|Year : 2022 | Volume
| Issue : 4 | Page : 153-159
Coronavirus Disease-2019 and the kidneys: A tragedy of reciprocal damage and management challenges
Eman Sobh1, Ahmed Salama Al-Adl2, Mohamed F Awadallah3, Khloud Gamal Abdelsalam4, Sohaila Sabry Awad5, Amal M Surrati6, Hani A Alhadrami7
1 Department of Chest Diseases, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Department of Respiratory Therapy, College of Medical Rehabilitation Sciences, Taibah University, Medina, Saudi Arabia
2 Department of Internal Medicine, Nephrology Unit, Faculty of Medicine, Al-Azhar University, Damietta, Egypt
3 Department of Chest Diseases, Faculty of Medicine, Al-Azhar University, Damietta, Egypt
4 Department of Chemistry, Biochemistry Unit, Faculty of Science, Damanhour University, Damanhour, Egypt
5 Department of Chemistry/Biochemistry, Faculty of Science, Cairo University, Cairo, Egypt
6 Department of Family and Community Medicine, College of Medicine, Taibah University, Medina, Saudi Arabia
7 Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences; Department of Medical Technology, Molecular Diagnostic Lab, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia
|Date of Submission||05-May-2021|
|Date of Decision||17-Aug-2021|
|Date of Acceptance||23-Aug-2021|
|Date of Web Publication||30-Oct-2021|
Prof. Eman Sobh
Department of Chest Diseases, Faculty of Medicine for Girls, Al-Azhar University, Cairo
Source of Support: None, Conflict of Interest: None
Coronavirus disease 2019 (COVID-19) has been reported to affect nearly all body systems. Kidney affection has been observed in several studies. The effect of COVID-19 on renal function is beyond that occurring in pneumonia or severe respiratory distress cases. Renal affection is attributed to several factors, including the mechanism of viral injury. Patients with preexisting kidney injury are at increased risk of infection. Early detection and management are crucial to avoid morbidity and mortality, prevent the spread and contamination of hemodialysis Units. Early detection and treatment of kidney involvement in COVID-19 are vital to avoid increased morbidity and mortality. Proper selection of drugs and fluid management is vital in cases with kidney involvement. This review aims to discuss the clinical and pathophysiological affection of the kidney in COVID-19.
Keywords: Acute kidney injury, chronic kidney disease, coronavirus, COVID-19, kidney injury, severe acute respiratory syndrome-coronavirus-2
|How to cite this article:|
Sobh E, Al-Adl AS, Awadallah MF, Abdelsalam KG, Awad SS, Surrati AM, Alhadrami HA. Coronavirus Disease-2019 and the kidneys: A tragedy of reciprocal damage and management challenges. J Med Sci 2022;42:153-9
|How to cite this URL:|
Sobh E, Al-Adl AS, Awadallah MF, Abdelsalam KG, Awad SS, Surrati AM, Alhadrami HA. Coronavirus Disease-2019 and the kidneys: A tragedy of reciprocal damage and management challenges. J Med Sci [serial online] 2022 [cited 2023 Dec 4];42:153-9. Available from: https://www.jmedscindmc.com/text.asp?2022/42/4/153/353043
| Introduction|| |
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is the causative agent of the current pandemic COVID-19 as announced by the World Health Organization (WHO) 1 year ago., SARS-CoV-2 is a novel single-strand RNA coronavirus. Although SARS-CoV-2 is a respiratory pathogen invading the respiratory tract mainly and causing several respiratory symptoms; several reports have been published describing hundreds of extrapulmonary manifestations affecting nearly everybody organ, including the cardiovascular, gastrointestinal, genitourinary, and central nervous systems. It is very important to understand the mechanisms, the clinical presentation, and the consequences of affection of these organs. Kidney involvement in COVID-19 is still not fully understood. In this review, we aim to investigate factors associated with kidney injury in COVID-19 and through light on the current situation, diagnosis, and management.
| Epidemiology and Evidence of Kidney Injury in COVID-19|| |
Several studies reported that kidney injury is prevalent in COVID-19 patients, especially those admitted to intensive care unit (ICU). The prevalence of acute kidney injury (AKI) in COVID-19 is widely different across reports. It ranges from 0.5% to 29%., The incidence rate is variable and is as high as 50% in ICU patients.,, Reports from countries outside China had higher rates of kidney injury in COVID-19.
