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Introduction Idiopathic nephrotic syndrome is the most common kidney disease in children. In these cases, empiric treatment with high-dose steroids is the current standard of care [1]. While the relatively [...], Background Empiric steroid therapy is the first-line therapy for pediatric nephrotic syndrome, but treatment response is variable. There are few predictors of steroid-responsiveness, although evidence for genetic factors does exist. Single nucleotide polymorphisms (SNPs) have been recently identified in the promoter region of glucocorticoid-induced transcript 1 gene (GLCCI1) which affect steroid-responsiveness in asthmatic patients. Independently, GLCCI1 was identified as a podocyte protein, the loss of which disrupts the function of the glomerular filtration barrier. We therefore examined whether SNPs associated with the steroid-responsive expression of GLCCI1 might predict steroid-responsiveness in nephrotic syndrome. Case-Diagnosis/Treatment A cohort of 211 pediatric patients with nephrotic syndrome and 102 controls were genotyped; among the cases, 117 were initial steroid responders, while 94 did not respond to oral steroids. No statistically significant differences were noted among the groups, although there was a trend based on the comparison of the small subgroups of steroid-responsive and non-responsive patients with biopsy-proven minimal change disease. Conclusions While larger cohorts are needed to ascertain the possibility of a small effect of GLCCI1 SNPs on the steroid-responsiveness of nephrotic syndrome, the GLCCI1 SNPs associated with steroid-responsiveness in asthmatic patients are unlikely to have a clinically actionable impact in pediatric nephrotic syndrome.

Introduction Nephrotic syndrome (NS), caused by massive proteinuria, leading to hypoalbuminemia and edema, seems to be the most common glomerular pathological condition in childhood [1]. Most children who have an [...], Background Recently, a number of reports have highlighted changes in the histopathology and response to corticosteroid treatment in childhood nephrotic syndrome; however, these involved ethnically mixed populations. For comparison, the purpose of our research was to search for changes in the characteristics of nephrotic syndrome in a homogeneous population of Caucasian children over two consecutive decades. Methods Chart analysis was performed to identify children with new-onset nephrotic syndrome. The children were admitted to the Division of Pediatric Nephrology, Zabrze, during two periods: 1986-1995 (76 patients) and 19962005 (102 patients). Specifically, a comparison of clinical characteristics and morphology of nephrotic syndrome between the two groups was performed. Steroid resistance was defined as no remission within 8 weeks of corticosteroid treatment. Histopathology was available in 36.8% and 43.1% of patients respectively. Results There was a significant increase in primary steroid resistance in the latter decade: 15.8% vs 31.4% (P = 0.017). Changes in the histopathology did not reach the level of statistical significance: minimal change nephrotic syndrome 25% vs 9% (P = 0.095), mesangial proliferative glomerulonephritis 46.4% vs 61.3% (P = 0.21), focal segmental glomerulosclerosis 17.9% vs 20.4% (P = 0.78), membranoproliferative glomerulonephritis 7.1% vs 6.8% (P = 1.0), membranous glomerulonephritis 3.6% vs 0% (P = 0.39). Conclusions Our results show the increasing incidence of primary steroid resistance in childhood nephrotic syndrome. Keywords Childhood nephrotic syndrome * Steroid resistance * Steroid sensitivity. Minimal change nephrotic syndrome * Focal segmental glomerulosclerosis

Introduction Although the efficacy of cyclosporine (CsA) in reducing steroid dosages and the relapse rate in children with frequently relapsing/steroid-dependent minimal change nephrotic syndrome (MCNS) is well established [1], one [...], Background Although once-daily cyclosporine (CsA) therapy may have greater nephrotoxic-sparing effects than standard twice-daily therapy, little information is available in children with steroid-dependent minimal change nephrotic syndrome (MCNS) regarding histological analysis after long-term once-daily administration. Case-Diagnosis/Treatment A prospective study of the clinical efficacy and comparison between pre- and post-treatment renal biopsy findings in ten children (mean age, 8.8 years) with steroid-dependent MCNS who were administered once-daily CsA therapy for more than 24 months (mean [+ or -] SD, 30 [+ or -] 3.7) was performed in Saitama Children's Medical Center. Administration of once-daily CsA therapy (mean dose, 2.8 [+ or -] 0.6 mg/kg/day; mean C2 levels, 670 [+ or -] 64 ng/ml) resulted in a significant reduction in the median relapse rate from 4.6 to 0.2 times per year, and five patients did not experience a relapse of NS. Furthermore, mean threshold of prednisolone dose significantly reduced from 1.2 to 0.02 mg/kg on alternate days. However, two patients showed evidence of chronic CsA nephrotoxicity (CsAN). Conclusions Once-daily CsA therapy appears to be effective in children with steroid-dependent MCNS. However, follow-up renal biopsies should be performed to investigate the presence of CsAN after more than 24 months of treatment with once-daily regimen as well as with the conventional twice-daily regimen. Keywords Once-daily cyclosporine therapy. Chronic cyclosporine nephrotoxicity. Minimal change nephrotic syndrome

