Steroid-sensitive Nephrotic Syndrome In Remission Research Articles

Impaired thiol/disulphide homoeostasis in children with steroid-sensitive nephrotic syndrome.

Abnormal thiol/disulphide homoeostasis (TDH) is responsible for the pathogenesis of various diseases. We aimed to examine the TDH in children with steroid-sensitive nephrotic syndrome (SSNS). A total of 131 children, 60 with SSNS and 71 healthy controls, participated in the study. Plasma total thiol (TT), native thiol (SH) and disulphide (SS) levels in the SSNS during remission and control groups were estimated using a new method developed by Erel and Neselioglu. Albumin, TT, SH levels and SH/TT ratio were decreased, whereas SS/SH and SS/TT ratios were elevated in SSNS group compared with control group. However, there was no significant difference in SS levels between the two groups. Albumin level was positively correlated with TT, SH and SS levels in the SSNS group. We found that TDH shifts in favour of oxidants in children with SSNS in remission. This shift indicates that SSNS patients are exposed to augmented oxidative stress.

Cytotoxic T- Lymphocyte Antigen-4 (CTLA4) Gene Expression and Urinary CTLA4 Levels in Idiopathic Nephrotic Syndrome.

To detect Cytotoxic T- Lymphocyte Antigen-4 (CTLA4) single nucleotide polymorphisms (SNPs) at +49A/G (rs231775) and -318C/T (rs5742909) positions in children with idiopathic nephrotic syndrome (INS) and also assay urinary soluble CTLA4 (sCTLA4) levels in children with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) and steroid sensitive nephrotic syndrome (SSNS) in remission. The study included 59 patients of INS (MCD-23, FSGS-15 and SSNS in remission-21) and 35 healthy controls. The CTLA4 SNPs profiling was done in peripheral blood mononuclear cells and urinary sCTLA4 level was assayed by ELISA kit. Although frequency of homozygous +49 GG (rs4553808) genotype (26.3% vs. 11.4%; p = 0.231) and G allele (52.6% vs. 40%; p = 0.216) were found to be higher in INS as compared to controls, the differences were statistically non-significant. Genotypes GG, AG, AA and alleles A and G frequencies were comparable among MCD, FSGS and controls. SNP at -318 C/T (rs5742909) did not show homozygous TT genotype both in INS as well as controls. Median urinary sCTLA4/creatinine level was significantly higher in MCD as compared to FSGS (p = 0.027), SSNS in remission (p = 0.001) and controls (p = 0.003). The positive associations of +49 GG genotype and G allele in patients with nephrotic syndrome were not observed. The frequencies did not differ significantly among MCD, FSGS and controls. Urinary sCTLA4 level was significantly increased in MCD; suggesting its possible role in the pathogenesis of disease.

Biochemical bone markers in children with steroid sensitive nephrotic syndrome in remission

Background: Glucocorticoids, the recommended first line treatment of steroid sensitive nephrotic syndrome (SSNS), are notorious for causing osteoporosis. There are very few studies from tropical countries looking at the lasting effects of a short course of glucocorticoids in SSNS. The objective is to study the effect of glucocorticoids and its dose on Vitamin D levels and biochemical markers of calcium metabolism in children with SSNS and to formulate a criterion to administer prophylactic calcium and vitamin D supplementation to such patients.Methods: A cross-sectional case-control study was conducted on 30 children with SSNS in remission and 30 healthy controls. Serum levels of 25 hydroxycholecalciferol [25(OH)D], calcium, phosphorous, albumin, alkaline phosphatase (ALP) and intact parathyroid (PTH) were measured. Total glucocorticoid exposure during the illness was summarized.Results: Children with SSNS had significantly lower height [median-100.00 (interquartile range {IQR}- 14.5) vs. controls [115.50 (17.5)] cm; P= 0.0003. Serum ALP levels was significantly higher in the cases [median 264 (IQR-80.7)] IU/L vs. controls [median 234 (IQR- 132)] IU/L; P= 0.028. Though hypovitaminosis D was universal in the study cohort; children with SSNS had worse Vitamin D status (76.7%) than healthy controls (50%). Levels of serum calcium, phosphorous, vitamin D and PTH were not significantly different between the two groups, nor were they related to total cumulative dose of steroid. Vitamin D levels showed no significant co-relation with number of relapses, age, calcium, phosphate, ALP, or PTH levels.Conclusions: Children with SSNS may benefit from routine measurement of 25 (OH) D and prophylactic supplementation with calcium and Vitamin D.

