Human leucocyte antigens in idiopathic nephrotic syndrome in children

An association of the idiopathic nephrotic syndrome (NS) with certain human leucocyte antigens (HLA) has been reported repeatedly. The aim of this study is to characterize further the clinical and histological features of patients with NS in relation to their HLA phenotypes. HLA antigens were determined in 132 paediatric patients with NS. In 91 steroid-sensitive patients (usually associated with minimal glomerular changes), the antigen frequencies of HLA-DR3, HLA-DR7, and HLA-B8,-DR3 combined were significantly increased compared with controls. The strongest association was observed with the combined occurrence of HLA-B8,-DR3,-DR7 (relative risk 21.5). This association and that with HLA-DR3 alone were strongest in the presence of frequent relapses and steroid dependence compared with children without or with infrequent relapses. The pattern of HLA antigens was similar in the 57 steroid-sensitive patients with biopsy-proven minimal glomerular changes. In 41 children with steroid-resistant NS (usually associated with focal segmental glomerulosclerosis) a similar trend for increased antigen frequencies was found but the data were significant only for the combined occurrence of HLA-B8,-DR3 and-DR7. In all patients combined the frequency of the HLA associations was significantly lower when the age of onset was greater than 8 years compared with that of younger patients. It is concluded that the immunogenetic background of the steroid-sensitive and steroid-resistant NS is different and age-dependent.     

Angiotensin converting enzyme gene polymorphisms do not predict the course of idiopathic nephrotic syndrome in Swiss children

AIM: Contradictory reports exist about a correlation of angiotensin I converting enzyme (ACE) gene polymorphisms to the outcome of idiopathic nephrotic syndrome (INS) in children. We investigated the frequency of ACE polymorphisms and their impact on the clinical course of INS in children in a Swiss hospital. METHODS: The ACE gene polymorphism (I, insertion; D, deletion) was assessed in 32 children - 22 with steroid-sensitive INS and 10 with steroid-resistant INS - with a median age at onset of INS of 2.9 years (range 1.1-15.0). Polymerase chain reaction amplification was performed on genomic DNA isolated from blood leucocytes. Results were correlated to clinical course and renal morphology. RESULTS: The ACE genotype was I/I, I/D and D/D in two, 12 and eight patients, respectively, with steroid-sensitive INS, and in one, eight and one patient, respectively, with steroid resistance. Renal morphology, available in 25 patients showed minimal change glomerulopathy in 17 patients (14 steroid-sensitive; three steroid-resistant) and focal segmental glomerulosclerosis in eight (one steroid-sensitive; seven steroid-resistant). There was no significant correlation between ACE genotype and steroid responsiveness, histology or outcome. ACE genotype was I/I, I/D and D/D in none, 12 and five patients, respectively, with minimal change glomerulopathy, and in one, five and two patients, respectively, with focal segmental glomerulosclerosis. Six patients with steroid-resistant nephrotic syndrome went into end stage renal disease; ACE genotype was I/I in one and I/D in five, but none were D/D. CONCLUSION: In contrast to previous reports, ACE gene polymorphism is irrelevant for clinical outcome, steroid responsiveness or morphology in Swiss children with INS.     

Nephrotic syndrome with focal segmental glomerulosclerosis after an insect bite

AIMS AND METHODS: Focal segmental glomerulosclerosis (FSGS) is a glomerular disease defined by a characteristic histologic pattern that occurs either as a primary kidney disease (primary FSGS) or as a result of a systemic illness (secondary FSGS). Proteinuria, often in the nephrotic range, is the hallmark of FSGS. The occurrence of nephrotic syndrome after an insect sting is rarely reported in the literature. We present a case of nephrotic syndrome with focal segmental glomerulosclerosis with a glomerular tip lesion developing after an insect bite. RESULTS: A 51-year-old Caucasian female was bitten by an insect on her left leg, which immediately became swollen. Generalized edema developed and she was admitted for further investigations. Urinary 24-h protein excretion was 7 g. Percutaneous renal biopsy was performed and showed focal segmental glomerulosclerosis of the tip variant. Nephrotic syndrome was steroid-resistant, and when we added cyclophosphamide for 8 weeks complete remission was achieved. There was no relapse of the disease during the 2-month follow-up. CONCLUSIONS: This report demonstrates the useful role of cyclophosphamide in the treatment of steroid-resistant nephrotic syndrome due to FSGS with glomerular tip lesion. A causal relationship between the insect bite and the nephrotic syndrome is suggested and an immune response could be responsible for the nephrotic syndrome.     

