RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS ASSOCIATED IN TIME WITH VACCINATION AGAINST COVID 19

The development of an effective vaccine against the new coronavirus is considered a priority in order to control the transmission and spread of the disease, however the side effects of these vaccines remain a concern that must be addressed. We report a case of pauci-immune glomerulonephritis with rapidly progressive deterioration of renal function, beginning a few days after the injection of the Adenovirus type 26 vaccine that encodes the SARS-CoV-2 spike glycoprotein * (Ad26. COV2-S) (Johnson & Johnson acute respiratory syndrome coronavirus 2 [SARS CoV-2] vaccine).

A previously healthy 33-year-old male was admitted to the emergency room due to abdominal pain in epigastrium of moderate intensity accompanied by macroscopic hematuria, asthenia, adynamia, as well as intermittent fever peaks of 5 days of evolution. Ten days earlier, he had received the first injection of the Johnson & Johnson COVID-19 vaccine. The patient denied chronic diseases as well as the use of non-steroidal anti-inflammatory drugs before or after vaccination. Upon admission, the blood pressure was 150/100 mm Hg and the heart rate was 90 beats / min. Nothing relevant to the physical examination did not show extrarenal manifestations. Laboratory tests revealed serum creatinine 2.5 mg / dl, serum urea nitrogen 26 mg / dl, albumin 3.2 g / dl, C-reactive protein 337, cholesterol 77 mg / dl, and triglycerides 113 mg / dl. Tests for hepatitis B surface antigen and hepatitis C virus antibodies were negative; Complement levels C3 and C4 were within reference ranges; and tests for antineutrophil cytoplasmic antibodies (ANCA), antiglomerular basement membrane antibodies (GBM) and antinuclear antibodies (ANA) also gave negative results as well as antinuclear antibodies

The polymerase chain reaction for SARS-CoV-2 gave negative results. Urinalysis revealed protein (0.477) and urinary sediment showed more than 5 red blood cells per high-power field with dysmorphic erythrocytes of 10%. Twenty-four hour urine collection revealed proteinuria of 1.2 grams. Nonenhanced computed tomography examination showed kidneys of normal size and no evidence of urinary tract obstruction. During the first days after admission, renal function continued to decline and serum creatinine increased to 3.4 mg / dl, urea 131 BUN 61, therefore, due to rapidly progressive renal deterioration, empirical treatment with methylprednisolone 1 gram each was started. 24 hrs for 3 days, and a percutaneous renal biopsy is performed where 46 glomeruli are obtained, in 26 of these (56.52% of the total glomeruli in the sample) you can see active extracapillary proliferative lesions (cellular crescents) that segment the tangles capillaries and are accompanied by karyorrhexis and fibrinoid necrosis (figure 1). These lesions lead to disruption of Bowman's capsules, with an intense periglomerular inflammatory reaction, even with areas of the granulomatous type. In addition, there are seven glomeruli (15.21%) in which segmental fibrinoid necrosis is exclusively observed, without crescents. the interstitium has areas of fibrosis with associated tubular atrophy affecting approximately 5-10% of the cortical surface (grade I). there is diffuse interstitial edema, which causes loss of the tubular “back-to-back” pattern, with foci of inflammatory infiltrate made up of lymphocytes, plasma cells, neutrophils and 2 eosinophils, which show extension towards the tubular walls (figure 2 and 3). the immunofluorescence report: negative IgG (figure 3). IgA negative. Positive IgM in the form of mesangial filaments. Negative C1q. C3c negative. C4c negative. positive fibrinogen in crescents and areas of fibrinoid necrosis. Negative albumin. Negative kappa. Negative lambda. reaching the conclusion of diffuse active extracapillary proliferative glomerulonephritis, of the pauciimmune type, with segmental fibrinoid necrotizing lesions. or active tubulointerstitial nephritis with eosinophils. or multifocal acute tubular injury with marked regenerative epithelial changes. or interstitial fibrosis grade I (5-10%).

Before such report, prednisone 60 mg-based treatment is continued every 24 hrs  and cyclophosphamide 15 mg / kg bolus is started, however it presents torpid evolution 24 hrs after starting steroid boluses, regarding the kidney at the beginning with oliguria and elevation of urea to 168 and creatinine of 3.9 mg / dl for which hemodialysis renal replacement treatment is started, it is worth mentioning that after steroid boluses, febrile peaks remit and the patient is referred asymptomatic with reversal of C-reactive protein levels to normal parameters. Due to poor renal evolution and when hemodialysis began, therapeutic plasma exchange treatment was started, 4 sessions every 48 hours with a subsequent bolus of 500mg cyclophosphamide. After sessions of therapeutic plasma exchange and cyclophosphamide boluses, no remission was observed with established treatment, so rituximab 1 gram I.V. every 7 days for 4 doses.

