Pathways of Renal Involvement in COVID-19 Infection

The causative agent of the highly infectious pandemic COVID-19 is SARS-CoV-2. According to WHO, as of August 18th 2020, the number of confirmed cases was and confirmed deaths was 771,635 from 216 countries. The most affected organ system in COVID-19 is the respiratory system. Later studies proved that the virus caused multiorgan infections. Several studies shows that SARS-CoV-2 causes damage to the renal system and; critically ill patients with associated renal damage show a higher mortality rate as compared to those patients with an unaffected renal system .This review article aims at updating the knowledge about associated kidney failure in covid-19 cases and its impact on the morbidity and mortality. The virus damages the renal system through two different mechanisms: Direct and Indirect pathway. The direct pathway explains how the virus damages the renal system by directly acting upon the target cells in the kidney.SARS-CoV-2 gains its entry by binding to the ACE2 receptors on the target cell. The SARS-CoV-2 progresses its journey and extensively spread the infection, damaging the kidneys leading to the failure of the renal system. The indirect pathway of damage speaks about the secondary damage caused to the renal system due to cytokine release syndrome caused by SARS-CoV-2.This pathway also points out the formation of microthrombi in the glomerular capillaries and also kidney hypoperfusion. AKI in covid-19 patients can occur secondary to multiorgan failure. This review aims to build a foundation concerning the direct pathway and indirect pathway by means of which SARS-Cov-2 infects the kidneys by summarizing the numerous researches carried out till date to update the knowledge gained thus far to aid in building better protocols for covid-19 management and decrease morbidity caused due to renal damage.

SLC22 Transporters in the Fly Renal System Regulate Response to Oxidative Stress In Vivo

Several SLC22 transporters in the human kidney and other tissues are thought to regulate endogenous small antioxidant molecules such as uric acid, ergothioneine, carnitine, and carnitine derivatives. These transporters include those from the organic anion transporter (OAT), OCTN/OCTN-related, and organic cation transporter (OCT) subgroups. In mammals, it has been difficult to show a clear in vivo role for these transporters during oxidative stress. Ubiquitous knockdowns of related Drosophila SLC22s—including transporters homologous to those previously identified by us in mammals such as the “Fly-Like Putative Transporters” FLIPT1 (SLC22A15) and FLIPT2 (SLC22A16)—have shown modest protection against oxidative stress. However, these fly transporters tend to be broadly expressed, and it is unclear if there is an organ in which their expression is critical. Using two tissue-selective knockdown strategies, we were able to demonstrate much greater and longer protection from oxidative stress compared to previous whole fly knockdowns as well as both parent and WT strains (CG6126: p < 0.001, CG4630: p < 0.01, CG16727: p < 0.0001 and CG6006: p < 0.01). Expression in the Malpighian tubule and likely other tissues as well (e.g., gut, fat body, nervous system) appear critical for managing oxidative stress. These four Drosophila SLC22 genes are similar to human SLC22 transporters (CG6126: SLC22A16, CG16727: SLC22A7, CG4630: SLC22A3, and CG6006: SLC22A1, SLC22A2, SLC22A3, SLC22A6, SLC22A7, SLC22A8, SLC22A11, SLC22A12 (URAT1), SLC22A13, SLC22A14)—many of which are highly expressed in the kidney. Consistent with the Remote Sensing and Signaling Theory, this indicates an important in vivo role in the oxidative stress response for multiple SLC22 transporters within the fly renal system, perhaps through interaction with SLC22 counterparts in non-renal tissues. We also note that many of the human relatives are well-known drug transporters. Our work not only indicates the importance of SLC22 transporters in the fly renal system but also sets the stage for in vivo studies by examining their role in mammalian oxidative stress and organ crosstalk.

Narrative review of recent studies on the role of vitamin D in the prevention of cardiac and renal risk and additional considerations for COVID-19 vulnerability

: The role of vitamin D in maintaining a healthy cardiovascular (CV) and the renal system has received increasing attention. Low vitamin D levels are associated with the incidence of hypertension, cardiac remodeling, and chronic congestive heart failure. Low vitamin D levels also influence renal disease progression and albuminuria deterioration. Moreover, recent research indicates that vitamin D deficiency can be a potential risk factor for coronavirus disease-19 (COVID-19) infection and poorer outcomes. Data are inconclusive as to whether supplementation with vitamin D agents reduces CV disease risk or COVID-19 severity. Conversely, in patients with kidney disease, vitamin D supplementation is associated with improved kidney function and albuminuria. This narrative review considers recent data on the effects of vitamin D on the CV and renal system, as well as its possible role regarding COVID-19 complications.