Response to cyclophosphamide in steroid-resistant focal segmental glomerulosclerosis: a reappraisal

The response to and clinical outcome of cyclophosphamide therapy were retrospectively assessed in 29 steroid-resistant patients with idiopathic nephrotic syndrome and focal segmental glomerulosclerosis (FSGS) to determine whether a partial response to this drug was associated with long-term clinical benefits. Twenty of the patients were nephrotic when cyclophosphamide was started and 9 were not. Three of the nephrotic patients had a complete response (i.e., sustained remission of disease) to cyclophosphamide. Nine nephrotic patients had partial responses. Of these, 8 have residual proteinuria and one has progressed to end-stage renal disease (ESRD). In contrast, of the 8 nephrotic patients who were resistant to cyclophosphamide, only one has residual proteinuria, while 7 have chronic renal failure (CRF) or ESRD. The incidence of CRF or ESRD in patients with a partial response to cyclophosphamide (1 of 9) was significantly lower (p = 0.004) than that in patients who were resistant to cyclophosphamide (7 of 8). The benefit of cyclophosphamide in patients who were not overtly nephrotic was less certain. This study indicates that a partial response to cyclophosphamide leads to improvement in the clinical outcome of many steroid-resistant nephrotic patients with FSGS.     

Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : workshop recommendations

Management of idiopathic glomerular disease associated with nephrotic syndrome (INS) remains controversial and one of the most complex areas relates to utilization of the drug cyclosporin. This is despite its demonstrated effectiveness in several histologic types of the INS in randomized controlled trials. Cyclosporin is effective in inducing remission of proteinuria in approximately 80% of steroid-sensitive cases of minimal change disease (MCD). Cyclosporin is also effective in both the induction of remission and long-term preservation of renal function in steroid-dependent/-resistant MCD and steroid-resistant focal segmental glomerulosclerosis (FSGS). The overall response rate in FSGS is lower than in MCD, and long-term therapy (>12 months) may be required to both achieve remission and sustain it. Cyclosporin therapy is also of benefit in reducing proteinuria in 70-80% of patients with steroid-resistant membranous nephropathy (MGN). In MGN, the maximum benefit is often delayed compared to MCD (>12 weeks). Cyclosporin is generally well tolerated and safe. The major concern remains the nephrotoxicity, but with careful monitoring of the patient's renal function; minimizing the maintenance dose and utilizing repeat renal biopsy in those receiving long-term therapy, this risk can be minimized. The algorithms have been developed derived from the best evidence in the literature in each of the histologic types to help provide a guide to the integration of cyclosporin into the management of INS for the practicing nephrologist.     

Epidemiology of primary nephrotic syndrome in Egyptian children

Background: Primary nephrotic syndrome is a common renal problem in pediatrics, with great variation in patients' characteristics in different regions of the world. The aim of this study was to define these characteristics in Egyptian children with primary nephrotic syndrome. Methods: Records of 100 primary nephrotic syndrome patients were retrospectively reviewed. Demographic, clinical, histopathological data and response to therapy were analyzed. Results: The mean age of onset was 4.43 ± 2.7 years. Thirty-four percent of patients were steroid resistant, and 66% showed initial steroid response; 46 of the latter were steroid dependent. Forty patients underwent a renal biopsy with minimal change nephrotic syndrome occurring in 30%, mesangioproliferative glomerulonephritis in 37.5% and focal segmental glomerulosclerosis in 30%. Nine percent of cases developed chronic renal insufficiency. Response to cyclophosphamide and cyclosporine occurred in 37.5% and 33.3% of steroid-resistant nephrotic syndrome patients, respectively. Conclusions: A greater percentage of steroid-resistant patients were found in our patients compared with those in other studies. Response to immunosuppressives was different from other studies, probably due to differences in the priority of selection for immunosuppressive therapy.     

