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%, 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.The abstract of this study was accepted as a poster for the 36th meeting of the European Society of Paediatric Nephrology, Bilbao, September 2002. This study was supported in part by a grant from the Istanbul University Research Fund (no T-849/17072000)     

Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome

Attempts to minimize the effects of prolonged steroid use in steroid-dependent nephrotic syndrome (SDNS) and the need to overcome steroid resistance (SRNS) justifies immunosuppressant therapy. We report our experience in a cohort of patients with SD/SRNS during the administration of mycophenolate mofetil (MMF) in a prospective protocol initiated in January 2001. Twenty-six children with idiopathic nephrotic syndrome were included (21 steroid dependent and 5 steroid resistant), whose response did not change after sequential treatment with cyclophosphamide (CPM) and cyclosporine (CsA). Histopathologic patterns were: 11 minimal change disease (MCD), 1 diffuse mesangial proliferation (DMP), 13 focal segmental glomerulosclerosis (FSGS) and membranous 1 glomerulonephritis (MGN). The median age of onset of NS was 2.8 years (range 1.2–12.5), and treatment with MMF was performed at a median age of 11.4 years (range 5–17) with an initial dose of 600 mg/m²/12 h, adjusted to maintain levels of mycophenolic acid (MPA) at 2.5–5 mcg/ml. The planned duration of study to assess treatment efficacy was 6 months. The mean MMF dose required was 624 (SD=136) mg/m²/12 h (range 415–970), which maintained mean C₀-MPA levels of 2.9 (SD=1.17) mcg/ml (range 1.2–5.9 mcg/ml). In the five patients with SRNS, only one achieved complete remission. In the patients with SDNS, steroid sparing was achieved in 15 and 9 remained in remission on MMF monotherapy. Withdrawal of MMF resulted in immediate relapse in 47%. In our study, MMF was a useful immunosuppressant due to its fewer undesirable effects and similar efficacy to other drugs used. It appears effective for the maintenance of remission in SDNS patients, with a response similar to that of CsA.     

Expression of nephrin in acquired forms of nephrotic syndrome in childhood

Nephrin is a podocyte adhesion molecule located at the slit diaphragm between adjacent glomerular epithelial cells. Mutations in the gene encoding nephrin result in the absence of nephrin or alterations in nephrin causing massive proteinuria in patients with congenital nephrotic syndrome. Given the importance of nephrin to the structural integrity of the glomerular filtration barrier, we postulated that it might also be altered in acquired forms of nephrotic syndrome (NS). To test this hypothesis, frozen kidney biopsy sections from 29 pediatric patients with acquired NS and 5 controls were examined for expression of nephrin. The pathological diagnoses were minimal change disease (MCNS) (19) and focal segmental glomerulosclerosis (FSGS) (10). To determine if nephrin expression differed between children and adults with NS, 10 adult patients and 3 controls were also examined. Nephrin expression was evaluated by immunoperoxidase staining with a monoclonal antibody against the extracellular FnIII portion of human nephrin. In all cases, nephrin expression was seen along the glomerular basement membrane in a finely granular/linear pattern. Expression of nephrin was similar to controls in all 19 patients with MCNS and all 10 patients with FSGS. Areas of sclerosis in patients with FSGS did not demonstrate nephrin expression. A distinctly granular pattern to nephrin expression was seen in adult patients with NS as well as controls. These findings suggest that an alteration in nephrin expression is not a feature of acquired forms of NS in childhood.     

