Membranous nephropathy after a recent SARS-CoV-2 infection

Background

Membranous nephropathy (MN) is a glomerulopathy characterised by the formation of immune complexes on the glomerular basement membrane, which results in the thickening of the membrane. The usual presentation is nephrotic syndrome, with hypoalbuminaemia and peripheral oedema.1

MN is most commonly idiopathic but can be secondary to other pathologies, such as immunological diseases (systemic lupus erythematosus), malignancies and infections (hepatitis C and B).1

SARS-CoV-2 infection can precipitate different types of kidney lesions.2 3 MN has been described after SARS-CoV-2, but it is rare.2 To date, only five cases were described in the literature.2 3

Here we present a case of nephrotic syndrome caused by phospholipase A2 receptor (PLA2R) MN and with primary onset after SARS-CoV-2. The patient was treated with rituximab, with proteinuria control.

Case presentation

A man in his eighth decade, with hypertension, presents with SARS-CoV-2 pneumonia. He was admitted to the hospital for partial respiratory failure with the need for supplemental oxygen. He was treated with azithromycin and hydroxychloroquine, and the evolution was favourable, with no kidney injury during the admission.

One month later, he noticed progressive malleolar oedema and worsening hypertension. On examination, his blood pressure was 143/66 mm Hg, heart rate was 66 beats per minute and he had exuberant bilateral oedema of the lower limbs, without pulmonary congestion.

Investigations

At this time, on laboratory assessment, the creatinine was 94.6 µmol/L, he had hypercholesterolaemia, hypoalbuminaemia (25 g/L), urine protein-creatinine ratio (uPCR) of 850.9 mg/mmol and urine albumin-creatinine ratio of 560.5 mg/mmol. On ultrasound, kidney size was normal, with microlithiasis.

In the presence of nephrotic syndrome, a complementary study was performed: complement (C3 and C4) was normal, and viral serologies (HIV, hepatitis B virus and hepatitis C virus) were negative. PLA2R antibodies were positive (268.8 RU/mL). He had no anaemia or thrombocytopenia and no peripheral schistocytes on the blood smear, and haptoglobin was normal. Gastrointestinal endoscopy and whole-body CT excluded neoplasm. Prostate-specific antigen was normal.

On follow-up, he showed persistent proteinuria despite renin-angiotensin system blockade and progressive kidney dysfunction (creatinine 198 µmol/L). He was submitted to a kidney biopsy.

Kidney biopsy revealed: 19 glomeruli, one of which was globally sclerotic and two with segmental sclerosis lesions. Glomeruli with segmental mesangial expansion, accompanied by a slight to moderate increase in mesangial cellularity and an increase in endocapillary cellularity, at the expense of neutrophils; associated peripheral fibrin thrombi in about four glomeruli. The basement membrane was thickened, showing rare spikes and inclusions in the silver stain. There was exuberant podocyte hyperplasia (figures 1 and 2). Proximal and distal tubules had mild degenerative and reactive changes, with some red blood cells being observed. There was stromal oedema; no interstitial inflammatory infiltrate. No interstitial fibrosis and no significant tubular atrophy (less than 2%). Arterioles with mild to moderate hyalinosis; arteries with mild fibrodysplasia. Congo red staining was negative. The immunofluorescence revealed fine granular deposits, with universal distribution along the glomerular capillary wall, of IgG, kappa and lambda light chain and sparse C3 (figure 3). Additionally, the search for SARS-CoV-2, using an immunohistochemistry antibody, was negative. A diagnosis of membranous glomerulopathy was rendered.

Treatment

Supportive treatment for the nephrotic syndrome was started to control fluid overload. The patient was advised to have a sodium-restricted diet, and furosemide was started, with a reduction of oedema. Hypercholesterolaemia was treated with simvastatin 20 mg per day.

For control of hypertension and proteinuria reduction, he was treated with irbesartan, which was progressively titrated until 300 mg per day.

Despite optimal supportive treatment, the patient showed progressive kidney function decline (maximum creatinine of 291.7 µmol/L) and worsening proteinuria (uPCR 1762.8 mg/mmol).

After biopsy confirmation of MN and in the absence of significant interstitial fibrosis, we decided to start immunosuppression. Because the patient was a frail 78-year-old man, we decided to administer rituximab: 1 g, two doses separated by 15 days.

Outcome and follow-up

After rituximab, there was a reduction of PLA2R serum levels (42.67 RU/mL) 1 month after therapy followed by progressive protein reduction and nephrotic syndrome control. There was only partial recovery of kidney function, with a nadir of creatinine 203 µmol/L.

At 12 months, the patient shows stable kidney function (creatinine 220 µmol/L) and uPCR of 79 mg/mmol. There were no infections or other complications.