Childhood Steroid-sensitive Nephrotic Syndrome Research Articles

Childhood Steroid Sensitive Nephrotic Syndrome: Characteristics and Predictors of Relapses; A study at a Single Center in Khartoum

Background: Childhood steroid-sensitive nephrotic syndrome (SSNS) usually has a favorable outcome in spite of its relapsing course. Our objective was to study the demographic and clinical characteristics, outcome and risk factors for relapses in children with SSNS at a single enter in Khartoum, Sudan.

Strong Association of the HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese Population.

Background Nephrotic syndrome is the most common cause of chronic glomerular disease in children. Most of these patients develop steroid-sensitive nephrotic syndrome (SSNS), but the loci conferring susceptibility to childhood SSNS are mainly unknown.Methods We conducted a genome-wide association study (GWAS) in the Japanese population; 224 patients with childhood SSNS and 419 adult healthy controls were genotyped using the Affymetrix Japonica Array in the discovery stage. Imputation for six HLA genes (HLA-A, -C, -B, -DRB1, -DQB1, and -DPB1) was conducted on the basis of Japanese-specific references. We performed genotyping for HLA-DRB1/-DQB1 using a sequence-specific oligonucleotide-probing method on a Luminex platform. Whole-genome imputation was conducted using a phased reference panel of 2049 healthy Japanese individuals. Replication was performed in an independent Japanese sample set including 216 patients and 719 healthy controls. We genotyped candidate single-nucleotide polymorphisms using the DigiTag2 assay.Results The most significant association was detected in the HLA-DR/DQ region and replicated (rs4642516 [minor allele G], combined Pallelic=7.84×10-23; odds ratio [OR], 0.33; 95% confidence interval [95% CI], 0.26 to 0.41; rs3134996 [minor allele A], combined Pallelic=1.72×10-25; OR, 0.29; 95% CI, 0.23 to 0.37). HLA-DRB1*08:02 (Pc=1.82×10-9; OR, 2.62; 95% CI, 1.94 to 3.54) and HLA-DQB1*06:04 (Pc=2.09×10-12; OR, 0.10; 95% CI, 0.05 to 0.21) were considered primary HLA alleles associated with childhood SSNS. HLA-DRB1*08:02-DQB1*03:02 (Pc=7.01×10-11; OR, 3.60; 95% CI, 2.46 to 5.29) was identified as the most significant genetic susceptibility factor.Conclusions The most significant association with childhood SSNS was detected in the HLA-DR/DQ region. Further HLA allele/haplotype analyses should enhance our understanding of molecular mechanisms underlying SSNS.

Long-term outcome of childhood steroid-sensitive nephrotic syndrome

Background: The long-term outcome of childhood steroid-sensitive nephrotic syndrome (SSNS) needs further evaluation. In this study, In this study, we report the long-term outcome of childhood SSNS at our center. Patients and Methods: This is a retrospective review of cohort of children with SSNS followed by cross-sectional follow-up evaluation. We included all children aged ≥16 years with a history of childhood SSNS. Of 45 children diagnosed with SSNS and contacted for follow-up, only 9 children were available for evaluation of long-term outcome. Demographic, socioeconomic, and disease history data were collected through a questionnaire. All the patients were examined and had their urine and blood samples collected for investigations. The data were analyzed using SPSS. Results: The mean age at onset for the 45 children was 7.3 ± 3.9 years. Follow-up revealed that 65.1% had frequent relapsing or steroid-dependent nephrotic syndrome and 34.9% had infrequent relapses. Of nine patients were included in the follow-up study for a median (range) duration of 11 (5–18) years, 2 of the patients were relapsing at the time of the study and two had one or more relapses during the previous year. Estimated glomerular filtration rate (eGFR) declined in two children and the mean eGFR for the whole group was lower at the time of last follow-up than at baseline (P = 0.032). Conclusion: Children with SSNS need careful long-term monitoring of disease activity and kidney function. A larger prospective study is required.