Lymphocyte ectoenzymes in childhood idiopathic nephrotic syndrome

Lymphocyte ectoenzymes with immunomodulatory function were investigated in 11 children with minimal change disease (MCD), 9 with primary focal segmental glomerulosclerosis (FSGS), and 17 age- and sex-matched healthy children. Basal, concanavalin A (Con A)-, and pokeweed mitogen (PWM)-stimulated lymphocyte ecto-5′-nucleotidase (5′-Nu), dipeptidyl peptidase IV (DPP IV), and alkaline phosphodiesterase I (APD) activities were determined. In MCD relapse ecto-APD activity of unstimulated lymphocytes was higher than controls. Ecto-APD of Con A-stimulated lymphocytes was below controls (23.0, range 7.2– 48.7 nmol/min per 10⁶ lymphocytes) in all active MCD (18.7, range 7.6–32.6), during corticosteroid treatment (14.6, range 4.5–54), and in remission (13.1, range 6.1–19.6), but was significant only in remission. Con A-stimulated DPP IV was significantly lower from controls (53.8, range 19.3–85.7 nmol/min per 10⁶ lymphocytes) in all active MCD (38.1, range 10.8–82.1), during treatment (37.5, range 20.2–58.7), and in remission (39.4, range 24.3–69.6). In FSGS, unstimulated lymphocyte ecto-APD activity was greater than controls. However, Con A-stimulated lymphocyte ecto-APD and DPP IV activities were not significantly different from controls. Con A stimulation of lymphocyte ecto-APD and DPP IV activity was significantly reduced in MCD relapse and in remission, but not in FSGS. Basal, Con A-, and PWM-stimulated ecto-5′-Nu in MCD and FSGS were not different from controls. These results suggest a role for abnormal T cell function in MCD but not in FSGS. The difference in mitogen-stimulated expression of these ectoenzymes suggests a different pathogenesis of childhood MCD and primary FSGS. Received June 30, 1997; received in revised form May 13, 1998; accepted May 27, 1998     

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.     

Interleukin-12 and interferon-γ production in childhood idiopathic nephrotic syndrome

Cellular immune disturbances, and T lymphocyte function in particular, have been previously implicated in idiopathic nephrotic syndrome (INS) of childhood. There are different patterns of cytokine expression in various forms of glomerulonephritis, which suggests that local production of these peptides plays an important role in the pathogenesis and progression of glomerulonephritis. To investigate T-cell and monocyte/macrophage cytokine production in INS, interleukin-12 (IL-12) and interferon-γ (IFN-γ) production by peripheral blood mononuclear cells (PBMC) of 11 children with steroid-sensitive nephrotic syndrome (SSNS), 9 with focal segmental glomerulosclerosis (FSGS), and 17 healthy controls was determined. Children with SSNS were studied in relapse, during corticosteroid treatment, and in stable remission, off corticosteroid treatment. IL-12 was not detected in serum, urine, and in supernatants of unstimulated PBMC. IL-12 production by concanavalin A (Con A)-stimulated PBMC of children with SSNS and FSGS was not different from controls. IFN-γ production by Con A-stimulated PBMC was decreased in children with relapsing SSNS, both in relapse and and during corticosteroid treatment. However, in stable remission it was similar to controls. Markedly decreased IFN-γ production (P<0.001) was observed by pokeweed mitogen-stimulated PBMC of relapsing SSNS patients and moderately decreased production by PBMC of FSGS patients. This study has established a decreased production of IFN-γ by PBMC of relapsing SSNS and FSGS patients, but does not allow differentiation between these two different conditions. IL-12 did not have a pathogenic role in either SSNS or FSGS. Received May 24, 1997; received in revised form March 19, 1998; accepted March 23, 1998     

Diagnostic value of urinary retinol-binding protein in childhood nephrotic syndrome

Urinary excretion of N-acetyl-β-d-glucosaminidase (NAG) and retinol-binding protein (RBP), sensitive markers of renal tubular damage and dysfunction respectively, were evaluated in paired remission and relapse urine samples from 16 patients (median age 12 years), with minimal change nephrotic syndrome (MCNS), in single samples from 5 nephrotic patients (median age 12 years) with focal segmental glomerulosclerosis (FSGS) and in 183 normal controls aged 2–16 years. The NAG and RBP data were expressed as a ratio over urinary creatinine (Cr). The NAG/Cr and RBP/Cr geometric means (ranges) for normal subjects were 11.1 (3.4–35.5) μmol 2-methoxy-4-(2"-nitrovinyl)-phenol (MNP)/h per mmol and 3.1 (0.3–38.8) μg/mmol, respectively. The NAG/Cr data revealed a weak negative correlation with age in normal children, whereas RBP/Cr was independent of age. RBP/Cr and NAG/Cr in MCNS in remission were the same as in controls. In MCNS in relapse, NAG/Cr was significantly elevated (P=<0.001), while in FSGS both RBP/Cr and NAG/Cr were significantly raised (P=<0.001 and P<0.008, respectively). These findings suggest that elevated NAG/Cr may be an indicator of relapse in both MCNS and FSGS and elevated RBP/Cr may allow differentiation between the two. Received May 7, 1997; received in revised form January 30, 1998; accepted February 4, 1998     

