Tehran University Medical Journal

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Background: Cyclosporin A (CsA) is now commonly used in the management of children with steroid-dependent and steroid resistant nephoitic syndrome. It has been reported to be effective in maintaining remission in 70-100 percent of patients with SDNS but somewhat SRNS 0-100 percent. The aim of this study was to evaluate the efficacy of long-term (CsA) in children with refractory nephrotic syndrome (RNS) and steroid dependent nephrotic syndrome (SDNS).

Materials and Methods: The long-term effect of (CsA) in 91 Iranian children aged 3 months to 11 years (54 with RNS and 37 with SDNS) was assessed between 1984 and 1999. Eighty of 91 children received renal biopsy prior to introduction of (CsA), and the other 11 patients had not consent for kidney biopsy. If the patients did not show remission aftre receiving 3-6 months of (CsA), the medication was discontinued.

Results: All patient were treated with (CsA) in combination with low dose alternate day prednisolone. In children with RNS and SDNS, therapy with (CsA) induced, remission in 25 of 54 (46.2 percent) and 27 of 37 (73 percent) respectively (P<0.02). Of the 32 patients with minimal change disease (MCD), 23 (72 percent) responded to therapy, compared with 4 of 18 (22 percent) with focal segmental glomerulosclerosis (FSGS) (P<0.005). Twenty-four (48 percent) of 50 who entered complete remission, had relapse 1-12 months after cessation of (CsA). The duration between the onset of nephrotic syndrome (NS) and administration of (CsA) and sexuality of patients had no effect in result of treatment. Side effects occurred in 25 patients (27.4 percent). No patients exhibited raised transaminases, 8 (8.7 percent) of the children developed hirsutism, 7 (7.6 percent) hypertension, 7 (7.6 percent) gingival hyperplasia, (2.2 percent) neurological toxicity and 1 (1 percent) increase in serum creatinine.

Conclusion: Our findings suggest that (CsA) can be used to induce a complete remission in a significant proportion of patients with RNS and SDNS, and patients with SDNS have areasonable potential for remission than children with RNS. Resistant to steroid and cyclophosphamid.

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Background: Urinary tract infection is a common bacterial infection in children and may lead to irreversible renal damage. TC 99-m Dimercaptosuccinic acid renal scintigraphy is the most sensitive method for diagnosing acute pyelonephritis. We designed a study to evaluate the ability of DMSA scan and ultrasonography to detect renal paranchymal lesion.

Materials and Methods: 62 children 1 month to 12 years of age with the first episode of acute pyelonephritis were prospectively studied with DMSA scan and ultrasonography during acute phase of infection. A Voiding Cystourethrogram was performed in 60 children when urine culture became negative. Children with renal paranchymal changes were older at the time of acute pyelonephritis (P=0.04) but no difference was found between the groups with regard to levels of CRP, ESR (P>0.05).

Results: Changes on the DMSA scan were found in 106 (85.5 percent) kidneys of 62 children but ultrasonography showed renal changes in 19.4 percent (sensitivity=20 percent, specificity=83 percent) (Kappa=0.06). Vesicoureteric reflux was found in 14 children (23.3 percent) but 83 percent of the affected kidneys were drained by non-refluxing ureters.

Conclusion: It is concluded that DMSA scan is more sensitive than ultrasonography in detecting renal paranchymal changes in acute pyelonephritis and we found out that renal paranchymal changes after acute pyelonephritis is common, even in those without VUR.

