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The COVID-19 outbreak has had substantial effects on the incidence and management of kidney diseases, including acute kidney injury (AKI), End-Stage Kidney Disease (ESKD), glomerulonephritis, and kidney transplantation. Initial reports from China suggested a lower AKI incidence in patients with COVID-19, but more recent studies from North America reveal a much higher incidence, likely due to higher prevalence of comorbid conditions such as hypertension, diabetes, and chronic kidney disease (CKD). AKI in this setting is associated with worse outcomes, including requirement for vasopressors or mechanical ventilation and death. Performing renal replacement therapy in those with AKI poses challenges such as limiting exposure of staff, preserving PPE, coagulopathy, and hypoxemia due to Acute Respiratory Distress Syndrome. Continuous Renal Replacement Therapy is the preferred modality, with sustained low-efficiency dialysis also an option, both managed without 1:1 hemodialysis nursing support. Regional citrate is the preferred anticoagulation, but systemic unfractionated heparin may be used in cases of coagulopathy. Ultrafiltration rate has to be set carefully, taking into consideration hypotension, hypoxemia, and responsiveness to presser and ventilatory support. Chance of transmission puts in-center chronic hemodialysis and other immunosuppressed patients at particularly increased risk. Limited data show that patients with CKD are also at increased risk for more severe disease if infected. Little is known about the virus's effects on immunocompromised patients with glomerular diseases and kidney transplants, which introduces challenges for management of immunosuppressant regimens. While there are no standardized guidelines regarding the management of immunosuppression, several groups recommend stopping the anti-metabolite in hospitalized transplant patients and continuing a reduced dose of calcineurin inhibitors. This comprehensive review critically appraises the best available evidence regarding the effect of COVID-19 on the incidence and management of kidney diseases. Where evidence is lacking, current expert opinion and clinical guidelines are reviewed and knowledge gaps worth investigation are identified.

Foxi1e is a zygotic transcription factor that is essential for the expression of early ectodermal genes. It is expressed in a highly specific pattern, only in the deep cell layers of the animal hemisphere, and in a mosaic pattern in which expressing cells are interspersed with non-expressing cells. Previous work has shown that several signals in the blastula control this expression pattern, including nodals, the TGFβ family member Vg1, and Notch. However, these are all inhibitory, which raises the question of what activates Foxi1e. In this work, we show that a related Forkhead family protein, Foxi2, is a maternal activator of Foxi1e. Foxi2 mRNA is maternally encoded, and highly enriched in animal hemisphere cells of the blastula. ChIP assays show that it acts directly on upstream regulatory elements of Foxi1e. Its effect is specific, since animal cells depleted of Foxi2 are able to respond normally to mesoderm inducing signals from vegetal cells. Foxi2 thus acts as a link between the oocyte and the early pathway to ectoderm, in a similar fashion to the vegetally localized VegT acts to initiate endoderm and mesoderm formation.

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Background Acute kidney injury (AKI) is a common complication in patients hospitalized with COVID-19 and may require renal replacement therapy (RRT). Dipstick urinalysis is frequently obtained, but data regarding the prognostic value of hematuria and proteinuria for kidney outcomes is scarce. Methods Patients with positive severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) PCR, who had a urinalysis obtained on admission to one of 20 hospitals, were included. Nested models with degree of hematuria and proteinuria were used to predict AKI and RRT during admission. Presence of Chronic Kidney Disease (CKD) and baseline serum creatinine were added to test improvement in model fit. Results Of 5,980 individuals, 829 (13.9%) developed an AKI during admission, and 149 (18.0%) of those with AKI received RRT. Proteinuria and hematuria degrees significantly increased with AKI severity (P < 0.001 for both). Any degree of proteinuria and hematuria was associated with an increased risk of AKI and RRT. In predictive models for AKI, presence of CKD improved the area under the curve (AUC) (95% confidence interval) to 0.73 (0.71, 0.75), P < 0.001, and adding baseline creatinine improved the AUC to 0.85 (0.83, 0.86), P < 0.001, when compared to the base model AUC using only proteinuria and hematuria, AUC = 0.64 (0.62, 0.67). In RRT models, CKD status improved the AUC to 0.78 (0.75, 0.82), P < 0.001, and baseline creatinine improved the AUC to 0.84 (0.80, 0.88), P < 0.001, compared to the base model, AUC = 0.72 (0.68, 0.76). There was no significant improvement in model discrimination when both CKD and baseline serum creatinine were included. Conclusions Proteinuria and hematuria values on dipstick urinalysis can be utilized to predict AKI and RRT in hospitalized patients with COVID-19. We derived formulas using these two readily available values to help prognosticate kidney outcomes in these patients. Furthermore, the incorporation of CKD or baseline creatinine increases the accuracy of these formulas.