Protective effects of vitamin D3 (cholecalciferol) on vancomycin-induced oxidative nephrotoxic damage in rats.

CONTEXT: Vancomycin (VCM), an important antibiotic against refractory infections, has been used to treat secondary infections in severe COVID-19 patients. Regrettably, VCM treatment has been associated with nephrotoxicity. Vitamin D3 can prevent nephrotoxicity through its antioxidant effect. OBJECTIVE: This study tests the antioxidant effect of vitamin D3 in the prevention of VCM-induced nephrotoxicity. MATERIALS AND METHODS: Wistar Albino rats (21) were randomly divided into 3 groups: (A) control; (B) VCM 300 mg/kg daily for 1 week; and (C) VCM plus vitamin D3 500 IU/kg daily for 2 weeks. All the rats were sacrificed and serum was separated to determine kidney function parameters. Their kidneys were also dissected for histological examination and for oxidative stress markers. RESULTS: Lipid peroxidation, creatinine, and urea levels decreased significantly (p < 0.0001) in the vitamin D3-treated group (14.46, 84.11, 36.17%, respectively) compared to the VCM group that was given VCM (MIC<2 µg/mL) only. A significant increase was observed in superoxide dismutase levels in the vitamin D3-treated group (p < 0.05) compared to rats without treatment. Furthermore, kidney histopathology of the rats treated with vitamin D3 showed that dilatation, vacuolization and necrosis tubules decreased significantly (p < 0.05) compared with those in the VCM group. Glomerular injury, hyaline dystrophy, and inflammation improved significantly in the vitamin D3 group (p < 0.001, p < 0.05, p < 0.05, respectively) compared with the VCM group. DISCUSSION AND CONCLUSIONS: Vitamin D3 can prevent VCM nephrotoxicity. Therefore, the appropriate dose of this vitamin must be determined, especially for those infected with COVID-19 and receiving VCM, to manage their secondary infections.

Editorial for the IJMS Special Issue on "Infection and the Kidney".

The coronavirus disease (COVID-19) pandemic has highlighted the close relationship between infection and kidney injury [...].

OPTN/SRTR 2021 Annual Data Report: Kidney.

The year 2021 marked both successes and challenges for the field of kidney transplantation, in the context of the ongoing COVID-19 pandemic and broader geographic organ distribution. The total number of kidney transplants in the United States reached a record count of 25,487, driven by growth in deceased donor kidney transplants. The total number of candidates listed for deceased donor kidney transplant rose slightly in 2021 but remained below 2019 listing levels, with nearly 10% of candidates having been waiting 5 years or longer. Pretransplant mortality declined slightly among candidates of Black, Hispanic, and other races, in parallel with increasing numbers of Black and Hispanic transplant recipients. In the context of broader organ sharing, there is growing disparity in pretransplant mortality among non-metropolitan compared with metropolitan residents. The proportion of deceased donor kidneys recovered but not used for transplant (nonuse rate) rose to a high of 24.6% overall, with greater nonuse among biopsied kidneys (35.9%), kidneys from donors aged 55 years or older (51.1%), and kidneys with kidney donor profile index (KDPI) of 85% or greater (66.6%). Nonuse of kidneys from donors who are hepatitis C virus (HCV) antibody positive only slightly exceeded that of HCV antibody-negative donors. Disparities in access to living donor kidney transplant persists, especially for non-White and publicly insured patients. Delayed graft function continues an upward trend and occurred in 24% of adult kidney transplants in 2021. Five-year graft survival after living compared with deceased donor transplant was 88.6% versus 80.7% for recipients aged 18-34 years, and 82.1% versus 68.0% for recipients aged 65 years or older. The total number of pediatric kidney transplants performed increased to 820 in 2021, the highest number since 2010. Despite numerous efforts, living donor kidney transplant remains low among pediatric recipients, with continued racial disparities. The rate of deceased donor transplants among pediatric candidates recovered in 2021 from a low in 2020. Congenital anomalies of the kidney and urinary tract remain the leading primary kidney disease diagnosis among pediatric candidates. Most pediatric deceased donor recipients receive a kidney from a donor with KDPI less than 35%. Graft survival continues to improve, with superior outcomes for living donor transplant recipients.

SerpinA3K Deficiency Reduces Oxidative Stress in Acute Kidney Injury.

