Tubulointerstitial nephritis and uveitis syndrome and SARS-CoV-2 infection in an adolescent: just a coincidence in time?

Abstract

Background: Despite recent well-established kidney tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), usually presenting as acute kidney injury (AKI), there are few published cases with SARS-CoV-2-related tubulointerstitial nephritis (TIN). We report an adolescent with TIN and delayed association with uveitis (TINU syndrome), where SARS-CoV-2 spike protein was identified in kidney biopsy.

Case-diagnosis/treatment: A 12-year-old girl was assessed for a mild elevation of serum creatinine detected during the evaluation of systemic manifestations including asthenia, anorexia, abdominal pain, vomiting, and weight loss. Data of incomplete proximal tubular dysfunction (hypophosphatemia and hypouricemia with inappropriate urinary losses, low molecular weight proteinuria, and glucosuria) were also associated. Symptoms had initiated after a febrile respiratory infection with no known infectious cause. After 8 weeks, the patient tested positive in PCR for SARS-CoV-2 (Omicron variant). A subsequent percutaneous kidney biopsy revealed TIN and immunofluorescence staining with confocal microscopy detected the presence of SARS-CoV-2 protein S within the kidney interstitium. Steroid therapy was started with gradual tapering. Ten months after onset of clinical manifestations, as serum creatinine remained slightly elevated and kidney ultrasound showed mild bilateral parenchymal cortical thinning, a second percutaneous kidney biopsy was performed, without demonstrating acute inflammation or chronic changes, but SARS-CoV-2 protein S within the kidney tissue was again detected. At that moment, simultaneous routine ophthalmological examination revealed an asymptomatic bilateral anterior uveitis.

Conclusions: We present a patient who was found to have SARS-CoV-2 in kidney tissue several weeks following onset of TINU syndrome. Although simultaneous infection by SARS-CoV-2 could not be demonstrated at onset of symptoms, since no other etiological cause was identified, we hypothesize that SARS-CoV-2 might have been involved in triggering the patient's illness.

Keywords: SARS-CoV-2; TINU syndrome; Tubulointerstitial nephritis; Uveitis.

Fig. 1

Immunofluorescence of kidney cells. Experiments with the first (A) and second (B) kidney biopsies (3 and 10 months following onset of clinical manifestations, respectively) are shown. The first column reveals cell nuclei using DAPI staining. In the second and third columns, SARS-CoV-2 S (spike) protein is shown in red, demonstrating a perinuclear pattern. A positive control spike-label slides from the intestine of the patient presented in the clinical case report by Mayordomo-Colunga et al. [6] is also included (C). Images were obtained by confocal microscopy (Leica SP8) and processed using ImageJ

Fig. 2

Time course of serum creatinine and urine beta-2-microglobulin over a 10-month period. The main clinical events are also indicated