COVID-19, AKI, and ESRD Research Roundup

Coronavirus disease 2019 (COVID-19) is primarily seen as a respiratory illness, but in some cases it can complicate hospital stays or recovery with systemic damage, particularly when it involves renal function. At the American Society of Nephrology’s Kidney Week, a variety of abstracts and sessions discussed not only the effect COVID-19 has on patients with existing renal comorbidities but also new attacks of acute kidney injury (AKI) that can cause severe illness or even death.

Here, we summarize several abstracts that delved into this topic. Many of the studies were conducted at hospitals in and around New York and New Jersey, which was an epicenter of the pandemic in the spring.

Kidney Biopsies Show Distinct Difference in Acute Injury

The pattern of damage seen in kidneys in patients infected SARS-CoV-2 recalls HIV-associated nephropathy, according to researchers.¹

Researchers from 6 institutions processed 10 renal biopsies for clincopathologic analysis using light microscopy, immunostaining (IS) and electron microscopy from patients presenting with presenting with acute kidney injury (AKI).

The 10 patients (5 male, 5 female) ranged from in age from 25 to 73, with a mean age of 43. The majority, 8, were Black; 1 was Hispanic and 1 was Asian Indian.

Nine of the 10 had obesity and/or nephrotic syndrome; other pre-existing comorbidities included hypertension in 7; diabetes in 5; proteinuria ranging from 1.5-25g/24hrs, lung symptoms or pneumonia in 7; or fever in 5.

Seven were positive by SARS-CoV-2 RT-PCR positive, 2 had positive IgG antibodies, and 1 was negative to both.

All kidney biopsies showed widespread acute tubular injury with focal necrosis. The majority also had features of segmental/global collapsing glomerulopathy in 10% to 53% of glomeruli. Up to 35% had global glomerulosclerosis. Other damage included tubular microcystic changes; tubulointerstitial inflammation and scarring; peritubular capillary inflammation; moderate vascular sclerosis; and diabetic kidney disease.

Immunostaining did not reveal immune deposits in any of the samples, but in 7 out of 10 biopsies, examination by electron microscope showed varied glomerular capillary wall wrinkling and collapse with segmental or global loss of patency as well as total foot process effacement. Protein droplets were noted on hyperplastic and vacuolated epithelial cells. Immunostaining identified viral particles within cells of glomeruli and tubulointerstitium, scattered or in cluster in the cytoplasm and endoplasmic reticulum vesicles.

The pattern of typical glomerular collapsing features with tubulointerstitial findings and localization of virus by electron microscope suggests a distinct viral-associated nephropathy, reminicent of HIV-associated nephropathy. “A role for viral cytopathic effect, cytokines and underlying APOL1 gene variants could be considered,” the authors.

Comparing COVID-19 Outcomes in ESRD

Another study looked at the impact of COVID-19 in patients with end-stage renal disease (ESRD). The observational study examined characteristics of patients with ESRD and COVID-19 hospitalized over a 7-week period.

Researchers compared rates of mechanical ventilation, shock, need for intensive care (ICU) and in-hospital mortality as outcome measures between patients with and without ESRD.

Of the 851 admissions for COVID-19 (67% Black), 49 (6%) patients also had a diagnosis of ESRD. Patients with ESRD as compared to those without were mostly male (61% vs 49%; P = 0.10) with a median age of 64 (38–90) years.

Those admitted to the ICU had a median body mass index (BMI) of 32 kg/m2 vs 27 kg/m2 of those sent to wards (P = .11).

Thirteen patients (27%) vs 293 (37%) in the non-ESRD group ( P = .16) were admitted to an ICU.

The in-hospital mortality rate for the ESRD group was 32% compared with 24% for those without ESRD (P = 0.21).

A subset of 161 patients with acute kidney injury (AKI) had greater mortality than those with ESRD: 50% compared with 32% (P = .027). But shock and/or mechanical ventilation requirement were comparable between the 2 groups.

Median serum ferritin level was significantly more elevated in ESRD compared with non-ESRD (2125 vs 633 ng/mL; P = .0019).

Clinical outcomes in individuals with ESRD with COVID19 appear similar to those without ESRD and COVID19, while the mortality in patients with ESRD and COVID19 is lower than that observed in AKI.

"The observed lack of increased mortality in ESRD does not align with the outcomes of this patient population in other critical illnesses. The ability to mount and exaggerated inflammatory response in COVID19 might be somewhat restricted in ESRD," the authors concluded.

AKI and COVID-19 in Hospitalized Patients

Researchers in New York sought to determine the incidence of AKI in patients hospitalized with COVID-19, evaluate the risk factors for developing AKI, and assess the effect of AKI on overall outcomes and kidney outcomes. ³

They reviewed the health records for all patients hospitalized with COVID-19 between March 1, and April 5, 2020, at 13 hospitals in metropolitan New York. Patients younger than 18 years of age, with ESRD or with a kidney transplant were excluded. Secondary outcomes included need for renal replacement therapy (RRT) and either hospital discharge or death.

Of 5449 patients admitted with COVID-19, AKI developed in 1993 (36.6%). The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4% and stage 3 in 31.1%. Of these, 14.3% required renal replacement therapy (RRT). AKI was primarily seen in patients with respiratory failure, with nearly 90% needing mechanical ventilation compared; in addition, the majority of patients needed RRT were on ventilators.

Of patients who required ventilation and developed AKI, 52.2% saw AKI develop within 24 hours of intubation.

Risk factors for AKI included older age, diabetes, cardiovascular disease, black race, hypertension, and need for ventilation and vasopressor medications. Among patients with AKI, 1136 died (57%), 519 (26%) were discharged and 338 (17%) were still hospitalized.

References

1. Seshan S, Salvatore S, Fyfe-Kirschner, BS, et al. COVID-19-associated nephropathy (COVAN): An emerging entity of severe viral podocyte injury and collapsing glomerulopathy in kidney biopsies. Presented at: American Society of Nephrology Kidney Week 2020. Poster PO-841.

2. Torres Ortiz AE, Mohamed M, Mitchell VT, Velez JCQ. Clinical outcomes of patients with ESRD hospitalized with COVID-19. Presented at: American Society of Nephrology Kidney Week 2020. Poster PO-0719

3. Hwei Ng J, Hirsch JS, Fishbane S, Jhaveri KD. AKI in patients hospitalized with COVID-19 Presented at: American Society of Nephrology Kidney Week 2020. Oral abstract SA-OR06