Contributed by Gaurav Kattel, MBBS, MD and Parmjeet S. Randhawa, MD
A man in his late 30's with a medical history of HIV, hypertension and chronic kidney disease presented with acute kidney Injury and positivity for COVID-19 infection. He was on anti-HIV medication (cobicistat-darunavir).
Lab results showed:
Urinalysis demonstrated the following:
Two cores of renal tissue measuring 1.5-1.6 cm in length and less than 0.1 cm cross sectional diameter were received. A 0.4 cm portion of the 1.6 cm core was submitted for immunofluorescence studies, and a 0.3 cm portion of the 1.5 cm core was submitted for electron microscopy (in Karnovsky's fixative). The remaining tissue was placed in 10% neutral buffered formalin and submitted for light microscopy.
LIGHT MICROSCOPIC EXAMINATION
The tissue examined by light microscopy consisted of two cores of formalin fixed, paraffin embedded renal cortex.
Glomeruli: The profiles of approximately 38 glomeruli were identified in the paraffin sections of which 24 (63%) were globally sclerotic. The non-globally sclerotic glomeruli were normal to increased in size, normocellular to mildly increased in mesangial cellularity and matrix. Focal segmental glomerulosclerosis was seen in 12 glomeruli with some showing hyalinosis (Fig. 3). Some glomeruli showed periglomerular fibrosis with retraction of glomerular tuft. 1 glomerulus showed shrinking of the glomerular tuft with more prominent overlying podocytes. No endocapillary proliferative lesion, necrotizing lesion, crescents, increased circulating white blood cells, glomerular basement membrane double contours or glomerular basement membrane breaks were seen on the Periodic Acid Schiff (PAS) or Jones stains.
Tubules: The tubules showed chronic atrophy (Fig. 4) involving approximately 70% of the cortex with presence of severe tubulitis. Scattered tubules showed dilation with hyaline casts. Some of the tubules showed attenuated tubular epithelium with occasional apoptotic cells. Eosinophilic inclusions described in the setting of HAART therapy were not seen. Interstitium: The interstitium showed diffuse moderate to severe lymphoplasmacytic infiltrate with moderate fibrosis and severe tubular atrophy (Fig.1. and Fig.2). Trichrome staining confirmed the presence of moderate fibrosis. IgG, kappa/lambda stains showed no light chain restriction. IgG4 stain was virtually negative. COVID-19 in-situ hybridization stain was negative. In-situ hybridization for EBER RNA showed scattered positive cells (Fig. 5).
Blood vessels: Approximately 11 interlobular sized arteries were present in the paraffin sections with moderate fibroelastic intimal thickening. There was presence of arteriolar hyalinosis. There was no evidence of active vasculitis or thromboemboli in the extra-glomerular blood vessels examined.
The findings showed glomerular staining for IgM, C1q, C3 and Properdin. There was presence of arteriolar staining for IgM, C1q and C3.
Glomerular basement membranes showed irregular thickness (mean 395 nm) with wrinkling and focal collapse. Effacement of podocyte foot processes was severe and associated with vacuolization and microfilament deposits in the podocyte cytoplasm. There was endothelial injury in the glomerular and peritubular capillaries with tubulo-reticular inclusions. Mesangial and paramesangial electron dense deposits were present. There was no substructure in these deposits. Tubules showed severe injury with vacuolization, mitochondrial swelling, mitochondrial pleomorphism, loss of cristae and lumina shedding of the cells. The tubular basement membranes were thick and contained vesicular debris as well as electron dense material.