Nephrotic Syndrome (NS) is one of the most frequent glomerular diseases seen in children. Children who go into complete remissin following treatment with corticosteroids are classified as having “steroid sensitive” NS. In developed countries over 80% of children with idiopathic NS have steroid sensitive disease although response to steroids is somewhat tempered in developing countries, especially in black children, the majority of whom have steroid resistant disease. The exact pathogenesis of this condition remains elusive. Podocyte injury and proteinuria are the two main issues in the pathogenesis. Recent studies suggest alterations in both innate and adaptive immune responses. There is release of cytokines by T-cells as well as a strong contribution of B-cell immunity. Genetic studies have reported human leucocyte antigen (HLA) class II antigens DR and DQ associations linked to steroid sensitive NS and in small case studies, single gene mutations e.g. PLCE1 although to date no homozygous mutations in NPHS1 or NPHS2 and WT-1 genes have been reported. Most children with steroid sensitive NS have multiple relapses and a significant percentage also develop steroid dependent NS. These children receive multiples courses of steroids and are at high risk of developing steroid toxicity. Patient with frequent relapses who develop steroid dependency thus require alternative treatment. Steroids sparing agents used include levamisole, cyclophosphamide, mycophenolate mofetil (MMF), calcineurin inhibitors (cyclosporine and tacrolimus), rituximab and vincristine. The steroid-sparing effects of these agents have greatly reduced the adverse effects seen with long-term use of steroids. Despite the wide arsenal of agents available, therapy needs to be individualised to achieve optimal care of each child. More randomised controlled trials are required to evaluate the therapeutic and economic efficacy of this agent, define criteria for selection of patients for use of particular agents and to determine the safety profile of these drugs in children. This article reviews the epidemiology, pathogenesis, clinical presentation, diagnosis, complications, management and long term outcome of children with steroid sensitive NS.

Objective: Urinary excretion of interleukin-6 (U-IL6) has been reported to be elevated and to represent the disease activity in adult IgA nephropathy (IgAN). We investigated the significance and the utility of U-IL6 activity in pediatric IgAN patients. Methods: We evaluated 55 pediatric IgAN patients (4–18 years; mean age, 10.7 years) and 53 healthy controls from 2007 to 2012. The U-IL6 concentrations (pg/mg creatinine) were estimated by ELISA at the time of renal biopsy and after 6 months of prednisolone therapy for IgAN. In addition, we evaluated the correlations between the U-IL6 level and clinic pathological parameters of IgAN. To elucidate the usefulness for early diagnosis of IgAN, we investigated U-IL6 in 45 asymptomatic hematuria (ASH) children who were diagnosed by school urine screening program. Results: U-IL6 activity was significantly higher in IgAN patients than in healthy controls and ASH children (p<0.01). In addition, U-IL6 was significantly decreased after 6 months of prednisolone therapy (p<0.01). With regard to the clinicopathological parameters, U-IL6 activity was correlated with degree of proteinuria (p<0.01, r=0.72), hematuria (p<0.01, r=0.54), urinary podocyte score (p<0.01, r=0.59), mesangial cell proliferation (p<0.05), endocapillary proliferation (p<0.01), and crescent formation (p<0.05). Interestingly, five children who transited to IgAN from ASH during the observation period showed high U-IL6 levels (p<0.01). Conclusions: The present results also suggest that U-IL6 represents the disease activity in pediatric IgAN patients. We consider that it is important to evaluate U-IL6 in patients with ASH detected by school urinary screening program for early detection and prevention of unrecognized progression of IgAN.

Hypercoagulability is a common complication in children with nephrotic syndrome and may cause venous thrombosis. This study explored the effectiveness of urokinase and low-molecular-weight (LMW) heparin used in conjunction in seven children with nephrotic syndrome complicated by intracranial venous thrombosis. The urokinase dose was 2,000-4,000 u/kg/day initially, with a pulse dose of 20,000-40,000 u given within 15-30 minutes and the remainder was pump-infused. From day 2, a dose of 2,000 u/kg/day was infused via the pump, and the total course duration was 3 to 7 days. During treatment, thrombin time (TT) and activated partial thromboplastin time (APTT) were tested three times per week, and particular attention was given to any bleeding. LMW heparin was used at a dosage of 100-120 anti-Xa IU/kg once or twice per day, given by abdominal subcutaneous injection for two weeks. The antiplatelet drug, dipyridamole 3-5 mg/kg, was also given orally two or three times per day for three months. In this study, the early use of urokinase, LMW heparin and anti-platelet drugs had good effect, the need for preventive therapy and early diagnosis of this complication in nephrotic syndrome should be given wider clinical consideration.

