Incidence and Relapse Triggers of Childhood Idiopathic Nephrotic Syndrome between 2006 and 2016: A Population-Based Study in Fukushima, Japan.

Childhood idiopathic nephrotic syndrome (NS) is defined by proteinuria and hypoproteinemia. The incidence of childhood idiopathic NS varies with age, race, residential areas, and social conditions. In Japan, its incidence was estimated to be 6.49 cases/100,000 children. Our study aimed to investigate the incidence, characteristics, and rate of relapse of idiopathic NS in Fukushima between 2006 and 2016. Overall, 158 children aged from 6 months to 15 years old (65.8% male) developed idiopathic NS (median age at onset, 5.3 years). The peak age at onset was three years. The average annual incidence of childhood idiopathic NS was 5.16 (range, 3.47-9.26) cases/100,000 children. The highest incidence was in 2011, which was the year of the Great East Japan Earthquake and nuclear power plant accident, and reportedly caused psychological distress in the children at the time. Conversely, the five-year birth cohort showed minor difference from 2008 to 2012. The rate of incidence in males aged < 5 years was thrice greater than in females of the same age and almost the same for males and females aged 11-15 years. Of 507 total relapses in 115 NS children, common triggers of relapses were steroid discontinuation or reduction and infection. The average annual incidence of childhood NS based on the Fukushima population was lower than previously reported in Japan, and the annual incidence has changed over an 11-year period. These changes may be affected by social or environmental factors, including mental stress associated with lifestyle changes after the disaster.

Effect of the Lactococcus Lactis 11/19-B1 Strain on Atopic Dermatitis in a Clinical Test and Mouse Model.

Some lactic acid bacteria (LAB) are known to improve atopic dermatitis (AD) through the regulation and stimulation of the host immune system. In this study, we found that ingestion of yogurt containing Lactococcus lactis 11/19-B1 strain (L. lactis 11/19-B1) daily for 8 weeks significantly improved the severity scoring of atopic dermatitis (SCORAD) system score from 38.8 ± 14.4 to 24.2 ± 12.0 in children suffering from AD. We tried to identify which LAB species among the five species contained in the test yogurt contributed to the improvement in AD pathology using an AD mouse model induced by repeated application of 1-fluoro-2, 4-dinitrobenzene (DNFB). AD-like skin lesions on the dorsal skin and ear were most improved by L. lactis 11/19-B1 intake among the five LAB species. In addition, analysis of CD4+ T cell subsets in Peyer's patches (PPs) and cervical lymph nodes (CLNs) indicated that the intake of L. lactis 11/19-B1 generally suppressed all subsets related to inflammation, i.e., Th1, Th2 and Th17, instead of activating the suppressive system, Treg, in the AD mouse model. Histological observations showed ingestion of L. lactis 11/19-B1 significantly suppressed severe inflammatory findings, such as inflammatory cell filtration, epidermal erosion and eosinophil infiltration. These results suggest that the immunomodulatory effects of L. lactis 11/19-B1 contribute to improvements in AD pathology.

Renal expression of alpha-smooth muscle actin and c-Met in children with Henoch-Schönlein purpura nephritis.

Alpha-smooth muscle actin (alpha-SMA) is the actin isoform that predominates within vascular smooth-muscle cells and plays an important role in fibrogenesis. On the other hand, c-Met is the receptor for hepatocyte growth factor (HGF), which plays a role in protection from injury and has anti-fibrogenetic effects. To clarify whether alpha-SMA and HGF are associated with the progression of renal injury in Henoch-Schönlein purpura nephritis (HSPN), we evaluated the renal expression of alpha-SMA and c-Met in HSPN patients. Patients were divided into three groups. Group 1 consisted of eight patients (male:female 4:4) with stage II or less in the classification of the International Study of Kidney Disease in Children (ISKDC), Group 2 consisted of 20 patients (male:female 11:9) with ISKDC stage III or greater and a good prognosis, and group 3 consisted of seven patients (male:female 3:4) with ISKDC stage III or greater and poor prognosis. Renal biopsy findings, including c-Met and alpha-SMA staining, were investigated for each group. At first biopsy, the mean scores for renal alpha-SMA and glomerular c-Met in groups 2 and 3 were higher than those in group 1, while mean scores for neither renal alpha-SMA nor glomerular c-Met differed between groups 2 and 3. At second biopsy, the mean scores for renal alpha-SMA staining in group 3 were higher than those in group 2, and mean score for glomerular c-Met staining in group 3 was lower than that in group 2. In groups 2 and 3, the mean scores for glomerular and interstitial alpha-SMA staining at first biopsy were correlated with the chronicity index (CI) at second biopsy, but the mean score for glomerular c-Met staining at first biopsy correlated with neither the activity index (AI) nor CI in the first or second biopsies in all groups. Our findings suggest that the expression of renal alpha-SMA may be associated with progression of renal injury in HSPN.