Controversary, Wang et al. evaluated reports of 116 hospitalized patients with COVID-19 confirmed cases from China. Using the standardized definitions of AKI and chronic kidney disease (CKD), they reported that 111 patients without CKD did not develop abnormal kidney function during the observation period. Twelve patients had a mild increase in blood urea nitrogen or serum creatinine after SARS-CoV-2 infection which did not meet the criteria for AKI (<26 μmol/L within 48 h and trace albuminuria). These abnormalities returned to normal during follow-up without treatment directed to the kidney. Furthermore, patients with CKD had a stable condition of kidney function without deterioration. They concluded that COVID-19 was not a cause of AKI or exacerbation of CKD despite the presence of SARS-CoV-2 RNA in the urine of some patients.
The high incidence of AKI in some reports of COVID-19 may be attributed to delayed hospitalizations and exhaustion of health care resources. The discrepancy in the frequency of kidney injury in COVID-19 in several studies may be attributed to the variability in the definition of AKI used in each study, different study types, sample size, frequency of serum creatinine testing, and clinical condition. Critically ill patients were more likely to develop AKI than stable cases.
Some studies reported evidence from renal biopsy and autopsy as evidence for the affection of both tubular and parenchymal components of the kidney. Light microscopy examination of the renal autopsy showed prominent proximal acute tubular injury, diffuse erythrocyte aggregation, and obstruction of peritubular and glomerular capillaries with no obvious thrombi or fragmentation. Few cases showed pyelonephritis, hemosiderin granules deposition, or nonspecific inflammation with lymphocyte infiltrations. No evidence of vasculitis, hemorrhage, or interstitial inflammation was detected. Electron microscopy showed coronavirus like particles in the renal tubular epithelium and podocytes. Kissling et al. reported a 63-year-old male with collapsing glomerulopathy; renal biopsy showed acute tubular necrosis and severe focal segmental glomerulosclerosis, reverse transcriptase-polymerase chain reaction was negative from both renal biopsy extract and blood. Electron microscopy revealed coronavirus like particles.
However, most of the case studies in Su et al.'s study were diabetic, hypertensive, or had cancers which all are risk factors of kidney injury. The patient in Kissling et al. report was also hypertensive., Besides, the detection of intracellular corona virus-like particles has been opposed to being naturally occurring intracellular organelles participating in cell metabolism, and it was detected in electron microscopic examination of renal biopsies from pre-COVID rea patients. It may be explained by the coating of endocytic vesicles by proteins which cause the electron-dense area around these vesicles mimicking the appearance of coronavirus particles. Isolation of SARS-CoV-2 virus has been reported in urine and in kidney tissue. Nucleoprotein antigens of SARS-CoV-2 were detected by indirect fluorescence method in a nuclear or cytoplasmic pattern in kidney tubules autopsies.
| The Spectrum of Kidney Involvement in COVID-19|| |
COVID-19 may be complicated by newonset AKI, worsening of preexisting chronic renal impairment. CKD and renal transplant patients may also suffer from increased risk for infection with SARS-CoV-2, and increased complications besides hemodialysis sessions may be postponed because of fear of getting infected. The management of kidney disease within the COVID-19 needs special considerations.
