Common Risk Variants in Are Associated With Childhood Steroid Sensitive Nephrotic Syndrome.

Introduction: Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of kidney disease in children worldwide. Genome-wide association studies (GWAS) have demonstrated the association of SSNS with genetic variation at and have identified several non- loci that aid in further understanding of disease pathophysiology. We sought to identify additional genetic loci associated with SSNS in children of Sri Lankan and European ancestry.

Snake bite associated with acute kidney injury.

Acute kidney injury (AKI) is a well-known life-threatening systemic effect of snake envenomation which commonly happens secondary to snake bites from families of Viperidae and Elapidae. Enzymatic toxins in snake venom result in injuries to all kidney cell types including glomerular, tubulo-interstitial and kidney vasculature. Pathogenesis of kidney injury due to snake envenomation includes ischaemia secondary to decreased kidney blood flow caused by systemic bleeding and vascular leakage, proteolytic degradation of the glomerular basement membrane by snake venom metalloproteinases (SVMPs), deposition of microthrombi in the kidney microvasculature (thrombotic microangiopathy), direct cytotoxic action of venom, systemic myotoxicity (rhabdomyolysis) and accumulation of large amounts of myoglobin in kidney tubules.

Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome.

To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.

Pediatric Continuous Renal Replacement Therapy (PCRRT) expert committee recommendation on prescribing prolonged intermittent renal replacement therapy (PIRRT) in critically ill children.

Introduction: Recently, prolonged intermittent renal replacement therapies (PIRRT) have emerged as cost-effective alternatives to conventional CRRT and their use in the pediatric population has started to become more prominent. However, there is a lack of consensus guidelines on the use of PIRRT in pediatric patients in an intensive care setting.

Methods: A literature search was performed on PubMed/Medline, Embase, and Google Scholar in conjunction with medical librarians from both India and the Cleveland Clinic hospital system to find relevant articles.

Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome.

Background: Steroid-sensitive nephrotic syndrome (SSNS), the most common form of nephrotic syndrome in childhood, is considered an autoimmune disease with an established classic HLA association. However, the precise etiology of the disease is unclear. In other autoimmune diseases, the identification of loci outside the classic HLA region by genome-wide association studies (GWAS) has provided critical insights into disease pathogenesis.

Genetic Testing for Steroid-Resistant-Nephrotic Syndrome in an Outbred Population.

Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children and young adults. Despite advances in genomic science that have led to the discovery of >50 monogenic causes of SRNS, there are no clear guidelines for genetic testing in clinical practice. Using high throughput sequencing, we evaluated 492 individuals from 181 families for mutations in 40 known SRNS genes.

HLA-DQA1 and APOL1 as Risk Loci for Childhood-Onset Steroid-Sensitive and Steroid-Resistant Nephrotic Syndrome.

Background: Few data exist for the genetic variants underlying the risk for steroid-sensitive nephrotic syndrome (SSNS) in children. The objectives of this study were to evaluate HLA-DQA1 and APOL1 variants as risk factors for SSNS in African American children and use classic HLA antigen types and amino acid inference to refine the HLA-DQA1 association.

Study Design: Case-control study.

Pulsed Vincristine Therapy in Steroid-Resistant Nephrotic Syndrome.

Steroid-resistant nephrotic syndrome (SRNS) poses a therapeutic challenge for the paediatric nephrologist. As relentless progression to renal failure occurs with continued proteinuria, such patients will be treated with different cytotoxic medications with variable success rates and side-effects. We present here our findings on administering the anticancer drug vincristine for SRNS patients at a single centre in Sri Lanka.

Short courses of daily prednisolone during upper respiratory tract infections reduce relapse frequency in childhood nephrotic syndrome.

Background: Relapses of childhood nephrotic syndrome (NS) are frequently precipitated by viral upper respiratory tract infections (URTIs). A review of the literature reveals that in patients with steroid-dependent NS on alternate day corticosteroids, a short course of daily corticosteroid therapy during the course of an URTI may reduce relapse frequency.

Objective: To assess the effect of a short course of low-dose corticosteroid therapy during the course of an URTI on relapse frequency in patients with steroid-sensitive NS who have not been taking any treatment for a minimum period of 3 months.

Efficacy of higher-dose levamisole in maintaining remission in steroid-dependant nephrotic syndrome.

Objective: Levamisole (LEV) has been used successfully on an alternate-day regime of 2.5 mg/kg in steroid-dependant nephrotic syndrome (SDNS) to maintain remission. This pilot study was carried out between 2010 and 2015 at a single center in Sri Lanka to evaluate the efficacy of LEV prescribed at 2.

Vaccinations in children on immunosuppressive medications for renal disease.

Renal diseases are often treated with immunosuppressive medications, placing patients at risk of infections, some of which are vaccine-preventable. However, in such patients vaccinations may be delayed or disregarded due to complications of the underlying disease process and challenges in its management. The decision to administer vaccines to immunosuppressed children is a risk-benefit balance as such children may have a qualitatively diminished immunological response or develop diseases caused by the vaccine pathogen.

HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome.

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS.

Adrenocortical suppression increases the risk of relapse in nephrotic syndrome.

Objective: Children with nephrotic syndrome (NS) are usually treated with long-term low dose alternate day prednisolone with or without glucocorticoid sparing therapy, such as levamisole or ciclosporin, to maintain remission. The degree of hypothalamic-pituitary-adrenal axis (HPA) suppression with such therapeutic strategies has not been studied systematically. HPA suppression could cause a relapse or adrenal crisis.

Predictors of long-term outcome of children with idiopathic focal segmental glomerulosclerosis.

Clinical and histological data of children presenting with steroid-resistant nephrotic syndrome and renal biopsy showing focal and segmental glomerulosclerosis from 1980 with a follow-up of over 10 years were reviewed. There were 66 patients; 38 male and 28 female. Age at onset ranged from 0.

The use of steroid-sparing agents in steroid-sensitive nephrotic syndrome.

Childhood nephrotic syndrome (NS) is frequently characterized by a relapsing course. There is no uniform agreement about the precise stage at which a steroid-sparing agent should be introduced to control the disease. In order to evaluate the treatment strategies and outcome of steroid-sensitive NS over the last 2 decades, a retrospective notes review was undertaken in a cohort of children treated at Great Ormond Street Children's Hospital between 1980 and 2000.