Nephrotic Syndrome Children Research Articles

Triple immunosuppressive therapy in steroid-resistant nephrotic syndrome children with tacrolimus resistance or tacrolimus sensitivity but frequently relapsing.

The treatment strategy for steroid-resistant nephrotic syndrome remains uncertain at present, especially in those with calcineurin inhibitor resistance or intolerance. To date, few studies have been published using multiple combination therapy of immunosuppressive reagents for children with calcineurin inhibitor-resistant or -intolerant nephrotic syndrome. Eighteen consecutive children with steroid- and tacrolimus (TAC)-resistant (n = 10) or TAC-sensitive but frequent relapsing nephrotic syndrome (n = 8) were randomly recruited in the present study. All of them received further triple-combination therapy by cyclophosphamide (CTX, n = 6), mycophenolate mofetil (MMF, n = 5) or leflunomide (LEF, n = 7). Their clinical data were collected and efficacy of triple-combination therapy was evaluated. Compared with previous double-combination therapy of prednisone (Pre) and TAC, the short-term remission rate in all 18 patients was significantly improved after the triple-combination therapy, while the frequent relapse rate in the following 12 months was also significantly decreased. Among three different subgroups with CTX, MMF or LEF therapy, no significant difference was found in short-term remission rate and the relapse rate within 1 year follow up by Kaplan-Meier plot. Triple-combination therapy with Pre + TAC + CTX/MMF/LEF is effective for short-term response and 1 year remission, without significant additional side-effects seen in children with steroid-resistant and tacrolimus-resistant or tacrolimus-sensitive but frequently relapsing nephrotic syndrome. Further study for evaluating long-term efficacy and safety of triple-combination therapy with Pre + TAC + CTX/MMF/LEF would be necessary for these patients.

Impact of Urinary Tract Infection on Steroid Response in Idiopathic Nephrotic Syndrome in Children

Context: UTI is one of the most common infection in nephrotic syndrome and may be a cause of delayed steroid response. Objective:To observe the impact of urinary tract infection on steroid response in idiopathic nephrotic syndrome children aged 2-6 years.Study design: Quasi experimental study Study period & place: Pediatric ward of Chittagong Medical College Hospital, Chittagong from 01.01.2009 to 31.12.2009. Participants: 52 Nephrotic syndrome children aged 2-6 years with typical clinical features Group A: Nephrotic syndrome with UTI, Group B: Nephrotic syndrome without UTI. Methods: Heat coagulation test, urine for R/M/E and C/S was done in every patient. Steroid was given according to standard regimen. Date of starting of steroid was recorded. Antibiotic was given in group A cases according to C/S report. Patients were followed for clinical and urinary remission. Group A and B were compared for remission time achieved by statistical method.Results: A male preponderance was noted about 57.7% against female about 42.3%. Generalized swelling of body & scanty micturation found in cent percent study group. Ascitis was found in 23.08%. Scrotal/labial swelling 7.69%.UTI developed in 30.8% of patients of NS. Male female ratio is 1:1. Infection delayed the remission of proteinuria. Mean remission time of NS without UTI patients was 7.39 days and with UTI patients was 9.31 days. In statistical analysis, mean remission time in group A =9.31+2.24 days(mean + SD), in group B=7.39+2.51 days(mean + SD), P value = <0.05, statistically significant.Conclusion: UTI in nephrotic syndrome causes delayed remission of proteinuria and may be asymptomatic.It should be screened in every nephrotic syndrome children routinely.DOI: http://dx.doi.org/10.3329/cmoshmcj.v13i2.21046

Brachial artery flow-mediated dilatation and carotid intima medial thickness in pediatric nephrotic syndrome: a cross-sectional case–control study