COVID-19 and acute kidney injury
AKI was reported in several viral infections, including SARS-CoV and H1N1 infections. AKI is frequently reported in COVID-19 patients. A dose-response relationship was present between stages of AKI and death. The risk of mortality was increased nearly four times in those with stage three AKI. In mild-to-moderate cases, AKI is infrequent. Clinical presentation is usually subclinical. Proteinuria, hematuria, and elevated levels of serum creatinine and/or blood urea nitrogen were found on hospital admission. Evidence of kidney injury was linked to more severe disease and increased mortality. While in critically ill patients, AKI was more frequent and was associated with nonsurvival. The presence of AKI is a bad prognostic factor.,
Mechanism of acute kidney injury in COVID-19:
The etiology is not well established and still questioned. Several mechanisms are proposed. Direct injury to the kidney cells as the virus enters the cell through angiotensin-converting enzyme receptors-2 which are abundantly expressed in the kidneys. This binding is activated by S-protein called TMPRSS2, which is called priming which is present in proximal tubules. Immune-related mechanisms including cytokine storm, immune complexes deposition, and dysregulation of the immune response to viral infection due to the imbalance between immune clearance and immune tolerance responses resulting in immune overreaction and damage to organs. Other mechanisms include endothelial cell injury, dysregulation in glucose, and lipid metabolism. Preexisting kidney injury can be exacerbated by viral infections, severe inflammation, and/or sepsis. The increased risk of infections in patients with CKD may be attributed to the effect of uremia on the immune system. Decreased renal function leads to increased uremic toxins and systemic inflammation resulting in oxidative stress and release of inflammatory cytokines., This effect is associated with impaired innate and adaptive immunity with impaired/altered immune cell function including monocytes, neutrophils, and lymphocytes., Dialysis is also associated with immune system dysregulation.
Several factors contribute to aggravated kidney injury in patients with preexisting kidney disease, including comorbidities as diabetes mellitus, anemia and cardiovascular disease, Vitamin D deficiency, sodium retention, oxidative stress, and complement activation. Hypoxemia also exaggerates renal injury.
Besides, drugs that are used in the treatment of COVID-19 may have adverse effects on renal function, isolation, and poor fluid management may increase dehydrating condition and lead to tubular necrosis. It is well established that acute lower respiratory tract infections such as pneumonia and severe respiratory impairment as ARDS may lead to AKI due to inflammatory cytokines, decreased renal blood flow, and dysfunction of the renal vascular bed. The indirect effect of COVID-19 on renal function may be attributed to delayed diagnosis and management due to fear of infection or lockdown in some areas.
On the other hand, patients with AKI are at increased risk of respiratory complications with increased morbidity and mortality. They are at risk to develop respiratory failure requiring mechanical ventilation (MV), prolonged duration of, and/or weaning from MV, cardiogenic pulmonary edema, and noncardiogenic pulmonary edema.
Consequences of both COVID-19 and AKI have a high risk of morbidity and mortality.
Diagnosis of AKI
AKI is defined as an abrupt decrease in kidney function, including both structural damage and loss of function. According to KDIGO clinical practice guideline for AKI, AKI is defined as any of the following: Increase in serum creatinine (SCr) by ≥0.3 mg/dl (≥26.5 μmol/l) within 48 h; or increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or urine volume <0.5 ml/kg/h for 6 h.
Urine analysis in COVID-19
Proteinuria and hematuria were found in mild to moderate diseases. Hematuria is nonspecific and can be attributed to several factors, including AKI, coagulopathy, and inflammatory process., Elevated serum creatinine and/or blood urea nitrogen. A recent study highlighted the importance of performing urine analysis in COVID-19 and may provide important information for risk prediction and clinical management. They examined data of urine samples collected at emergency department admission in 226 patients who have been diagnosed with COVID-19 and found that urine samples white blood cells and red blood cells in 81.4% and 70.4% of samples, respectively. Bacteria were found in 19.9% of cases, while nearly half of the cases (49.1%) had casts including hyaline-granular, hyaline, granular, epithelial, and leukocytes, casting (31.9%, 26.1%, 6.6%, 1.8%, and 0.4%, respectively). In-hospital deaths significantly had more prevalent tubular cells and granular casts compared to those with favorable outcomes.