Development of glomerular endothelial cells, podocytes and mesangial cells in the human fetus and infant.

The process of glomerular development consists of four developmental stages: vesicle (V) stage, S-shaped body (S) stage, capillary loop (C) stage and maturation (M) stage. However, the development of glomerular endothelial, mesangial and epithelial cells in fetal and infant kidneys remains unclear. In order to determine the characteristics of human glomerular development, we investigated the process of glomerular development by staining fetal and infant kidneys for CD31, CD34 and FB21, markers for endothelial cells, alpha-smooth muscle actin (alpha-SMA), a marker for mesangial cells, and nephrin, a marker for podocytes. These series of studies were carried out on kidneys obtained at autopsy from 27 fetuses and 5 infants. The fetuses were divided into the following 5 groups according to gestational age; 13-19, 20-24, 25-29, 30-34 and 35-39 weeks. In each group, glomerular development was classified according to the developmental stage and the staining patterns for CD31, CD34, FB21, alpha-SMA and nephrin. The proportion of V-stage development in 100 glomeruli examined was highest at 13-19 weeks. After 20 weeks, the V-stage proportion decreased gradually, and the proportion of S stage became highest at 20-24 weeks. The C-stage proportion was highest at 25-29 weeks, while the M-stage proportion was highest in infants aged 1-6 months. The staining patterns for CD31, CD34 and FB21 were similar in endothelial cells after 25 weeks of gestation. Staining of alpha-SMA and nephrin was first observed in the S stage. In conclusion, maturation of endothelial cells starts at 25 weeks and is completed by 35 weeks of gestation. Epithelial cells and mesangial cells first appear during the S stage.

Renal effects of Coxsackie B4 virus in hyper-IgA mice.

For clarification of the pathogenetic role of viral infection in chronic glomerulonephritis, the renal effects of Coxsackie B4 virus (CB4) were examined in hyper-IgA (HIGA) mice. In experiment 1, HIGA mice (n = 75) were inoculated intravenously with live CB4 and inactivated CB4 once a month from 1 to 12 mo of age. In experiment 2, HIGA mice (n = 45) were inoculated intravenously with live CB4 and inactivated CB4 once at 6 wk of age. In experiment 3, 60 mice were inoculated intravenously with carbon and live or inactivated CB4 once at 6 wk of age. Mice in the control group were inoculated with vehicle. The kidneys were extirpated from five mice of each group killed with time after inoculation for histologic evaluation. The scores for mesangial IgA deposition, PCNA-positive cells, and matrix at 20 wk were higher in mice with live CB4 than in mice with inactivated CB4 or without CB4. On electron microscopic examination, swelling and detachment of endothelial cells from 24 h after inoculation and increase of serum IFN-gamma concentration were found in mice with live CB4. Many carbon particles were present in peripheral and central zones of the mesangium from 5 to 10 d in mice with carbon and live CB4. These results suggest that CB4 provokes exacerbation of renal pathologic findings in HIGA mice via endothelial injury, IFN-gamma production, and dysfunction of the mesangial pathway.

Glomerulonephritis associated with chronic infection from long-term central venous catheterization.

There have been few reports on immune complex-mediated glomerulonephritis associated with chronic infection from long-term central venous catheterization in adulthood. We report here on a 13-year-old boy with nephritis who exhibited glomerulonephritis that had been induced by the long-term use of central venous catheters, and its resolution after extraction of the central venous catheter. A diagnosis of glomerulonephritis associated with chronic infection caused by long-term central venous catheterization was made, based on the absence of clinical findings after removal of the catheter, hypocomplementemia, pathology findings resembling membranoproliferative glomerulonephritis, and detection of Staphylococcus epidermidis from culture of the removed catheter culture. For clinicians using long-term central venous access for parenteral feeding, rapid catheter exchange is necessary for patients with fever of unknown origin.