A previously healthy 33-year-old male was admitted to the emergency room due to abdominal pain in epigastrium of moderate intensity accompanied by macroscopic hematuria, asthenia, adynamia, as well as intermittent fever peaks of 5 days of evolution. Ten days earlier, he had received the first injection of the Johnson & Johnson COVID-19 vaccine. The patient denied chronic diseases as well as the use of non-steroidal anti-inflammatory drugs before or after vaccination. Upon admission, the blood pressure was 150/100 mm Hg and the heart rate was 90 beats / min. Nothing relevant to the physical examination did not show extrarenal manifestations. Laboratory tests revealed serum creatinine 2.5 mg / dl, serum urea nitrogen 26 mg / dl, albumin 3.2 g / dl, C-reactive protein 337, cholesterol 77 mg / dl, and triglycerides 113 mg / dl. Tests for hepatitis B surface antigen and hepatitis C virus antibodies were negative; Complement levels C3 and C4 were within reference ranges; and tests for antineutrophil cytoplasmic antibodies (ANCA), antiglomerular basement membrane antibodies (GBM) and antinuclear antibodies (ANA) also gave negative results as well as antinuclear antibodies

The polymerase chain reaction for SARS-CoV-2 gave negative results. Urinalysis revealed protein (0.477) and urinary sediment showed more than 5 red blood cells per high-power field with dysmorphic erythrocytes of 10%. Twenty-four hour urine collection revealed proteinuria of 1.2 grams. Nonenhanced computed tomography examination showed kidneys of normal size and no evidence of urinary tract obstruction. During the first days after admission, renal function continued to decline and serum creatinine increased to 3.4 mg / dl, urea 131 BUN 61, therefore, due to rapidly progressive renal deterioration, empirical treatment with methylprednisolone 1 gram each was started. 24 hrs for 3 days, and a percutaneous renal biopsy is performed where 46 glomeruli are obtained, in 26 of these (56.52% of the total glomeruli in the sample) you can see active extracapillary proliferative lesions (cellular crescents) that segment the tangles capillaries and are accompanied by karyorrhexis and fibrinoid necrosis (figure 1). These lesions lead to disruption of Bowman's capsules, with an intense periglomerular inflammatory reaction, even with areas of the granulomatous type. In addition, there are seven glomeruli (15.21%) in which segmental fibrinoid necrosis is exclusively observed, without crescents. the interstitium has areas of fibrosis with associated tubular atrophy affecting approximately 5-10% of the cortical surface (grade I). there is diffuse interstitial edema, which causes loss of the tubular “back-to-back” pattern, with foci of inflammatory infiltrate made up of lymphocytes, plasma cells, neutrophils and 2 eosinophils, which show extension towards the tubular walls (figure 2 and 3). the immunofluorescence report: negative IgG (figure 3). IgA negative. Positive IgM in the form of mesangial filaments. Negative C1q. C3c negative. C4c negative. positive fibrinogen in crescents and areas of fibrinoid necrosis. Negative albumin. Negative kappa. Negative lambda. reaching the conclusion of diffuse active extracapillary proliferative glomerulonephritis, of the pauciimmune type, with segmental fibrinoid necrotizing lesions. or active tubulointerstitial nephritis with eosinophils. or multifocal acute tubular injury with marked regenerative epithelial changes. or interstitial fibrosis grade I (5-10%).

 Before such report, prednisone 60 mg-based treatment is continued every 24 hrs  and cyclophosphamide 15 mg / kg bolus is started, however it presents torpid evolution 24 hrs after starting steroid boluses, regarding the kidney at the beginning with oliguria and elevation of urea to 168 and creatinine of 3.9 mg / dl for which hemodialysis renal replacement treatment is started, it is worth mentioning that after steroid boluses, febrile peaks remit and the patient is referred asymptomatic with reversal of C-reactive protein levels to normal parameters. Due to poor renal evolution and when hemodialysis began, therapeutic plasma exchange treatment was started, 4 sessions every 48 hours with a subsequent bolus of 500mg cyclophosphamide. After sessions of therapeutic plasma exchange and cyclophosphamide boluses, no remission was observed with established treatment, so rituximab 1 gram I.V. every 7 days for 4 doses.

Multiple studies have reported various glomerulopathies associated with the mRNA vaccine (BNT162b2- Pfizer BiNTech, mRNA1273-Moderna): IgA nephropathy (relapse1), minimal change disease (de novo2,3, relapse4,5), associated vasculitis a ANCA (de novo6,7), membranous nephropathy (relapse8). It is possible that antigenic exposure in susceptible patients (2 hit theory) triggers the inflammatory response in situ that promotes glomerular injury with a clinical spectrum ranging from isolated podocyte injury (minimal change disease), mesangial (IgA nephropathy). ), and a deep destruction of the glomerular structure with the formation of cell crescents.