Common Risk Variants in AHI1 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 HLA-DQ/DR and have identified several non-HLA 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. Methods: We conducted a GWAS in a cohort of Sri Lankan individuals comprising 420 pediatric patients with SSNS and 2339 genetic ancestry matched controls obtained from the UK Biobank. We then performed a transethnic meta-analysis with a previously reported European cohort of 422 pediatric patients and 5642 controls. Results: Our GWAS confirmed the previously reported association of SSNS with HLA-DR/DQ (rs9271602, P = 1.12 × 10−27, odds ratio [OR] = 2.75). Transethnic meta-analysis replicated these findings and identified a novel association at AHI1 (rs2746432, P = 2.79 × 10−8, OR = 1.37), which was also replicated in an independent South Asian cohort. AHI1 is implicated in ciliary protein transport and immune dysregulation, with rare variation in this gene contributing to Joubert syndrome type 3. Conclusions: Common variation in AHI1 confers risk of the development of SSNS in both Sri Lankan and European populations. The association with common variation in AHI1 further supports the role of immune dysregulation in the pathogenesis of SSNS and demonstrates that variation across the allele frequency spectrum in a gene can contribute to disparate monogenic and polygenic diseases

Antibiotic sensitivity patterns in childhood urinary tract infections

Objectives To assess the current antibiotic sensitivity pattern of urinary pathogens and compare it with the pattern 5 years previously. Method A retrospective analysis was performed on 2650 urine samples in 1997 and 2062 samples in 2002 received by the medical laboratory at the Teaching Hospital, Peradeniya from the paediatric ward and paediatric clinics. Results In 1997 there were 155 urine culture reports with significant colony counts of>10 5 for which ABSTs were performed. 111 were from males and 44 from females. In 2002 there were 278 positive cultures of which 179 were from males and 99 from females. Predominant organism was the coliform, accounting for 90 % of isolates in both 1997 and 2002. In 1997 nalidixic acid and nitrofurantoin had high sensitivities of 73.8 % and 73.1 % respectively, while ciprofloxacin and mecillinam had low sensitivities of 51.9 % and 35.5%. In 2002 coamoxiclav had the highest antibiotic sensitivity of 86.7%, while nitrofurantoin, nalidixic acid and norfloxacin had high sensitivities of 80%, 76.6 % and 75.7 % respectively. Ciprofloxacin and mecillinam had low sensitivity levels both in 1997 and 2002. A change was seen in cotrimoxazole and cephalexin, which had low sensitivities of 40.2 % and 54.8 % in 1997 and relatively higher sensitivities of 63.8 % and 69.2 % in 2002 respectively