The etiology of kidney stones is divided in three broad categories: (i) Metabolic abnormalities that lead to excessive urinary excretion of solutes those are susceptible to crystallization or reduced excretion of inhibitors of crystallization (ii) Anatomic defects that cause disturbances in voiding or urinary stasis (iii) Idiopathic. The laboratory assessment has focused on 24-hour urine collections to measure excretion of calcium, oxalate, citrate, cystine, uric acid, magnesium, and creatinine, selective blood tests, and imaging studies to determine renal structure and function. This article reviews recent data suggesting that the incidence of kidney stones is rising in children and adolescents.

Background: Hemolytic uremic syndrome (HUS) is one of the major causes of renal failure in children. In most cases the disease is caused by infection with Shiga toxin- producing Escherichia coli (STEC) and preceded by diarrhea. Only in 15% of cases STEC infection leads to HUS. Genetic predisposition of a patient to develop HUS after STEC infection might play a role, but very few reports on this subject are available. We describe a novel missense mutation in the GP1BA gene encoding platelet-receptor glycoprotein Ibα (GPIbα) in a severely affected HUS patient.
Methods: GP1BA was screened by Sanger sequencing. Binding of recombinant GPIbα and von Willebrand factor (VWF) fragments was analyzed using surface plasmon resonance (SPR). The hematological studies using patient blood were performed.
Results: The detected heterozygous mutation p.Pro46Leu is located in the proximity to one of the two GPIbα-VWF binding sites. SPR experiments show that the p.Pro46Leu leads to a small increase in GPIbα-VWF binding (p<0.001). The hemostatic parameters of patient blood after recovery from HUS show normal values.
Conclusions: The described mutation affects GPIbα interaction with VWF in a mild gain-of-function manner and might have contributed to a prothrombotic state in the patient and to development of HUS.

Malignant hypertension is able to induce glomerular Thrombotic Microangiopathy (TMA) and Hemolytic Uremic Syndrome (HUS) in the absence of Glomerulonephritis (GN). It is therefore commonly admitted that hypertension is the only cause of Glomerular Endothelial Cells (GEC) damage leading to TMA and HUS observed in GN. However, recent literature on TMA in IgA nephropathy calls this hypothesis into question. It is also questionable why so few cases of HUS are reported in association with Post-Infectious GN (PIGN) for which more than 50% of cases necessitate anti-hypertension treatment, we report the case of a 10 years old girl presenting with an extensive cutaneous streptococcal infection, hematuria, nephrotic syndrome, hypertension (146/106) and HUS needing dialysis. The kidney biopsy revealed a severe exudative GN, 30% of crescentic glomeruli and TMA. Immunofluorescence and electron microscopy suggested intense complement activation at the basal level of GEC and podocytes. Genotyping of complement factors was normal. A rapid recovery of a normal renal function was observed after intensive Plasma Exchange (PE) therapy. We speculate that a high amount of group A streptococcal (GAS) toxins produced in extensive cutaneous lesions might have facilitated TMA initiation by: 1/ a direct damage of endothelial cells; 2/ an intense complement activation induced by the binding of GAS toxins to the complement factor H (CFH), leading to GEC and podocytes’ lesions. The favorable effect of PE can be explained by removal of GAS toxins and inactivated CFH on one side and by supply of free CFH on another side. Multicentre studies should be initiated in order to evaluate the frequency and the pathophysiology of TMA and HUS in PIGN.

Jaundice is a frequently encountered problem in the neonatal period. It may be associated with hemolytic, enzymatic, metabolic, endocrine disorders or infections. Recently it has been thought to be one of the clinical signs of urinary tract infections (UTIs) in the neonatal period. Although they are concurrently observed, the association between neonatal jaundice and UTI is still unidentified. Common belief is that the bilirubin levels rise as a result of UTIs and jaundice may be considered as an important clinical sign in that period. However, there is no strong recommendation for screening UTI in all neonates with jaundice. It is only recommended to screen for UTI in neonates with prolonged hyperbilirubinemia and direct bilirubinemia. On the other hand, there are conflicting data on the protective effects of bilirubin on renal tissue. In this review, all those questionable topics were discussed in the light of clinical and experimental studies.