ABSTRACT
Introduction: Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) characterized by dysregulated complement activation. Antibodies to factor H (anti-FH), a regulator of the alternative complement pathway, are a recognized cause of aHUS particularly in children. We present the case of an elderly patient who developed aHUS following COVID-19. Case Description: A 74-year-old male presented with weakness, petechial rash involving extremities and diarrhea for 2 weeks. Prior history included hepatitis C infection status-post treatment 2 years ago with associated cirrhosis. Three weeks ago, the patient had been diagnosed with COVID-19. His symptoms of sore throat, cough and fever had by now resolved. Initial investigations showed leukocytosis and AKI with an active urinary sediment and nephrotic range proteinuria (Fig 1). Hemoglobin and platelets were normal and a blood smear was negative for hemolysis. Imaging revealed small bowel enteritis suggestive of an infectious or vasculitic process. Infectious workup returned negative. Autoimmune serologies revealed a borderline positive ANA, low C3 and low-normal C4. Renal biopsy revealed diffuse endothelial injury with swollen endothelial cells, focal mesangiolysis and glomerular basement membrane duplication. Hence, pulse dose steroids were started and complement function panel sent. Soon after steroid initiation, the patient's renal function, leukocytosis and rash improved. Ultimately, complement testing returned positive for anti-FH. At follow-up, renal function had returned to baseline with continued steroid taper. Discussion(s): COVID-19 is associated with TMA likely due to endothelial toxicity or complement pathway dysregulation. Our patient had no prior history of renal or hematologic disease. Given the chronology of events, it is likely that COVID-19 triggered formation of anti-FH, in turn leading to development of aHUS in our patient.
ABSTRACT
Immunization with COVID-19 mRNA vaccines has been associated with new-onset and relapse of glomerulonephritis (GN)1,2. We present a case of new onset, seronegative, full-house immune-complex GN after mRNA COVID-19 vaccination. A 24-year-old male with history of idiopathic portal vein thrombosis in childhood, portal hypertension post splenorenal shunt and splenectomy 5 years prior presented with 9 weeks of progressive edema, ascites, and foamy urine. His symptoms started then worsened after his 1st and 2nd doses of the mRNA- 1273 COVID-19 vaccination (Moderna). Cr peaked at 3.04mg/dl (baseline 0.7) and UPCR at 50.52 g/g. Serum albumin 0.9 g/dl. Complements were low. ANA and anti-DS DNA were negative as were other serologies. Infectious work up was also negative. Kidney biopsy showed membranoproliferative pattern of injury on light microscopy with one fibrocellular crescent and without IFTA. IF revealed “full house” staining and EM showed severe subepithelial deposits with subendothelial and mesangial deposits. No tubuloreticular inclusions were present (Figure 1). The patient received cyclophosphamide 750 mg and high dose steroids. One month after treatment, Cr improved to 0.92 and proteinuria fell to 6.05g/g. Complements returned to normal. The high potency of mRNA COVID-19 vaccine can induce a robust immune response which may incite or unmask GNs2. Our patient had a rapid and robust response to immunosuppression. Seronegative full-house immune complex GN may occur after receiving mRNA SARS-CoV-2 vaccination and nephrologists should be aware of potential association. Prompt recognition and treatment may lead to favorable outcomes. (Figure Presented)
ABSTRACT
Introduction: Messenger RNA COVID-19 vaccine is more effective than traditional vaccines due to superior immune activation. However, the impact of mRNA COVID-19 vaccine on glomerulonephritis (GN) is limited. We report 4 cases of patients who developed new or had relapse of GN post vaccination. Case Description: Case 1: A 43-year-old male with prior COVID-19 infection and baseline serum creatinine (SCr) of 1.2 mg/dl received Moderna vaccine 9 months after recovering from COVID-19 infection. Two weeks after the 1st dose, SCr increased to 2.5 mg/dl. He received 2nd dose 2 weeks later and SCr 3 days after was 2.7 mg/dl. Urinalysis (UA) showed 21-30 RBC/hpf and 24 hr urine protein (UP) was 14.4 g/d. A kidney biopsy revealed IgAN with moderate interstitial nephritis. He was treated with prednisone and ramipril. Case 2: A 66-year-old male with atrial fibrillation with baseline SCr 1.1 mg/dl received 1st dose of Moderna vaccine and two weeks later SCr was 1.5 mg/ dl. Eight weeks after the 2nd dose, SCr was 2.4 mg/dl. UA showed 51-100 RBC/hpf and 24 hr UP 1.2 g/d. A kidney biopsy revealed IgAN with acute tubular injury and RBC casts. He was treated conservatively. Case 3: A 29-year-old female with minimal change disease who had been in remission for 2 years, received 2 doses of Pfizer vaccine. Three weeks after the 2nd dose, she developed leg edema with albumin 2.2 g/dl, 24 hr UP 10 g/d, and SCr 0.6 mg/dl. A repeat kidney biopsy showed focal segmental glomerulosclerosis, tip variant. She was treated with prednisone and tacrolimus. Case 4: A 39-year-old male with PLA2R+ membranous nephropathy who was in remission and off immunosuppressive therapy for 1.5 years received 2 doses of Pfizer vaccine. Two weeks after the 2nd dose, he developed leg edema with SCr 1.1 mg/dl, albumin 2.0 g/dl, and 24 hr UP 8.7 g/d. Tacrolimus was re-initiated. Discussion: New cases and relapse of GN can present shortly after mRNA COVID-19 vaccination. Messenger RNA COVID-19 vaccine may be associated with reactivation of known glomerulonephritis or unmask presence of previously undiagnosed GN such as IgAN possibly due to potent immune activation. However, mechanism remains unknown and additional studies are needed.