• Users Online: 112
  • Print this page
  • Email this page

Table of Contents
Year : 2020  |  Volume : 17  |  Issue : 3  |  Page : 153-156

Acute renal complications of COVID-19 : Impact of pathophysiology on management

Department of Nephrology, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, India

Date of Submission19-Jun-2020
Date of Acceptance26-Jun-2020
Date of Web Publication06-Aug-2020

Correspondence Address:
Jayant Kumar Hota
51 F Sector 7, Jasola Vihar, New Delhi - 110 025
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/am.am_52_20

Rights and Permissions

The ongoing pandemic of coronavirus disease-2019 (COVID-19) due to a novel coronavirus named severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) by the World Health Organization has already wreaked havoc all over the world. About 5%–10% of all the patients of COVID-19 have severe diseases including acute respiratory distress syndrome, septic shock, disseminated intravascular coagulation, and multi-organ failure in different population. Acute renal complications are not unusual and can range from mild proteinuria to advanced acute kidney injury requiring some form of renal replacement therapy. Many studies have shown that renal dysfunction is associated with very high mortality. Understanding the underlying pathophysiologic mechanisms may help the treating physicians to recognize the renal complications early and to prevent and manage the complications adequately.

Keywords: Acute kidney injury, acute respiratory distress syndrome, coronavirus disease-2019, pathophysiology, renal replacement therapy, severe acute respiratory syndrome coronavirus 2

How to cite this article:
Hota JK. Acute renal complications of COVID-19 : Impact of pathophysiology on management. Apollo Med 2020;17:153-6

How to cite this URL:
Hota JK. Acute renal complications of COVID-19 : Impact of pathophysiology on management. Apollo Med [serial online] 2020 [cited 2020 Oct 29];17:153-6. Available from: https://www.apollomedicine.org/text.asp?2020/17/3/153/291591

  Introduction Top

As the whole world is struggling with the onslaught of corona virus disease-2019 (COVID-19) due to a novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by the World Health Organization, we are noticing a spectrum of effects ranging from asymptomatic or mildly symptomatic to fatal acute respiratory distress syndrome (ARDS).[1] About 5%–10% of all the patients of COVID-19 have severe diseases including ARDS, septic shock, disseminated intravascular coagulation (DIC), and multi-organ failure in different populations at different places around the globe.[2],[3] Renal manifestations are not infrequent in these patients which are seen in more than one-third of hospitalized patients in different series, but severe acute kidney injury (AKI) has been found to be affecting 20–40% of patients in intensive care units (ICUs) on ventilators.[2],[3] About one-fifth of the patients of AKI may eventually need some form of renal replacement therapy (RRT).[4],[5],[6] The severity of AKI has been found in many studies to be proportional to the degree of respiratory failure, and there is a strong correlation between the severity of AKI and mortality in these patients.[7],[8] The underlying pathophysiologic mechanisms of AKI in these patients are varied, and proper understanding of the causative factors may help the treating physicians to recognize AKI early and to prevent and manage the complications adequately.

  Acute Renal Manifestations Top

COVID-19 can involve the kidneys in many ways leading to minimal symptoms to total renal shutdown. It has been found to involve all the three different structures of the kidneys like the glomerulus, the tubule–interstitium, and the microvasculature.[6],[7],[8] Depending on the structures involved, the patient will experience mild proteinuria, hematuria, frank nephrotic/nephritic syndrome, or oligo-anuric AKI.[6],[7],[8] Renal involvement in many studies varies from about 20% of hospital admission to 30%–40% of patients in ICUs.[3],[4],[5],[6] Clinically, many of these patients exhibiting renal involvement present with a decrease in urine output, but as the disease progresses, especially those with SARS on ventilators may have oligo-anuric AKI requiring RRT.[7],[8] Patients with severe AKI may have symptoms of fluid overload, making ventilation more difficult. The opacities in the X-ray chest may confuse the physicians about the possible deterioration of the ongoing ARDS. Some of these patients can have mild proteinuria to nephrotic range proteinuria which can worsen the serum albumin level and can lead to extracellular volume overload. Patients with nephrotic syndrome can have exaggerated the already deteriorating prothrombotic and hypercoagulable state of these patients because of the loss of anticoagulants in the urine which can cause deep-vein thrombosis or pulmonary thromboembolism if not diagnosed early.[4],[8] Many of these patients can have microscopic to gross hematuria which at times can pose a difficult challenge as many of these patients are already receiving very high doses of heparin.[9] A proper urine examination with a phase-contrast microscope showing crenated RBCs can differentiate between glomerular hematuria from other causes like bleeding disorders.[10]