Children with nephrotic syndrome (NS) have hyperlipidemia, which may lead to endothelial dysfunction. This study evaluated endothelial function and structural atherosclerosis in NS children with disease duration more than 2 years, by assessment of brachial artery flow-mediated dilatation (FMD) and carotid intima medial thickness (CIMT). This is a cross-sectional case-control study recruiting 32 subjects aged 1-13 years with NS and 32 matched controls. Clinical details, FMD and CIMT were recorded. Lipid profile and oxidative stress were also analyzed in the subjects. The proportionate change in FMD was significantly lower in cases (5.65 ± 6.08 %) compared to controls (15.21 ± 9.41 %) (p < 0.01). No significant differences in CIMT were observed (p = 0.383). Blood malondialdehyde was significantly higher (p = 0.006) in the cases. Overall, 25 NS children (78 %) were in remission for more than 6 months, and in them, 9 (36 %) had deranged lipid profile. On stepwise linear regression, age of the patient was found to be a determinant of FMD (model R (2) = 18.9 %, p value = 0.048). The significantly low proportionate change in FMD in NS children suggests an ongoing process of endothelial dysfunction. Further studies are needed to confirm these findings. A long-term follow-up of children with NS may be required for identification of CIMT derangements.

A study of PT, APTT, fibrinogen and urinary protein-creatinine ratio in paediatric patients with nephrotic syndrome

Background: Nephrotic Syndrome (NS) is very common in children. The typical laboratory finding is high urinary protein creatinine ratio. Apart from it low serum albumin, high cholesterol contribute to hyper coagulable states. Due to this the risk of thromboembolism in both arterial and venous circulation is significant in children and adults. Patients at risk for thromboembolism traditionally have to be screened by ventilation/perfusion scans and Dopplers for the definitive diagnosis of thromboembolic disease. There are several studies performed on adult nephrotic syndrome and thromboembolic events in them worldwide. We wanted to look for simple, affordable tests, that can be performed even when state of the art technology is not available, and can point towards at risk thromboembolic patients. Methods: The study was conducted in 17 nephrotic syndrome children in active disease, 13 nephrotic syndrome children in remission and 15 healthy children as controls, all between 4-14 years age group. Study included both male and female children. Results: Our results revealed prolonged. APTT in NS with active disease when compared to remission and control groups. High fibrinogen levels in relapse group indicated hypercoagulative state, along with routine parameters such as high cholesterol and low albumin. Both relapse and remission groups had proteinuria, with very high P/C ratio in relapse group, indicating at risk group for thromboembolic complications along with basic coagulation parameters. Conclusion: We suggest that when there are indications of hypercoagulable state antiplatelet drugs such as a low dose aspirin 75 mg or low dose warfarin may be given as prophylactic treatment for thromboembolic disease.

Subclinical cardiovascular disease and its association with risk factors in children with steroid-resistant nephrotic syndrome

The aim of this study was to evaluate the presence of subclinical cardiovascular disease (CVD) and its relation to risk factors in pediatric patients with steroid-resistant nephrotic syndrome (NS). Thirty-seven patients with normal renal function were compared with 22 healthy controls regarding the presence of subclinical CVD. Measurements included aortic pulse wave velocity (PWV), carotid intima media thickness (IMT), and left ventricular mass (LVM). Patients were additionally assessed for blood pressure (BP) pattern and the presence of hypertension by 24-h ambulatory blood pressure monitoring. Compared with the controls, patients had significantly higher mean aortic PWV-standard deviation scores (SDS), mean carotid IMT-SDS, and LVM index (p < 0.001 for all). Increased aortic PWV was noted in 5 % of patients, increased carotid IMT in 22 %, and increased LVM index in 19 %. Five patients (14 %) were hypertensive, and mean BP indexes, SDS, and BP loads during nighttime were significantly higher than those during daytime (p < 0.001 for all). Multivariate analysis revealed a significant relationship between PWV-SDS and ferritin (R(2) = 0.269, p = 0.006) and between carotid IMT-SDS and proteinuria (R(2) = 0.141, p = 0.022). The LVM index was independently associated only with higher body mass index SDS (R(2) = 0.317, p < 0.001). In addition, six patients (16 %) had multiple abnormal subclinical CVD markers, and increased subclinical CVD risk was independently associated only with higher low-density lipoprotein cholesterol (R(2) = 0.292, p = 0.044). Based on these results, steroid-resistant NS children generally are at high risk of cardiovascular complications, but the increased risk is likely to be multifactorial.

Hepatitis B virus vaccination in children with steroid sensitive nephrotic syndrome: Immunogenicity and safety?