Urinary Neutrophil Gelatinase- Associated Lipocalin in Children with Idiopathic Nephrotic Syndrome: A Biomarker to Differentiate Between Steroid Sensitive and Resistant Forms of Disease

Background: Objectives of the study were to find out the ability of urinary neutrophil gelatinase- associated lipocalin (NGAL) as a biomarker to differentiate between steroid resistant nephrotic syndrome (SRNS) and steroid sensitive nephrotic syndrome (SSNS), and also to observe variation in levels, if any, between focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) in SRNS patients.Methods: The study included 63 patients of idiopathic nephrotic syndrome (19 SSNS in relapse, 19 SSNS in remission and 25 SRNS), aged 2.5-16 years, along with 17 controls. Urinary NGAL was measured by ELISA and the values were normalised with urinary creatinine.Results: Median urinary NGAL/creatinine level was significantly raised in SRNS as compared to SSNS relapse, SSNS remission and controls (p 18.3 ng/mg had sensitivity of 84%, specificity of 97.4% and area under the curve of 0.935 (p< 0.001, 95% confidence interval 0.871-0.998) to differentiate SRNS from SSNS patients. Median urinary NGAL/creatinine value was significantly raised in children with FSGS as compared to MCD (p=0.003) in SRNS patients. It had significant positive correlations with duration of illness (r=0.342, p=0.006), urine protein creatinine ratio (r=0.594, p< 0.001) and negative correlation with serum albumin (r=0.470, p<0.001).Conclusion: Urinary NGAL/creatinine level correlated with activity of the disease and it can distinguish not only SRNS from SSNS but also FSGS and MCD histopathological sub-types of SRNS in children.

Vitamin D insufficiency in steroid-sensitive nephrotic syndrome in remission

Serum 25-hydroxyvitamin D [25(OH)D] concentrations are the best indicator of vitamin D nutritional status. We measured serum 25(OH)D concentrations in 94 healthy controls and in 41 subjects (aged 4-22 years) with steroid-sensitive nephrotic syndrome (SSNS) in remission. Children with remitted SSNS had significantly lower 25(OH)D concentrations than healthy controls (median 16.4 ng/ml versus 23.9 ng/ml, P<0.001). In a multivariable logistic regression model, the odds ratios (OR) of vitamin D insufficiency [25(OH)D <20 ng/ml] were independently increased in SSNS subjects [OR 11.2 (95% confidence interval 3.5-36.2)], non-whites [OR 12.9 (4.6-36.2)], older children [OR 1.20 per year (1.06-1.36)], and winter months [OR 6.7 (2.5-18.4)]. Within the SSNS subjects, multiple linear regression determined that serum 25(OH)D concentrations were not associated with SSNS disease characteristics measured in this study, such as duration of disease, number of relapses, cumulative glucocorticoids, and interval since last relapse. In conclusion, children with remitted SSNS have lower serum 25(OH)D concentrations than healthy controls. This difference persisted after adjusting for the potential confounding effects of age, race, season, and milk intake. Children with remitted SSNS may benefit from routine measurement of 25(OH)D, but the clinical significance of low 25(OH)D in this population remains unclear.

Varicella vaccination in children with steroid-sensitive nephrotic syndrome.