  Pathophysiology of Advanced Acute Kidney Injury in COVID-19 Top

Till date, the exact pathophysiology of AKI in COVID-19 is still elusive and like in any other non-COVID AKI, it is multifactorial ranging from hemodynamic factors to direct viral cytopathic effects.[11] Older patients with other comorbidities such as diabetes, hypertension, obesity, or coronary artery disease with poor left ventricular function are more susceptible to develop AKI.[2],[3],[12],[13] Hemodynamic factors such as hypovolemia, hypotension, or cardiogenic shock are few of the common causes of AKI in these patients.[14],[15] Many of these patients may have associated severe hypoxia due to lung involvement which can cause renal tubular cell injury.[14],[15] Hyperventilation-associated rhabdomyolysis has also been found in many cases to be contributing to AKI.[15] Some of these patients might be getting nephrotoxic agents which can precipitate AKI.[14],[15] Direct viral cytopathic effects especially on the renal endothelium causing renal endotheliitis happens to be a major site of renal injury in these patients.[16] In the first of its kind Chinese series of postmortem findings in patients of COVID-19 with renal involvement, it was found that there was evidence of coronavirus-like particles with distinctive spikes in the renal epithelium and podocytes.[17] There is a lot of concern about the use of angiotensin-converting enzyme (ACE) inhibitors in these patients, as SARS-COV-2 can infect the renal tubular epithelium and glomerular podocytes through ACE-dependent mechanisms. In fact, many studies have shown that there is a heightened expression of ACE2 receptors in the tubular epithelium in these patients.[18],[19],[20] Patients of diabetes, especially those with preexisting kidney disease, are more prone to develop AKI because of the heightened upregulation of ACE which can be pro-inflammatory and prothrombotic.[21] Through ACE-dependent mechanisms, these patients can have many other histopathological changes like mitochondrial dysfunction, tubular cell necrosis to collapsing variant of focal segmental glomerulosclerosis.[17],[20] There has been a lot of studies on the implications of cytokine storm due to the activation of both innate and adaptive immunities in the overall morbidities and mortalities in these patients'.[21],[22],[23],[24] Overexpression of interleukin (IL)-2, IL-6, IL-7, IL-10, granulocyte colony-stimulating factor, interferon gamma-induced protein 10 (CXCL10), monocyte chemoattractant protein-1, macrophage inflammatory protein-1 alpha, and tumor necrosis factor-alpha has been found by many researchers.[21],[22],[23],[24] Furthermore, there is excessive activation of T-lymphocytes leading to an increase of pro-inflammatory CCR4+CCR6+Th17 cells. These helper T-cells secrete many different cytokines as described above, leading to a cascading effect causing further immune-mediated damage.[25] Nevertheless, cytokine storm plays a very important role in causing endothelial dysfunction and subsequent renal injury in these patients.[17],[26],[27],[28],[29]

  Diagnosis of Renal Injury Top

The diagnosis of COVID-19 is beyond the scope of this article. Here, we are focusing only on the diagnosis of renal injury. Besides the routine tests, specific tests of renal involvement include a detailed kidney function test, urine biochemical and microscopic study, urine protein-to-creatinine ratio, and phase-contrast microscopic examination of urine only in patients with hematuria. An ultrasound examination of the abdomen is needed to rule out any postrenal cause of AKI and to exclude evidence of chronicity. In patients with nephrotic range proteinuria, a detailed serological workup including antinuclear antibodies; dS DNA; complements such as C3 and C4; and PLA2R and antiphospholipid antibodies may need to be done before going for a more invasive kidney biopsy. Recently, novel biomarkers are found to be quite useful in the early and timely diagnosis of AKI in many cases, the importance of these biomarkers in the setting of COVID-19 is still to be fully elucidated though.[28]