Introduction Most pediatric patients with idiopathic nephrotic syndrome (INS) respond to steroids, but approximately 60% present long-term steroid dependency [1]. Prolonged and repeated use of high-dose steroids results in serious [...], Mycophenolate mofetil (MMF) has emerged as a new therapeutic option in steroid-dependent nephrotic syndrome (SDNS). We conducted a phase II Bayesian trial of MMF in children with SDNS. Phase II trials, usually single-arm studies, investigate the effect of new treatments. Standard Fleming&apos;s procedure relies on observed results (relapse rate during the trial), whereas Bayesian approach combines observed results with prior information (expected relapse rate according to prior studies and clinical experience). All patients were required to have received prior alkylating-agent treatment. Sixty-seven percent of them had also received levamisole. Patients received MMF (1,200 mg/[m.sup.2]/day) and prednisone according to a defined schedule [reduction of alternate-day (e.o.d) dose to 50% of pre-MMF dose at 3 months, 25% at 6 months]. Twenty-four children (median age 6.0 years, 2.8-14.4) entered the study and 23 completed it. Bayesian analysis showed that adding four patients would not change significance of results, allowing stopping inclusions. Four patients relapsed during the first 6 months (estimated probability 17.6%, 95% credibility interval: 5.4-35.0%) and two at months 8 and 11.5. In the 19 patients free of relapse during the first 6 months, median (Q1-Q3) prednisone maintenance dose decreased from 25 (10-44) to 9 (7.5-11.2) mg/[m.sup.2] e.o.d (p < 0.001) and cumulative dose from 459 (382-689) to 264 (196-306) mg/[m.sup.2]/month (p < 0.001) before and on MMF respectively. Pre-MMF patient characteristics and MMF pharmacokinetics did not differ between patients with or without relapse. MMF reduces relapse rate and steroid dose in children with SDNS and should be proposed before cyclosporine and cyclophosphamide. Keywords Idiopathic nephrotic syndrome * Steroid-dependent nephrotic syndrome * Mycophenolate mofetil * Mycophenolic acid pharmacokinetics * Bayesian trial

Introduction Two treatment regimens for the initial treatment of nephrotic syndrome (NS) are commonly used. The International Study of Kidney Disease in Children (ISKDC) has recommended a standard initial prednisone [...], Although prednisone is the treatment of choice for nephrotic syndrome (NS) in childhood, the dosing regimen varies between 60 mg/[m.sup.2]/day, as recommended in early studies, to the often prescribed 2 mg/kg/day dose, which is used in common practice. Mathematical models have demonstrated that weight-based dosing can be less than body surface area (BSA)-based dosing in smaller children. To test our hypothesis that weight-based dosing would result in altered treatment outcomes in children with NS, we analyzed a cohort of 56 children (mean age 5.4[+ or -] 3.8 years) treated with a weight-based dosing regimen. Theoretical underdosing of corticosteroids was tested by calculating a relative underdosing percentage (RUP), which was defined as the dose difference between the theoretical BSA-based dose and the actual weight-based doses divided by the BSA-based dose x 100. We found that the mean "actual" prednisone dose in our patients was 43.6[+ or -] 19.3 mg/day; in contrast, the mean theoretical BSA-based dose was calculated to be 48.8[+ or -] 16.7 mg/day. Among the 56 patients, 43 (76.7%) were initial responders, of whom 58% followed a frequently relapsing (FR) course. RUP was significantly higher in FR (16.6[+ or -]7.9%) than in infrequent relapsers (8.7[+ or -]9.8%) (P=0.03). RUP was not significantly different among initial responders and non-responders. Based on these results, we conclude that prednisone underdosing, when dosing is prescribed according to weight, does not affect the initial response to treatment, but it does increase the likelihood of a FR course in responders. Keywords Nephrotic syndrome * Prednisone * Weight * Body-surface area

Introduction Idiopathic nephrotic syndrome (INS) in children is characterized by high sensitivity to steroids and about 77% had minimal change disease (MCD) [1]. Approximately 80% of children with steroid-sensitive NS [...], Cyclophosphamide (CP) has been used for over 40 years in patients with steroid-sensitive nephrotic syndrome (SSNS) presenting frequent relapses or steroid dependence (SD). We evaluated retrospectively and tried to identify parameters possibly associated with a prolonged and sustained remission (PSR+) [greater than or equal to] 5 years in 108 children with steroid-dependent nephrotic syndrome (SDNS) treated with oral CP. Patients had a follow-up time [greater than or equal to] 5 years and were divided into two groups according to achievement of PSR (+ and -). Gender, histological injury, cumulative doses of CP, age of onset of illness, and start of treatment and prednisone dose on the occasion of relapse were analyzed. The overall cumulative sustained remission for 5 and 10 years was 25 and 21.6%, respectively. The only factor that influenced a PSR was the degree of SD: the group PSR+ relapsed at prednisone dose of 0.96 [+ or -] 0.51 mg/kg vs. 1.2 9[+ or -] 0.59 mg/kg in group PSR- (p=0.01). Also, patients who relapsed in the presence of prednisone doses [less than or equal to] 1.4 mg/kg showed a cumulative sustained remission of 43, 35, and 32.7% at 2, 5, and 10 years, respectively, versus 22.5, 12.5, and 5% in those with prednisone >1.4 mg/kg (p=0.001). Our findings suggest that patients with SDNS who relapse on prednisone dose >1.4 mg/kg are especially prone to an unfavorable response to CP use. Keywords: Nephrotic syndrome. Cyclophosphamide. Immunosuppressive agent. Therapy. Child. Adolescent

