Active clinical trials for "Nephrotic Syndrome"

The purpose of this study is to describe the hormones controlling fluid balance in pediatric patients with nephrotic syndrome. Further more, an analysis of the urinary and plasma proteins will be done using proteomics. Different composition of proteins in the urine or plasma might indicate if the patients will respond to treatment or not.

Nephrotic syndrome (NS) is among the most common pediatric kidney diseases and is defined as massive proteinuria (>40 mg/m2/h or urine protein to creatinine ratio >2 g/g) leading to hypoalbuminemia (<2.5 g/dL), edema, and hyperlipidemia. 60-70 % of patients present prior to age of 6 years

Patients with proteinuria to start treatment with Acthar and watch a variety of clinical parameters with a goal of decreasing proteinuria between 50-100% over a period of nine months with every 3 months increasing the dose of medication until a decrease of either 50- 100 % of protein excretion is achieved. In addition addition podocyte function will be assessed monthly by measuring suPar levels, tnf alpha, podocyte/creatinine levels as well as podocyte function studies.

Nephrotic syndrome (NS) represents one of the most common diagnoses in pediatric and adult nephrology, with a prevalence of 16 per 100,000 children and 3 per 100,000 adults in Western countries. In most cases, the pathogenesis of NS remains elusive, and the clinical phenotype of patients does not allow discrimination among different causes. Thus, children with NS are usually treated with corticosteroids before a biopsy is taken, and approximately 80% of them respond to such a treatment. According to this observation, pediatric NS has been separated into two broad categories; Steroid-Sensitive Nephrotic Syndrome (SSNS) and Steroid-Resistant Nephrotic Syndrome (SRNS). In both these categories the biopsy result is usually Minimal Change Disease (MCD) while a few may show Focal and Segmental Glomerulosclerosis (FSGS). Although children affected by SSNS have good long-term prognosis, most patients with SRNS progress to End Stage Renal Disease (ESRD) within 2-10 years of diagnosis . In adults a biopsy diagnosis of FSGS is more common than in children and more patients will not respond to corticosteroids alone and will need additional immunosuppressant medication. About 40% will progress to ESRD within 10 years . Currently, at least 19 genes have been clearly identified with association to SRNS harboring ~300 independent mutations, conferring a considerable genetic heterogeneity to the disorder. Genetic testing is emerging as a useful diagnostic tool in SRNS as it has implications for clinical course, treatment response, risk for posttransplant proteinuria and prenatal diagnosis. An approach for genetic testing based on the current evidence seems cost-effective and may help in the best possible management of SRNS . The NPHS2 gene, is located on chromosome 1 and is also known as the Podocin gene. It encodes the podocin protein. Podocin is a 383-amino acid lipid-raft-associated protein localized at the slit diaphragm, where it is required for the structural organization and regulation of the glomerular filtration barrier. Its interaction with other slit diaphragm proteins eg. nephrin, NEPH1, CD2AP and TRPC6 is important in mechanosensation signaling, podocyte survival, cell polarity, and cytoskeletal organization . . It has been reported that variants in the NPHS2 gene are associated with NS . The commonly studied rs61747728 NPHS2 gene polymorphism also known as p.R229Q has been reported to be associated with NS and SRNS . However others have failed to report an association , which might be due to population differences. The rs61747728 is a non-synonymous variant found on exon 5 which is suggested to be involved in in altering the functional properties of podocin in vitro and possibly in vivo . The investigators will therefore investigate the frequency of the p.R229Q variant in Middle East patients with NS. Genetic analysis will have important implications in several aspects:- Understanding the biology of the disease in this part of the world. Counselling patients about their clinical course and what medication they will respond to. Counselling patients about the possibility of a kidney transplant sooner in their disease course

Tacrolimus is recommended to be the first line therapeutic medication within the several immunosuppressive agents when treating refractory pediatric nephrotic syndrome, because of its definite efficacy and low toxicity. But there are still some key problems which hinder the using of tacrolimus in clinic, such as its narrow therapeutic widow, great individual difference of pharmacokinetics. Routine therapeutic drug monitoring(TDM) is needed in practice. But the disadvantage of TDM is hysteresis, which could lead to treatment failure or toxicity. To find out the reasons of great pharmacokinetic difference between patients and find out the individual proper dosage before administration are important for the clinical using of tacrolimus. It is hot in research of tacrolimus in organ transplant field, such as the association between gene polymorphisms of cytochrome P-450 3A4, 3A5 and multiple drug resistant gene(MDR1) and concentration of tacrolimus. However, there is few study about pharmacogenomics and metabonomics of tacrolimus in patients of nephrotic syndrome. The aim is to study the relationships between pharmacogenomics, metabonomics of tacrolimus and its efficacy, toxicity and blood concentration in patients of nephrotic syndrome, to find out the exact dosage before administration, to provide reference to individual drug administration.

Childhood nephrotic syndrome is the most frequent glomerular disease that presents during childhood,primarily owing to a disturbed immune function.This disease is characterized by alterations in selectivity at the glomerular capillary wall that lead to an inability to restrict the urinary loss of protein.

The nephrotic syndrome is a rare disease defined by a proteinuria >3g/24h and a hypoalbuminemia < 30g/L. Genetic and immune are the main causes. The acquired idiopathic nephrotic syndrome presents histologically minimal glomerular lesions, sometimes associated with segmental and focal hyalinosis. The idiopathic nephrotic syndrome (INS) represents 85% of children's glomerular nephropathy and 25-30% of adult's. Relapses are frequents, and can be pejorative up to 10% and lead to end-stage kidney failure. Another immune cause is the extramembranous glomerulonephritis mediated by molecular targets specific autoantibodies expressed at the podocytes surface. Other immune causes include lupus nephropathy, ANCA vascularitis, Goodpasture disease, Berger disease. Easy diagnosis between these causes can be made with the renal biopsy. Miss-1, a new protein activated during a inflammatory event, could be an actor in nephrotic syndromes by modifying the podocyte's adhesion on the glomerular basal membrane. This would modulate the structure and function of the slit diaphragm, as well as junctions between the podocyte and the glomerular basal membrane, regulating podocytes' apoptosis.

This study will use a multi-center, prospective design, with a "Real World Study" model, to include 200 patients with nephrotic syndrome. based on the Population Pharmacokinetics (PPK) model, it will study genotype and clinical factors in patients with nephrotic syndrome, to explore the Pharmacokinetics/ Pharmacodynamics (PK/PD) relationship of Tacrolimus in patients with nephrotic syndrome, and develop an optimal medication regimen.

CHILDNEPH is a pan-Canadian project to observe clinical care for children with nephrotic syndrome. Previous studies have indicated that there is wide practice variation in how health care providers treat this remitting and relapsing disease of childhood. The disease mechanism is not yet understood, and long-term use of steroids can affect children's health. This study involves assessment of routine clinical care and establishing a long-term patient registry for children with nephrotic syndrome.