BackgroundSteroid-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. Previously conducted GWAS of SSNS have not identified non-HLA loci achieving genome-wide significance.MethodsIn an attempt to identify additional loci associated with SSNS, we conducted a GWAS of a large cohort of European ancestry comprising 422 ethnically homogeneous pediatric patients and 5642 ethnically matched controls.ResultsThe GWAS found three loci that achieved genome-wide significance, which explain approximately 14% of the genetic risk for SSNS. It confirmed the previously reported association with the HLA-DR/DQ region (lead single-nucleotide polymorphism [SNP] rs9273542, P=1.59×10−43; odds ratio [OR], 3.39; 95% confidence interval [95% CI], 2.86 to 4.03) and identified two additional loci outside the HLA region on chromosomes 4q13.3 and 6q22.1. The latter contains the calcium homeostasis modulator family member 6 gene CALHM6 (previously called FAM26F). CALHM6 is implicated in immune response modulation; the lead SNP (rs2637678, P=1.27×10−17; OR, 0.51; 95% CI, 0.44 to 0.60) exhibits strong expression quantitative trait loci effects, the risk allele being associated with lower lymphocytic expression of CALHM6.ConclusionsBecause CALHM6 is implicated in regulating the immune response to infection, this may provide an explanation for the typical triggering of SSNS onset by infections. Our results suggest that a genetically conferred risk of immune dysregulation may be a key component in the pathogenesis of SSNS.

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There are fewer acute rejection episodes following CLKT compared to isolated KT, and we noted a higher mean e-GFR at 1, 5, and 10 years with significantly lesser decline in e-GFR from 5 to 10 years in the CLKT group.

Background Distal (Type 1) renal tubular acidosis (dRTA) is characterized by inability to secrete hydrogen irons from the distal tubule. The aetiology of dRTA is diverse and can be either inherited or acquired. Common clinical presentations of dRTA in the paediatric age group include polyuria, nocturia, failure to thrive, constipation, abnormal breathing and nephrolithiasis. Though persistent hypokalemia is frequently seen in dRTA, hypokalemic muscular paralysis is uncommon and rarely described in children. Case presentation Three and a half years old girl was referred for evaluation of progressive loss of gross motor milestones over 6 months and acute episode of paralysis. Her other developmental domains were age appropriate. Notably, there was no history of polyuria, polydipsia, nocturia and abnormal breathing. Physical examination revealed proximal myopathy (waddling gait and positive Gower’s sign), diminished lower limb reflexes and muscle tone. Her serum potassium was low (2.1 meq/l) and she was subsequently investigated for hypokalemic paralysis. Diagnosis of distal renal tubular acidosis was made, based on hypokalemic hyperchloremic metabolic acidosis with normal anion gap, high urine pH, borderline hypercalciuria, medullary nephrocalcinosis and exclusion of other differential diagnosis. The child showed complete symptomatic recovery upon commencement of standard treatment for distal renal tubular acidosis. Conclusions This case report highlights the importance of considering hypokalemia and renal tubular acidosis in the differential diagnosis of acute flaccid paralysis and proximal myopathy. Early diagnosis will prevent costly investigations and enable rapid clinical recovery in the affected child.

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