05). In conclusion, our data did not confirm the conventional opinion that the risk of renal scarring after pyelonephritis is low in children over the age of 5 years. Our findings suggest that renal scintigraphy may be a more appropriate method of investigation than VCUG for evaluation of the children over 5 years with acute pyelonephritis. Additionally, the frequency of scintigraphic changes is high, and a strategy based exclusively on ultrasound findings would miss about 61% of the abnormal renal units. We recommend that all children, irrespective of age, will benefit from further investigations that might prevent or limit the development of scarring process and renal complications.

The incidence of vesicoureteral reflux (VUR) in the general population is less than 1%, but it is high in families with reflux. The reported prevalence of VUR among siblings of index patients with reflux has ranged from 4.7% to 51%. Reflux carries an increased risk of pyelonephritis and long-term renal impairment. The purpose of this study was to identify the age-related incidence and severity of reflux, and the frequency of associated renal parenchymal damage in siblings of children with reflux in order to assess the use of screening at different ages. Between October 1994 and February 2003, 40 siblings of 34 index patients were screened with direct voiding cystography. 99( m ) technetium (Tc)-dimercaptosuccinic acid (DMSA) nuclear renal scans were performed in siblings with VUR to detect renal scarring. The cystograms were interpreted as showing the presence or absence of VUR and the DMSA scan as symmetrical or asymmetrical differential function, with or without renal scarring. Of 40 siblings, 17 had VUR, representing an incidence of 42.5%. The mean age at study entry of the 15 boys and 25 girls was 63 months (range 6 months to 12 years). The majority of siblings with abnormal DMSA scans were asymptomatic. Reflux was unilateral in 12 siblings and bilateral in 5. Of the 17 refluxing siblings (22 refluxing ureters), 7 (41.17%) had a history of symptomatic urinary tract infection (UTI). The frequency of VUR was nearly equal in siblings over 6 years and those younger than 6 years. Of the 17 siblings with VUR, 16 had DMSA scintigraphy. Of these, 5 were normal and 11 (68.75%) showed abnormalities (7 asymmetrical differential function and 4 parenchymal defect), which was bilateral in 7 and unilateral in 4. In conclusion, this study confirms a significant overall incidence of VUR and renal parenchymal damage in the siblings of patients with known reflux. The prevalence of reflux in older siblings is similar to that in younger siblings. Our review suggests that all siblings over 6 years should undergo a screening cystogram, even in the absence of urinary tract infection. DMSA scintigraphy of asymptomatic siblings appears to be beneficial in preventing renal injury.

Glomerular disease constitutes an important part of renal disease. The purpose of this study was to describe and correlate the types of glomerular diseases reported in native kidney biopsy specimens and their clinical presentations in Iranian children. The medical records and pathological diagnoses of patients with glomerular disease whose native kidney biopsy specimens were received by our hospital during a 10-year period were reviewed. In each patient, pathological diagnosis, clinical presentation, age at onset of disease, gender, and presence of nephrotic proteinuria, hematuria, and hypertension, were determined. Minimal-change disease was the most frequent glomerular disease and nephrotic syndrome was the most frequent clinical presentation encountered. For each disease, correlations between the clinical presentation and pathological diagnosis were made. This study describes various glomerular diseases encountered in Iranian children, with their respective clinical presentations.