Management of acute kidney injury in COVID-19
The management of AKI during COVID-19 is the same as non-COVID-19 cases in addition to special precautions regarding fluid therapy and doses of some drugs and ventilator strategies that have minimal adverse effects on the kidneys. Infection control measures should be taken into considerations to avoid contamination of hemodialysis units or cross-transmission among health care personnel and other patients. COVID-19 patients with AKI or at risk of AKI should be closely observed for hemodynamic status, especially blood pressure and cardiac output. Nephrotoxic drugs should be avoided. In those with ARDS or respiratory failure, proper choice of MV settings to avoid worsening of renal injury or hemodynamic status. Conservative fluid therapy, optimal RRT, and control of acid-base status are advised for those on invasive MV. The optimal time to start hemodialysis in AKI is not clear and conservative therapy should be tried to avoid hemodialysis. Continuous renal replacement therapy (CRRT) has been proven to be effective for the removal of inflammatory cytokines in several viral infections, including SARS, MERS, as well as in sepsis. RRT decision depends on volume status, kidney function, potassium level, and acid-base status. Early RRT in COVID-19 can prevent worsening of AKI and provide organs perfusion, especially for those with hemodynamic instability. Anticoagulation therapy is required to avoid thrombotic events.
COVID-19 and chronic kidney disease
CKD is defined as abnormalities in structure or function of the kidney detected as decreased glomerular filtration rate (GFR) <60 ml/min/1.73 m2 and/ or presence of one or more markers of kidney damage as albuminuria, urine sediment abnormalities, electrolytes, and other abnormalities due to tubular disorders, structural abnormalities detected by histology, imaging, or history of kidney transplantation. The duration of these abnormalities should be present for more than 3 months.
Infectious complications are serious in patients with end-stage renal disease. It contributes to 10% of deaths of dialysis patients. CKD was associated with an increased risk of pneumonia. Pneumonia in dialysis patients was associated with cardiovascular disease and death. CKD was associated with an increased risk of severe SARS-CoV-2 infection. Patients with CKD and COVID-19 were more likely to be hospitalized and admitted to the critical care unit. T-cell immunity is diminished in transplant recipients so they are at increased risk of bacterial and viral infections. Previous influenza pandemic (H1N1) was associated with increased hospitalization and mortality in patients with end-stage renal disease. Annual mortality secondary to sepsis is increased in dialysis patients and further increased in kidney transplant recipients.
COVID-19 and hemodialysis
COVID-19 has a rapid rate of transmission which is variable in the general population. Meanwhile, the prognosis is still unclear in those on hemodialysis. Patients with CKD receiving hemodialysis therapy are more vulnerable to infections because of advanced age, comorbidities, and impaired immune system. Moreover, hemodialysis patients have a higher risk of exposure than the general population, attributed to their need to attend the dialysis center by public transport several times a week, the long exposure time at dialysis units, and waiting areas thus favoring cross-contamination. Respiratory infections, especially pneumonia are one of the most common causes of increased morbidity and mortality in hemodialysis patients. A large percentage of patients may be asymptomatic and share vehicles during their way to the hemodialysis center. Owing to the rapid rate of transmission of SARS-CoV-2 and the increased number of cases reported among hemodialysis patients, prevention and isolation measures should be strictly applied to minimize the risk of spread across hemodialysis patients and healthcare professionals.
Several scientific societies and international organizations developed guidelines for prevention and containment of COVID-19 in hemodialysis centers which are updated frequently. Hemodialysis centers need also to adopt their own protocols for the implementation of these guidelines. Hemodialysis patients should be provided by information leaflets about the current epidemic and triage to screen for suspicious symptoms related to COVID-19, physical separation, and evaluation before entry into the dialysis room. A real-time polymerase chain reaction (RT-PCR) of the nasopharyngeal swab and chest radiography are performed. Those patients should receive their dialysis session in a separate room till the results of RT-PCR are obtained. Patients with positive results for SARS-CoV-2 should receive their hemodialysis sessions in the COVID-19 zone. All patients and healthcare professionals should follow infection control measures, including personal protective equipment and using special elevators and track for movement of RT-PCR-positive cases in the center. Critically ill patients with COVID-19 who require renal transplant are kept on CRRT till the resolution of infection.