Impact of recurrent nephrotic syndrome after renal transplantation in young patients

Recurrent disease is a frequent complication of patients transplanted for steroid-resistant nephrotic syndrome associated with focal segmental glomerulosclerosis. Its long-term prognosis has rarely been studied. We examined 39 patients aged 4–25 (mean 13.5) years at the time of first transplantation (TX). Twelve of these (30%) developed nephrotic syndrome after the first TX and 2 of 8 after the second TX. The mean observation period from first TX to last observation with a functioning graft or graft loss was 5.4 (0.1–19.3) years. We confirmed that recurrent disease is associated with older age at onset of the primary disease, shorter time from onset to end-stage renal disease, and diffuse mesangial proliferation in the initial kidney biopsy. Remissions occurred in all 3 children undergoing early repeated plasma exchange and in 1 adolescent following introduction of cyclosporin A 7 years after TX. At last observation 42% of relapsing and 48% of non-relapsing patients with a similar follow-up period had a functioning first graft. Median first graft survival was almost identical in the relapsing and the non-relapsing patients (4.3 vs. 4.2 years). Histological lesions of focal glomerulosclerosis were detected in the posttranplant biopsies of only 3 patients. In conclusion, young patients with nephrotic syndrome associated with focal segmental sclerosis have a similar graft survival with and without recurrence of the nephrotic syndrome. Received October 29, 1997; received in revised form February 17, 1998; accepted February 18, 1998     

Steroid-resistant,cyclosporine-responsive,relapsing nephrotic syndrome

Eighteen children with steroid-resistant nephrotic syndrome received cyclosporine A (CsA), including 7 patients with minimal change disease, 4 with focal segmental glomerulosclerosis and 7 with mesangial hypercellurarity. Doses were adjusted to maintain whole blood trough levels at 80–200 ng/ml and ranged from 5 to 10 mg/kg (mean 7 mg/kg). Fourteen patients responded after 2 months of therapy with either a complete or partial remission, and received a total of 12 months of CsA with low-dose corticosteroids. Remission rates were similar among the three histological types, although complete remissions occurred more commonly in minimal change disease, while the other two histological types tended to have partial responses. Serum creatinine values ranged from 0.3 to 1.2 mg/dl at the start of treatment and were stable in 17 of 18 patients during CsA therapy. CsA was discontinued after 12 months in 11 responders. Relapses were a significant problem. Nine patients had 16 relapses, all occurring within 6 months after discontinuing CsA; 13 of 16 relapses responded to CsA and corticosteroids. Five children had multiple relapses. Three patients who initially responded to treatment had CsA-resistant relapses. There were no differences among the histological types with respect to the occurrence of relapses or response to CsA after relapsing. Four patients developed chronic renal failure, including 2 of 4 who failed initial therapy and 2 of 3 who developed CsA-resistant relapses. In conclusion, initial therapy with CsA was effective in resolving nephrotic syndrome in steroid-resistant patients. However, CsA dependency, frequent relapses and the development of chronic renal failure presented significant problems.     

Focal glomerulosclerosis in children: an argentinian experience

Twenty-six children presenting with idiopathic nephrotic syndrome and a histological diagnosis of focal glomerulosclerosis were studied retrospectively to evaluate their response to treatment, outcome and clinicopathological correlations. Twenty-two patients (84.6%) were steroid resistant; of these, 8 of the 19 with focal segmental glomerulosclerosis and 2 of the 3 with focal global within 16 weeks of starting therapy. Seven patients relapsed after a CY-induced remission, but 5 of them became steroid responsive. After an average follow-up of 83 months, 17 patients are in remission with normal renal function, 3 patients have persistent nephrotic range proteinuria and 6 patients are in chronic renal failure. Persistence of proteinuria, a high percentage of segmentally selerotic glomeruli and diffuse mesangial proliferation were indicators of poor prognosis. We believe longer courses of CY therapy than those traditionally utilized are responsible for the relatively good results in our patients. Present address: University of Virginia, Department of Pediatrics/Nephrology, MR4 Building, Room 2001, Charlottesville, VA 22908, USA     

Possible genetic predisposition to idiopathic focal segmental glomerulosclerosis

HLA-A, B, and DR antigen frequencies were studied in a group of 57 patients to determine possible inborn susceptibility to idiopathic focal segmental glomerulosclerosis (FSGS). There were 34 white patients and 23 black patients, most of whom had nephrotic syndrome and later developed renal failure. HLA-DR4 was significantly increased in both patient groups when compared with their respective control groups. This association has not been previously reported. Of note, the association with DR4 was most striking in patients with adult onset disease (in blacks, relative risk equals 5.2; in whites, relative risk equals 5.8). No other antigen was increased in both patient groups but HLA-A28 was increased in blacks. These data support the notion of genetic predisposition to focal segmental glomerulosclerosis in two different ethnic groups.     

