Although pulmonary infection is the main manifestation in the course of COVID-19, other organs, such as the kidney, may be of interest as well.

Previous studies of SARS and MERS CoV documented the development of acute kidney injury (AKI) in 5–15% of patients with a high mortality rate.

Early reports on COVID-19 documented 3–9% of AKI in patients with COVID infection (6–8). Other data report higher incidence of up to 25% (9).

Two recent reports from New York city noted an incidence of AKI in patients hospitalized with COVID-19 at 31% (10) and of 36.6% (11) respectively.

One study documented that patients on admission affected by leukocyturia, albuminuria, and hematuria, principally when associated with low albumin serum concentration and low antithrombin III concentration, will easily develop AKI (12).

In the renal histopathological analyses of 26 postmortem findings of patients with COVID-19 in China, Su et al. (13) were able to document renal lesions as proximal tubule injury, vacuolar degeneration, and necrosis. By electron microscopy, the same authors were able to find Coronavirus particles in the tubular epithelium and podocytes. In addition, an upregulation of angiotensin converting enzyme 2 (ACE2), the receptor of COVID, was found.

The question remains as to how the COVID-19 virus may enter the renal cells. Another study from Varga et al. (14) has documented that vascular damage in addition to respiratory disease may be observed in the course of COVID-19. Indeed, SARS CoV-2 infects the patient binding to the ACE2 receptor, which is expressed both on the pulmonary epithelium and on the endothelium of several organs, including the kidney. The endothelium involvement may be the way through which the virus enters the cells. Indeed, several studies have documented that during the COVID-19 disease, several organs may be affected in addition to lungs, such as the myocardium and the kidney (15).

In an observational study, Diao et al. (16) documented that, in a retrospective analysis of 85 patients with COVID-19 infection, confirmed in Wuhan, 23 patients (27.06%) exhibited acute renal failure (ARF), principally related to tubular necrosis, as histologically documented by Su (13). In addition, Diao et al. documented activation of CD68+ macrophages together with complement activation. Further studies have documented that SARS CoV-2 infection, in addition to the release of proinflammatory cytokines, may induce ARF by rhabdomyolysis, hypoxemia, and dehydrated and microvascular thrombosis related to complement activation (17, 18) (Figures 1 and 2). Another cause of ARF in COVID-19 is associated with the collapsing glomerulopathy as documented in two different case reports in which ARF associated with heavy proteinuria affected black patients (19–21). All the patients were black with an APOL1 high-risk genotype.

Overall, COVID-19 patients show signs of renal injury including proteinuria (44%), hematuria (26.9%), and increased plasma creatinine (15.5%) (22). The presence of virus particles, both in urine and in renal parenchymal cells, is probably related to the penetration of the virus through the endothelium and the glomerular barrier (23). In another study, Pei et al. (24) documented a renal involvement in 251 out of 333 patients affected by COVID-19. Proteinuria was present in 65.8% of patients and hematuria in 41.7%.

The aforementioned study (11) on COVID-19 patients hospitalized in New York city documented, during univariate and multivariate logistic regression analyses, the risk factors associated with the development of AKI (Table 1).

To date, the exact mechanism of viral penetration inside the kidney and the subsequent renal damage has not been completely understood. The binding to ACE2 principally in the renal tubules represents the first step (25). The transmembrane protease, serine 2 (TMPRSS2), mediates this first priming step (26, 27). Once inside the kidney, several pathways may be activated as complement activation, cytokine storm, and interstitial inflammation. Viral replication in podocytes could mediate proteinuria (28). Rhabdomyolysis has also been documented in patients with COVID-19 and could contribute to the development of AKI (29).

Useful guidelines and suggestions may be obtained from the previous epidemics involving the coronavirus, in particular, the MERS epidemic.

During such epidemics, useful recommendations have been given by the Korean Society of Nephrology (30). According to such recommendations, the following key points should be followed:

Patients on hemodialysis with suspected or confirmed MERS-CoV infection should be transferred to a MERS clinic or to a hemodialysis center with facilities, such as isolation rooms.