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The nephrotic syndrome is the most common chronic renal disease of childhood.
Materials and Methods: In this study the clinical course, risk factors for relapse and the predictors of long-term outcome of 502 patients (median age 5 years)with primary nephrotic syndrome were followed for an average of 60 months (3.5 to 240 months) from 1981 to 2000.
Results: Among the 502 patients 5 (1%) achieved spontaneous remission and 313 children were initial responder. One hundred eighty four patients received at least 1 kidney biopsy (78 prior and 106 after initiation of treatment). Of 104 children with frequently relapsing steroid sensitive and steroid dependent nephrotic syndrome, levamisole induced prolong remission in 33 ( 31.7%) of patients. Cyclophosphamid and cyclosporine A induced prolong remission in 49 (50%) of 98 and 28 (41.3%) of 68 patients respectively. At the time of the final clinical evaluation, 73 patients (14.5%) were on remission 301 (59.9%) had relapsing 43 (8.6%) had persistent nephrotic syndrome 33 (6.6%) of patients evolving to end-stage renal disease (ESRD) and 6 (1.2%) of them with chronic renal failure died (infection and cardio respiratory were the cause of death in 5 and 1 patient respectively). Young age (1-5 y) at onset of disease and atopy were identified as an independent risk factors for relapse (P0.05). Patients with steroid dependent nephrotic syndrome (SDNS) or MCNS had better response to cyclophosphamide or cyclosporin than children with steroid resistance nephrotic syndrome (SRNS) or FSGS (P0.05). Persistent proteinuria, hypertension, microscopic or macroscopic hematuia, glucosuria were associated with progression to chronic renal failure (PO.05).
Conclusion: Steroid dependency and histopathology of MCNS in patients with nephrotic syndrome were significantly associated with good long-term prognosis. In contrast persistent proteinuria, histopatholoy of FSGS, hypertension, macroscopic or microscopic hematuria, and glucosoria were significantly correlated with unfavorable long-term outcome. Additionally our study showed a positive correlation between young age and atopy with higher rate of relapse.

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Background: Despite several years of intensive investigation, relatively few studies have been made of children with lupus nephritis. The prognosis of children with lupus nephritis is poor for those with diffuse proliferative glomerulonephritis and active interstitial inflammation. As newer treatment modalities become available for patients with severe lupus nephritis, it become increasingly important to identify patients at risk for renal failure. The aim of this study was to evaluate the clinical course, histopathology, serologic features and prognostic significance of some parameters, to identify the risk factors for renal failure and mortality in children with lupus nephritis.

Materials and Methods: Retrospectively 30 children under 16 years of age with lupus nephritis from 1989 to 1999 were studied. All patients received renal biopsy and follow-up biopsies were performed in 3 children. Lupus nephritis was classified by the World Health Organization (WHO) criteria. The clinical and serologic parameters at the time of renal biopsy were recorded.

Results: All children underwent renal biopsy within 1 year of disease onset. There were 1 (3.3%) patients with class II, 5 (16.7%) with class III, 21 (%70) with class IV, and 3 (%10) with class V nephritis based on initial biopsy according to the WHO classification. The mean follow-up time was 60 months. Follow-up biopsies were histologically stationary in 2 patients and progressive in one. The overall renal and patient 5- year survival rates were 46.66% (14/30) and 93.33 %( 2/30) respectively. They were 47.61% (10/21) and 95.21 %( 20/21), respectively, of patients with class IV proliferative glomerulonephritis. Children with renal pathology (class V in the WHO classification system) at initial biopsy, were at high risk for renal failure 66.66% (2/3) or morality %33.33 (1/3) despite aggressive treatment. The results revealed that those with persistent hypertension, anemia, and decreased creatinine clearance rate, nephrotic proteinuria, at initial biopsy were more prone to develop renal failure (P<0.01).

Conclusion: The prognosis of children with class IV nephritis in our study was better than reported in other series in recent years. However, those with class V disease, persistent hypertension, anemia, low creatinine clearance and nephrotic proteinuria at the time of diagnosis are at increased risk for renal failure. The improved results may be due to initial histological classification, better supportive care and selective use of aggressive therapy such as methylprednisolone pulse therapy and intravenous cyclophosphamide for those with high risk factors.

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Background: Impairment in the function of the lower urinary tract can be the cause of recurrent urinary tract infections (UTI) and vesico-ureteral reflux (VUR) in children. The purpose of our research was to evaluate the frequency of occurrence of bladder instability in children with UTI.

Methods: The research involved 133 children (11 boys, 122 girls), ranging in age from seven months to 14 years. Group A consisted of 78 children with a history of recurrent UTI, while Group B included 55 children with recurrent UTI and VUR. Urodynamic tests (cystometry) were performed on all the children.

