Mutational analysis of <Emphasis Type="Italic">NPHS2</Emphasis> and <Emphasis Type="Italic">WT1</Emphasis> in frequently relapsing and steroid-dependent nephrotic syndrome

Idiopathic nephrotic syndrome is a common pediatric kidney disease, 80% of all cases are steroid sensitive (SSNS). A significant proportion of children with SSNS will have a frequently relapsing or steroid-dependent course (FRNS/SDNS) that is associated with significant treatment-related morbidity. Mutations in NPHS2 account for more than 28% of all cases of steroid-resistant nephrotic syndrome (SRNS) and dominant mutations in WT1 for 5%; while mutations are absent from children with uncomplicated SSNS. Since FRNS/SDNS is phenotypically positioned within a spectrum between SSNS and SRNS, we hypothesized that heterozygous mutations of NPHS2 may be causing FRNS/SDNS. Mutational analysis of NPHS2 and WT1 was carried out in a single-center cohort of 20 children with FRNS/SDNS, ten children with uncomplicated SSNS (control), and 22 children with SRNS (control). Renal biopsy findings were available in 15/20 children with FRNS/SDNS and revealed IgM nephropathy, MCNS, and FSGS in six, five, and four children, respectively. Children with FRNS/SDNS were significantly younger at first presentation than those with SSNS and SRNS (median age: 3.0 years in FRNS/SDNS patients, 7.0 years in SSNS patients, and 5.0 in SRNS patients; p < 0.001). No NPHS2 or WT1 mutations were found in patients with FRNS/SDNS and uncomplicated SSNS. The hypothesis that FRNS/SDNS may be associated with heterozygous mutations in NPHS2 or WT1 was not confirmed.     

Rituximab and minimal change nephrotic syndrome: a therapeutic option

Minimal change nephrotic syndrome (MCNS) usually responds to steroids but frequently relapses, requiring additional treatment with immunosuppressive agents. Rituximab is a chimeric murine/human monoclonal immunoglobulin G1 antibody that targets CD20, a B-cell differentiation marker. B-cell recovery begins at approximately 6 months following the completion of treatment. Rituximab has a beneficial effect, with the sustained remission or reduction of proteinuria in patients with steroid-dependent MCNS. Relapses are thought to be associated with an increase in CD19 cells. The mean serum half-life of rituximab was reported to be 10–15 days in patients with steroid-dependent nephrotic syndrome. Only infusion reactions, such as rash and chills, occurred after single-dose rituximab infusion and can be managed by pre-medication or infusion rate adjustments. Even though severe adverse effects of rituximab are not expected, physicians must be aware of potentially life-threatening adverse effects. Controlled randomized trials that include adult patients with steroid-dependent or steroid-resistant MCNS are required to prove the efficacy and safety of rituximab and to evaluate the cost-effectiveness of rituximab treatment.     

DD genotype of ACE gene in boys: may it be a risk factor for minimal change nephrotic syndrome?

It has been shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects the circulating and cellular levels of ACE and may be a risk factor in several renal diseases. We analyzed the association of ACE gene I/D polymorphism with the clinical presentation of minimal change nephrotic syndrome (MCNS) in a Turkish child population. This study consisted of 97 children with MCNS and 144 healthy controls. Genotyping of ACE gene was performed using polymerase chain reaction (PCR). The distributions of ACE genotypes were II in 13%, ID in 49%, and DD in 38% in patient group, and 9%, 49%, and 42% in control group, respectively. The frequency of the D allele was 63% and that of the I allele was 37% in patients. There were no relevant differences in the allele frequencies and genotypes of ACE I/D polymorphism between patients and controls. However, DD genotype was higher in boys in children with MCNS (78.4%. vs. 50.0%, p = 0.004). The frequencies of DD genotype and D allele in boys were 7.25 and 2.56 times higher than II genotype and I allele in the patient group, respectively. We suggest that DD genotype in boys may be one of the risk factors for MCNS.     

