Other viral syndromes have been associated with the second hit in transplant recipients of kidneys from donors with 2 APOL1 risk alleles [10,11]. We previously reported a patient who was identified as homozygous for the APOL1 G1 and G2 risk alleles and developed FSGS 18 years after renal transplantation from an identical twin sibling [12]. hospital discharge. This suggests that COVID-19 vaccination may not provide protection from infection-associated focal segmental glomerulosclerosis in patients with APOL1 risk alleles. Vaccination against coronavirus disease 2019 (COVID-19) has played a primary role in reducing the spread of the novel coronavirus infection and in reducing the associated morbidity and mortality [1]. However, it is clear that COVID-19 vaccination does not confer equal protection to all populations. Organ transplant recipients have exhibited lower rates of immune response to COVID-19 vaccination in comparison to the general population [2,3]. This is particularly the case for patients who have recently had a transplant and those transplant recipients on higher doses of immunosuppression at the time of COVID-19 vaccination [4]. However, even in patients with an antibody response to vaccination, it is not known whether vaccination confers protection against all complications of COVID-19 infection, such as focal segmental glomerulosclerosis (FSGS) associated with APOL1 risk alleles. Collapsing FSGS has been reported in association with COVID-19 infection in patients with the APOL1 risk alleles. There have been multiple case reports of patients with 2 APOL1 G1 risk alleles and a patient who had the G1 and G2 risk alleles who developed native kidney collapsing FSGS associated with COVID-19 infection [5], [6], [7]. Collapsing FSGS has also been described in association with COVID-19 infection in a patient who was heterozygous for wild-type and G1 alleles of APOL1 [8]. Among renal transplant recipients, a patient with primary FSGS who received a kidney transplant was reported to develop proteinuria and biopsy-proven FSGS in association with COVID-19 infection and positive staining of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein RNA in renal tubular epithelial cells Rabbit polyclonal to ANGPTL1 [9]. COVID-19 infection may act as a second hit for the development of FSGS in patients with APOL1 risk alleles. Other viral syndromes have been associated with the second hit in transplant YHO-13351 free base recipients of kidneys from donors with 2 APOL1 risk alleles [10,11]. We previously reported a patient who was identified as homozygous for YHO-13351 free base the APOL1 G1 and G2 risk alleles and developed FSGS 18 years after renal transplantation from an identical twin sibling [12]. Here we report a case of rapid-onset collapsing FSGS associated with COVID-19 infection in the same patient after successful COVID-19 vaccination. Case Presentation A 57-year-old female with a history of renal transplantation from her identical twin, 2 risk alleles for APOL1, and FSGS in the transplant kidney was admitted with shortness of breath, cough, nausea, and vomiting and was diagnosed with COVID-19 infection based on nucleic acid amplification test. The patient had a history of end-stage renal disease due YHO-13351 free base to biopsy-proven FSGS prior to receiving a preemptive kidney transplant from her identical twin sister 23 years before this presentation. She received reduced immunosuppression with no induction therapy of anti-lymphocyte antibodies or IL-2 YHO-13351 free base receptor antagonists. Maintenance immunosuppression consisted of mycophenolate 750 mg twice a day and prednisone 5 mg daily. She had received cyclosporine only during the first year posttransplant. She had excellent renal function posttransplant with serum creatinine ranging between 0.8 and 1.1 mg/dL and urine protein-creatinine ratio ranging between 0.3 and 0.8. However, 18 years after transplantation, the patient was noted on routine follow-up laboratory testing to have a UPCR of 1 1.8 gm/d. Serum creatine also increased to 1.5 mg/dL. She underwent allograft biopsy at this time, which was negative for rejection but showed focal global (30%) and segmental glomerulosclerosis (NOS [not otherwise specified] type; Fig?1 ), patchy interstitial fibrosis and tubular atrophy (30%) with associated nonspecific inflammation, mild arteriosclerosis, and hyaline arteriolosclerosis. Immunofluorescence was negative. Electron microscopy showed 30% to 40% foot process effacement. Genetic testing revealed that she and her twin donor carried both a G1 and a G2 risk allele for APOL1. The patient was treated with losartan and spironolactone and UPCR improved to 0.26 by 1 year post biopsy. Serum creatinine remained at 1.5 mg/dL on regular follow-up testing, the last of which was 3 months earlier, and the last UPCR 6 months earlier was 0.74 gm/d prior to presentation. The patient had received the second dose of the Moderna SARS-CoV-2 vaccine approximately 6 weeks prior to presentation. Open in a separate window Fig 1 Representative glomerulus from the first biopsy showing segmental glomerulosclerosis, not otherwise specified type, Jones methenamine silver stain; original magnification 200. On presentation, the patient’s oxygen saturation was 98% on room air, and throughout her hospitalization for COVID-19, her oxygen saturation fluctuated between 92% to.