Introduction

SARS-COV-2 infection has been shown to involve the kidney. Many studies have shown the presence of acute kidney injury with high grade proteinuria [1,2]. In a case series, nephrotic syndrome with AKI has been reported during an ongoing COVID -19 infection. Most of these patients were from African ancestry and the histopathological examination revealed podocytopathy and collapsing glomerulopathy [3]. Other studies have also alluded to the development of proteinuria secondary to COVID -19 infection. There are also increasing number of reports on the development/relapse of glomerular disease following COVID -19 vaccination [4]. We report three cases of young adults who developed nephrotic syndrome four to six weeks following a COVID 19 infection.

Case Series

Case 1

An 18- year- old man from South Asian ancestry presented to our outpatient department with progressive swelling of his face and legs of two weeks duration. He had no history of any medical illness. He gave a history of fever and cough six weeks back. His evaluation revealed the presence of COVID -19 infection (rt-PCR positive). As he had mild symptoms, he was managed at home. His evaluation at our clinic revealed proteinuria, hypoalbuminemia and abnormal renal functions (Table 1). He underwent a renal biopsy which was reported as focal segmental glomerulosclerosis (NOS) (Figure 1). He was offered a trial of steroids (1 mg/kg daily). Over the next 6 months as his steroids were tapered, his nephrotic syndrome relapsed. He was restarted on steroids again. We plan to start Tacrolimus when he achieves remission and taper steroids slowly.

Case 2

A 20-year- old engineering student from rural South India presented to us with progressive weight gain and oliguria. Clinical examination revealed pedal oedema, facial puffiness and free fluid in the abdomen. He gave an history of COVID -19 infection 4 weeks back. He underwent a renal biopsy, which was essentially normal on histopathology and immunofluorescence. His electron microscopy revealed diffuse foot process effacement (Figure 2). A diagnosis of minimal change disease was made and he was started on steroids. He has completed 8 weeks of treatment and has achieved complete clinical and biochemical remission. His recent investigations after 3 months of follow up show normal renal function and a urine protein of 0.1 gram/day.

Case 3

24 -year -old woman presented to us with facial puffiness, swelling of legs and abdominal bloating. She gave a history of symptomatic COVID 19 infection 6 weeks back. She was evaluated and found to have nephrotic syndrome. She underwent a renal biopsy, which revealed the features of focal segmental glomerulosclerosis (tip lesion) (Figure 3). She was started on steroids and was treated with tapering dose of steroids for three months. Her current urinary protein excretion is 1.8 grams /day. As she did not achieve

complete remission, she was started on Tacrolimus. Currently she is on 0.1 mg/kg/day tacrolimus and her sub-nephrotic proteinuria persists.

Discussion

Acute kidney injury in COVID 19 infected patients requires immediate evaluation and therapeutic intervention, but what is often not highlighted is that proteinuria is an important and not so uncommon renal manifestation in COVID 19 infected patients [5]. In a biopsy series, glomerular involvement was noted in four out of ten patients. The patients in this series had features of collapsing glomerulopathy (CG) [6]. Collapsing glomerulopathy seems to be the common glomerular disease in patients with COVID 19 infection (Table 2) [7,8]. Also, there have been cases of new onset/relapse of nephrotic syndrome (NS) in children and young adults who developed COVID 19 infection. In most of these patients, biopsies were done during an ongoing COVID 19 infection [9,10,11]. Our patients are cases who developed NS four to six weeks after documented COVID 19 infection .All these young adults had relatively mild/asymptomatic COVID 19 infection. Focal segmental glomerulosclerosis was the histology in 2 out of 3 patients. None of them had histopathological evidence of collapsing glomerulopathy. None had evidence of high-risk ApoL1 genotype. The absence of CG may reflect the racial differences in extent and type of glomerular involvement in COVID 19 infection. The development of NS following COVID 19 infection may not reflect a causality but maybe considered as a chance association with SARS-CoV-2 infection. However, the nimmunomodulatory nature of the virus makes us speculate that there may exist some correlation with COVID 19 infection and development of NS [12]. Further studies are required to understand this unique propensity of the virus and its implication in the development of glomerular disease.

Conclusion

Glomerular diseases are increasingly recognised in kidney biopsies of patients with COVID 19 infection. NS (new onset and relapse) is also described in literature. We report the development of nephrotic syndrome in three cases four to six weeks following a COVID 19 infection. Nephrotic syndrome have an underlying immunological mechanism and we speculate that the immunopathology engendered by COVID 19 infection might explain this association.

Data availability: All data pertaining to this submission is with the corresponding author and can be made available on reasonable request.

Figures

Tables

References

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