Increased HLA-A*11 in Chinese children with steroid-responsive nephrotic syndrome

Human leukocyte antigen (HLA) associations have been frequently reported in childhood steroid-responsive nephrotic syndrome (SRNS) in other populations. The aim of this study was to characterize the immunogenetic background of Singaporean Chinese patients with childhood SRNS. We determined the HLA class I (HLA-A* and HLA-B*) as well as class II (HLA-DRB1*, HLA-DQB1*) gene polymorphisms using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique, in patients with SRNS (n=64) and normal controls (n=236 for HLA-A*, n=80 for HLA-B*, HLA-DRB1* and HLA-DQB1*). The frequency of HLA-A*11 allele was significantly higher in the SRNS patients compared to controls (78.1% vs 54.2%, respectively; relative risk, RR=3.01, Pc=0.011). However, there was no significant difference in the allele frequencies of HLA-B*, HLA-DRB1* and HLA-DQB1* between the SRNS patients and controls, unlike that in previous studies. Our data suggest that the immunogenetic background of Singaporean Chinese with childhood SRNS was different from that in other populations. As HLA-A*11 has been strongly associated with other autoimmune diseases, it is conceivable that the HLA-A*11-specific motif may play a role in the development of the abnormal T-cell-mediated immune response that may be responsible for triggering the proteinuria seen in SRNS. Received: 24 April 2001 / Revised: 14 November 2001 / Accepted: 18 November 2001     

HLA-DRB1 alleles in Kuwaiti children with idiopathic nephrotic syndrome

We have studied the effect of HLA-DRB1 alleles on the clinical presentation of 61 Kuwaiti Arab children with idiopathic nephrotic syndrome. DR7(*0701) was the most prevalent DR allele, found in 41/61 patients (67%) compared with 10/59 healthy controls (17%) (p<0.001). DR3(*0301–0308) allele was the second most common, found in 25% of patients compared with 26% of controls (not significant). There was no significant difference between DRB1*0701(DR7)-positive and DRB1*0701-negative patients in terms of steroid sensitivity, steroid dependency, or steroid resistance. Nevertheless, the former group had a significantly lower mean age of onset (35 months vs 53 months) and a shorter remission period following treatment with cyclophosphamide or chlorambucil (8 months vs 29 months). Our data highlight the role of the DRB1*0701 allele in predisposing Kuwaiti Arab children with idiopathic nephrotic syndrome to a more prolonged course of the disease. Received: 2 July 1999 / Revised: 20 April 2000 / Accepted: 23 April 2000     

Association of the macrophage migration inhibitory factor −173*C allele with childhood nephrotic syndrome

Macrophage migration inflammatory factor (MIF) is a proinflammatory cytokine with a unique role as the physiologic counterregulator of the immunosuppressive effects of glucocorticoids. MIF has been implicated in the pathogenesis of glomerular inflammation. The MIF promoter contains a G/C polymorphism that is functionally relevant, with the C allele being associated with higher MIF production and linked to susceptibility to inflammatory diseases. We genotyped the MIF −173 polymorphism in 257 children with idiopathic nephrotic syndrome (INS) and 355 controls. Frequency of carriers of the high-producer MIF −173*C allele was higher in patients with INS (31.7%) than in controls (22.0%) [odds ratio (OR) 1.67, p = 0.006] The MIF −173 C allele was more frequent in steroid-resistant patients (43.5%) compared with steroid responders (22.8%) (OR 2.61, p = 0.0005). This difference was particularly evident in focal segmental glomerulosclerosis patients (OR 14.0, p = 0.002). No association with response to cyclosporin A was found. Carriers of the MIF −173*C allele had a significantly higher probability of end-stage renal disease (ESRD) compared with G/G homozygous patients within 5 years from onset (log rank 5.11 p = 0.024). These results underscore the role of MIF in INS disease progression and in the response to glucocorticoid treatment and suggest that screening of MIF genotype at disease onset may identify patients requiring a more aggressive therapeutic approach. Marina Vivarelli and Leila Emma D’Urbano contributed equally to the work.     