We previously showed that SerpinA3K is present in urine from rats and humans with acute kidney injury (AKI) and chronic kidney disease (CKD). However, the specific role of SerpinA3K during renal pathophysiology is unknown. To begin to understand the role of SerpinA3K on AKI, SerpinA3K-deficient (KOSA3) mice were studied 24 h after inducing ischemia/reperfusion (I/R) and compared to wild type (WT) mice. Four groups were studied: WT+S, WT+IR, KOSA3+S, and KOSA3+IR. As expected, I/R increased serum creatinine and BUN, with a GFR reduction in both genotypes; however, renal dysfunction was ameliorated in the KOSA3+IR group. Interestingly, the increase in UH2O2 induced by I/R was not equally seen in the KOSA3+IR group, an effect that was associated with the preservation of antioxidant enzymes' mRNA levels. Additionally, FOXO3 expression was initially greater in the KOSA3 than in the WT group. Moreover, the increase in BAX protein level and the decrease in Hif1a and Vegfa induced by I/R were not observed in the KOSA3+IR group, suggesting that these animals have better cellular responses to hypoxic injury. Our findings suggest that SerpinA3K is involved in the renal oxidant response, HIF1α/VEGF pathway, and cell apoptosis.

Knowing When to Ignore the Numbers: Single-Center Experience Transplanting Deceased Donor Kidneys with Poor Perfusion Parameters.

BACKGROUND: Hypothermic machine perfusion is frequently used in evaluating marginal kidneys with poor perfusion parameters (PPP) contributing to delays in kidney placement or discard. We examined outcomes in deceased donor kidney transplants with PPP compared with those with optimal perfusion parameters (OPP). STUDY DESIGN: We conducted a retrospective single-center cohort study from 2001 to 2021 comparing PPP (n = 91) with OPP (n = 598) deceased donor kidney transplants. PPP was defined as terminal flow ≤80 mL/min and terminal resistance ≥0.40 mmHg/mL/min. OPP was defined as terminal flow ≥120 mL/min and terminal resistance ≤0.20 mmHg/mL/min. RESULTS: Mean terminal flow was PPP 66 ± 16 vs OPP 149 ± 21 mL/min and resistance was PPP 0.47 ± 0.10 vs OPP 0.15 ± 0.04 mmHg/mL/min (both p < 0.001). Donor age, donation after cardiac death, and terminal serum creatinine levels were similar between groups. Mean Kidney Donor Profile Index was higher among PPP donors (PPP 65 ± 23% vs OPP 52 ± 27%, p < 0.001). The PPP transplant group had more females and lower weight and BMI. Delayed graft function was comparable (PPP 32% vs OPP 27%, p = 0.33) even though cold ischemia times trended toward longer in PPP kidneys (PPP 28 ± 10 vs OPP 26 ± 9 hours, p = 0.09). One-year patient survival (PPP 98% vs OPP 97%, p = 0.84) and graft survival (PPP 91% vs OPP 92%, p = 0.23) were equivalent. PPP did predict inferior overall and death-censored graft survival long-term (overall hazard ratio 1.63, 95% CI 1.19 to 2.23 and death-censored hazard ratio 1.77, 95% CI 1.15 to 2.74). At 1 year, the estimated glomerular filtration rate was higher with OPP kidneys (PPP 40 ± 17 vs OPP 52 ± 19 mL/min/1.73 m 2 , p < 0.001). CONCLUSIONS: Short-term outcomes in PPP kidneys were comparable to OPP kidneys despite higher Kidney Donor Profile Index and longer cold ischemia times, suggesting a role for increased utilization of these organs with careful recipient selection.

Kidney health for all: preparedness for the unexpected in supporting the vulnerable.

As the rate of natural disasters and other devastating events caused by human activities increases, the burden on the health and well-being of those affected by kidney disease has been immeasurable. Health system preparedness, which involves creating a resilient system that is able to deal with the health needs of the entire community during times of unexpected disruptions to usual care, has become globally important. In the wake of the COVID-19 pandemic, there is a heightened awareness of the amplification of negative effects on the renal community. Paradoxically, the complex medical needs of those who have kidney diseases are not met by systems handling crises, often compounded by an acute increase in burden via new patients as a result of the crisis itself. Disruptions in kidney care as a result of unexpected events are becoming more prevalent and likely to increase in the years to come. It is therefore only appropriate that the theme for this year's World Kidney Day will focus on Kidney Health for All: preparedness for the unexpected in supporting the vulnerable.