We have studied serological and clinical response to live, attenuated varicella zoster virus (VZV) vaccine (Varilrix, SmithKline Beecham) in 20 patients with steroid-sensitive nephrotic syndrome (SSNS) in remission and 22 normal controls who had no history of varicella and no detectable antibody to VZV. Nephrotic patients included 15 boys and 5 girls, with a mean age of 4.7 years (range 2-11.4 years). The controls were healthy age-matched children (13 girls and 9 boys). Seventeen patients with SSNS (85%) and 19 healthy controls (86%) seroconverted 8 weeks after vaccination. One patient with SSNS had a relapse 20 days after vaccination, and 1 child in the control group had a rash. Two years after vaccination, antibodies to VZV were detected in 12 of 17 responders, 2 of 3 non-responders, and 13 of 22 controls. Within 2 years of vaccination, 3 of the vaccine responder children with SSNS had a mild varicella infection. Two responder and 1 non-responder nephrotic children and 9 controls were lost to long-term follow-up. Our results show that immunization with a single dose of VZV vaccine is safe and effective in children with SSNS in remission.

Lymphocyte subpopulations, interleukin-2 and interleukin-2 receptor expression in childhood nephrotic syndrome.

Abnormal T lymphocyte function and reduced interleukin-2 (IL-2) production have been implicated in the pathogenesis of the nephrotic syndrome (NS). We investigated: (1) lymphocyte subpopulations and expression of IL-2 receptor (IL-2R) on T cells using two-colour flow cytometry, (2) serum IL-2 and (3) the soluble component of IL-2R (sIL-2R) in serum, using enzyme-linked immunosorbent assay, in 38 children with NS. All children, except those in remission, had marked proteinuria. They were divided into groups according to renal pathology: (1) steroid-sensitive NS (SSNS) not receiving prednisolone therapy, (2) SSNS on prednisolone, (3) focal segmental glomerulosclerosis (FSGS), (4) SSNS in remission and not receiving prednisolone therapy, (5) congenital NS (CNS). Results were compared with 26 age-matched controls. Total T lymphocytes (CD3) were reduced in groups 1 and 2; CD4 count was reduced in groups 1-4; CD8 count increased in groups 2 and 3; CD8 and CD19 (B lymphocytes) were significantly reduced in group 5. Increased IL-2R expression (CD25) on CD4 lymphocytes was noted in groups 1, 2 and 3 implying activation of these cells. In patients with SSNS, increased serum sIL-2R was recorded during relapse (1,273 +/- 497 U/l vs. 913 +/- 401 U/l in remission, P < 0.005) but free serum IL-2 was not detectable at any stage. The specific alterations in lymphocyte subpopulations in SSNS and FSGS would imply an involvement of the immune system distinct from that in CNS.

Lipoprotein profiles at different stages of the nephrotic syndrome.

We investigated lipoprotein profiles in 24 children with normal renal function at different stages of the idiopathic nephrotic syndrome (NS). Four groups of patients were studied: (I) steriod-resistant NS with persistent proteinuria; (II) untreated steroid-sensitive NS during a relapse; (III) steroid-sensitive NS in remission induced by steroid-treatment; (IV) steroid-sensitive NS in long-term remission without therapy. Triglycerides (TG), cholesterol (CHOL), and phospholipids (PLP) were measured in plasma as well as in the lipoprotein fractions of very low (VLDL), intermediate (IDL), low (LDL) and high density (HDL). Apoproteins (Apo) AI, AII, B and C-apoproteins were measured in patients of groups I and IV. Results were compared to those obtained in 24 healthy control subjects. All patients with active NS (groups I-III) had significantly elevated CHOL levels. TG and CHOL in the VLDL, IDL, LDL, and CHOL in HDL2, but not HDL3 were inversely correlated with the serum albumin level. Patients with active NS had increased concentrations of TG and CHOL in lipoprotein fractions of lower density. Total and fractionated HDL-CHOL was not significantly different from control levels in any group. Patients in group I had significantly reduced Apo AI levels, whereas an increase of Apo AI and Apo AII in HDL3 and of most C-apoproteins in both HDL fractions was observed in patients of group IV. While changes in HDL apoprotein composition during long-term remission are of yet unknown clinical significance, our data indicate an increased risk of atherosclerosis only in those paediatric patients with persistent steroid-resistant NS.