Sodium dodecyl sulphate polyacrylamide gel electrophoresis of urinary proteins in steroid-responsive and steroid-resistant nephrotic syndrome in children

Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) of urinary proteins was performed in 56 children with nephrotic syndrome during relapse, of whom 31 had their urines tested within 2 months of the onset of disease. The urines of all 32 steroid-sensitive [presumed minimal change nephrotic syndrome (MCNS)] patients revealed albumin and transferrin bands only; whereas 19 steroid-resistant children with focal glomerular sclerosis showed additional excretion of IgG and low molecular weight proteins (lysozyme, ₂). This mixed pattern of proteinuria was also detected in 5 other steroid-resistant patients, 3 of whom were Africans with MCNS on biopsy and 2 who were Indians and not biopsied. Findings in patients studied within 2 months of presentation were identical to those investigated later in the course of the disease. SDS PAGE analysis of urine, which appears to distinguish steroid-responsive from steroid-resistant patients, may provide a valuable adjunct to the management of childhood nephrotic syndrome.     

Genetic forms of nephrotic syndrome

Mutations of NPHS1, NPHS2 , or WT1 may be responsible for severe forms of nephrotic syndrome in children, progressing to end-stage renal failure. Recent studies have shown that congenital nephrotic syndrome may be secondary to mutations of one of these three genes and that some patients have a digenic inheritance of NPHS1 and NPHS2 mutations. The clinical spectrum of NPHS2 mutations has broadened, with the demonstration that mutations in the respective gene podocin may be responsible for nephrotic syndrome occurring at birth, in childhood, or in adulthood. It is now well recognized that podocin mutations are found in 10%–30% of sporadic cases of steroid-resistant nephrotic syndrome with focal segmental glomerulosclerosis. Data from large cohorts indicate that the risk of recurrence of nephrotic syndrome after renal transplantation in patients with podocin mutations is very low.     

Apolipoprotein E ɛ 4 allele and nephrotic glomerular diseases in children

 Hyperlipidemia is a well-recognized complication of the nephrotic syndrome and is a factor contributing to the progression of the initial glomerular injury and the development of glomerulosclerosis. Apolipoprotein E (apoE) is a plasma protein and apoE ɛ 4 allele is associated with higher plasma cholesterol levels. With this in mind, we studied apoE phenotypes and alleles in children with nephrotic glomerular diseases (NGD, n=29), including idiopathic nephrotic syndrome (n=16), membranoproliferative glomerulonephritis (n=7), and focal segmental glomerulosclerosis (FSGS, n=6). Children with NGD had a higher ɛ 4 allele frequency (20.7%) than controls (10.8%), and those with FSGS had both higher apoE4/3 (66.7%) and ɛ 4 allele (33.3%) frequencies than controls (20.4% and 10.8%, respectively). In IgA nephropathy (n=30, disease controls), no significant association with specific apoE was found. Further studies are needed to clarify the significance of the observed high frequencies of apoE ɛ 4 allele in children with NGD and apoE4/3 phenotype distribution in FSGS. Received: 19 December 1997 / Revised: 26 August 1998 / Accepted: 26 August 1998     

原发性肝细胞癌与HLA-DRB1基因多态性及DR抗原表达的关系

目的 探讨肝细胞癌(HCO与HLA-DRBl基因多态性及DR抗原表达的关系.方法 应用PCR-SSP方法与免疫组化技术对61例吉林地区汉族慢性乙型肝炎,44例乙型肝炎肝硬化病人,62例HCC病人及50名健康献血员作对照,进行了HLA-DRB1等位基因分型比较以及肝细胞癌癌组织、癌旁组织及正常肝组织的HLA-DR抗原表达进行检测.结果 慢性乙型肝炎组HLA-DRB1*1201-3等位基因表达频率为17.21%,明显高于正常对照组8.00%(P=0.0427,RR=2.391);慢性乙型肝炎组、乙型肝炎肝硬化组与肝癌组HLA-DRB1*0701等位基因频率分别为11.48%、12.50%、11.29%,明显高于正常对照组2.00%(P=0.0066,RR=6.35;P=0.0046,RR=7.00;P=0.0073,RR=6.236);HLA-DRB1*1501-5等位基因表达频率在肝癌组为18.55%,明显高于正常对照组9.00%(P=0.0423,RR=2.303);正常肝组织、肝癌旁组织肝细胞中HLA-DR抗原表达阴性,而34.2%的肝癌组织肝细胞膜和(或)胞浆中可见HLA-DR抗原表达,呈灶状分布,表达程度与肿瘤大小、癌周血管浸润及转移无关(P>0.05),与分化程度有关(P<0.05).结论 HLA-DRB1*1201-3、HLA-DRB1*0701等基因型与吉林地区汉族人群慢性乙型肝炎患病相关联,乙型肝炎肝硬化患病与HLA-DRB1*0701等位基因型相关联,肝癌患病与HLA-DRB1*1501-5、HLA-DRB1*0701等位基因型及DR表达量相关联.     