In patients of AKI staging is done according to the Kidney Disease Improving Global Outcomes staging criteria of AKI.[29]

  Management of Renal Manifestations Top

General measures

Understanding the pathophysiology of AKI in these patients will help the physicians to recognize and prevent AKI early. Correction of hemodynamic factors with particular preference to keep the mean arterial pressure of about 70 mmHg to preserve renal autoregulation is the first step in the management of AKI in these circumstances.[29] Adequate oxygenation with either high-flow oxygen nasal prongs, noninvasive ventilation, or as the case demands invasive mechanical ventilation is a must in these patients to prevent tissue hypoxia, especially those with severe ARDS.[29],[30] Avoidance of nephrotoxic drugs and proper dosing of drugs as per the creatinine clearance are absolutely necessary to prevent further renal injury.[28] In patients who are on ACE inhibitors or angiotensin receptor blockers, it is preferable to avoid these once the patient is in AKI to prevent further worsening.[29] Daily intake–urine output measurement, central venous pressure measurement in patients with central venous line, or a more noninvasive bedside measurement of hemodynamic factors by two-dimensional echocardiography are very useful to guide the fluid status. A bedside X-ray chest may also be quite useful, especially in a patient of AKI needing more oxygen to maintain proper oxygen saturation. There have been a lot of studies which have raised concern about overhydration, the so-called volutrama and the critical implications of it in management of ventilation in these patients.[30],[31] Many of these volume-overloaded patients may eventually need RRT to maintain euvolumia and for proper ventilation.[31] Good nutrition to maintain a protein requirement of about 1.2–1.5 g/kg body weight is recommended.[29] The role of antivirals if any in the treatment of AKI is still under investigation, and the general treatment of COVID-19 as deemed necessary should be good enough for renal recovery, though till today, we are still far from an ideal antiviral agent.[3] Many of these patients may have secondary sepsis which needs proper antibiotic therapy according to the sensitivity. It is to be remembered that some of the antibiotics, especially vancomycin, aminoglycosides, and colistin (polymyxin E), are nephrotoxic and require proper dosing according to the creatinine clearance.[29] There has been a lot of enthusiasm on the role of low-dose steroid, especially in moderate-to-severe cases, as was the case in earlier coronavirus infections which has been substantiated by mortality benefit after the interim release of data by the RECOVERY trial, a UK-based research group.[32],[33],[34] There has not been any special comment on the renal recovery by steroids in this trial.[34] Nevertheless, any intervention which can decrease the mortality is definitely going to have a positive effect on the renal recovery.

  Renal Replacement Therapy Top

Patients with advanced AKI, especially those with volume overload RRT becomes imperative to maintain proper ventilation and tissue oxygenation.[31] The modality of RRT depends on the hemodynamic status of the patient and the sicker patients on inotropic support invariably need continuous RRT (CRRT).[31] Less sick patients with preserved hemodynamics can be managed with either conventional intermittent hemodialysis (HD) or slow, low-efficiency daily dialysis.

Since many of these patients need frequent prone positioning ideal vascular access is a central venous catheter rather than a venous access as the latter is more likely to be kinked during patient's maneuvering.[35] If a patient needs extracorporeal membrane oxygenation (ECMO) in addition to the RRT, an additional venous access is desired to prevent circuit clotting.[36] However, as there may be a paucity of venous access if both have to be connected to together, it is preferable to connect the preoxygenator limb of ECMO to the outflow limb of the CRRT to minimize the chance of air embolism,[31],[36]

As far as the different modalities of CRRT are concerned, continuous venovenous HD is preferred over other modalities. A high flux moderate-to-high-efficiency dialyzer should ideally be used to filter middle molecules.[29] A minimum dose of 20–25 ml/kg body weight/h as recommended in non-COVID AKI is good enough in these circumstances as well.[30] Since many of these patients have hypercoagulable state, these patients on CRRT need adequate anticoagulation in the form of unfractionated or low-molecular weight heparin, the latter has been found to be better in a study by Zhou et al.[2],[37] In patients with bleeding disorders or with significant thrombocytopenia, regional anticoagulation with proper monitoring of activated thromboplastin time keeping it around 60–90 s is highly desired.[31]