HLA-DQA1 and APOL1 as Risk Loci for Childhood-Onset Steroid-Sensitive and Steroid-Resistant Nephrotic Syndrome

Few data exist for the genetic variants underlying the risk for steroid-sensitive nephrotic syndrome (SSNS) in children. The objectives of this study were to evaluate HLA-DQA1 and APOL1 variants as risk factors for SSNS in African American children and use classic HLA antigen types and amino acid inference to refine the HLA-DQA1 association. Case-control study. African American children with SSNS or steroid-resistant nephrotic syndrome (SRNS) were enrolled from Duke University and centers participating in the Midwest Pediatric Nephrology Consortium. Genetic variants in HLA-DQA1 (C34Y [rs1129740]; F41S [rs1071630]) and APOL1 high-risk alleles. SSNS and SRNS. Direct sequencing for the HLA-DQA1 and APOL1 variants in 115 African American children (65 with SSNS and 50 with SRNS). Imputation of classic HLA alleles and amino acids was done in 363 South Asian children. The 2 HLA-DQA1 variants were significantly associated with SSNS in African American children (C34Y: P=5.7× 10-11; OR, 3.53; 95% CI, 2.33-5.42; F41S: P=1.2× 10-13; OR, 4.08; 95% CI, 2.70-6.28), but not with SRNS (C34Y: P=0.6; F41S: P=0.2). APOL1 high-risk variants were not associated with SSNS (P=0.5) but showed significant associations with SRNS (P=1.04× 10-7; OR, 4.17; 95% CI, 2.23-7.64). HLA-DQA1*0201, HLA-DQB1*0201, and HLA-DRB1*0701 were the classic HLA alleles with the most significant associations with SSNS risk. The most significantly associated amino acid positions were HLA-DQα1 56 and 76 (both P=2.8× 10-7). Conditional analysis revealed that these variants most likely account for the observed association. Modest sample size and limited statistical power to detect small to moderate effect sizes. Children studied may not be representative of all African American children in the United States. HLA-DQA1 is a risk locus for SSNS, but not SRNS, in African American children, consistent with its role in SSNS risk in children of European, Asian, and African ancestries. There is little evidence of a significant role for the APOL1 high-risk alleles in childhood SSNS in African American children. Refinement of the HLA-DQA1 association identified the critical classic HLA antigen types and amino acids of the HLA-DQ α1 molecule.

Seroconversion following hepatitis B vaccination in childhood steroid sensitive nephrotic syndrome

Background: The commonest factor associated with frequent relapse in minimal change nephrotic syndrome is infection, either bacterial sepsis or viral infection. Among the viral infections, hepatitis B virus (HBV) has a prominent role. Steroid sensitive nephrotic syndrome (SSNS) patients are immunocompromised because of the disease itself as well its treatment with a steroid. Thus, their seroprotection will not be enough with conventional dose as that of a healthy person. Objective: To evaluate the seroresponse among SSNS with hepatitis B (HB) vaccination when they were in remission, to compare the antibody titre between single and double dose and to find out whether there were any complications following HB vaccination. Method: A prospective study was conducted among thirty SSNS children from July 2012 to June 2013; children were randomly assigned to be given either 10μg (Group-A) or 20μg (Group-B) of HBV vaccine. The vaccine was administered intramuscularly according to 0, 1, 2 months protocol. After one month of the last dose of vaccine, seroprotection rate was measured. Results: The mean vaccine titres of Group-A and Group-B were 25.60 ±19.97 mIU/ml and 617.47 ± 292.11 mIU/ml respectively. The mean vaccine titre difference between the 2 groups was statistically significant. Conclusion: Seroconversion was better observed by double dose (1ml) of HB vaccine in comparison to the single dose (0.5 ml) in children with SSNS during the remission period. There were no complications following HB vaccine during the study period.