The leukotriene B4 receptor antagonist ONO-4057 inhibits mesangioproliferative changes in anti-Thy-1 nephritis.

OBJECTIVE: ONO-4057 is a specific leukotriene B4 (LTB4) receptor antagonist which inhibits human neutrophil aggregation, chemotaxis and degranulation induced by LTB4. This study was conducted to evaluate the role of LTB4 in glomerulonephritis, and to examine whether ONO-4057 moderated anti-Thy-1 nephritis. METHODS: Experiment 1: Sixty Wistar rats were divided into three groups. Rats of Group A (n = 20) underwent intraperitoneal administration of placebo as a control group, rats of Group B (n = 20) first underwent intraperitoneal administration of 100 mg/kg ONO-4057 and rats of Group C (n = 20) first underwent intraperitoneal administration of 300 mg/kg ONO-4057 daily from day 3 before anti-Thy-1 antibody (OX7) injection to day 14 after OX7 injection, respectively. Experiment 2: Forty rats were divided into two groups. ONO-group (n = 20) was treated with 300 mg/kg BW of ONO-4057 and placebo-group (n = 20) with placebo daily from days 1 to 13 after OX7 injection. Urine and blood samples were collected and the kidneys were extirpated from five rats of each group sacrificed at 3 h, 24 h, day 7 or day 14 after the injection of OX7 in both experiments. Urinary protein excretion, renal function and pathological findings were analysed in each group of both experiments. RESULTS: (1) Glomerular infiltration by polymorphonuclear leucocytes (PMNs) and macrophages at 3 h was less in Groups B and C than in Group A, and matrix scores at day 7 were lower in Groups B and C than in Group A. Injury scores did not differ among the groups. (2) Urinary protein excretion at day 7 was less in Group C than in Group A. (3) Neither pathological findings nor urinary protein excretion differed between ONO-group and placebo-group. CONCLUSION: These results suggest that LTB4 is associated not with the pathogenesis of complement-dependent mesangial cell lysis but with that of mesangial proliferative change in anti-Thy-1 nephritis.

Detection of enteroviruses in renal biopsies from patients with immunoglobulin A nephropathy.

Viruses have been suspected to be one of the causes of IgA nephropathy (IgAN). Recent studies have detected viruses in renal tissues of patients with IgAN. Enteroviruses have been reported as pathogenic agents in some renal diseases. We previously reported that group B coxsackieviruses cause pathological changes in experimentally infected mouse kidney. The aim of the present study was to examine the participation of enteroviruses in the pathogenesis of renal diseases including IgAN. Renal biopsies of ten patients with IgAN (group 1) and of 19 patients with non-IgAN renal disease (group 2) were analyzed by polymerase chain reaction (PCR) for the presence of enteroviral RNA. Positive PCR results were obtained for three patients (30%) of group 1. We confirmed by sequencing that the positive PCR products were derived from strains of enteroviruses. One of these three patients also had a positive result for lymphocytes from peripheral blood. In contrast, enteroviral RNA was detected in none of the 19 patients of group 2. The incidence of enteroviral RNA detection in patients of group 1 was higher than that in group 2 (P<0.05). Our findings suggest that enteroviral infection may have the possibility of becoming one of the factors involved in the mechanism of onset or evolution of IgAN.

Mizoribine oral pulse therapy for steroid-dependent nephrotic syndrome.

There have been reports of the use of mizoribine (MZB) oral pulse therapy for the treatment of systemic lupus erythematosus. We report its efficacy in a 9-year-old girl with steroid- and cyclosporine-dependent nephrotic syndrome (NS). The patient experienced relapses of NS when prednisolone was tapered to 20 mg/day after discontinuing cyclosporine due to biopsy proven toxicity. When methylprednisolone pulse therapy combined with prednisolone therapy (40 mg/day) failed to result in a complete remission after 3 weeks, oral MZB pulse therapy (total dose of 500 mg, 10 mg/kg per day in three divided daily doses twice a week) was given. This therapy was continued for 9 months and resulted in complete remission of the NS for 6 months despite the discontinuation of prednisolone. The serum concentration of MZB was above 2.5 microg/ml for about 10 h (from 3 h after the first dose of MZB to 2 h after the final dose). Thus, our results suggest that this regimen may be effective for patients with steroid-dependent NS.

