Collapsing glomerulopathy in a patient with APOL1 intermediate-risk genotype triggered by lupus nephritis and SARS-CoV-2 infection: lessons for the clinical nephrologist

Excerpt

A 21-year-old woman of African ancestry presented with skin rash and joint pain associated with edema. Her BMI was 20.2 kg/m². Laboratory tests revealed nephrotic syndrome (protein-to-creatinine ratio (PCR) of 8.5 g/g , serum albumin 1.8 g/dL) without normal kidney function (serum creatinine (SCr) 0.7 mg/dl, estimated GFR by MDRD was 130 ml/min/1.73m²). Immunology work-up revealed a high antinuclear antibody titer (> 1:2560; normal range < 1:80) and positive anti-double-stranded DNA antibody (> 400 IU/ml; normal range < 30), C3 and C4 serum levels were decreased (0.27 g/L; normal range 0.9–1.8 and 0.09 g/L; normal range 0.1–0.4 g/L, respectively). Renal biopsy found active class IV lupus nephritis: all glomeruli showed global subendothelial deposits (wire-loops), hyaline thrombi, hematoxylin bodies and 50% glomerular endocapillary hypercellularity (Fig. 2A). Immunofluorescence microscopy showed full house bright staining (supplementary Figure). As summarized in Fig. 1, the patient was started on steroids (1 mg/kg orally, tapered by 25% every 2 weeks, then continued at 10 mg/day) and mycophenolate mofetil (2 g/day). Treatment was switched to cyclophosphamide (500 mg/15 days, i.v.) owing to the onset of neurological involvement (cranial neuropathy) and increase in serum creatinine. Whilst clinical and serological parameters improved, she presented with necrotizing fasciitis complicated by septic shock. This led to the discontinuation of immunosuppressants, except for steroids (hydrocortisone hemisuccinate i.v. in intensive care, then the resumption of prednisone at 10 mg/day). After a 1-month stay in intensive care, following surgical treatment of the infection, she was admitted to the division of physical medicine and rehabilitation. Another month later, while double-stranded DNA antibody levels increased again (307 IU/mL) clinical activity remained low and renal parameters were consistent with remission (PCR 3.0 g/g, serum gamma globulin 7.6 g/L, SCr 1.2 mg/dL). One week after this reassuring work-up, she presented with fever without any other symptoms, and SARS-CoV-2 infection was diagnosed. She had no respiratory involvement and no specific treatment was administered, however within a week edema recurred, and proteinuria and serum creatinine increased again (PCR 6.0 g/g, SCr 1.3 mg/dL). A second renal biopsy was performed. Glomeruli showed focal active lesions of lupus nephritis different from those of the first biopsy: karyorrhexis and/or neutrophils without necrosis in 46%, glomerular endocapillary hypercellularity and subendothelial deposits in 8%. Otherwise, all showed glomerular sclerosis with segmental or global collapse of the glomerular tuft associated with adhesions to Bowman’s capsule and podocyte hypertrophy. Twenty-three percent of glomeruli presented extracapillary hypercellularity and pseudocrescents with striking podocyte hypertrophy/hyperplasia, attributable to concurrent collapsing glomerulopathy (CG) (Fig. 2B, C). Finally, glomerular full house immunostaining was present, as in the first biopsy, with a lower intensity. APOL1 genotype was assessed and revealed intermediate risk (G2 deletion/wild type). We concluded that the glomerular injuries were active lupus nephritis associated with collapsing glomerulopathy presumably due to concomitant mechanisms: (1) the SLE flare itself, (2) SARS-CoV-2 infection, against a background of genetic predisposition. We resumed immunosuppressant therapy with steroids, mycophenolate mofetil and low dose tacrolimus. However, due to a rapid increase in serum creatinine suggestive of nephrotoxicity, tacrolimus was discontinued. Current serological activity is low, but renal function has only partially improved while proteinuria remains unchanged.

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