Risk factors for relapse in childhood steroid sensitive nephrotic syndrome

Background: Nephrotic syndrome (NS) generally tends to follow a benign and chronic relapsing course. Relapses are a major problem in children with steroid sensitive NS (SSNS). Objective: To identify the risk factors for frequent relapse (FR) in the first episode childhood SSNS. Methods: This prospective study was conducted in the Government Dharmapuri Medical College Hospital, Tamil Nadu, between July 2013 and January 2016. Children aged 9 months - 12 years with a diagnosis of SSNS (first episode) who came for follow-up for at least 12 months in the pediatric nephrology clinic were included. The enrolled cases were divided into 2 groups: (1) frequent relapser (FR) and (2) infrequent relapser (IFR). 9 factors were studied as possible risk factorsfor relapse. The data collected were analyzed using Chi-square test and Student’s t-test. Results: Of 160 SSNS children, there were 92 (57.5%) cases of IFR and 68 (42.5%) cases of FR. There were 97 males (60.6%) and 63 females (39.4%) with a male to female ratio of 1.5:1. The mean age of presentation was 4.37±2.32 years. The mean time taken to achieve remission during the first episode was 1.94±1.04 weeks. The interval between remission and first relapse was 5.56±4.51 months. Incidence of infection and hypertension was 31.9% and 37.5%, respectively. Risk factors significantly associated with FR were: Time taken to achieveremission during the first episode (>14 days) (p<0.0001), mean duration of interval between remission and first relapse (within 6 months) (p<0.0001), associated infections (p<0.0001) and hypertension (p<0.0001). Age at onset, sex, serum albumin, 24 h urine protein, and azotemia did not influence the FR in our study. Conclusion: More than 14 days to achieve remission during the first episode, relapse within first 6 months, associated infections and hypertension were the factors associated with FRs.

Genetics of childhood steroid-sensitive nephrotic syndrome.

The pathogenesis of childhood-onset nephrotic syndrome (NS), disparity in incidence of NS among races, and variable responses to therapies in children with NS have defied explanation to date. In the last 20years over 50 genetic causes of steroid-resistant nephrotic syndrome (SRNS) have been identified, and at least two disease loci for two pathologic variants of SRNS (focal segmental glomerulosclerosis and membranous nephropathy) have been defined. However, the genetic causes and risk loci for steroid-sensitive nephrotic syndrome (SSNS) remain elusive, partly because SSNS is relatively rare and also because cases of SSNS vary widely in phenotypic expression over time. A recent study of a well-defined modest cohort of children with SSNS identified variants in HLA-DQA1 as a risk factor for SSNS. Here we review what is currently known about the genetics of SSNS and also discuss how recent careful phenotypic and genomic studies reinforce the role of adaptive immunity in the molecular mechanisms of SSNS.

Oxidative stress in childhood steroid sensitive nephrotic syndrome and its correlation with DNA damage

Oxidative stress in childhood steroid sensitive nephrotic syndrome and its correlation with DNA damage

Disease course in childhood steroid sensitive nephrotic syndrome: Is it changeable?

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Has the incidence of childhood steroid sensitive nephrotic syndrome changed?

Nephrotic syndrome is among the most common types of pediatric kidney disease. However, there are few published data on its incidence and racial patterns. This study examines the incidence and racial patterns of childhood steroid sensitive nephrotic syndrome (SSNS). For the period 1/1/1996 to 12/31/2006, a retrospective chart review was performed of children less than 10 years of age who presented to Le Bonheur Children's Hospital in Memphis, TN with newly diagnosed SSNS. At the time of diagnosis, 38 children were found to reside in Shelby County, TN, with 31 children residing within the Memphis city limits. The annual incidence of SSNS in Shelby County was 2.4 cases/100,000 children. The incidence was higher in males (4.0/100,000) (p = 0.0002), children less than 5 years of age (3.6/100,000) (p = 0.007), and African Americans (3.7/100,000) compared to Caucasians (0.9/100,000) (p = 0.00006). These findings confirm that SSNS is a rare pediatric disease. They also suggest that the incidence of SSNS in Shelby County is comparable to that in prior reports. Our study is one of the first to show that SSNS may be more common in African Americans.