Epstein-Barr virus-associated hemophagocytic syndrome in a patient with lupus nephritis.

Hemophagocytic syndrome (HPS) is an unusual but severe illness associated with a variety of infections, as well as genetic, malignant tumors, and autoimmune diseases. We report an 11-year-old girl with systemic lupus erythematosus and nephritis who developed HPS associated with Epstein-Barr virus reactivation. In our patient, the onset of reactive HPS might be related to immunosuppressive treatment during the course of lupus nephritis.

Efficacy of multidrug therapy combined with mizoribine in children with diffuse IgA nephropathy in comparison with multidrug therapy without mizoribine and with methylprednisolone pulse therapy.

AIM: To evaluate the efficacy of prednisolone, warfarin, and dipyridamole therapy combined with mizoribine (PWDM) in the treatment of diffuse immunoglobulin A (IgA) nephropathy in comparison with prednisolone, warfarin, and dipyridamole therapy without mizoribine (PWD) and with methylprednisolone pulse therapy (PWD pulse). METHODS: We collected data on 61 patients diagnosed with diffuse IgA nephropathy, and these patients were retrospectively divided into three groups without randomization. Group A included 21 patients before 1987 who were treated with PWD for 24 months, group B included 20 patients from 1987 to 1989 who were treated with PWD pulse therapy for 24 months, and group C included 20 patients after 1990 who were treated with PWDM for 24 months. Clinical features and pathological findings in each group were analyzed retrospectively. RESULTS: The time from initiation of therapy in group A, group B, and group C was 8.9 +/- 5.2, 8.1 +/- 3.9, and 7.7 +/- 3.8 years, respectively. At the latest follow-up examination, the mean urinary protein excretion (mg/m2/h) was 17 +/- 10 in group A, 22 +/- 20 in group B, and 6 +/- 6 in group C and had decreased significantly in group C as compared with the other groups. The activity index in all three groups was lower at the second biopsy than that at the first biopsy (5.1 +/- 0.8 vs. 6.5 +/- 2.1 in group A, p < 0.05; 5.6 +/- 0.9 vs. 6.6 +/- 1.7 in group B, p < 0.01, and 4.5 +/- 1.0 vs. 6.8 +/- 1.9 in group C, p < 0.01). The chronicity index in groups A and B at second biopsy was higher than at first biopsy (7.3 +/- 1.4 vs. 4.8 +/- 1.0 in group A, p < 0.01, and 8.1 +/- 2.0 vs. 5.3 +/- 0.9 in group B, p < 0.01), but was unchanged in group C. At the latest follow-up examination, 1 patient (4.8%) in group A, 3 patients (15%) in group B, and none (0%) in group C had renal insufficiency. CONCLUSION: These results suggest that PWDM appears to be more effective than PWD or PWD pulse in ameliorating proteinuria and histological severity of patients with IgA nephropathy.

FB21, a monoclonal antibody that reacts with a sialic-acid-dependent carbohydrate epitope, is a marker for glomerular endothelial cell injury.

BACKGROUND: FB21 is reactive with glomerular endothelial cells and distal tubules of the human kidney and is bound to a sialic-acid-dependent cell-surface antigen. We evaluated FB21 staining in fetal kidneys and kidneys of children and adults with normal kidneys and glomerulonephritis and investigated whether FB21 can be used as a marker for endothelial cell injury. METHODS: This study was performed on 6 children, 10 adults, and 12 fetuses with normal kidneys and 113 patients diagnosed with primary and secondary glomerulonephritis. We evaluated renal staining for FB21 in children with normal kidneys and glomerulonephritis and measured serum E-selectin concentrations in patients with hemolytic uremic syndrome (HUS) and Henoch-Schönlein purpura nephritis (HSPN). RESULTS: (1) FB21 was reactive with endothelial cells of normal kidneys and detected on the surface of endothelial cells by immunoelectron microscopy. (2) FB21 was reactive with endothelial cells in kidneys of fetuses older than 32 weeks. (3) Endothelial cell FB21 staining scores in the first renal biopsy specimens of patients with HUS and HSPN were lower than those in normal kidneys of children and correlated negatively with serum E-selectin concentrations. (4) Endothelial cell FB21 staining of crescentic and sclerotic glomerular lesions in patients with immunoglobulin A nephropathy, membranoproliferative glomerulonephritis, and focal glomerulosclerosis was weaker than that in normal kidneys. CONCLUSION: These results suggest that FB21 can be used as a marker for glomerular endothelial cell injury in various types of glomerulonephritis.