Treatment of tacrolimus or cyclosporine A in children with idiopathic nephrotic syndrome

Background

Cyclosporine A (CsA) and tacrolimus (TAC) are often alternative treatment choices for patients with nephrotic syndrome.

Methods

In this prospective study, the efficacy and safety of CsA and TAC in inducing and maintaining remission in 74 children with idiopathic nephrotic syndrome (INS) were evaluated.

Results

In terms of short-term efficacy, TAC was more effective than CsA in children with steroid-resistant nephrotic syndrome (χ²?=?13.75, P?=?0.001), although no significant difference in number of episodes of relapse were found in patients with complete remission between the two treatment groups (first year: χ²?=?0.261, P?=?0.88; second year: χ²?=?2.685, P?=?0.26). In patients with frequently relapsing or steroid-dependent nephrotic syndrome, no significant difference in short-term remission (χ²?=?1.908, P?=?0.39) or in relapse frequency during follow-up (within first year: χ²?=?1.046, P?=?0.59; within second year: χ²?=?0.587, P?=?0.75) were found between the two groups. There was a difference in the rate of adverse effects between the two treatment groups [nephrotoxicity: 4/24 (CsA) vs .0/50 (TAC), P?=?0.002; hirsutism: 8/24 (CsA) vs. 0/50 (TAC), P?<?0.001].

Conclusions

In our pediatric patient cohort, the treatment of steroid-resistant nephrotic syndrome with tacrolimus was associated with higher efficacy and lower renal toxicity in comparison to CsA, although no favorable outcome in relapse rate during long-term follow-up was seen. On the other hand, tacrolimus was not always the better choice to replace CsA in the treatment of severe frequently relapsing or steroid-dependent nephrotic syndrome.     

Nephrotoxicity of once-daily cyclosporine A in minimal change nephrotic syndrome

Background  

Although once-daily cyclosporine (CsA) therapy may have greater nephrotoxic-sparing effects than standard twice-daily therapy, little information is available in children with steroid-dependent minimal change nephrotic syndrome (MCNS) regarding histological analysis after long-term once-daily administration.     

Genetic forms of nephrotic syndrome: a single-center experience in Brussels

The aim of the study was to present our experience in treating children with genetic forms of nephrotic syndrome and diagnosing these diseases. We retrospectively reviewed the clinical data, mutational analyses, histopathological features, treatment modalities, and outcome of 26 consecutive children (20 families) suffering from congenital and/or steroid-resistant nephrotic syndrome who were assessed by genetic analysis. Ten out of 26 children (38%) had congenital nephrotic syndrome, 4/26 (15%) had infantile nephrotic syndrome, 10/26 (38%) had late-onset nephrotic syndrome, and 2/26 (9%) had asymptomatic proteinuria. We detected a mutation in 21/26 (81%) patients and in 15/20 (75%) families. NPHS1 mutation analyses were positive in 4/20 (20%), NPHS2 mutations in 4/20 (20%), WT1 mutations in 4/20 (20%), and PLCE1 mutations in 3/20 (15%) families. NPHS1 and PLCE1 mutations were solely found in patients with the earliest onset. The majority of patients, especially those with early onset of nephrotic syndrome, had serious adverse events related to the nephrotic status, and 19/26 (73%) reached end-stage renal failure at a median age of 27 months. Genetic forms of nephrotic syndrome comprise a heterogeneous group of genetic mutations. The progression toward end-stage renal failure is the rule but is highly variable between patients. Other participating authors are listed in the appendix. An erratum to this article can be found at     

Is typing for HLA class II alleles beneficial in Indian children with idiopathic nephrotic syndrome?

