Efficacy of rituximab therapy in children with nephrotic syndrome: a 10-year experience from an Iranian pediatric hospital.

BACKGROUND: There are controversy results in the optimal management of children with steroid-dependent and steroid-resistant nephrotic syndrome (SDNS, SRNS). This study aimed to determine the efficacy and safety of rituximab (RTX) in these pediatric patients. METHODS: Medical records of 1-18-year-old Iranian children with SDNS (n = 26) and SRNS (n = 22) with a follow-up for at least 24 months were included from 2009 to 2019. The short- and long-term responses to RTX were respectively evaluated to determine the random protein-to-creatinine ratio after 6 and 24 months and classified as complete (CR) and partial (PR) remission or no response. RESULTS: Male patients (n = 26) were slightly predominate. The median age of patients at the time of RTX therapy was 8.6 ± 4.01 years. At the end of the 6-month follow-up, CR and PR occurred in 23 (47.9%) and 12 (25%) patients, respectively. Of 23 patients with CR, 18 (69.2%) and 5(22.7%) had SDNS and SRNS, respectively (p < 0.005). However, only 18 (37.5%) of patients after 24 months had been in CR. No significant difference in the CR rate was found between the two groups. RTX was more effective when administered during the proteinuria-free period (p = 0.001). CONCLUSION: In the short term, RTX significantly was efficient in inducing complete or PR in SDNS and SRNS patients. However, the favorable response rate in a long-term follow-up was insignificantly lower between the two groups.

Comparative Analysis between Urinary Calprotectin and Serum Creatinine for Early Detection of Intrinsic Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is a common and important clinical condition that may lead to chronic kidney disease if it is not diagnosed and treated in its early stages. Urinary calprotectin is a valuable recognized biomarker that can be used to differentiate prerenal and intrinsic AKI. However, till date only a few reports on urine calprotectin measurement in early diagnosis of intrinsic AKI are available. In this study, we compared the sensitivity and specificity of urinary calprotectin with those of serum creatinine in detecting early intrinsic AKI. METHODS: Over 6 months period (April to October 2018), 81 of 408 patients admitted to the pediatric intensive care unit met the criteria of this cross-sectional study. Their serum creatinine and urinary calprotectin were measured on the first and third day of admission using Jaffe and Elisa radioimmunoassay methods, respectively. The AKI was defined according to the pRIFLE criteria. RESULTS: Of the total 81 patients, 67 had the criteria of intrinsic AKI. Of these 62% were female and 38% were male. The mean age of the patients was 22 months. According to data analysis, the area under the curve of ROC of urinary calprotectin on day-1 to detect renal failure is 0.93 with the best cutoff point obtained at 530 ng/mL. The sensitivity, specificity, positive, and negative predictive values of urinary calprotectin levels in diagnosing AKI at this cutoff point are 92.5%, 92.8%, 98.4, and 72.2%, respectively. Besides, urinary calprotectin changes occur much earlier than the rising of serum creatinine. CONCLUSION: Urinary level of calprotectin is a very sensitive biomarker for early diagnosis of intrinsic AKI in children and it can be used in intensive care units or anywhere critically ill children admitted to detect intrinsic AKI. Besides, this study shows that urine calprotectin may be a more sensitive and specific biomarker than serum creatinine in the early phases of intrinsic AKI.

The Effect of Oral Cyclophosphamide in the Treatment of Children with Refractory Idiopathic Nephrotic Syndrome.

INTRODUCTION: Nephrotic syndrome (NS) is the most common chronic kidney disease in children. Patients who do not respond to steroids are steroid resistance nephrotic syndrome (SRNS). Cyclophosphamide (CP) has been used in the treatment of SRNS, but its effectiveness has been questioned. The aim of this study was to evaluate the drug response and side effects of CP in the treatment of SRNS. METHODS: This study performed as a historical cohort (1997 to 2017) in idiopathic SRNS patients over one year of age who did not enter remission and used oral. All patients were followed up with CBC and regular visits to control drug side effects. RESULTS: In this study, 52 SRNS patients with a mean age of 5.3 ± 5.3 years were studied, of whom 24 (46%) were male and 22 (54%) were female. The follow-up period of patients was 1 to 264 months. In this study, 38.5% of patients were sensitive to CP and 61.5% of patients were resistant to CP. The response to CP was not significantly different between the ages of higher 6 years and under (P > .05). There was no significant relationship between remission rate and type of pathology and CP addition to treatment. But there was a significant difference between ESRD and CP resistance. CONCLUSION: It can be concluded that CP has no significant effect on the remission of SRNS patients, but has made a significant difference in the development of ESRD in patients.