Plasmapheresis therapy for rapidly progressive Henoch-Schönlein nephritis.

Six Japanese children with rapidly progressive Henoch-Schönlein purpura nephritis (HSPN) received multiple drug therapy combined with plasmapheresis (PP). After five courses of PP, multiple drug therapy, including methylprednisolone and urokinase pulse therapy, oral prednisolone, cyclophophamide, dipyridamole, and warfarin was given. At presentation, urine protein excretion and histological indices of the mean activity and chronicity were 245+/-101 mg/m(2) per hour, 6.6+/-1.2, and 1.5+/-1.3, respectively. After 6 months of therapy, urinary protein excretion had decreased significantly ( P<0.001). The activity index decreased significantly at the second renal biopsy performed at a mean interval of 4.3 months after the first (2.8+/-1.4, P<0.05), while the chronicity index did not change. At the most recent observation, all showed clinical improvement. Two patients had normal urine, three had proteinuria of <20 mg/m(2) per hour, one had proteinuria of >20 mg/m(2) per hour, and none had renal insufficiency. Although this case series is without controls, our treatment protocol may be of benefit to children with rapidly progressive HSPN.

Evaluation of T helper-1/-2 balance on the basis of IgG subclasses and serum cytokines in children with glomerulonephritis.

BACKGROUND: To clarify the mechanism of deposition of immunoglobulin G (IgG) subclasses in glomerulonephritis in children, we investigated IgG subclasses in glomerular deposits and T helper subtype 1 (T(H)1)/T(H)2 cytokine balance in pediatric patients with glomerulonephritis. METHODS: We enrolled 95 children in whom glomerulonephritis had been diagnosed in our hospital between 1993 and 2000. Patients were divided into 5 groups according to histological diagnosis: 31 patients with lupus nephritis (LN), 22 patients with membranoproliferative glomerulonephritis (MPGN), 7 patients with membranous glomerulonephritis (MGN), 20 patients with Henoch-Schönlein purpura nephritis, and 20 patients with IgA nephropathy. We compared serum IgG subclass values, serum cytokine (interleukin-2 [IL-2] receptor [IL-2R], IL-2, IL-4) values, and immunofluorescence evidence of glomerular IgG subclasses in the kidney among groups. RESULTS: (1) High serum IgG1 and IgG2 values and glomerular IgG1 and IgG2 deposits were found frequently in the LN group. (2) High serum IgG3 values and glomerular IgG3 deposits were found frequently in the MPGN group. (3) High serum IgG4 values and glomerular IgG4 deposits were found frequently in the MGN group. (4) Conversely, cytokine measurements showed high serum IL-2 and IL-2R values in the LN and MPGN groups, and serum IL-4 values were high in the MGN group. CONCLUSION: These findings suggest that the pathogenetic mechanism of LN may involve both the T(H)1 and T(H)2 pattern, the pathogenetic mechanism of MPGN may involve the T(H)1 pattern, and the pathogenetic mechanism of MGN may involve the T(H)2 pattern.

Efficacy of prednisolone and mizoribine therapy for diffuse IgA nephropathy.

OBJECTIVE: There have been only a few studies concerning oral prednisolone and mizoribine therapy for diffuse IgA nephritis (IgAN). We evaluated the efficacy of prednisolone and mizoribine therapy for diffuse IgAN. METHODS: We enrolled 34 patients who had been diagnosed as having diffuse IgAN with severe proteinuria during the period from 1992 to 1999. Following diagnostic renal biopsy, the patients were treated with prednisolone, mizoribine, warfarin and dilazep dihydrochloride. The clinical features, laboratory data and pathological findings between pre- and post-therapy were investigated. RESULTS: The mean urinary protein excretion after 6 months of treatment had decreased significantly compared to pre-therapy. The incidence of hematuria in post-therapy was lower than that of pre-therapy. The grading index decreased significantly from 4.8 +/- 2.1 at the first biopsy to 2.3 +/- 1.7 at the second biopsy (p < 0.001) and the staging index decreased significantly from 4.1 +/- 1.9 at the first biopsy to 2.7 +/- 2.4 at the second biopsy (p < 0.05). Macrophage infiltration and alpha-smooth muscle actin-positive cells in the glomerulus and interstitial region decreased significantly in post-therapy compared with pre-therapy. At the most recent follow-up, none of the 34 patients had renal insufficiency. CONCLUSIONS: Our study suggested that prednisolone and mizoribine therapy is effective for those patients with the risk of progression of IgAN.