Divergent Effects of Glucocorticoids on Cortical and Trabecular Compartment BMD in Childhood Nephrotic Syndrome

Glucocorticoid (GC) effects on skeletal development have not been established. The objective of this pQCT study was to assess volumetric BMD (vBMD) and cortical dimensions in childhood steroid-sensitive nephrotic syndrome (SSNS), a disorder with minimal independent deleterious skeletal effects. Tibia pQCT was used to assess trabecular and cortical vBMD, cortical dimensions, and muscle area in 55 SSNS (age, 5-19 yr) and >650 control participants. Race-, sex-, and age-, or tibia length-specific Z-scores were generated for pQCT outcomes. Bone biomarkers included bone-specific alkaline phosphatase and urinary deoxypyridinoline. SSNS participants had lower height Z-scores (p < 0.0001) compared with controls. In SSNS, Z-scores for cortical area were greater (+0.37; 95% CI = 0.09, 0.66; p = 0.01), for cortical vBMD were greater (+1.17; 95% CI = 0.89, 1.45; p < 0.0001), and for trabecular vBMD were lower (-0.60; 95% CI, = -0.89, -0.31; p < 0.0001) compared with controls. Muscle area (+0.34; 95% CI = 0.08, 0.61; p = 0.01) and fat area (+0.56; 95% CI = 0.27, 0.84; p < 0.001) Z-scores were greater in SSNS, and adjustment for muscle area eliminated the greater cortical area in SSNS. Bone formation and resorption biomarkers were significantly and inversely associated with cortical vBMD in SSNS and controls and were significantly lower in the 34 SSNS participants taking GCs at the time of the study compared with controls. In conclusion, GCs in SSNS were associated with significantly greater cortical vBMD and cortical area and lower trabecular vBMD, with evidence of low bone turnover. Lower bone biomarkers were associated with greater cortical vBMD. Studies are needed to determine the fracture implications of these varied effects.

Plasma and urinary platelet activating factor concentrations and leukotriene releasing activity of leukocytes in steroid sensitive nephrotic syndrome of childhood.

Platelet activating factor (PAF) is synthesized and secreted by glomerular mesangial and endothelial cells. It increases glomerular basement membrane permeability and induces proteinuria. Leukotrienes (LT) are mediators released by either leukocytes or glomerular cells under the PAF effect. The possible role of PAF in steroid sensitive nephrotic syndrome (SSNS) of childhood was studied in 8 children with SSNS in the acute stage, 5 children in remission and 8 healthy controls. The PAF concentrations in urine and plasma were determined. Leukocytes were stimulated in vitro and the LT release in response to stimulation was determined. The urinary and plasma concentrations of PAF were significantly higher in the acute phase than in remission and in control patients. Children with SSNS were found to have peripheral leukocytes with increased LT releasing activity in vitro. These results are in accordance with clinical and experimental observations indicating that PAF originates in the kidney and plays a role in normal kidney physiology. Urinary PAF concentrations may be related to proteinuria because they were strongly correlated in the present study. Elevated plasma PAF concentrations in the acute stage of SSNS could result from either its secretion from the circulating leukocytes or decreased acetyl hidrolase activity needed for its hydrolysis in plasma. The increased LT release in vitro suggests that these cells might have been activated by PAF secreted from glomeruli. It is proposed that PAF and different LT in systemic and glomerular circulation are important mediators in childhood SSNS.