To mitigate the risk of COVID-19 in dialysis facilities, the following points have been recently suggested (32):

A systemic screening should be adopted for all dialysis patients (symptomatic or not).

At the beginning of the COVID-19 spread in Europe, the European Dialysis (EUDIAL) Working Group of the European Renal Association–European Dialysis and Transplant Association (ERA–EDTA) recommended the following measures for the prevention, mitigation, and containment of the emerging SARS-CoV-2 pandemic in hemodialysis centers (42).

Different sets of recommendations are needed for both the healthcare team and the dialysis patients:

Recommendations for the health care team:

The health care team should be trained in the use of personal protective equipment.

The health care team should be aware of possible symptoms, so that they can avoid contact with suspected persons.

The health care team should be instructed on the use of protective equipment, such as masks (possible FFP2), goggles, mobcap, and disposable surgical gowns and gloves.

Italy has been deeply affected by the COVID-19 infection, especially Northern Italy.

From an overall population of 643 hemodialysis patients who reported in four dialysis centers in the province of Brescia (Lombardy region), in March 2020, 94 patients (15%) were positive for SARS-CoV-2 RNA.

The data published (43) through univariate analysis and noted as significant causes of death were a history of ischemic heart disease (0.05), fever (0.005), cough (0.01) and shortness of breath at diagnosis (0.001), and elevated C reactive protein (CRP) (0.001). Through multivariate analysis significant factors included fever (0.02), cough (0.05), and CRP at baseline (43).

There is not much data available on COVID-19 infection in renal transplant patients, and often they are related to case reports (58–60).

Akalin et al. collected data on 36 adult kidney transplant recipients positive for COVID-19 (61) in New York. Patients were treated in different ways according to the severity of their illness. All received reduced immunosuppressive therapy. Overall, there was a high mortality rate (28% at 3 weeks), and all transplanted patients documented a more rapid clinical progression than the general population affected by COVID-19.

In a different study (62), 10 kidney transplant patients tested positive for SARS-CoV-2 by PCR. Among them, three patients died (30%) and five developed acute kidney injury (AKI) (50%).

Better outcomes were observed at Columbia University Hospital, where 15 kidney transplant patients required hospitalization for confirmed COVID-19 (63). Six patients (40%) had AKI and four patients required intubation or mechanical ventilation. Two patients died. The authors themselves do not understand the reason for this lower mortality rate with respect to similar patients in the same area (61). The small patient number does not allow a statistical comparison.

A study from Iran (64) described 12 renal transplant patients with COVID-19 infection. In this group, eight patients died and four were discharged.

Twenty kidney transplant patients were admitted for SARS-CoV-2 pneumonia in the Brescia hospital (65): six patients developed AKI and five patients (25%) died. The study confirms a rapid clinical deterioration in renal transplant patients. Transplant patients are at a higher risk of developing a severe COVID-19 infection. To reduce this risk, several prophylactic and therapeutic measures should be adopted:

Prophylaxis. As aforementioned, a careful and repeated washing of hands with soap and alcohol is recommended, both for patients and the health care team.

Vaccinations as antipneumococcal are similarly recommended to avoid preventable infections.

Transplant patients should not travel, and the same holds good for their partners and family. Lockdown at home is recommended in areas with a high rate of COVID-19 spread.

Patients should wear a mask covering their mouth and nose when venturing out of home, and are recommended to stay at a distance from other people. As previously mentioned, the frequency of which mask should be used is open to wide discussion.

Prophylactic measures should be particularly adopted for patients with mild fever or cough and for those who had been in close contact with people suspected to have had Covid-19 in the last 14 days (66). In the case of patients with symptoms, they should stay in a protected site and should follow the guidelines that are continuously updated by the Center for Disease Control and Prevention (CDC) (67).

The adoption of such measures has reduced the transplantation activity. Preliminary Italian data show a reduction of procured organs by about 25% in the first 4 weeks of the COVID-19 outbreak (70).