COVID-19 and kidney transplantation
Kidney transplant recipients are at increased susceptibility to many viral infections leading to justifiable anxiety about the effects of COVID-19. Clinical presentation and imaging of COVID-19 in kidney transplant patients were like that of nontransplant patients. The most common manifestations reported in a systematic review included fever (52% to 95%), cough (49% to 78%), and dyspnea (28% to 70%). Gastrointestinal symptoms were high as 53% in one study. AKI at presentation or graft dysfunction at presentation.,, asymptomatic infection was not reported in the studies included in the systematic review.
Nair et al. studied 10 kidney transplant recipients who tested positive for SARS-CoV-2, 9 of them were admitted to the hospital. Comorbidities were prevalent in these cases. 20% of them had leukopenia. 90% were receiving immunosuppression, and 70% were receiving prednisolone. 50% developed AKI and 30% died. Causes of death in ESRD and kidney transplant patients are attributed to cytokine storm and immunosuppression, comorbid conditions, advanced age, and increased risk of exposure during dialysis.
Early data reported indicate that hospitalized kidney transplant recipients infected with COVID-19 have high mortality. Comprehensive reporting regarding screening, comorbidities, investigations, management, and outcomes of this category of patients is important to improve the current knowledge.
| EFFECT OF COVID-19 MEDICATIONS ON THE KIDNEYS|| |
Kidney injury can affect the metabolism of some drugs used in the treatment of COVID-19. Some drugs are excreted through the kidneys as hydroxychloroquine (HCQ), and remdesivir. Some vitamin supplementations that are given empirically are metabolized in the kidneys as cholecalciferol (Vitamin D).
Chloroquine and HCQ may have immunomodulatory effect and decrease inflammatory cytokines; however, studies showed no beneficial value in COVID-19 patients, in addition, it may be associated with increased mortality. Renal insufficiency is a reported side effect of HCQ. Obeidat et al. presented a case of male patient infected with SARS-CoV-2 who received HCQ for 5 days and stopped due to cardiac and renal toxicity. Postmortem examination of the kidneys revealed acute tubular injury and glomerulosclerosis, microangiopathy and intracapillary thrombosis, and tubular vacuolization. The case is highly suspected to be due to HCQ drug-induced phospholipidosis (DIPL). Another case of DIPL was reported in systemic lupus erythematosus patient receiving HCQ. HCQ was linked to sudden cardiac arrest in hemodialysis patients.
Remdesivir side effects on the kidneys include acute renal failure, elevated serum creatinine, decreased estimated GFR, and decreased creatinine clearance. There are limited data available about the use and safety of remdesivir in those with severe renal impairment. Lopinavir/Ritonavir reported side effects to include increased serum concentration of some drugs, hematuria, and renal failure. All are uncommon and can occur in nearly 2% of cases.
Off-label Vitamin D supplements are used in COVID-19 patients. Overdoses can lead to increased cholecalciferol levels in the blood with some side effects due to hypercalcemia and may cause renal failure. Patients with CKD may need supplementation with Vitamin D due to altered metabolism, so caution should be taken as the correction is only needed.
| Prevention of Kidney Injury in COVID-19|| |
Early suspicion and diagnosis of COVID-19 patients and management are important to avoid AKI. Caution during the treatment of CKD patients should be taken during the choice of drugs, fluid replacement, and infection control measures. In COVID-19 patients, it is recommended to use isotonic crystalloid solutions for correction of hypovolemia, avoid or stop nephrotoxic drugs if not essential, besides conservative fluid management strategy in those with respiratory failure. Daily monitoring of serum creatinine and urine output for patients with ARDS or respiratory failure.
| Concluding Remarks|| |
Kidney injury is common in COVID-19. It may be due to direct or indirect viral injury. Early detection and management are important to prevent morbidity and mortality. Conservative fluid strategy and optimal MV settings in COVID-19 patients with respiratory failure are essential to avoid worsening of kidney functions. Early renal replacement therapy is advised in AKI.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, et al
. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003;348:1953-66.
Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al.
Extrapulmonary manifestations of COVID-19. Nat Med 2020;26:1017-32.
Nadim MK, Forni LG, Mehta RL, Connor MJ Jr., Liu KD, Ostermann M, et al.
