Aphasia Associated With Acute on Chronic Kidney Failure in an Adolescent.

Acute and chronic kidney disease (CKD) have known neurological associations resulting from uremia, electrolyte disturbances, comorbidities such as hypertension, or other toxin accumulation. Reversible focal neurological deficits are relatively uncommon and poorly understood sequelae of kidney disease. Herein, we describe an unusual case of an adolescent male who developed acute aphasia during his initial presentation for acute kidney injury (AKI) superimposed on progressive CKD stage 5 associated with uremia and multiple electrolyte derangements. Symptoms resolved within one day of initiating continuous renal replacement therapy (CRRT) and gradual electrolyte and uremia correction. Such transient focal neurological deficits in AKI superimposed on progressive CKD in the pediatric population has not been widely reported.

Genetic risk variants for childhood nephrotic syndrome and corticosteroid response.

Introduction: The etiology of most cases of nephrotic syndrome (NS) remains unknown, therefore patients are phenotypically categorized based on response to corticosteroid therapy as steroid sensitive NS (SSNS), or steroid resistant NS (SRNS). Genetic risk factors have been identified for SSNS from unbiased genome-wide association studies (GWAS), however it is unclear if these loci are disease risk loci in other forms of NS such as SRNS. Additionally, it remains unknown if these risk loci are associated with response to therapy. Thus, we investigated the association between SSNS risk loci and therapy response in a large, multi-race cohort of children along the entire spectrum of childhood-onset NS. Methods: We enrolled 1,000 patients with childhood-onset NS comprised of SSNS and SRNS. Genotyping was done using TaqMan and Direct Sanger Sequencing for 9 previously reported childhood SSNS risk loci. We compared the allele frequencies (AF) and variant burden between NS vs. controls and SRNS vs. SSNS. Results: All 9 risk loci were associated with NS compared with healthy controls (p = 3.5 × 10-3-<2.2 × 10-16). Variant burden greater than 7 was associated with risk of SRNS (OR 7.4, 95% CI 4.6-12.0, p = 8.2 × 10-16). Conclusion: Our study showed that genetic risk loci for childhood SSNS are associated with pattern of therapy response, may help predict disease outcome, and set the stage for individualized treatment of NS.

Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in NUP93 Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene Mutations.

Background: Focal segmental glomerulosclerosis (FSGS) is a major cause of end stage kidney disease, with the collapsing form having the worst prognosis. Study of families with hereditary FSGS has provided insight into disease mechanisms. Methods: In this report, we describe a sibling pair with NUP93 mutations and collapsing FSGS (cFSGS). For each brother, we performed next generation sequencing and segregation analysis by direct sequencing. To determine if the variants found in the index family are a common cause of cFSGS, we screened 7 patients with cFSGS, gleaned from our cohort of 200 patients with FSGS, for variants in NUP93 as well as for APOL1 high-risk genotypes. Results: We identified segregating compound heterozygous NUP93 variants (1) c.1772G > T p.G591V, 2) c.2084T > C p.L695S) in the two brothers. We did not find any pathogenic variants in the seven patients with cFSGS from our cohort, and as expected five of these seven patients carried the APOL1 high-risk genotype. Conclusion: To the best of our knowledge, this is the first report of cFSGS in patients with NUP93 mutations, based on this report, mutations in NUP93 and other nucleoporin genes should be considered when evaluating a child with familial cFSGS. Determining the mechanisms by which these variants cause cFSGS may provide insight into the pathogenesis of the more common primary and virus-mediated forms of cFSGS.

Atypical recurrent Kawasaki disease with retropharyngeal involvement: A case study and literature review.

Kawasaki disease (KD) is a systemic inflammatory condition primarily affecting young children. We present an adolescent male with two episodes of complete KD between the age of 2 and 14 years. At age 14, he presented with findings suggestive of a retropharyngeal abscess. This was later determined to be a recurrence of KD, diagnosed after the development of coronary artery aneurysms. Our case reinforces the role of maintaining a high index of suspicion for KD, both in patients with prior KD episodes and in those with persistent fever who do not fulfill the diagnostic criteria for typical KD. This is particularly important for patients presenting with atypical symptoms not commonly associated with KD, such as inflammation of the retropharyngeal and parapharyngeal spaces.