Plasma exchange for recurrent nephrotic syndrome following renal transplantation

Patients with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis (FGS) who develop end-stage renal disease are at risk for recurrence of the disease following renal transplantation. Recurrence of the nephrotic syndrome in renal allografts of two children with primary FGS was successfully controlled by plasma exchange. This report suggests that plasma exchange instituted early in the course of recurrent nephrotic syndrome may be beneficial in some patients with steroid-resistant nephrotic syndrome and FGS.     

Treatment of steroid-resistant nephrotic syndrome with cyclosporine: study of 17 cases and a literature review

BACKGROUND: Cyclosporine (CsA) has been used in steroid-resistant idiopathic nephrotic syndrome (INS) in many previous studies. OBJECTIVE: To evaluate if CsA is a therapeutic option for steroid-resistant nephrotic syndrome. METHODS: We performed a retrospective cohort study to evaluate the effects of CsA in 17 steroid-resistant INS patients.The main laboratorial data, before and after the use of CsA, and the response to CsA were evaluated. A literature review on this subject was also done. RESULTS: Patient age ranged from 2-43 yrs. Pre-treatment renal biopsy demonstrated focal segmental glomerulosclerosis (FSGS) (64%), membranous nephropathy (MGN) (12%), mesangial glomerulonephritis (MSGN) (12%) and minimal change disease (MCD) (12%). Pre-treatment laboratory tests showed a mean 24-hr proteinuria of 4372 +/- 2686 mg/dL. Treatment with CsA was given for a minimum of 3 months and a maximum of 98 months. Mean 24-hr proteinuria declined from 3181 +/- 2277 before CsA to 915 +/- 1140 mg/24 hr after CsA (p<0.001). Remission was seen in 70.5% of patients, being 52.9% complete and 17.6% partial. The adverse effects observed were nephrotoxicity (11.7%), hypertrichosis (5.8%) and gingival hyperplasia (5.8%). Relapses were seen in eight patients (47%), with posterior remission in six patients (75%). CONCLUSION: Data from the literature suggest that CsA is a good therapeutic option for patients with steroid-resistant INS, being effective in reducing proteinuria. The beneficial effect of CsA demonstrated in our study was limited due to its design and the small sample size.     

Association of HLA-DRw8 and DQw3 with minimal change nephrotic syndrome in Japanese adults

The HLA systems of forty Japanese patients with adult-onset nephrotic syndrome and biopsy-proven minimal change were investigated. HLA-DRw8 was found in 35% of the patients and HLA-DQw3 in 95%, compared to 12.6 and 63.1% of the control, respectively (DRw8: and Pc less than 0.01, RR = 3.74; DQw3: Pc less than 0.02, RR = 11.1). The phenotype frequencies of all but one HLA-DR antigens, DR4, DR5, DRw8, and DRw9 associating with DQw3, were observed to increase (patient vs. control: DR4, 65 vs. 41.4%; DR5, 10 vs. 4.3%; DRw9, 20 vs. 23%). These results suggest that HLA-DQw3 may be a primary genetic marker associated with a major susceptibility gene to adult-onset minimal change nephrotic syndrome in the Japanese population.     

No evidence for a specific role of IgM in mesangial proliferation of idiopathic nephrotic syndrome

To define the relationship of mesangial IgM to various morphologic categories of idiopathic nephrotic syndrome (INS), an analysis of 100 patients was carried out in which five morphologic subgroups were evaluated: group 1, minimal glomerular change (38 patients); group 2, minimal change with focal global sclerosis (18 patients); group 3, focal segmental glomerulosclerosis ( FSG ) (23 patients); group 4, mesangial proliferation (12 patients); group 5, focal segmental glomerulosclerosis with mesangial proliferation (9 patients). Immunohistochemical studies failed to demonstrate any differences between these five groups. The intensities of immunofluorescence and the percentage of tissue samples demonstrating IgM and/or C3 in the glomerular mesangium and subendothelial regions were similar. In addition, the presence or intensity of mesangial IgM did not predict the patients' current status or responsiveness to steroid therapy. Morphologic transitions were observed in patients who had more than one biopsy: one of five in group 2 and two of eight in group 3 developed mesangial proliferation; and nine of ten patients with mesangial proliferation in the first biopsy continued to show this finding in the second. In general, a complete response to steroid therapy and a favorable outcome is less likely in patients with this morphologic abnormality. In nine of the 27 repeat biopsies, there was lack of agreement between the first and second tissue samples with respect to the presence or absence of mesangial IgM. Although mesangial proliferation is a consistent feature of the morphology of certain patients with INS, these studies do not support a unique association with mesangial IgM.     