Association of HLA class II and history of atopy and frequent relapse of childhood steroid-sensitive nephrotic syndrome

Background The association between HLA class II and frequentrelapse of nephrotic syndrome (FRNS) has been reported.Objective To identify the association between HLA class II,history of atopy, and upper respiratory tract infection (URTI)with FRNS.Methods This was a case control study conducted at theDepartment of Child Health, Hasan Sadikin Hospital Bandungand Cipto Mangunkusumo Hospital Jakarta from November 2002to October 2003 on children aged 1-14 years with FRNS. Thesubjects consisted of 40 FRNS and 84 healthy children. HLAclass II was typed by polymerase chain reaction-sequence specificoligonucleotide (PCR-SSO) in Leiden, the Netherlands. Theassociation between HLA class II and FRNS was expressed byodds ratio (OR). The association between such factors and FRNSwas analyzed by logistic regression.Results Atopy was higher in patients than that in controls(P=0.013). URTI did not differ in both groups (P=0.173). HLA-DRB1*03 and DRB1*04 (OR=4.43, P=0.03), DQB1*02(OR=3.43, P=0.00), and DQB1*04 (OR=12.06, P=0.01) weresignificantly higher among patients than those in controls whereasHLA-DRB1*12 (OR=0.34, P=0.02) and DQB1*0301p(OR=0.35, P=0.02) were significantly lower among patients thanthose in controls. Using logistic regression analysis, only HLA-DRB1*12, DQB1*02 and atopy took part in FRNS.Conclusion HLA-DRB1*12, DQB1*02, and atopy all togetherhave association with FRNS.

Heparanase activity is dysregulated in children with steroid-sensitive nephrotic syndrome

Immune cells express heparanase, an endoglycosidase, able to degrade heparan sulfate glycosaminoglycan (HSGAG) in the glomerular capillary wall (GCW) and potentially induce proteinuria. The aim of this study was to determine whether dysregulated heparanase expression is associated with the heavy proteinuria of childhood steroid-sensitive nephrotic syndrome (SSNS). Plasma and urinary heparanase activity and peripheral blood mononuclear cell (PBMC) mRNA heparanase levels [real-time polymerase chain reaction (PCR)] were measured in children with SSNS in relapse and remission. Plasma and urinary heparanase activity was determined in adult patients with nephrotic syndrome and in age- and gender-matched controls. Plasma heparanase activity was reduced in SSNS with relapse (811.2 units) compared to remission (1147.96 units) (P= 0.003) and control subjects (1390.51 units) (P < 0.001). In adult nephrotic syndrome, plasma heparanase activity was significantly lower in patients compared to controls. However, there was no difference between remission and relapse states. In children, urinary heparanase activity/urinary creatinine ratio was highest in SSNS relapse (14.26 units/mg) compared with remission (7.43 units/mg) (P= 0.016) and controls (2.29) (P < 0.001). However, PBMC heparanase mRNA expression was not different between these three groups. In adult nephrotic syndrome, urinary heparanase activity/urinary creatinine levels were lower in both remission and relapse compared to controls and there was no difference between remission and relapse states. In childhood SSNS, there is a qualitative and quantitative difference in urinary heparanase activity expression that is not paralleled in adult nephrotic syndrome. These data suggest that dysregulated heparanase expression may play a significant role in the pathogenesis of SSNS, possibly through an abnormality in post-translational control of latent heparanase activation.

Combined T- and B-cell activation in childhood steroid-sensitive nephrotic syndrome.

