Covid-19 and adolescent acute kidney injury: Renal recovery with combined enalapril and estrogen therapy

Covid-19 in adolescence with multisystem inflammatory injury (MIS-C) is a newly described condition sharing key features with Kawasaki disease and toxic shock syndrome. A May 2020 United Nations WHO brief covering findings from North America and Europe drew notice to this acute post-viral illness characterized by severe, diffuse hyperinflammation leading to multiorgan failure. While females diagnosed with Covid-19 generally have more favorable outcomes than males, this protection is negated by a low estrogen state. This case reports on acute kidney injury/MIS-C with amenorrhea from ovarian insufficiency in childhood, itself an uncommon presentation of idiopathic hypogonadism. Three exon variants were previously identified in a healthy, phenotypically normal 46,XX adolescent who subsequently underwent whole genome sequencing (WGS). She had only two spontaneous menses with a provisional diagnosis of premature ovarian insufficiency made by age 15. Against this background, Covid-19 infection necessitated hospital admission where progressively reduced renal function was a prime component of MIS-C. Combined angiotensin-converting enzyme inhibitor plus transdermal estrogen replacement therapy resulted in normalized estimated glomerular filtration rate (eGFR) from baseline 43 to 68 ml/min/1.73 m2, post-treatment. Serum cystatin-C also improved during this interval from 1.69 to 1.19 mg/L. Among 7 Covid-19 high risk intron variants identified was rs3131294 (6p21), near NOTCH4. Another finding at rs8068318 (17q23) was associated with creatine level and eGFR. This is the first work to explore Covid-19 and associated kidney injury as a component of MIS-C at the intersection of rare multigene variants and functional ovarian loss. The context of transition from adolescence to adulthood is also considered, where successful recovery of renal function was achieved with combined enalapril and supplemental estrogen.