Bladder Dysfunction and Re-Absorbable Bulking Agent Affect Success Rate in Children Underwent Endoscopic Treatment for Vesicoureteral Reflux: A Long-Term Follow-Up Study

This paper is designed to evaluate the results (at long-term follow-up of) children affected by dilating VUR. Our attention was focused on how VUR grade, laterality, bladder dysfunction (BD), the double renal system, and the type of bulking substance may affect VUR resolution in the long-term period. The charts of 93 children with dilating VUR who underwent endoscopic treatment (ET) and with a minimum post-operative follow-up of 7 years were reviewed (mean follow-up time was 9.6 + 1.4). The majority of patients had severe and bilateral VUR. Polydimetilsiloxane or hyaluronic acid/dextranomer (PDS or Ha/Dx) were used as bulking agents. VUR persistence following endoscopic injection was independent with respect to grade, laterality, duplex renal system, and BD. However, the rate of VUR persistence was significantly higher in children with BD. Children treated with Ha/Dx had a higher rate of VUR persistence. This research demonstrated that ET of VUR is also effective at very long term follow up (and without the development of significant complications). We also showed that patients treated with absorbable bulking agents such as Ha/Dx may experience a higher recurrence rate at the long-term follow-up). We also confirm that the only preoperative condition affecting VUR recurrence was bladder dysfunction.

Nefarious to noteworthy: Lipid droplets shed their negative image

Lipid droplets kill pathogens and serve a crucial role in the body’s immune response. Their accumulation inside the kidney cells could protect the renal system from the damaging effects of a high-fat diet. These findings prove that lipid droplets serve a far greater purpose in the body than once imaged, opening the door for further investigations and possible treatment applications.

Study of subacute renal toxicity of Bisphenol A in rats

Background and Aims: Bisphenol A (BPA) falls in the category of hormonal disruptors due to its widespread application, and several studies have revealed its toxicity in different doses. However, few studies have investigated the effect of BPA on the renal system. Therefore, the present study aimed to investigate the effect of BPA on renal system function in rats. Materials and Methods: Initially, the rats were divided into 6 groups (n=6). Group 1 received only the carrier substance. The rats in the second to sixth groups were gavaged with BPA in 0.1, 1, 10, 50, and, 100 mg/kg/BW/day doses for 29 days, respectively. On the 30th day, blood samples were taken from the heart and kidney tissues were separated after collecting 24 h urine. Biochemical parameters including urea, creatinine, total urine and serum protein, and serum albumin were measured subsequently. Eventually, kidney tissue was sent to a laboratory for histological examination. Results: There was no significant difference in serum creatinine levels in rats treated with different doses of bisphenol A. However, its level in urine increased at 50 mg/kg dose, compared to 1 and 10 mg/kg doses (P<0.001). Serum and urine urea increased significantly only at of 10 mg/kg dose, compared to 1 and 0.1 mg/kg doses (P<0.001). Serum albumin was reduced at 100 mg/kg dose, compared to controls. Total serum protein decreased at doses of 50 and 100 mg/kg, compared to controls and increased in urine at 50mg/kg dose (P<0.001). The protein/creatinine ratio increased significantly at doses of 1 to 50 mg/kg (P<0.001). Histological examination also revealed that BPA caused degenerative, infiltration, and dilation changes in kidney tissue in a dose-dependent manner. Conclusion: Based on the obtained data, BPA at 50 and 100 mg/kg concentrations could lead to kidney tissue damage in rats and subsequent renal failure.

Manifestations of renal system involvement in hospitalized patients with COVID-19 in Saudi Arabia

Background Although COVID-19 is an acute disease that usually resolves rapidly in most cases, the disease can be fatal and has a mortality rate of about 1% to 56%. Alveolar injury and respiratory failure are the main causes of death in patients with COVID 19. In addition, the effect of the disease on other organs is not fully understood. Renal system affection has been reported in patients with COVID 19 and is associated with a higher rate of diverse outcomes, including mortality. Therefore, in the present work, we reported the clinical characteristics and laboratory data of hospitalized patients with COVID-19 and analyzed the manifestations that indicated renal system involvement and their impact on clinical outcomes. Materials and methods This was an observational retrospective study conducted at King Fahd Specialist Hospital, Buraydah, Saudi Arabia. All patients with COVID-19 who were admitted to this Hospital from April to December 2020 were included in the study. The patients’ findings at presentation were recorded. Demographic data and laboratory results (hematuria, proteinuria, urinary sediment cast and pus cell presence, and kidney function tests) were retrieved from electronic patient records. Results One hundred and ninety-three patients with confirmed COVID 19 were included in the study. Dipstick examinations of all urine samples showed proteinuria and hematuria in 53.9% and 22.3% of patients, respectively, whereas microscopic examination revealed the presence of pus and brown muddy granular casts in 33.7% and 12.4% of samples, respectively. Acute kidney injury was reported in 23.3% of patients. A multivariable analysis demonstrated that hematuria was associated with acute kidney injury (AKI) (OR, 2.4; 95% CI, 1.2–4.9; P = 0.001), ICU admission (OR, 3.789; 95% CI, 1.913–7.505; P = 0.003), and mortality (OR, 8.084; 95% CI, 3.756–17.397; P = 0.002). Conversely, proteinuria was less significantly associated with the risk of AKI (OR, 1.56; 95% CI, 1.91–7.50; P = 0.003), ICU admission (OR, 2.493; 95% CI, 1.25–4.72; P = 0.001), and mortality (OR, 2.764; 95% CI, 1.368–5.121; P = 0.003). Patients with AKI had a higher probability for mortality than did those without AKI (OR, 14.208; 95% CI, 6.434–31.375; P = 0.003). Conclusion The manifestations of the involvement of the renal system are not uncommon in COVID-19. These manifestations included proteinuria, hematuria, and AKI and were usually associated with a poor prognosis, including high incidences of both ICU admission and mortality.