We investigated the efficacy and safety of Hepatitis B vaccine (HBVac) in steroid sensitive nephrotic syndrome (SSNS) children.41 patients with SSNS and 30 controls were vaccinated with HBVac(Engerix B®). Patients were divided into 3 subgroups:full dose steroid users, alternate-day steroid users and steroid non-users. Seroconversion rate was lower in steroid users than non-users at the 6th(p=0.015) and 12th(p=0.036) months. Antibody to Hepatitis B surface antigen(HBsAb) titers were significantly different between subgroups and controls at the 15th month. However, HBsAb and response rates were not different between subgroups at the 12th and 15th months (p>0.05). Five patients were unresponsive to HBVac. Relapse rates after the vaccination were higher than those in the prevaccination period (p=0.002).HBVac is less effective in producing immune response in SSNS children with steroid therapy. HBVac may trigger relapse in some patients. We recommend HBVac to SSNS children with low dose steroid therapy or after steroids are discontinued.

Increased Serum and Urinary MicroRNAs in Children with Idiopathic Nephrotic Syndrome

MicroRNAs (miRNAs) are present in body fluids and may have the potential to serve as disease biomarkers. This study explored the clinical value of miRNAs in serum and urine as biomarkers for idiopathic childhood nephrotic syndrome (NS). We obtained serum samples from 159 NS children (24 steroid resistant and 135 steroid sensitive), 109 age/sex-matched healthy controls and 44 children with other kidney diseases. Serum miRNAs were analyzed with the TaqMan Low Density Array and then validated with a quantitative reverse-transcription PCR assay with 126 individual samples. Moreover, we collected paired serum samples from 50 patients before and after treatment to determine the value of these miRNAs for condition assessment. In addition, urine samples from these patients were examined for candidate miRNAs. The concentrations of serum miR-30a-5p, miR-151-3p, miR-150, miR-191, and miR-19b were highly increased in NS children compared with controls (P < 0.0001). The urinary miR-30a-5p concentration was also increased in NS (P = 0.001). The area under the ROC curve and the odds ratio for the combined 5 serum miRNAs were 0.90 (95% CI, 0.86-0.94; P < 0.0001) and 40.7 (95% CI, 6.06-103; P < 0.0001), respectively. Moreover, the concentrations of the 5 serum miRNAs and urinary miR-30a-5p markedly declined with the clinical improvement of the patients. We determined that 5 distinct serum miRNAs and urinary miR-30a-5p were increased in NS children. These circulating or urinary miRNAs may represent potential diagnostic and prognostic biomarkers for idiopathic pediatric NS.

NPHS2 and CD2AP gene mutation in children with primary steroid-resistant nephrotic syndrome in Guangdong province

Objective To study NPHS2 and CD2AP gene mutation with primary steroid-resistant nephrotic syndrome (SRNS) children in Guangdong province, and to investigate the relationship between NPHS2, CD2AP gene mutation and SRNS, so as to provide a theoretical basis for the diagnosis and treatment of SRNS in children. Methods Twenty-six SRNS children and 20 cases of the healthy children as controls were chosen randomly in Guangdong pro-vince.Genomic DNA was isolated from peripheral blood leucocytes of these patients and the healthy children.Mutational analysis was performed in 8 exons of NPHS2 gene and 18 exons of CD2AP gene after sequencing directly.The results were compared with United States National Center for Biotechnology Information(NCBI) gene database, the detected gene mutation. Results The variation analysis revealed 3 polymorphisms (288C>T, 954T>C, 1038A>G) in 14 cases out of 26 patients and 4 cases of the healthy children studied, which had been reported before, but there was no significant difference in the genotypic and allelic frequencies of these polymorphisms between the patients and the controls(all P>0.05). One CD2AP heterozygous mutation(1917+ 20 C>G) was detected in intron in 2 cases of SRNS children. Conclusions NPHS2 gene variation may not be the main mechanism of SRNS in Guangdong province.CD2AP gene mutation may increase the possibility of SRNS and focal segmental glomerulosclerosis in children.CD2AP mutation in intron may involve in the pathogenesis of SRNS. Key words: Steroid-resistant nephrotic syndrome; NPHS2 gene; CD2AP gene