Use of medicines for covid-19 treatment in patients with loss of kidney function: a narrative review.

Covid-19 has been identified as the cause of acute respiratory disease with interstitial and alveolar pneumonia, but it can affect several organs, such as kidneys, heart, blood, nervous system and digestive tract. The disease-causing agent (Sars-CoV-2) has a binding structure to the angiotensin-converting enzyme 2 (ACE2) receptor, enabling entry into cells that express ACE2, such as the pulmonary alveolar epithelial cells. However, studies also indicate the possibility of damage to renal cells, since these cells express high levels of ACE2. Currently, there is no evidence to indicate a specific treatment for covid-19. Several drugs have been used, and some of them may have their excretion process altered in patients with abnormal kidney function. To date, there are no studies that assist health professionals in adjusting the dose of these drugs. Thus, this study aims to review and discuss the topic, taking into account factors associated with kidney injury in covid-19, as well as pharmacokinetic aspects and dose recommendations of the main drugs used for covid-19.

Identification of berberine as a potential therapeutic strategy for kidney clear cell carcinoma and COVID-19 based on analysis of large-scale datasets.

Background: Regarding the global coronavirus disease 2019 (COVID)-19 pandemic, kidney clear cell carcinoma (KIRC) has acquired a higher infection probability and may induce fatal complications and death following COVID-19 infection. However, effective treatment strategies remain unavailable. Berberine exhibits significant antiviral and antitumour effects. Thus, this study aimed to provide a promising and reliable therapeutic strategy for clinical decision-making by exploring the therapeutic mechanism of berberine against KIRC/COVID-19. Methods: Based on large-scale data analysis, the target genes, clinical risk, and immune and pharmacological mechanisms of berberine against KIRC/COVID-19 were systematically investigated. Results: In total, 1,038 and 12,992 differentially expressed genes (DEGs) of COVID-19 and KIRC, respectively, were verified from Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively, and 489 berberine target genes were obtained from official websites. After intersecting, 26 genes were considered potential berberine therapeutic targets for KIRC/COVID-19. Berberine mechanism of action against KIRC/COVID-19 was revealed by protein-protein interaction, gene ontology, and Kyoto Encyclopedia of Genes and Genomes with terms including protein interaction, cell proliferation, viral carcinogenesis, and the PI3K/Akt signalling pathway. In COVID-19 patients, ACOX1, LRRK2, MMP8, SLC1A3, CPT1A, H2AC11, H4C8, and SLC1A3 were closely related to disease severity, and the general survival of KIRC patients was closely related to ACOX1, APP, CPT1A, PLK1, and TYMS. Additionally, the risk signature accurately and sensitively depicted the overall survival and patient survival status for KIRC. Numerous neutrophils were enriched in the immune system of COVID-19 patients, and the lives of KIRC patients were endangered due to significant immune cell infiltration. Molecular docking studies indicated that berberine binds strongly to target proteins. Conclusion: This study demonstrated berberine as a potential treatment option in pharmacological, immunological, and clinical practice. Moreover, its therapeutic effects may provide potential and reliable treatment options for patients with KIRC/COVID-19.

Post COVID-19 AA amyloidosis of the kidneys with rapidly progressive renal failure.

Coronavirus disease 2019 (COVID-19) pandemic has taken the world by a storm, posing a gruelling challenge to the medical fraternity globally. Besides its very high infectivityinfectivity, significant organ dysfunction occurs in critically ill COVID-19 patients, leading to severe morbidity and mortality. Pulmonary involvement is the leading cause of death in these patients to be followed by the cardiovascular involvement. Kidney involvement due to COVID-19 is becoming more discernible with AKI adversely affecting the outcome. Besides AKI, a few cases of collapsing FSGS in genetically vulnerable patients and thrombotic microangiopathies have been reported as well. We report a case of AA amyloidosis of the kidney with a rapidly progressive renal failure and congestive heart failure with preserved left ventricular functions, which complicated a moderate COVID-19 pneumonia providing some clues to a possible association of this novel virus disease with this complication, which needs to be confirmed in future studies.