There have been a lot of studies on the use of cytokine hemoadsorption (CytosorbR) in patients with AKI due to sepsis.[38],[39] Whether these hemoadsorption techniques will give any added advantage in the COVID-19 AKI with cytokine storm as a principal cause of AKI still remains to be proved but has been used with some success in some centers.[27]

  Glomerular Disease With COVID-19 Top

In patients with glomerular involvement as revealed by ancillary tests and confirmed by kidney biopsy, patients may need immunosuppressive therapy. However, in view of the COVID-19 infection, it may be wise to defer the treatment till the patients improve from the acute viral syndrome. Individualized therapy with steroid with or without calcineurin inhibitors or antimetabolites seem to be adequate in these patients.[40] However, many of these patients may have severe acute tubular injury needing long-term RRT. In patients needing long-term RRT, permacath should be put as a vascular access.[20]

  Conclusion Top

Renal involvement is not unusual in COVID-19 due to SARS CoV-2 as a part of the multisystem involvement in these patients because of the hemodynamic factors, cytokine storm, or direct viral cytopathic effects. Proper understanding of the pathophysiology helps the physician to recognize, prevent, and treat the AKI judiciously. In some patients, AKI can be advanced and may need some form of RRT in addition to the general measures. Some experimental extracorporeal therapies like the role of immuno/hemeoadsorption are still to be proved by proper trials in these patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

