ABSTRACT
Introduction: Hydralazine is a direct vasodilator that is widely used for treatment of hypertension and heart failure with reduced ejection fraction. This medication has been associated with autoimmune diseases including ANCA-associated vasculitis (AAV) Case Description: A 73-year-old lady with a past medical history of uncontrolled hypertension and myelodysplastic syndrome presented to the hospital with an asymptomatic increase in serum creatinine on routine blood work that was 2.5 mg/dL. The patient had COVID-19 infection 3 weeks prior to blood work that required no treatment or hospitalization. Patient had been on hydralazine for years at 50 mg three times daily to treat hypertension. Basic metabolic panel showed creatinine of 2.60 mg/dL, BUN of 50 mg/dL. Urinalysis revealed a protein of 100 mg/dL. Microscopy showed RBCs of 90 per hpf and WBC of 11 per hpf. Spot urine protein/creatinine ratio was 1.6 g/g. C-ANCA was negative but P-ANCA was positive with a titers greater than 1:5120, PR-3 antibodies were negative with myeloperoxidase antibodies positive at 1.4 AI. Antihistone antibodies came back positive at 6.8 units. She was started on IV methylprednisolone 500 mg daily for 3 days. The kidney biopsy was performed and showed glomerulosclerosis of 20/70 glomeruli, cellular and fibrocellular crescents in 14 of 50 viable glomeruli. Immunofluorescence was completely negative for IgG, IgA, C3 and C1q with mild mesangial IgM deposition, (+2). Biopsy findings were compatible with ANCA-associated, pauci-immune proliferative glomerulonephritis with crescent formation. Following IV methylprednisolone she was switched to oral prednisone, 60 mg daily. The patient was also given one gram of IV rituximab and discharged with a creatinine level of 1.9 mg/dL. Discussion(s): This case shows the importance of considering the diagnosis of hydralazine ANCA associated vasculitis when treating patients with nephritic syndrome. It also highlights the importance of reconsidering treatment with hydralazine for hypertension or heart failure and reserve it to certain groups of patients with few alternatives.
ABSTRACT
Background: Acute kidney injury (AKI) is common in patients with COVID-19 and associated with poor outcomes. Urinary biomarkers have been associated with adverse kidney outcomes in other settings and may provide additional prognostic information in patients with COVID-19. Methods: We evaluated 19 urinary biomarkers of injury, inflammation, and repair in patients hospitalized with COVID-19 at 2 academic medical centers between April and June 2020. We associated biomarkers with a primary composite outcome of KDIGO stage 3 AKI, requirement for dialysis, or death within 60 days of admission. We also compared various kidney biomarker levels in the setting of COVID-19 versus other common AKI settings. Results: Out of 157 patients, 24 (15.3%) experienced the primary outcome. Twofold higher levels of neutrophil gelatinase-associated lipocalin (NGAL) (HR: 1.53;95% CI: 1.33-1.76), monocyte chemoattractant protein (MCP-1) (HR: 1.86;95% CI: 1.48-2.33), and kidney injury molecule-1 (KIM-1) (HR: 2.32;95% CI: 1.69-3.18) were associated with highest risk of the primary outcome. Higher epidermal growth factor (EGF) levels were associated with a lower risk of the primary outcome (HR 0.52;95% CI: 0.40-0.69). Individual biomarkers provided moderate discrimination and biomarker combinations improved discrimination for the primary outcome. Conclusions: Urinary biomarkers are associated with severe kidney complications in patients with COVID-19 and provide valuable information to monitor kidney disease recovery and progression.
ABSTRACT
Background: Patients hospitalized with COVID-19 are at risk for major adverse kidney events (MAKE). Predicting which patients will experience progression of disease and poor outcomes remains elusive. We sought to develop a biomarker-based risk model for predicting MAKE in patients hospitalized with COVID-19. Methods: We applied least absolute shrinkage and regression methodology (LASSO) to a prospectively enrolled cohort of 432 patients admitted with COVID-19 who had blood specimens collected (median 2 days [IQR 2-4 days] from admission) from March 2020-January 2021, at three large academic medical centers. Clinical variables and 26 plasma biomarkers were used as candidate features in the prediction models for the outcome of MAKE, defined as KDIGO stage 3 AKI, dialysis-requiring AKI, or in hospital mortality. Cross-validation was used for optimal shrinkage parameter selection and model AUCs were optimism-corrected using bootstrapping. Results: MAKE occurred in 85 (20%) patients within 60 days of admission. Application of LASSO to the 26 biomarkers selected IL-12, IL-13, IL-6, Tie2, FLT1, NGAL, MCP1, YKL40, Ang1, Ang2, and TNFR1, which yielded an AUC of 0.88 (95% CI 0.85-0.91). Plasma TNFR-1 alone had an AUC of 0.88 (0.84,0.91). When LASSO was applied on the clinical variables and TNFR1, 4 clinical variables (age, black race, obesity, WHO COVID severity score) and TNFR1 were selected with an AUC was 0.88 (95% CI 0.87-0.89). Random Forest models of biomarkers and clinical variables had similar prediction performance. A cutoff of TNFR1 at 3005 pg/ml had a sensitivity of 69%, specificity of 89%, PPV of 60% and NPV of 92% for occurrence of MAKE over 60 days. Conclusions: In this multi-center cohort study, plasma TNFR1 by itself produced a robust prediction for MAKE in patients hospitalized with COVID-19 that did not improve when combined with multiple clinical variables and was equivalent to combined inputs of 10 other plasma biomarkers.