BackgroundAcute kidney injury (AKI) is a complication of coronavirus disease 2019 (COVID-19) that is associated with high mortality. Despite documented kidney tropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are no consistent reports of viral detection in urine or correlation with AKI or COVID-19 severity. Here we hypothesize that quantification of SARS-CoV-2 viral load in urine sediment from COVID-19 patients correlates with occurrence of AKI and mortality. MethodsSARS-CoV-2 viral load in urine sediments (U-viral load) was quantified by qRT-PCR in 52 patients with PCR-confirmed COVID-19 diagnosis, hospitalized between March 15th and June 8th, 2020. Immunolabeling of SARS-CoV-2 proteins Spike and Nucleocapsid was performed in two COVID-19 kidney biopsies and urine sediments. Viral infectivity assays were performed from 32 urine sediments. ResultsTwenty COVID-19 patients (39%) had detectable SARS-CoV-2 U-viral load, of which 17 (85%) developed AKI with an average U-viral load 4-times higher than non-AKI COVID-19 patients. U-viral load was highest (7.7-fold) within two weeks after AKI diagnosis. A higher U-viral load correlated with mortality but not with albuminuria or AKI stage. SARS-CoV-2 proteins partially colocalized with the viral receptor ACE2 in kidney biopsies in tubules and parietal cells, and in urine sediment cells. Infective SARS-CoV-2 was not detected in urine sediments. ConclusionOur results further support SARS-CoV-2 kidney tropism. A higher SARS-CoV-2 viral load in urine sediments from COVID-19 patients correlated with increased incidence of AKI and mortality. Urinary viral detection could inform medical care of COVID-19 patients with kidney injury to improve prognosis.

Background and Objectives: African Americans and males have elevated risks of infection, hospitalization, and death from SARS-CoV-2 in comparison with other populations. We report immune responses and renal injury markers in African American male patients hospitalized for COVID-19. Methods: This was a single-center, retrospective study of 56 COVID-19 infected hospitalized African American males 50+ years of age selected from among non-intensive care unit (ICU) and ICU status patients. Demographics, hospitalization-related variables, and medical history were collected from electronic medical records. Plasma samples collected close to admission (≤2 days) were evaluated for cytokines and renal markers; results were compared to a control group (n = 31) and related to COVID-19 in-hospital mortality. Results: Among COVID-19 patients, eight (14.2%) suffered in-hospital mortality; seven (23.3%) in the ICU and one (3.8%) among non-ICU patients. Interleukin (IL)-18 and IL-33 were elevated at admission in COVID-19 patients in comparison with controls. IL-6, IL-18, MCP-1/CCL2, MIP-1α/CCL3, IL-33, GST, and osteopontin were upregulated at admission in ICU patients in comparison with controls. In addition to clinical factors, MCP-1 and GST may provide incremental value for risk prediction of COVID-19 in-hospital mortality. Conclusions: Qualitatively similar inflammatory responses were observed in comparison to other populations reported in the literature, suggesting non-immunologic factors may account for outcome differences. Further, we provide initial evidence for cytokine and renal toxicity markers as prognostic factors for COVID-19 in-hospital mortality among African American males.

Background The renal mechanisms involved in the maintenance of human hypertension and resistance to treatment are not well understood. Animal studies suggest that chronic renal inflammation contributes to hypertension. We studied cells shed in first‐morning urine samples from individuals who were hypertensive who exhibited difficult‐to‐control blood pressure (BP). We performed bulk RNA sequencing of these shed cells to develop transcriptome‐wide associations with BP. We also analyzed nephron‐specific genes and used an unbiased bioinformatic approach to find signaling pathways activated in difficult‐to‐control hypertension. Methods and Results Participants who completed the SPRINT (Systolic Blood Pressure Intervention Trial) at a single trial site were recruited, and cells shed in first‐morning urine samples collected. A total of 47 participants were divided into 2 groups based on hypertension control. The BP‐difficult group (n=29) had systolic BP>140 mm Hg, >120 mm Hg after intensive treatment for hypertension, or required more than the median number of antihypertensive drugs used in SPRINT. The easy‐to‐control BP group (n=18) comprised the remainder of the participants. A total of 60 differentially expressed genes were identified with a >2‐fold change in the BP‐difficult group. In BP‐difficult participants, 2 of the most upregulated genes were associated with inflammation: Tumor Necrosis Factor Alpha Induced Protien 6 (fold change, 7.76; P =0.006) and Serpin Family B Member 9 (fold change, 5.10; P =0.007). Biological pathway analysis revealed an overrepresentation of inflammatory networks, including interferon signaling, granulocyte adhesion and diapedesis, and Janus Kinase family kinases in the BP‐difficult group ( P <0.001). Conclusions We conclude that transcriptomes from cells shed in first‐morning urine identify a gene expression profile in difficult‐to‐control hypertension that associates with renal inflammation.