Recurrent nephrotic syndrome with three successive renal allografts

A girl with idiopathic steroid-resistant nephrotic syndrome was studied at onset of the disease at 6 years of age and during recurrences of the nephrotic syndrome after successive transplantations of three renal allografts. Focal glomerulosclerosis was demonstrated shortly after onset of the original disease with progression to renal insufficiency over 14 months. Recurrence of the nephrotic syndrome was documented 4 weeks following transplantation of the first renal allograft and a biopsy demonstrated focal segmental glomerulosclerosis without evidence of rejection. By 13 months, recurrent disease had caused renal failure requiring dialysis. After transplantation of the next long-functioning graft, the nephrotic syndrome rapidly recurred with urinary protein excretion of 8 g/day and normal glomerular filtration rate at 8 weeks. After the 5th month, progressive renal insufficiency developed and dialysis was resumed at 10 months after transplantation. The nephrectomy specimen showed advanced focal segmental glomerulosclerosis and chronic rejection. Early after the last renal allograft, she had mild persistent proteinuria and then developed nephrotic syndrome at 10 months which was attributed to chronic rejection. The graft was lost to delayed accelerated rejection at 17 months. The rapid recurrence of nephrotic syndrome after transplantation of each of the first two long-functioning allografts to this patient is most consistent with recurrence of original disease. However, observations in a subsequent graft demonstrated that rapid recurrence of the original disease is not inevitable.     

Primary nephrotic syndrome in Arab children in Kuwait

Fifty-five Arab children with primary nephrotic syndrome (PNS) were seen at two regional hospitals in Kuwait over a 5-year period. There were 35 boys and 20 girls with a mean age of 5.3 years. The annual incidence was 7.2 and 6.0 per 100,000 children below 10 and 12 years of age, respectively. An initial response to steroids was noted in 84% with almost 50% responding within 1 week of therapy. Nine patients did not respond to steroids; histopathological classification of their renal biopsies showed 5 cases of membranoproliferative nephritis, 3 cases of focal segmental glomerulosclerosis and 1 case of membranous nephropathy. Microscopic haematuria was noted at presentation in 7 of 46 steroid responders, in all 5 patients with membranoproliferative disease and in 1 of 3 with focal segmental glomerulosclerosis. We conclude that the incidence of PNS seems to be higher among Arab children than in Western countries. With regard to initial biochemical abnormalities, steroid response and subsequent relapses, the pattern is the same as elsewhere.     

Urinary proteome of steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome of childhood

The response to steroid therapy is used to characterize the idiopathic nephrotic syndrome (INS) of childhood as either steroid-sensitive (SSNS) or steroid-resistant (SRNS), a classification with a better prognostic capability than renal biopsy. The majority (approximately 80%) of INS is due to minimal change disease but the percentage of focal and segmental glomerulosclerosis is increasing. We applied a new technological platform to examine the urine proteome to determine if different urinary protein excretion profiles could differentiate patients with SSNS from those with SRNS. Twenty-five patients with INS and 17 control patients were studied. Mid-stream urines were analyzed using surface enhanced laser desorption and ionization mass spectrometry(SELDI-MS). Data were analyzed using multiple bioinformatic techniques. Patient classification was performed using Biomarker Pattern Software and a generalized form of Adaboost and predictive models were generated using a supervised algorithm with cross-validation. Urinary proteomic data distinguished INS patients from control patients, irrespective of steroid response, with a sensitivity of 92.3%, specificity of 93.7%, positive predictive value of 96% and a negative predictive value of 88.2%. Classification of patients as SSNS or SRNS was 100%. A protein of mass 4,144 daltons was identified as the single most important classifier in distinguishing SSNS from SRNS. SELDI-MS combined with bioinformatics can identify different proteomic patterns in INS. Characterization of the proteins of interest identified by this proteomic approach with prospective clinical validation may yield a valuable clinical tool for the non-invasive prediction of treatment response and prognosis.     

Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid-dependent and -resistant nephrotic syndrome

A retrospective study was made on 37 children with idiopathic nephrotic syndrome (INS). At the beginning, all patients were steroid sensitive but received more than one steroid course (median 4). Following several relapses, they became steroid dependent or steroid resistant. Group 1 consisted of 22 children [3 focal segmental glomerulosclerosis (FSGS), 19 minimal-change NS (MCNS)] who received cyclophosphamide (CP) orally for 2.5 +/- 0.5 months. Group 2 consisted of 15 children (7 FSGS, 8 MCNS) who received cyclosporine-A (CSA) for 28 +/- 15 months. The level of proteinuria decreased significantly and remained low during the follow-up. The relapse-free period was significantly longer in the CP group (CP 30 +/- 21.5; CSA 26.2 +/- 18 months, p < 0.001). The relapse rate decreased significantly in both groups and remained in this lower level during the follow-up (from 3.4 +/- 2.8 to 0.1 +/- 0.2/year in group 1, and from 3.7 +/- 3.1 to 0.6 +/- 0.8/year in group 2). At the end of the 5-year follow-up, 20/22 patients (90.9%) and 10/15 patients (66.6%) were in remission in groups 1 and 2 respectively, with or without treatment (p < 0.05). In the long term, both CP and CSA is effective second-line therapy following steroid monotherapy in INS patients, but the relapse rate was lower and the relapse free period was significantly longer in the CP-treated group.     

Mycophenolate mofetil therapy in frequently relapsing steroid-dependent and steroid-resistant nephrotic syndrome of childhood: current status and future directions

Clinicians are often faced with therapeutic dilemmas and challenges while treating children with frequently relapsing steroid-dependent nephrotic syndrome (SDNS) and steroid-resistant nephrotic syndrome (SRNS). In the past, children with SDNS have been treated with long-term alternate day steroids cyclophosphamide, cyclosporine (CSA), chlorambucil, levamisole, and azathioprine. The essential aim of these therapies is to maintain remission while limiting exposure to steroids. These medications have variable efficacy and undesirable toxicity profiles. Recently, mycophenolate mofetil (MMF) has emerged as a new therapeutic option for the management of SDNS in a few uncontrolled clinical trials. Preliminary data are encouraging. MMF was found to be useful in maintaining remission and has a steroid-sparing effect. Clearly, more data are needed to further characterize the safety and efficacy of MMF, define adequate length of treatment, and optimize drug exposure and monitoring. The management of SRNS is primarily aimed at decreasing proteinuria and inducing remission, if possible. By doing so, one would aim to preserve renal function. CSA therapy is known to be useful in this regard but has undesirable side effects, the most concerning being nephrotoxicity. MMF in combination with steroids and angiotensin-converting enzyme-inhibitor drugs is known to have some efficacy in the management of SRNS. These preliminary data have prompted the National Institutes of Health to sponsor a multicentric controlled trial to compare the safety and efficacy of MMF with that of CSA in the treatment of steroid-resistant focal segmental glomerulosclerosis (FSGS). If MMF therapy is found to be efficacious, it would help obviate the need for CSA and its associated nephrotoxicity. Clearly, MMF has emerged as an important new therapeutic option for the treatment of childhood nephrotic syndrome and FSGS. Further data are required to assess those conditions most likely to respond.     

Does cyclosporine achieve a real advantage for treatment of idiopathic nephrotic syndrome in children? A long-term efficacy and safety study

Background Cyclosporine (CsA) was found to be efficient in decreasing proteinuria in both steroid-dependent and steroid-resistant nephrotic patients. We aimed to explore the potential long-term benefits and hazards of CsA and their predictors among a large group of nephrotic patients. Methods In this retrospective analysis, we included 197 pediatric patients with idiopathic nephrotic syndrome (INS) of whom 103 were steroid dependent and 94 steroid resistant. Results CsA induced complete remission in 132 (67%) and partial response in 13 (6.6%). Cyclosporine was received for a period of 22.16 ± 12.21 months. Univariate analysis showed that the response to CsA was significantly better in steroid-dependent children, in minimal change disease (MCD), diffuse mesangial proliferative glomerulonephritis (DMP) and focal segmental glomerulosclerosis (FSGS) than in other pathological lesions and in those who had lower quantities of pretreatment proteinuria. Only the prior response to steroids and concomitant use of ketoconazole with CsA were valid predictors for better response to CsA with multivariate analysis. Discontinuation of the drug in 40 patients resulted in relapse in 26 patients while the remaining 14 patients maintained remission. Renal dysfunction developed in 18 patients of whom 12 recovered completely on drug discontinuation. Thirty-seven patients developed hypertension. Multivariate analysis showed that all side-effects were significantly more prevalent in CsA-resistant patients. Conclusion CsA is effective and well tolerated in the long-term treatment of INS in children, however two thirds of cases showed relapse after CsA discontinuation