COVID-19-associated acute kidney injury: Consensus report of the 25th
Acute Disease Quality Initiative (ADQI) workgroup. Nat Rev Nephrol 2020;16:747-64.
Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al
. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al.
Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med 2020;8:475-81.
Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al.
Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ 2020;368:m1091.
Pei G, Zhang Z, Peng J, Liu L, Zhang C, Yu C, et al.
Renal involvement and early prognosis in patients with COVID-19 pneumonia. J Am Soc Nephrol 2020;31:1157-65.
Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al.
Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area. JAMA 2020;323:2052-9.
Wang L, Li X, Chen H, Yan S, Li D, Li Y, et al.
Coronavirus disease 19 infection does not result in acute kidney injury: An analysis of 116 hospitalized patients from Wuhan, China. Am J Nephrol 2020;51:343-8.
Official Journal of the International Society of Nephrology KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Available from: http://www.publicationethics.org
. [Last accessed on 2020 Dec 04].
Su H, Yang M, Wan C, Yi LX, Tang F, Zhu HY, et al.
Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int 2020;98:219-27.
Kissling S, Rotman S, Gerber C, Halfon M, Lamoth F, Comte D, et al.
Collapsing glomerulopathy in a COVID-19 patient. Kidney Int 2020;98:228-31.
Miller SE, Brealey JK. Visualization of putative coronavirus in kidney. Kidney Int 2020;98:231-2.
Calomeni E, Satoskar A, Ayoub I, Brodsky S, Rovin BH, Nadasdy T. Multivesicular bodies mimicking SARS-CoV-2 in patients without COVID-19. Kidney Int 2020;98:233-4.
Sun J, Zhu A, Li H, Zheng K, Zhuang Z, Chen Z, et al.
Isolation of infectious SARS-CoV-2 from urine of a COVID-19 patient. Emerg Microbes Infect 2020;9:991-3.
Wichmann D, Sperhake JP, Lütgehetmann M, Steurer S, Edler C, Heinemann A, et al.
Autopsy findings and venous thromboembolism in patients with COVID-19: A prospective cohort study. Ann Intern Med 2020;173:268-77.
Chu KH, Tsang WK, Tang CS, Lam MF, Lai FM, To KF, et al.
Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Kidney Int 2005;67:698-705.
Kumar A, Zarychanski R, Pinto R, Cook DJ, Marshall J, Lacroix J, et al.
Critically ill patients with 2009 influenza A (H1N1) infection in Canada. JAMA 2009;302:1872-9.
Martinez-Rojas MA, Vega-Vega O, Bobadilla NA. Is the kidney a target of SARS-CoV-2? Am J Physiol Renal Physiol 2020;318:F1454-62.
Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al.
Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int 2020;97:829-38.
Vanmassenhove J, Kielstein J, Jörres A, Biesen WV. Management of patients at risk of acute kidney injury. Lancet 2017;389:2139-51.
Raza A, Estepa A, Chan V, Jafar MS. Acute renal failure in critically ill COVID-19 patients with a focus on the role of renal replacement therapy: A review of what we know so far. Cureus 2020;12:e8429.
Wang M, Xiong H, Chen H, Li Q, Ruan XZ. Renal injury by SARS-CoV-2 infection: A systematic review. Kidney Dis (Basel) 2021;7:100-10.
Lamarche C, Iliuta IA, Kitzler T. Infectious disease risk in dialysis patients: A transdisciplinary approach. Can J Kidney Health Dis 2019;6:1-11.
Vaziri ND. CKD impairs barrier function and alters microbial flora of the intestine: A major link to inflammation and uremic toxicity. Curr Opin Nephrol Hypertens 2012;21:587-92.
Chonchol M. Hematology: Issues in the dialysis patient: Neutrophil dysfunction and infection risk in end-stage renal disease. Semin Dial 2006;19:291-6.
Betjes MG, Litjens NH. Chronic kidney disease and premature ageing of the adaptive immune response. Curr Urol Rep 2015;16:471.