Elevated serum β2-GPI-Lp(a) complexes levels in children with nephrotic syndrome

BackgroundThe complexes of β2-glycoprotein I (β2-GPI) with lipoprotein(a) [β2-GPI-Lp(a)] exist in human circulation and are increased in serum from patients with some autoimmune diseases. This study aims to investigate the concentration of β2-GPI-Lp(a) in serum of children with idiopathic nephrotic syndrome (NS) and its relationship with serum lipids, oxidized lipoprotein and renal function parameters to explore the potential of the complexes as an additional marker for evaluating pediatric NS. MethodsSerum concentrations of β2-GPI-Lp(a) complexes and oxidized Lp(a) [ox-Lp(a)] were measured by “Sandwich” ELISAs in 80 NS children and 82 age/sex-matched healthy controls. The levels of serum lipids and kidney parameters were also determined. Multivariate logistic regression analysis was performed to identify correlate of β2-GPI-Lp(a) and NS. ResultsThe serum concentrations of β2-GPI-Lp(a) complexes in children with NS were significantly higher than those in controls (median 0.95U/ml vs 0.28U/ml, P<0.0001). Ox-Lp(a) levels were also markedly elevated (median 14.55mg/l vs 2.60mg/l, P<0.0001] in NS children. The concentrations of β2-GPI-Lp(a) were positively correlated with ox-Lp(a) (r=0.246, P=0.028), but not with Lp(a) level, and the concentrations of ox-Lp(a) were positively related with Lp(a) (r=0.301, P=0.007) in NS children. Multivariate logistic regression analysis identified a positive association between NS and β2-GPI-Lp(a) (OR=13.694, 95% CI 6.400–29.299, P<0.0001), after adjusting for kidney function parameters, serum lipids and ox-Lp(a). ConclusionsElevated β2-GPI-Lp(a) level was an independent and significant risk factor for pediatric NS and, enhanced Lp(a) oxidation partly contributes to the formation of β2-GPI-Lp(a) complexes.

A spectrum of novel NPHS1 and NPHS2 gene mutations in pediatric nephrotic syndrome patients from Pakistan

BackgroundMutations in the NPHS1 and NPHS2 genes are among the main causes of early-onset and familial steroid resistant nephrotic syndrome respectively. This study was carried out to assess the frequencies of mutations in these two genes in a cohort of Pakistani pediatric NS patients. MethodsMutation analysis was carried out by direct sequencing of the NPHS1 and NPHS2 genes in 145 nephrotic syndrome (NS) patients. This cohort included 36 samples of congenital or infantile onset NS cases and 39 samples of familial cases obtained from 30 families. ResultsA total of 7 homozygous (6 novel) mutations were found in the NPHS1 gene and 4 homozygous mutations in the NPHS2 gene. All mutations in the NPHS1 gene were found in the early onset cases. Of these, one patient has a family history of NS. Homozygous p.R229Q mutation in the NPHS2 gene was found in two children with childhood-onset NS. ConclusionsOur results show a low prevalence of disease causing mutations in the NPHS1 (22% early onset, 5.5% overall) and NPHS2 (3.3% early onset and 3.4% overall) genes in the Pakistani NS children as compared to the European populations. In contrast to the high frequency of the NPHS2 gene mutations reported for familial SRNS in Europe, no mutation was found in the familial Pakistani cases. To our knowledge, this is the first comprehensive screening of the NPHS1 and NPHS2 gene mutations in sporadic and familial NS cases from South Asia.

SOCS3 and SOCS5 mRNA expressions may predict initial steroid response in nephrotic syndrome children

