BACKGROUND. RNA sequencing (RNA-Seq) is a molecular tool to analyze global transcriptional changes, deduce pathogenic mechanisms, and discover biomarkers. We performed RNA-Seq to investigate gene expression and biological pathways in urinary cells and kidney allograft biopsies during an acute rejection episode and to determine whether urinary cell gene expression patterns are enriched for biopsy transcriptional profiles. METHODS.We performed RNA-Seq of 57 urine samples collected from 53 kidney allograft recipients (patients) with biopsies classified as acute T cell-mediated rejection (TCMR; n = 22), antibody-mediated rejection (AMR; n = 8), or normal/nonspecific changes (No Rejection; n = 27). We also performed RNA-Seq of 49 kidney allograft biopsies from 49 recipients with biopsies classified as TCMR (n = 12), AMR (n = 17), or No Rejection (n = 20). We analyzed RNA-Seq data for differential gene expression, biological pathways, and gene set enrichment across diagnoses and across biospecimens. RESULTS.We identified unique and shared gene signatures associated with biological pathways during an episode of TCMR or AMR compared with No Rejection. Gene Set Enrichment Analysis demonstrated enrichment for TCMR biopsy signature and AMR biopsy signature in TCMR urine and AMR urine, irrespective of whether the biopsy and urine were from the same or different patients. Cell type enrichment analysis revealed a diverse cellular landscape with an enrichment of immune cell types in urinary cells compared with biopsies.CONCLUSIONS. RNA-Seq of urinary cells and biopsies, in addition to identifying enriched gene signatures and pathways associated with TCMR or AMR, revealed genomic changes between TCMR and AMR, as well as between allograft biopsies and urinary cells.
Because of the unprecedented increase in critically ill patients with coronavirus disease 2019 (COVID-19), capacity to provide continuous RRT (CRRT) for AKI may quickly be overwhelmed (1). Exacerbating this resource crunch is the hypercoagulability observed in COVID-19 (2,3). Frequent CRRT circuit clotting leads to blood loss and wastage of already overextended resources, and need for troubleshooting increases health care provider exposure to infected patients. At our quaternary care academic institution, we perform CRRT using a uniform protocol in five intensive care units (ICUs). We do not use anticoagulation routinely but add it (mostly heparin) as needed. Additionally, for more than a decade, we have used regional citrate anticoagulation (RCA) as the default protocol in our surgical ICU. During the COVID-19 pandemic, our hospital added ten more ICUs. Systemic anticoagulation was available in all 16 ICUs, whereas RCA remained restricted to the surgical ICU, albeit with less frequent postfilter ionized calcium monitoring to reduce nurse exposure to infected patients. Herein, we describe our experience with the life of 502 CRRT circuits on different anticoagulation regimens in 80 patients with RT-PCR-confirmed COVID-19 who received continuous venovenous hemodialysis (NxStage System One) between March 5 and May 8, 2020 (Figure 1A). These circuits were categorized by their anticoagulation regimen at the time of filter stoppage: heparin (systemic unfractionated or low-mol wt heparin [LMWH]), prefilter heparin, argatroban, RCA (citrate), citrate plus heparin (when patients received systemic heparin for medical indications), or no anticoagulation (none). Circuit clotting was our analysis end point. Circuit life was the time (hours) from initiation of CRRT to clotting or censoring. Circuits that functioned beyond 72 hours were censored at 72 hours. Circuits terminated for reasons other than clotting were censored at the time of termination. We determined the association between circuit clotting and anticoagulation groups by Cox regression in Stata 16 software.
AKI is a recognized complication of coronavirus disease 2019 (COVID-19) (1). In this study, we characterized the AKI incidence and outcomes in patients with COVID-19 and AKI. We conducted a retrospective cohort study of 1002 patients admitted from March 1 to April 19, 2020 through the Emergency Department at NewYork-Presbyterian/ Weill Cornell Medical Center. Patient follow-up was until at least June 20, 2020, at which time 22 patients were still hospitalized and nine were transferred to another hospital facility. Baseline creatinine was defined as the closest creatinine prior to March 1, 2020 or, if none was available, the creatinine at time of hospital presentation. The Weill Cornell Institutional Review Board approved this study. AKI, defined by the Kidney Disease Improving Global Outcomes criteria (2), occurred in 294 (29%) of the 1002 patients: stage 1 AKI (n5182, 18%); stage 2 AKI (n529, 3%); and stage 3 AKI (n583, 8%). KRT was performed in 59 patients (6%); 53 received hemodialysis and/or continuous venovenous hemodialysis, five received a combination of acute peritoneal dialysis and hemodialysis/continuous venovenous hemodialysis, and one received acute peritoneal dialysis. The time from hospitalization to AKI was a median of 2.2 days in stage 1 AKI, 2.4 days in stage 2 AKI, and 1.6 days in stage 3 AKI. We evaluated the urine electrolytes and microscopy associated with the AKI event within 3 days. Among those available, the fractional excretion of sodium (FENa) was ,1% in 76%, and urine microscopy had granular casts in 21%. The presumed etiology of stage 3 AKI on the basis of manual chart review was acute tubular necrosis (ATN) in 28%, prerenal in 13%, prerenal/ATN in 11%, other causes in 4%, and unknown in 45% of patients. Granular casts were observed more frequently in stage 3 AKI than stage 1 AKI and stage 2 AKI (33% versus 16%, P50.006). We compared clinical characteristics of the patients with AKI with those without AKI (Table 1). Patients who developed AKI were older and more frequently had a history of hypertension, diabetes mellitus, congestive heart failure, CKD, and kidney transplantation than patients without AKI (P,0.001). Proteinuria and hematuria were
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