This study was conducted to test the hypothesis that analysis of HLA class II type alleles will give important information on the prognosis of NS in children. We prospectively studied 100 consecutive children with idiopathic nephrotic syndrome and 202 controls belonging to the same geoethnic background. Typing for HLA Class II alleles at DR and DQ locus was carried out by using SSP (sequence specific oligonucleotides based method). In our study children were more likely to have nephrotic syndrome if the allele DQ-β1*020X was present as compared to controls. On the other hand, DR-β1*1001, DR-β1*130X and DQ-β1*030X were significantly lower among patients and likely to be protective. On analysing the different steroid response categories, we observed that the allele DQ-β1*020X was significantly higher in infrequent relapsers (IFR) with a high etiological fraction of 0.714. Children were more likely to be steroid resistant if the allele DR-β1*150X was present and the etiological fraction was high (0.754). The allele DQ-β1*030X was significantly lower in steroid resistant patients (p=0.019, RR=0.1819, 95% CI=0.04430–0.7471) and likely to be protective. On analysing the haplotype distribution, we observed that occurrence of DR-β1*070X-DQ-β1*020X haplotype was significantly more common among patients with steroid sensitive nephrotic syndrome (23.94%) as compared to controls (12.5%) (p=0.01). In the steroid resistant group we observed that the haplotype DR-β1*150X-DQ-β1*060X was significantly more frequent as compared to steroid sensitive patients as well as controls p=0.01. We conclude that HLA typing in Indian children with NS helps to predict relapse frequency and steroid resistance.     

HLA-DRB1* alleles in Egyptian children with post-streptococcal acute glomerulonephritis

To investigate the association between HLA-DRB1* alleles and post-streptococcal acute glomerulonephritis (PSAGN) in Egyptian children, 32 unrelated patients with PSAGN and 380 healthy individuals from the same locality were typed for DRB1* alleles using the polymerase chain-reverse hybridization technique. Patients with PSAGN had significantly increased frequency of both DRB1* 03011 (46.9 vs. 19.2% in controls, P  = 0.00025) and DRB1* 1105 (31.1 vs. 15.6% in controls, P = 0.0097) alleles. However, after correction of P values, only the difference for DRB1* 03011 allele remained significant (Pc = 0.025). Their relative risks were significantly high (3.71, confidence interval [CI] = 1.8–7.8, and 3.57, CI = 1.4–8.9 respectively). No significant differences in the frequency of the two alleles were observed among patients with different grades of hypertension or proteinuria. In conclusion, DRB1* 03011, and possibly 1105, alleles confer susceptibility to PSAGN. However, the severity of the disease is not determined by these two alleles.     

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     

Glucocorticoid receptors expression and histopathological types in children with nephrotic syndrome

Background: Some children with idiopathic nephrotic syndrome (NS) patients fail to respond even when given high dose of steroid. The aim of this study was to assess the GCR expression on the T lymphocytes of children with NS and its relation to the response to steroid and to histopathological type. Methods: Forty-six pediatric patients with idiopathic NS and 20 age and sex matched apparently healthy children as controls were included. Flow cytometry was employed to determine the percentage of CD3+/GCR+ cells which then correlated with pattern of steroid response. Renal biopsy was done for steroid-dependent and steroid-resistant cases for determination of the underlying histopathological type. Results: The mean percentage of T lymphocyte expression of GCRs (CD3+/GCR) was significantly higher in early steroid responders than in late responders and was slightly lower than the controls. There was a significantly lower GCRs expression in steroid-resistant patients in comparison to early responders, late responders and controls. Renal biopsy showed that most cases of late responders were of the focal segmental glomerulosclerosis (FSGS) type. The mean percentage of lymphocyte expression of GCRs was significantly higher in patients with minimal change disease (MCD) compared to patients with FSGS. Conclusion: Evaluation of the expression of intracellular GCRs in T lymphocytes at time of diagnosis of NS can predict the response to steroid therapy and can help in determination of the outcome of NS patients regarding future relapses.     