Remission of relapsing childhood nephrotic syndrome with mycophenolate mofetil

We report a 21-year-old male with childhood-onset familial nephrotic syndrome and frequent relapses who manifested toxicity or treatment resistance to corticosteroids, cyclophosphamide, cyclosporin-A, and tacrolimus. Monotherapy with mycophenolate mofetil (MMF) resulted in maintenance of clinical remission for 14 months without noticeable toxicity, while allowing resolution of steroid-induced side effects. Our observation suggests that MMF may be useful in maintaining remission in nephrotic patients who manifest toxicity to standard immunosuppressive agents. Received: 6 April 1999 / Revised: 10 August 1999 / Accepted: 13 August 1999     

Vincristine in steroid-resistant nephrotic syndrome

The therapeutic response to vincristine was examined in seven children (aged 2–15 years) with corticosteroid-resistant (CR) nephrotic syndrome (NS) with focal and segmental glomerulosclerosis (FGS). Five were also resistant to cyclophosphamide. Vincristine was given weekly (1.5 mg/m² intravenously) for 8 weeks. Simultaneously, prednisone (60 mg/m² per day, orally) was given for 4 weeks and then gradually tapered. Two of these patients had a complete and stable remission; in five no benefit was observed. It was not possible to identify any characteristics to predict the response to vincristine. Although there is a case for trying vincristine therapy in CR NS with FGS, the results of this study are not encouraging and a better understanding of its action and indications is necessary.     

Efficacy of intravenous pulse cyclophosphamide treatment versus combination of intravenous dexamethasone and oral cyclophosphamide treatment in steroid-resistant nephrotic syndrome

We compared, in a randomized controlled trial, the efficacy of a regimen based on intravenous (i.v.) cyclophosphamide therapy with a combination of i.v. dexamethasone and oral cyclophosphamide therapy in inducing remission in patients with steroid-resistant nephrotic syndrome (SRNS). During April 2001 to December 2003, 52 consecutive patients with idiopathic SRNS, normal renal function and renal histology findings showing minimal change disease, focal segmental glomerulosclerosis or mesangioproliferative glomerulonephritis were enrolled into the study. Patients in group I received i.v. injection of cyclophosphamide once a month for 6 months and prednisolone on alternate days. Those in group II received i.v. treatment with dexamethasone (initially on alternate days, later fortnightly and monthly; total 14 doses), oral cyclophosphamide therapy (for 3 months) and prednisolone on alternate days. Data from 49 patients (26 in group I, 23 in group II) were analyzed; their clinical and biochemical features were similar at inclusion. Following treatment, complete remission was seen in 53.8% and 47.8% patients in groups I and II, respectively (P = 0.6). Long-term follow up showed favorable outcome in 14 (53.8%) patients in group I, and 9 (39.1%) in group II. Chief adverse effects, including cushingoid features and serious infections, were similar in both groups. Patients receiving i.v. dexamethasone therapy commonly showed hypertension and hypokalemia, while vomiting and reversible alopecia occurred in those receiving i.v. treatment with cyclophosphamide. In patients with SRNS, the efficacy of treatment intravenously with cyclophosphamide and orally with prednisolone was similar to the combination of dexamethasone intravenously, orally administered cyclophosphamide and prednisolone.     