Lim WH, Kireta S, Leedham E, Russ GR, Coates PT. Uremia impairs monocyte and monocyte-derived dendritic cell function in hemodialysis patients. Kidney Int 2007;72:1138-48.
Anding K, Gross P, Rost JM, Allgaier D, Jacobs E. The influence of uraemia and haemodialysis on neutrophil phagocytosis and antimicrobial killing. Nephrol Dial Transplant 2003;18:2067-73.
Fernández-Fresnedo G, Ramos MA, González-Pardo MC, de Francisco AL, López-Hoyos M, Arias M. B lymphopenia in uremia is related to an accelerated in vitro
apoptosis and dysregulation of Bcl-2. Nephrol Dial Transplant 2000;15:502-10.
Sester U, Sester M, Hauk M, Kaul H, Köhler H, Girndt M. T-cell activation follows Th1 rather than Th2 pattern in haemodialysis patients. Nephrol Dial Transplant 2000;15:1217-23.
Galli F. Protein damage and inflammation in uraemia and dialysis patients. Nephrol Dial Transplant 2007;22 Suppl 5:v20-36.
Jesú Puchades M, Romero-Parra M, Gimenez-Civera E, José Soler M, Ortiz A, Luis Gorriz J, et al
. OUP accepted manuscript. Clin Kidney J 2020;13:297-306.
Suh SH, Kim CS, Choi JS, Bae EH, Ma SK, Kim SW. Acute kidney injury in patients with sepsis and septic shock: Risk factors and clinical outcomes. Yonsei Med J 2013;54:965-72.
Faubel S, Edelstein CL. Mechanisms and mediators of lung injury after acute kidney injury. Nat Rev Nephrol 2016;12:48-60.
Makris K, Spanou L. Acute kidney injury: Definition, pathophysiology and clinical phenotypes. Clin Biochem Rev 2016;37:85-98.
Willis GC, Tewelde SZ. The approach to the patient with hematuria. Emerg Med Clin North Am 2019;37:755-69.
Bonetti G, Manelli F, Bettinardi A, Borrelli G, Fiordalisi G, Marino A, et al.
Urinalysis parameters for predicting severity in coronavirus disease 2019 (COVID-19). Clin Chem Lab Med 2020;58:e163-5.
Ibernon M, Bueno I, Rodríguez-Farré N, Ruiz P, Sánchez A, Massó E, et al.
The impact of COVID-19 in hemodialysis patients: Experience in a hospital dialysis unit. Hemodial Int 2021;25:205-13.
Joannidis M, Forni LG, Klein SJ, Honore PM, Kashani K, Ostermann M, et al.
Lung-kidney interactions in critically ill patients: Consensus report of the Acute Disease Quality Initiative (ADQI) 21 workgroup. Intensive Care Med 2020;46:654-72.
Ronco C, Bagshaw SM, Bellomo R, Clark WR, Husain-Syed F, Kellum JA, et al.
Extracorporeal blood purification and organ support in the critically ill patient during COVID-19 pandemic: Expert review and recommendation. Blood Purif 2021;50:17-27.
Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The novel coronavirus 2019 epidemic and kidneys. Kidney Int 2020;97:824-8.
Collins AJ, Foley RN, Gilbertson DT, Chen SC. United States renal data system public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int Suppl 2015;5:2-7.
Chou CY, Wang SM, Liang CC, Chang CT, Liu JH, Wang IK, et al.
Risk of pneumonia among patients with chronic kidney disease in outpatient and inpatient settings: A nationwide population-based study. Medicine (Baltimore) 2014;93:e174.
Guo H, Liu J, Collins AJ, Foley RN. Pneumonia in incident dialysis patients – The United States renal data system. Nephrol Dial Transplant 2008;23:680-6.
Henry BM, Lippi G. Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection. Int Urol Nephrol 2020;52:1193-4.
CDC COVID-19 Response Team. Preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease 2019 - United States, February 12-March 28, 2020. MMWR Morb Mortal Wkly Rep 2020;69:382-6.
Nair V, Jandovitz N, Hirsch JS, Nair G, Abate M, Bhaskaran M, et al.