Minimal change disease with IgM+ immunofluorescence: a subtype of nephrotic syndrome

Immunoglobulin (Ig) M nephropathy is defined by electron-dense mesangial deposits and mesangial IgM visible by immunofluorescence (IF) without other histopathologic and immunofluorescent microscopic abnormalities. Certain patients have only immuno-positive (IgM+) IF. Children presenting with steroid-dependent or steroid-resistant nephrotic syndrome have a high prevalence of IgM+ IF with or without electron-dense deposits. We reviewed the clinical course of children with steroid-dependent or steroid-resistant nephrotic syndrome who underwent renal biopsy at Texas Children‘s Hospital from 1989 to 2006 to further characterize IgM+ IF in children with nephrotic syndrome. Of the 55 children with steroid-resistant or -dependent minimal change disease (MCD), 23 had IgM+ IF. Of these 23 children, 61% had microscopic hematuria at presentation, 48% (11/23) were steroid-dependent, and 48% (11/23) steroid-resistant (one underwent biopsy prior to steroid therapy). We compared the efficacy of adjuvant treatment with cyclophosphamide and cyclosporine: 18% initially treated with cyclophosphamide obtained remission, while 55% had no response; 83% obtained subsequent remission with cyclosporine. Of those initially treated with cyclosporine, 88% obtained complete or partial remission. IgM+ IF may be surrogate marker for the severity of MCD. Based on our results, children with MCD and IgM+ IF have a better response to cyclosporine than cyclophosphamide.     

A novel mutation of<Emphasis Type="Italic"> NPHS2</Emphasis> identified in a Chinese family

Since the identification of the NPHS2 gene, which encodes podocin, several groups from European, Middle Eastern, and North American countries have reported NPHS2 mutations in families with steroid-resistant nephrotic syndrome (SRNS) or focal segmental glomerulosclerosis (FSGS). Families with SRNS have also been reported in China with a population of more than 1.3 billion. However, to our knowledge, there is no mutational analysis of the NPHS2 gene in familial SRNS or FSGS in China. We identified a novel mutation of NPHS2 (467_468insT and 503G>A) in a Chinese family with autosomal recessive SRNS using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing techniques. The results demonstrate that there is also NPHS2 mutation in Chinese familial SRNS. Therefore, Chinese SRNS patients with a familial history of NS should also be screened for possible mutations of NPHS2. We also detected clearly decreased staining with a specific podocin C-terminal antibody (P35) and negative staining with a specific podocin N-terminal antibody (P21). These results were contrary to those predicted from the mutated sites. Further studies are needed to explore the mechanism and impact of the mutant gene on the expression and localization of the relevant protein.     

<Emphasis Type="Italic">NPHS2</Emphasis> mutation associated with recurrence of proteinuria after transplantation

Mutations in the NPHS2 gene encoding podocin are associated with steroid-resistant nephrotic syndrome (SRNS) in childhood. Patients usually present with focal segmental glomerulosclerosis (FSGS). It is unclear to what extent SRNS due to NPHS2 mutations predisposes to recurrence of proteinuria/FSGS after renal transplantation (RTx). A 4-year-old girl with infantile SRNS was started on peritoneal dialysis because of end-stage renal disease due to FSGS. Mutational screening of the patient and her parents revealed a novel single nucleotide deletion in exon 8 of the NHPS2 gene (948delT), for which the patient was homozygous and her parents confirmed heterozygous asymptomatic carriers. At the age of 4.5 years the patient received a renal graft from her mother. On day 7 after RTx, the patient developed progressive proteinuria (urine protein/creatinine ratio 2.4 g/g), which responded within 1 week to prednisone pulse therapy, an increased cyclosporin A dosage, and ramipril therapy. The patient has maintained stable graft function and no further recurrence of proteinuria has been observed. In conclusion, patients with SRNS due to NPHS2 mutations are not protected from recurrence of proteinuria after RTx. The quick response to increased immunosuppression in our patient suggests an immune-mediated pathomechanism for recurrence of proteinuria.