ABSTRACT
Background: COVID-19-associated nephropathy (COVAN) is a type of collapsing glomerulopathy that leads to acute kidney injury (AKI) and overt proteinuria in individuals with apolipoprotein L1 (APOL1) polymorphism infected with SARS-CoV-2. Although the severity of the acute presentation of COVAN is well described, the long-term renal prognosis has not been clearly established. Method(s): We retrospectively identified native kidney biopsies from patients with diagnosis of COVAN discharged alive between January 2020 and March 2021. Time of biopsy pathological and clinical data were collected. We performed APOL1 genotyping for G1/G2 risk alleles. We examined the rate of end-stage kidney disease (ESKD), de novo or progressive chronic kidney disease (CKD) and death. Factors associated with those outcomes were assessed by logistic regression. Result(s): A total of 43 patients with COVAN with median follow-up at 244 days were included. Mean age was 53 +/- 12 years (range 30-78), 49% women, and 85% were of African descent. High-risk APOL1 genotypes were found in 86%. Most presented with AKI (91%) and nephrotic-range proteinuria (81%). Sixteen patients required dialysis at presentation (AKI-RRT), 8 of which reached ESKD and dialysis dependence at followup. Additionally, 6 patients without AKI-RRT developed ESKD and required dialysis at follow-up. Forty patients (93%) either developed de novo CKD or progressed to advanced stage of CKD [mean serum creatinine (sCr) 3.1 +/- 1.9 mg/dL]. Overall, 35% reached the combined endpoint of ESKD, progressive CKD or death. Predictive factors of ESKD included older age (59.1 +/- 13.9 vs. 50.4 +/- 10.7 years, p=0.03), increased sCr at time of biopsy (9.4 +/- 3.2 vs. 6.0 +/- 4.9, p=0.03), increased glomerular obsolescence (52.8 +/- 21.3 vs. 25.0 +/- 23.2%, p=0.0005), and IFTA [moderate-severe vs. mild, OR 9.8 (CI: 1.1-85.2), p=0.03]. AKI-RRT, sex, proteinuria at the time of biopsy, and absence vs. presence of an APOL1 high-risk genotype were not predictive of ESKD. Conclusion(s): COVAN is associated with ominous long-term renal sequelae. Serum creatinine at time of biopsy, patient age, glomerular obsolescence, and IFTA are associated with greater risk of ESKD.
ABSTRACT
Background: Vaccination is considered safe in patients with chronic kidney disease. However, given the ability to activate the immune system, immunizations carry a risk of inducing inflammatory disease flares. The mass vaccination for SARS-CoV-2 provides a unique opportunity to investigate potential vaccine-associated glomerular diseases. Methods: Kidney biopsies from patients who presented with acute kidney injury (AKI) and/or nephritic/nephrotic syndrome within three weeks of SARS-CoV-2 vaccination were included in the study (n=16). Kidney biopsies were reviewed at a single center and clinical information was provided from nephrologists for clinicopathologic correlation. Results: Sixteen patients with a new onset of kidney disease or flare within 3 weeks of SARS-CoV-2 vaccination were identified and all had glomerular disease on biopsy. Eleven patients had two vaccine doses prior to symptom onset. The patient cohort included 6 males and 10 females, with a mean age of 58 years. Biopsy diagnoses included IgA nephropathy (n=7), minimal change disease (n=4), ANCA-associated glomerulonephritis (n=3), membranous glomerulopathy (n=1), and diffuse lupus nephritis (n=1). Thirteen patients had co-morbid medical conditions, including hypertension (n=10), diabetes mellitus (n=4), autoimmune disease (n=5), and chronic kidney disease (n=4). The most common clinical presentation was AKI with concurrent nephritic or nephrotic syndrome (n=9), followed by nephritic syndrome with preserved kidney function (n=5), nephrotic syndrome with preserved kidney function (n=1), and isolated hematuria (n=1). Three patients with AKI required dialysis. A majority of patients had an elevated serum creatinine (mean 3.4 mg/dL), 14 had proteinuria (nephrotic range in 4), 11 had hematuria, and 10 had hypoalbuminemia (mean 2.9 g/dL). Six patients had antinuclear antibodies and 4 had a positive ANCA serology at the time of biopsy. Clinical follow-up is ongoing. Conclusions: IgA nephropathy, minimal change disease, ANCA-associated glomerulonephritis, membranous glomerulopathy, and lupus nephritis were identified with temporal association with SARS-CoV-2 vaccination. In the setting of mass vaccination, causality is unclear, but a new onset of glomerular disease should be monitored as a potential adverse event.