Suppressors of Cytokine Signaling (SOCS) inhibit Signal Transducers and Activators of Transcription (STATs) phosphorylation by binding and inhibiting Janus Kinases (JaKs). The aim of the present study was to evaluate the influence of glucocorticosteroids on the JaK/STAT signaling pathway in the leukocytes of nephrotic syndrome (NS) patients. The study group was composed of 34 steroid sensitive NS (SSNS) children and 20 steroid resistant NS (SRNS) subjects. Gene expression was assessed by real-time PCR using pre-designed human JaK/STAT PCR array. Protein expression was evaluated using ELISA assay (plasma concentration) and immunofluorescence (in situ protein expression). In SSNS children, the initial increased expression of JaK1, JaK2, JaK3, STAT1, STAT2, STAT6, TYK2, SOCS1, SOCS2, SOCS3, SOCS4 and SOCS5 was reduced back to the control limits. Similarly, in SRNS patients the increased levels of almost all mRNA expressions for the abovementioned genes were decreased, with the exceptions of SOCS3 and SOCS5 expressions. These mRNA expressions were still significantly increased and correlated with early unfavorable course of nephrotic syndrome in children. Plasma levels of SOCS3, SOCS5, IL-6 and IL-20 were significantly increased in SRNS subjects after six weeks of steroids medication compared to SSNS and control participants. We conclude that SOCS3 and SOCS5 increased mRNA expressions might predict initial resistance to steroids in NS patients.

SOCS3 and SOCS5 mRNA expressions may predict initial steroid response in nephrotic syndrome children

SOCS3 and SOCS5 mRNA expressions may predict initial steroid response in nephrotic syndrome children

The level of native and oxidized lipoprotein(a) in children with nephrotic syndrome

ObjectiveTo investigate lipoprotein(a) [Lp(a)], oxidized Lp(a) [ox-Lp(a)] and Lp(a) immune complex [Lp(a)-IC] levels in children with nephrotic syndrome (NS). Design and methodsPlasma Lp(a), ox-Lp(a) and Lp(a)-IC levels were determined in 106 NS children in acute-period, 42 in remission and 155 controls. ResultsLp(a) and ox-Lp(a) levels were significantly higher in acute-period and remission NS than in control. Ox-Lp(a) levels in acute-period NS were higher than in remission. Lp(a)-IC levels in acute-period NS were higher than in control. Lp(a), ox-Lp(a) and Lp(a)-IC were found negatively related with albumin in NS. Lp(a), ox-Lp(a) and Lp(a)-IC levels decreased after use of steroid therapy. Multiple linear regression analysis found relative change of albumin, creatinine, urea, triglyceride and high density lipoprotein cholesterol accounted for 78.9% of variation in ox-Lp(a). ConclusionsLp(a), ox-Lp(a) and Lp(a)-IC levels were increased in NS children, which may play an important role in the processes of atherosclerosis.

MDR-1 gene polymorphisms in steroid-responsive versus steroid-resistant nephrotic syndrome in children

The putative genetic regulation of multidrug resistance gene-1 (MDR-1) gene expression and P-glycoprotein function has not yet been clearly delineated in patients with nephrotic syndrome (NS). We undertook this study to examine the distribution of three most frequent MDR-1 exonic polymorphisms G3435C, G2677T/A and C1236T in patients with NS and control children to investigate their usefulness as markers of responsiveness of the disease to steroids. Two hundred and sixteen children with NS and 216 healthy controls were genotyped for three exonic MDR-1 polymorphisms (G3435C, G2677T/A and C1236T) by using the polymerase chain reaction-restriction fragment length polymorphism technique. The frequency distribution of genotypes/alleles was compared between patients with NS and controls and also between steroid-sensitive NS (SSNS) and steroid-resistant NS (SRNS) patients. Of the total 216 cases of NS (median age of onset 5 years, 165 males), 137 had SSNS, and 79 had SRNS. Homozygous mutants of C3435T (TT versus CC, P = 0.034) and G2677T/A (TT + AA versus GG), P = 0.030) were significantly higher in patients with NS compared to controls. The frequency distribution of homozygous mutant TT + AA compared to wild genotype GG was significantly higher in SRNS than SSNS patients (P = 0.011) for G2677T/A, while the mutant genotypes for C3435T and C1236T were not different between SRNS and SSNS patients. The combination-bearing mutant genotype either of C3435T or G2677T/A exhibited a significantly higher frequency of mutant genotypes distribution in SRNS patients. MDR-1 haplotypes did not differ significantly between SSNS and SRNS patients. Patients with NS carrying homozygous mutants of single nucleotide polymorphism (SNP) G2677T/A are prone to develop SRNS. The synergistic effect of mutant genotypes of SNPs G2677T/A and C3435T in different combinations increase the risk of developing steroid resistance in patients with NS.