Chronic Kidney Disease in Iran: First Report of the National Registry in Children and Adolescences.

PURPOSE: Knowing the epidemiological aspects of chronic kidney disease (CKD) in children is crucial for early recognition, identification of reversible causes, and prognosis. Here, we report the epidemiological characteristics of childhood CKD in Iran. MATERIALS AND METHODS: This cross-sectional study was conducted during 1991 - 2009. The data were collected using the information in the Iranian Pediatric Registry of Chronic Kidney Disease (IPRCKD) core dataset. RESULTS: A total of 1247 children were registered. The mean age of the children at registration was 0.69 ± 4.72 years (range, 0.25 -18 years), 7.79 ± 3.18 years for hemodialysis (HD), 4.24 ± 1.86 years for continuous ambulatory peritoneal dialysis (CAPD), and 3.4±1.95 years for the children who underwent the renal transplantation (RT) (P < .001). The mean year of follow-up was 7.19 ± 4.65 years. The mean annual incidence of CKD 2-5 stages was 3.34 per million age-related population (pmarp). The mean prevalence of CKD 2-5 stages was 21.95 (pmarp). The cumulative 1-, 5-, and 10-year patients' survival rates were 98.3%, 90.7%, and 84.8%, respectively. The etiology of the CKD included the congenital anomalies of the kidney and urinary tract (CAKUT) (40.01%), glomerulopathy (19.00%), unknown cause (18.28%), and cystic/hereditary/congenital disease (11.14%). CONCLUSION: The incidence and prevalence rate of pediatric CKD in Iran is relatively lower than those reported in Europe and other similar studies. CAKUT was the main cause of the CKD. Appropriate management of CAKUT including early urological intervention is required to preserve the renal function. Herein, the long-term survival rate was higher among the children with CKD than the literature.

Failure of isolated kidney transplantation in a pediatric patient with primary hyperoxaluria type 2.

PH type 2 is caused by decreased activity of GRHPR enzyme that eventually leads to ESRD and systemic oxalosis. Here, we describe an Iranian pediatric patient with PH2 and early ESRD development who received recommended treatment by undergoing isolated kidney transplantation. Diagnosis criteria included a history of reoccurring calcium oxalate renal stones and elevated oxalate levels combined with liver biopsy and decreased enzymatic activity at age five. ESRD prompted transplantation and was performed at age nine. On Day 12 post-op, his serum creatinine level increased. A graft biopsy showed calcium oxalate crystal deposits in renal tubes with no evidence of acute rejection, which resolved with intensive hydration and administration of a potassium citrate solution. Subsequent biopsies confirmed results found in first biopsy. Despite the immunosuppressive therapy, his serum creatinine level increased again after 11 months. Renal tubular obstruction then led to graft nephrectomy. Pathological analysis of tissue confirmed findings of past biopsies. This was a very rare case of early ESRD in PH2 resulting in a failed isolated kidney transplant. As the GRHPR enzyme is predominantly expressed in liver, we suggest a combined liver-kidney transplant may be beneficial in patients with PH2.

Novel NPHS1 Gene Mutation in an Iranian Patient with Congenital Nephrotic Syndrome of the Finnish Type

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Urinary calcium and uric acid excretion in children with vesicoureteral reflux.

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.

Clinical course and outcome of children with steroid-sensitive nephrotic syndrome.

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.

Is There Any Association between Spina bifida occulta and Primary Vesicoureteral Reflux?

OBJECTIVE: Spina bifida occulta (SBO) has been largely considered a benign entity without clinical significance; however, there has been dispute among various authorities, and some believe that the lesion may be linked with various neurologic conditions like urologic dysfunctions. Vesicoureteral reflux (VUR) and lower urinary tract dysfunction are closely related. We examined whether the existence of SBO is related to the prevalence and severity of VUR in children. METHODS: We investigated 359 children, 2-14 years old, referred to radiology department for obtaining voiding cystourethrogram after the first attack of febrile urinary tract infection. After treatment of infection, with written order of responsible physicians all underwent a standard voiding cystourethrogram to detect VUR and other lower urinary tract anomalies. The patients were divided into two groups: group1 patients who had not SBO and group 2 patients with SBO in postvoiding or KUB films. In each group the presence and severity of VUR was determined in relation to the location of SBO. FINDINGS: Out of 359 children, 228 (63.5%) had normal spine and 131 (36.5%) had SBO. Fifty four (23.7%) out of 228 children with normal spine had VUR and 40 (30.5%) out of 131 children with SBO had VUR. The prevalence of VUR in children without SBO and children with SBO was not statistically different. Also we compared the severity of VUR between the two groups and there was no significant difference or trend between presence of SBO and severity of reflux (Chi(2) for trend). VUR was more common in children with SBO in L5-S1 (38.3%). There was no significant relation between location of SBO and prevalence of VUR. CONCLUSION: Location of SBO and prevalence of VUR are not related.

