A Comprehensive Review of Manifestations of Novel Coronaviruses in the Context of Deadly COVID-19 Global Pandemic

doi:10.1016/j.amjms.2020.05.006

Table 5

Renal manifestations of SARS-CoV, MERS-CoV and COVID-19.

SARS (only studies with large study population included)
Study	Booth et al (2003) N = 144, confirmed cases Retrospective study	Choi et al (2003) N = 267 (227 confirmed cases) Retrospective study	Zou et al (2004) N = 165, confirmed cases Retrospective study	Chan et al (2004) N = 669, (323 tested positive) Clinicopathologic study	Huang et al (2004) N = 78, probable Retrospective study	Ding et al (2004) N = 8 (4 confirmed cases, 4 control) Clinicopathologic study	Chu et al (2005) N = 536, confirmed cases Retrospective study
Clinical features	Renal dysfunction	ARF (6%) during course of hospitalization	Renal dysfunction	N/A	ARF (17%). 7.2 ± 4.3 days after admission	N/A	ARF (6.7%) within 5-48 days of onset (median 20)
Key findings on investigations	• ↑ Cr • ↑ Urea • ↓Ca++ (60%) • ↓K+ (26%) • ↓Mg++ (18%) • ↓P+ (27%) • ↑ LDH (87%)	↑ Cr	↑ Cr ↑ Urea	• Virus first detected in urine on day 7, stared to decline after day 16	↑ Cr	N/A	Cr normal at presentation, then ↑
Histopathology	N/A	N/A	N/A	N/A	N/A	Virus detected in distal convoluted renal tubule	Acute tubular necrosis, no evidence of glomerular pathology
Key study findings and message	↑ Urea > ↑ Cr associated with mortality (P = 0.003, P = 0.02)	↑ Cr associated with mortality (P < 0.001, univariate)	↑ Cr, ↑ Urea associated with poor prognosis (P = 0.001, P = 0.003)	Virus can persist >30 days after symptom onset in urine	• ARF more common in older age, males (P < 0.05), diabetics (P < 0.01), patients with heart failure (P < 0.001) • Renal features may be due to pre-renal factors, hypotension, rhabdomyolysis, comorbidities including diabetes, age	ACE2 expressed and virus detected in kidneys	• ARF significant risk factor for mortality (P < 0.001) (uni and multivariate) • ARF more likely in older age group, patients with ARDS, and requiring inotropes (P < 0.001) • ↓albumin, ↑ ALT at presentation, ↑ peak CPK after admission associated with development of ARF (P < 0.001, P = 0.004,P < 0.001) • Renal features likely multiorgan failure related, no direct viral pathology

MERS
Study	Assiri et al (2013) N = 47, confirmed cases Retrospective study	Arabi et al (2014) N = 12 (11 confirmed cases, 1probable) Case series	Saad et al (2014) N = 70, confirmed cases Retrospective study	Cha et al (2015) N = 30, confirmed cases Retrospective study	Yeung et al (2016) Ex-vivo organ culture Nonhuman primate model Clinicopathologic	Alsaad et al (2017) N = 1, confirmed cases Clinicopathologic study
Clinical feature	Coexisting chronic renal disease (49%)	• Coexisting chronic renal disease (42%) • ARF requiring RRT (58%)	ARF (42.9%)	• Coexisting chronic renal disease (10%) • ARF (26.7%)	N/A
Histopathology	N/A	N/A	N/A	N/A	Smad7 and FGF2 expression elevated in kidneys of infected animals	• Tubular epithelial cell degenerative and regenerative changes • Mild glomerular ischemic changes • Viral particles detected in proximal tubular epithelial cells
Key study findings and message	Chronic renal disease was a common comorbidity	Renal features may be due to: • Cytokine dysregulation • Direct viral invasion • Autoimmune	Acute kidney injury is a common complication	• AKI more likely in older patients (P = 0.016) • Preexisting CKD not associated with later development of AKI • AKI, RRT risk factors for mortality (univariate)	MERS-CoV induced apoptosis via upregulation of Smad7 and FGF2 expression	Tissue trophism in kidneys

COVID-19
Study	Wang et al (2020) N = 138, confirmed cases Retrospective study	Cheng et al (2020) N = 701, confirmed cases Retrospective study	Wang et al (2020) N = 205, confirmed cases Clinicopathologic	Li et al (2020) N = 193, confirmed cases Retrospective study	Zhou et al (2020) N = 191, confirmed cases Retrospective study
Clinical Features	• Coexisting chronic renal disease (2.9%) • AKI (3.6%)	• Coexisting chronic renal disease (2%) • AKI (3.2%)	N/A	• AKI (28%)	• AKI (15%) (Av 15 days after symptom onset)
Key findings on investigations	↑ Cr	• ↑ Cr (14.4%) • ↑ Urea (13.1%) • eGFR<60 (13.1%) • Proteinuria (43.9%) • Hematuria (26.7%)	No viral detection in urine (72 samples)	• ↑ Cr (10%) • ↑ Urea (14.%) • Proteinuria (59%) • Hematuria (44%)	↑ Cr
Key study findings and message	• ICU patients more likely to have ↑ Cr (P = 0.04), ↑ BUN (0.001) • Cr and urea increased with disease progression	• ↑ Cr at admission more common in males, older patients, more severe disease (P < 0.001, P < 0.001, P = 0.026) • AKI, in hospital death, mechanical ventilation more common in patients with baseline ↑ Cr (P < 0.001, P < 0.001, P = 0.012) • Higher in hospital death rate with proteinuria, hematuria, baseline ↑ Cr, Urea, AKI Stage 2 or 3 (P < 0.001; P = 0.003 for AKI stage 1) • Renal features may be due to direct viral effect, immune mediated, virus induced cytokines and mediators.	No viral shedding in urine	AKI associated with severe outcome (P < 0.001)	• ↑ Cr associated with in-hospital death (P = 0.045) • Higher incidence of AKI in nonsurvivors (P < 0.001)

ACE2, Angiotensin-converting enzyme 2; AKI, acute kidney injury; ARF, acute renal failure; BUN, blood urea nitrogen; CKD, chronic kidney disease; CPK, creatine phosphokinase; Cr, creatinine; eGFR, estimated glomerular filtration rate; LDH, lactate dehydrogenase; MERS-CoV, middle east respiratory syndrome coronavirus; SARS-COV, severe acute respiratory syndrome coronavirus; RRT, rapid response team.