Comparisons of bone mineral density in steroid dependent, frequent relapse, and infrequent relapse nephrotic syndrome children

Background Children with nephrotic syndrome, especially those with steroid dependent and frequent relapse are at greater risk of reduced bone mineral density (BMD).Objective To determine bone mineral density (BMD) in steroid dependent and frequent relapse compared to infrequent relapse nephrotic syndrome.Methods We conducted a cross-sectional study at the Child Health Department, Cipto Mangunkusumo Hospital, from August until November 2009. Subjects were 5 to 18 year-old children with steroid dependent nephrotic syndrome (SDNS), frequent relapsenephrotic syndrome (FRNS), or infrequent relapse nephrotic syndrome (IRNS). Ionized calcium level, vitamin 25(OH)D3 level, and BMD were measured us ng dual energy x-ray absorptiometry (DEXA).Results 11 SDNS and 11 FRNS cbildren (group I) were compared with 22 IRNS children (Group II). Children of SDNS and FRNS had significantly longer duration of illness, more relapses, longer steroid therapy duration, and greater cumulative steroid dose compared to group 11 (IRNS). There were no differences between the two groups with regard to mean ionized calcium level and vitamin 25(OH)D3 level. Children in group I had lower z-scores compared to group lI, but the difference was not statistically significant r mean (SD) -1.182 (1.21) vs. -0.795 (1.25), P=0.305]. Subgroup analysis showed that SDNS children had lower z-scores than FRNS [-1.791 (1.17) vs. -0.57 (0.94), P=0.019] and IRNS [-1.791 (1.17) vs. -0.795 (1.25), P=O.026].Conclusion Children with SDNS have significantly lower BMD z-scores compared to those with FRNS and IRNS.

Study on the differentially expressed genes of steroid-resistant and steroid-sensitive nephrotic syndrome

To identify the genes differentially expressed among the steroid-resistant nephrotic syndrome (SRNS), steroid-sensitive nephrotic syndrome (SSNS) and normal children, and understand the molecular mechanism of SRNS. Affymetrix microarray technology was used to obtain such a profile. The differentially expressed genes among these groups were identified based on signal-to-noise ratios by GCOS software; real-time PCR analysis was performed to confirm the microarray results. There were 157 genes differentially expressed among these groups. The genes up-regulated both in SRNS and SSNS were involved primarily in ionic transportation, immuno-signal transduction and apoptosis. In particular, CLNS1A gene was down regulated in SRNS but up regulated in SSNS. Several differentially expressed genes, such as CLNS1A and HLA-DRB4 were found to be closely related to the pathogenesis of SRNS and SSNS. This DNA microarray analysis has provided some important clue to the molecular mechanism of SRNS.

Treatment of Severe Edema in Children with Nephrotic Syndrome with Diuretics Alone — A Prospective Study

Severe edema in children with nephrotic syndrome (NS) may be associated with volume contraction (VC) or volume expansion (VE). Usually, severe edema in children is treated with intravenous (IV) albumin and diuretics, which is appropriate for VC patients. However, in VE patients, this can precipitate fluid overload. The objective of this study was to evaluate treatment of severe edema in NS with diuretics alone. Thirty NS patients with severe edema were enrolled in this prospective study in two phases. VC was diagnosed based on fractional excretion of sodium (FeNa) <1%. VC patients received IV albumin and furosemide. VE patients received IV furosemide and oral spironolactone. On the basis of phase 1 observations, FeNa <0.2% identified VC in 20 phase 2 patients. All phase 1 patients had FeNa <1%. Phase 1 patients when reanalyzed based on a FeNa cutoff of 0.2%; it was noted that VC patients had higher BUN, BUN/creatinine ratio, urine osmolality, and lower FeNa and urine sodium compared with VE patients. Similar results were observed in phase 2. VC patients had significantly higher renin, aldosterone, and antidiuretic hormone levels. In phase 2, 11 VE patients received diuretics alone and 9 VC patients received albumin and furosemide. There was no difference in hospital stay and weight loss in VC and VE groups after treatment. FeNa is useful in distinguishing VC versus VE in NS children with severe edema. The use of diuretics alone in VE patients is safe and effective.