Comparison between fractional excretions of urea and sodium in children with acute kidney injury.

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 outcome of Iranian children on continuous ambulatory peritoneal dialysis: the first report of Iranian National Registry.

BACKGROUND: Continuous ambulatory peritoneal dialysis is not a very common modality to treat Iranian children with end-stage renal disease; however, there is sometimes no choice but to offer this therapy to salvage the patient. Obviously, promotion in each program needs re-evaluation to find the pitfalls. Therefore, a nation-wide survey on pediatric continuous ambulatory peritoneal dialysis was conducted to find the cause of death or termination of dialysis. METHODS: All children, younger than 14 years old, treated by continuous ambulatory peritoneal dialysis in nine main pediatric nephrology wards in Iran between 1993 and 2006 were included in this historical cohort study. Patient and technique survival rates were determined. Kaplan-Mayer and Cox-regression analysis were used to compare the survival. 2 x 2 table was used to calculate the risk ratio. A P<0.05 was considered significant. RESULTS: One hundred twenty children with a mean age of 47.6 months were on continuous ambulatory peritoneal dialysis. The most frequent cause of renal failure was hereditary-metabolic-cystic disease. One hundred eighty-two peritoneal dialysis catheters were inserted surgically. The median first catheter exchange was 0.74 year (95%CI: 0.5 - 0.98). The most frequent cause of catheter replacement was catheter outflow failure due to displacement, adhesion, and infection (persistent peritonitis or tunnel infection). The mean patient survival was 1.22 years (95%CI: 0.91 - 1.53). The mortality rate was 55% before 1997, and 60% between 1998 and 2001, which declined to 23% after 2002 (P<0.05). Young age (<24 months) was the only independent factor that predicted mortality (P<0.05). The outcome of children was as follows: recovery of renal function (6.7%), renal transplantation (8.3%), switch to hemodialysis (16.7%), still on continuous ambulatory peritoneal dialysis (23.3%), death (43.3%), and lost to follow-up (1.7%). CONCLUSION: The mortality is still high among Iranian children on peritoneal dialysis. Young age is the most important factor influencing on survival and mortality.

Posterior urethral valve in a child presenting as recurrent epididymo-orchitis.

Epididymo-orchitis is an uncommon complication of posterior urethral valve. A four-year-old boy was admitted because of right-sided epididymo-orchitis. Scintigraphy of the scrotum showed increased uptake of radiotracer on the right side. The posterior urethral valve was disclosed by voiding cystourethrography. Ablation of the valve and antibiotic therapy made the patient free of symptoms.

Outcome of lupus nephritis in Iranian children: prognostic significance of certain features.

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.

Fungal peritonitis in Iranian children on continuous ambulatory peritoneal dialysis: a national experience.

INTRODUCTION: Fungal peritonitis (FP), causing catheter obstruction, dialysis failure, and peritoneal dysfunction, is a rare but serious complication of peritoneal dialysis. In this study, the frequency and risk factors of FP are evaluated in children who underwent peritoneal dialysis. MATERIALS AND METHODS: A retrospective multicenter study was performed at the 5 pediatric peritoneal dialysis centers in Iran from 1971 to 2006, and FP episodes among 93 children were reviewed. Risk ratios were calculated for the clinical and demographic variables to determine the risk factors of FP. RESULTS: Ninety-three children aged 39 months on average were included in study. Sixteen out of 155 episodes of peritonitis were fungi infections, all by Candida albicans. The risk of FP was higher in those with relapsing bacterial peritonitis (P = .009). Also, all of the patients had received antibiotics within the 1 month prior to the development of FP. Catheters were removed in all patients after 1 to 7 days of developing FP. Six out of 12 patients had catheter obstruction and peritoneal loss after the treatment and 5 died due to infection. CONCLUSIONS: Fungal peritonitis, accompanied by high morbidity and mortality in children should be reduced by prevention of bacterial peritonitis. Early removal of catheter after recognition of FP should be considered.

Serum zinc and copper levels in children with chronic renal failure.

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.

Screening for vesicoureteral reflux and renal scars in siblings of children with known reflux.

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.