COVID-19 in kidney transplant recipients. Am J Transplant 2020;20:1819-25.
Marcelli D, Marelli C, Richards N. Influenza A(H1N1) v pandemic in the dialysis population: First wave results from an international survey. Nephrol Dial Transplant 2009;24:3566-72.
Sarnak MJ, Jaber BL. Mortality caused by sepsis in patients with end-stage renal disease compared with the general population. Kidney Int 2000;58:1758-64.
Vaziri ND, Pahl MV, Crum A, Norris K. Effect of uremia on structure and function of immune system. J Ren Nutr 2012;22:149-56.
Albalate M, Arribas P, Torres E, Cintra M, Alcázar R, Puerta M, et al
. High prevalence of asymptomatic COVID-19 in hemodialysis. Daily learning during first month of COVID-19 pandemic. Nefrologia 2020;40:279-86.
Basile C, Combe C, Pizzarelli F, Covic A, Davenport A, Kanbay M, et al.
Recommendations for the prevention, mitigation and containment of the emerging SARS-CoV-2 (COVID-19) pandemic in haemodialysis centres. Nephrol Dial Transplant 2020;35:737-41.
Mahalingasivam V, Craik A, Tomlinson LA, Ge L, Hou L, Wang Q, et al
. A systematic review of COVID-19 and kidney transplantation. Kidney Int Rep 2021;6:24-45.
Chaudhry ZS, Williams JD, Vahia A, Fadel R, Parraga Acosta T, Prashar R, et al.
Clinical characteristics and outcomes of COVID-19 in solid organ transplant recipients: A cohort study. Am J Transplant 2020;20:3051-60.
Mohamed IH, Chowdary PB, Shetty S, Sammartino C, Sivaprakasam R, Lindsey B, et al.
Outcomes of renal transplant recipients with SARS-CoV-2 infection in the eye of the storm: A comparative study with waitlisted patients. Transplantation 2021;105:115-20.
Devresse A, Belkhir L, Vo B, Ghaye B, Scohy A, Kabamba B, et al.
COVID-19 infection in kidney transplant recipients: A single-center case series of 22 cases from Belgium. Kidney Med 2020;2:459-66.
Chen TY, Farghaly S, Cham S, Tatem LL, Sin JH, Rauda R, et al.
COVID-19 pneumonia in kidney transplant recipients: Focus on immunosuppression management. Transpl Infect Dis 2020;22:e13378.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al.
COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033-4.
Plaquenil ® Hydroxychloroquine Sulfate Tablets, USP Description . [cited 2020 Dec 10]. Available from: http://www.cdc.gov/malaria
Rosenberg ES, Dufort EM, Udo T, Wilberschied LA, Kumar J, Tesoriero J, et al.
Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. JAMA 2020;323:2493-502.
Obeidat M, Isaacson AL, Chen SJ, Ivanovic M, Holanda D. Zebra-like bodies in COVID-19: Is phospholipidosis evidence of hydroxychloroquine induced acute kidney injury? Ultrastruct Pathol 2020;44:519-23.
Sperati CJ, Rosenberg AZ. Hydroxychloroquine-induced mimic of renal Fabry disease. Kidney Int 2018;94:634.
Purif B, Mevlut AM, Dincer T, Karaca C, Murt A. Case Report Sudden Cardiac Death in Haemodialysis Patients under Hydroxychloroquine Treatment for COVID-19: A Report of Two Cases; 2020. Available from: http://www.karger.com/bpu
. [Last accessed on 2020 Dec 10].
Adamsick ML, Gandhi RG, Bidell MR, Elshaboury RH, Bhattacharyya RP, Kim AY, et al
. Remdesivir in patients with acute or chronic kidney disease and COVID-19. J Am Soc Nephrol 2020;31:1384-6.
Rudd KE, Cizmeci EA, Galli GM, Lundeg G, Schultz MJ, Papali A, et al.
Pragmatic recommendations for the prevention and treatment of acute kidney injury in patients with COVID-19 in low- and middle-income countries. Am J Trop Med Hyg 2021;104 3 Suppl: 87-98.