World Health Organization Novel Corona Virus – China; January, 2020. Available from: https://www.who.int/csr.don/12-january-2020- novel-corona virus-china/en/(Date 20). [Last accessed on 2020 Jun 15].  Back to cited text no. 1
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.  Back to cited text no. 2
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.  Back to cited text no. 3
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.  Back to cited text no. 4
Hirch JS, Ng JH, Ross DW, Sharma P, Shah HH, Barnett RL, et al. Ross acute kidney injury in patients hospitalised with COVID-19. Kidney Int 2020;98:209-18.  Back to cited text no. 5
Acute Kidney Injury in COVID-19 Patients. ESICMtv Webinar. Posted; 17 April, 2020. Available from: https://www.esicm.org/blog/p=2789. [Last accessed on 2020 Jun 15].  Back to cited text no. 6
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.  Back to cited text no. 7
Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18:844-7.  Back to cited text no. 8
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.  Back to cited text no. 9
Moammad KS, Bdesha AS, Snell ME, Witherow RO, Coleman DV. Phase contrast microscopic examination of urinary erythrocytes to localize source of bleeding: An overlooked technique? J Clin Pathology1993;46:642-6.  Back to cited text no. 10
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020;395:507-13.  Back to cited text no. 11
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel corona virus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.  Back to cited text no. 12
Diao B, Wang C, Wang R, Feng Z, Tan Y, Wang H, et al. Human kidney is a target for novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection. medRxiv. Available from: https://doi.org/10.1101/2020.03.04.20031120. [Last accessed on 2020 Jun 18].  Back to cited text no. 13
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.  Back to cited text no. 14
Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with corona virus disease 2019: Retrospective study. BMJ 2020;368:M1091.  Back to cited text no. 15
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020;395:1417-8.  Back to cited text no. 16
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.  Back to cited text no. 17
Mackey K, King VJ, Gurley S, Kiefer M, Liederbauer E, Vela K, et al. Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults. Ann Intern Med 2020;M15:1515. Available from: https://doi: 10.7326/M20-1515. [Last accessed on 2020 Jun 18].  Back to cited text no. 18
Zhang P, Zhu L, Cai J, Lei F, Quin JJ, Jing X, et al. Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res 2020;126:1671.  Back to cited text no. 19
Larsen CP, Bourne TD, Wilson JD, Saqqa O, Sharshir MA. Collapsing glomerulopathy in a patient with coronavirus disease 2019 (COVID-19). Kidney Int Rep 2020;5:535-9.  Back to cited text no. 20
Batlle D, Soler MJ, Sparks MA, Swapnil H, South AM, Welling PA, et al. Acute Kidney Injury in COVID 19: Emerging evidence of a distinct pathophysisology : JASN 2020;31:1380-3.  Back to cited text no. 21
Soy M, Keser G, Atagunduz P, Tabak F, Atagunduz I, Kayhan S. Cytokine storm in COVID-19: Pathogenesis and overview of antu-inflammatory agents used in treatment. Clin Rhematol 2020.  Back to cited text no. 22
Sarzi-Puttni P, Giorgi V, Sirotti S, Marotto D, Ardizzone S, Rizzardini G, et al. COVID-19 cytokine and immunosupression; what can we learn from severe acute respiratory syndrome ? Clin Exp Rheumatol 2020;38:337-42.  Back to cited text no. 23
Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharma Anal 2020;10:102-8.  Back to cited text no. 24
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020;8:420-2.  Back to cited text no. 25
Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Xiang W, et al. Coagulapathy and antiphospholipid antibodies in patients with COVID-19 N Engl J Med 2020;382:e38.  Back to cited text no. 26
Ronco C, Reis T. Kidney involvement in COVID-19 and rationale of extracorporeal therapies. Nat Rev Nephrol 2020;16:308-10.  Back to cited text no. 27
Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet 2019;394:1949-64.  Back to cited text no. 28
Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012;2:1-138.  Back to cited text no. 29
Mattehay MA, Aldrich JM, Gotts JE. Treatment for severe acute respiratory distress syndrome from COVID-19. Lancet Respir Med 2020;8:433-4.  Back to cited text no. 30
Ronco C, Reis T, Husain-Syed F. Management of acute kidney injury in patients with COVID-19. Lancet Respir Med 2020;8:240-1.  Back to cited text no. 31
Chen RC, Tang XP, Tan SY, Liang BL, Wan ZY, Fang JQ, et al. Treatment of severe acute respiratory syndrome with glucocoricoids. The Gangzhou experience. Chest 2006;1 29:1441-52.  Back to cited text no. 32
Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA, Hussein Md A, et al. Coricosteroid therapy for critically ill patients with middle eas respiratory syndrome.AM j Respir Crit Care Med 2018;197:757-67.  Back to cited text no. 33
Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial Available from: http://www.recoverytrial.net. [Last accessed on 2020 Jun 18].  Back to cited text no. 34
Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA 2020;323:1574-81.  Back to cited text no. 35
Husain-Syed F, Ricci Z, Brodie D, Vincent JL, Renieri VM, Slutsky AS, et al. Extracorporeal organ support (ECOS) in critical illness and acute kidney injury from native to artificial organ cross talk. Intensive Care Med 2018;44:1447-59.  Back to cited text no. 36
Joannids M, Kountchev J, Rauchenzauner M, Schusterschitz N, Ulmer H, Mayr A, et al. Enoxaparin vs. unfractioned heparin anticoagulation during continuous veno-venous hemofiltration: A randomized controlled cross over study. Intensive Care Med 2007;33:1571-9.  Back to cited text no. 37
Shum HP, Yan WW, Chan TM. Extracorporeal blood prificaionfor sepsis. Hong Kong Med J 2016;22:478-85.  Back to cited text no. 38
Mehta Y, Mehta C, Kumar A, George JV, Gupta A, Nanda S, et al. Experience with hemoadsorption (CytoSorb®) in the management of septic shock patients. World J Crit Care Med 2020;9:1-2.  Back to cited text no. 39
Gulati S, Prasad N, Sahay M, Kute V, Agarwal SK on behalf of COVID-19 working group of the Indian society of nephrology. Glomerular disease with reference to COVID-19. Indian J Nephrology 2020;30:158-60.  Back to cited text no. 40


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
Acute Renal Mani...
Pathophysiology ...
Diagnosis of Ren...
Management of Re...
Renal Replacemen...
Glomerular Disea...

 Article Access Statistics
    PDF Downloaded30    
    Comments [Add]    

Recommend this journal