Growing evidence shows that steroid-sensitive nephrotic syndrome (SSNS) is the result of a primary T-cell disturbance and leads to secondary anatomical and functional, however, not to immunological glomerular changes. In addition, immunoglobulin abnormalities in SSNS indicate a role of B-cell involvement. We therefore analyzed T- and B-cell activation markers in children with SSNS at different stages of the disease including different treatment regimens by measuring the soluble IL-2 receptor (sCD25) and the soluble low-affinity IgE receptor (sCD23), respectively. Seventy-five patients with SSNS (median age 8.0, range 2.5 - 18 years) were studied, 33 in relapse (RL) including 21 patients relapsing during alternate-day steroids (RL-SD). Forty-two patients were studied in remission (RM; 14 off treatment and 28 on alternate-day steroids (RM-AD)) and 22 age-matched children served as controls. Serum concentrations of sCD25 were increased in RL (113.6 +/- 19.5 micromol/l) compared to RM (79.8 +/- 8 micromol/l, p < 0.02) and controls (74.8 +/- 0.9 micromol/l, p < 0.02). Patients with RL-SD did not have elevated sCD25. In relapse, sCD25 was inversely correlated with age (R = -0.36, p < 0.04) and positively correlated with total IgG (R = 0.37, p < 0.04). Urinary excretion of sCD25 was also significantly elevated in RL of SSNS compared to RM and controls (71.2 +/- 11.9 micromol/g creatinine vs. 39.1 +/- 4.8 and 32.0 +/- 4.2 micromol/g, p < 0.05). Serum levels of sCD 23 were significantly elevated in RL (6.22 +/- 0.65 microg/l) compared to RM (3.1 +/- 0.83 microg/l, p < 0.02) and to controls (3.4 +/- 0.93 microg/l). The highest values, however, were found in RL-SD (7.8 +/- 1.7 microg/l) vs. untreated RL (p < 0.007) and RM-AD (p < 0.002). In untreated RL there was a significant correlation of sCD23 and total IgE (R = 0.67, p < 0.02) and in RL-SD with total IgG (R = 0.45, p < 0.05). sCD23 and sCD25 were not correlated with each other. These data document parallel abnormalities of both CD23-mediated B as well as CD25-mediated T-cell activation and suggest that SSNS is not solely a disorder of T-cell dysfunction.

Steroid-sensitive nephrotic syndrome: From childhood to adulthood

Background: The clinical presentation, treatment, and outcome of steroid-sensitive nephrotic syndrome (SSNS) during childhood have been extensively studied. Conversely, few data regarding the outcome in adulthood of childhood SSNS have been published previously. We undertook to conduct a retrospective study of the outcome in adulthood of a large cohort of patients diagnosed with an SSNS during childhood. Methods: We identified all children born between 1970 and 1975 who had been admitted to our institution for an SSNS. Data regarding the outcome in adulthood of these patients were obtained through mailed questionnaires or phone calls to patients and/or their parents or through attending physicians. Results: One hundred seventeen patients were identified. Data regarding the outcome of SSNS in adulthood were available for 102 patients (87.2%). Forty-three patients (42.2%) experienced at least one relapse of nephrotic syndrome in adulthood. By univariate analysis, young age at onset (<6 years) and more severe disease in childhood, indicated by a greater number of relapses (12.9 for adulthood relapsers versus 5.4 for adulthood nonrelapsers; P < 0.0001) and more frequent use of immunosuppressors (74.4% versus 31.6%; P < 0.0001) or cyclosporine (42.9% versus 7.3%; P < 0.0001) were predictive of the occurrence of SSNS relapse in adulthood. Conversely, relapse rate in the first 6 months of disease was not predictive of further relapses in adulthood. By multivariate analysis, only number of relapses during childhood was predictive of adulthood relapses (P < 0.0058). Long-term side effects of steroids were found in 44.2% of adulthood relapsers; the most frequent were osteoporosis and excess weight. Conclusion: The incidence of childhood SSNS relapses in adulthood was relatively high in our study. Further studies are required to assess long-term complications in adults with relapses and a history of prolonged steroid and immunosuppressor use. Am J Kidney Dis 41:550-557. © 2003 by the National Kidney Foundation, Inc.

Steroid-sensitive nephrotic syndrome and vascular endothelial growth factor gene polymorphisms.