High-sensitivity C-reactive protein (hs-CRP) level in children with nephrotic syndrome

The aim of this study was to assess the serum concentration of high-sensitivity C-reactive protein (hs-CRP) in children with nephrotic syndrome (NS) treated with prednisone and cyclosporine A (CyA). Patients were divided into three groups: (I) 20 NS children (aged 4-14 years) in relapse and examined twice, (A) before treatment and (B) after proteinuria regression (a 3-4 week course of prednisone therapy); (II) 20 children with steroid-dependent or steroid-resistant NS, treated with CyA, also examined twice, (D) before treatment with CyA, (E) 6 months after therapy. A control group (C) consisted of 20 healthy children. Serum hs-CRP level was determined by a nephelometric method with a Behring Nephelometer 100 Analyzer, Dade Behring. The results showed that median hs-CRP concentration was the highest in children with relapsing steroid-sensitive NS before treatment (IA). After proteinuria regression (IB), the hs-CRP level had decreased and did not differ from that of healthy controls (C) (P>0.05). In group II, before CyA administration (IID), the level of hs-CRP was normal, but it had increased after 6 months of treatment (IIE) up to a level six-times higher than that of the control group (P<0.01). We concluded that, in children with steroid-sensitive nephrotic syndrome in relapse, the serum hs-CRP level is increased but returns to normal after 3-4 weeks of glucocorticoid treatment. In children chronically treated with CyA due to NS, serum hs-CRP level increases significantly during the therapy.

Expression of multidrug resistance P-glycoprotein on lymphocytes from nephrotic children treated with cyclosporine A and ACE-inhibitor

The aim of this work was to determine the expression of P-glycoprotein (P-gp) on peripheral lymphocytes (CD3) in children with steroid-dependent nephrotic syndrome (SDNS) during cyclosporine A (CyA) and ACE-inhibitor (ACE-I) treatment. The study group (I) consisted of 20 children with SDNS aged 5-18 years, with a subsequent proteinuria relapse at the time of prednisone dose reduction. All nephrotic syndrome (NS) children were examined three times: A--at proteinuria relapse, before CyA treatment; B--after 3 months; C--after 12 months of CyA administration. The control group (II) consisted of 20 healthy children. CD3/P-gp was measured using a flow cytometry assay. The serum CyA level was assessed by means of the immunofluorescence method. The expression of CD3/P-gp in NS relapse, prior to CyA+ACE-I administration, was much higher (median 9.15%, range 1.50-13.50%) when compared to healthy controls (median 1.20%, range 0.30-5.70%). The absolute number of CD3/P-gp in this examination was almost five times higher when compared to healthy controls (p<0.01). After 3 months of CyA+ACE-I therapy, the expression of CD3/P-gp decreased dramatically and was similar to the controls. Similar results were obtained after 12 months of treatment. A strong negative correlation was found between CD3/P-gp and serum CyA concentration in both examinations (r=-0.624, p<0.01; r=-0.464, p<0.01). We conclude that the results of our studies indicate that CyA+ACE-I in SDNS inhibits the expression of P-gp. CyA is an alternative therapy that may lead to the optimization of glucocorticoid (GC) doses, thus, reducing the risk that is associated with the treatment.

Role of Nutrition Guidance on Nephrotic Syndrome in Children

目的 为能使NS患儿得到及时的营养治疗,纠正疾病造成营养不良的影响,通过营养指导配合临床治疗,探讨符合小儿NS营养治疗方案.方法2002～2004年在本院普通儿科住院中的92例2～12岁住院患儿分为两组,一组为感染组46例,另一组为肾病组46例,同样让患儿自选食谱,不作任何干预,进行膳食调查,营养指导,回顾性分析.结果感染组除WBC升高外,其他无异常,肾病组患儿TP、ALB、TG、CHO有异常.两组患儿同时存在热量摄入严重不足的现象.结论热量不足是造成营养不良的主要原因,长期低热饮食,对小儿NS患儿危害非常大,提示在治疗小儿NS患儿应用药物治疗的同时不能忽视对惠儿及家属正确的营养指导,只要患儿积极配合,提高良好的依从性才能逐步改善患儿营养不良状况,保证患儿正常发育。