Introduction Hypokalemia is one of the most common pathological states observed during the perioperative period. However, moderate and severe hypokalemia with persistent hypertension may be a consequence of more serious [...], Both severe hypokalemia and persistent hypertension are clinical symptoms of hyperaldosteronism. Hyperaldosteronism may occur as a primary or secondary syndrome. Excess ACTH produced ectopically by tumors may induce hyperaldosteronism through the mineralocorticoid activity of glucocorticoids that are upregulated by ACTH. Licorice, with the active ingredient glycyrrhiza, is also a well-known inducer of hyperaldosteronism under specific conditions. In this report, we describe a case of severe hypokalemia caused by ectopic ACTH syndrome (EAS) elicited by an intrathoracic carcinoid tumor, which had transformed to produce ACTH during the 6-year clinical course, and was modulated by licorice ingestion. Hypokalemia was not clearly recognized preoperatively but became obvious within 3 h of general anesthesia with epidural blockade. At the end of anesthesia, arterial blood gas analysis indicated severe hypokalemia ([[K.sup.+]] = 1.7 mEq/l) and metabolic alkalosis (pH 7.56, PaC[O.sub.2] = 54.9 mmHg, HC[O.sub.3.sup.-] = 44.5 mmol/l, BE = 21.8 mmol/l), without any typical symptoms such as muscle weakness or ECG abnormalities. The hypokalemia was resistant to potassium supplementation and persisted for 4 days. Perioperative imbalance between the administration and elimination of potassium and surgical stress might contribute to the rapid exacerbation and induce the clinical manifestation of EAS. Keywords Hypokalemia * Ectopic ACTH syndrome * Cushing's syndrome * Licorice * Perioperative period

Introduction Recent studies have established that the majority of young adults with a history of childhood-onset end-stage renal disease (ESRD) suffered significant cardiovascular morbidity and mortality. The risks of coronary [...], Obesity and hypertension frequently complicate renal transplantation (RTxp). The objective was to assess relations among obesity, hypertension, and glucocorticoids in pediatric RTxp recipients. A retrospective cohort study was carried out in 141 RTxp recipients, 2-21 years of age, with ≥ 12 months of follow-up. Body mass index Z-score (BMI-Z), systolic and diastolic blood pressure Z-scores (SBP-Z and DBP-Z), and medications at 1, 3, 6, and 12 months and annually thereafter were recorded. Quasi-least squares regression analysis was used. The prevalence of obesity (BMI >95th percentile) increased from 13% at baseline to >30% from 3 months onward. Greater glucocorticoid exposure (mg/kg/day) was associated with greater increases in BMI-Z (p Keywords Obesity * Hypertension * Renal transplant * Children * Glucocorticoid

Introduction Genetic disorders are responsible for the majority of cases of congenital nephrotic syndrome [1]. Mutations in NPHS2 and NPHS1 are the most common causes of hereditary nephrotic syndrome, accounting [...], Although there are clinical data suggesting a direct relationship between neonatal nephrotic syndrome and placental transfer of proinflammatory cytokines from mothers with HELLP syndrome, there is no direct evidence that these inflammatory cytokines are pathogenic. Here, the first human model of placental transfer of proinflammatory cytokines from a mother with HELLP syndrome to a newborn, resulting in neonatal nephrotic syndrome is described. Forty-eight hours after delivery, the neonate developed nephrotic syndrome and abnormalities in renal function which resolved completely during the 5 days following the initiation of therapy with hydrocortisone, albumin, and furosemide. The newborn&apos;s cord blood showed increased concentrations of interleukin (IL)-1|3, IL-6, and tumor necrosis factor alpha that were identical to those found in the mother&apos;s serum. Hydrocortisone therapy was discontinued after a 2-week course. Clinical and laboratory improvements were associated with a marked decline in serum cytokine levels, indicating that the proinflammatory cytokines were pathogenic. The neonate remained in remission with no recurrence of nephrotic syndrome during 12 months of follow-up. These findings demonstrate that the placental transmission of circulating cytokines causing HELLP syndrome occurred during pregnancy and may have resulted in nephrotic syndrome in the neonate. Keywords Newborn * Nephrotic syndrome * HELLP syndrome * Placenta transmission of cytokines