NPHS2 (podicin) mutations in Turkish children with idiopathic nephrotic syndrome

The podocin (NPHS2) gene encodes podocin protein, which has an important role in glomerular ultrafiltration and controlling slit membrane permeability. The detection of an NPHS2 mutation affects the treatment plan for children with nephritic syndrome (NS). The frequency and spectrum of podocin mutations in the Turkish population have remained largely unknown. The aim of this study was to screen for podocin mutations in Turkish patients with steroid-resistant NS (SRNS) and to compare it with other published series. There were 295 children with SRNS, originating from Turkey, included in this study. Forty-one patients (13.8%) had familial NS and 254 patients (86.2%) had sporadic NS. Mutation analysis was performed in all eight exons of the NPHS2 gene with the direct DNA sequencing method. There were 53 different pathogenetic NPHS2 mutations detected, including 37 novel mutations. The mutation detection rate was 24.7% for all patients, 29.2% for familial, and 24% for sporadic SRNS. The most common mutated exon was exon 5 (52 allele). The presence of mutations in exon 4 was found to increase the risk of end-stage renal disease (ESRD). Among patients with mutations, the rates of renal failure and/or ESRD (26%) were significantly higher than in those without mutations (12.6%). The mean time of progression to renal failure and ESRD in patients with mutations (1.8 ± 2.5 years) was significantly shorter than in patients without mutations (3.7 ± 4.0 years). Additionally, in patients with heterozygote mutations, fewer cases (13.6%) progressed to renal failure and/or ESRD than in with patients who had homozygote/compound heterozygote mutations (31.3%). In conclusion, podocin mutations are responsible for some of both familial and sporadic SRNS cases in Turkey. The mutations in this gene should be searched for in every child after presentation with the first episode of NS.     

Treatment with mycophenolate mofetil and prednisolone for steroid-dependent nephrotic syndrome

The management of patients with steroid-dependent nephrotic syndrome (SDNS) refractory to treatment with long-term steroids, levamisole and cyclophosphamide is difficult. We report our experience on long-term treatment with mycophenolate mofetil (MMF) and alternate-day prednisolone in 42 patients with SDNS previously treated with levamisole (n = 35) and/or cyclophosphamide (n = 37). The mean age (range) at onset of nephrotic syndrome was 37 (13–92) months and at treatment with MMF 104.7 (32–187) months. MMF was administered at a mean daily dose of 26.5 (16.6–31.3) mg/kg for 14.3 (6–45) months. The mean 6-monthly relapse rates decreased from 3.0 episodes before therapy to 0.9 episodes in the first 6 months, 0.7 in next 6 months, and 0.3 in those treated longer than 12 months (P < 0.0001). While on therapy, 32 (76.2%) patients showed 50% or more reduction in relapse rates, and nine (21.4%) had sustained remission. The cumulative dose of prednisolone declined significantly from 0.6 mg/kg per day before to 0.3 mg/kg per day while receiving MMF. Prednisolone requirement was reduced by 50% or more in 16 patients and between 40% and 50% in eight patients. Treatment continuation beyond 12 months resulted in sustained steroid sparing and reduced need for alternative treatments while maintaining low relapse rates. No patients had diarrhea, hematological abnormalities, or impaired renal function. This data confirms the efficacy and safety of treatment with MMF and tapering doses of alternate-day prednisolone in patients with SDNS and supports its use for longer than 12 months.     

Acute renal failure at the onset of idiopathic nephrotic syndrome in two children

Two children with idiopathic nephrotic syndrome (INS) developed acute renal failure (ARF) at the onset of the disease. Although the initial renal biopsy showed minimal change (MC) lesions with prominent interstitial edema, repeat renal biopsy revealed focal segmental glomerulosclerosis (FSGS). ARF has been reported to be a relatively rare complication in childhood INS. However, the initial manifestation of ARF may increase the risk for subsequent progression to FSGS in a proportion of children with INS with MC lesions. Received: April 3, 2000 / Accepted: October 31, 2000     

Therapies for steroid-resistant nephrotic syndrome

Between 10 and 20% of children with primary nephrotic syndrome are steroid-resistant (SRNS). From earlier studies in children with SRNS, we know that cyclosporin (with or without alternate-day prednisone) and cyclophosphamide (with pulse intravenous corticosteroids) result in comparable complete or partial remission rates of about 60%. An evaluation of the relative effectiveness of cyclophosphamide and cyclosporin has not been possible because of the absence of a head-to-head randomised trial. The Arbeitsgemeinschaft für Pädiatrische Nephrologie trial, published in this issue of Pediatric Nephrology, has filled this gap in our evidence base. Although there was no difference in the number of patients achieving complete remission, those patients receiving cyclosporin treatment were significantly more likely to achieve partial remission than those receiving intravenous cyclophosphamide. This result suggests that cyclosporin rather than cyclophosphamide should be used as first line therapy for children with SRNS.     