Genetic polymorphisms have been recognized as important determinants of gene expression. Three common single nucleotide polymorphisms have been identified in the promoter and 5' untranslated region of the vascular endothelial growth factor (VEGF) gene: -460 C --> T, -141 A --> C and +405 G --> C. As VEGF has been postulated to play a role in the pathogenesis of childhood steroid-sensitive nephrotic syndrome (SSNS), this study tested the hypothesis that VEGF genotype may be associated with susceptibility to SSNS. We examined the genotype frequencies of these polymorphisms in a total of 116 children with SSNS and 150 control subjects, using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). There were no statistically significant differences in any of the genotype frequencies between SSNS patients and controls. We conclude that VEGF -460, -141 and +405 genotypes are not associated with susceptibility to childhood SSNS.

Family structure and the course of steroid-sensitive nephrotic syndrome.

The number of children in nontraditional families is growing. The objective of this study was to determine the effects of family structure on the course of childhood steroid-sensitive idiopathic nephrotic syndrome (SSNS). Sixteen children, 2-15 years of age, with SSNS were enrolled in the study. The effects of family structure (traditional versus nontraditional) on the number of hospitalizations and outpatient visits for the previous 2 years and disease relapses for the preceding year were evaluated. Behavior differences were assessed using the Child Behavior Checklist (CBCL). Of the 16 families, 9 were traditional and 7 nontraditional. Hospitalizations, outpatient visits, and behavior were not different between family groups. However, children from nontraditional homes relapsed 3 times more than children from traditional homes (P=0.003). We conclude that children with SSNS from nontraditional homes may be at risk for more relapses compared with children from traditional families. Heightened support and monitoring is necessary for these children.

Circulating vascular endothelial growth factor is not increased during relapses of steroid-sensitive nephrotic syndrome

An uncharacterized circulating factor that increases vascular permeability has previously been described in childhood steroid-sensitive nephrotic syndrome (SSNS). The aim of this study was to determine whether this factor is vascular endothelial growth factor (VEGF), the recently described endothelial cell mitogen and enhancer of vascular permeability. Plasma and urine VEGF levels were measured in children with SSNS in both relapse and remission and in normal age- and sex-matched controls. Semiquantitative reverse transcriptase-polymerase chain reaction studies investigating VEGF mRNA expression were performed on peripheral blood mononuclear cells isolated from children with SSNS in relapse and controls. In two experimental models (one-hour and three-day follow-up postinfusion), Sprague-Dawley rats were intravenously administered 50 microg rVEGF to determine whether this induced either proteinuria or glomerular histologic change. Plasma VEGF levels and urine VEGF/creatinine ratios were not elevated in SSNS relapse compared with remission and control samples. Peripheral blood mononuclear cell VEGF mRNA expression was no different in SSNS patients compared with controls. The administration of VEGF to rats induced an acute reversible fall in systemic blood pressure but did not result in the development of either proteinuria or glomerular histologic change. Increased circulating VEGF levels are not responsible for the proteinuria observed during relapses of SSNS. Further studies are warranted to investigate intrarenal VEGF expression.

Childhood steroid-sensitive nephrotic syndrome: Does the histology matter?

Renal biopsy specimens from 51 children with steroid-sensitive nephrotic syndrome who were following a frequently relapsing or steroid-dependent course were reviewed by two histopathologists. In all cases the biopsy was performed prior to the commencement of an 8-week course of cyclophosphamide. The clinical courses of these patients both prebiopsy and for a minimum of 2 years after completion of cyclophosphamide therapy were analyzed using retrospective case note analyses. The distribution of histologic diagnoses differed significantly from that reported by the International Study of Kidney Disease in Children in their study of children who underwent biopsy at the time of presentation, there being an excess of focal segmental glomerulosclerosis and mild mesangial hypercellularity in this series. The prebiopsy clinical course did not predict for histologic diagnosis, and there was no correlation between prebiopsy course or histology and postcyclophosphamide course. The findings of this study support the clinical impression that steroid sensitivity rather than histology is the major determinant of prognosis in childhood nephrotic syndrome and that frequency of relapse alone is not an indication for biopsy.