Renal Thrombotic Microangiopathy: A Review.

Thrombotic microangiopathy (TMA), a pathological lesion observed in a wide spectrum of diseases, is triggered by endothelial injury and/or dysfunction. Although TMA lesions are often accompanied by clinical features of microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end-organ injury, renal-limited forms of TMA are not infrequently encountered in clinical practice. The presence of renal-limited manifestations can be diagnostically challenging, often delaying the initiation of targeted therapy. Prompt investigation and empirical treatment of TMA is warranted to reduce associated morbidity and mortality. Major advances have been made with respect to the pathophysiology of primary TMA entities, with the subsequent development of novel diagnostic tools and lifesaving therapies for diseases like thrombotic thrombocytopenic purpura and complement-mediated TMA. This article will review the clinical presentation and pathologic hallmarks of TMA involving the kidney, and the disease-specific mechanisms that contribute to the endothelial injury that characterizes TMA lesions. Diagnostic approach and both empirical and disease-specific treatment strategies will be discussed, along with the potential role for emerging targeted disease-specific therapies.

Personalised recommendations for hospitalised patients with Acute Kidney Injury using a Kidney Action Team (KAT-AKI): protocol and early data of a randomised controlled trial.

INTRODUCTION: Although studies have examined the utility of clinical decision support tools in improving acute kidney injury (AKI) outcomes, no study has evaluated the effect of real-time, personalised AKI recommendations. This study aims to assess the impact of individualised AKI-specific recommendations delivered by trained clinicians and pharmacists immediately after AKI detection in hospitalised patients. METHODS AND ANALYSIS: KAT-AKI is a multicentre randomised investigator-blinded trial being conducted across eight hospitals at two major US hospital systems planning to enrol 4000 patients over 3 years (between 1 November 2021 and 1 November 2024). A real-time electronic AKI alert system informs a dedicated team composed of a physician and pharmacist who independently review the chart in real time, screen for eligibility and provide combined recommendations across the following domains: diagnostics, volume, potassium, acid-base and medications. Recommendations are delivered to the primary team in the alert arm or logged for future analysis in the usual care arm. The planned primary outcome is a composite of AKI progression, dialysis and mortality within 14 days from randomisation. A key secondary outcome is the percentage of recommendations implemented by the primary team within 24 hours from randomisation. The study has enrolled 500 individuals over 8.5 months. Two-thirds were on a medical floor at the time of the alert and 17.8% were in an intensive care unit. Virtually all participants were recommended for at least one diagnostic intervention. More than half (51.6%) had recommendations to discontinue or dose-adjust a medication. The median time from AKI alert to randomisation was 28 (IQR 15.8-51.5) min. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of each study site (Yale University and Johns Hopkins institutional review board (IRB) and a central IRB (BRANY, Biomedical Research Alliance of New York). We are committed to open dissemination of the data through clinicaltrials.gov and sharing of data on an open repository as well as publication in a peer-reviewed journal on completion. TRIAL REGISTRATION NUMBER: NCT04040296.

Melatonin Treatment in Kidney Diseases.

Melatonin is a neurohormone that is mainly secreted by the pineal gland. It coordinates the work of the superior biological clock and consequently affects many processes in the human body. Disorders of the waking and sleeping period result in nervous system imbalance and generate metabolic and endocrine derangements. The purpose of this review is to provide information regarding the potential benefits of melatonin use, particularly in kidney diseases. The impact on the cardiovascular system, diabetes, and homeostasis causes melatonin to be indirectly connected to kidney function and quality of life in people with chronic kidney disease. Moreover, there are numerous reports showing that melatonin plays a role as an antioxidant, free radical scavenger, and cytoprotective agent. This means that the supplementation of melatonin can be helpful in almost every type of kidney injury because inflammation, apoptosis, and oxidative stress occur, regardless of the mechanism. The administration of melatonin has a renoprotective effect and inhibits the progression of complications connected to renal failure. It is very important that exogenous melatonin supplementation is well tolerated and that the number of side effects caused by this type of treatment is low.

Role of FXR in Renal Physiology and Kidney Diseases.

