Case Report: SARS-CoV-2 Associated Acute Interstitial Nephritis in an Adolescent

Abstract

Acute interstitial nephritis (AIN) has been recently recognized as one of the infrequent kidney involvement phenotypes among adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although SARS-CoV-2 associated intrinsic kidney disease has been scarcely reported in children, only one case of AIN temporally associated with the infection has been described in the pediatric population so far. We presented a case of a 12-year old boy who presented with fatigue, anorexia, and polydipsia following an RT-PCR that confirmed SARS-CoV-2 infection seven weeks prior to admission. Initial workup revealed increased serum creatinine (235 μmol/L), glucosuria, low-molecular-weight proteinuria, mild leukocyturia, and microhematuria with hyaline and granular casts on microscopy. Antibodies against the SARS-CoV-2 S protein receptor-binding domain confirmed prior infection with high titers. Kidney biopsy showed diffuse active interstitial nephritis with negative immunofluorescence and positive immunohistochemistry for SARS-CoV-2 in the inflammatory cells within the interstitium. Electron microscopy revealed several SARS-CoV-2-like particles. Kidney function continued to deteriorate despite several days of supportive therapy only (peak serum creatinine 272 μmol/L); thus, treatment with methylprednisolone pulse-dose therapy was initiated and was followed by oral prednisolone with gradual tapering. Kidney function completely recovered after 3 weeks post-discharge and remained normal after 11 weeks of follow-up (last estimated glomerular filtration rate 106 ml/min/1.73 m²) with only residual microhematuria. Our case adds to the emerging evidence of SARS-CoV-2 as a potential etiological agent of AIN in children and also suggests that interstitial kidney injury may result from secondary inflammatory damage. Epidemiological history, serologic testing, and SARS-CoV-2 detection in biopsy should be considered in the work-up of children with AIN of unknown etiology.

Keywords: COVID-19; SARS-CoV-2; acute interstitial nephritis; children; coronavirus; pediatric.

Figure 1

Histological features of kidney biopsy showing diffuse active tubulointerstitial nephritis. (A) H&E slide. Marked lymphocytic infiltration in the interstitium with an admixture of neutrophils and plasma cells. Focal features of acute tubulitis are also present (arrowheads). Glomeruli reveal no apparent histological changes. (B) Electron microscopy sample is taken from interstitium between renal tubules. Few virus-like particles in size of ~120 nm with barely visible spikes are present intracellularly. Cross-sections of the particles contain interior electron-dense black dots which could be interpreted as helical nucleocapsid (lower magnification is available in Supplementary Figure 1). (C,D) Immunohistochemistry (IHC) for Anti-SARS-CoV-2 spike glycoprotein highlighted positive scattered immune cells in the interstitium of renal parenchyma (arrows). Rabbit polyclonal antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (ab272504, Abcam) was applied. Lung tissue of a deceased COVID-19-infected patient was used as a positive tissue control and a negative reagent control was performed on a consecutive biopsy tissue section to ensure sensitivity and specificity of the IHC test.

Figure 2

Time course of serum creatinine since the admission to the hospital.