Results: Abnormal functioning of the lower urinary tract was found in 98 children (73.1%) from Group A and 41 children (78.8%) from Group B. The most common dysfunction was detrusor-sphincter dyssynergia (DSD), which was found in 54% of all subjects, 46.2% of patients in Group A and 60% of patients in Group B (p<0.05). Unstable bladder was found in 42 (33%) children with no significant difference between the two groups. In 17 children (12.6%) DSD was accompanied by bladder instability. In both groups about 20% of the children did not present with symptoms indicative of urination dysfunction, where as 80% reported various symptoms, of which the most common were constipation and urinary urgency. In half of the children from Group A and one-fourth of the children from Group B there were several co-occurring symptoms: frequency, urgency, intermittent voiding, incontinence, dribbling and retention, and constipation.

Conclusions: The most common disturbance of lower urinary tract function in these children with recurrent UTI was DSD, which occurred more often in children with VUR.

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Background: Nephrotic syndrome is one of the most remarkable diseases in childhood. The majority of patients have prompt response to corticosteroids.

Methods: In this study, we retrospectively evaluate the outcome of patients with steroid-responsive nephritic syndrome. Medical records from January 1996 to September 2006 were reviewed to identify all children with steroid sensitive nephrotic syndrome at the Pediatric Medical Center, Tehran, Iran. Initial steroid therapy was 60 mg/m² per day for four weeks. Levamisole, a steroid-sparing agent, was prescribed at a dose of 2.5 mg/kg on alternate days in conjunction with alternate-day prednisolone. If no benefit was observed by three months, levamisole was discontinued and immunosuppressive therapy with cyclophosphamide at a dose of 3 mg/kg daily for 8 weeks, or cyclosporin A at a dose of 3-5 mg/kg was prescribed.  

Result: Of 745 children with steroid sensitive nephrotic syndrome, 63.1% of patients were male. The most common causes were minimal change disease (98/324, 30.2%) and focal segmental glomerulosclerosis (81/324, 25%). At presentation, microscopic hematuria was found in 22.6% of the patients. During follow-up, 9.2% had no relapse at any time, while 15.8% were frequent relapsers. The remission period ranged from 3.5 to 168 months. At the last follow-up, 57.6% of the patients were in remission, 37.7% relapsed and 29 children developed chronic renal failure. The outcome of nephrotic syndrome was not associated with age or gender. The end clinical status of patients correlated with duration of remission, number of subsequent relapses and response to cytotoxic agents.

Conclusions: Steroid-responsive nephrotic syndrome in children should be followed over a long period, especially patients with early relapse. Relapse was seen in more than 90% of patients. Documentation of histopathology by renal biopsy may be helpful to identify those at increased risk for a poor outcome.

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Background: Childhood nephrotic syndrome is frequently characterized by a relapsing course. Due to their adverse effects, the use of corticosteroids for the management of frequently relapsing nephrotic syndrome is limited. Levamisole, a steroid sparing agent, has been found to have low toxicity. This study was conducted to evaluate the efficacy of levamisole in steroid-sensitive nephrotic syndrome (SDNS). 

Methods: In this retrospective study from January 1988 to September 2006, we included data from 305 pediatric SDNS patients at the Children's Medical Center clinics in Tehran, Iran. Nephrotic syndrome was diagnosed using classic criteria. None of the patients had any signs or symptoms of secondary causes of nephrotic syndrome. All had received prednisolone 60 mg/m²/day. After remission, prednisolone administration was reduced to every other day and the steroid was tapered over the next three months. With every recurrence, prednisolone was prescribed with the same dosage, but after remission it was continued at a lower dosage for another six months or longer if there was risk of recurrence. Levamisole was administered to all patients at a dose of 2 mg/kg every other day.         

Results: Patients ranged in age from 1 to 20 years (mean±SD: 4.84 ±3.1) and 70.8% were male. At the last follow up, 84 (27.5%) were in remission, while 220 (72.1%) patients had relapsed or needed a low dose of steroid. Levamisole was effective in reducing the prednisolone dosage and long-term remission in 68 (22.3%) and 90 (29.5%) cases, respectively. A comparison of before vs. after levamisole treatment revealed a had significant decrease in the number of relapses (2.05±0.88 vs. 1.1±1.23 P<0.0001) and the prednisolone dosage (0.74±0.39 vs. 0.32±0.38 mg/kg/day P<0.0001). Only one patient developed levamisole-induced neutropenia.

Conclusions: In childhood steroid-dependent nephrotic syndrome, levamisole is an efficacious, safe initial therapy in maintaining remission while decreasing steroid dose, in addition to reducing the rate of relapse.