Farnesoid X receptor, also known as the bile acid receptor, belongs to the nuclear receptor (NR) superfamily of ligand-regulated transcription factors, which performs its functions by regulating the transcription of target genes. FXR is highly expressed in the liver, small intestine, kidney and adrenal gland, maintaining homeostasis of bile acid, glucose and lipids by regulating a diverse array of target genes. It also participates in several pathophysiological processes, such as inflammation, immune responses and fibrosis. The kidney is a key organ that manages water and solute homeostasis for the whole body, and kidney injury or dysfunction is associated with high morbidity and mortality. In the kidney, FXR plays an important role in renal water reabsorption and is thought to perform protective functions in acute kidney disease and chronic kidney disease, especially diabetic kidney disease. In this review, we summarize the recent advances in the understanding of the physiological and pathophysiological function of FXR in the kidney.

Comparison of vector elements and process conditions in transient and stable suspension HEK293 platforms using SARS-CoV-2 receptor binding domain as a model protein.

BACKGROUND: Mammalian cell lines are frequently used as protein expression hosts because of their ability to correctly fold and assemble complex proteins, produce them at high titers, and confer post-translational modifications (PTMs) critical to proper function. Increasing demand for proteins with human-like PTMs, particularly viral proteins and vectors, have made human embryonic kidney 293 (HEK293) cells an increasingly popular host. The need to engineer more productive HEK293 platforms and the ongoing nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presented an opportunity to study strategies to improve viral protein expression in transient and stable HEK293 platforms. RESULTS: Initial process development was done at 24 deep well plate (DWP) -scale to screen transient processes and stable clonal cell lines for recombinant SARS-CoV-2 receptor binding domain (rRBD) titer. Nine DNA vectors that drove rRBD production under different promoters and optionally contained Epstein-Barr virus (EBV) elements to promote episomal expression were screened for transient rRBD production at 37 °C or 32 °C. Use of the cytomegalovirus (CMV) promoter to drive expression at 32 °C led to the highest transient protein titers, but inclusion of episomal expression elements did not augment titer. In parallel, four clonal cell lines with titers higher than that of the selected stable pool were identified in a batch screen. Flask-scale transient transfection and stable fed-batch processes were then established that produced rRBD up to 100 mg/L and 140 mg/L, respectively. While a bio-layer interferometry (BLI) assay was crucial for efficiently screening DWP batch titers, an enzyme-linked immunosorbent assay (ELISA) was used to compare titers from the flask-scale batches due to varying matrix effects from different cell culture media compositions. CONCLUSION: Comparing yields from the flask-scale batches revealed that stable fed-batch cultures produced up to 2.1x more rRBD than transient processes. The stable cell lines developed in this work are the first reported clonal, HEK293-derived rRBD producers and have titers up to 140 mg/L. As stable production platforms are more economically favorable for long-term protein production at large scales, investigation of strategies to increase the efficiency of high-titer stable cell line generation in Expi293F or other HEK293 hosts is warranted.

Impact of monocyte-related modulators and kidney function on mortality in hospitalized patients with COVID-19.

Patients with chronic kidney disease (CKD) are at high risk of severe complications from COVID-19 and functional monocyte disturbances have been implicated to play a role. Our objective was to analyse the association between kidney function and monocyte modulatory factors, with risk of mortality in patients with COVID-19. Hospitalized patients with COVID-19 (n = 110) were included and in-hospital mortality was analysed with unadjusted and adjusted multiple logistic regression analysis. Plasma levels of monocyte chemoattractant factors (MIP-1α, MCP-1, IL-6) and a monocyte immune modulator (sCD14) were analysed and correlated to kidney function and risk of mortality. Monocyte modulatory factors were also determined in CKD patients without infection (disease controls) and in healthy subjects. Patients who died in hospital were more often in CKD stages 3-5, with lower estimated glomerular filtration rate (eGFR) and had significantly higher MIP-1α and IL-6 levels than survivors. In multiple regression analyses adjusted for age, sex and eGFR, both high MCP-1 and high MIP-1α were significantly associated with risk of in-hospital mortality. Apart from impaired kidney function, also the concentrations of MCP-1 and MIP-1α add important prognostic information in hospitalized patients with COVID-19. These data provide an increased understanding of the impact of monocyte modulators in patients with COVID-19 and normal or impaired kidney function, and warrant consideration in the pursuit of new effective therapies.