Lithium-induced nephrotic syndrome in a young pediatric patient

Lithium-induced nephrotic syndrome is a rare complication of lithium therapy and is even rarer in children. Most reported cases have been secondary to minimal change disease, which reverses within 1–4 weeks on discontinuation of lithium therapy. However, focal glomerulosclerosis (FSGS) has occasionally been reported and is not always reversible with discontinuation of lithium. We report an 11-year-old child with lithium-induced FSGS nephrotic syndrome who went into full remission after lithium was discontinued. Received: 11 June 2001 / Revised: 9 October 2001 / Accepted: 9 October 2001     

Immunosuppressive therapy in the nephrotic syndrome in children

The high incidence of remission and prevention of relapse of minimal change nephrotic syndrome (MCNS) in children, produced by corticosteroids is reviewed. With the introduction of corticosteroids over 30 years ago and the increased expertise in their use, the mortality rate has been reduced to less than 5%. There is no justification for a clinical trial to test the effect of corticosteroids in inducing remission, but the need remains to evaluate methods of administration in order to achieve therapeutic benefit with minimum toxicity. children with frequently relapsing, steroid-dependent MCNS will usually enter remission following treatment with an alkylating agent such as cyclophosphamide. In about 50% no further relapse in experienced. The results of recent experience using cyclosporin A immunosuppression suggest a beneficial effect associated with steroid responsiveness. Approximately 30% of children with focal segmental glomerulosclerosis enter remission following treatment with corticosteroids. Some 30% require dialysis and transplantation within 5 years of diagnosis and immunosuppressive therapy to prevent deterioration of renal function is probably justified.     

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.     

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     

Apolipoprotein E polymorphism in childhood nephrotic syndrome

Recent clinical reports have demonstrated that the progression and prognosis of renal diseases are possibly influenced by apolipoprotein E (apoE) genotypes and alleles. In this study we investigated whether apoE genotypes and alleles can be a prognostic criterion for the steroid responsiveness in childhood nephrotic syndrome. One hundred and seven pediatric patients with primary idiopathic nephrotic syndrome and 83 healthy volunteers were enrolled in the study. Eighty-seven of the patients had steroid-sensitive nephrotic syndrome (SSNS) and 20 had steroid-resistant nephrotic syndrome (SRNS). The ɛ2 allele frequency and ɛ2/3 genotype frequency of the SNRS group were statistically higher when compared with SSNS and control groups (P<0.05). The higher frequency of the ɛ2 allele in steroid resistant nephrotic patients suggests that the ɛ2 allele gives a possible genetic predisposition to steroid resistance in our population, but further studies are needed to clarify this subject. Received: 15 November 2000 / Revised: 15 November 2001 / Accepted: 18 November 2001     

Nephrotic syndrome and rituximab: facts and perspectives

Idiopathic nephrotic syndrome is the most frequent glomerular disease that presents during childhood and is mainly due to minimal change nephropathy (MCNS) and focal-segmental glomerulosclerosis (FSGS). Its treatment is still challenging, with up to 50% of the patients who are initially steroid sensitive (usually MCNS) being frequent relapsers and requiring additional long-term immunosuppression. However, current immunosuppressive regimens are associated with severe toxicity. Only half of the steroid-resistant patients (usually FSGS) achieve long-term remission even with intensive immunosuppression and plasma exchange. Rituximab (RTX), a chimeric monoclonal antibody inhibiting CD20-mediated B-cell proliferation and differentiation, has recently gained attention as a potentially successful therapy for complicated idiopathic nephrotic syndrome in children. A number of case reports and one prospective non-controlled multicenter trial point to the beneficial effects of RTX as a rescue therapy in children with steroid/cyclosporine-dependent or -resistant nephrotic syndrome. However, publication bias often results in positive outcomes being more likely to be reported than negative ones and, in particular, the safety profile of this drug in this group of patients remains unclear. Therefore, controlled randomized studies are required to assess this issue, to develop treatment guidelines, to evaluate the therapeutic and economical efficacy, and to define criteria for the selection of patients.