Efficacy of methylprednisolone and urokinase pulse therapy for severe Henoch-Schönlein nephritis.

OBJECTIVE: To evaluate the efficacy of methylprednisolone and urokinase pulse therapy (MUPT) for severe Henoch-Schönlein nephritis, we examined the clinical manifestation and prognosis of patients with MUPT on long-term observation. METHODS: We enrolled 56 patients with Henoch-schönlein nephritis who had been diagnosed with at least type IIIb from 1980 to 1998 on long-term observation and had been treated with MUPT. The clinical features, laboratory data, and pathologic findings between "pre-MUPT" and "post-MUPT," and the prognosis of these patients on long-term observation were retrospectively investigated. RESULTS: The mean urinary protein excretion after 6 months of treatment had decreased significantly compared with "pre-MUPT." Hypercoagulant state in "after the completion of urokinase pulse therapy" improved compared with "pre-MUPT." First renal biopsies were performed in all patients and second biopsies were performed in 27 patients. The activity index decreased significantly from 4.1 +/- 1.9 at first biopsy to 2.5 +/- 1.7 at second biopsy, while the chronicity index did not differ between first and second biopsy. None had renal insufficiency and renal survival rate was 100% for the decade. CONCLUSIONS: Although uncontrolled, our study suggested that MUPT is effective for those patients with the risk of progression of their nephropathy, especially if started early during the course of the disease before the crescents become fibrous.

Oral disodium cromoglycate and ketotifen for a patient with eosinophilic gastroenteritis, food allergy and protein-losing enteropathy.

We present a case report of a 10 years old boy with protein-losing enteropathy and eosinophilic gastroenteritis who had positive histamine release tests, increased allergen-specific IgE antibodies to some food items, and low levels of total serum protein and albumin. Upper gastrointestinal endoscopy revealed a number of polyps and diffuse gastritis. Biopsy specimens of the stomach and duodenum showed widespread eosinophilia and neutrophilia. Although a restricted diet was recommended, a diet which excluded foods with positive results to both histamine release test and allergen-specific IgE antibodies was poorly tolerated, and the patient rejected systemic administration of corticosteroids. Thus, we initiated an oral disodium cromoglycate (DSCG) and ketotifen therapy. After oral DSCG and ketotifen administration, the patient's condition improved gradually. Therefore, oral DSCG and ketotifen therapy might be considered as treatment option in patients with eosinophilic gastroenteritis and protein-losing enteropathy caused by food allergy.

Prediction of relapse by plasma lipoprotein(a) concentration in children with steroid-sensitive nephrotic syndrome.

AIM: To clarify whether plasma lipoproteins, including Lp(a), can predict relapse pattern in the first years after diagnosis of nephrotic syndrome (NS), we evaluated them in patients with steroid-sensitive NS. METHODS: We analyzed the medical records of 35 patients with steroid-sensitive NS who were seen by us from January 1992 to December 1999 followed for at least 1 year. These patients were divided into two groups. Group 1 consisted of 20 patients who infrequently relapse (IR: <2 in 6 months or <3 in a year), group 2 consisted of 15 patients who frequently relapse (FR: > or =2 in 6 months or > or =3 in a year). Clinical and laboratory findings such as age at onset, gender, urinalysis, serum level of total protein, albumin, and concentrations of serum lipid including lipoprotein(a) (Lp(a)) were investigated between group 1 and group 2. RESULTS: The concentration of plasma Lp(a) in group 2 was higher than that in group 1 (81.0 +/- 35.2 vs. 35.9 +/- 26.5 mg/dl, p < 0.01). On multivariate analysis using logistic regression model, the concentration of plasma Lp(a) was an independent risk factor for relapse of NS. CONCLUSIONS: Our findings suggest that of all the laboratory data examined, high values of Lp(a) can predict future relapse of NS and should be well documented.