Effect of remdesivir on adverse kidney outcomes in hospitalized patients with COVID-19 and impaired kidney function.

BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for mortality from COVID-19. Remdesivir has been shown to shorten time to recovery in patients with severe COVID-19. However, exclusion of patients with severe kidney function impairment in clinical trials has led to concerns about kidney safety of remdesivir in patients with pre-existing kidney disease. METHODS: Retrospective propensity score matched cohort study of hospitalized patients with COVID-19 admitted with estimated glomerular filtration rate (eGFR) between 15 - 60 mL/min/1.73m2. Remdesivir-treated patients were 1:1 matched to historical comparators admitted during the first wave of COVID-19 (between March-April 2020) prior to emergency use authorization of remdesivir using propensity scores accounting for factors predicting treatment assignment. Dependent outcomes included in-hospital peak creatinine, incidence of doubling of creatine, rate of kidney replacement therapy initiation and eGFR among surviving patients at day 90. RESULTS: 175 remdesivir-treated patients were 1:1 matched to untreated historical comparators. Mean age was 74.1 (SD 12.8), 56.9% were male, 59% patients were white, and the majority (83.1%) had at least one co-morbidity. There were no statistically significant differences in peak creatinine during hospitalization (2.3mg/dL vs. 2.5 mg/dL, P = 0.34), incidence of doubling of creatinine (10.3% vs. 13.1%, P = 0.48), and rate of kidney replacement therapy initiation (4.6% vs. 6.3%, P = 0.49) in remdesivir-treated patients versus matched untreated historical comparators, respectively. Among surviving patients, there was no difference of the average eGFR at day 90 (54.7 ± 20.0 mL/min/1.73m2 for remdesivir-treated patients vs. 51.7 ± 19.5 mL/min/1.73m2 for untreated comparators, P = 0.41). CONCLUSIONS: Remdesivir use in patients with impaired kidney function (eGFR between 15 - 60 mL/min/1.73m2) who present to the hospital with COVID-19 is not associated with increased risk of adverse kidney outcomes.

Identification of the regulatory mechanism of ACE2 in COVID-19-induced kidney damage with systems genetics approach.

Studies showed that SARS-CoV-2 can directly target the kidney and induce renal damage. As the cell surface receptor for SARS-CoV-2 infection, the angiotensin-converting enzyme 2 (ACE2) plays a pivotal role for renal physiology and function. Thus, it is important to understand ACE2 through which pathway influences the pathogenesis of renal damage induced by COVID-19. In this study, we first performed an eQTL mapping for Ace2 in kidney tissues in 53 BXD mice strains. Results demonstrated that Ace2 is highly expressed and strongly controlled by a genetic locus on chromosome 16 in the kidney, with six genes (Dnase1, Vasn, Usp7, Abat, Mgrn1, and Rbfox1) dominated as the upstream modulator, as they are highly correlated with Ace2 expression. Gene co-expression analysis showed that Ace2 co-variates are significantly involved in the renin-angiotensin system (RAS) pathway which acts as a reno-protector. Importantly, we also found that Ace2 is positively correlated with Pdgf family members, particularly Pdgfc, which showed the most association among the 76 investigated growth factors. Mammalian Phenotype Ontology enrichment indicated that the cognate transcripts for both Ace2 and Pdgfc were mainly involved in regulating renal physiology and morphology. Among which, Cd44, Egfr, Met, Smad3, and Stat3 were identified as hub genes through protein-protein interaction analysis. Finally, in aligning with our systems genetics findings, we found ACE2, pdgf family members, and RAS genes decreased significantly in the CAKI-1 kidney cancer cells treated with S protein and receptor binding domain structural protein. Collectively, our data suggested that ACE2 work with RAS, PDGFC, as well as their cognate hub genes to regulate renal function, which could guide for future clinical prevention and targeted treatment for COVID-19-induced renal damage outcomes. KEY MESSAGES: • Ace2 is highly expressed and strongly controlled by a genetic locus on chromosome 16 in the kidney. • Ace2 co-variates are enriched in the RAS pathway. • Ace2 is strongly correlated with the growth factor Pdgfc. • Ace2 and Pdgfc co-expressed genes involved in the regulation of renal physiology and morphology. • SARS-CoV-2 spike glycoprotein induces down-regulation of Ace2, RAS, and Pdgfc.